Association of Adverse Childhood Experiences and Resilience With Depression and Anxiety During Pregnancy
This was a retrospective cohort study of pregnant individuals in the Kaiser Permanente Northern California system who were screened for adverse childhood experiences and resilience as part of standard prenatal care at about 16 weeks of gestation. Overall, 14,625 pregnancies were included; 17.0% had newly identified depression; 9.8% had newly identified depression symptoms; and 8.9% had newly identified anxiety during the pregnancy with no known preexisting diagnosis. We found that adverse childhood experiences and low resilience were independently associated with newly identified depressive disorders, depression symptoms, and anxiety disorders during pregnancy. When adverse childhood experiences and resilience were modeled in combination, the greatest odds of each outcome occurred in individuals with a combination of four or more adverse childhood experiences and low resilience (vs no adverse childhood experiences and high resilience): depression adjusted odds ratio (aOR) 6.43 (95% CI, 5.23-7.90), depression symptoms aOR 9.49 (95% CI, 7.50-12.0), and anxiety disorder aOR 4.79 (95% CI, 3.81-6.02). Routine screening for adverse childhood experiences and resilience may identify individuals at risk of developing prenatal depression and anxiety, allowing faster resource linkage and potentially improved maternal and child outcomes.
Authors: Watson, Carey R;Eaton, Abigail;Campbell, Cynthia I;Alexeeff, Stacey E;Avalos, Lyndsay A;Ridout, Kathryn K;Young-Wolff, Kelly C
Obstet Gynecol. 2024 May 01;143(5):707-710. Epub 2024-02-29.
Self-reported pain severity and use of cannabis and opioids in persons with HIV in an urban primary care setting in Northern California: A cross-sectional study
Persons with HIV (PWH) experience high levels of pain. We examined the relationship of pain severity with use of cannabis and prescription opioids among PWH. This cross-sectional study evaluated associations between self-reported pain (moderate/severe vs mild/none) and cannabis and prescription opioid use in a primary care sample of PWH enrolled in an alcohol use treatment study at Kaiser Permanente, San Francisco. Prevalence ratios (PR) for moderate/severe pain associated with cannabis, opioid use, or both in the prior 30 days were obtained from Poisson regression models. Adjusted models included race/ethnicity, education, employment, HIV ribonucleic acid levels, depression, and anxiety. Overall, 614 PWH completed baseline questionnaires from May 2013 to May 2015, among whom 182/614 (29.6%) reported moderate/severe pain. The prevalence of moderate/severe pain varied by substances: 19.1% moderate/severe pain among study participants who reported neither cannabis or opioids, 30.2% for cannabis alone, 41.2% for opioids alone, and 60.9% for those reporting both substances. In adjusted models, compared with PWH who reported neither substance (reference), prevalence of moderate/severe pain was higher for those using cannabis alone (PR 1.54; 95% CI 1.13-2.09), opioids alone (PR 1.96; 95% CI 1.31-2.94), and those reporting both (PR 2.66; 95% CI 1.91-3.70). PWH who reported opioid and/or cannabis use were more likely to report moderate/severe pain compared with PWH who did not report use of these substances. To improve patient care, it is vital to assess patients’ approaches to pain management including substance use and target appropriate interventions to reduce pain in PWH.
Authors: Kim, Hannah J;Satre, Derek D;Leyden, Wendy;Leibowitz, Amy S;Campbell, Cynthia I;Silverberg, Michael J
Medicine (Baltimore). 2024 Mar 29;103(13):e37581.
Reimbursement for a Broader Array of Services in Coordinated Specialty Care for Early Psychosis
Despite the growing evidence supporting the benefits of coordinated specialty care (CSC) for early psychosis, access to this multimodal, evidence-based program in the United States has been hindered by a lack of funding for core CSC services and activities. The recent approval of team-based reimbursement codes by the Centers for Medicare and Medicaid Services has the potential to fund substantially more CSC services for clients with insurance coverage that accepts the new team-based billing codes. This streamlined and more inclusive billing strategy may reduce administrative burden and support the financial viability of CSC programs.
Authors: Hirschtritt, Matthew E;Staglin, Brandon;Buttlaire, Stuart;Ahearn, Kerry;Oglesby, Sarada;Dixon, Lisa B;Shern, David;Ewing, Toby;Niendam, Tara A
Psychiatr Serv. 2024 Mar 27:appips20230551.
The Association Between Physical Activity and Cognition in a Racially/Ethnically Diverse Cohort of Older Adults: Results From the Kaiser Healthy Aging and Diverse Life Experiences Study
Most prior research on physical activity (PA) and cognition is based on predominantly white cohorts and focused on associations of PA with mean (average) cognition versus the distribution of cognition. Quantile regression offers a novel way to quantify how PA affects cognition across the entire distribution. The Kaiser Healthy Aging and Diverse Life Experiences study includes 30% white, 19% black, 25% Asian, and 26% Latinx adults age 65+ living in Northern California (n = 1600). The frequency of light or heavy PA was summarized as 2 continuous variables. Outcomes were z-scored executive function, semantic memory, and verbal episodic memory. We tested associations of PA with mean cognition using linear regression and used quantile regression to estimate the association of PA with the 10th-90th percentiles of cognitive scores. Higher levels of PA were associated with higher mean semantic memory (b = 0.10; 95% CI: 0.06, 0.14) and executive function (b = 0.05; 95% CI: 0.01, 0.09). Associations of PA across all 3 cognitive domains were stronger at low quantiles of cognition. PA is associated with cognition in this racially/ethnically diverse sample and may have larger benefits for individuals with low cognitive scores, who are most vulnerable to dementia.
Authors: Almeida, Mariana L;Gilsanz, Paola;Glymour, M Maria;et al.
Alzheimer Dis Assoc Disord. 2024 Mar 27.
Validation of a Multivariable Model to Predict Suicide Attempt in a Mental Health Intake Sample
Given that suicide rates have been increasing over the past decade and the demand for mental health care is at an all-time high, targeted prevention efforts are needed to identify individuals seeking to initiate mental health outpatient services who are at high risk for suicide. Suicide prediction models have been developed using outpatient mental health encounters, but their performance among intake appointments has not been directly examined. To assess the performance of a predictive model of suicide attempts among individuals seeking to initiate an episode of outpatient mental health care. This prognostic study tested the performance of a previously developed machine learning model designed to predict suicide attempts within 90 days of any mental health outpatient visit. All mental health intake appointments scheduled between January 1, 2012, and April 1, 2022, at Kaiser Permanente Northern California, a large integrated health care delivery system serving over 4.5 million patients, were included. Data were extracted and analyzed from August 9, 2022, to July 31, 2023. Suicide attempts (including completed suicides) within 90 days of the appointment, determined by diagnostic codes and government databases. All predictors were extracted from electronic health records. The study included 1 623 232 scheduled appointments from 835 616 unique patients. There were 2800 scheduled appointments (0.17%) followed by a suicide attempt within 90 days. The mean (SD) age across appointments was 39.7 (15.8) years, and most appointments were for women (1 103 184 [68.0%]). The model had an area under the receiver operating characteristic curve of 0.77 (95% CI, 0.76-0.78), an area under the precision-recall curve of 0.02 (95% CI, 0.02-0.02), an expected calibration error of 0.0012 (95% CI, 0.0011-0.0013), and sensitivities of 37.2% (95% CI, 35.5%-38.9%) and 18.8% (95% CI, 17.3%-20.2%) at specificities of 95% and 99%, respectively. The 10% of appointments at the highest risk level accounted for 48.8% (95% CI, 47.0%-50.6%) of the appointments followed by a suicide attempt. In this prognostic study involving mental health intakes, a previously developed machine learning model of suicide attempts showed good overall classification performance. Implementation research is needed to determine appropriate thresholds and interventions for applying the model in an intake setting to target high-risk cases in a manner that is acceptable to patients and clinicians.
Authors: Papini, Santiago;Hsin, Honor;Kipnis, Patricia;Liu, Vincent X;Lu, Yun;Girard, Kristine;Sterling, Stacy A;Iturralde, Esti M
JAMA Psychiatry. 2024 Mar 27.
Implementation and Evaluation of Adverse Childhood Experiences Screening in Pediatrics and Obstetrics Settings
Screening for adverse childhood experiences (ACEs) in prenatal and pediatric populations is recommended by the California ACEs Aware initiative and is a promising practice to interrupt ACEs in children and mitigate ACEs-related health complications in children and families. Yet, integrating ACEs screening into clinical practice poses several challenges. The objective of this report was to evaluate the Kaiser Permanente Northern California and Kaiser Permanente Southern California pilots and implementation of ACEs screening into routine prenatal (Kaiser Permanente Northern California) and pediatric (Kaiser Permanente Southern California) care. These pilots were evaluated and compared to identify common challenges to implementation and offer promising practices for negotiating these challenges. Evaluation methods included feedback from staff, clinicians, and patients, as well as comparisons of methods to overcome various barriers to screening implementation. Implementing ACEs screening, like implementation of any new component of clinical care, takes careful planning, education, creation of content and workflows, and continuous integration of feedback from both patients and staff. This evaluation can serve as support for care teams who are considering implementing ACEs screening or who are already screening for ACEs. More research is needed regarding the relationship between ACEs and preventable and treatable health outcomes to improve health for patients and their families.
Authors: Watson, Carey R;Young-Wolff, Kelly C;Negriff, Sonya;Dumke, Kelly;DiGangi, Mercie
Perm J. 2024 Mar 15;28(1):180-187. Epub 2024-01-29.
Racial and ethnic differences in the association between depressive symptoms and cognitive outcomes in older adults: Findings from KHANDLE and STAR
Depressive symptoms are associated with higher risk of dementia, but how they impact cognition in diverse populations is unclear. Asian, Black, Latino, or White participants (n = 2227) in the Kaiser Healthy Aging and Diverse Life Experiences (age 65+) and the Study of Healthy Aging in African Americans (age 50+) underwent up to three waves of cognitive assessments over 4 years. Multilevel models stratified by race/ethnicity were used to examine whether depressive symptoms were associated with cognition or cognitive decline and whether associations differed by race/ethnicity. Higher depressive symptoms were associated with lower baseline verbal episodic memory scores (-0.06, 95% CI: -0.12, -0.01; -0.15, 95% CI: -0.25, -0.04), and faster decline annually in semantic memory (-0.04, 95% CI: -0.07, -0.01; -0.10, 95% CI: -0.15, -0.05) for Black and Latino participants. Depressive symptoms were associated with lower baseline but not decline in executive function. Depressive symptoms were associated with worse cognitive outcomes, with some evidence of heterogeneity across racial/ethnic groups. We examined whether baseline depressive symptoms were differentially associated with domain-specific cognition or cognitive decline by race/ethnicity. Depressive symptoms were associated with worse cognitive scores for all racial/ethnic groups across different domains examined. Higher depressive symptoms were associated with faster cognitive decline for semantic memory for Black and Latino participants. The results suggest a particularly harmful association between depressive symptoms and cognition in certain racial/ethnic groups.
Authors: Jimenez, Marcia P;Gilsanz, Paola;Glymour, Medellena Maria;et al.
Alzheimers Dement. 2024 Mar 13.
2023 lifetime achievement award: “If you want to go fast, go alone; if you want to go far, go together”
This article is based on the address given by the author at the 2023 meeting of The American Society of Human Genetics (ASHG). A video of the original address can be found at the ASHG website.
Authors: Risch, Neil
Am J Hum Genet. 2024 Mar 07;111(3):412-423.
On- and Off-Label Atypical Antipsychotic Prescription Trends Across a Nine-Year Period Among Adolescents Pre- to Post-COVID-19
This study examined atypical antipsychotic prescribing by Food and Drug Administration (FDA) approved-use (on-label) status for adolescents before and during the COVID-19 pandemic. Retrospective data were collected from electronic health records (EHRs) of adolescents aged 10-17 years in Kaiser Permanente Northern California. New outpatient atypical antipsychotic prescription orders during 2013-2021 were evaluated. Prescriptions were categorized as on-label if linked in EHRs to autism, psychosis, bipolar disorder, or Tourette’s diagnoses; otherwise, they were potentially off-label (herein, off-label). Trend analysis of monthly prescribing rates assessed slope change at pandemic onset for the cohort and by sex and age groups. Among 5828 patients, 74.5% of new antipsychotic orders were off-label in 2021. Overall prescribing decreased significantly until early 2020 (slope = -0.045, P < .01) but then significantly increased through 2021 (post-March 2020 slope change = 0.211, P = .01). Off-label prescriptions increased at a similar rate during the COVID-19 time period, but on-label prescriptions did not change significantly. Males and younger adolescents (ages 10-14 years) showed significant decreases until early 2020, while females and older adolescents (ages 15-17 years) did not. Females and younger adolescents exhibited significant increases in overall and off-label prescribing rates following pandemic onset; older adolescents exhibited increases in overall prescriptions while males had no detectable changes. Antipsychotic prescribing declined slightly but then increased significantly following COVID-19 onset for overall and off-label prescriptions. Pandemic onset differentially impacted antipsychotic prescribing by sex and age, with overall and off-label prescribing driven by increases among female and younger adolescents.
Authors: Costales, Brianna;Slama, Natalie E;Penfold, Robert B;Nugent, Joshua R;Spalding, Scott R;Sterling, Stacy A;Iturralde, Esti
Acad Pediatr. 2024 Mar 06.
Psychiatric and substance use disorders among adults over age 50 who use cannabis: A matched cohort study using electronic health record data
Adults over age 50 increasingly use cannabis, but few studies have examined co-occurring psychiatric and substance use disorders (SUDs) in this population. The current study utilized electronic health record (EHR) data to compare adults age 50 + with ICD-10 cannabis codes (cases) and matched controls on common psychiatric and SUDs from 2016 to 2020. Patients age 50 + from an integrated healthcare system in Hawai’i were identified using ICD-10 codes for cannabis (use, abuse, and dependence) from 2016 to 2018. In a matched cohort design, we selected non-cannabis-using controls (matched on sex and age) from the EHR (n = 275) and compared them to cases (patients with an ICD-10 cannabis code; n = 275) on depressive and anxiety disorders and SUDs (i.e., tobacco, opioid, and alcohol use disorders) over a two-year follow-up period. Participants were 62.8 years (SD = 7.3) old on average; and were White (47.8 %), Asian American (24.4 %), Native Hawaiian or Pacific Islander (19.3 %), or Unknown (8.5 %) race/ethnicity. Conditional multiple logistic regression was used to estimate odds ratios comparing cases vs controls. Participants with an ICD-10 cannabis code had a significantly greater risk of major depressive disorder (OR = 10.68, p < 0.0001) and any anxiety disorder (OR = 6.45, p < 0.0001), as well as specific anxiety or trauma-related disorders (e.g., generalized anxiety disorder, PTSD) and SUDs (ORs 2.72 - 16.00, p < 0.01 for all). Over a two-year period, diverse adults age 50 + in Hawai'i with ICD-10 cannabis codes experienced higher rates of subsequent psychiatric and SUDs compared to controls. These findings can guide efforts to inform older adults about possible cannabis-related risks.
Authors: Phillips, Kristina T;Pedula, Kathryn L;Simiola, Vanessa;Satre, Derek D;Choi, Namkee G
Addict Behav. 2024 Mar;150:107927. Epub 2023-11-28.
Association between lifetime smoking and cutaneous squamous cell carcinoma: A 2-sample Mendelian randomization study
Cutaneous squamous cell carcinoma (cSCC) is one of the most common malignancies worldwide. While several environmental risk factors for cSCC are well established, there is conflicting evidence on cigarette smoking (and its potential causal effect) and cSCC risk. Furthermore, it is unclear if these potential associations represent causal, modifiable risk factors for cSCC development. This study aims to assess the nature of the associations between cigarette smoking traits (smoking initiation, amount smoked, and lifetime smoking exposure) and cSCC risk using two-sample Mendelian randomization analyses. Genetic instruments, based on common genetic variants associated with cigarette smoking traits (P < 5 × 10-8), were derived from published genome-wide association studies (GWASs). For cSCC, we used GWAS summary statistics from the Kaiser Permanente GERA cohort (7701 cSCC cases and 60,167 controls; all non-Hispanic Whites). We found modest evidence that genetically determined lifetime smoking was associated with cSCC (inverse-variance weighted method: OR[95% CI] = 1.47[1.09-1.98]; P = .012), suggesting it may be a causal risk factor for cSCC. We did not detect any evidence of association between genetically determined smoking initiation or amount smoked and cSCC risk. Study findings highlight the importance of smoking prevention and may support risk-stratified cSCC screening strategies based on carcinogen exposure and other genetic and clinical information.
Authors: Lee, Truelian;George, Christopher D;Jiang, Chen;Asgari, Maryam M;Nijsten, Tamar;Pardo, Luba M;Choquet, Hélène
JAAD Int. 2024 Mar;14:69-76. Epub 2023-12-03.
Telehepatology Satisfaction Is Associated with Ethnicity: The Real-World Experience of a Vulnerable Population with Fatty Liver Disease
Since the coronavirus disease 2019 (COVID-19) pandemic began, telemedicine use has transformed healthcare delivery. Yet there is concern that telemedicine may widen care disparities for vulnerable populations, and patient experience data are limited. We aimed to assess patient satisfaction with hepatology-related telemedicine (telehepatology) for delivery of fatty liver disease (FLD) care in a safety-net healthcare system. Adult patients with FLD were surveyed regarding satisfaction with telehepatology. Clinical, demographic, resources, and social determinants of health (SDoH) data were collected to identify factors associated with satisfaction through multivariable modeling. From June 2020 to March 2022, 220 participants were enrolled: the median age was 52 years, 37% were men, and 68% were Hispanic. One hundred nineteen (54%) had prior telehepatology experience. Overall, satisfaction was high; 70% reported being somewhat or very satisfied. On univariate analysis, Hispanic ethnicity (versus non-Hispanic, OR 0.34, 95% CI 0.1-0.9, p = 0.03) and limited access to personal cellphone/internet (OR 0.16, 95% CI 0.04-0.6, p = 0.01) were associated with lower satisfaction. On multivariable logistic regression modeling adjusted for pandemic duration, age, sex, severity of liver disease, and coexisting liver disease, Hispanic ethnicity and lack of personal cellphone/internet remained independently associated with lower telehepatology satisfaction (OR 0.24, 95% CI 0.07-0.9, p = 0.03 and OR 0.2, 95% CI 0.04-0.9, p = 0.04, respectively). The association remained statistically significant after inclusion of various SDoH in the multivariable model. Satisfaction with telehepatology among FLD patients in a safety-net clinical setting was high overall. However, Hispanic ethnicity and lack of personal cellphone/internet were independently associated with lower telehepatology satisfaction. A better understanding of patients’ experience with telehepatology is needed to identify reasons for dissatisfaction, and in-person visits should remain an option for patients to ensure equitable care.
Authors: Kim, Rebecca G;Patel, Shyam;Satre, Derek D;Shumway, Martha;Chen, Jennifer Y;Magee, Catherine;Wong, Robert J;Monto, Alexander;Cheung, Ramsey;Khalili, Mandana
Dig Dis Sci. 2024 Mar;69(3):732-742. Epub 2024-01-13.
Racial and Ethnic Variation in Dementia Prevalence in a Diverse Cohort of Adults with Hip Fracture
Authors: Lee, David R;Lo, Joan C;Chandra, Malini;Lee, Catherine;Gilsanz, Paola
J Gen Intern Med. 2024 Mar;39(4):716-719. Epub 2023-12-24.
Alcohol Use Patterns During and After the COVID-19 Pandemic Among Veterans in the United States
Veterans may be especially susceptible to increased alcohol consumption following the COVID-19 pandemic. We aim to evaluate trends in alcohol use among US Veterans prior to, during, and following the onset of the COVID-19 pandemic. All US Veterans utilizing Veterans Affairs health care facilities in the United States from March 1, 2018 to February 28, 2023 with ≥1 AUDIT-C score were categorized into 1) No alcohol use (AUDIT-C = 0), 2) Low-risk alcohol use (AUDIT-C 1-2 for women, 1-3 for men), and 3) High-risk alcohol use (AUDIT-C ≥ 3 for women, ≥ 4 for men). Trends in the proportion of Veterans reporting high-risk alcohol use, stratified by sex, age, race/ethnicity, and urbanicity were evaluated. Among a cohort of 2.15 to 2.60 million Veterans, 15.5% reported high-risk alcohol use during March 2018-February 2019, which decreased to 14.6% during the first year of the pandemic, increased to 15.2% in the second year, and then decreased to 14.9% from March 2022-February 2023. Among non-Hispanic whites, African Americans, Asians, and Hispanics, the proportion of women reporting high-risk alcohol use surpassed that of men during the onset of the pandemic and beyond. The greatest proportion of high-risk alcohol use was observed among young Veterans ages 18-39 years (17%-27%), which was consistent across all race/ethnic groups. High-risk alcohol use among US Veterans has increased since the COVID-19 pandemic onset, and in the third year following pandemic onset, 15% of Veterans overall and over 20% of young Veterans ages 18-39 years reported high-risk alcohol use.
Authors: Wong, Robert J;Yang, Zeyuan;Ostacher, Michael;Zhang, Wei;Satre, Derek;Monto, Alexander;Khalili, Mandana;Singal, Ashwani K;Cheung, Ramsey
Am J Med. 2024 Mar;137(3):236-239.e2. Epub 2023-12-03.
Tools to implement measurement-based care (MBC) in the treatment of opioid use disorder (OUD): toward a consensus
The prevalence and associated overdose death rates from opioid use disorder (OUD) have dramatically increased in the last decade. Despite more available treatments than 20 years ago, treatment access and high discontinuation rates are challenges, as are personalized medication dosing and making timely treatment changes when treatments fail. In other fields such as depression, brief measures to address these tasks combined with an action plan-so-called measurement-based care (MBC)-have been associated with better outcomes. This workgroup aimed to determine whether brief measures can be identified for using MBC for optimizing dosing or informing treatment decisions in OUD. The National Institute on Drug Abuse Center for the Clinical Trials Network (NIDA CCTN) in 2022 convened a small workgroup to develop consensus about clinically usable measures to improve the quality of treatment delivery with MBC methods for OUD. Two clinical tasks were addressed: (1) to identify the optimal dose of medications for OUD for each patient and (2) to estimate the effectiveness of a treatment for a particular patient once implemented, in a more granular fashion than the binary categories of early or sustained remission or no remission found in The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). Five parameters were recommended to personalize medication dose adjustment: withdrawal symptoms, opioid use, magnitude (severity and duration) of the subjective effects when opioids are used, craving, and side effects. A brief rating of each OUD-specific parameter to adjust dosing and a global assessment or verbal question for side-effects was viewed as sufficient. Whether these ratings produce better outcomes (e.g., treatment engagement and retention) in practice deserves study. There was consensus that core signs and symptoms of OUD based on some of the 5 DSM-5 domains (e.g., craving, withdrawal) should be the basis for assessing treatment outcome. No existing brief measure was found to meet all the consensus recommendations. Next steps would be to select, adapt or develop de novo items/brief scales to inform clinical decision-making about dose and treatment effectiveness. Psychometric testing, assessment of acceptability and whether the use of such scales produces better symptom control, quality of life (QoL), daily function or better prognosis as compared to treatment as usual deserves investigation.
Authors: Rush, A John;Campbell, Cynthia I;Tai, Betty;et al.
Addict Sci Clin Pract. 2024 Feb 28;19(1):14. Epub 2024-02-28.
Addiction Medicine Treatment Utilization by Race/Ethnicity Among Adolescents With Substance Use Problems Before Versus During the COVID-19 Pandemic
To examine changes in addiction medicine treatment utilization during the COVID-19 pandemic among adolescents (aged 13-17 years) and differences by race/ethnicity. We compared treatment initiation (overall and telehealth), engagement, and 12-week retention between insured adolescents with substance use problems during pre-COVID-19 (March to December 2019, n = 1,770) and COVID-19 (March to December 2020, n = 1,177) using electronic health record data from Kaiser Permanente Northern California. Compared to pre-COVID-19, odds of treatment initiation, overall (adjusted odds ratio [95% confidence interval] = 1.42 [1.21-1.67]), and telehealth (5.98 [4.59-7.80]) were higher during COVID-19, but odds of engagement and retention did not significantly change. Depending on the outcome, Asian/Pacific Islander, Black, and Latino/Hispanic (vs. White) adolescents had lower treatment utilization across both periods. Changes in utilization over time did not differ by race/ethnicity. Addiction medicine treatment initiation increased among insured adolescents during the pandemic, especially via telehealth. Although racial/ethnic disparities in treatment utilization persisted, they did not worsen.
Authors: Palzes, Vanessa A;Chi, Felicia W;Metz, Verena E;Sterling, Stacy;Asyyed, Asma;Ridout, Kathryn K;Campbell, Cynthia I
J Adolesc Health. 2024 Feb 26.
Intentions to Use Cannabis Postpartum: A Qualitative Study of Pregnant Individuals Who Used Cannabis During Early Pregnancy
Objective: To examine plans for postpartum cannabis use among pregnant individuals who used cannabis during early pregnancy. Materials and Methods: Eighteen virtual focus groups were conducted from November 17, 2021, to December 17, 2021, with 23 Black and 30 White pregnant adults in Kaiser Permanente Northern California, who self-reported prenatal cannabis use during early pregnancy. Focus groups were recorded, transcribed, and analyzed using thematic analysis. Results: The sample (N = 53) had a mean age of 30.3 years (standard deviation = 5.2) at recruitment; 70% reported daily, 25% weekly, and 6% ≤ monthly cannabis use at entrance to prenatal care. Some participants viewed cannabis as critical for coping with postpartum mental and physical health challenges, while others questioned whether cannabis use would fit with their parental lifestyle, and some planned to abstain altogether. Most planned to use cannabis postpartum, but with lower frequency than before pregnancy, and in ways consistent with harm reduction (e.g., smoking outside to avoid secondhand or thirdhand smoke exposure). Many were motivated to abstain from cannabis while breastfeeding, and some desired more data on the safety of cannabis and breastfeeding, or intended to “pump and dump,” believing it would reduce potential transfer of Δ9-tetrahydrocannabinol (THC) to their infant. Responses from Black and White participants were generally similar, but White participants were more likely to report plans to use cannabis while breastfeeding and to want information about cannabis and breastfeeding. Conclusions: Pregnant individuals with prenatal cannabis use had varied plans for cannabis use postpartum. Many were motivated to abstain or use cannabis less frequently than pre-pregnancy, especially during lactation.
Authors: Young-Wolff, Kelly C;Iturralde, Esti;Foti, Tara R;et al.
J Womens Health (Larchmt). 2024 Feb 24.
Evidence supports a causal association between allele-specific vitamin D receptor binding and multiple sclerosis among Europeans
Although evidence exists for a causal association between 25-hydroxyvitamin D (25(OH)D) serum levels, and multiple sclerosis (MS), the role of variation in vitamin D receptor (VDR) binding in MS is unknown. Here, we leveraged previously identified variants associated with allele imbalance in VDR binding (VDR-binding variant; VDR-BV) in ChIP-exo data from calcitriol-stimulated lymphoblastoid cell lines and 25(OH)D serum levels from genome-wide association studies to construct genetic instrumental variables (GIVs). GIVs are composed of one or more genetic variants that serve as proxies for exposures of interest. Here, GIVs for both VDR-BVs and 25(OH)D were used in a two-sample Mendelian Randomization study to investigate the relationship between VDR binding at a locus, 25(OH)D serum levels, and MS risk. Data for 13,598 MS cases and 38,887 controls of European ancestry from Kaiser Permanente Northern California, Swedish MS studies, and the UK Biobank were included. We estimated the association between each VDR-BV GIV and MS. Significant interaction between a VDR-BV GIV and a GIV for serum 25OH(D) was evidence for a causal association between VDR-BVs and MS unbiased by pleiotropy. We observed evidence for associations between two VDR-BVs (rs2881514, rs2531804) and MS after correction for multiple tests. There was evidence of interaction between rs2881514 and a 25(OH)D GIV, providing evidence of a causal association between rs2881514 and MS. This study is the first to demonstrate evidence that variation in VDR binding at a locus contributes to MS risk. Our results are relevant to other autoimmune diseases in which vitamin D plays a role.
Authors: Adams, Cameron;Manouchehrinia, Ali;Quach, Hong L;Quach, Diana L;Olsson, Tomas;Kockum, Ingrid;Schaefer, Catherine;Ponting, Chris P;Alfredsson, Lars;Barcellos, Lisa F
Proc Natl Acad Sci U S A. 2024 Feb 20;121(8):e2302259121. Epub 2024-02-12.
Adolescent utilization of eating disorder higher level of care: roles of family-based treatment adherence and demographic factors
Outpatient family-based treatment (FBT) is effective in treating restrictive eating disorders among adolescents. However, little is known about whether FBT reduces higher level of care (HLOC) utilization or if utilization of HLOC is associated with patient characteristics. This study examined associations between utilization of eating disorder related care (HLOC and outpatient treatment) and reported adherence to FBT and patient characteristics in a large integrated health system. This retrospective cohort study examined 4101 adolescents who received care for restrictive eating disorders at Kaiser Permanente Northern California. A survey was sent to each medical center to identify treatment teams as high FBT adherence (hFBT) and low FBT adherence (lFBT). Outpatient medical and psychiatry encounters and HLOC, including medical hospitalizations and higher-level psychiatric care as well as patient characteristics were extracted from the EHR and examined over 12 months post-index. 2111 and 1990 adolescents were treated in the hFBT and lFBT, respectively. After adjusting for age, sex, race/ethnicity, initial percent median BMI, and comorbid mental health diagnoses, there were no differences in HLOC or outpatient utilization between hFBT and lFBT. Females had higher odds of any utilization compared with males. Compared to White adolescents, Latinos/Hispanics had lower odds of HLOC utilization. Asian, Black, and Latino/Hispanic adolescents had lower odds of psychiatric outpatient care than Whites. Reported FBT adherence was not associated with HLOC utilization in this sample. However, significant disparities across patient characteristics were found in the utilization of psychiatric care for eating disorders. More efforts are needed to understand treatment pathways that are accessible and effective for all populations with eating disorders. Adolescents with restrictive eating treated by Family-Based Treatment (FBT) teams had better early weight gain but no differences in the use of intensive outpatient, residential, partial hospital programs or inpatient psychiatry care when compared to those treated by teams with a low adherence to the FBT approach. Factors such as sex, race, ethnicity, mood disorders, and suicidality were associated with the use of psychiatric services. These findings are consistent with previously documented systematic disparities in accessing psychiatric services across patient demographics and should be used to inform the development of proposed care models that are more inclusive and accessible to all patients.
Authors: Lau, Josephine S;Kline-Simon, Andrea H;Schmittdiel, Julie A;Sterling, Stacy A
J Eat Disord. 2024 Feb 02;12(1):22. Epub 2024-02-02.
Problematic alcohol use and its impact on liver disease quality of life in a multicenter study of patients with cirrhosis
Management of cirrhosis is challenging and has been complicated by the COVID-19 pandemic due to decreased access to care, increased psychological distress, and alcohol misuse. Recently, The National Institute on Alcohol Abuse and Alcoholism has broadened the definition of recovery from alcohol use disorder to include quality of life (QoL) as an indicator of recovery. This study examined the associations of alcohol-associated cirrhosis etiology and problematic drinking with liver disease QoL (LDQoL). Patients with cirrhosis (N=329) were recruited from 3 sites (63% from 2 Veterans Affairs Health Care Systems and 37% from 1 safety net hospital) serving populations that are economically or socially marginalized. Cirrhosis etiology was ascertained by chart review of medical records. Problematic drinking was defined by ≥8 on the Alcohol Use Disorders Identification Test. Multivariable general linear modeling adjusting for age, sex, race/ethnicity, site, pandemic-related stress, and history of anxiety/depressive disorder were conducted. Sensitivity analyses further adjusted for indicators of liver disease severity. Participants were on average 64.6 years old, 17% female, 58% non-White, 44% with alcohol-associated cirrhosis, and 17% with problematic drinking. Problematic drinking was significantly associated with worse LDQoL scores in the overall scale and in the memory/concentration and health distress subscales. These associations remained significant after adjusting for indicators of liver disease severity, including Model for End-Stage Liver Disease-Sodium score and decompensated cirrhosis status. Among patients with cirrhosis, problematic drinking was associated with worse LDQoL, especially in the domains of memory/concentration and health distress. Assessment and awareness of cognitive deficits and negative emotionality within the context of cirrhosis and problematic drinking may help clinicians provide better integrated care for this population.
Authors: Luk, Jeremy W;Khalili, Mandana;et al.
Hepatol Commun. 2024 Feb 01;8(2). Epub 2024-02-03.
Race, community disadvantage, and cognitive decline: Findings from KHANDLE and STAR
Community disadvantage is associated with late-life cognition. Few studies examine its contribution to racial disparities in cognition/cognitive change. Inverse probability weighted models estimated expected mean differences in cognition/cognitive change attributed to residing in less advantaged communities, defined as cohort top quintile of Area Deprivation Indices (ADI): childhood 66-100; adulthood ADI 5-99). Interactions by race tested. More Black participants resided in less advantaged communities. Semantic memory would be lower if all participants had resided in less advantaged childhood (b = -0.16, 95% confidence interval [CI] = -0.30, -0.03) or adulthood (b = -0.14, 95% CI = -0.22, -0.04) communities. Race interactions indicated that, among Black participants, less advantaged childhood communities were associated with higher verbal episodic memory (interaction p-value = 0.007) and less advantaged adulthood communities were associated with lower semantic memory (interaction p-value = 0.002). Examining racial differences in levels of community advantage and late-life cognitive decline is a critical step toward unpacking community effects on cognitive disparities.
Authors: Peterson, Rachel L;Pejak, Rebecca;George, Kristen M;Gilsanz, Paola;Ko, Michelle;Meyer, Oanh L;Mayeda, Elizabeth Rose;Kind, Amy;Whitmer, Rachel A
Alzheimers Dement. 2024 Feb;20(2):904-913. Epub 2023-10-10.
Association of initial opioid prescription duration and an opioid refill by pain diagnosis: Evidence from outpatient settings in ten US health systems
The Centers for Disease Control and Prevention’s 2022 Clinical Practice Guideline for Prescribing Opioids for Pain cautioned that inflexible opioid prescription duration limits may harm patients. Information about the relationship between initial opioid prescription duration and a subsequent refill could inform prescribing policies and practices to optimize patient outcomes. We assessed the association between initial opioid duration and an opioid refill prescription. We conducted a retrospective cohort study of adults ≥19 years of age in 10 US health systems between 2013 and 2018 from outpatient care with a diagnosis for back pain without radiculopathy, back pain with radiculopathy, neck pain, joint pain, tendonitis/bursitis, mild musculoskeletal pain, severe musculoskeletal pain, urinary calculus, or headache. Generalized additive models were used to estimate the association between opioid days’ supply and a refill prescription. Overall, 220,797 patients were prescribed opioid analgesics upon an outpatient visit for pain. Nearly a quarter (23.5%) of the cohort received an opioid refill prescription during follow-up. The likelihood of a refill generally increased with initial duration for most pain diagnoses. About 1 to 3 fewer patients would receive a refill within 3 months for every 100 patients initially prescribed 3 vs. 7 days of opioids for most pain diagnoses. The lowest likelihood of refill was for a 1-day supply for all pain diagnoses, except for severe musculoskeletal pain (9 days’ supply) and headache (3-4 days’ supply). Long-term prescription opioid use increased modestly with initial opioid prescription duration for most but not all pain diagnoses examined.
Authors: Nguyen, Anh P;Metz, Verena E;Campbell, Cynthia I;Campbell, Cynthia I;et al.
Prev Med. 2024 Feb;179:107828. Epub 2023-12-16.
Hoarding Symptoms in Late Life Depression are Associated With Greater Executive Dysfunction and Disability and Poorer Response to Depression Treatment
Late life depression (LLD) and hoarding disorder (HD) are common in older adults and characterized by executive dysfunction and disability. We aimed to determine the frequency of co-occurring HD in LLD and examine hoarding severity as an additional contributor to executive dysfunction, disability, and response to psychotherapy for LLD. Cross-sectional. Outpatient psychiatry program. Eighty-three community-dwelling adults ages 65-90 with LLD. Problem-solving therapy. Measures of executive function, disability, depression, and hoarding severity were completed at post-treatment. Pearson’s chi-squared tests evaluated group differences in rates of cognitive impairment, disability, and depression treatment response between participants with HD (LLD+HD) and LLD only. Separate linear regressions assessed associations between hoarding severity and executive function, disability, and psychotherapy response. Covariates included age, education, gender, and depression severity. 30.1% (25/83) of LLD participants met HD criteria. Relative to LLD, LLD+HD participants demonstrated greater impairment rates on measures of executive function (Letter-Number-Sequencing, X2(1)=4.0, p = 0.045; Stroop-Interference, X2(1) = 4.8, p = 0.028). Greater hoarding severity was associated with poorer executive functioning performance (Letter-Number-Sequencing (t[70] = -2.1, β = -0.05, p = 0.044), Digit-Span (t[71] = -2.4, β = -0.07, p = 0.019), Letter-Fluency (t[ 71] = -2.8, β = -0.24, p = 0.006)). Rates of disability were significantly higher for LLD+HD (88.0%) than LLD (62.3%), (X2[1] = 5.41, p = 0.020) and higher hoarding severity was related to greater disability (t[72] = 2.97, β = 0.13, p = 0.004). Depression treatment response rates were significantly lower for LLD+HD (24.0%) compared to LLD (48.3%), X2(1) = 4.26, p = 0.039, and HD status predicted psychotherapy response, t(67) = -2.15, β = -15.6, p = 0.035. We found 30.1% co-occurrence of HD in LLD, which was accompanied by greater executive dysfunction, disability, and poorer response to depression treatment. Results underscore the need for increased screening of hoarding behaviors in LLD and tailored interventions for this LLD+HD group.
Authors: Kassel, Michelle T;Kryza-Lacombe, Maria;Insel, Philip S;Rhodes, Emma;Satre, Derek D;Nelson, J Craig;Tosun, Duygu;Mathews, Carol A;Mackin, R Scott
Am J Geriatr Psychiatry. 2024 Feb;32(2):137-147. Epub 2023-09-01.
Telehealth Collaborative Care Led by Clinical Pharmacists for People With Psychosis or Bipolar Disorder: A Propensity Weighted Comparison With Usual Psychiatric Care
Objective: People with psychosis or bipolar disorder (severe and persistent mental illness [SPMI]) are at high risk for poor psychiatric and chronic illness outcomes, which could be ameliorated through improved health care quality. This study assessed whether a telehealth, collaborative care program managed by psychiatric clinical pharmacists (SPMI Population Care) was associated with improved health care quality for adults with SPMI in a large California health system. Methods: This retrospective cohort study used electronic health record data to compare 968 program enrollees at 6 demonstration sites (Population Care) to 8,339 contemporaneous patients with SPMI at 6 non-program sites (Usual Care). SPMI diagnoses were based on ICD-10-CM diagnostic codes. Primary outcomes were optimal psychotropic medication adherence, guideline-recommended glycemic screening, annual psychiatrist visit, and emergency department use. Difference-in-difference analyses assessed change in outcomes from 12 months pre- to 12 months post-enrollment using overlap weighting with high dimensional propensity scores to balance participant characteristics across groups. Participant data were collected from January 1, 2020, to June 30, 2022. Results: From pre- to post-enrollment, Population Care was associated with greater achievement of psychotropic medication adherence and glycemic screening (+6 and +9 percentage points), but unexpectedly with a decrease in annual psychiatrist visits (-6 percentage points) and no significant change in emergency department use, relative to Usual Care. More than 75% of Population Care participants attended an intake and ≥ 1 follow-up visits. Participants with psychosis (26% of sample) had similar results as those with bipolar disorder. Conclusions: Clinical pharmacist-led telehealth collaborative care has potential to improve psychopharmacologic treatment adherence and recommended disease preventive screening for people with psychosis or bipolar disorder.
Authors: Iturralde, Esti;Fazzolari, Lisa;Slama, Natalie E;Alexeeff, Stacey E;Sterling, Stacy A;Awsare, Sameer;Koshy, Maria T;Shia, Macy
J Clin Psychiatry. 2024 Jan 29;85(1). Epub 2024-01-29.
A patient activation intervention in primary care for patients with chronic pain on long term opioid therapy: results from a randomized control trial
Given significant risks associated with long-term prescription opioid use, there is a need for non-pharmacological interventions for treating chronic pain. Activating patients to manage chronic pain has the potential to improve health outcomes. The ACTIVATE study was designed to evaluate the effectiveness of a 4-session patient activation intervention in primary care for patients on long-term opioid therapy. The two-arm, pragmatic, randomized trial was conducted in two primary care clinics in an integrated health system from June 2015-August 2018. Consenting participants were randomized to the intervention (n = 189) or usual care (n = 187). Participants completed online and interviewer-administered surveys at baseline, 6- and 12- months follow-up. Prescription opioid use was extracted from the EHR. The primary outcome was patient activation assessed by the Patient Activation Measure (PAM). Secondary outcomes included mood, function, overall health, non-pharmacologic pain management strategies, and patient portal use. We conducted a repeated measure analysis and reported between-group differences at 12 months. At 12 months, the intervention and usual care arms had similar PAM scores. However, compared to usual care at 12 months, the intervention arm demonstrated: less moderate/severe depression (odds ratio [OR] = 0.40, 95%CI 0.18-0.87); higher overall health (OR = 3.14, 95%CI 1.64-6.01); greater use of the patient portal’s health/wellness resources (OR = 2.50, 95%CI 1.42-4.40) and lab/immunization history (OR = 2.70, 95%CI 1.29-5.65); and greater use of meditation (OR = 2.72; 95%CI 1.61-4.58) and exercise/physical therapy (OR = 2.24, 95%CI 1.29-3.88). At 12 months, the intervention arm had a higher physical health measure (mean difference 1.63; 95%CI: 0.27-2.98). This trial evaluated the effectiveness of a primary care intervention in improving patient activation and patient-reported outcomes among adults with chronic pain on long-term opioid therapy. Despite a lack of improvement in patient activation, a brief intervention in primary care can improve outcomes such as depression, overall health, non-pharmacologic pain management, and engagement with the health system. The study was registered on 10/27/14 on ClinicalTrials.gov (NCT02290223).
Authors: Does, Monique B;Adams, Sara R;Kline-Simon, Andrea H;Marino, Catherine;Charvat-Aguilar, Nancy;Weisner, Constance M;Rubinstein, Andrea L;Ghadiali, Murtuza;Cowan, Penney;Young-Wolff, Kelly C;Campbell, Cynthia I
BMC Health Serv Res. 2024 Jan 22;24(1):112. Epub 2024-01-22.
Cardiovascular Disease Risk Factor Control in People With and Without Human Immunodeficiency Virus
Management of hypertension, dyslipidemia, diabetes and other modifiable factors may mitigate the cardiovascular disease (CVD) risk in people with human immunodeficiency virus (HIV, PWH) compared with people without HIV (PWoH). This was a retrospective cohort study of 8285 PWH and 170 517 PWoH from an integrated health system. Risk factor control was measured using a novel disease management index (DMI) accounting for amount/duration above treatment goals (0% to 100% [perfect control]), including 2 DMIs for hypertension (diastolic and systolic blood pressure), 3 for dyslipidemia (low-density lipoprotein, total cholesterol, triglycerides), and 1 for diabetes (HbA1c). CVD risk by HIV status was evaluated overall and in subgroups defined by DMIs, smoking, alcohol use, and overweight/obesity in adjusted Cox proportional hazards models. PWH and PWoH had similar DMIs (80%-100%) except for triglycerides (worse for PWH) and HbA1c (better for PWH). In adjusted models, PWH had an elevated risk of CVD compared with PWoH (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.07-1.31). This association was attenuated in subgroups with controlled dyslipidemia and diabetes but remained elevated for PWH with controlled hypertension or higher total cholesterol. The strongest HIV status association with CVD was seen in the subgroup with frequent unhealthy alcohol use (HR, 2.13; 95% CI, 1.04-4.34). Control of dyslipidemia and diabetes, but not hypertension, attenuated the HIV status association with CVD. The strong association of HIV and CVD with frequent unhealthy alcohol use suggests enhanced screening and treatment of alcohol problems in PWH is warranted.
Authors: Silverberg, Michael J;Alexeeff, Stacey E;Flamm, Jason A;Lam, Jennifer O;Sterling, Stacy A;Satre, Derek D;Satre, Derek D;et al.
Clin Infect Dis. 2024 Jan 16.
Multi-ancestry genome-wide meta-analysis identifies novel basal cell carcinoma loci and shared genetic effects with squamous cell carcinoma
Basal cell carcinoma (BCC) is one of the most common malignancies worldwide, yet its genetic determinants are incompletely defined. We perform a European ancestry genome-wide association (GWA) meta-analysis and a Hispanic/Latino ancestry GWA meta-analysis and meta-analyze both in a multi-ancestry GWAS meta-analysis of BCC, totaling 50,531 BCC cases and 762,234 controls from four cohorts (GERA, Mass-General Brigham Biobank, UK Biobank, and 23andMe research cohort). Here we identify 122 BCC-associated loci, of which 36 were novel, and subsequently fine-mapped these associations. We also identify an association of the well-known pigment gene SLC45A2 as well as associations at RCC2 and CLPTM1L with BCC in Hispanic/Latinos. We examine these BCC loci for association with cutaneous squamous cell carcinoma (cSCC) in 16,407 SCC cases and 762,486 controls of European ancestry, and 33 SNPs show evidence of association. Our study findings provide important insights into the genetic basis of BCC and cSCC susceptibility.
Authors: Choquet, Hélène;Jiang, Chen;Yin, Jie;Kim, Yuhree;Hoffmann, Thomas J;23andMe Research Team,;Jorgenson, Eric;Asgari, Maryam M
Commun Biol. 2024 Jan 05;7(1):33. Epub 2024-01-05.
Multi-ancestry transcriptome-wide association studies of cognitive function, white matter hyperintensity, and Alzheimer’s disease
Genetic variants increase the risk of neurocognitive disorders in later life including Vascular Dementia (VaD) and Alzheimer’s disease (AD), but the precise relationships between genetic risk factors and underlying disease etiology are not well understood. Transcriptome-wide association studies (TWAS) can be leveraged to better characterize the genes and biological pathways underlying genetic influences on disease. To date, almost all existing TWAS have been conducted using expression studies from individuals of a single genetic ancestry, primarily European. Using the joint likelihood-based inference framework in Multi-ancEstry TRanscriptOme-wide analysis (METRO), we leveraged gene expression data from European (EA) and African ancestries (AA) to identify genes associated with general cognitive function, white matter hyperintensity (WMH), and AD. Regions were fine-mapped using Fine-mapping Of CaUsal gene Sets (FOCUS). We identified 266, 23, 69, and 2 genes associated with general cognitive function, WMH, AD (using EA GWAS summary statistics), and AD (using AA GWAS), respectively (Bonferroni-corrected alpha=P<2.9−10-6), some of which were previously identified. Enrichment analysis showed that many of the identified genes were in pathways related to innate immunity, vascular dysfunction, and neuroinflammation. Further, downregulation of ICA1L was associated with higher WMH and with AD, indicating its potential contribution to overlapping AD and VaD neuropathology. To our knowledge, our study is the first TWAS of cognitive function and neurocognitive disorders that used expression mapping studies in multiple ancestries. This work may expand the benefits of TWAS studies beyond a single ancestry group and help to identify gene targets for pharmaceutical or preventative treatment for dementia.
Authors: Chaar, Dima L;Smith, JA;et al.
medRxiv [Preprint]. 2023 Jan 01:2024.01.03.24300768. doi: 10.1101/2024.01.03.24300768
Evaluation of racial and ethnic heterogeneity in the associations of sleep quality and sleep apnea risk with cognitive function and cognitive decline
The prevalence of poor sleep quality and sleep apnea differs by race and ethnicity and may contribute to racial disparities in cognitive aging. We investigated whether sleep quality and sleep apnea risk were associated with cognitive function and decline and whether the associations differed by race/ethnicity. Participants from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE; N = 1690; mean age: 75.7 years) study, a cohort of Asian, Black, Latino, and White participants, completed a modified Pittsburgh Sleep Quality Index assessing subjective sleep quality, latency, duration, disturbances, sleep medication use, and daytime dysfunction. Sleep apnea risk was measured by questions about snoring, tiredness, and whether apnea was observed. Executive function and verbal episodic memory were assessed at three time points over an average of 2.7 years with the Spanish and English Neuropsychological Assessment Scale. We fit linear mixed-effect models and stratified analyses by race/ethnicity. Higher sleep apnea risk was associated with faster declines in verbal episodic memory (β^ sleep apnea = -0.02, 95% confidence interval [CI], -0.04, -0.001) but not in executive function. Poorer sleep quality was associated with lower levels of and faster decline in executive function but not in verbal episodic memory. Race/ethnicity modified these associations: compared to estimated effects among White participants, poorer global sleep quality (β^ sleep*time = -0.02, 95% CI, -0.02, -0.01) was associated with larger effects on decline in executive function among Black participants. Estimated effects of some individual sleep quality components were also modified by race/ethnicity; for example, sleep medication use was associated with faster declines in executive function (β^ sleep*time = -0.05, 95% CI, -0.07, -0.03) and verbal episodic memory β^ sleep*time = -0.04, 95% CI, -0.07, -0.02) among Black participants compared to White participants. Observational evidence indicates sleep quality is a promising target for addressing racial/ethnic disparities in cognitive aging, especially among Black older adults. Sleep apnea risk was associated with faster declines in verbal episodic memory but not executive function among all participants.Global sleep quality was associated with lower levels of and faster decline in executive function but not verbal episodic memory among all participants.Black older adults were particularly susceptible to the estimated adverse cognitive impacts of global sleep quality, particularly the use of sleep medication.
Authors: Chen, Ruijia;Gilsanz, Paola;Glymour, M Maria;et al.
Alzheimers Dement (N Y). 2024 Jan-Mar;10(1):e12441. Epub 2024-02-11.
Agreement Between Self-reports and Urine Toxicology Measures of Illicit Methamphetamine and Cocaine Use During Early Pregnancy
This study aimed to assess agreement between self-report and urine toxicology measures assessing use of 2 illicit simulants (methamphetamine and cocaine) during early pregnancy. This cross-sectional study of 203,053 pregnancies from 169,709 individuals receiving prenatal care at Kaiser Permanente Northern California between January 1, 2011, and December 31, 2019, assessed agreement ( κ , sensitivity, and specificity) between self-reported frequency and urine toxicology measures of methamphetamine and cocaine early in pregnancy. Prenatal use of the illicit stimulants was rare according to toxicology (n = 244 [0.12%]) and self-report measures (n = 294 [0.14%]). Agreement between these measures was low ( κ < 0.20). Of the 498 positive pregnancies, 40 (8.03%) screened positive on both measures, 204 (40.96%) screened positive on toxicology tests only, and 254 (51.00%) screened positive by self-report only. Relative to toxicology tests, sensitivity of any self-reported use was poor with 16.39% (95% confidence interval [CI], 11.75%-21.04%) of pregnancies with a positive toxicology test self-reporting any use in pregnancy. Relative to self-report, sensitivity of toxicology tests was also poor with 13.61% (95% CI, 9.69%-17.52%) of pregnancies who self-reported any use having positive urine toxicology tests. The sensitivity improved slightly at higher frequencies of self-reported use: daily, 17.50% (95% CI, 5.72%-29.29%); weekly, 25.00% (95% CI, 11.58%-38.42%); and monthly or less, 11.06% (95% CI, 6.89%-15.23%). Specificity was high (>99%), reflecting the high negative rate of use. Findings suggest that using self-report and toxicology measures in combination likely provides the most accurate information on methamphetamine and cocaine use in early pregnancy. Findings also highlight the need to provide supportive nonstigmatizing environments in which pregnant individuals feel comfortable disclosing substance use without fear of punishment.
Authors: Sujan, Ayesha C;Avalos, Lyndsay A;Young-Wolff, Kelly C;Young-Wolff, Kelly C;et al.
J Addict Med. 2024 Jan-Feb 01;18(1):28-32. Epub 2023-10-05.
Timing and level of educational attainment and late-life cognition in the KHANDLE study
The timing of educational attainment may modify its effects on late-life cognition, yet most studies evaluate education only at a single time point. Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study cohort participants (N = 554) reported educational attainment (dichotomized at any college education) at two time points, and we classified them as having low, high, or later-life high educational attainment. Linear mixed-effects models estimated associations between educational attainment change groups and domain-specific cognitive outcomes (z-standardized). Compared to low educational attainment, high (β= 0.59 SD units; 95% confidence interval [CI]: 0.39, 0.79) and later-life high educational attainment (β = 0.22; 95% CI: 0.00, 0.44) were associated with higher executive function. Only high educational attainment was associated with higher verbal episodic memory (β = 0.27; 95% CI: 0.06, 0.48). Level and timing of educational attainment are both associated with domain-specific cognition. A single assessment for educational attainment may inadequately characterize protective associations with late-life cognition. Few studies have examined both level and timing of educational attainment on cognition. Marginalized populations are more likely to attain higher education in adulthood. Higher educational attainment in late life is also associated with higher cognition.
Authors: Soh, Yenee;Quesenberry, Charles P;Gilsanz, Paola;Gilsanz, Paola;et al.
Alzheimers Dement. 2024 Jan;20(1):593-600. Epub 2023-09-26.
Development of the Protective Strategies for Psychedelics Scale: A novel inventory to assess safety strategies in the context of psychedelics
Individuals who use psychedelics take efforts to mitigate unintended consequences. Despite the demonstrated utility of analogous protective behavioral strategies (PBS) assessments for other substances, no standardized scale exists to capture these protective strategies for psychedelic use. The present study addresses a notable gap concerning the assessment of psychedelic use, specifically by developing a scale measuring the protective strategies employed around use, called the Protective Strategies for Psychedelics Scale (PSPS). A sample (Mage = 36.85 years old, standard deviation = 10.3; male = 61.9%; White = 85.2%) of 434 adults with lifetime use of psychedelics reported on initial qualitatively developed items for the PSPS, PBS scales for cannabis and alcohol, and use of alcohol, cannabis, and psychedelics. Iterative principal components analyses began with 37 items and yielded a 32-item two-factor solution demonstrating excellent internal reliability (Cronbach’s α = .95) and accounted for 51.3% of the variance. Nineteen items loaded on PSPS factor 1, which focused on long-term preparation, emphasizing strategies focused on mood/intentions, preparing the substance, environment, and scheduling episode of use; 13 items loaded on factor 2, which focused on short-term preparation, highlighting strategies surrounding social context, health, and other substances. The PSPS demonstrated convergent validity with validated PBS scales for cannabis and alcohol (r = 0.71-0.79, p < 0.001), and was moderately associated with lifetime psychedelic use (r = 0.28, p < 0.001). The PSPS demonstrates promising psychometric properties, and future work validating the scale for diverse samples across research and clinical settings is warranted.
Authors: Mian, Maha N;Altman, Brianna R;Low, Fiona;Earleywine, Mitch
J Psychopharmacol. 2024 Jan;38(1):101-109. Epub 2023-12-04.
Development and validation of a machine learning model using electronic health records to predict trauma- and stressor-related psychiatric disorders after hospitalization with sepsis
A significant minority of individuals develop trauma- and stressor-related disorders (TSRD) after surviving sepsis, a life-threatening immune response to infections. Accurate prediction of risk for TSRD can facilitate targeted early intervention strategies, but many existing models rely on research measures that are impractical to incorporate to standard emergency department workflows. To increase the feasibility of implementation, we developed models that predict TSRD in the year after survival from sepsis using only electronic health records from the hospitalization (n = 217,122 hospitalizations from 2012-2015). The optimal model was evaluated in a temporally independent prospective test sample (n = 128,783 hospitalizations from 2016-2017), where patients in the highest-risk decile accounted for nearly one-third of TSRD cases. Our approach demonstrates that risk for TSRD after sepsis can be stratified without additional assessment burden on clinicians and patients, which increases the likelihood of model implementation in hospital settings.
Authors: Papini, Santiago;Iturralde, Esti;Lu, Yun;Greene, John D;Barreda, Fernando;Sterling, Stacy A;Liu, Vincent X
Transl Psychiatry. 2023 Dec 18;13(1):400. Epub 2023-12-18.
Clinical impacts of an integrated electronic health record-based smoking cessation intervention during hospitalisation
To assess the effects of an electronic health record (EHR) intervention that prompts the clinician to prescribe nicotine replacement therapy (NRT) at hospital admission and discharge in a large integrated health system. Retrospective cohort study using interrupted time series (ITS) analysis leveraging EHR data generated before and after implementation of the 2015 EHR-based intervention. Kaiser Permanente Northern California, a large integrated health system with 4.2 million members. Current smokers aged ≥18 hospitalised for any reason. EHR-based clinical decision supports that prompted the clinician to order NRT on hospital admission (implemented February 2015) and discharge (implemented September 2015). Primary outcomes included the monthly percentage of admitted smokers with NRT orders during admission and at discharge. A secondary outcome assessed patient quit rates within 30 days of hospital discharge as reported during discharge follow-up outpatient visits. The percentage of admissions with NRT orders increased from 29.9% in the year preceding the intervention to 78.1% in the year following (41.8% change, 95% CI 38.6% to 44.9%) after implementation of the admission hard-stop intervention compared with the baseline trend (ITS estimate). The percentage of discharges with NRT orders increased acutely at the time of both interventions (admission intervention ITS estimate 15.5%, 95% CI 11% to 20%; discharge intervention ITS estimate 13.4%, 95% CI 9.1% to 17.7%). Following the implementation of the discharge intervention, there was a small increase in patient-reported quit rates (ITS estimate 5.0%, 95% CI 2.2% to 7.8%). An EHR-based clinical decision-making support embedded into admission and discharge documentation was associated with an increase in NRT prescriptions and improvement in quit rates. Similar systemic EHR interventions can help improve smoking cessation efforts after hospitalisation.
Authors: Banerjee, Somalee;Alabaster, Amy;Adams, Alyce S;Fogelberg, Renee;Patel, Nihar;Young-Wolff, Kelly
BMJ Open. 2023 Dec 06;13(12):e068629. Epub 2023-12-06.
Nurse Care Management for Opioid Use Disorder Treatment: The PROUD Cluster Randomized Clinical Trial
Few primary care (PC) practices treat patients with medications for opioid use disorder (OUD) despite availability of effective treatments. To assess whether implementation of the Massachusetts model of nurse care management for OUD in PC increases OUD treatment with buprenorphine or extended-release injectable naltrexone and secondarily decreases acute care utilization. The Primary Care Opioid Use Disorders Treatment (PROUD) trial was a mixed-methods, implementation-effectiveness cluster randomized clinical trial conducted in 6 diverse health systems across 5 US states (New York, Florida, Michigan, Texas, and Washington). Two PC clinics in each system were randomized to intervention or usual care (UC) stratified by system (5 systems were notified on February 28, 2018, and 1 system with delayed data use agreement on August 31, 2018). Data were obtained from electronic health records and insurance claims. An implementation monitoring team collected qualitative data. Primary care patients were included if they were 16 to 90 years old and visited a participating clinic from up to 3 years before a system’s randomization date through 2 years after. The PROUD intervention included 3 components: (1) salary for a full-time OUD nurse care manager; (2) training and technical assistance for nurse care managers; and (3) 3 or more PC clinicians agreeing to prescribe buprenorphine. The primary outcome was a clinic-level measure of patient-years of OUD treatment (buprenorphine or extended-release injectable naltrexone) per 10 000 PC patients during the 2 years postrandomization (follow-up). The secondary outcome, among patients with OUD prerandomization, was a patient-level measure of the number of days of acute care utilization during follow-up. During the baseline period, a total of 130 623 patients were seen in intervention clinics (mean [SD] age, 48.6 [17.7] years; 59.7% female), and 159 459 patients were seen in UC clinics (mean [SD] age, 47.2 [17.5] years; 63.0% female). Intervention clinics provided 8.2 (95% CI, 5.4-∞) more patient-years of OUD treatment per 10 000 PC patients compared with UC clinics (P = .002). Most of the benefit accrued in 2 health systems and in patients new to clinics (5.8 [95% CI, 1.3-∞] more patient-years) or newly treated for OUD postrandomization (8.3 [95% CI, 4.3-∞] more patient-years). Qualitative data indicated that keys to successful implementation included broad commitment to treat OUD in PC from system leaders and PC teams, full financial coverage for OUD treatment, and straightforward pathways for patients to access nurse care managers. Acute care utilization did not differ between intervention and UC clinics (relative rate, 1.16; 95% CI, 0.47-2.92; P = .70). The PROUD cluster randomized clinical trial intervention meaningfully increased PC OUD treatment, albeit unevenly across health systems; however, it did not decrease acute care utilization among patients with OUD. ClinicalTrials.gov Identifier: NCT03407638.
Authors: Wartko, Paige D;Campbell, Cynthia I;Burganowski, Rachael P;et al.
JAMA Intern Med. 2023 Dec 01;183(12):1343-1354.
Risk factors for inguinal hernia repair among US adults
To investigate demographic, clinical, and behavioral risk factors for undergoing inguinal hernia repair within a large and ethnically diverse cohort. We conducted a retrospective case-control study from 2007 to 2020 on 302,532 US individuals from a large, integrated healthcare delivery system with electronic health records, who participated in a survey of determinants of health. Participants without diagnosis or procedure record of an inguinal hernia at enrollment were included. We then assessed whether demographic (age, sex, race/ethnicity), clinical, and behavioral factors (obesity status, alcohol use, cigarette smoking and physical activity) were predictors of undergoing inguinal hernia repair using survival analyses. Risk factors showing statistical significance (P < 0.05) in the univariate models were added to a multivariate model. We identified 7314 patients who underwent inguinal hernia repair over the study period, with a higher incidence in men (6.31%) compared to women (0.53%). In a multivariate model, a higher incidence of inguinal hernia repair was associated with non-Hispanic white race/ethnicity, older age, male sex (aHR = 13.55 [95% confidence interval 12.70-14.50]), and more vigorous physical activity (aHR = 1.24 [0.045]), and alcohol drinker status (aHR = 1.05 [1.00-1.11]); while African-American (aHR = 0.69 [0.59-0.79]), Hispanic/Latino (aHR = 0.84 [0.75-0.91]), and Asian (aHR = 0.35 [0.31-0.39]) race/ethnicity, obesity (aHR = 0.33 [0.31-0.36]) and overweight (aHR = 0.71 [0.67-0.75]) were associated with a lower incidence. The use of cigarette was significantly associated with a higher incidence of inguinal hernia repair in women (aHR 1.23 [1.09-1.40]), but not in men (aHR 0.96 [0.91-1.02]). Inguinal hernia repair is positively associated with non-Hispanic white race/ethnicity, older age, male sex, increased physical activity, alcohol consumption and tobacco use (only in women); while negatively associated with obesity and overweight status. Findings from this large and ethnically diverse study may support future prediction tools to identify patients at high risk of this surgery.
Authors: Cowan, B;Kvale, M;Yin, J;Patel, S;Jorgenson, E;Mostaedi, R;Choquet, H
Hernia. 2023 Dec;27(6):1507-1514. Epub 2023-11-10.
Risk profiles of adults with heavy alcohol use: Drinking patterns, behavioral and metabolic factors, health problems, and racial and ethnic disparities
Heavy alcohol use is a growing risk factor for chronic disease, yet little is known about its co-occurrence with other risk factors and health problems. This study aimed to identify risk profiles of adults with heavy alcohol use and examined potential disparities by race and ethnicity. This cross-sectional study included 211,333 adults with heavy alcohol use (in excess of daily or weekly limits recommended by National Institute on Alcohol Abuse and Alcoholism) between June 1, 2013 and December 31, 2014 in Kaiser Permanente Northern California. Latent class analysis was used to examine how heavy drinking patterns clustered with other behavioral and metabolic risk factors and health problems to form risk profiles. Multinomial logistic regression models were fit to examine associations between race, ethnicity, and risk profiles. A 5-class model was selected as best fitting the data and representing clinically meaningful risk profiles: (1) “heavy daily drinking and lower health risks” (DAILY, 44.3%); (2) “substance use disorder and mental health disorder” (SUD/MH, 2.3%); (3) “heavy weekly drinking and lower health risks” (WEEKLY, 19.6%); (4) “heavy daily drinking and more health risks” (DAILY-R, 18.5%); (5) “heavy weekly drinking and more health risks” (WEEKLY-R, 15.3%). American Indian or Alaska Native (AIAN) and Black patients had higher odds than White patients of being in the SUD/MH, DAILY-R, and WEEKLY-R profiles than the DAILY profile. AIAN, Black, and Latino/Hispanic patients had higher odds than White patients of being in the SUD/MH, DAILY-R, and WEEKLY-R profiles rather than the WEEKLY profile. AIAN, Black, and Latino/Hispanic patients with self-reported heavy drinking were more likely to be in risk profiles with greater alcohol consumption, more health risks, and higher morbidity. Targeted, culturally appropriate interventions for heavy alcohol use that may address other modifiable risk factors are needed to work towards health equity.
Authors: Palzes, Vanessa A;Chi, Felicia W;Weisner, Constance;Kline-Simon, Andrea H;Satre, Derek D;Sterling, Stacy
Alcohol Clin Exp Res (Hoboken). 2023 Dec;47(12):2301-2312. Epub 2023-10-27.
Low- and High-Density Lipoprotein Cholesterol and Dementia Risk Over 17 Years of Follow-up Among Members of a Large Health Care Plan
The associations of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) with dementia risk in later life may be complex, and few studies have sufficient data to model nonlinearities or adequately adjust for statin use. We evaluated the observational associations of HDL-C and LDL-C with incident dementia in a large and well-characterized cohort with linked survey and electronic health record (EHR) data. Kaiser Permanente Northern California health plan members aged 55 years and older who completed a health behavior survey between 2002 and 2007, had no history of dementia before the survey, and had laboratory measurements of cholesterol within 2 years after survey completion were followed up through December 2020 for incident dementia (Alzheimer disease-related dementia [ADRD]; Alzheimer disease, vascular dementia, and/or nonspecific dementia) based on ICD-9 or ICD-10 codes in EHRs. We used Cox models for incident dementia with follow-up time beginning 2 years postsurvey (after cholesterol measurement) and censoring at end of membership, death, or end of study period. We evaluated nonlinearities using B-splines, adjusted for demographic, clinical, and survey confounders, and tested for effect modification by baseline age or prior statin use. A total of 184,367 participants [mean age at survey = 69.5 years, mean HDL-C = 53.7 mg/dL (SD = 15.0), mean LDL-C = 108 mg/dL (SD = 30.6)] were included. Higher and lower HDL-C values were associated with elevated ADRD risk compared with the middle quantile: HDL-C in the lowest quintile was associated with an HR of 1.07 (95% CI 1.03-1.11), and HDL-C in the highest quintile was associated with an HR of 1.15 (95% CI 1.11-1.20). LDL-C was not associated with dementia risk overall, but statin use qualitatively modified the association. Higher LDL-C was associated with a slightly greater risk of ADRD for statin users (53% of the sample, HR per 10 mg/dL increase = 1.01, 95% CI 1.01-1.02) and a lower risk for nonusers (HR per 10 mg/dL increase = 0.98; 95% CI 0.97-0.99). There was evidence for effect modification by age with linear HDL-C (p = 0.003) but not LDL-C (p = 0.59). Both low and high levels of HDL-C were associated with elevated dementia risk. The association between LDL-C and dementia risk was modest.
Authors: Ferguson, Erin L;Gilsanz, Paola;Schaefer, Catherine A;Glymour, M Maria;et al.
Neurology. 2023 Nov 21;101(21):e2172-e2184. Epub 2023-10-04.
Neonatal Outcomes Associated with In Utero Cannabis Exposure: A Population-Based Retrospective Cohort Study
The full spectrum of associations between in utero cannabis exposure and adverse neonatal outcomes is still unclear. This study evaluates associations between in utero cannabis exposure and neonatal outcomes. This population-based retrospective cohort study of singleton births among Kaiser Permanente Northern California members (January 1, 2011- July 31, 2020) included parent-infant dyads in which the pregnant parent was screened for cannabis use as part of standard prenatal care, generally upon entrance into care. Data were ascertained from electronic health records. Generalized estimating equation models were adjusted for sociodemographic characteristics, other non-cannabis prenatal substance use, medical and mental health comorbidities, and adequacy of prenatal care. In utero cannabis exposure was defined as self-report since becoming pregnant and/or a positive urine toxicology test for cannabis at any time during pregnancy (yes/no; primary) and frequency of use (self-report daily, weekly, ≤ monthly, never, unknown; secondary). Neonatal outcomes included low birth weight (LBW), small for gestational age (SGA), preterm birth, neonatal intensive care unit (NICU) admission, and infant respiratory support. Of 364,924 infants, 22,624 (6.2%) were exposed to cannabis in utero. After adjustment for potential confounders including in utero exposure to other substances, in utero exposure to cannabis was associated with greater odds of LBW (adjusted odds ratio [aOR],1.20; 95%CI, 1.12-1.28), SGA (aOR, 1.24; 95%CI, 1.18-1.30), preterm birth (<37 weeks; aOR,1.06; 95%CI, 1.00-1.13), and NICU admission (aOR,1.06; 95%CI, 1.01-1.11). There was a suggestive association with early preterm birth (<34 weeks; aOR, 1.11; 95%CI, 1.00-1.23, P=.055), but no significant association with respiratory support (aOR,1.07; 95%CI, 0.97-1.18). Dose-response analysis found an increasing likelihood of LBW and SGA with increasing frequency of prenatal cannabis use by the pregnant individual. Sensitivity analyses further supported an increased likelihood of LBW and SGA although associations with other outcomes did not reach significance. In utero cannabis exposure was associated with an increased likelihood of LBW, SGA, preterm birth, and NICU admission. Clinicians should counsel individuals who are pregnant or considering pregnancy about the potential adverse neonatal health outcomes associated with prenatal cannabis use.
Authors: Avalos, Lyndsay A;Adams, Sara R;Alexeeff, Stacey E;Oberman, Nina R;Does, Monique B;Ansley, Deborah;Goler, Nancy;Padon, Alisa A;Silver, Lynn D;Young-Wolff, Kelly C
Am J Obstet Gynecol. 2023 Nov 18.
Prescription Opioid Dose Reductions and Potential Adverse Events: a Multi-site Observational Cohort Study in Diverse US Health Systems
In response to the opioid crisis in the United States, population-level prescribing of opioids has been decreasing; there are concerns, however, that dose reductions are related to potential adverse events. Examine associations between opioid dose reductions and risk of 1-month potential adverse events (emergency department (ED) visits, opioid overdose, benzodiazepine prescription fill, all-cause mortality). This observational cohort study used electronic health record and claims data from eight United States health systems in a prescription opioid registry (Clinical Trials Network-0084). All opioid fills (excluding buprenorphine) between 1/1/2012 and 12/31/2018 were used to identify baseline periods with mean morphine milligram equivalents daily dose of ≥ 50 during six consecutive months. We identified 60,040 non-cancer patients with ≥ one 2-month dose reduction period (600,234 unique dose reduction periods). Analyses examined associations between dose reduction levels (1- < 15%, 15- < 30%, 30- < 100%, 100% over 2 months) and potential adverse events in the month following a dose reduction using logistic regression analysis, adjusting for patient characteristics. Overall, dose reduction periods involved mean reductions of 18.7%. Compared to reductions of 1- < 15%, dose reductions of 30- < 100% were associated with higher odds of ED visits (OR 1.14, 95% CI 1.10, 1.17), opioid overdose (OR 1.41, 95% CI 1.09-1.81), and all-cause mortality (OR 1.39, 95% CI 1.16-1.67), but lower odds of a benzodiazepine fill (OR 0.83, 95% CI 0.81-0.85). Dose reductions of 15- < 30%, compared to 1- < 15%, were associated with higher odds of ED visits (OR 1.08, 95% CI 1.05-1.11) and lower odds of a benzodiazepine fill (OR 0.93, 95% CI 0.92-0.95), but were not associated with opioid overdose and all-cause mortality. Larger reductions for patients on opioid therapy may raise risk of potential adverse events in the month after reduction and should be carefully monitored.
Authors: Metz, Verena E;Campbell, Cynthia I;Campbell, Cynthia I;et al.
J Gen Intern Med. 2023 Nov 06.
What is the association between adverse childhood experiences and late-life cognitive decline? Study of Healthy Aging in African Americans (STAR) cohort study
Adverse childhood experiences (ACEs) are associated with higher risk of chronic disease, but little is known about the association with late life cognitive decline. We examined the longitudinal association between ACEs and late-life cognitive decline in the Study of Healthy Aging in African Americans (STAR). Linear mixed models with random intercepts and slope examined the association of individual and composite ACEs with cognitive change adjusting for years from baseline (timescale), baseline age, sex, parental education, childhood socioeconomic status and childhood social support. Participants reported whether they had experienced nine types of ACEs. Executive function and verbal episodic memory were measured up to three times over a 3-year period using the Spanish and English Neuropsychological Assessment Scales. Kaiser Permanente Northern California members living in the Bay Area. STAR is a cohort study of cognitive ageing launched in 2018 that has enrolled 764 black Americans ages ≥50 years (mean age=67.5; SD=8.5). Twenty-one per cent of participants reported no ACEs, 24% one ACE, 20% two ACEs, 17% three ACEs and 17% four or more ACEs. Compared with no ACEs, two ACEs (β=0.117; 95% CI 0.052 to 0.182), three ACEs (β=0.075; 95% CI 0.007 to 0.143) and four or more ACEs (β=0.089; 95% CI 0.002 to 0.158) were associated with less decline in executive function. There were no significant associations between number of ACEs and baseline or longitudinal verbal episodic memory or between individual ACEs and executive function or verbal episodic memory. In this cohort of older black Americans, there was no association between ACEs and baseline cognition or cognitive change in verbal episodic memory; however, experiencing ≥ 2 ACEs was associated with less decline in executive function. These results may indicate that participants who survived to age 50+ and experienced ACEs may have cognitive resilience that warrants further investigation.
Authors: Lor, Yi;George, Kristen M;Gilsanz, Paola;Meunier, Claire C;Peterson, Rachel L;Hayes-Larson, Eleanor;Barnes, Lisa L;Mungas, Dan;Whitmer, Rachel A
BMJ Open. 2023 Nov 02;13(11):e072961. Epub 2023-11-02.
European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation
Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities.
Authors: Budu-Aggrey, Ashley;Choquet, Hélène;Paternoster, Lavinia;et al.
Nat Commun. 2023 Oct 04;14(1):6172. Epub 2023-10-04.
Metformin Cessation and Dementia Incidence
Prior studies suggested that metformin may be associated with reduced dementia incidence, but associations may be confounded by disease severity and prescribing trends. Cessation of metformin therapy in people with diabetes typically occurs due to signs of kidney dysfunction but sometimes is due to less serious adverse effects associated with metformin. To investigate the association of terminating metformin treatment for reasons unrelated to kidney dysfunction with dementia incidence. This cohort study was conducted at Kaiser Permanente Northern California, a large integrated health care delivery system, among a cohort of metformin users born prior to 1955 without history of diagnosed kidney disease at metformin initiation. Dementia follow-up began with the implementation of electronic health records in 1996 and continued to 2020. Data were analyzed from November 2021 through September 2023. A total of 12 220 early terminators, individuals who stopped metformin with normal estimated glomerular filtration rate (eGFR), were compared with routine metformin users, who had not yet terminated metformin treatment or had terminated (with or without restarting) after their first abnormal eGFR measurement. Early terminators were matched with routine users of the same age and gender who had diabetes for the same duration. The outcome of interest was all-cause incident dementia. Follow-up for early terminators and their matched routine users was started at age of termination for the early terminator. Survival models adjusted for sociodemographic characteristics and comorbidities at the time of metformin termination (or matched age). Mediation models with HbA1c level and insulin usage 1 and 5 years after termination tested whether changes in blood glucose or insulin usage explained associations between early termination of metformin and dementia incidence. The final analytic sample consisted of 12 220 early terminators (5640 women [46.2%]; mean [SD] age at start of first metformin prescription, 59.4 [9.0] years) and 29 126 routine users (13 582 women [46.6%]; mean [SD] age at start of first metformin prescription, 61.1 [8.9] years). Early terminators had 1.21 times the hazard of dementia diagnosis compared with routine users (hazard ratio, 1.21; 95% CI, 1.12 to 1.30). In mediation analysis, contributions to this association by changes in HbA1c level or insulin use ranged from no contribution (0.00 years; 95% CI, -0.02 to 0.02 years) for insulin use at 5 years after termination to 0.07 years (95% CI, 0.02 to 0.13 years) for HbA1c level at 1 year after termination, suggesting that the association was largely independent of changes in HbA1c level and insulin usage. In this study, terminating metformin treatment was associated with increased dementia incidence. This finding may have important implications for clinical treatment of adults with diabetes and provides additional evidence that metformin is associated with reduced dementia risk.
Authors: Zimmerman, Scott C;Whitmer, Rachel A;Gilsanz, Paola;Schaefer, Catherine;Ackley, Sarah F;et al.
JAMA Netw Open. 2023 Oct 02;6(10):e2339723. Epub 2023-10-02.
All-cause hospitalisation among people living with HIV according to gender, mode of HIV acquisition, ethnicity, and geographical origin in Europe and North America: findings from the ART-CC cohort collaboration
Understanding demographic disparities in hospitalisation is crucial for the identification of vulnerable populations, interventions, and resource planning. Data were from the Antiretroviral Therapy Cohort Collaboration (ART-CC) on people living with HIV in Europe and North America, followed up between January, 2007 and December, 2020. We investigated differences in all-cause hospitalisation according to gender and mode of HIV acquisition, ethnicity, and combined geographical origin and ethnicity, in people living with HIV on modern combination antiretroviral therapy (cART). Analyses were performed separately for European and North American cohorts. Hospitalisation rates were assessed using negative binomial multilevel regression, adjusted for age, time since cART intitiaion, and calendar year. Among 23 594 people living with HIV in Europe and 9612 in North America, hospitalisation rates per 100 person-years were 16·2 (95% CI 16·0-16·4) and 13·1 (12·8-13·5). Compared with gay, bisexual, and other men who have sex with men, rates were higher for heterosexual men and women, and much higher for men and women who acquired HIV through injection drug use (adjusted incidence rate ratios ranged from 1·2 to 2·5 in Europe and from 1·2 to 3·3 in North America). In both regions, individuals with geographical origin other than the region of study generally had lower hospitalisation rates compared with those with geographical origin of the study country. In North America, Indigenous people and Black or African American individuals had higher rates than White individuals (adjusted incidence rate ratios 1·9 and 1·2), whereas Asian and Hispanic people living with HIV had somewhat lower rates. In Europe there was a lower rate in Asian individuals compared with White individuals. Substantial disparities exist in all-cause hospitalisation between demographic groups of people living with HIV in the current cART era in high-income settings, highlighting the need for targeted support. Royal Free Charity and the National Institute on Alcohol Abuse and Alcoholism.
Authors: Rein, Sophia M;Guest, Jodie L;Smith, Colette J;et al.
Lancet Public Health. 2023 Oct;8(10):e776-e787.
Association between maternal prenatal cannabis use and missed child preventive care visits in an integrated health care delivery system in Northern California
The periodicity of well-child visits recommended by the American Academy of Pediatrics emphasizes the importance of continuity of care in health management. Exposure to cannabis in utero has been associated with adverse development, and adherence to well-child visits is critical for earlier detection and intervention. To assess whether maternal prenatal cannabis use was associated with missed well-child visits in the first three years after birth we conducted a longitudinal cohort study in Kaiser Permanente Northern California of pregnant individuals and their children born between January 1, 2011 and December 31, 2018. Maternal prenatal cannabis use was defined as any self-reported cannabis use since becoming pregnant and/or a positive urine toxicology test for cannabis during pregnancy. Well-child visits were defined as an encounter for a well-child visit or physical exam and categorized into seven time periods from birth to 36 months. Modified Poisson regression models were conducted. Of the 168,589 eligible pregnancies, 3.4% screened positive for maternal prenatal cannabis use. Compared to no use, maternal prenatal cannabis use was associated with more missed well-child visits at every time period; (missed 12-month visit: adjusted relative risk (aRR): 1.43, 95%CI: 1.32-1.54; missed 3-year visit: aRR: 1.15, 95%CI: 1.11-1.20). Maternal prenatal cannabis use was also associated with missing two or more well-child visits through 36 months of age (35.8% among cannabis users vs. 23.0% among non-users, Χ2p < .001). Educating pregnant individuals who use cannabis on the importance of well-child visits may benefit children's health and development.
Authors: Avalos, Lyndsay A;Oberman, Nina;Alexeeff, Stacey E;Croen, Lisa A;Adams, Sara R;Davignon, Meghan;Young-Wolff, Kelly C
Prev Med. 2023 Oct;175:107716. Epub 2023-09-28.
Psychiatric Diagnoses, Medication, and Service Use Among Patients Who Receive Emergency Care for Inflammatory Bowel Diseases
This study examined relative psychiatric burden among patients who presented to the emergency department once or more than once for inflammatory bowel disease visits. Results highlight the need for integration of psychiatric and gastrointestinal care among high-risk inflammatory bowel disease patients.
Authors: He, Jimmy Z;Hirschtritt, Matthew E;Wei, Julia;Ramalingam, Nirmala D;Kahane, Shellie M;Velayos, Fernando S;Hassid, Benjamin G
Inflamm Bowel Dis. 2023 Sep 04.
Patient Perceptions of Prenatal Cannabis Use and Implications for Clinicians
To understand pregnant patients’ reasons for prenatal cannabis use and perceptions of safety, desired and undesirable health care experiences, and desired information about prenatal cannabis use and secondarily to understand racial differences in these perceptions and preferences. We conducted a qualitative study including 18 semi-structured, race-concordant virtual focus groups with pregnant individuals who self-reported cannabis use at prenatal care entry in a large integrated health care system in Northern California from November 2021 to December 2021. The focus groups included semi-structured questions that were recorded, transcribed, and coded by the research team. Thematic analysis was used to analyze the data. Overall, 53 participants were included; 30 self-identified, as White and 23 self-identified as Black. Participants averaged 30.3 years of age (SD 5.2 years) and were on average at 20.9 weeks of gestation at study enrollment; 69.8% reported daily cannabis use, 24.5% reported weekly cannabis use, and 5.7% reported monthly or less cannabis use at entrance to prenatal care. Although some participants quit cannabis use in early pregnancy because of concerns about potential health risks, many perceived a lack of scientific evidence or believed that prenatal cannabis use was safe. Many preferred cannabis to over-the-counter or prescription medications for treating mood, morning sickness, pain, and sleep. Participants valued open interactions with obstetricians that acknowledged their motivations for use, and they desired information about potential risks through conversations and educational materials. White and Black participants’ perspectives were generally similar, but a few Black participants uniquely described concerns about racial bias related to their prenatal cannabis use. Pregnant patients used cannabis to manage mood and medical symptoms, and many believed that prenatal cannabis use was safer than the use of prescription medications. Obstetrician-initiated, patient-centered conversations around prenatal cannabis use, advice to discontinue cannabis use during pregnancy, and exploration of willingness to switch to medically recommended interventions for pregnancy-related symptoms may benefit patients.
Authors: Foti, Tara R;Green, Andrea;Altschuler, Andrea;Iturralde, Esti;Does, Monique B;Jackson-Morris, Melanie;Adams, Sara R;Goler, Nancy;Ansley, Deborah;Conway, Amy;Young-Wolff, Kelly C
Obstet Gynecol. 2023 Aug 10.
Acupuncture for chronic low back pain in older adults: Design and protocol for the BackInAction pragmatic clinical trial
Back pain prevalence and burden increase with age; approximately one-third of U.S. adults 65 years of age and older experience lower back pain (LBP). For chronic low back pain (cLBP), typically defined as lasting three months or longer, many treatments for younger adults may be inappropriate for older adults given their greater prevalence of comorbidities with attendant polypharmacy. While acupuncture has been demonstrated to be safe and effective for cLBP in adults overall, few studies of acupuncture have either included or focused on adults ≥65 years old. The BackInAction study is a pragmatic, multi-site, three-arm, parallel-groups randomized controlled trial designed to test the effectiveness of acupuncture needling for improving back pain-related disability among 807 older adults ≥65 years old with cLBP. Participants are randomized to standard acupuncture (SA; up to 15 treatment sessions across 12 weeks), enhanced acupuncture (EA; SA during first 12 weeks and up to 6 additional sessions across the following 12 weeks), and usual medical care (UMC) alone. Participants are followed for 12 months with study outcomes assessed monthly with the primary outcome timepoint at 6 months. The BackInAction study offers an opportunity to further understand the effectiveness, dose-dependence, and safety of acupuncture in a Medicare population. Additionally, study results may encourage broader adoption of more effective, safer, and more satisfactory options to the continuing over-reliance on opioid- and invasive medical treatments for cLBP among older adults. ClinicalTrials.gov Identifier: NCT04982315. Clinical trial registration date: July 29, 2021.
Authors: DeBar, Lynn L; Avins, Andrew L; Wellman, Robert; et al.
Contemp Clin Trials. 2023 May;128:107166. Epub 2023-03-27.
Assessing cognitive impairment in an ethnically diverse cohort of oldest-old: the life after 90 study
Though dementia rates vary by racial or ethnic groups, it is unknown if these disparities remain among those aged 90 or older. To test this hypothesis, we used baseline clinical evaluation of 541 ethnically and racially diverse individuals participating in the LifeAfter90 Study to assess how associations between core demographic characteristics and measures of physical and cognitive performance differ across the racial/ethnic groups. Participants in this study were long-term non-demented members of Kaiser Permanente Northern California. They were clinically evaluated and diagnosed with normal or impaired cognition (mild cognitive impairment and dementia) through an in-person comprehensive clinical assessment consisting of a detailed medical history, physical and neurological examination, functional, and cognitive tests. The average age at enrollment was 93.0 ± 2.6 years, 62.4% female and 34.2% non-Hispanic White. At initial evaluation 301 participants had normal cognition and 165 had mild cognitive impairment (MCI) and despite screening, 69 participants were determined to have dementia. Age, education, 3MS, FAQ and CDR scores were significantly associated with cognitive impairment (normal versus MCI and dementia), but not gender. There was a significant univariate association between race/ethnicity and cognitive impairment (p < 0.02) being highest among Black (57.4%) and lowest among Asian (32.7%) individuals. After adjustment for age, gender, and education, however, prevalence of cognitive impairment was not influenced by race or ethnicity. Our results confirm the ability to reliably assess clinical diagnosis in a diverse sample of very old individuals.
Authors: Petrosyan, Diana; Gilsanz, Paola; DeCarli, Charles; et al.
Aging Clin Exp Res. 2023 May;35(5):979-986. Epub 2023-03-04.
Rare and low-frequency coding genetic variants contribute to pediatric-onset multiple sclerosis
Rare genetic variants are emerging as important contributors to the heritability of multiple sclerosis (MS). Whether rare variants also contribute to pediatric-onset multiple sclerosis (POMS) is unknown. To test whether genes harboring rare variants associated with adult-onset MS risk (PRF1, PRKRA, NLRP8, and HDAC7) and 52 major histocompatibility complex (MHC) genes are associated with POMS. We analyzed DNA samples from 330 POMS cases and 306 controls from the US Network of Pediatric MS Centers and Kaiser Permanente Northern California for which Illumina ExomeChip genotypes were available. Using the gene-based method “SKAT-O,” we tested the association between candidate genes and POMS risk. After correction for multiple comparisons, one adult-onset MS gene (PRF1, p = 2.70 × 10-3) and two MHC genes (BRD2, p = 5.89 × 10-5 and AGER, p = 7.96 × 10-5) were significantly associated with POMS. Results suggest these are independent of HLA-DRB1*1501. Findings support a role for rare coding variants in POMS susceptibility. In particular, rare minor alleles within PRF1 were more common among individuals with POMS compared to controls while the opposite was true for rare variants within significant MHC genes, BRD2 and AGER. These genes would not have been identified by common variant studies, emphasizing the merits of investigating rare genetic variation in complex diseases.
Authors: Horton, Mary K; Schaefer, Catherine; Barcellos, Lisa F; et al.
Mult Scler. 2023 Apr;29(4-5):505-511. Epub 2023-02-08.
Genetically Predicted Serum Vitamin C Levels and Cutaneous Squamous Cell Carcinoma Risk
Authors: Kim, Yuhree; Yin, Jie; Le Breton, Stephen; Jorgenson, Eric; Huang, Hailiang; Choquet, Hélène; Asgari, Maryam M
J Invest Dermatol. 2023 Apr;143(4):664-667. Epub 2022-11-05.
Performance of a Prediction Model of Suicide Attempts Across Race and Ethnicity
This study examines whether race disparities exist in the prediction of suicide attempts and if have they have detrimental effects on individuals and health care systems.
Authors: Papini, Santiago; Hsin, Honor; Kipnis, Patricia; Liu, Vincent X; Lu, Yun; Sterling, Stacy A; Iturralde, Esti
JAMA Psychiatry. 2023 Apr 01;80(4):399-400.
State-Level Indicators of Childhood Educational Quality and Incident Dementia in Older Black and White Adults
Higher educational attainment is associated with reduced dementia risk, but the role of educational quality is understudied, presenting a major evidence gap, especially as it may contribute to racial inequities. To evaluate the association between state-level educational quality during childhood and dementia risk. This cohort study analyzed longitudinal data collected from January 1, 1997, through December 31, 2019 (23-year follow-up period). The sample comprised members of Kaiser Permanente Northern California (KPNC), a large integrated health care delivery system, who completed an optional survey during 1964-1972. Eligible individuals were US born; non-Hispanic Black or non-Hispanic White; aged 65 years or older as of January 1, 1996; were still alive; and did not have a dementia diagnosis or lapse in KPNC membership greater than 90 days between January 1 and December 31, 1996. Historical state-level administrative indicators of school quality (school term length, student-teacher ratio, and attendance rates) linked to participants using birth state and birth year (with a 6-year lag) and divided into tertiles using the pooled sample. Dementia diagnoses from electronic health records between 1997 and 2019 were analyzed between March 1 and August 31, 2022. The associations of educational quality with incident dementia were estimated using Cox proportional hazards regression models. Among 21 450 KPNC members who participated in the optional survey, individuals born before availability of educational quality records (n = 87) and missing educational attainment (n = 585) were excluded. The final analytic sample was 20 778 individuals (56.5% women, 43.5% men; mean [SD] age, 74.7 [6.5] years; 18.8% Black; 81.2% White; 41.0% with less than high school education). Among Black individuals, 76.2% to 86.1% (vs 20.8%-23.3% of White individuals) attended schools in states in the lowest educational quality tertiles. Highest (vs lowest) educational quality tertiles were associated with lower dementia risk (student-teacher ratio: hazard ratio [HR], 0.88 [95% CI, 0.83-0.94]; attendance rates: HR, 0.80 [95% CI, 0.73-0.88]; term length: HR, 0.79 [95% CI, 0.73-0.86]). Effect estimates did not differ by race and were not attenuated by adjustment for educational attainment. In this cohort study, lower state-average educational quality was more common among Black individuals and associated with higher dementia risk. Differential investment in high-quality education due to structural racism may contribute to dementia disparities.
Authors: Soh, Yenee; Whitmer, Rachel A; Mayeda, Elizabeth Rose; Glymour, M Maria; Peterson, Rachel L; Eng, Chloe W; Quesenberry, Charles P; Manly, Jennifer J; Gilsanz, Paola
JAMA Neurol. 2023 Apr 01;80(4):352-359.
Racial-Ethnic Differences in Treatment Initiation for New Diagnoses of Perinatal Depression
The adverse consequences of untreated perinatal depression highlight the need to identify populations to target in order to increase treatment rates. The authors sought to evaluate treatment initiation for a new diagnosis of depression during pregnancy or postpartum and to describe racial-ethnic differences in initiation and type (psychotherapy, antidepressants) of treatment in a large health care system with universal perinatal depression screening. This retrospective cohort study included women who delivered a live birth in the Kaiser Permanente Northern California system between October 2012 and May 2017. Black, Latina, Asian, and White women ages ≥15 years were eligible. New depression diagnoses were defined by using ICD-9 and ICD-10 codes from electronic health records. Treatment initiation was defined as receiving at least one antidepressant medication dispensation or psychotherapy visit up to 90 days after the diagnosis. Modified Poisson regression was used to estimate the risk for initiating treatment and the type of treatment initiated. In total, 13,637 women with a new depression diagnosis (prenatal: N=7,041, 51.6%; postpartum: N=6,596, 48.4%) were identified. Of the pregnant women, 31.4% initiated treatment, and of the postpartum women, 73.1% initiated treatment. Latina and Asian women were less likely than White women to initiate treatment postpartum. During pregnancy and postpartum, non-White women were more likely to initiate psychotherapy. White women were more likely to initiate antidepressant medication during pregnancy and postpartum or a combination of antidepressant medication and psychotherapy during the postpartum period. Research is warranted to identify patient-, provider-, and system-level barriers that contribute to racial-ethnic disparities in perinatal mental health care.
Authors: Avalos, Lyndsay A; Nance, Nerissa; Iturralde, Esti; Badon, Sylvia E; Quesenberry, Charles P; Sterling, Stacy; Li, De-Kun; Flanagan, Tracy
Psychiatr Serv. 2023 Apr 01;74(4):341-348. Epub 2022-10-13.
Disparities in the Receipt of Alcohol Brief Intervention: The Intersectionality of Sex, Age and Race/ethnicity
The increasing trend in alcohol consumption among women, exacerbated by the COVID-19 pandemic, is of growing concern. Screening, Brief Intervention, and Referral to Treatment in primary care is an efficacious and cost-effective treatment approach for unhealthy alcohol use. However, disparities exist in delivery of brief interventions by sex, age and race/ethnicity. This study measures brief intervention rates among eligible patients by sex, age and race/ethnicity and their intersectionality, in the context of a program of systematic alcohol screening and brief intervention program in adult primary care in a large, integrated healthcare delivery system. Population-based observational study. Primary care clinics in an integrated healthcare delivery system in Northern California, USA. Adult (18+) patients (N=287,551) screening positive for unhealthy alcohol use between January 2014 and December 2017. Receipt of brief intervention, patient and provider characteristics from electronic health records. Multilevel logistic regression showed that women had lower odds of receiving brief intervention than men, across all age, racial/ethnic groups and drinking levels. Sex differences were greater among those aged 35-49 (odds ratio [OR] [95% confidence interval [CI]] = 0.67 [0.64, 0.69]) and 50-65 years (OR [95% CI] = 0.69 [0.66, 0.72]) than among other age groups. Sex differences in odds of receiving brief intervention were greater for the Latino/Hispanic group for women vs. men (OR [95% CI] = 0.69 [0.66, 0.72]) and smaller for the Asian/Pacific Islander group (OR [95% CI] = 0.76 [0.72, 0.81]). In the United States, compared with men, women appear to have lower odds of receiving brief intervention for unhealthy alcohol use across all age groups, particularly during middle age. Black women and Latina/Hispanic women appear to be less likely to receive brief intervention than women in other race/ethnicity groups. Receipt of brief intervention does not appear to differ by drinking levels between men and women.
Authors: Parthasarathy, Sujaya; Chi, Felicia; Metz, Verena; Kline-Simon, Andrea; Asyyed, Asma; Campbell, Cynthia; Sterling, Stacy
Addiction. 2023 Mar 29.
Considerations for the Writing of Certification Letters Endorsing Use of Emotional Support Animals
Emotional support animals (ESAs) are different from service animals, therapy animals, and other disability-related assistance animals. Although pet ownership may confer psychological benefits, limited research has supported the use of ESAs to realize such benefits. If clinicians are asked to write a letter of support for use of an ESA, they need to be familiar with relevant federal, state, and local laws that regulate ESAs and with the essential components of an ESA evaluation. This article provides an overview of terminology; federal, state, and local laws related to ESAs; and clinical and ethical considerations for clinicians who decide to write these letters. The authors also review liability issues related to writing these letters, including those related to ESA aggression.
Authors: Binder, Renee L; Gandhi, Tanuja; Menon, Meera; Audu, Alexandra; Nesbit, Ariana; Ridout, Kathryn K; Campbell, Jorien; Garayalde, Stephanie; Dike, Charles C
Psychiatr Serv. 2023 Mar 29:appips20220487.
A Cross-Trait, Mendelian Randomization Study to Investigate Whether Migraine Is a Risk Factor for Multiple Sclerosis
Migraine is common among people with multiple sclerosis (MS), but the reasons for this are unknown. We tested 3 hypothesized mechanisms for this observed comorbidity, including migraine is a risk factor of MS, genetic variants are shared between the conditions, and migraine is because of MS. Data were from 2 sources: publicly available summary statistics from genome-wide association studies of MS (N = 115,748) and migraine (N = 375,752 and N = 361,141) and a case-control study of MS recruited from the Kaiser Permanente Northern California Health Plan (N = 1,991). For the latter participants, migraine status was ascertained using a validated electronic health record migraine probability algorithm or self-report. Using the public summary statistics, we used 2-sample Mendelian randomization to test whether a migraine genetic instrumental variable was associated with MS. We used linkage disequilibrium score regression and LOGODetect to ascertain whether MS and migraine shared genetic variants across the genome and regionally. Using the Northern California MS cohort, we used logistic regression to identify whether people with both MS and migraine had different odds of clinical characteristics (e.g., age at MS onset, Perceived Deficits Questionnaire, and depression) or MS-specific risk factors (e.g., body mass index, smoking status, and infectious mononucleosis status) compared with people with MS without migraine. We did not find evidence supporting migraine as a causal risk factor of MS (p = 0.29). We did, however, identify 4 major histocompatibility complex (MHC) loci shared between MS and migraine. Among the Northern California MS cohort, 774 (39%) experienced migraine. People with both MS and migraine from this cohort were more likely to ever smoke (odds ratio [OR] = 1.30, 95% CI: 1.08-1.57), have worse self-reported cognitive deficits (OR = 1.04, 95% CI: 1.02-1.06), and ever experience depression (OR = 1.48, 95% CI: 1.22-1.80). Our findings do not support migraine as a causal risk factor of MS. Several genetic variants, particularly in the MHC, may account for some of the overlap. It seems likely that migraine within the context of MS is because of MS. Identifying what increases the risk of migraine within MS might lead to an improved treatment and quality of life.
Authors: Horton, Mary K; Schaefer, Catherine A; Barcellos, Lisa F; et al.
Neurology. 2023 Mar 28;100(13):e1353-e1362. Epub 2023-01-11.
Patient and Visit Characteristics Associated With Physical Restraint Use in the Emergency Department
Objective Physical restraints are used in emergency departments (EDs) to address behavioral emergencies in situations in which less restrictive methods have failed. The objective of this study was to evaluate for associations between patient/visit characteristics and physical restraint use. Study Design This study was designed as a cross-sectional, retrospective study of all encounters at Kaiser Permanente Northern California EDs from January 1, 2016, to December 31, 2019, to evaluate differences in patient and visit characteristics between visits involving physical restraint use and those without. Methods Using electronic health record data, this study identified physical restraint use among ED encounters and extracted demographic, clinical, and facility characteristics. The authors calculated odds ratios for physical restraint placement, adjusting for patient and visit characteristics and accounting for within-patient clustering. Results Among 4,410,816 encounters (representing 1,791,673 patients), 6369 encounters (0.1%) involved physical restraint use among 5,554 patients (0.3%). Variables associated with the lowest odds of physical restraint included female sex, presentation to the ED in more recent years, and presence of intentional self-harm/suicidal ideation. Variables associated with the highest odds of physical restraint included higher visit acuity and weekend presentations to the ED. Discussion This study, which leveraged a large, diverse patient sample generalizable to the Northern California population, found several patient and visit characteristics associated with physical restraint use in the ED. Conclusion Results of this study may help identify patient groups and situational factors that are most likely to lead to physical restraint use and structural factors contributing to disparities in care, thereby informing interventions to reduce physical restraint use when possible.
Authors: Walia, Harbir; Tucker, Lue-Yen S; Manickam, Raj N; Kene, Mamata V; Sharp, Adam L; Berdahl, Carl T; Hirschtritt, Matthew E
Perm J. 2023 Mar 15;27(1):94-102. Epub 2022-12-04.
Association of Education With Dementia Incidence Stratified by Ethnicity and Nativity in a Cohort of Older Asian American Individuals
High education protects against dementia, but returns on educational attainment may be different across sociodemographic groups owing to various social factors. Asian American individuals are a growing and diverse group, but little research has assessed dementia determinants in this population. To examine the association of education with dementia in a large cohort of Asian American individuals, stratifying by ethnicity and nativity. This cohort study used electronic health record (EHR) and survey data from the Research Program on Genes, Environment, and Health and the California Men’s Health Study surveys (2002-2020). Data are from Kaiser Permanente Northern California, an integrated health care delivery system. This study used a volunteer sample who completed the surveys. Participants included Chinese, Filipino, and Japanese individuals who were aged 60 to less than 90 years without a dementia diagnosis in the EHR at the time of the survey (baseline) and who had 2 years of health plan coverage before baseline. Data analysis was performed from December 2021 to December 2022. The main exposure was educational attainment (college degree or higher vs less than a college degree), and the main stratification variables were Asian ethnicity and nativity (born in the US or born outside the US). The primary outcome was incident dementia diagnosis in the EHR. Dementia incidence rates were estimated by ethnicity and nativity, and Cox proportional hazards and Aalen additive hazards models were fitted for the association of college degree or higher vs less than a college degree with time to dementia, adjusting for age (timescale), sex, nativity, and an interaction between nativity and college degree. Among 14 749 individuals, the mean (SD) age at baseline was 70.6 (7.3) years, 8174 (55.4%) were female, and 6931 (47.0%) had attained a college degree. Overall, among individuals born in the US, those with a college degree had 12% lower dementia incidence (HR, 0.88; 95% CI, 0.75-1.03) compared with those without at least a college degree, although the confidence interval included the null. The HR for individuals born outside the US was 0.82 (95% CI, 0.72-0.92; P = .46 for the college degree by nativity interaction). The findings were similar across ethnicity and nativity groups except for Japanese individuals born outside the US. These findings suggest that college degree attainment was associated with lower dementia incidence, with similar associations across nativity. More work is needed to understand determinants of dementia in Asian American individuals and to elucidate mechanisms linking educational attainment and dementia.
Authors: Hayes-Larson, Eleanor; Ikesu, Ryo; Fong, Joseph; Mobley, Taylor M; Gee, Gilbert C; Brookmeyer, Ron; Whitmer, Rachel A; Gilsanz, Paola; Mayeda, Elizabeth Rose
JAMA Netw Open. 2023 Mar 01;6(3):e231661. Epub 2023-03-01.
Influenza Vaccination Uptake and Associated Factors Among Adults With and Without HIV in a Large, Integrated Health Care System
Influenza vaccination is recommended for adults regardless of HIV status. There may be facilitators or barriers to vaccinating people with HIV (PWH) that differ from people without HIV (PWoH). We sought to describe the uptake of influenza vaccination by HIV status and identify factors associated with vaccination. We abstracted data from the electronic health records of PWH and PWoH in Kaiser Permanente Northern California during six influenza seasons (2013-2018). We determined vaccination uptake and used Poisson regression models to evaluate factors associated with vaccination in PWH and PWoH. 9,272 PWH and 194,393 PWoH matched by age, sex, and race/ethnicity were included (mean age: 48 vs 49 years; men: 91% vs 90%; white race: 53%). PWH were more likely to receive the influenza vaccine (65%-69% across years for PWH and 37%-41% for PWoH) with an adjusted risk ratio for all years of 1.48 (95% CI: 1.46-1.50). For PWH, lower vaccination uptake was associated with several factors that suggested more complex health needs, such as lower CD4 cell counts, higher HIV viral loads, prior depression diagnoses, having Medicare insurance, and having a higher number of comorbidities. Associations with vaccination uptake were attenuated in PWH, compared with PWoH, for smoking, alcohol, and demographic factors. PWH had an almost 50% higher uptake of influenza vaccination than PWoH, possibly reflecting greater engagement with the healthcare system. We also found that PWH with more complex health needs had reduced vaccination uptake. Findings may inform outreach strategies to increase influenza vaccination in PWH.
Authors: Imp, Brandon M; Levine, Tory; Satre, Derek D; Skarbinski, Jacek; Luu, Mitchell N; Sterling, Stacy A; Silverberg, Michael J
Clin Infect Dis. 2023 Mar 01.
Accuracy of diagnostic codes for prenatal opioid exposure and neonatal opioid withdrawal syndrome
Determine the accuracy of diagnostic codes in identifying Prenatal Opioid Exposure (POE) and Neonatal Opioid Withdrawal Syndrome (NOWS). A cross-sectional study of 374,222 mother-infant dyads with delivery from 01/01/2010 to 12/31/2019. We ascertained maternal diagnostic codes for opioid use during pregnancy and infant diagnostic codes for drug exposure and withdrawal. We assessed sensitivity and positive predictive value (PPV) for POE and NOWS, defined using laboratory, pharmacy, and clinical data. Maternal codes had low sensitivity (36.4%) and PPV (34.7%) for POE. Infant codes for drug exposure were neither sensitive for POE (14%) nor NOWS (31.6%) and had low PPV. Codes for newborn withdrawal had low sensitivity (31.6%) for detecting NOWS, but high PPV (85%). Sensitivity improved (95.1%) for NOWS requiring pharmacologic treatment. Diagnostic codes identify POE and NOWS poorly. Improved case identification would include pharmacy and laboratory results, and clearly defined criteria for evidence of withdrawal.
Authors: Kuzniewicz, Michael W; Campbell, Cynthia I; Li, Sherian; Walsh, Eileen M; Croen, Lisa A; Comer, Sandra D; Pimentel, Samuel D; Hedderson, Monique; Sun, Lena S
J Perinatol. 2023 Mar;43(3):293-299. Epub 2022-09-21.
The impact of attending historically Black colleges and universities on cognitive decline in Black adults: A longitudinal analysis in the KHANDLE and STAR cohorts
Black students attending predominantly White institutions (PWIs) versus historically Black colleges and universities (HBCUs) report more harmful discrimination and develop worse mental health outcomes, potentially offsetting the established benefits of college for lowering dementia incidence. Black participants in two cohorts (the Kaiser Healthy Aging and Diverse Life Experiences [KHANDLE] and the Study of Healthy Aging in African Americans [STAR]) who had attended college (N = 716) self-reported the college name (classified as HBCU vs. PWI) and completed three waves of executive function (EF) and verbal episodic memory (VEM) assessments. HBCU effects on cognitive level and decline were estimated using adjusted linear mixed-effects models. HBCU (vs. PWI) attendees averaged better EF (β = 0.05 [-0.22, 0.32]) and VEM (β = 0.21 [-0.06, 0.46]) at age 70 though neither association was statistically significant. HBCU attendance was associated with slightly faster VEM decline (β = -0.03 [-0.05, 0.00]). Harmonized analyses with larger studies are needed to estimate important effects of HBCU attendance. Higher education is robustly linked to lower dementia risk, yet Black-White inequities persist among college-educated adults. Black students attending predominantly White institutions (PWIs) versus historically Black colleges and universities (HBCUs) report more harmful discrimination and develop worse mental health outcomes, which may offset the established benefits of college for lowering dementia incidence. HBCU (vs. non-HBCU) attendees averaged better executive function and verbal episodic memory (VEM) at average age 70, though confidence intervals were wide and associations were not statistically significant, and averaged slightly faster decline in VEM. Harmonized analyses using larger nationally representative studies are likely needed to avoid underestimating the health effects of HBCU attendance.
Authors: Thomas, Marilyn D; Calmasini, Camilla; Khela, Harmon; Mobley, Taylor M; Mayeda, Elizabeth Rose; Mangurian, Christina; Barnes, Lisa L; Gilsanz, Paola; Whitmer, Rachel A; Glymour, M Maria
Alzheimers Dement. 2023 Feb 17.
Polygenic risk score association with multiple sclerosis susceptibility and phenotype in Europeans
Polygenic inheritance plays a pivotal role in driving multiple sclerosis susceptibility, an inflammatory demyelinating disease of the CNS. We developed polygenic risk scores (PRS) of multiple sclerosis and assessed associations with both disease status and severity in cohorts of European descent. The largest genome-wide association dataset for multiple sclerosis to date (n = 41 505) was leveraged to generate PRS scores, serving as an informative susceptibility marker, tested in two independent datasets, UK Biobank [area under the curve (AUC) = 0.73, 95% confidence interval (CI): 0.72-0.74, P = 6.41 × 10-146] and Kaiser Permanente in Northern California (KPNC, AUC = 0.8, 95% CI: 0.76-0.82, P = 1.5 × 10-53). Individuals within the top 10% of PRS were at higher than 5-fold increased risk in UK Biobank (95% CI: 4.7-6, P = 2.8 × 10-45) and 15-fold higher risk in KPNC (95% CI: 10.4-24, P = 3.7 × 10-11), relative to the median decile. The cumulative absolute risk of developing multiple sclerosis from age 20 onwards was significantly higher in genetically predisposed individuals according to PRS. Furthermore, inclusion of PRS in clinical risk models increased the risk discrimination by 13% to 26% over models based only on conventional risk factors in UK Biobank and KPNC, respectively. Stratifying disease risk by gene sets representative of curated cellular signalling cascades, nominated promising genetic candidate programmes for functional characterization. These pathways include inflammatory signalling mediation, response to viral infection, oxidative damage, RNA polymerase transcription, and epigenetic regulation of gene expression to be among significant contributors to multiple sclerosis susceptibility. This study also indicates that PRS is a useful measure for estimating susceptibility within related individuals in multicase families. We show a significant association of genetic predisposition with thalamic atrophy within 10 years of disease progression in the UCSF-EPIC cohort (P < 0.001), consistent with a partial overlap between the genetics of susceptibility and end-organ tissue injury. Mendelian randomization analysis suggested an effect of multiple sclerosis susceptibility on thalamic volume, which was further indicated to be through horizontal pleiotropy rather than a causal effect. In summary, this study indicates important, replicable associations of PRS with enhanced risk assessment and radiographic outcomes of tissue injury, potentially informing targeted screening and prevention strategies.
Authors: Shams, Hengameh; Schaefer, Catherine; Oksenberg, Jorge R; et al.
Brain. 2023 Feb 13;146(2):645-656.
Circulating insulin-like growth factors and risks of overall, aggressive and early-onset prostate cancer: a collaborative analysis of 20 prospective studies and Mendelian randomization analysis
Previous studies had limited power to assess the associations of circulating insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with clinically relevant prostate cancer as a primary endpoint, and the association of genetically predicted IGF-I with aggressive prostate cancer is not known. We aimed to investigate the associations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 concentrations with overall, aggressive and early-onset prostate cancer. Prospective analysis of biomarkers using the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset (up to 20 studies, 17 009 prostate cancer cases, including 2332 aggressive cases). Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression. For IGF-I, two-sample Mendelian randomization (MR) analysis was undertaken using instruments identified using UK Biobank (158 444 men) and outcome data from PRACTICAL (up to 85 554 cases, including 15 167 aggressive cases). Additionally, we used colocalization to rule out confounding by linkage disequilibrium. In observational analyses, IGF-I was positively associated with risks of overall (OR per 1 SD = 1.09: 95% CI 1.07, 1.11), aggressive (1.09: 1.03, 1.16) and possibly early-onset disease (1.11: 1.00, 1.24); associations were similar in MR analyses (OR per 1 SD = 1.07: 1.00, 1.15; 1.10: 1.01, 1.20; and 1.13; 0.98, 1.30, respectively). Colocalization also indicated a shared signal for IGF-I and prostate cancer (PP4: 99%). Men with higher IGF-II (1.06: 1.02, 1.11) and IGFBP-3 (1.08: 1.04, 1.11) had higher risks of overall prostate cancer, whereas higher IGFBP-1 was associated with a lower risk (0.95: 0.91, 0.99); these associations were attenuated following adjustment for IGF-I. These findings support the role of IGF-I in the development of prostate cancer, including for aggressive disease.
Authors: Watts, Eleanor L; Schaefer, Catherine A; Van Den Eeden, Stephen K; Travis, Ruth C; et al.
Int J Epidemiol. 2023 Feb 08;52(1):71-86.
Association of the COVID-19 Pandemic With Unstable and/or Unsafe Living Situations and Intimate Partner Violence Among Pregnant Individuals
The social, behavioral, and economic consequences of the COVID-19 pandemic may be associated with unstable and/or unsafe living situations and intimate partner violence (IPV) among pregnant individuals. To investigate trends in unstable and/or unsafe living situations and IPV among pregnant individuals prior to and during the COVID-19 pandemic. A cross-sectional population-based interrupted time-series analysis was conducted among Kaiser Permanente Northern California members who were pregnant and screened for unstable and/or unsafe living situation and IPV as part of standard prenatal care between January 1, 2019, and December 31, 2020. COVID-19 pandemic (prepandemic period: January 1, 2019, to March 31, 2020; during pandemic period: April 1 to December 31, 2020). The 2 outcomes were unstable and/or unsafe living situations and IPV. Data were extracted from electronic health records. Interrupted time-series models were fit and adjusted for age and race and ethnicity. The study sample included 77 310 pregnancies (74 663 individuals); 27.4% of the individuals were Asian or Pacific Islander, 6.5% were Black, 29.0% were Hispanic, 32.3% were non-Hispanic White, and 4.8% were other/unknown/multiracial, with a mean (SD) age of 30.9 (5.3) years. Across the 24-month study period there was an increasing trend in the standardized rate of unsafe and/or unstable living situations (2.2%; rate ratio [RR], 1.022; 95% CI, 1.016-1.029 per month) and IPV (4.9%; RR, 1.049; 95% CI, 1.021-1.078 per month). The ITS model indicated a 38% increase (RR, 1.38; 95% CI, 1.13-1.69) in the first month of the pandemic for unsafe and/or unstable living situation, with a return to the overall trend afterward for the study period. For IPV, the interrupted time-series model suggested an increase of 101% (RR, 2.01; 95% CI, 1.20-3.37) in the first 2 months of the pandemic. This cross-sectional study noted an overall increase in unstable and/or unsafe living situations and IPV over the 24-month period, with a temporary increase associated with the COVID-19 pandemic. It may be useful for emergency response plans to include IPV safeguards for future pandemics. These findings suggest the need for prenatal screening for unsafe and/or unstable living situations and IPV coupled with referral to appropriate support services and preventive interventions.
Authors: Avalos, Lyndsay A; Ray, G Thomas; Alexeeff, Stacey E; Adams, Sara R; Does, Monique B; Watson, Carey; Young-Wolff, Kelly C
JAMA Netw Open. 2023 Feb 01;6(2):e230172. Epub 2023-02-01.
Evaluating interpersonal discrimination and depressive symptoms as partial mediators of the effects of education on cognition: Evidence from the Study of Healthy Aging in African Americans (STAR)
Education is correlated with positive health outcomes, but associations are sometimes weaker among African Americans. The extent to which exposure to discrimination and depressive symptoms attenuates the education-cognition link has not been investigated. Study of Healthy Aging in African Americans (STAR) participants (n = 764; average age 69 years) completed the Spanish and English Neuropsychological Assessment Scales. We assessed everyday and major lifetime discrimination and depressive symptoms as mediators of education effects on cognition using G-estimation with measurement error corrections. Education was correlated with greater major lifetime and everyday discrimination but lower depressive symptoms. Accounting for discrimination and depressive symptoms slightly reduced the estimated effect of education on cognition. The estimated total effect of graduate education (vs Authors: Cintron, Dakota W; Calmasini, Camilla; Barnes, Lisa L; Mungas, Dan M; Whitmer, Rachel A; Eng, Chloe W; Gilsanz, Paola; George, Kristen M; Peterson, Rachel L; Glymour, M Maria Alzheimers Dement. 2023 Feb 01.
What Will It Take to Meet Adolescents’ Mental Health Needs?
Authors: Hirschtritt, Matthew E; Rodgers, Caryn R R
J Adolesc Health. 2023 Feb;72(2):175-176.
Association of cannabis use during pregnancy with severe acute respiratory syndrome coronavirus 2 infection: a retrospective cohort study
Cannabis use is increasingly common among pregnant individuals and might be a risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to test whether prenatal cannabis use is associated with increased risk of SARS-CoV-2 infection during pregnancy. This is a retrospective cohort study. The study was conducted in California, USA. A total of 58?114 pregnancies (with outcomes from 5 March 2020 to 30 September 2021) among 57?287 unique pregnant women aged 14-54?years who were screened for prenatal substance use, enrolled in Kaiser Permanente Northern California (KPNC) (a health-care system) and had not tested positive for COVID-19 prior to pregnancy onset. We utilized data from the KPNC electronic health record. Cannabis use status (current, recently quit and non-user) was based on universal screenings during prenatal care (including urine toxicology testing and self-reported use on a self-administered questionnaire). SARS-CoV-2 infection [based on polymerase chain reaction (PCR) tests] was estimated in time-to-event analyses using Cox proportional hazard regression models adjusting for covariates. Secondary analyses examined differences in (a) SARS-CoV-2 testing rates and (b) SARS-CoV-2 infection rates among those tested. We observed 348?810 person-months of follow-up time in our cohort with 41?064 SARS-CoV-2 PCR tests and 6% (n?=?2414) of tests being positive. At the start of follow-up, 7% of pregnant individuals had current use, 12% had recently quit and 81% did not use cannabis. Adjusting for covariates, current use was associated with lower rates of SARS-CoV-2 infection [adjusted hazard ratio (aHR)?=?0.60, 95% confidence interval (CI)?=?0.49-0.74 than non-use. Those who had recently quit did not differ from non-cannabis users in infection rates (aHR?=?0.96, 95% CI?=?0.86-1.08). Sensitivity analyses among patients who received a SARS-CoV-2 test also found lower odds of infection associated with current versus no cannabis use (aOR?=?0.76, CI?=?0.61-0.93). Current cannabis use appears to be associated with a reduced risk of SARS-CoV-2 infection among pregnant individuals.
Authors: Young-Wolff, Kelly C; Ray, G Thomas; Alexeeff, Stacey E; Benowitz, Neal; Adams, Sara R; Does, Monique B; Goler, Nancy; Ansley, Deborah; Conway, Amy; Avalos, Lyndsay A
Addiction. 2023 Feb;118(2):317-326. Epub 2022-10-12.
A Brief Course on Forensic Psychiatry Principles
Authors: Weiner, Stephen; Lingafelter, Nathan; Ali, Musaab; Wu, Johnathan; Walia, Harbir; Wasser, Tobias; Hirschtritt, Matthew E
Acad Psychiatry. 2023 Feb;47(1):107-108. Epub 2022-07-19.
Fulfilling the Goals of 988 Through Crisis Stabilization Care
Recent implementation of the nationwide 988 Suicide and Crisis Lifeline has expanded telephone-based mental health crisis services and created a unified framework for crisis care in the United States. However, the infrastructure for the final step of the crisis continuum-an appropriate mental health service for persons in crisis to receive the care they need-is fragmented, unevenly distributed, underfunded, and understudied. Given the few options for individuals in crisis, most often inpatient psychiatric hospitals are the default option. In this Open Forum, the authors describe the scope of the problem and propose how clinicians, policy makers, and researchers can improve the availability of evidence-based disposition options for individuals in crisis.
Authors: Hirschtritt, Matthew E; Howard, Caren A; Simon, Gregory E
Psychiatr Serv. 2023 Jan 31:appips20220503.
Associations between alcohol brief intervention in primary care and drinking and health outcomes in adults with hypertension and type 2 diabetes: a population-based observational study
To evaluate associations between alcohol brief intervention (BI) in primary care and 12-month drinking outcomes and 18-month health outcomes among adults with hypertension and type 2 diabetes (T2D). A population-based observational study using electronic health records data. An integrated healthcare system that implemented system-wide alcohol screening, BI and referral to treatment in adult primary care. Adult primary care patients with hypertension (N=72 979) or T2D (N=19 642) who screened positive for unhealthy alcohol use between 2014 and 2017. We examined four drinking outcomes: changes in heavy drinking days/past 3 months, drinking days/week, drinks/drinking day and drinks/week from baseline to 12-month follow-up, based on results of alcohol screens conducted in routine care. Health outcome measures were changes in measured systolic and diastolic blood pressure (BP) and BP reduction ≥3 mm Hg at 18-month follow-up. For patients with T2D, we also examined change in glycohaemoglobin (HbA1c) level and ‘controlled HbA1c’ (HbA1c<8%) at 18-month follow-up. For patients with hypertension, those who received BI had a modest but significant additional -0.06 reduction in drinks/drinking day (95% CI -0.11 to -0.01) and additional -0.30 reduction in drinks/week (95% CI -0.59 to -0.01) at 12 months, compared with those who did not. Patients with hypertension who received BI also had higher odds for having clinically meaningful reduction of diastolic BP at 18 months (OR 1.05, 95% CI 1.00 to 1.09). Among patients with T2D, no significant associations were found between BI and drinking or health outcomes examined. Alcohol BI holds promise for reducing drinking and helping to improve health outcomes among patients with hypertension who screened positive for unhealthy drinking. However, similar associations were not observed among patients with T2D. More research is needed to understand the heterogeneity across diverse subpopulations and to study BI's long-term public health impact.
Authors: Chi, Felicia W; Weisner, Constance M; Satre, Derek D; Grant, Richard W; Metz, Verena E; Sterling, Stacy A; et al.
BMJ Open. 2023 Jan 19;13(1):e064088. Epub 2023-01-19.
Factors Associated with Bothersome Symptoms in Individuals With and Without HIV Who Report Alcohol Use
Bothersome symptoms potentially related to drinking are commonly reported by people with and without HIV (PWH/PWoH). However, the relationship between bothersome symptoms and level of alcohol use is often not appreciated by patients or providers. Therefore, among persons reporting prior-year alcohol use, we assessed whether alcohol use level (AUDIT-C score), HIV status, and demographic covariates influenced the likelihood of the patient reporting a bothersome symptom. We used the Veterans Aging Cohort Study (VACS) surveys (2002-2018), including a validated symptoms index. Among 3679 PWH and 3830 PWoH currently drinking alcohol, the most commonly reported symptoms were muscle/joint pain (52%), sleep disturbance (51%), and fatigue (50%). Level of alcohol use was independently associated with 18 of 20 bothersome symptoms, including seven symptoms more common among PWH. Results can help inform PWH/PWoH who drink alcohol about the strong relationship between level of alcohol use and bothersome symptoms, potentially motivating reduced use.
Authors: Bahji, Anees; Gordon, Kirsha S; Crystal, Stephen; Satre, Derek D; Wiliams, Emily C; Edelman, E Jennifer; Justice, Amy C
AIDS Behav. 2023 Jan 09.
Cigarette Smoking and Risk of SARS-CoV-2 infection and Disease Severity Among Adults in an Integrated Health Care System in California
The relationship between tobacco smoking status and SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) severity is highly debated. We conducted a retrospective cohort study of?>2.4 million adults in a large healthcare system to evaluate whether smoking is associated with SARS-CoV-2 infection and disease severity. This retrospective cohort study of 2,427,293 adults in KPNC from March 5, 2020 (baseline) to December 31, 2020 (pre-vaccine) included smoking status (current, former, never), socio-demographics, and comorbidities from the electronic health record. SARS-CoV-2 infection (identified by a positive PCR test) and COVID-19 severity (hospitalization, ICU admission or death???30 days of COVID-19 diagnosis) were estimated in time-to-event analyses using Cox proportional hazard regression models adjusting for covariates. Secondary analyses examined COVID-19 severity among patients with COVID-19 using logistic regression. During the study, 44,270 patients had SARS-CoV-2 infection. Current smoking was associated with lower adjusted rates of SARS-CoV-2 infection (aHR?=?0.64 95% CI: 0.61-0.67), COVID-19-related hospitalization (aHR?=?0.48 95% CI: 0.40-0.58), ICU admission (aHR?=?0.62 95% CI: 0.42-0.87), and death (aHR?=?0.52 95% CI: 0.27-0.89) than never-smoking. Former smoking was associated with a lower adjusted rate of SARS-CoV-2 infection (aHR?=?0.96 95% CI: 0.94-0.99) and higher adjusted rates of hospitalization (aHR?=?1.10 95% CI: 1.03-1.08) and death (aHR?=?1.32 95% CI: 1.11-1.56) than never-smoking. Logistic regression analyses among patients with COVID-19 found lower odds of hospitalization for current versus never-smoking and higher odds of hospitalization and death for former versus never-smoking. In the largest US study to date on smoking and COVID-19, current and former smoking showed lower risk of SARS-CoV-2 infection than never-smoking, while a history of smoking was associated with higher risk of severe COVID-19. In this cohort study of 2.4 million adults, adjusting for socio-demographics and medical comorbidities, current tobacco smoking was associated with a lower risk of both SARS-CoV-2 infection and severe COVID-19 illness compared to never-smoking. A history of smoking was associated with a slightly lower risk of SARS-CoV-2 infection and a modestly higher risk of severe COVID-19 illness compared to never-smoking. The lower observed COVID-19 risk for current versus never-smoking deserves further investigation. Results support prioritizing individuals with smoking-related comorbidities for vaccine outreach and treatments as they become available.
Authors: Young-Wolff, Kelly C; Slama, Natalie; Alexeeff, Stacey E; Sakoda, Lori C; Fogelberg, Renee; Myers, Laura C; Campbell, Cynthia I; Adams, Alyce S; Prochaska, Judith J
Nicotine Tob Res. 2023 Jan 05;25(2):211-220.
Rural residence across the life course and late-life cognitive decline in KHANDLE: A causal inference study
Modifiable risks for dementia are more prevalent in rural populations, yet there is a dearth of research examining life course rural residence on late-life cognitive decline. The association of rural residence and socioeconomic status (SES) in childhood and adulthood with late-life cognitive domains (verbal episodic memory, executive function, and semantic memory) and cognitive decline in the Kaiser Healthy Aging and Diverse Life Experiences cohort was estimated using marginal structural models with stabilized inverse probability weights. After adjusting for time-varying SES, the estimated marginal effect of rural residence in childhood was harmful for both executive function (β = -0.19, 95% confidence interval [CI] = -0.32, -0.06) and verbal episodic memory (β = -0.22, 95% CI = -0.35, -0.08). Effects of adult rural residence were imprecisely estimated with beneficial point estimates for both executive function (β = 0.19; 95% CI = -0.07, 0.44) and verbal episodic memory (β = 0.24, 95% CI = -0.07, 0.55). Childhood rurality is associated with poorer late-life cognition independent of SES.
Authors: Peterson, Rachel L; Gilsanz, Paola; Lor, Yi; George, Kristen M; Ko, Michelle; Wagner, Jenny; Soh, Yenee; Meyer, Oanh L; Glymour, M Maria; Whitmer, Rachel A
Alzheimers Dement (Amst). 2023 Jan-Mar;15(1):e12399. Epub 2023-02-03.
Telemedicine along the cascade of care for substance use disorders during the COVID-19 pandemic in the United States
The COVID-19 pandemic has changed the landscape of healthcare service delivery. This review aims to describe telemedicine-delivered substance use disorder (SUD) treatments and services along the cascade of care in the U.S. after the start of the COVID-19 pandemic. A literature review was conducted on PubMed, Embase, Web of Science, and Cochrane Library (Wiley). English-language articles that describe any healthcare services for patients with SUDs using telemedicine in the U.S. since the onset of the COVID-19 pandemic were identified (N = 33). We narratively summarized telemedicine-based service provision along the cascade of SUD care, such as screening/assessment, prescription, monitoring, recovery support, and other services. Soon after the onset of COVID-19 and mandated restrictions, cadres of healthcare providers from different specialties mobilized to ramp up video- and audio-based services to remotely treat patients with SUDs. Medication prescription (48.5%) and individual counseling (39.4%) were the most frequently reported services delivered via telemedicine. Other steps of SUD care delivered by telemedicine characterized in our review included SUD screening and assessment (30.3%), induction (21.2%), medication management (27.3%), monitoring (27.3%), recovery support (15.2%), and referral (24.2%). Feasibility issues and challenges to implementing telemedicine included patients’ lack of access to technology and health insurance coverage, providers’ capacity limits and concerns, and clinics’ financial and office-space constraints. The COVID-19 pandemic has offered a window of opportunity to advance telemedicine expertise by formalizing clinical guidance and routinizing provider in-service training in virtual SUD treatment. Findings suggest enhanced efforts to reduce disparities in telemedicine-based services.
Authors: Lin, Chunqing; Pham, Huyen; Zhu, Yuhui; Clingan, Sarah E; Lin, Lewei Allison; Murphy, Sean M; Campbell, Cynthia I; Sorrell, Tanya R; Liu, Yanping; Mooney, Larissa J; Hser, Yih-Ing
Drug Alcohol Depend. 2023 Jan 01;242:109711. Epub 2022-11-23.
The association between buprenorphine treatment duration and mortality: a multi-site cohort study of people who discontinued treatment
Buprenorphine is an effective medication for opioid use disorder that reduces mortality; however, many patients are not retained in buprenorphine treatment, and an optimal length of treatment after which patients can safely discontinue treatment has not been identified. This study measured the association between buprenorphine treatment duration and all-cause mortality among patients who discontinued treatment. Secondary objectives were to measure the association between treatment duration and drug overdose and opioid-related overdoses. Multi-site cohort study. Eight US health systems. Patients who initiated and discontinued buprenorphine treatment between 1 January 2012 and 31 December 2018 (n = 6550). Outcomes occurring after patients discontinued buprenorphine treatment were compared between patients who initiated and discontinued treatment after 8-30, 31-90, 91-180, 181-365 and > 365 days. Covariate data were obtained from electronic health records (EHRs). Mortality outcomes were derived from EHRs and state vital statistics. Non-fatal opioid and drug overdoses were obtained from diagnostic codes. Four sites provided cause-of-death data to identify fatal drug and opioid-related overdoses. Adjusted frailty regression was conducted on a propensity-weighted cohort to assess associations between duration of the final treatment episode and outcomes. The mortality rate after buprenorphine treatment was 1.82 per 100 person-years (n = 191 deaths). In regression analyses with > 365 days as the reference group, treatment duration was not associated with all-cause mortality and drug overdose (P > 0.05 for both). However, compared with > 365 days of treatment, 91-180 days of treatment was associated with increased opioid overdose risk (hazard ratio = 2.94, 95% confidence interval = 1.11-7.79). Among patients who discontinue buprenorphine treatment, there appears to be no treatment duration period associated with a reduced risk for all-cause mortality. Patients who discontinue buprenorphine treatment after 91-180 days appear to be at heightened risk for opioid overdose compared with patients who discontinue after > 365 days of treatment.
Authors: Glanz, Jason M; Campbell, Cynthia I; et al.
Addiction. 2023 Jan;118(1):97-107. Epub 2022-07-23.
Walking the Benzodiazepine High Wire
The number of benzodiazepine (BZD) prescriptions has substantially increased over the past decade, leading to a parallel rise in rates of misuse and overdose. These increases have prompted the U.S. Food and Drug Administration to update its “boxed warning” and have caused organizations to revisit prescribing guidelines. Concurrently, strong evidence from clinical trials supports the anxiolytic efficacy of BZDs. Although antidepressants and psychotherapy remain preferred treatments for chronic anxiety, BZDs remain helpful in treating acute or severe and persistent anxiety that does not respond to first-line therapy. Provider and patient education, coupled with prescribing surveillance, may be preferable to an overly stringent regulatory approach to guiding BZD use.
Authors: Kroenke, Kurt; Hirschtritt, Matthew E
Psychiatr Serv. 2023 Jan 01;74(1):73-75. Epub 2022-11-02.
Neighborhood disadvantage and dementia incidence in a cohort of Asian American and non-Latino White older adults in Northern California
Some evidence suggests that neighborhood socioeconomic disadvantage is associated with dementia-related outcomes. However, prior research is predominantly among non-Latino Whites. We evaluated the association between neighborhood disadvantage (Area Deprivation Index [ADI]) and dementia incidence in Asian American (n = 18,103) and non-Latino White (n = 149,385) members of a Northern California integrated health care delivery system aged 60 to 89 at baseline. Race/ethnicity-specific Cox proportional hazards models adjusted for individual-level age, sex, socioeconomic measures, and block group population density estimated hazard ratios (HRs) for dementia. Among non-Latino Whites, ADI was associated with dementia incidence (most vs. least disadvantaged ADI quintile HR = 1.09, 95% confidence interval [CI] = 1.02-1.15). Among Asian Americans, associations were close to null (e.g., most vs. least disadvantaged ADI quintile HR = 1.01, 95% CI = 0.85-1.21). ADI was associated with dementia incidence among non-Latino Whites but not Asian Americans. Understanding the potentially different mechanisms driving dementia incidence in these groups could inform dementia prevention efforts.
Authors: Mobley, Taylor M; Shaw, Crystal; Hayes-Larson, Eleanor; Fong, Joseph; Gilsanz, Paola; Gee, Gilbert C; Brookmeyer, Ron; Whitmer, Rachel A; Casey, Joan A; Mayeda, Elizabeth Rose
Alzheimers Dement. 2023 Jan;19(1):296-306. Epub 2022-04-06.
Generation and age of immigration on later life cognitive performance in KHANDLE
We examined the association of generational status and age at immigration with later life cognitive outcomes in a diverse sample of Latinos and Asian Americans. Baseline data were obtained from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study, and a prospective cohort is initiated in 2017. Older adults in Northern California. Our cohort consisted of Asians (n = 411) and Latinos (n = 340) who were on average 76 years old (SD = 6.8). We used multivariable linear regression models to estimate associations between generational status and age at immigration (collapsed into one five-level variable) with measures of verbal episodic memory, semantic memory, and executive function, adjusting for age, gender, race and ethnicity, and own- and parental education. Generational status and age at immigration were associated with cognitive outcomes in a graded manner. Compared to third-generation or higher immigrants, first-generation immigration in adulthood was associated with lower semantic memory (β = -0.96; 95% CI: -1.12, -0.81) than immigration in adolescence (β = -0.68; 95% CI: -0.96, -0.41) or childhood (β = -0.28; 95% CI: -0.49, -0.06). Moreover, immigration in adulthood was associated with lower executive function (β = -0.63; 95% CI: -0.78, -0.48) than immigration in adolescence (β = -0.49; 95% CI: -0.75, -0.23). Similarly, compared to third-generation individuals, first-generation immigrants had lower executive functioning scores. Our study supports the notion that sociocontextual influences in early life impact later life cognitive scores. Longitudinal studies are needed to further clarify how immigration characteristics affect cognitive decline.
Authors: Meyer, Oanh L; Eng, Chloe W; Ko, Michelle J; Chan, Michelle L; Ngo, Uyen; Gilsanz, Paola; Glymour, M Maria; Mayeda, Elizabeth Rose; Mungas, Dan M; Whitmer, Rachel A
Int Psychogeriatr. 2023 Jan;35(1):17-28. Epub 2020-12-23.
Adverse childhood experiences in early life increase the odds of depression among adults with multiple sclerosis
Adverse childhood experiences are demonstrated risk factors for depression, a common co-morbidity of multiple sclerosis, but are understudied among people with multiple sclerosis. Estimate the association between adverse childhood experiences and depression among 1,990 adults with multiple sclerosis. Participants were members of Kaiser Permanente Northern California from two studies between 2006 and 2021 and were diagnosed with multiple sclerosis by a neurologist. Adverse childhood experiences were assessed using two instruments, including the Behavioral Risk Factor Surveillance System. Participants self-reported ever experiencing a major depressive episode. Meta-analysis random effects models and logistic regression were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) to assess the relationship between adverse childhood experiences and a history of depression across study samples. Adverse childhood experiences were expressed as any/none, individual events, and counts. Models adjusted for sex, birth year, race, and ethnicity. Exposure to any adverse childhood experiences increased the odds of depression in people with multiple sclerosis (OR: 1.71, 95% CI: 1.21-2.42). Several individual adverse childhood experiences were also strongly associated with depression, including “significant abuse or neglect” (OR: 2.79, 95% CI: 2.11-3.68). Findings suggest that adverse childhood experiences are associated with depression among people with multiple sclerosis. Screening for depression should be done regularly, especially among people with multiple sclerosis with a history of adverse childhood experiences.
Authors: Guerrero, Karla S;Horton, Mary K;Choudhary, Vidhu;Bellesis, Kalliope H;Dorin, Pete;Mei, Jin;Chinn, Terrence;Meyers, Travis J;Schaefer, Catherine A;Barcellos, Lisa F
Mult Scler J Exp Transl Clin. 2023 Oct-Dec;9(4):20552173231202638. Epub 2023-10-04.
Racial, ethnic, and age disparities in the association of mental health symptoms and polysubstance use among persons in HIV care
We characterized polysubstance use burden and associations with mental health problems across demographic subgroups of PWH. In 2018-2020, as part of a primary care-based intervention study, PWH in care at three medical centers in Kaiser Permanente Northern California were screened for depression (PHQ-9≥10), anxiety (GAD-2≥3), and substance use (Tobacco, Alcohol, Prescription medication, and other Substance use [TAPS]≥1 per substance). We used Poisson regression to estimate prevalence ratios (PRs) comparing polysubstance use prevalence (TAPS≥1 for ≥2 substances) between PWH with positive screens for depression or anxiety vs. neither, among all PWH, and stratified by race/ethnicity and age (restricted to men), adjusting for sociodemographics, CD4, and HIV load. Screened PWH (N = 2865) included 92% men, 56% White, 19% Black, and 15% Hispanic PWH, with a median age of 55 years. Overall, polysubstance use prevalence was 26.4% (95% CI 24.9%-28.1%). PWH with depression or anxiety (n = 515) had an adjusted polysubstance use PR of 1.26 (1.09-1.46) vs. PWH with neither (n = 2350). Adjusted PRs were 1.47 (1.11-1.96), 1.07 (0.74-1.54), and 1.10 (0.85-1.41) among Black, Hispanic, and White men, respectively. Adjusted PRs did not differ by age group. Interventions should consider jointly addressing mental health and substance use problems and potential drivers, e.g. stigma or socioeconomic factors.
Authors: Davy-Mendez, Thibaut;Flamm, Jason A;Iturralde, Esti;Silverberg, Michael J;Satre, Derek D;Satre, Derek D;et al.
PLoS One. 2023;18(11):e0294483. Epub 2023-11-28.
Baseline representativeness of patients in clinics enrolled in the PRimary care Opioid Use Disorders treatment (PROUD) trial: comparison of trial and non-trial clinics in the same health systems
Pragmatic primary care trials aim to test interventions in “real world” health care settings, but clinics willing and able to participate in trials may not be representative of typical clinics. This analysis compared patients in participating and non-participating clinics from the same health systems at baseline in the PRimary care Opioid Use Disorders treatment (PROUD) trial. This observational analysis relied on secondary electronic health record and administrative claims data in 5 of 6 health systems in the PROUD trial. The sample included patients 16-90 years at an eligible primary care visit in the 3 years before randomization. Each system contributed 2 randomized PROUD trial clinics and 4 similarly sized non-trial clinics. We summarized patient characteristics in trial and non-trial clinics in the 2 years before randomization (“baseline”). Using mixed-effect regression models, we compared trial and non-trial clinics on a baseline measure of the primary trial outcome (clinic-level patient-years of opioid use disorder (OUD) treatment, scaled per 10,000 primary care patients seen) and a baseline measure of the secondary trial outcome (patient-level days of acute care utilization among patients with OUD). Patients were generally similar between the 10 trial clinics (n = 248,436) and 20 non-trial clinics (n = 341,130), although trial clinics’ patients were slightly younger, more likely to be Hispanic/Latinx, less likely to be white, more likely to have Medicaid/subsidized insurance, and lived in less wealthy neighborhoods. Baseline outcomes did not differ between trial and non-trial clinics: trial clinics had 1.0 more patient-year of OUD treatment per 10,000 patients (95% CI: - 2.9, 5.0) and a 4% higher rate of days of acute care utilization than non-trial clinics (rate ratio: 1.04; 95% CI: 0.76, 1.42). trial clinics and non-trial clinics were similar regarding most measured patient characteristics, and no differences were observed in baseline measures of trial primary and secondary outcomes. These findings suggest trial clinics were representative of comparably sized clinics within the same health systems. Although results do not reflect generalizability more broadly, this study illustrates an approach to assess representativeness of clinics in future pragmatic primary care trials.
Authors: Wartko, Paige D; Campbell, Cynthia I; Bradley, Katharine A; et al.
BMC Health Serv Res. 2022 Dec 29;22(1):1593. Epub 2022-12-29.
Evaluating Implementation and Outcomes of the Achieving Depression and Anxiety Patient-Centered Treatment Collaborative Care Program in a Large, Integrated Health Care System: A Mixed Methods Observational Study Protocol
Background Collaborative care is an evidence-based multidisciplinary model shown to improve patient depression and anxiety outcomes. Although there is robust literature showing the effectiveness of collaborative care on depression and anxiety symptoms, there is little published on outcomes of collaborative care implementation or the efficacy of collaborative care compared with psychiatric referrals. Reported here is a study protocol examining a novel depression and anxiety collaborative care program in a large, integrated health care system. Methods This is a mixed methods study of the Achieving Depression and Anxiety Patient-Centered Treatment (ADAPT) program as compared to outpatient psychiatric care at Kaiser Permanente Northern California, a large, integrated health care delivery system. The ADAPT program was designed using collaborative care principles, including measurement-based care, accurate diagnosis, and population management. Eligible participants will be ≥ 18 years old with mild to moderate-severe depressive symptoms as measured by the Patient Health Questionnaire-9. Exclusion criteria include acute suicide risk and serious mental health comorbidities. Implementation is examined using the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework and interviews with program stakeholders. Results Pending. Conclusion Study data will help inform future collaborative care efforts while expanding the literature base. The Achieving Depression and Anxiety Patient-Centered Treatment program may improve patient outcomes and access to quality depression and/or anxiety care.
Authors: Ridout, Kathryn K; Ridout, Samuel J; Alavi, Mubarika; Koshy, Maria T; Harris, Brooke; Awsare, Sameer; Fazzolari, Lisa; Weisner, Constance M; Iturralde, Esti
Perm J. 2022 Dec 19;26(4):39-48. Epub 2022-11-10.
Electroconvulsive Therapy Anesthetic Choice and Clinical Outcomes
Etomidate and methohexital are the 2 commonly used anesthetics for electroconvulsive therapy (ECT) in the United States. The objective of this study was to examine how anesthetic choice between etomidate and methohexital is associated with real-world clinical outcomes. This naturalistic retrospective cohort study examined longitudinal electronic health records for 495 adult patients who received 2 or more ECT treatments from 2010 to 2019 in Kaiser Permanente North California, a large integrated health care system. Study outcomes included 12-month posttreatment depression remission as measured by the 9-item Patient Health Questionnaire, psychiatric and all-cause emergency department visits, and psychiatric and all-cause hospitalizations. Anesthetic choice was not significantly related to depression severity, emergency department visits, or psychiatric hospitalizations at 12 months after completing ECT. In exploratory analyses, we found that etomidate compared with methohexital was associated with higher rates of patient discomfort adverse effects-postictal agitation, phlebitis, and myoclonus (2.4% vs 0.4%; P < 0.001). We present the first large comparison of etomidate and methohexital as anesthetics for ECT and their associations with real-world outcomes. Our study showed no significant difference on depression remission, emergency department visits, or hospitalizations 12-months posttreatment. Thus, clinicians should focus on other patient or treatment characteristics when deciding on anesthetics for ECT. Further investigation is needed to confirm our exploratory findings that etomidate use was correlated with a higher rate of patient discomfort adverse effects relative to methohexital.
Authors: Li, Kevin J; Slama, Natalie E; Hirschtritt, Matthew E; Anshu, Prachi; Iturralde, Esti
J ECT. 2022 Dec 09.
Genetic diversity fuels gene discovery for tobacco and alcohol use
Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury1-4. These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries5. Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.
Authors: Saunders, Gretchen R B; Choquet, Hélène; Vrieze, Scott; et al.
Nature. 2022 Dec;612(7941):720-724. Epub 2022-12-07.
Trends in Self-reported and Biochemically Verified Cocaine and Methamphetamine Use Among Pregnant Individuals in Northern California, 2011-2019
This cross-sectional study uses data from the Kaiser Permanente Northern California health care system with universal screening via self-report and urine toxicology at prenatal care entrance to examine trends in cocaine and methamphetamine use among pregnant individuals from 2011 to 2019.
Authors: Young-Wolff, Kelly C; Slama, Natalie E; Sarovar, Varada; Terplan, Mishka; Ansley, Deborah; Adams, Sara R; Alexeeff, Stacey E
JAMA Netw Open. 2022 Dec 01;5(12):e2248055. Epub 2022-12-01.
COVID-19 pandemic-related changes in utilization of telehealth and treatment overall for alcohol use problems
During the COVID-19 pandemic, specialty alcohol treatment transitioned rapidly to telehealth, which may have created barriers for some patients but increased access for others. This study evaluated the impact of the COVID-19 pandemic on alcohol treatment utilization and potential disparities. We analyzed electronic health record and claims data from Kaiser Permanente Northern California for adults with alcohol use problems (alcohol use disorder or unhealthy alcohol use diagnoses) during pre-COVID-19 (March to December 2019, n = 32,806) and COVID-19 onset (March to December 2020, n = 26,763). Generalized estimating equation models were fit to examine pre-COVID-19 to COVID-19 onset changes in alcohol treatment initiation, engagement, and retention (days in treatment). Heterogeneity in pre-COVID-19 to COVID-19 onset changes in treatment utilization by age, race, and ethnicity; neighborhood deprivation index (NDI); and comorbid medical and psychiatric disorders were also examined. Treatment initiation increased during the COVID-19 onset period (adjusted odds ratio [aOR] = 1.46; 95% CI = 1.41-1.52). The increases in odds of treatment initiation during the COVID-19 onset period compared with the pre-COVID period were largest among patients aged 18-34 years (aOR = 1.59; 95% CI = 1.48-1.71), those without medical conditions (aOR = 1.56; 95% CI = 1.49-1.65), and those without psychiatric disorders (aOR = 1.60; 95% CI = 1.51-1.69). Patients aged 18-34 years (aOR = 5.21; 95% CI = 4.67-5.81), those with the second highest NDIs (aOR = 4.63; 95% CI = 4.12-5.19), and those without medical (aOR = 4.34; 95% CI = 4.06-4.65) or psychiatric comorbidities (aOR = 4.48; 95% CI = 4.11-4.89) had the greatest increases in telehealth treatment initiation from pre-COVID-19 to COVID-19 onset. Treatment engagement and retention also increased during COVID-19 onset, with the greatest increase among patients aged 35-49 years who initiated treatment via telehealth (engagement: aOR = 2.33; 95% CI = 1.91-2.83; retention: adjusted mean difference [aMD] = 3.3 days; 95% CI = 2.6-4.1). We found no significant variation of changes in treatment utilization by race and ethnicity. The transition to telehealth in this healthcare system may have attracted subgroups of individuals who have historically underutilized care for alcohol use problems, particularly younger and healthier adults, without exacerbating pre-pandemic racial and ethnic disparities in treatment utilization.
Authors: Palzes, Vanessa A; Chi, Felicia W; Metz, Verena E; Campbell, Cynthia; Corriveau, Caroline; Sterling, Stacy
Alcohol Clin Exp Res. 2022 Dec;46(12):2280-2291. Epub 2022-12-17.
Perceptions About Cannabis Following Legalization Among Pregnant Individuals With Prenatal Cannabis Use in California
As rates of prenatal cannabis use increase and cannabis legalization spreads across the US, studies are needed to understand the potential impacts of legalization from the perspectives of pregnant individuals who use cannabis. To characterize pregnant individuals’ perspectives on legalization of cannabis for adult use in California (effective in 2018) in relation to prenatal cannabis use behaviors and beliefs. This qualitative study was conducted in Kaiser Permanente Northern California, a large health care system with universal screening for self-reported cannabis use at entrance to prenatal care. Eighteen semistructured focus groups were conducted from November 17 to December 17, 2021, using a secure video conferencing platform with Black and White pregnant participants who self-reported cannabis use during early pregnancy. Data were analyzed from March to June 2022. Video-recorded interviews were transcribed and analyzed using thematic analysis to identify major themes and subthemes. Among 53 participants (mean [SD] age, 30.3 [5.2] years), 23 (43%) identified as non-Hispanic Black and 30 (57%) identified as non-Hispanic White; 16 participants (30%) reported continued cannabis use at the time of recruitment. Major themes regarding the perceived impact of legalization included easier access (via retailers and delivery), greater acceptance (including reduced stigma and more discussions about prenatal cannabis use with health care practitioners), and trust in cannabis retailers (including safety and effectiveness of diverse products sold and perceptions of cannabis retailer employees as knowledgeable, nonjudgmental, and caring). Responses were mixed about whether retailer marketing and advertising were associated with prenatal cannabis use and whether legalization resulted in reduced concerns about Child Protective Services involvement. The findings of this qualitative study suggest pregnant individuals perceive cannabis legalization as having reduced barriers to prenatal cannabis use and that legalization has created challenges and opportunities for supporting the health of pregnant individuals. The results of this qualitative study highlight key areas that can be further explored in future educational materials, public health campaigns, and policy adaptations to address increasing rates of prenatal cannabis use.
Authors: Young-Wolff, Kelly C; Mian, Maha N; Iturralde, Esti; et al.
JAMA Netw Open. 2022 Dec 01;5(12):e2246912. Epub 2022-12-01.
Sex Differences in Comorbid Mental and Substance Use Disorders Among Primary Care Patients With Opioid Use Disorder
The authors sought to characterize the 3-year prevalence of mental disorders and nonnicotine substance use disorders among male and female primary care patients with documented opioid use disorder across large U.S. health systems. This retrospective study used 2014-2016 data from patients ages ≥16 years in six health systems. Diagnoses were obtained from electronic health records or claims data; opioid use disorder treatment with buprenorphine or injectable extended-release naltrexone was determined through prescription and procedure data. Adjusted prevalence of comorbid conditions among patients with opioid use disorder (with or without treatment), stratified by sex, was estimated by fitting logistic regression models for each condition and applying marginal standardization. Females (53.2%, N=7,431) and males (46.8%, N=6,548) had a similar prevalence of opioid use disorder. Comorbid mental disorders among those with opioid use disorder were more prevalent among females (86.4% vs. 74.3%, respectively), whereas comorbid other substance use disorders (excluding nicotine) were more common among males (51.9% vs. 60.9%, respectively). These differences held for those receiving medication treatment for opioid use disorder, with mental disorders being more common among treated females (83% vs. 71%) and other substance use disorders more common among treated males (68% vs. 63%). Among patients with a single mental health condition comorbid with opioid use disorder, females were less likely than males to receive medication treatment for opioid use disorder (15% vs. 20%, respectively). The high rate of comorbid conditions among patients with opioid use disorder indicates a strong need to supply primary care providers with adequate resources for integrated opioid use disorder treatment.
Authors: Braciszewski, Jordan M; Campbell, Cynthia I; Boudreau, Denise M; et al.
Psychiatr Serv. 2022 Dec 01;73(12):1330-1337. Epub 2022-06-16.
Effectiveness of a pharmacist-delivered primary care telemedicine intervention to increase access to pharmacotherapy and specialty treatment for alcohol use problems: Protocol for the alcohol telemedicine consult cluster-randomized pragmatic trial
Alcohol use problems are associated with serious medical, mental health and socio-economic consequences. Yet even when patients are identified in healthcare settings, most do not receive treatment, and use of pharmacotherapy is rare. This study will test the effectiveness of the Alcohol Telemedicine Consult (ATC) Service, a novel, personalized telehealth intervention approach for primary care patients with alcohol use problems. This cluster-randomized pragmatic trial, supplemented by qualitative interviews, will include adults with a primary care visit between 9/10/21-3/10/23 from 16 primary care clinics at two large urban medical centers within Kaiser Permanente Northern California, a large, integrated healthcare system. Clinics are randomized to the ATC Service (intervention), including alcohol pharmacotherapy and SBIRT (screening, MI (Motivational Interviewing)-based brief intervention and referral to addiction treatment) delivered by clinical pharmacists, or the Usual Care (UC) arm that provides systematic alcohol SBIRT. Primary outcomes include a comparison of the ATC and UC arms on 1) implementation outcomes (alcohol pharmacotherapy prescription rates, specialty addiction treatment referrals); and 2) patient outcomes (medication fills, addiction treatment initiation, alcohol use, healthcare services utilization) over 1.5 years. A general modeling approach will consider clustering of patients/providers, and a random effects model will account for intra-class correlations across patients within providers and across clinics. Qualitative interviews with providers will examine barriers and facilitators to implementation. The ATC study examines the effectiveness of a pharmacist-provided telehealth intervention that combines pharmacotherapy and MI-based consultation. If effective, the ATC study could affect treatment models across the spectrum of alcohol use problems. This study has been registered on ClinicalTrials.gov (NCT05252221).
Authors: Metz, Verena E; Leibowitz, Amy; Satre, Derek D; Parthasarathy, Sujaya; Jackson-Morris, Melanie; Cocohoba, Jennifer; Sterling, Stacy A
Contemp Clin Trials. 2022 Dec;123:107004. Epub 2022-11-13.
The effect of the COVID-19 pandemic on prenatal cannabis use by pre-conception depression and anxiety status
Authors: Avalos, Lyndsay A; Ray, G Thomas; Alexeeff, Stacey E; Adams, Sara R; Does, Monique; Ansley, Deborah; Tucker, Lue-Yen; Conway, Amy; Ettenger, Allison; Goler, Nancy; Young-Wolff, Kelly C
J Affect Disord Rep. 2022 Dec;10:100432. Epub 2022-11-11.
A Novel Introduction to Transgender and Nonbinary Mental Health
Authors: Frawley, Erin M; Norris, Ryan; Chen, Ingrid L; Hirschtritt, Matthew E
Acad Psychiatry. 2022 Dec;46(6):787-788. Epub 2022-05-03.
Consideration of sex and gender in Alzheimer’s disease and related disorders from a global perspective
Sex or gender differences in the risk of Alzheimer’s disease and related dementias (ADRD) differ by world region, suggesting that there are potentially modifiable risk factors for intervention. However, few epidemiological or clinical ADRD studies examine sex differences; even fewer evaluate gender in the context of ADRD risk. The goals of this perspective are to: (1) provide definitions of gender, biologic sex, and sexual orientation. and the limitations of examining these as binary variables; (2) provide an overview of what is known with regard to sex and gender differences in the risk, prevention, and diagnosis of ADRD; and (3) discuss these sex and gender differences from a global, worldwide perspective. Identifying drivers of sex and gender differences in ADRD throughout the world is a first step in developing interventions unique to each geographical and sociocultural area to reduce these inequities and to ultimately reduce global ADRD risk. HIGHLIGHTS: The burden of dementia is unevenly distributed geographically and by sex and gender. Scientific advances in genetics and biomarkers challenge beliefs that sex is binary. Discrimination against women and sex and gender minority (SGM) populations contributes to cognitive decline. Sociocultural factors lead to gender inequities in Alzheimer’s disease and related dementias (ADRD) worldwide.
Authors: Mielke, Michelle M; Gilsanz, Paola; Diversity and Disparity Professional Interest Area Sex and Gender Special Interest Group,; et al.
Alzheimers Dement. 2022 Dec;18(12):2707-2724. Epub 2022-04-08.
SNP-by-CpG Site Interactions in ABCA7 Are Associated with Cognition in Older African Americans
SNPs in ABCA7 confer the largest genetic risk for Alzheimer’s Disease (AD) in African Americans (AA) after APOE ε4. However, the relationship between ABCA7 and cognitive function has not been thoroughly examined. We investigated the effects of five known AD risk SNPs and 72 CpGs in ABCA7, as well as their interactions, on general cognitive function (cognition) in 634 older AA without dementia from Genetic Epidemiology Network of Arteriopathy (GENOA). Using linear mixed models, no SNP or CpG was associated with cognition after multiple testing correction, but five CpGs were nominally associated (p < 0.05). Four SNP-by-CpG interactions were associated with cognition (FDR q < 0.1). Contrast tests show that methylation is associated with cognition in some genotype groups (p < 0.05): a 1% increase at cg00135882 and cg22271697 is associated with a 0.68 SD decrease and 0.14 SD increase in cognition for those with the rs3764647 GG/AG (p = 0.004) and AA (p = 2 × 10-4) genotypes, respectively. In addition, a 1% increase at cg06169110 and cg17316918 is associated with a 0.37 SD decrease (p = 2 × 10-4) and 0.33 SD increase (p = 0.004), respectively, in cognition for those with the rs115550680 GG/AG genotype. While AD risk SNPs in ABCA7 were not associated with cognition in this sample, some have interactions with proximal methylation on cognition.
Authors: Chaar, Dima L;Nguyen, Kim;Wang, Yi-Zhe;Ratliff, Scott M;Mosley, Thomas H;Kardia, Sharon L R;Smith, Jennifer A;Zhao, Wei
Genes (Basel). 2022 Nov 18;13(11):pii: 2150. doi: 10.3390/genes13112150..
Accuracy of ICD-10-CM encounter diagnoses from health records for identifying self-harm events
Assess the accuracy of ICD-10-CM coding of self-harm injuries and poisonings to identify self-harm events. In 7 integrated health systems, records data identified patients reporting frequent suicidal ideation. Records then identified subsequent ICD-10-CM injury and poisoning codes indicating self-harm as well as selected codes in 3 categories where uncoded self-harm events might be found: injuries and poisonings coded as undetermined intent, those coded accidental, and injuries with no coding of intent. For injury and poisoning encounters with diagnoses in those 4 groups, relevant clinical text was extracted from records and assessed by a blinded panel regarding documentation of self-harm intent. Diagnostic codes selected for review include all codes for self-harm, 43 codes for undetermined intent, 26 codes for accidental intent, and 46 codes for injuries without coding of intent. Clinical text was available for review for 285 events originally coded as self-harm, 85 coded as undetermined intent, 302 coded as accidents, and 438 injury events with no coding of intent. Blinded review of full-text clinical records found documentation of self-harm intent in 254 (89.1%) of those originally coded as self-harm, 24 (28.2%) of those coded as undetermined, 24 (7.9%) of those coded as accidental, and 48 (11.0%) of those without coding of intent. Among patients at high risk, nearly 90% of injuries and poisonings with ICD-10-CM coding of self-harm have documentation of self-harm intent. Reliance on ICD-10-CM coding of intent to identify self-harm would fail to include a small proportion of true self-harm events.
Authors: Simon, Gregory E; Sterling, Stacy; Yaseen, Zimri S; et al.
J Am Med Inform Assoc. 2022 Nov 14;29(12):2023-2031.
“A Lot of Things Stopped with COVID”: Screening Pregnant Patients for Opioid Use and Related Conditions During the COVID-19 Pandemic
We explored the impact of COVID-19 on universal screening programs for opioid use and related conditions among practicing clinicians or staff who work with pregnant patients. Semi-structured, in-depth qualitative interviews (n = 15) were conducted with practicing clinicians or staff in West-Central Florida between May and October 2020, representing both a range of professions and clinical settings that serve pregnant patients. Interviews were recorded, transcribed verbatim, and reviewed for accuracy. Independent coders conducted thematic content analysis iteratively in MaxQDA to identify emergent themes. Four main themes were identified: worsening health and life conditions of pregnant patients, impaired patient-provider interactions, lack of priority and resources, and conducting opioid screening remotely. Pregnant patients often faced worsening mental health, lack of connection with health care providers, and socioenvironmental factors that increased the risk of overdose and intimate partner violence. Health care providers and facilities faced an infectious disease pandemic that simultaneously increased mental burden and reduced resources. Telehealth improved access to health care for many, but also came with implementation challenges such as inadequate technology, the need to address barriers to developing rapport with patients, and difficulty with certain social screens. These themes describe facilitators of and barriers to implementing opioid and related screening programs during the COVID-19 pandemic, as well as the increasing urgency of screening because of socioenvironmental factors. Patients, health care providers, and health practices may benefit from emergency plans that anticipate screening challenges given their increased importance during times of heightened risk, including disasters and epidemics.
Authors: Foti, Tara R; Vereen, Shanda; Vamos, Cheryl; Sappenfield, William; Kirby, Russell S
Womens Health Issues. 2022 Nov 07.
Smoking Behaviors and Prognosis in Patients With Non-Muscle-Invasive Bladder Cancer in the Be-Well Study
Tobacco smoking is an established risk factor associated with bladder cancer, yet its impact on bladder cancer prognosis is unclear. To examine associations of use of tobacco (cigarettes, pipes, and cigars), e-cigarettes, and marijuana with risk of recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) and to explore use of smoking cessation interventions. The Be-Well Study is a prospective cohort study of patients with NMIBC diagnosed from 2015 to 2019 and followed-up for 26.4 months in the Kaiser Permanente Northern and Southern California integrated health care system. Eligibility criteria were age at least 21 years, first NMIBC diagnosis (stages Ta, Tis, or T1), alive, and not in hospice care. Exclusion criteria were previous diagnosis of bladder cancer or other cancer diagnoses within 1 year prior to or concurrent with NMIBC diagnosis. Data were analyzed from April 1 to October 4, 2022. Use of cigarettes, pipes, cigars, e-cigarettes, and marijuana was reported in the baseline interview. Use of smoking cessation interventions (counseling and medications) was derived from electronic health records. Hazard ratios (HRs) and 95% CIs of recurrence and progression of bladder cancer were estimated by multivariable Cox proportional hazards regression. A total of 1472 patients (mean [SD] age at diagnosis, 70.2 [10.8%] years; 1129 [76.7%] male patients) with NMIBC were enrolled at a mean (SD) of 2.3 (1.3) months after diagnosis, including 874 patients (59.4%) who were former smokers and 111 patients (7.5%) who were current cigarette smokers; 67 patients (13.7%) smoked pipes and/or cigars only, 65 patients (4.4%) used e-cigarettes, 363 patients (24.7%) used marijuana. Longer cigarette smoking duration and more pack-years were associated with higher risk of recurrence in a dose-dependent manner, with the highest risks for patients who had smoked for 40 or more years (HR, 2.36; 95% CI, 1.43-3.91) or 40 or more pack-years (HR, 1.97; 95% CI, 1.32-2.95). There was no association of having ever smoked, being a former or current cigarette smoker, and years since quit smoking with recurrence risk. No associations with pipes, cigars, e-cigarettes, or marijuana were found. Of 102 patients offered a smoking cessation intervention, 57 (53.8%) received an interventions after diagnosis, with female patients more likely than male patients to engage in such interventions (23 of 30 female patients [76.7%] vs 34 of 76 male patients [44.7%]; P = .003). These findings suggest that longer duration and more pack-years of cigarette smoking were associated with higher risk of NMIBC recurrence. Cigarette smoking remains a critical exposure before and after diagnosis in survivors of NMIBC.
Authors: Kwan, Marilyn L; Young-Wolff, Kelly C; Ergas, Isaac J; Quesenberry, Charles P; Kushi, Lawrence H; Tang, Li; et al.
JAMA Netw Open. 2022 Nov 01;5(11):e2244430. Epub 2022-11-01.
Geographic Accessibility of Retail Cannabis in Northern California and Prenatal Cannabis Use During the COVID-19 Pandemic
Prenatal cannabis use is associated with health risks for mothers and their children. Prior research suggests that rates of prenatal cannabis use in Northern California increased during the COVID-19 pandemic, but it is unknown whether increases varied with the local cannabis retail and policy environment. To test whether pandemic-related increases in prenatal cannabis use were greater among pregnant individuals with greater retail availability of cannabis around their homes or among those living in jurisdictions that allowed storefront retailers. A cross-sectional, population-based time series study used data from pregnancies in the Kaiser Permanente Northern California health care system screened for cannabis use before (January 1, 2019, to March 31, 2020) and during (April 1 to December 31, 2020) the early COVID-19 pandemic. Proximity to the nearest retailer and number of retailers within a 15-minute drive from one’s home and local cannabis storefront retailer policy (banned vs permitted) were calculated. Interrupted time series models were fit using multiplicative and additive Poisson regression, adjusting for age and race and ethnicity. The COVID-19 pandemic. Prenatal cannabis use based on universal urine toxicology tests conducted during early pregnancy at entrance to prenatal care. The sample (n = 99 127 pregnancies) included 26.2% Asian or Pacific Islander, 6.8% Black, 27.6% Hispanic, 34.4% non-Hispanic White, and 4.9% other, unknown, or multiracial individuals, with a mean (SD) age of 30.8 (5.3) years. Prenatal cannabis use before (6.8%) and during (8.2%) the pandemic was associated with closer proximity to a retailer, greater retailer density, and residing in a jurisdiction that permitted vs banned retailers. There was a greater absolute increase in cannabis use from before to during the pandemic among those within a 10-minute drive (<10 minutes: adjusted rate difference [aRD], 0.93 cases/100 patients; 95% CI, 0.56-1.29 cases/100 patients; ≥10 minutes: aRD, 0.40 cases/100 patients; 95% CI, 0.12-0.68 cases/100 patients; interaction P = .02). Otherwise, relative and absolute rates increased similarly across categories of cannabis retailer proximity/density and local policy (interaction P > .05). Prenatal cannabis use was more common among individuals living in areas with greater retail availability of cannabis. Although relative rates increased similarly during the pandemic regardless of local cannabis retail and policy environment, there was a larger absolute increase associated with living closer to a storefront cannabis retailer. Continued monitoring of local cannabis policy, the retail environment, and prenatal cannabis use is needed.
Authors: Young-Wolff, Kelly C; Alexeeff, Stacey E; Campbell, Cynthia I; Avalos, Lyndsay A; et al.
JAMA Netw Open. 2022 Nov 01;5(11):e2244086. Epub 2022-11-01.
Patterns of Health Care Use 5 Years After an Intervention Linking Patients in Addiction Treatment With a Primary Care Practitioner
Substance use disorders are associated with high rates of emergency department (ED) use and challenges engaging with primary care services. To examine 5-year health care engagement and utilization outcomes for participants in the LINKAGE trial, given previously reported associations of LINKAGE with improved care engagement in the short term. In this post hoc analysis of a nonrandomized controlled trial, participants were assigned to the LINKAGE or usual care (UC) groups using a nonrandomized 3-month alternating off and on strategy over 30 months. Baseline through 5-year follow-up data were collected from April 2011 to October 2018. The trial was conducted at an urban outpatient addiction treatment clinic within a large health system among patients newly enrolled in addiction treatment. Data analysis was conducted from April 2021 to February 2022. The LINKAGE intervention included 6 group-based sessions emphasizing patient agency, skill, and motivation in navigating health care services as well as a facilitated telephone or email connection with a primary care practitioner. The UC group received medical education. Substance use problem discussions with primary care practitioners (by patient self-report at 1-, 2-, and 5-year follow-up interview) and annual use of the electronic patient portal, primary care, and ED based on electronic health records. A total of 503 participants, with a mean (SD) age of 42 (12) years, 346 (69%) male participants and 37 (7%) African American, 34 (7%) Asian, and 101 (20%) Hispanic participants, were assigned to LINKAGE (252 participants) or UC (251 participants). Compared with UC participants, LINKAGE participants were significantly more likely to discuss substance use problems with a primary care practitioner at 1-year follow-up (risk ratio [RR], 1.30; 95% CI, 1.03-1.65; P = .03) and use the electronic patient portal at 1- and 2-year follow-up (eg, messaging clinicians at 2 years: RR, 1.24; 95% CI, 1.04-1.47; P = .02). The LINKAGE group had small, statistically significant 5-year annual increases in primary care use (RR, 1.03; 95% CI, 1.003-1.07; P = .03) and significant annual decreases in substance-related ED use (RR, 0.79; 95% CI, 0.64-0.97; P = .03), relative to UC. The LINKAGE group did not significantly differ from the UC group on other types of ED utilization. In this study, a patient activation intervention embedded in outpatient addiction treatment was associated with sustained improvements in health care engagement beyond previously reported 6-month outcomes and with long-term improvements in health care use patterns. ClinicalTrials.gov Identifier: NCT01621711.
Authors: Iturralde, Esti; Weisner, Constance M; Adams, Sara R; Chi, Felicia W; Ross, Thekla B; Cunningham, Sarah F; Ghadiali, Murtuza; Asyyed, Asma H; Satre, Derek D; Campbell, Cynthia I; Sterling, Stacy A
JAMA Netw Open. 2022 Nov 01;5(11):e2241338. Epub 2022-11-01.
Predicting severe alcohol use disorders in primary care using number of heavy drinking days
Although screening for unhealthy alcohol use is becoming more common, severe alcohol use disorders (AUDs) associated with the most severe medical and socio-economic sequelae still often go unidentified in primary care. To improve identification of severe AUDs and aid clinical decision-making, we aimed to identify a threshold of heavy drinking days (HDDs) associated with severe AUDs. This cohort study analyzed electronic health record data of 138 765 adults who reported ≥ 1 HDD (4+ drinks/occasion for women and men aged ≥ 65 years, 5+ for men aged 18-64 years) during a 3-month period at a routine alcohol screening in primary care in a large Northern California, USA health-care system from 2014 to 2017. Our sample was 66.5% male, 59.7% white, 11.0% Asian/Pacific Islander, 5.0% black, 17.4% Latino/Hispanic and 7.0% other/unknown race/ethnicity; the mean age was 40.6 years (standard deviation = 15.2). We compared sensitivity and specificity of different thresholds of the reported number of HDDs during a 3-month period for predicting severe AUD diagnoses in the following year, in the full sample and by sex and age. The prevalence of severe AUD diagnoses in the year after the screening was 0.6%. The optimal threshold predicting future severe AUD diagnoses in the full sample was ≥ 5 HDDs during a 3-month period [sensitivity = 68.9%, 95% confidence interval (CI) = 65.9, 72.0; specificity = 63.2%, 95% CI = 62.9, 63.4], but varied by sex and age. Women had a lower threshold than men (4 versus 6 HDDs), which decreased as women aged (from 5 HDDs among 18-24 years to 4 HDDs ≥ 25 years), but increased as men aged (from 5 HDDs among 18-24 years to 6 HDDs among 25-64 years, to 7 HDDs ≥ 65 years). Five or more heavy drinking days in a 3-month period may indicate heightened risk of future severe alcohol use disorder in an adult primary care population. The optimal thresholds are lower for women than for men, and thresholds decrease as women age but increase as men age.
Authors: Metz, Verena E; Palzes, Vanessa A; Kline-Simon, Andrea H; Chi, Felicia W; Weisner, Constance M; Sterling, Stacy A
Addiction. 2022 Nov;117(11):2847-2854. Epub 2022-07-25.
Patient-Reported Bothersome Symptoms Attributed to Alcohol Use Among People With and Without HIV
Helping people with HIV (PWH) and without HIV (PWoH) understand the relationship between physical symptoms and alcohol use might help motivate them to decrease use. In surveys collected in the Veterans Aging Cohort Study from 2002 to 2018, PWH and PWoH were asked about 20 common symptoms and whether they thought any were caused by alcohol use. Analyses were restricted to current alcohol users (AUDIT-C > 0). We applied generalized estimating equations. The outcome was having any Symptoms Attributed to Alcohol use (SxAA). Primary independent variables were each of the 20 symptoms and HIV status. Compared to PWoH, PWH had increased odds of SxAA (OR 1.54; 95% CI 1.27, 1.88). Increased AUDIT-C score was also associated with SxAA (OR 1.32; 95% CI 1.28, 1.36), as were trouble remembering, anxiety, and weight loss/wasting. Evidence that specific symptoms are attributed to alcohol use may help motive people with and without HIV decrease their alcohol use.
Authors: Gordon, Kirsha S; Becker, William C; Bryant, Kendall J; Crystal, Stephen; Maisto, Stephen A; Marshall, Brandon D L; McInnes, D Keith; Satre, Derek D; Williams, Emily C; Edelman, E Jennifer; Justice, Amy C
AIDS Behav. 2022 Nov;26(11):3589-3596. Epub 2022-05-13.
Accounting for lack of representation in dementia research: Generalizing KHANDLE study findings on the prevalence of cognitive impairment to the California older population
Most dementia studies are not population-representative; statistical tools can be applied to samples to obtain critically-needed population-representative estimates, but are not yet widely used. We pooled data from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study and the California Behavioral Risk Factor Surveillance System (CA-BRFSS), a population-representative study. Using weights accounting for sociodemographic/health differences between KHANDLE and CA-BRFSS, we estimated cognitive impairment prevalence and age- and sex-adjusted racial/ethnic inequalities in California adults 65+ without prior dementia diagnosis. After weighting KHANDLE, the estimated cognitive impairment prevalence in California was 20.3% (95% confidence interval 17.8-23.0); unweighted prevalence was 24.8% (23.1%-26.6%). Inequalities (larger prevalences) were observed among Black and Asian groups versus whites. We used a novel statistical approach to estimate population-representative cognitive impairment prevalence and inequalities. Such statistical tools can help obtain population-representative estimates from existing studies and inform efforts to reduce racial/ethnic disparities.
Authors: Hayes-Larson, Eleanor; Mobley, Taylor M; Mungas, Dan; Seamans, Marissa J; Glymour, M Maria; Gilsanz, Paola; DeCarli, Charles; Whitmer, Rachel A; Mayeda, Elizabeth Rose
Alzheimers Dement. 2022 Nov;18(11):2209-2217. Epub 2022-02-01.
Pregnant women’s perspectives on screening for adverse childhood experiences and resilience during prenatal care
To examine the acceptability of routine screening for adverse childhood experiences (ACEs) and resilience during prenatal care. This study examined pregnant women’s perspectives (N = 119) on ACEs and resilience screening during prenatal care in two medical centers via postscreening telephone surveys. Chi-square tests and Fisher’s Exact Tests examined whether responses varied with ACEs (0 [62.2%], 1-2 [21.0%], 3+ [16.8%]) or resilience (high [64.7%] vs. low [35.3%]). The sample (N = 119) was 36.1% non-Hispanic White, 26.1% Hispanic, 8.4% Black, 23.5% Asian/Pacific Islander, and 5.9% Other, with a median age of 31 (IQR: 28-34) and average neighborhood median household income of $100,734 (SD = $37,079). Most women thought prenatal care should include conversations about ACEs (82.2%) and resilience (94.0%) and very strongly believed that good coping skills can help reduce the harmful effects of childhood stress (79.0%). Nearly half (41.2%) used ≥1 mental health resource from the resource handout provided at screening. Some women thought conversations could be improved if they took place with a mental health professional (37.3%), with more provider empathy (40.7%), more education about ACEs and health (55.1%), and if the screening included additional stressors (53.4%). Notably, most women (73.5%) would like their partner to also receive the screening. Women with more ACEs were more likely to want a longer conversation, and those with low versus high resilience were more likely to prefer that a mental health professional conduct the screening. Results indicate that women value ACEs screening during prenatal care and provide actionable recommendations to improve future screenings and discussions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Authors: Watson, Carey; Wei, Julia; Varnado, Nicole; Rios, Normelena; Staunton, Mary; Ferguson, Dorothy; Young-Wolff, Kelly C
Psychol Trauma. 2022 Nov;14(8):1299-1303. Epub 2022-01-13.
Association of Social Integration with Cognitive Status in a Multi-Ethnic Cohort: Results From the Kaiser Healthy Aging and Diverse Life Experiences Study
We evaluated overall and race-specific relationships between social integration and cognition in older adults. Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) cohort participants included 1343 Asian, Black, Latino, or non-Latino White Kaiser Permanente Northern California members. We estimated the effect of social integration on verbal episodic memory, semantic memory, and executive function derived from the Spanish and English Neuropsychological Assessment (SENAS) Scales. Social integration scores included marital status; volunteer activity; and contact with children, relatives, friends, and confidants. We estimated covariate-adjusted linear mixed-effects models for baseline and 17-month follow-up cognition. Social integration was associated with higher baseline cognitive scores (average β = 0.066 (95% confidence interval: 0.040, 0.092)) overall and in each racial/ethnic group. The association did not vary by race/ethnicity. Social integration was not associated with the estimated rate of cognitive change. In this cohort, more social integration was similarly associated with better late-life cognition across racial/ethnic groups.
Authors: Calmasini, Camilla; Swinnerton, Kaitlin N; Zimmerman, Scott C; Peterson, Rachel L; George, Kristen M; Gilsanz, Paola; Hayes-Larson, Eleanor; Mayeda, Elizabeth Rose; Mungas, Dan M; Whitmer, Rachel A; Glymour, Medellena Maria
J Geriatr Psychiatry Neurol. 2022 11;35(6):789-799. Epub 2022-01-25.
Patterns of Substance Use During Early Pregnancy and Associations With Behavioral Health Characteristics
The aims of the study are to identify patterns of early pregnancy substance use and to examine how these patterns relate to behavioral health conditions measured in early pregnancy. We conducted a retrospective observational study (N= 265,274 pregnancies) screened for alcohol, cannabis, nicotine, pharmaceutical opioids, and stimulants during the first trimester via self-report and urine toxicology tests in Kaiser Permanente Northern California from January 1, 2012, to December 31, 2019. To identify patterns of prenatal substance use, we conducted latent class analysis. We then calculated the prevalence of depression, anxiety, intimate partner violence, and family drug use history for each prenatal substance use group and compared the prevalences by estimating prevalence ratios using modified Poisson regression, adjusting for sociodemographic characteristics. We identified the following 4 latent groups with different patterns of substance use: (a) predominantly alcohol and no other substances (9.30%), (b) predominantly cannabis and no other substances (4.88%), (c) predominantly nicotine and some pharmaceutical opioids (1.09%), and (d) high-polysubstance (alcohol, cannabis, nicotine, and stimulants; 0.36%); these pregnancies were compared with (e) no prenatal substance use (84.37%). The prevalence of all behavioral health conditions was elevated in all prenatal substance use groups compared with the no substance use group. Furthermore, the prevalence of depressive and anxiety disorders, intimate partner violence and family drug use history were greater in the high-polysubstance cluster than the alcohol and cannabis clusters. Results highlight the importance of screening and interventions for all types of substance use during early pregnancy and suggest a particularly high need to prioritize targeting early interventions to pregnant and reproductive age individuals with polysubstance use.
Authors: Sujan, Ayesha C; Alexeeff, Stacey E; Slama, Natalie; Avalos, Lyndsay A; Adams, Sara R; Conway, Amy; Ansley, Deborah; Young-Wolff, Kelly C
J Addict Med. 2022 Oct 18.
Young Adult Substance Use and Healthcare Use Associated With Screening, Brief Intervention and Referral to Treatment in Pediatric Primary Care
Screening, brief intervention, and referral to treatment (SBIRT) may impact future comorbidity and healthcare utilization among adolescents screening positive for substance use or mood problems. In a randomized trial sample, we compared an SBIRT group to usual care for substance use, mental health, medical diagnoses, and healthcare utilization over 7 years postscreening. In logistic regression models adjusting for patient characteristics, the SBIRT group had lower odds of any substance (Odds Ratio[OR] = 0.80, 95% Confidence Interval [CI] = 0.66-.98), alcohol (OR = 0.69, 95% CI = 0.51-0.94), any drug (OR = 0.73, 95% CI = 0.54-0.98), marijuana (OR = 0.70, 95% CI = 0.50-0.98), and tobacco (OR = 0.83, 95% CI = 0.69-1.00) diagnoses, and lower odds of any inpatient hospitalizations (OR = 0.59, 95% CI = 0.41-0.85) compared with usual care. Negative binomial models examining number of visits among adolescents with at least one visit of that type found that those in the SBIRT group had fewer primary care (incidence rate ratio[iRR] = 0.90, p < .05) and psychiatry (iRR = 0.64, p < .01) and more addiction medicine (iRR = 1.52, p < .01) visits over 7 years compared with usual care. In posthoc analyses, we found that among Hispanic patients, those in the SBIRT group had lower odds of any substance, any drug and marijuana use disorder diagnoses compared with usual care, and among Black/African American patients, those in the SBIRT group had lower odds of alcohol use disorder diagnoses compared with usual care. Beneficial effects of adolescent SBIRT on substance use and healthcare utilization may persist into young adulthood.
Authors: Sterling, Stacy; Parthasarathy, Sujaya; Jones, Ashley; Weisner, Constance; Metz, Verena; Hartman, Lauren; Saba, Katrina; Kline-Simon, Andrea H
J Adolesc Health. 2022 Oct;71(4S):S15-S23.
Comparing the effectiveness of a brief intervention to reduce unhealthy alcohol use among adult primary care patients with and without depression: A machine learning approach with augmented inverse probability weighting
The combination of unhealthy alcohol use and depression is associated with adverse outcomes including higher rates of alcohol use disorder and poorer depression course. Therefore, addressing alcohol use among individuals with depression may have a substantial public health impact. We compared the effectiveness of a brief intervention (BI) for unhealthy alcohol use among patients with and without depression. This observational study included 312,056 adult primary care patients at Kaiser Permanente Northern California who screened positive for unhealthy drinking between 2014 and 2017. Approximately half (48%) received a BI for alcohol use and 9% had depression. We examined 12-month changes in heavy drinking days in the previous three months, drinking days per week, drinks per drinking day, and drinks per week. Machine learning was used to estimate BI propensity, follow-up participation, and alcohol outcomes for an augmented inverse probability weighting (AIPW) estimator of the average treatment (BI) effect. This approach does not depend on the strong parametric assumptions of traditional logistic regression, making it more robust to model misspecification. BI had a significant effect on each alcohol use outcome in the non-depressed subgroup (-0.41 to -0.05, all ps < .003), but not in the depressed subgroup (-0.33 to -0.01, all ps > .28). However, differences between subgroups were nonsignificant (0.00 to 0.11, all ps > .44). On average, BI is an effective approach to reducing unhealthy drinking, but more research is necessary to understand its impact on patients with depression. AIPW with machine learning provides a robust method for comparing intervention effectiveness across subgroups.
Authors: Papini, Santiago; Chi, Felicia W; Schuler, Alejandro; Satre, Derek D; Liu, Vincent X; Sterling, Stacy A
Drug Alcohol Depend. 2022 Oct 01;239:109607. Epub 2022-08-27.
Development and Testing of a Communication Intervention to Improve Chronic Pain Management in Primary Care: A Pilot Randomized Clinical Trial
Effective communication skills are essential for optimally managing chronic pain and opioids. This exploratory, sequential mixed methods study tested the effect of a novel framework designed to improve pain-related communication and outcomes. Study 1 developed a novel 5-step framework for helping primary care clinicians discuss chronic pain and opioids with patients. Study 2 pilot tested an intervention for teaching this framework using standardized patient instructors-actors trained to portray patients and provide immediate clinician feedback-deployed during regular clinic hours. Primary care physicians were randomized to receive either the intervention or pain management recommendations from the Centers for Disease Control and Prevention. Primary outcomes were pain-related interference at 2 months and clinician use of targeted communication skills (coded from transcripts of audio-recorded visits); secondary outcomes were pain intensity at 2 months, clinician self-efficacy for communicating about chronic pain, patient experience, and clinician-reported visit difficulty. We enrolled 47 primary care physicians from 2 academic teaching clinics and recorded visits with 48 patients taking opioids for chronic pain who had an appointment scheduled with an enrolled physician. The intervention was not associated with significant changes in primary or secondary outcomes other than clinician self-efficacy, which was significantly greater in the intervention group. This study developed a novel framework and intervention for teaching clinician pain-related communications skills. Although the intervention showed promise, more intensive or multicomponent interventions may be needed to have a significant impact on clinicians’ pain-related communication and pain outcomes.
Authors: Henry, Stephen G; Fenton, Joshua J; Campbell, Cynthia I; Sullivan, Mark; Weinberg, Gary; Naz, Hiba; Graham, Wyatt M; Dossett, Michelle L; Kravitz, Richard L
Clin J Pain. 2022 10 01;38(10):620-631. Epub 2022-10-01.
A population-health approach to characterizing migraine by comorbidity: Results from the Mindfulness and Migraine Cohort Study
The heterogeneity of migraine has been reported extensively, with identified subgroups usually based on symptoms. Grouping individuals with migraine and similar comorbidity profiles has been suggested, however such segmentation methods have not been tested using real-world clinical data. To gain insights into natural groupings of patients with migraine using latent class analysis based on electronic health record-determined comorbidities. Retrospective electronic health record data analysis of primary-care patients at Sutter Health, a large open healthcare system in Northern California, USA. We identified migraine patients over a five-year time period (2015-2019) and extracted 29 comorbidities. We then applied latent class analysis to identify comorbidity-based natural subgroups. We identified 95,563 patients with migraine and found seven latent classes, summarized by their predominant comorbidities and population share: fewest comorbidities (61.8%), psychiatric (18.3%), some comorbidities (10.0%), most comorbidities – no cardiovascular (3.6%), vascular (3.1%), autoimmune/joint/pain (2.2%), and most comorbidities (1.0%). We found minimal demographic differences across classes. Our study found groupings of migraine patients based on comorbidity that have the potential to be used to guide targeted treatment strategies and the development of new therapies.
Authors: Sudat, Sylvia Ek; Jacobson, Alice S; Avins, Andrew L; Lipton, Richard B; Pressman, Alice R
Cephalalgia. 2022 10;42(11-12):1255-1264. Epub 2022-05-31.
Promising Practices for Implementing Adverse Childhood Experiences and Resilience Screening in Obstetric Care
Authors: Watson, Carey; Kathryn, Ridout K; Nancy, Goler; Kelly, Young-Wolff C
J Womens Health (Larchmt). 2022 10;31(10):1377-1379. Epub 2022-09-15.
Characterizing Unhealthy Alcohol Use Patterns and Their Association with Alcohol Use Reduction and Alcohol Use Disorder During Follow-Up in HIV Care
Outcomes of PWH with unhealthy alcohol use, such as alcohol use reduction or progression to AUD, are not well-known and may differ by baseline patterns of unhealthy alcohol use. Among 1299 PWH screening positive for NIAAA-defined unhealthy alcohol use in Kaiser Permanente Northern California, 2013-2017, we compared 2-year probabilities of reduction to low-risk/no alcohol use and rates of new AUD diagnoses by baseline use patterns, categorized as exceeding: only daily limits (72% of included PWH), only weekly limits (17%), or both (11%), based on NIAAA recommendations. Overall, 73.2% (95% CI 70.5-75.9%) of re-screened PWH reduced to low-risk/no alcohol use over 2 years, and there were 3.1 (95% CI 2.5-3.8%) new AUD diagnoses per 100 person-years. Compared with PWH only exceeding daily limits at baseline, those only exceeding weekly limits and those exceeding both limits were less likely to reduce and likelier to be diagnosed with AUD during follow-up. PWH exceeding weekly drinking limits, with or without exceeding daily limits, may have a potential need for targeted interventions to address unhealthy alcohol use.
Authors: Davy-Mendez, Thibaut; Sterling, Stacy A; Weisner, Constance M; Silverberg, Michael J; Satre, Derek D; et al.
AIDS Behav. 2022 Sep 28.
Ischemic Stroke in Patients With Asymptomatic Severe Carotid Stenosis Without Surgical Intervention-Reply
Authors: Chang, Robert W; Nguyen-Huynh, Mai N; Avins, Andrew L
JAMA. 2022 09 27;328(12):1257.
Association Between Myopic Refractive Error and Primary Open-Angle Glaucoma: A 2-Sample Mendelian Randomization Study
Refractive error (RE) is the most common form of visual impairment, and myopic RE is associated with an increased risk of primary open-angle glaucoma (POAG). Whether this association represents a causal role of RE in the etiology of POAG remains unknown. To evaluate shared genetic influences and investigate the association of myopic RE with the risk for POAG. Observational analyses were used to evaluate the association between mean spherical equivalent (MSE) RE (continuous trait) or myopia (binary trait) and POAG risk in individuals from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. To quantify genetic overlap, genome-wide genetic correlation analyses were performed using genome-wide association studies (GWAS) of MSE RE or myopia and POAG from GERA. Potential causal effects were assessed between MSE RE and POAG using 2-sample Mendelian randomization. Genetic variants associated with MSE RE were derived using GWAS summary statistics from a GWAS of RE conducted in 102 117 UK Biobank participants. For POAG, we used GWAS summary statistics from our previous GWAS (3836 POAG cases and 48 065 controls from GERA). Data analyses occurred between July 2020 and October 2021. Our main outcome was POAG risk as odds ratio (OR) caused by per-unit difference in MSE RE (in diopters). Our observational analyses included data for 54 755 non-Hispanic White individuals (31 926 [58%] females and 22 829 [42%] males). Among 4047 individuals with POAG, mean (SD) age was 73.64 (9.20) years; mean (SD) age of the 50 708 controls was 65.38 (12.24) years. Individuals with POAG had a lower refractive MSE and were more likely to have myopia or high myopia compared with the control participants (40.2% vs 34.1%, P = 1.31 × 10-11 for myopia; 8.5% vs 6.8%, P = .004 for high myopia). Our genetic correlation analyses demonstrated that POAG was genetically correlated with MSE RE (rg, -0.24; SE, 0.06; P = 3.90 × 10-5), myopia (rg, 0.21; SE, 0.07; P = .004), and high myopia (rg, 0.23; SE, 0.09; P = .01). Genetically assessed refractive MSE was negatively associated with POAG risk (inverse-variance weighted model: OR per diopter more hyperopic MSE = 0.94; 95% CI, 0.89-0.99; P = .01). These findings demonstrate a shared genetic basis and an association between myopic RE and POAG risk. This may support population POAG risk stratification and screening strategies, based on RE information.
Authors: Choquet, Hélène; Khawaja, Anthony P; Jiang, Chen; Yin, Jie; Melles, Ronald B; Glymour, M Maria; Hysi, Pirro G; Jorgenson, Eric
JAMA Ophthalmol. 2022 Sep 01;140(9):864-871.
Osteoporosis identification among previously undiagnosed individuals with vertebral fractures
Because osteoporosis is under-recognized in patients with vertebral fractures, we evaluated characteristics associated with osteoporosis identification. Most patients with vertebral fractures did not receive evaluation or treatment for osteoporosis. Black, younger, and male participants were particularly unlikely to have had recognized osteoporosis, which could increase their risk of negative outcomes. Vertebral fractures may be identified on imaging but fail to prompt evaluation for osteoporosis. Our objective was to evaluate characteristics associated with clinical osteoporosis recognition in patients who had vertebral fractures detected on their thoracolumbar spine imaging reports. We prospectively identified individuals who received imaging of the lower spine at primary care clinics in 4 large healthcare systems who were eligible for osteoporosis screening and lacked indications of osteoporosis diagnoses or treatments in the prior year. We evaluated characteristics of participants with identified vertebral fractures that were associated with recognition of osteoporosis (diagnosis code in the health record; receipt of bone mineral density scans; and/or prescriptions for anti-osteoporotic medications). We used mixed models to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). A total of 114,005 participants (47% female; mean age 65 (interquartile range: 57-72) years) were evaluated. Of the 8579 (7%) participants with vertebral fractures identified, 3784 (44%) had recognition of osteoporosis within the subsequent year. In adjusted regressions, Black participants (OR (95% CI): 0.74 (0.57, 0.97)), younger participants (age 50-60: 0.48 (0.42, 0.54); age 61-64: 0.70 (0.60, 0.81)), and males (0.39 (0.35, 0.43)) were less likely to have recognized osteoporosis compared to white participants, adults aged 65 + years, or females. Individuals with identified vertebral fractures commonly did not have recognition of osteoporosis within a year, particularly those who were younger, Black, or male. Providers and healthcare systems should consider efforts to improve evaluation of osteoporosis in patients with vertebral fractures.
Authors: Gold, L S; Avins, A L; Jarvik, J G; et al.
Osteoporos Int. 2022 Sep;33(9):1925-1935. Epub 2022-06-03.
Electronic cigarette use and risk of COVID-19 among young adults without a history of cigarette smoking
It is unknown whether use of e-cigarettes increases susceptibility to COVID-19. In a large clinical sample of young adults, we evaluated whether current or ever e-cigarette use was associated with polymerase chain reaction (PCR)-confirmed COVID-19. To address the confounding of combustible smoking, the sample was restricted to never smokers. This retrospective cohort study analyzed data from the electronic health records of 74,853 young adults (aged 18-35 years), without a history of cigarette smoking, who were screened for e-cigarette use (current, former, never) in the Kaiser Permanente Northern California (KPNC) healthcare system from 3/5/2020 (baseline) to 11/30/2020 (pre-vaccine). COVID-19 risk was estimated in time-to-event analyses using multivariable Cox proportional hazard regression models, adjusted for socio-demographics and medical comorbidities. E-cigarette status in the cohort was: 1.6% current, 1.2% former, and 97.2% never. During follow-up, 1965 (2.6%) patients acquired COVID-19. We did not find evidence that current (vs never) e-cigarette use was associated with risk of COVID-19 (aHR = 1.12 95%CI:0.77-1.62). However, we did find suggestive evidence that former (versus never) e-cigarette use may be associated with greater risk of COVID-19 (aHR = 1.39 95%CI:0.98-1.96). While e-cigarette use is associated with health risks for young adults, results from this study suggest that current use of e-cigarettes may not increase susceptibility for COVID-19 among young adults who have never smoked cigarettes.
Authors: Young-Wolff, Kelly C; Slama, Natalie E; Alexeeff, Stacey E; Prochaska, Judith J; Fogelberg, Renee; Sakoda, Lori C
Prev Med. 2022 09;162:107151. Epub 2022-07-06.
Natural History of Asymptomatic Moderate Carotid Artery Stenosis in a Large Community-Based Cohort
Moderate carotid artery stenosis is a poorly defined risk factor for ischemic stroke. As such, practice recommendations are lacking. In this study, we describe the long-term risk of stroke in patients with moderate asymptomatic stenosis in an integrated health care system. All adult patients with asymptomatic moderate (50%-69%) internal carotid artery stenosis between 2008 and 2012 were identified, with follow-up through 2017. The primary outcome was acute ischemic stroke attributed to the ipsilateral carotid artery. Stroke rates were calculated using competing risk analysis. Secondary outcomes included disease progression, ipsilateral intervention, and long-term survival. Overall, 11 614 arteries with moderate stenosis in 9803 patients were identified. Mean age was 74.2±9.9 years with 51.4% women. Mean follow-up was 5.1±2.9 years. There were 180 ipsilateral ischemic strokes (1.6%) identified (crude annual risk, 0.31% [95% CI, 0.21%-0.41%]), of which thirty-one (17.2%) underwent subsequent intervention. Controlling for death and intervention as competing risks, the cumulative incidence of stroke was 1.2% (95% CI, 1.0%-1.4%) at 5 years and 2.0% (95% CI, 1.7%-2.4%) at 10 years. Of identified strokes, 50 (27.8%) arteries had progressed to severe stenosis or occlusion. During follow-up, there were 17 029 carotid studies performed in 5951 patients, revealing stenosis progression in 1674 (14.4%) arteries, including 1614 (13.9%) progressing to severe stenosis and 60 (0.5%) to occlusion. The mean time to stenosis progression was 2.6±2.1 years. Carotid intervention occurred in 708 arteries (6.1%). Of these, 66.1% (468/708) had progressed to severe stenosis. The overall mortality rate was 44.5%, with 10.5% of patients lost to follow-up. In this community-based sample of patients with asymptomatic moderate internal carotid artery stenosis followed for an average of 5 years, the cumulative incidence of stroke is low out to 10 years. Future research is needed to optimize management strategies for this population.
Authors: Gologorsky, Rebecca C; Lancaster, Elizabeth; Tucker, Lue-Yen; Nguyen-Huynh, Mai N; Rothenberg, Kara A; Avins, Andrew L; Kuang, Hui C; Chang, Robert W
Stroke. 2022 Sep;53(9):2838-2846. Epub 2022-06-08.
Cost-Effectiveness of Motivational Interviewing to Reduce Alcohol and Cannabis Use Among Patients With Depression
Motivational interviewing (MI) is a promising intervention for helping patients with mental health problems reduce their substance use. Examining the cost-effectiveness of MI and associations between MI and the use of health services can inform appropriate intervention strategies for these patients. Kaiser Permanente adult patients with depression symptoms (Patient Health Questionnaire [PHQ-9] score > 5) seen in outpatient psychiatry (N = 302) who reported unhealthy alcohol use or other substance use (primarily cannabis) were randomized to three sessions of MI (intervention) or printed literature (control) with telephone follow-up interviews at 6 and 12 months. Cost-effectiveness analyses compared intervention costs associated with 30-day abstinence from unhealthy alcohol use (i.e., any days of ≥4/≥5 drinks for women/men) and cannabis use. Multivariable analyses examined associations between MI and healthcare utilization at 12 months (emergency department, primary care, psychiatry, and addiction treatment). MI resulted in greater likelihood of abstaining from unhealthy alcohol use (70.0% vs. 60.2%, p < .01) and cannabis use (74.6% vs. 63.9%, p < .01) than the control at 6 months, but outcomes did not differ at 12 months. The 6-month incremental cost-effectiveness ratios were $1,207-$1,523 per abstinent patient for unhealthy drinking and $1,040-$1,313 per abstinent patient for cannabis. There were no differences between groups on health service utilization. MI cost more than the control condition but yielded better outcomes at 6 months; MI had no relationship to health service utilization. Findings can inform implementation of substance use interventions through understanding MI's potential clinical and cost impact and its relationship to health services use.
Authors: Satre, Derek D; Parthasarathy, Sujaya; Young-Wolff, Kelly C; Meacham, Meredith C; Borsari, Brian; Hirschtritt, Matthew E; Van Dyke, Lucas; Sterling, Stacy A
J Stud Alcohol Drugs. 2022 Sep;83(5):662-671.
The Opioid Use Disorder Core Outcomes Set (OUD-COS) for treatment research: findings from a Delphi consensus study
There is no gold-standard and considerable heterogeneity in outcome measures used to evaluate treatments for opioid use disorder (OUD) along the opioid treatment cascade. The aim of this study was to develop the US National Institute on Drug Abuse (NIDA) National Drug Abuse Treatment Clinical Trials Network (CTN) opioid use disorder core outcomes set (OUD-COS). Four-round, e-Delphi expert panel consensus study and plenary research group discussion and targeted consultation. United States. A panel of 25 members including clinical practitioners, clinical researchers and administrative staff from the CTN, the network’s affiliated clinical and community sites and the NIDA Centre for the CTN. From a pool of 24 candidate items in four domains (biomedical/disease status; behaviors, symptoms and functioning; opioid treatment cascade; and morbidity and mortality), the panel completed an on-line questionnaire to rank items with defined specification on a 9-point scale for importance, with a standard 70% consensus criterion. After the fourth round of the questionnaire and subsequent discussion, consensus was reached for five outcomes: two patient-reported (global impression of improvement and incident non-fatal overdose); one clinician-reported (illicit/non-medical drug toxicology); and two from administrative records (duration of treatment and fatal opioid poisoning). An e-Delphi consensus study has produced the US National Institute on Drug Abuse (NIDA) National Drug Abuse Treatment Clinical Trials Network opioid use disorder core outcomes set (version 1) for opioid use disorder treatment efficacy and effectiveness research.
Authors: Karnik, Niranjan S; Campbell, Cynthia I; Wu, Li-Tzy; et al.
Addiction. 2022 Sep;117(9):2438-2447. Epub 2022-04-25.
In-utero cannabis exposure and long-term psychiatric and neurodevelopmental outcomes: The limitations of existing literature and recommendations for future research
Given increases in cannabis use in pregnancy and animal model research showing effects of in-utero cannabis exposure, high-quality information on long-term consequences of in-utero cannabis exposure in humans is needed. While reviews have summarized findings from observational studies with humans, reviews have not focused on limitations of these studies and recommendations for future research. Therefore, we critically reviewed observational research on in-utero cannabis exposure and psychiatric and neurodevelopmental outcomes measured at or after age 3 and provided recommendations for future research. We used Web of Science, Google Scholar, and work cited from relevant identified publications to identify 46 papers to include in our review. Our review includes two main sections. The first section highlights the extensive limitations of the existing research, which include small and nongeneralizable samples, reliance on self-reported data, lack of detail on timing and amount of exposure, inclusion of older exposure data only, not accounting for important confounders, inclusion of potential mediators as covariates, not including outcome severity measures, and not assessing for offspring sex differences. The second section provides recommendations for future research regarding exposure and outcome measures, sample selection, confounder adjustment, and other methodological considerations. For example, with regard to exposure definition, we recommend that studies quantify the amount of cannabis exposure, evaluate the influence of timing of exposure, and incorporate biological measures (e.g., urine toxicology measures). Given that high-quality information on long-term consequences of in-utero cannabis exposure in humans does not yet exit, it is crucial for future research to address the limitations we have identified.
Authors: Sujan, Ayesha C; Young-Wolff, Kelly C; Avalos, Lyndsay A
Birth Defects Res. 2022 08 01;114(13):689-713. Epub 2022-06-16.
Cognitive outcomes are differentially associated with depression severity trajectories during psychotherapy treatment for late life major depressive disorder
Late Life Depression (LLD) is associated with persistent cognitive dysfunction even after depression symptoms improve. The present study was designed to examine cognitive outcomes associated with the pattern of depression severity change during psychotherapy intervention for LLD. 96 community-dwelling adults ages 65-91 with major depressive disorder completed 12 sessions of Problem-Solving Therapy at the University of California, San Francisco. Nonlinear trajectories of depression severity ratings using the Hamilton Depression Rating Scale were computed from multiple time points collected throughout the weekly psychotherapy intervention. Performance on measures of cognition (information processing speed, executive functioning, verbal learning, memory) was assessed at baseline and post-treatment. Linear mixed-effects models examined associations between nonlinear depression severity trajectories and post-treatment change in cognitive performance. Broadly, different patterns of depression change during treatment were associated with improved cognition post-treatment. Greater and more consistent interval improvements in depression ratings were differentially associated with improvements in aspects of verbal learning, memory, and executive function post-treatment, while no associations were found with information processing speed. The heterogeneity of depression trajectories associated with improved cognitive outcomes suggests that the temporal pattern of depression response may impact specific cognitive processes distinctly. Results suggest that use of nonlinear depression severity trajectories may help to elucidate complex associations between the time course of depression response and cognitive outcomes of psychotherapy in LLD. These findings have important implications for identifying treatment targets to enhance clinical and cognitive outcomes of psychotherapy in LLD.
Authors: Kassel, Michelle T; Rhodes, Emma; Insel, Philip S; Woodworth, Kai; Garrison-Diehn, Christina; Satre, Derek D; Nelson, J Craig; Tosun, Duygu; Mackin, R Scott
Int J Geriatr Psychiatry. 2022 Aug;37(8).
A randomized clinical trial of the effects of brief versus extended opioid overdose education on naloxone utilization outcomes by individuals with opioid use disorder
Overdose education and naloxone distribution (OEND) trains people who use opioids (PWUO) in how to intervene in cases of opioid overdose but best practices have not been assessed empirically. PWUO along with a significant other (SO) were randomized to one of three training conditions. In the Treatment-as-Usual (TAU) condition, participants were randomized to receive minimal overdose-related education. In the extended training (ET) condition, PWUO received an extended training, while their SO received no overdose training. In the final condition, both the participant and SO received the extended overdose training (ETwSO). Outcome measures were naloxone use and overdose knowledge and competency assessed immediately before and after training, and at 1-, 3-, 6-, and 12-month timepoints following training. Three hundred and twenty-one PWUO (w/ a SO) were randomized. All intensities of OD training were associated with sustained increases in OD knowledge/ competency (versus pre-training baseline p’s < 0.01). PWUO intervened in 166 ODs. The 12-month incidence of naloxone use did not significantly differ between groups. Extended training (ET + ETwSO) compared to TAU resulted in significantly greater naloxone utilization by: 30 days (10.1% vs 4.1%, p = 0.041), 60 days (16.4% vs 5.2%, p<0.001) and 90 days (17.9% vs 9.5%, p = 0.039). All intensities of OD training were associated with sustained increases in OD knowledge and competency, and equivalent rates of successful naloxone use. More extensive training increased naloxone utilization during the first 3 months. However, the benefits of more comprehensive training should be balanced against feasibility.
Authors: Jones, Jermaine D; Metz, Verena E; Comer, Sandra D; et al.
Drug Alcohol Depend. 2022 08 01;237:109505. Epub 2022-05-23.
The role of nativity in heterogeneous dementia incidence in a large cohort of three Asian American groups and white older adults in California
Literature shows lower dementia incidence in Asian American groups versus whites, varying by Asian ethnicity. One hypothesized driver is nativity differences (eg, healthy immigrant effect). We followed a cohort of 6243 Chinese, 4879 Filipino, 3256 Japanese, and 141,158 white Kaiser Permanente Northern California members for incident dementia (2002 to 2020), estimating age-adjusted dementia incidence rates by ethnicity and nativity, and hazard ratios (HR) for nativity on dementia incidence using ethnicity-stratified age- and sex-adjusted Cox proportional hazards models. Dementia incidence appeared higher in foreign- versus US-born Filipinos (HR, 95% confidence interval: 1.39, 1.02 to 1.89); differences were small in Japanese (1.07, 0.88 to 1.30) and Chinese (1.07, 0.92 to 1.24). No nativity differences were observed among whites (1.00, 0.95 to 1.04). Nativity does not explain lower dementia incidence in Asian Americans versus whites, but may contribute to heterogeneity across Asian ethnicities. Future research should explore differential impacts of social and cardiometabolic factors.
Authors: Hayes-Larson, Eleanor; Fong, Joseph; Mobley, Taylor M; Gilsanz, Paola; Whitmer, Rachel A; Gee, Gilbert C; Brookmeyer, Ron; Mayeda, Elizabeth Rose
Alzheimers Dement. 2022 Aug;18(8):1580-1585. Epub 2022-02-01.
Mortality Among Patients Prescribed Buprenorphine for Opioid Use Disorder After Disenrollment from an Insurance Plan and Healthcare System
Authors: Nguyen, Anh P; Glanz, Jason M; Shoup, Jo Ann; Campbell, Cynthia I; Clarke, Christina L; Ford, Morgan A; Binswanger, Ingrid A
J Gen Intern Med. 2022 Aug;37(11):2882-2884. Epub 2022-01-26.
Coping strategies for COVID-19 pandemic-related stress and mental health during pregnancy
Increased stress has likely contributed to the observed high prevalence of depression and anxiety in pregnant individuals during the COVID-19 pandemic. The objective of this study was to assess the prevalence of coping strategies for COVID-19 pandemic-related stress and associations of these coping strategies with depression and anxiety symptoms during pregnancy. 8320 members of Kaiser Permanente Northern California who were pregnant between June 22, 2020 and May 10, 2021 completed an online survey including questions about coping strategies since the start of the COVID-19 pandemic and current depression and anxiety symptoms. We used weighted regression to estimate prevalence ratios for moderate/severe depression and anxiety symptom severity associated with coping strategies. The most common coping strategies for COVID-19 pandemic-related stress were talking with friends and family (77%), outdoor physical activity (54%), and increasing screen time activities (52%). Exercising using online programs or videos, outdoor physical activity, talking with friends and family, and engaging in more family activities were associated with 29% to 38% lower prevalence of moderate/severe depression symptom severity and 16% to 34% lower prevalence of moderate/severe anxiety symptom severity. We are unable to rule out reverse temporality as an explanation for the observed results because of the cross-sectional design; depression or anxiety symptom severity may influence use of specific coping strategies. Our results suggest that physical activity and connecting with others are coping strategies for COVID-19 pandemic-related stress that may be associated with better mental health in pregnant individuals.
Authors: Badon, Sylvia E; Croen, Lisa A; Ferrara, Assiamira; Ames, Jennifer L; Hedderson, Monique M; Young-Wolff, Kelly C; Zhu, Yeyi; Avalos, Lyndsay A
J Affect Disord. 2022 Jul 15;309:309-313. Epub 2022-04-28.
Modest effect of statins on fasting glucose in a longitudinal electronic health record based cohort
Prior studies of the glycemic effect of statins have been inconsistent. Also, most studies have only considered a short duration of statin use; the effect of long-term statin use on fasting glucose (FG) has not been well examined. The aim of this work is to investigate the effect of long-term statin exposure on FG levels. Using electronic health record (EHR) data from a large and diverse longitudinal cohort, we defined long-term statin exposure in two ways: the cumulative years of statin use (cumulative supply) and the years’ supply-weighted sum of doses (cumulative dose). Simvastatin, lovastatin, atorvastatin and pravastatin were included in the analysis. The relationship between statin exposure and FG was examined using linear regression with mixed effects modeling, comparing statin users before and after initiating statins and statin never-users. We examined 593,130 FG measurements from 87,151 individuals over a median follow up of 20 years. Of these, 42,678 were never-users and 44,473 were statin users with a total of 730,031 statin prescriptions. FG was positively associated with cumulative supply of statin but not comulative dose when both measures were in the same model. While statistically significant, the annual increase in FG attributable to statin exposure was modest at only 0.14 mg/dl, with only slight and non-significant differences among statin types. Elevation in FG level is associated with statin exposure, but the effect is modest. The results suggest that the risk of a clinically significant increase in FG attributable to long-term statin use is small for most individuals.
Authors: Haldar, Tanushree; Oni-Orisan, Akinyemi; Hoffmann, Thomas J; Schaefer, Catherine; Iribarren, Carlos; Krauss, Ronald M; Medina, Marisa W; Risch, Neil
Cardiovasc Diabetol. 2022 Jul 14;21(1):132. Epub 2022-07-14.
Ancestry- and sex-specific effects underlying inguinal hernia susceptibility identified in a multiethnic genome-wide association study meta-analysis
Inguinal hernias are some of the most frequently diagnosed conditions in clinical practice and inguinal hernia repair is the most common procedure performed by general surgeons. Studies of inguinal hernias in non-European populations are lacking, though it is expected that such studies could identify novel loci. Further, the cumulative lifetime incidence of inguinal hernia is nine times greater in men than women, however, it is not clear why this difference exists. We conducted a genome-wide association meta-analysis of inguinal hernia risk across 513 120 individuals (35 774 cases and 477 346 controls) of Hispanic/Latino, African, Asian and European descent, with replication in 728 418 participants (33 491 cases and 694 927 controls) from the 23andMe, Inc dataset. We identified 63 genome-wide significant loci (P < 5 × 10-8), including 41 novel. Ancestry-specific analyses identified two loci (LYPLAL1-AS1/SLC30A10 and STXBP6-NOVA1) in African ancestry individuals. Sex-stratified analyses identified two loci (MYO1D and ZBTB7C) that are specific to women, and four (EBF2, EMX2/RAB11FIP2, VCL and FAM9A/FAM9B) that are specific to men. Functional experiments demonstrated that several of the associated regions (EFEMP1 and LYPLAL1-SLC30A10) function as enhancers and show differential activity between risk and reference alleles. Our study highlights the importance of large-scale genomic studies in ancestrally diverse populations for identifying ancestry-specific inguinal hernia susceptibility loci and provides novel biological insights into inguinal hernia etiology.
Authors: Choquet, Hélène; Li, Weiyu; Yin, Jie; Bradley, Rachael; Hoffmann, Thomas J; Nandakumar, Priyanka; 23andMe Research Team,; Mostaedi, Rouzbeh; Tian, Chao; Ahituv, Nadav; Jorgenson, Eric
Hum Mol Genet. 2022 07 07;31(13):2279-2293.
Development and implementation of a prescription opioid registry across diverse health systems
Develop and implement a prescription opioid registry in 10 diverse health systems across the US and describe trends in prescribed opioids between 2012 and 2018. Using electronic health record and claims data, we identified patients who had an outpatient fill for any prescription opioid, and/or an opioid use disorder diagnosis, between January 1, 2012 and December 31, 2018. The registry contains distributed files of prescription opioids, benzodiazepines and other select medications, opioid antagonists, clinical diagnoses, procedures, health services utilization, and health plan membership. Rates of outpatient opioid fills over the study period, standardized to health system demographic distributions, are described by age, gender, and race/ethnicity among members without cancer. The registry includes 6 249 710 patients and over 40 million outpatient opioid fills. For the combined registry population, opioid fills declined from a high of 0.718 per member-year in 2013 to 0.478 in 2018, and morphine milligram equivalents (MMEs) per fill declined from 985 MMEs per fill in 2012 to 758 MMEs in 2018. MMEs per member declined from 692 MMEs per member in 2012 to 362 MMEs per member in 2018. This study established a population-based opioid registry across 10 diverse health systems that can be used to address questions related to opioid use. Initial analyses showed large reductions in overall opioid use per member among the combined health systems. The registry will be used in future studies to answer a broad range of other critical public health issues relating to prescription opioid use.
Authors: Ray, G Thomas; Campbell, Cynthia I; et al.
JAMIA Open. 2022 Jul;5(2):ooac030. Epub 2022-05-17.
California Cannabis Markets-Why Industry-Friendly Regulation Is Not Good Public Health
Authors: Young-Wolff, Kelly C; Pacula, Rosalie Liccardo; Silver, Lynn D
JAMA Health Forum. 2022 07 01;3(7):e222018. Epub 2022-07-01.
Association Between Prenatal Cannabis Use and Psychotropic Medication Use in Pregnant Patients With Depression and Anxiety
This cross-sectional study examined associations between prenatal cannabis use and prescribed psychotropic medication use among pregnant patients with depression or anxiety in a large, integrated healthcare system. Study patients had a confirmed pregnancy and a depressive or anxiety disorder defined by International Classification of Diseases codes between 2012 and 2018 at Kaiser Permanente Northern California. Patients were screened for prenatal substance use via a self-reported questionnaire and urine toxicology test as part of standard prenatal care. Generalized estimating equation models tested for associations between prenatal cannabis use and any dispensation of antidepressants, benzodiazepines, and hypnotics during gestation. Models were stratified by diagnosis (depression or anxiety) and depression symptom severity. This study included 35,047 pregnancies (32,278 patients; 17.6% aged <25 years, 48.1% non-Hispanic White). Adjusting for patient age, income, race/ethnicity, and depression symptom severity, the 12.6% of patients who screened positive for prenatal cannabis use demonstrated higher odds of prenatal benzodiazepine (adjusted odds ratios [aOR] = 1.40; 95% confidence interval [CI] = 1.20-1.62) and hypnotic (aOR = 1.28; 95% CI = 1.11-1.48), but not antidepressants (aOR = 1.05, 95% CI = 0.96-1.14) use. This pattern persisted when diagnostic groups were examined separately. The odds of prenatal benzodiazepine and hypnotic use associated with prenatal cannabis use were higher among pregnancies with severe depression symptom severity (31.8% of the sample). Among pregnant patients with depression or anxiety, prenatal cannabis use was associated with higher odds of prenatal benzodiazepine and hypnotic use. As patients may be using cannabis to address depression and anxiety, prescribers should remain vigilant for under- or untreated psychiatric symptoms among pregnant patients and provide evidence-based treatments.
Authors: Hirschtritt, Matthew E; Avalos, Lyndsay A; Sarovar, Varada; Ridout, Kathryn K; Goler, Nancy C; Ansley, Deborah R; Satre, Derek D; Young-Wolff, Kelly C
J Addict Med. 2022 Jul-Aug 01;16(4):e269-e273. Epub 2022-01-22.
GWAS identifies two common loci associated with pigment dispersion syndrome/pigmentary glaucoma and implicate myopia in its development
To identify genetic variants associated with pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG) in unrelated patients and to further understand the genetic and potentially causal relationships between PDS and associated risk factors. A 2-stage genome-wide association meta-analysis with replication and subsequent in silico analyses including Mendelian randomization. A total of 574 cases with PG or PDS and 52 627 controls of European descent. Genome-wide association analyses were performed in 4 cohorts and meta-analyzed in 3 stages: (1) a discovery meta-analysis was performed in 3 cohorts, (2) replication was performed in the fourth cohort, and (3) all 4 cohorts were meta-analyzed to increase statistical power. Two-sample Mendelian randomization was used to determine whether refractive error and intraocular pressure exert causal effects over PDS. The association of genetic variants with PDS and whether myopia exerts causal effects over PDS. Significant association was present at 2 novel loci for PDS/PG. These loci and follow-up analyses implicate the genes gamma secretase activator protein (GSAP) (lead single nucleotide polymorphism [SNP]: rs9641220, P = 6.0×10-10) and glutamate metabotropic receptor 5 (GRM5)/TYR (lead SNP: rs661177, P = 3.9×10-9) as important factors in disease risk. Mendelian randomization showed significant evidence that negative refractive error (myopia) exerts a direct causal effect over PDS (P = 8.86×10-7). Common SNPs relating to the GSAP and GRM5/TYR genes are associated risk factors for the development of PDS and PG. Although myopia is a known risk factor, this study uses genetic data to demonstrate that myopia is, in part, a cause of PDS and PG.
Authors: Simcoe, Mark J; Choquet, Hélène; Hammond, Christopher J; et al.
Ophthalmology. 2022 06;129(6):626-636. Epub 2022-01-11.
Trends in Cannabis Polysubstance Use During Early Pregnancy Among Patients in a Large Health Care System in Northern California
Rates of prenatal cannabis use are increasing alongside perceptions that cannabis is a harmless therapeutic for pregnancy-related ailments, while rates of prenatal use of alcohol and tobacco are decreasing. It is important to examine whether cannabis use during pregnancy is increasing similarly among patients with and patients without co-occurring substance use. To examine trends in cannabis polysubstance use during pregnancy and to test differences in cannabis use over time among pregnant individuals who use only cannabis vs those who use cannabis and other substances. This cross-sectional time-series study used data from 367 138 pregnancies among 281 590 unique pregnant patients universally screened for prenatal substance use as part of standard care in Kaiser Permanente Northern California from January 1, 2009, to December 31, 2018. Statistical analysis was performed from October 5, 2021, to April 18, 2022. Time (calendar year). Use of substances during early pregnancy was assessed via universal screening with a self-administered questionnaire (for cannabis, alcohol, stimulants, and nicotine) and/or positive results of a urine toxicology test (for cannabis, alcohol, stimulants, and pharmaceutical opioids), and data were extracted from the electronic health record. The study sample of 367 138 pregnancies from 281 590 unique pregnant patients (median gestation at time of screening, 8.6 weeks [IQR, 7.3-10.6 weeks]) was 25.9% Asian or Pacific Islander, 6.6% Black, 25.8% Hispanic, 38.0% non-Hispanic White, and 3.6% other race or ethnicity; 1.1% were aged 11 to 17 years, 14.9% were aged 18 to 24 years, 61.9% were aged 25 to 34 years, and 22.1% were aged 35 years or older; and the median neighborhood household income was $70 455 (IQR, $51 563-$92 625). From 2009 to 2018, adjusted rates of use of only cannabis during pregnancy (no other substances) increased substantially from 2.39% (95% CI, 2.20%-2.58%) in 2009 to 6.30% (95% CI, 6.00%-6.60%) in 2018, increasing at an annual relative rate of 1.11 (95% CI, 1.10-1.12). The rate of use of cannabis and 1 other substance also increased (annual relative rate, 1.04 [95% CI, 1.03-1.05]), but not as rapidly (P < .001 for difference), while the rate of use of cannabis and 2 or more other substances decreased slightly (annual relative rate, 0.97 [95% CI, 0.96-0.99]). Adjusted rates of prenatal use of cannabis and alcohol (1.04 [95% CI, 1.03-1.06]) and cannabis and stimulants (1.03 [95% CI, 1.01-1.06]) increased over time, while rates of prenatal use of cannabis and nicotine (0.97 [95% CI, 0.96-0.98]) decreased. In this cross-sectional time-series study, rates of prenatal cannabis use during early pregnancy increased significantly more rapidly among patients without co-occurring substance use, which could reflect increased acceptability of cannabis and decreased perceptions of cannabis-related harms. Furthermore, increased rates of use of cannabis with alcohol and stimulants warrant continued monitoring.
Authors: Young-Wolff, Kelly C; Alexeeff, Stacey E; et al.
JAMA Netw Open. 2022 Jun 01;5(6):e2215418. Epub 2022-06-01.
Alcohol brief intervention, specialty treatment and drinking outcomes at 12 months: Results from a systematic alcohol screening and brief intervention initiative in adult primary care
Alcohol screening, brief intervention and referral to treatment (SBIRT) in adult primary care is an evidence-based, public health strategy to address unhealthy alcohol use, but evidence of effectiveness of alcohol brief intervention (ABI) in real-world implementation is lacking. We fit marginal structural models with inverse probability weighting to estimate the causal effects of ABI on 12-month drinking outcomes using longitudinal electronic health records data for 312,056 adults with a positive screening result for unhealthy drinking between 2014 and 2017 in a large healthcare system that implemented systematic primary care-based SBIRT. We examined effects of ABI with and without adjusting for receipt of specialty alcohol use disorder (AUD) treatment, and whether effects varied by patient demographic characteristics and alcohol use patterns. Receiving ABI resulted in significantly greater reductions in heavy drinking days (mean difference [95% CI] = -0.26 [-0.45, -0.08]), drinking days per week (-0.04 [-0.07, -0.01]), drinks per drinking day (-0.05 [-0.08, -0.02]) and drinks per week (-0.16 [-0.27, -0.04]). Effects of ABI on 12-month drinking outcomes varied by baseline consumption level, age group and whether patients already had an AUD, with better improvement in those who were drinking at levels exceeding only daily limits, younger, and without an AUD. Systematic ABI in adult primary care has the potential to reduce drinking among people with unhealthy drinking considerably on both an individual and population level. More research is needed to help optimize ABI, in particular tailoring it to diverse sub-populations, and studying its long-term public health impact.
Authors: Chi, Felicia W; Weisner, Constance; Satre, Derek D; Campbell, Cynthia I; Elson, Joseph; Sterling, Stacy A; et al.
Drug Alcohol Depend. 2022 06 01;235:109458. Epub 2022-04-12.
Modes of cannabis administration in the year prior to conception among patients in Northern California
Cannabis use among individuals before and during pregnancy is increasing alongside the proliferation of new products with various modes of administration. Preconception cannabis use is a strong predictor of prenatal cannabis use. Yet little is known about how individuals administer cannabis during the preconception period, particularly in socioeconomically vulnerable populations. This study examined the prevalence and correlates of modes of cannabis administration (smoke, vape, blunts, edible/oral, dabs/wax, lotion/topical) during the year before conception, among patients who self-reported preconception cannabis use during universal screening in prenatal care. Descriptive statistics included sociodemographic characteristics, preconception cannabis use frequency, and modes of administration. Chi-square tests examined whether mode was associated with sociodemographic characteristics and use frequency. The sample (N = 11,936, screened from February 2020-May 2021) was 59.8% non-White and 26.1% were < 26 years old; 50.7% reported monthly or less, 21.8% weekly, and 27.4% daily preconception cannabis use; 69.7% smoked (any method), 34.5% smoked blunts, 53.4% used edibles/oral, 28.2% vaped, 9.9% used lotion/topical; 54.2% reported 1 mode, 30.4% reported 2 modes, 15.4% reported 3+ modes. Smoking was more common among daily users, younger patients, those with greater neighborhood deprivation, and Black and Hispanic patients, while edibles/oral were more common among ≤ monthly users, older patients, those with less neighborhood deprivation, and Asian patients. Use of other modes also varied by sociodemographic characteristics and use frequency. Research is needed to understand preconception cannabis use in vulnerable subpopulations, continuation of use during pregnancy, and whether health risks associated with preconception and prenatal cannabis use differ by administration mode.
Authors: Young-Wolff, Kelly C; Adams, Sara R; Brown, Qiana L; Weisner, Constance; Ansley, Deborah; Goler, Nancy; Skelton, Kara R; Satre, Derek D; Foti, Tara R; Conway, Amy
Addict Behav Rep. 2022 Jun;15:100416. Epub 2022-02-22.
Health Service Utilization Among Children and Adolescents with Posttraumatic Stress Disorder: A Case-Control Study
Trauma exposure is widely prevalent, with more than 60% of adolescents having experienced at least 1 traumatic event and a third of those at high risk to develop posttraumatic stress disorder (PTSD). Data are scarce and out of date on the services children and adolescents with PTSD receive, impeding efforts to improve care and outcomes. This study examines health service use for a large and diverse sample of children and adolescents with and without a diagnosis of PTSD. Using a matched case-control study, we gathered information from 4 large health care systems participating in the Mental Health Research Network. Data from each site’s electronic medical records on diagnoses, health care encounters, and demographics were analyzed. Nine hundred fifty-five 4- to 18-year-olds with a diagnosis of PTSD were identified and matched on a 1:5 ratio to 4770 controls. We compared cases with controls on frequency of service use in outpatient primary care, medical specialty care, acute care, and mental health care. We also assessed psychotropic medication use. Children and adolescents diagnosed with PTSD used nearly all physical and mental health service categories at a higher rate than controls. However, one-third of children and adolescents did not receive even 1 outpatient mental health visit (36.86%) during the year-long sampling window. Our findings suggest that children and adolescents diagnosed with PTSD may have unmet mental health needs. They are high utilizers of health services overall, but lower utilizers of the sectors that may be most helpful in resolving their symptoms.
Authors: Goger, Pauline; Zerr, Argero A; Weersing, V Robin; Dickerson, John F; Crawford, Phillip M; Sterling, Stacy A; Waitzfelder, Beth; Daida, Yihe G; Ahmedani, Brian K; Penfold, Robert B; Lynch, Frances L
J Dev Behav Pediatr. 2022 Jun-Jul 01;43(5):283-290. Epub 2021-11-23.
Incidence of Ischemic Stroke in Patients With Asymptomatic Severe Carotid Stenosis Without Surgical Intervention
Optimal management of patients with asymptomatic severe carotid stenosis is uncertain, due to advances in medical care and a lack of contemporary data comparing medical and surgical treatment. To estimate stroke outcomes among patients with medically treated asymptomatic severe carotid stenosis who did not undergo surgical intervention. Retrospective cohort study that included 3737 adult participants with asymptomatic severe (70%-99%) carotid stenosis diagnosed between 2008 and 2012 and no prior intervention or ipsilateral neurologic event in the prior 6 months. Participants received follow-up through 2019, and all were members of an integrated US regional health system serving 4.5 million members. Imaging diagnosis of asymptomatic carotid stenosis of 70% to 99%. Occurrence of ipsilateral carotid-related acute ischemic stroke. Censoring occurred with death, disenrollment, or ipsilateral intervention. Among 94 822 patients with qualifying imaging studies, 4230 arteries in 3737 (mean age, 73.8 [SD 9.5 years]; 57.4% male) patients met selection criteria including 2539 arteries in 2314 patients who never received intervention. The mean follow-up in this cohort was 4.1 years (SD 3.6 years). Prior to any intervention, there were 133 ipsilateral strokes with a mean annual stroke rate of 0.9% (95% confidence interval [CI], 0.7%-1.2%). The Kaplan-Meier estimate of ipsilateral stroke by 5 years was 4.7% (95% CI, 3.9%-5.7%). In a community-based cohort of patients with asymptomatic severe carotid stenosis who did not undergo surgical intervention, the estimated rate of ipsilateral carotid-related acute ischemic stroke was 4.7% over 5 years. These findings may inform decision-making regarding surgical and medical treatment for patients with asymptomatic severe carotid artery stenosis.
Authors: Chang, Robert W; Tucker, Lue-Yen; Rothenberg, Kara A; Lancaster, Elizabeth; Faruqi, Rishad M; Kuang, Hui C; Flint, Alexander C; Avins, Andrew L; Nguyen-Huynh, Mai N
JAMA. 2022 05 24;327(20):1974-1982.
Prevalence of Instrumental Activities of Daily Living (IADL) Difficulties and Associated Cognitive Predictors Across Racial/Ethnic Groups: Findings from the KHANDLE Study
Cognitive functioning is associated with instrumental activity of daily living (IADL) performance among older adults. The present study examines potential differences in the prevalence of IADL difficulty and association with cognition across diverse groups. Participants included 455 non-Hispanic Whites, 395 Blacks, 370 Asians, and 296 Latinos aged 65 years and older without a current dementia diagnosis from the Kaiser Healthy Aging and Diverse Life Experience cohort. Participants’ self-reported IADL functioning and cognition was measured across episodic memory and executive functioning. Older age, male gender, and being Black were associated with more IADL difficulties. Executive functioning showed a stronger association with IADLs than memory, and it was independent of health status, whereas memory was not. In joint models including both cognitive domains, executive functioning remained a significant predictor of IADL difficulty, but memory did not. Results for both cognitive domains were attenuated with self-rated health added to the joint model. These relationships did not significantly differ across racial/ethnic groups. Our study supports previous work suggesting that Black older adults are at increased risk for IADL disability. This is the first study we are aware of that examined the association between specific cognitive domains and IADL performance across multiple racial/ethnic groups. Findings indicate that cognitive functioning has similar associations with self-reported IADL disability across diverse groups, and that executive functioning plays a particularly important role in IADL disability among older adults without dementia; however, health status largely attenuates the relationship between IADL difficulty and cognition.
Authors: Chan, Michelle L; Eng, Chloe W; Gilsanz, Paola; Whitmer, Rachel A; Mungas, Dan; Meyer, Oanh; Farias, Sarah Tomaszewski
J Gerontol B Psychol Sci Soc Sci. 2022 05 05;77(5):885-894.
Comparison of Medical Cannabis Use Reported on a Confidential Survey vs Documented in the Electronic Health Record Among Primary Care Patients
Patients who use cannabis for medical reasons may benefit from discussions with clinicians about health risks of cannabis and evidence-based treatment alternatives. However, little is known about the prevalence of medical cannabis use in primary care and how often it is documented in patient electronic health records (EHR). To estimate the primary care prevalence of medical cannabis use according to confidential patient survey and to compare the prevalence of medical cannabis use documented in the EHR with patient report. This study is a cross-sectional survey performed in a large health system that conducts routine cannabis screening in Washington state where medical and nonmedical cannabis use are legal. Among 108 950 patients who completed routine cannabis screening (between March 28, 2019, and September 12, 2019), 5000 were randomly selected for a confidential survey about cannabis use, using stratified random sampling for frequency of past-year use and patient race and ethnicity. Data were analyzed from November 2020 to December 2021. Survey measures of patient-reported past-year cannabis use, medical cannabis use (ie, explicit medical use), and any health reason(s) for use (ie, implicit medical use). Survey data were linked to EHR data in the year before screening. EHR measures included documentation of explicit and/or implicit medical cannabis use. Analyses estimated the primary care prevalence of cannabis use and compared EHR-documented with patient-reported medical cannabis use, accounting for stratified sampling and nonresponse. Overall, 1688 patients responded to the survey (34% response rate; mean [SD] age, 50.7 [17.5] years; 861 female [56%], 1184 White [74%], 1514 non-Hispanic [97%], and 1059 commercially insured [65%]). The primary care prevalence of any past-year patient-reported cannabis use on the survey was 38.8% (95% CI, 31.9%-46.1%), whereas the prevalence of explicit and implicit medical use were 26.5% (95% CI, 21.6%-31.3%) and 35.1% (95% CI, 29.3%-40.8%), respectively. The prevalence of EHR-documented medical cannabis use was 4.8% (95% CI, 3.45%-6.2%). Compared with patient-reported explicit medical use, the sensitivity and specificity of EHR-documented medical cannabis use were 10.0% (95% CI, 4.4%-15.6%) and 97.1% (95% CI, 94.4%-99.8%), respectively. These findings suggest that medical cannabis use is common among primary care patients in a state with legal use, and most use is not documented in the EHR. Patient report of health reasons for cannabis use identifies more medical use compared with explicit questions about medical use.
Authors: Lapham, Gwen T; Campbell, Cynthia I; Bradley, Katharine A; et al.
JAMA Netw Open. 2022 May 02;5(5):e2211677. Epub 2022-05-02.
Exome sequencing in bipolar disorder identifies AKAP11 as a risk gene shared with schizophrenia
We report results from the Bipolar Exome (BipEx) collaboration analysis of whole-exome sequencing of 13,933 patients with bipolar disorder (BD) matched with 14,422 controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in patients with BD among genes under strong evolutionary constraint in both major BD subtypes. We find enrichment of ultra-rare PTVs within genes implicated from a recent schizophrenia exome meta-analysis (SCHEMA; 24,248 cases and 97,322 controls) and among binding targets of CHD8. Genes implicated from genome-wide association studies (GWASs) of BD, however, are not significantly enriched for ultra-rare PTVs. Combining gene-level results with SCHEMA, AKAP11 emerges as a definitive risk gene (odds ratio (OR) = 7.06, P = 2.83 × 10-9). At the protein level, AKAP-11 interacts with GSK3B, the hypothesized target of lithium, a primary treatment for BD. Our results lend support to BD’s polygenicity, demonstrating a role for rare coding variation as a significant risk factor in BD etiology.
Authors: Palmer, Duncan S; Schaefer, Catherine; Scott, Laura; Neale, Benjamin M; et al.
Nat Genet. 2022 05;54(5):541-547. Epub 2022-04-11.
Closing the Care Gap for People with Severe and Persistent Mental Illness: Collaborative Care, Telehealth, and Clinical Pharmacy
People with severe and persistent mental illness (SPMI) frequently struggle to maintain their recovery from recurring suicidality, psychosis, and debilitating mood episodes. They also face a high risk of chronic health conditions. Traditional – often short-term – psychiatric care is ill-equipped to meet the health needs of people with SPMI. Patients often require regular and sustained follow-up to support medication effectiveness and adherence and to screen for and treat cardiovascular disease and other common health risks. Kaiser Permanente Northern California has implemented a novel telehealth-based collaborative care program, SPMI Population Care, led by advanced practice clinical pharmacists, to improve the mental and physical health of its patients with SPMI. Although the individual program components of telehealth, collaborative care, and clinical pharmacy service have been employed successfully in the past for mental health care, the SPMI Population Care model combines the components and extends this approach to individuals at the most severe end of the psychiatric illness spectrum.
Authors: Iturralde, Esti; Fazzolari, Lisa; Shia, Macy; Slama, Natalie; Leang, Jessica; Awsare, Sameer; Nguyen, Lily T
NEJM Catal Innov Care Deliv. 2022 May;3(5).
Chronic health conditions, acute health events, and healthcare utilization among adults over age 50 in Hawai’i who use cannabis: A matched cohort study
Research on cannabis-related health outcomes in diverse older adults is limited. The current study utilized a matched cohort study design to compare older adults in Hawai’i with identified cannabis diagnoses and matched controls on chronic health conditions, acute health events, and healthcare utilization from 2016 to 2020. Patients age 50 + were identified using ICD-10 diagnostic codes for cannabis use, abuse, and dependence using electronic health record data from an integrated health system (Kaiser Permanente Hawai’i). Those with cannabis diagnoses (n = 275) were compared to matched non-using controls (n = 275; based on age, sex) on chronic health conditions (coronary heart disease, hypertension, COPD, chronic non-cancer pain), acute health events (myocardial infarction, respiratory symptoms, stroke, persistent or cyclic vomiting, injuries), and healthcare utilization (outpatient, inpatient, and emergency department visits) following case identification for two years. Participants were 19.3% Native Hawaiian/Pacific Islander, 24.4% Asian, 47.8% White, and 8.5% Other/Unknown, with an average age of 62.8 years (SD=7.3). Adjusting for covariates as possible, participants with a cannabis diagnosis had significantly greater risk of coronary heart disease, chronic non-cancer pain, stroke, myocardial infarction, cyclic vomiting, and injuries, over time, compared to controls. Cannabis use was associated with any and greater frequency of outpatient, inpatient, and emergency department visits. In a diverse sample, older adults who used cannabis had worse health conditions and events and used more health services over a two-year period. Future studies should evaluate cannabis-related health outcomes, effects of cannabis problem severity, as well as implications for healthcare in aging populations.
Authors: Phillips, Kristina T; Pedula, Kathryn L; Choi, Namkee G; Tawara, Kylee-Ann K; Simiola, Vanessa; Satre, Derek D; Owen-Smith, Ashli; Lynch, Frances F; Dickerson, John
Drug Alcohol Depend. 2022 05 01;234:109387. Epub 2022-03-03.
Genome-wide association study of actinic keratosis identifies new susceptibility loci implicated in pigmentation and immune regulation pathways
Actinic keratosis (AK) is a common precancerous cutaneous neoplasm that arises on chronically sun-exposed skin. AK susceptibility has a moderate genetic component, and although a few susceptibility loci have been identified, including IRF4, TYR, and MC1R, additional loci have yet to be discovered. We conducted a genome-wide association study of AK in non-Hispanic white participants of the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort (n = 63,110, discovery cohort), with validation in the Mass-General Brigham (MGB) Biobank cohort (n = 29,130). We identified eleven loci (P < 5 × 10-8), including seven novel loci, of which four novel loci were validated. In a meta-analysis (GERA + MGB), one additional novel locus, TRPS1, was identified. Genes within the identified loci are implicated in pigmentation (SLC45A2, IRF4, BNC2, TYR, DEF8, RALY, HERC2, and TRPS1), immune regulation (FOXP1 and HLA-DQA1), and cell signaling and tissue remodeling (MMP24) pathways. Our findings provide novel insight into the genetics and pathogenesis of AK susceptibility.
Authors: Kim, Yuhree; Yin, Jie; Huang, Hailiang; Jorgenson, Eric; Choquet, Hélène; Asgari, Maryam M
Commun Biol. 2022 Apr 21;5(1):386. Epub 2022-04-21.
Impact of COVID-19 on the Incidence and Severity of Obstetric and Gynecologic Emergency Department Visits in an Integrated Health Care System
COVID-19 has had an unprecedented impact on medical care use and delivery, including stark reductions in emergency department (ED) volume. The aim of this study was to assess changes in incidence of OB/GYN ED visits and disease severity at time of presentation during the COVID-19 pandemic. We conducted a multicenter retrospective study of OB/GYN-related ED visits before and during the COVID-19 pandemic. Incidence rates (IRs) and severity measures were compared across time periods and years. A total of 18,668 OB/GYN ED encounters occurred between January 1 and December 31, 2020, compared to 21,014 encounters between January 1 and December 31, 2019. During shelter-in-place, visits decreased by 41% compared to the pre-pandemic period in 2020 before returning to typical rates (incidence rate ratio (IRR) = 0.98 in fall/winter). We found a similar proportion of patients with hemoglobin < 7 g/dL for diagnoses associated with bleeding and patients with white blood cell count > 12,000 per µL in the setting of infection comparing corresponding time periods in 2019 and 2020. There were fewer formal OB/GYN consults, hospital admissions at time of presentation, and urgent surgical procedures performed across all periods in 2020; however, hospitalization within 7 days substantially increased in the first half of 2020. The incidence of OB/GYN ED visits declined substantially between March and August 2020 but then returned to pre-pandemic levels by fall/winter 2020. The decreased incidence was not accompanied by an increase in severity of presentation.
Authors: Tierney, Cassidy E; Abel, Mary Kathryn; Alavi, Mubarika M; Weintraub, Miranda Ritterman; Avins, Andrew; Zaritsky, Eve
Perm J. 2022 Apr 05;26(1):38-46. Epub 2022-04-05.
Addressing adolescent substance use in an urban pediatric federally qualified health center
Screening, brief intervention, and referral to treatment (SBIRT) is a systematic approach to identification and intervention for individuals at risk for substance use disorders. Prior research indicates that SBIRT is underutilized in pediatric primary care. Yet few studies have examined procedures for identifying and addressing substance use in clinics that serve publicly insured adolescents (i.e., federally qualified health centers [FQHC]). This descriptive, multi-method study assessed adolescent substance use frequency and provider perspectives to inform SBIRT implementation in an urban pediatric FQHC in California. A medical record review assessed substance use frequency and correlates among publicly insured adolescents aged 12-17 years who completed a well-child visit in pediatric primary care between 2014 and 2017 (N = 2252). Data on substance use (i.e., alcohol, illicit drugs, and tobacco) were from a health assessment tool mandated by Medicaid. Semi-structured interviews with 12 providers (i.e., pediatricians, nurse practitioners, behavioral health clinicians) elicited information about the current clinic workflow for adolescent substance use and barriers and facilitators to SBIRT implementation. Of 1588 adolescents who completed the assessment (70.5%), 6.8% reported current substance use. Self-reported use was highest among non-Hispanic Black (15.2%) adolescents and those with co-occurring depressive symptoms (14.4%). Provider-reported challenges to implementing SBIRT included a lack of space for confidential screening and a lack of referral options. Providers favored implementing technology-based tools such as tablets for adolescent pre-visit screening and electronic medical record-based decision support to facilitate brief intervention and treatment referrals. This study fills a substantial research gap by examining factors that impede and support SBIRT implementation in pediatric FQHC settings. Successful SBIRT implementation in these settings could significantly reduce the unmet need for substance use treatment among uninsured and publicly insured adolescents. Pediatric primary care and urgent care providers perceived SBIRT to be feasible, and health information and digital technologies may facilitate the integration of SBIRT into clinic workflows. Ensuring confidentiality for screening and expanding referral options for adolescents in need of community-based addiction treatment are also critical to increasing SBIRT uptake.
Authors: Yonek, Juliet C; Velez, Sarah; Satre, Derek D; Margolis, Kathryn; Whittle, Amy; Jain, Shonul; Tolou-Shams, Marina
J Subst Abuse Treat. 2022 04;135:108653. Epub 2021-10-28.
Substance use disorders among primary care patients screening positive for unhealthy alcohol use
Despite high prevalence of polysubstance use, recent data on concurrent alcohol use in patients with specific substance use disorders (SUDs) are lacking. To examine associations between specific SUDs and alcohol consumption levels. Using electronic health record data, we conducted a cross-sectional study of 2,720,231 primary care adults screened for alcohol use between 2014 and 2017 at Kaiser Permanente Northern California. Alcohol consumption levels were categorized as no reported use, low-risk use, and unhealthy use (exceeding daily, weekly, or both recommended drinking limits). Using multinomial logistic regression, and adjusting for sociodemographic and health characteristics, we examined the odds of reporting each alcohol consumption level in patients with a prior-year SUD diagnosis (alcohol, cannabis, cocaine, inhalant, opioid, sedative/anxiolytic, stimulant, other drug, nicotine, any SUD except nicotine) compared to those without. The sample was 52.9% female, 48.1% White; the mean age was 46 years (SD = 18). Patients with SUDs were less likely to report low-risk alcohol use relative to no use compared with patients without SUDs. Patients with alcohol or nicotine use disorder had higher odds of reporting unhealthy alcohol use relative to no use; however, patients with all other SUDs (except cocaine) had lower odds. Among patients who reported any alcohol use (n = 861,427), patients with SUDs (except opioid) had higher odds of exceeding recommended limits than those without. The associations of unhealthy alcohol use and SUDs suggest that screening for both alcohol and drug use in primary care presents a crucial opportunity to prevent and treat SUDs early.
Authors: Metz, Verena E; Palzes, Vanessa A; Kline-Simon, Andrea Hessel; Chi, Felicia W; Campbell, Cynthia I; Weisner, Constance M; Sterling, Stacy A
Fam Pract. 2022 03 24;39(2):226-233.
A refined procedure for esophageal resection using a full minimally invasive approach
Newer minimally invasive approaches to esophagectomy have brought substantial benefits to esophageal-cancer patients and continue to improve. We report here our experience with a streamlined procedure as part of a comprehensive perioperative-care program that provides additional advances in the continued evolution of this procedure. All patients with primary esophageal cancer referred for resection to the Oakland Medical Center of the Kaiser-Permanente Northern California health plan who underwent this approach between January 2013 and August 2018 were included. Operative and clinical outcome variables were extracted from the electronic medical record, operating-room files, and manual chart review. 142 patients underwent the new procedure and care program; 121 (85.2%) were men with mean age of 64.5 years. 127 (89.4%) were adenocarcinoma; 117 (82.4%) were clinical stage III or IVA. 115 (81.0%) required no jejunostomy. Median hospital length-of-stay was 3 days and 8 (5.6%) patients required admission to the intensive care unit. Postoperative complications occurred in 22 (15.5%) patients within 30 days of the procedure. There were no inpatient deaths; one patient (0.7%) died within 30 days following discharge and three additional deaths (2.1%) occurred through 90 days of follow-up. This approach resulted in excellent clinical outcomes, including short hospital stays with limited need for the intensive care unit, few perioperative complications, and relatively few patients requiring feeding tubes on discharge. This comprehensive approach to esophagectomy is feasible and provides another clinically meaningful advance in the progress of minimally invasive esophagectomy. Further development and dissemination of this method is warranted.
Authors: Ashiku, Simon K; Patel, Ashish R; Horton, Brandon H; Velotta, Jeffrey; Ely, Sora; Avins, Andrew L
J Cardiothorac Surg. 2022 Mar 04;17(1):29. Epub 2022-03-04.
Comparison of dementia incidence and prevalence between individuals with and without HIV infection in primary care from 2000 to 2016
To compare dementia incidence and prevalence after age 50 years by HIV status. Observational cohort, 2000-2016. People with HIV (PWH) on antiretroviral therapy (ART) and demographically similar people without HIV (PWoH), all aged 50 years and older, were identified from Kaiser Permanente healthcare systems in Northern California, Southern California, and Mid-Atlantic States (Maryland, Virginia, Washington DC). Dementia diagnoses were obtained from electronic health records. Incidence and prevalence of dementia, overall and by time period (i.e. 2000-2002, 2003-2004, …, 2015-2016), were calculated using Poisson regression. Trends were examined using Joinpoint regression. Rate ratios were used to compare dementia by HIV status with adjustment for sociodemographics, substance use, and clinical factors. The study included 13 296 PWH and 155 354 PWoH (at baseline: for both, mean age = 54 years, 89% men; for PWH, 80% with HIV RNA <200 copies/ml). From 2000 to 2016, overall incidence of dementia was higher among PWH [adjusted incidence rate ratio (aIRR) = 1.80, 95% confidence interval (CI) = 1.60-2.04]. Dementia incidence decreased among both PWH and PWoH (-8.0 and -3.1% per period, respectively) but remained higher among PWH in the most recent time period, 2015-2016 (aIRR = 1.58, 95% CI = 1.18-2.12). The overall prevalence of dementia from 2000 to 2016 was higher among PWH [adjusted prevalence ratio (aPR) = 1.86, 95% CI = 1.70-2.04] and was also higher among PWH in 2015-2016 (aPR = 1.75, 95% CI = 1.56-1.97). Reductions in dementia incidence are encouraging and may reflect ART improvement, but PWH are still more likely to have dementia than PWoH. Monitoring the burden of dementia among PWH is important as this population ages.
Authors: Lam, Jennifer O; Lee, Catherine; Gilsanz, Paola; Hou, Craig E; Leyden, Wendy A; Satre, Derek D; Flamm, Jason A; Towner, William J; Horberg, Michael A; Silverberg, Michael J
AIDS. 2022 03 01;36(3):437-445.
Equity in access to long-acting injectables in the USA
Authors: Hojilla, J Carlo; Gandhi, Monica; Satre, Derek D; Johnson, Mallory O; Saberi, Parya
Lancet HIV. 2022 03;9(3):e145-e147. Epub 2022-02-04.
Comparison of cognitive function in older adults with type 1 diabetes, type 2 diabetes, and no diabetes: results from the Study of Longevity in Diabetes (SOLID)
The incidence of both type 1 diabetes (T1D) and type 2 diabetes (T2D) is increasing. Life expectancy is improving in T1D, resulting in a growing population of elderly adults with diabetes. While it is well established that older adults with T2D are at increased risk of cognitive impairment, little is known regarding cognitive aging in T1D and how their cognitive profiles may differ from T2D. We compared baseline cognitive function and low cognitive function by diabetes status (n=734 T1D, n=232 T2D, n=247 without diabetes) among individuals from the Study of Longevity in Diabetes (mean age=68). We used factor analysis to group cognition into five domains and a composite measure of total cognition. Using linear and logistic regression models, we examined the associations between diabetes type and cognitive function, adjusting for demographics, comorbidities, depression, and sleep quality. T1D was associated with lower scores on total cognition, language, executive function/psychomotor processing speed, and verbal episodic memory, and greater odds of low executive function/psychomotor processing speed (OR=2.99, 95% CI 1.66 to 5.37) and verbal episodic memory (OR=1.92, 95% CI 1.07 to 3.46), compared with those without diabetes. T2D was associated with lower scores on visual episodic memory. Compared with T2D, T1D was associated with lower scores on verbal episodic memory and executive function/psychomotor processing speed and greater odds of low executive function/psychomotor processing speed (OR=1.74, 95% CI 1.03 to 2.92). Older adults with T1D had significantly poorer cognition compared with those with T2D and those without diabetes even after accounting for a range of comorbidities. Future studies should delineate how to reduce risk in this vulnerable population who are newly surviving to old age.
Authors: Lacy, Mary E; Moran, Chris; Gilsanz, Paola; Beeri, Michal S; Karter, Andrew J; Whitmer, Rachel A
BMJ Open Diabetes Res Care. 2022 03;10(2).
Prenatal Cannabis Use Before and During the COVID-19 Pandemic-Reply
Authors: Young-Wolff, Kelly C; Ansley, Deborah; Avalos, Lyndsay A
JAMA. 2022 02 08;327(6):587-588.
Whole genome sequence analysis of platelet traits in the NHLBI trans-omics for precision medicine initiative
Platelets play a key role in thrombosis and hemostasis. Platelet count (PLT) and mean platelet volume (MPV) are highly heritable quantitative traits, with hundreds of genetic signals previously identified, mostly in European ancestry populations. We here utilize whole genome sequencing (WGS) from NHLBI’s Trans-Omics for Precision Medicine initiative (TOPMed) in a large multi-ethnic sample to further explore common and rare variation contributing to PLT (n = 61 200) and MPV (n = 23 485). We identified and replicated secondary signals at MPL (rs532784633) and PECAM1 (rs73345162), both more common in African ancestry populations. We also observed rare variation in Mendelian platelet-related disorder genes influencing variation in platelet traits in TOPMed cohorts (not enriched for blood disorders). For example, association of GP9 with lower PLT and higher MPV was partly driven by a pathogenic Bernard-Soulier syndrome variant (rs5030764, p.Asn61Ser), and the signals at TUBB1 and CD36 were partly driven by loss of function variants not annotated as pathogenic in ClinVar (rs199948010 and rs571975065). However, residual signal remained for these gene-based signals after adjusting for lead variants, suggesting that additional variants in Mendelian genes with impacts in general population cohorts remain to be identified. Gene-based signals were also identified at several genome-wide association study identified loci for genes not annotated for Mendelian platelet disorders (PTPRH, TET2, CHEK2), with somatic variation driving the result at TET2. These results highlight the value of WGS in populations of diverse genetic ancestry to identify novel regulatory and coding signals, even for well-studied traits like platelet traits.
Authors: Little, Amarise; Correa, Adolfo; Raffield, Laura M; et al.
Hum Mol Genet. 2022 02 03;31(3):347-361.
Perceived Discrimination, Nativity, and Cognitive Performance in a Multi-ethnic Study of Older Adults: Findings from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study
Despite growing research on the association between discrimination and disparities in cognitive aging, an evidence gap remains on how the association varies by racial/ethnic group. This study evaluates the associations of experiences of discrimination with cognitive function and whether these associations varied by race/ethnicity and nativity. Using the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) cohort (N = 1 712) with approximately equal groups of Black, White, Latino, and Asian community-dwelling older adults aged 65 years and older, we evaluated the associations between self-reported experiences of everyday and major lifetime discrimination with overall cognitive performance and domain-specific cognition (verbal episodic memory, semantic memory, and executive functioning) across race/ethnicity and nativity. Linear regression models examined the cross-sectional association between self-reported experiences of everyday and major lifetime discrimination with z-standardized coefficients for cognition. We tested for effect modification by race and nativity. All models controlled for age, sex, and education. Among KHANDLE participants (mean age: 76 years; SD: 6.8), everyday discrimination was not associated with cognitive scores. Major lifetime discrimination was associated with better average cognitive scores among Black participants but not among other racial/ethnic groups. Major lifetime discrimination was associated with better average cognitive scores among U.S.-born but not among non-U.S.-born individuals. Our findings do not imply that discrimination improves cognition, but rather suggest that future research should include more detailed measures on discrimination and unfair treatment that could help disentangle the extent to which relationships are causal or reflect some other underlying factor.
Authors: Meza, Erika; Peterson, Rachel; Gilsanz, Paola; George, Kristen M; Miles, Sunita J; Eng, Chloe W; Mungas, Dan M; Mayeda, Elizabeth Rose; Glymour, M Maria; Whitmer, Rachel A
J Gerontol A Biol Sci Med Sci. 2022 02 03;77(2):e65-e73.
Measuring cognitive health in ethnically diverse older adults
Understanding racial/ethnic disparities in late-life cognitive health is a public health imperative. We used baseline data from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study to examine how age, education, gender, and clinical diagnosis, a proxy for brain health, are associated with cross-sectional measures of cognition in diverse racial/ethnic groups. Comprehensive measures of cognition were obtained using the Spanish and English Neuropsychological Assessment Scales and the National Institutes of Health Toolbox Cognitive Health Battery in a sample of 1,695 KHANDLE participants (Asians 24%, Blacks 26%, Latinos 20%, Whites 29%). A 25% random subsample was clinically evaluated and diagnosed with normal cognition, mild cognitive impairment (MCI), or dementia. Cognitive test scores were regressed on core demographic variables and diagnosis in the combined sample and in multiple group analyses stratified by racial/ethnic group. Race/ethnicity and education were variably associated with test scores with strongest associations with tests of vocabulary and semantic memory. Older age was associated with poorer performance on all measures, and gender differences varied across cognitive tests. Clinical diagnosis of MCI or dementia was associated with average decrements in test scores that ranged from -0.41 to -0.84 SD, with largest differences on tests of executive function and episodic memory. With few exceptions, associations of demographic variables and clinical diagnosis did not differ across racial/ethnic groups. The robust associations of cognitive test results with clinical diagnosis independent of core demographic variables and race/ethnicity support the validity of cognitive tests as indicators for brain health in diverse older adults.
Authors: Hernandez Saucedo, Hector; Whitmer, Rachel A; Glymour, Maria; DeCarli, Charles; Mayeda, Elizabeth-Rose; Gilsanz, Paola; Miles, Sunita Q; Bhulani, Nihal; Farias, Sarah Tomaszewski; Olichney, John; Mungas, Dan
J Gerontol B Psychol Sci Soc Sci. 2022 02 03;77(2):261-271.
Full title: A large-scale transcriptome-wide association study (TWAS) of 10 blood cell phenotypes reveals complexities of TWAS fine-mapping
Hematological measures are important intermediate clinical phenotypes for many acute and chronic diseases and are highly heritable. Although genome-wide association studies (GWAS) have identified thousands of loci containing trait-associated variants, the causal genes underlying these associations are often uncertain. To better understand the underlying genetic regulatory mechanisms, we performed a transcriptome-wide association study (TWAS) to systematically investigate the association between genetically predicted gene expression and hematological measures in 54,542 Europeans from the Genetic Epidemiology Research on Aging cohort. We found 239 significant gene-trait associations with hematological measures; we replicated 71 associations at p < 0.05 in a TWAS meta-analysis consisting of up to 35,900 Europeans from the Women's Health Initiative, Atherosclerosis Risk in Communities Study, and BioMe Biobank. Additionally, we attempted to refine this list of candidate genes by performing conditional analyses, adjusting for individual variants previously associated with hematological measures, and performed further fine-mapping of TWAS loci. To facilitate interpretation of our findings, we designed an R Shiny application to interactively visualize our TWAS results by integrating them with additional genetic data sources (GWAS, TWAS from multiple reference panels, conditional analyses, known GWAS variants, etc.). Our results and application highlight frequently overlooked TWAS challenges and illustrate the complexity of TWAS fine-mapping.
Authors: Tapia, Amanda L; Choquet, Hélène; Raffield, Laura M; et al.
Genet Epidemiol. 2022 02;46(1):3-16. Epub 2021-11-15.
Connecting Research and Practice: Implementation of Suicide Prevention Strategies in Learning Health Care Systems
The health care systems affiliated with the Mental Health Research Network strive to be learning health care systems that identify and address evidence gaps of importance to clinicians, patients, and funders. This column describes how research guides clinical care and clinical care guides research in the area of suicide prevention as well as some of the challenges of conducting embedded research.
Authors: Rossom, Rebecca C; Sterling, Stacy; Liu, Vincent; Simon, Greg E; et al.
Psychiatr Serv. 2022 02 01;73(2):219-222. Epub 2021-06-30.
Marginal structural models for life-course theories and social epidemiology: Definitions, sources of bias, and simulated illustrations
Social epidemiology aims to identify social structural risk factors, thus informing targets and timing of interventions. Ascertaining which interventions will be most effective and when they should be implemented is challenging because social conditions vary across the life course and are subject to time-varying confounding. Marginal structural models (MSMs) may be useful but can present unique challenges when studying social epidemiologic exposures over the life course. We describe selected MSMs corresponding to common theoretical life-course models and identify key issues for consideration related to time-varying confounding and late study enrollment. Using simulated data mimicking a cohort study evaluating the effects of depression in early, mid-, and late life on late-life stroke risk, we examined whether and when specific study characteristics and analytical strategies may induce bias. In the context of time-varying confounding, inverse-probability-weighted estimation of correctly specified MSMs accurately estimated the target causal effects, while conventional regression models showed significant bias. When no measure of early-life depression was available, neither MSMs nor conventional models were unbiased, due to confounding by early-life depression. To inform interventions, researchers need to identify timing of effects and consider whether missing data regarding exposures earlier in life may lead to biased estimates.
Authors: Gilsanz, Paola; Young, Jessica G; Glymour, M Maria; Tchetgen Tchetgen, Eric J; Eng, Chloe W; Koenen, Karestan C; Kubzansky, Laura D
Am J Epidemiol. 2022 01 24;191(2):349-359.
Case-control study of adverse childhood experiences and multiple sclerosis risk and clinical outcomes
Adverse childhood experiences (ACEs) are linked to numerous health conditions but understudied in multiple sclerosis (MS). This study’s objective was to test for the association between ACEs and MS risk and several clinical outcomes. We used a sample of adult, non-Hispanic MS cases (n = 1422) and controls (n = 1185) from Northern California. Eighteen ACEs were assessed including parent divorce, parent death, and abuse. Outcomes included MS risk, age of MS onset, Multiple Sclerosis Severity Scale score, and use of a walking aid. Logistic and linear regression estimated odds ratios (ORs) (and beta coefficients) and 95% confidence intervals (CIs) for ACEs operationalized as any/none, counts, individual events, and latent factors/patterns. Overall, more MS cases experienced ≥1 ACE compared to controls (54.5% and 53.8%, respectively). After adjusting for sex, birthyear, and race, this small difference was attenuated (OR = 1.01, 95% CI: 0.87, 1.18). There were no trends of increasing or decreasing odds of MS across ACE count categories. Consistent associations between individual ACEs between ages 0-10 and 11-20 years and MS risk were not detected. Factor analysis identified five latent ACE factors, but their associations with MS risk were approximately null. Age of MS onset and other clinical outcomes were not associated with ACEs after multiple testing correction. Despite rich data and multiple approaches to operationalizing ACEs, no consistent and statistically significant effects were observed between ACEs with MS. This highlights the challenges of studying sensitive, retrospective events among adults that occurred decades before data collection.
Authors: Horton, Mary K; McCurdy, Shannon; Shao, Xiaorong; Bellesis, Kalliope; Chinn, Terrence; Schaefer, Catherine; Barcellos, Lisa F
PLoS One. 2022;17(1):e0262093. Epub 2022-01-13.
Hereditary Spherocytosis
Hereditary spherocytosis (HS) is the most prevalent cause of hemolytic anemia due to an abnormal red cell membrane and classifies as a type of congenital hemolytic anemia. Oskar Minkowsky first described it in the early 1900s.[1] Erythrocytes are unable to maintain their normal biconcave shape due to genetic mutations in membrane/cytoskeletal proteins that play a role in structural morphologic stability. Deficient or abnormal proteins may include spectrin, ankyrin, band 3, and band 4.2, encoded by different genes.[2][3] The clinical manifestations vary based on the severity of disease and the type of genetic mutation.[1][2][3]
Authors: Zamora, Edgar A.; Schaefer, Catherine A.
Treasure Island (FL): StatPearls Publishing; 2022.
Relationships Between Telomere Length, Plasma Glucagon-like Peptide 1, and Insulin in Early-Life Stress-Exposed Nonhuman Primates
Early-life stress is associated with alterations in telomere length, a marker of accumulated stress and aging, and a risk factor for psychiatric disorders. Nonhuman primate maternal variable foraging demand (VFD) is a validated early-life stress model, resulting in anxiety- and depressive-like symptoms in offspring. Previous studies reported increased plasma glucagon-like peptide 1 (pGLP-1) along with insulin resistance in this model. We investigated whether VFD rearing related to adult telomere length and to these neuroendocrine markers. Adult leukocyte telomere length was measured in VFD-reared (12 males, 13 females) and non-VFD-reared (9 males, 26 females) bonnet macaques. Associations between adult telomere length and adolescent fasting pGLP-1 or insulin resistance in VFD-reared versus non-VFD-reared groups were examined using regression modeling, controlling for sex, weight, and age. VFD subjects had relatively longer telomeres than non-VFD subjects (p = .017), and females relatively longer than males (p = .0004). Telomere length was positively associated with pGLP-1 (p = .0009) and with reduced insulin sensitivity (p < .0001) in both sexes, but not as a function of rearing group. Unexpectedly, VFD was associated with longer adult telomere length. Insulin resistance may lead to higher pGLP-1 levels in adolescence, which could protect telomere length in VFD offspring as adults. Associations between adult telomere length and adolescent insulin resistance and high pGLP-1 may reflect an adaptive, compensatory response after early-life stress exposure.
Authors: Ridout, Kathryn K; Coplan, Jeremy; et al.
Biol Psychiatry Glob Open Sci. 2022 Jan;2(1):54-60. Epub 2021-08-03.
A mobile app to promote alcohol and drug SBIRT skill translation among multi-disciplinary health care trainees: Results of a randomized controlled trial
Adherence to clinical practice guidelines for alcohol and drug screening, brief intervention, and referral to treatment (SBIRT) is often inadequate. Mobile apps developed as clinical translation tools could improve the delivery of high fidelity SBIRT. Methods: This study tested the effectiveness of an SBIRT mobile app conceptually aligned with the Theory of Planned Behavior (TPB) to support SBIRT delivery by health care trainees (nursing, social work, internal medicine, psychiatry, and psychology) working in clinical settings (N = 101). Bivariate analyses examined the rate of SBIRT delivery between trainees assigned to the experimental (app) and control (no app) study conditions; as well as the relationship between TPB-based constructs, intention to deliver SBIRT, and screening rates. Results: No significant differences were identified between the study conditions in SBIRT delivery. Significant correlations were found between intent to screen and TPB variables including attitudes/behavioral beliefs concerning substance use treatment (r = .49, p = .01); confidence in clinical skills (r = .36, p = .01); subjective norms (r = .54, p = .01) and perceived behavioral control over appointment time constraints (r = .42, p = .01). Also significant were correlations between percent of patients screened and confidence (r = .24, p = .05); subjective norms (r = .22, p = .05) and perceived behavioral control (r = .28, p = .01). Conclusions: The negative results of the study condition comparisons indicate the need for further investigation of strategies to optimize mobile app utilization, engagement, and effectiveness as a clinical translation tool. Findings of significant correlations between substance use screening rates and both norms and confidence support the potential value of the TPB model in explaining behavior of health care learners in SBIRT delivery.
Authors: Curtis AC; Satre DD; Sarovar V; Wamsley M; Ly K; Satterfield J
Subst Abus. 2022;43(1):13-22. Epub 2019-11-11.
Preconception cannabis use: An important but overlooked public health issue
Cannabis is the most commonly used federally illicit drug among pregnant women in the United States, and the prevalence and frequency of prenatal cannabis use are increasing. The preconception period – typically thought of as the 3-12 months immediately preceding pregnancy – is a distinct and critical period for women’s health that has often been overlooked when examining prenatal cannabis use. Given that substance use behaviors typically develop before pregnancy, and risk factors associated with prenatal cannabis use are often present prior to conception, preventive approaches to addressing prenatal cannabis use would benefit from focusing on women who use cannabis prior to pregnancy. In order to ensure preconception cannabis use is brought to the forefront of cannabis prevention efforts, we recommend additional research, patient education, and clinician training focused on preconception cannabis use.
Authors: Skelton, Kara R; Young-Wolff, Kelly C
Womens Health (Lond). 2022 Jan-Dec;18:17455057221124071.
Alcohol Use Among Young Adults in Northern California During the COVID-19 Pandemic-An Electronic Health Records-Based Study
Individuals globally were affected by the COVID-19 pandemic in myriad of ways, including social isolation and economic hardship, resulting in negative impacts on mental health and substance use. Young adults have been subjected to extraordinary challenges such as job loss, virtual school, or childcare issues, but have received limited attention from research so far. Using electronic health record data from a large integrated healthcare system in Northern California, this longitudinal observational study examined changes in the prevalence of unhealthy alcohol use (identified via systematic alcohol screening in adult primary care) from pre- (3/1/2019-12/31/2019) to post-COVID onset (3/1/2020-12/31/2020) among young adults (18-34 years). Among the 663,111 and 627,095 young adults who utilized primary care in the pre- and post-COVID onset periods, 342,889 (51.9%) and 186,711 (29.8%) received alcohol screening, respectively. We fit generalized estimating equation Poisson models to estimate the change in prevalence of unhealthy alcohol use from pre- to post-COVID onset among those who were screened, while using inverse probability weighting to account for potential selection bias of receiving alcohol screening. Heterogeneity in the change of prevalence by patient characteristics was also examined. Overall, the unadjusted prevalence of unhealthy alcohol use slightly decreased from 9.2% pre-COVID to 9.0% post-COVID onset. After adjusting for patient covariates, the prevalence of unhealthy alcohol use decreased by about 2% [adjusted prevalence ratio (aPR) = 0.98, 95% CI = 0.96, 1.00]. The prevalence of unhealthy alcohol use increased among women by 8% (aPR = 1.08, 95% CI = 1.06, 1.11), patients 18-20 years by 7% (aPR = 1.07, 95% CI = 1.00, 1.15), and Latino/Hispanic patients by 7% (aPR = 1.07, 95% CI = 1.03, 1.11). While the prevalence of unhealthy alcohol use decreased among men by 12% (aPR = 0.88, 95% CI = 0.86, 0.90), patients 21-34 years by 2% (aPR = 0.98, 95% CI = 0.96, 0.99), White patients by 3% (95% CI = 0.95, 1.00), and patients living in neighborhoods with the lowest deprivation indices by 9% (aPR = 0.91, 95% CI = 0.88, 0.94), their unadjusted prevalence remained higher than their counterparts post-COVID onset. There was no variation in the change of prevalence by comorbid mental health conditions or drug use disorders. While changes in unhealthy alcohol use prevalence among young adults were small, findings raise concerns over increased drinking among women, those younger than the U.S. legal drinking age, and Latino/Hispanic patients.
Authors: Metz, Verena E; Palzes, Vanessa A; Chi, Felicia W; Campbell, Cynthia I; Sterling, Stacy A
Front Psychiatry. 2022;13:883306. Epub 2022-07-12.
Associations of COVID-19-Related Health, Healthcare and Economic Factors With Prenatal Depression and Anxiety
Objective: This study evaluated whether COVID-19 pandemic-related health, healthcare and economic factors during pregnancy are associated with prenatal depression and anxiety. Methods: We conducted a cross-sectional study of 6,628 pregnant members of Kaiser Permanente Northern California who responded to a survey between 22 June and 30 September 2020. The survey included questions about depression (Patient Health Questionnaire) and anxiety (Generalized Anxiety Disorder) symptoms and COVID-19-related health and healthcare (e.g., had COVID-19) and economic (e.g., food insecurity) factors. Results: Over one third of individuals reported depression (25% mild, 8% moderate, 3% severe) or anxiety (22% mild, 8% moderate, 5% severe) symptoms. In multivariable analyses, COVID-19 during pregnancy, employment with greater risk of COVID-19, distress over changes in prenatal care, job loss, changes in childcare and food insecurity were associated with greater odds of prenatal depression or anxiety. Conclusion: Findings suggest the COVID-19 pandemic may have severe mental health repercussions for pregnant individuals. Support services for pregnant individuals experiencing these COVID-19-related factors and monitoring of those who had moderate/severe prenatal depression and anxiety symptoms during the COVID-19 pandemic is warranted.
Authors: Avalos, Lyndsay A; Nance, Nerissa; Badon, Sylvia E; Young-Wolff, Kelly; Ames, Jennifer; Zhu, Yeyi; Hedderson, Monique M; Ferrara, Assiamira; Zerbo, Ousseny; Greenberg, Mara; Croen, Lisa A
Int J Public Health. 2022;67:1604433. Epub 2022-05-04.
The Feasibility and Utility of Harnessing Digital Health to Understand Clinical Trajectories in Medication Treatment for Opioid Use Disorder: D-TECT Study Design and Methodological Considerations
Across the U.S., the prevalence of opioid use disorder (OUD) and the rates of opioid overdoses have risen precipitously in recent years. Several effective medications for OUD (MOUD) exist and have been shown to be life-saving. A large volume of research has identified a confluence of factors that predict attrition and continued substance use during substance use disorder treatment. However, much of this literature has examined a small set of potential moderators or mediators of outcomes in MOUD treatment and may lead to over-simplified accounts of treatment non-adherence. Digital health methodologies offer great promise for capturing intensive, longitudinal ecologically-valid data from individuals in MOUD treatment to extend our understanding of factors that impact treatment engagement and outcomes. This paper describes the protocol (including the study design and methodological considerations) from a novel study supported by the National Drug Abuse Treatment Clinical Trials Network at the National Institute on Drug Abuse (NIDA). This study (D-TECT) primarily seeks to evaluate the feasibility of collecting ecological momentary assessment (EMA), smartphone and smartwatch sensor data, and social media data among patients in outpatient MOUD treatment. It secondarily seeks to examine the utility of EMA, digital sensing, and social media data (separately and compared to one another) in predicting MOUD treatment retention, opioid use events, and medication adherence [as captured in electronic health records (EHR) and EMA data]. To our knowledge, this is the first project to include all three sources of digitally derived data (EMA, digital sensing, and social media) in understanding the clinical trajectories of patients in MOUD treatment. These multiple data streams will allow us to understand the relative and combined utility of collecting digital data from these diverse data sources. The inclusion of EHR data allows us to focus on the utility of digital health data in predicting objectively measured clinical outcomes. Results may be useful in elucidating novel relations between digital data sources and OUD treatment outcomes. It may also inform approaches to enhancing outcomes measurement in clinical trials by allowing for the assessment of dynamic interactions between individuals’ daily lives and their MOUD treatment response. Identifier: NCT04535583.
Authors: Marsch, Lisa A; Campbell, Cynthia I; et al.
Front Psychiatry. 2022;13:871916. Epub 2022-04-29.
Contributions of COVID-19 Pandemic-Related Stressors to Racial and Ethnic Disparities in Mental Health During Pregnancy
This study aimed to identify racial and ethnic disparities in prenatal mental health and identify COVID-19 pandemic-related health/healthcare and economic contributors to these disparities, using an established framework for disparity investigation. This cross-sectional study includes 10,930 pregnant people at Kaiser Permanente Northern California who completed an online survey between June 22, 2020 and April 28, 2021 on COVID-19 pandemic-related health/healthcare and economic stressors, depression, and anxiety. Self-reported race and ethnicity were extracted from electronic health records. Weighted analyses were used to evaluate the association between racial and ethnic category and prenatal depression and anxiety; the prevalence of each stressor by race and ethnicity; and the relationship between each stressor and prenatal depression and anxiety in each racial and ethnic category. The sample was 22% Asian, 3% Black, 20% Hispanic, 5% Other/Multiracial/Unknown, and 49% White. Compared to White people, Black and Hispanic people had a higher prevalence of prenatal depression (aPR: 1.85, 95% CI: 1.45, 2.35 and aPR: 1.17, 95% CI: 1.00, 1.37, respectively) and anxiety (aPR: 1.71, 95% CI: 1.34, 2.18 and aPR: 1.10, 95% CI: 0.94, 1.29, respectively). Compared to White people, Black and Hispanic people had a higher prevalence of moderate/severe distress due to changes in prenatal care (24 vs. 34 and 31%), and food insecurity (9 vs. 31 and 24%). Among Black and Hispanic people, distress due to changes in prenatal care was associated with a greater prevalence of prenatal depression (aPR: 2.27, 95% CI: 1.41, 3.64 and aPR: 2.76, 95% CI: 2.12, 3.58, respectively) and prenatal anxiety (aPR: 3.00, 95% CI: 1.85, 4.84 and aPR: 2.82, 95% CI: 2.15, 3.71, respectively). Additionally, among Hispanic people, high-risk employment and food insecurity were associated with a greater prevalence of prenatal depression and anxiety. This study identified racial and ethnic disparities in mental health for pregnant Black and Hispanic people. Distress due to prenatal care changes contributed to the observed disparities in prenatal depression and anxiety for Black and Hispanic people and food insecurity additionally contributed to the observed disparities for Hispanic people. Addressing distress due to changes to prenatal care and food insecurity specifically in Black and Hispanic people may help reduce the high burden of poor mental health and reduce observed disparities in these communities.
Authors: Avalos, Lyndsay A; Nance, Nerissa; Zhu, Yeyi; Croen, Lisa A; Young-Wolff, Kelly C; Zerbo, Ousseny; Hedderson, Monique M; Ferrara, Assiamira; Ames, Jennifer L; Badon, Sylvia E
Front Psychiatry. 2022;13:837659. Epub 2022-03-14.
Clinical documentation of patient-reported medical cannabis use in primary care: Toward scalable extraction using natural language processing methods
Background: Most states have legalized medical cannabis, yet little is known about how medical cannabis use is documented in patients’ electronic health records (EHRs). We used natural language processing (NLP) to calculate the prevalence of clinician-documented medical cannabis use among adults in an integrated health system in Washington State where medical and recreational use are legal. Methods: We analyzed EHRs of patients ≥18 years old screened for past-year cannabis use (November 1, 2017-October 31, 2018), to identify clinician-documented medical cannabis use. We defined medical use as any documentation of cannabis that was recommended by a clinician or described by the clinician or patient as intended to manage health conditions or symptoms. We developed and applied an NLP system that included NLP-assisted manual review to identify such documentation in encounter notes. Results: Medical cannabis use was documented for 16,684 (5.6%) of 299,597 outpatient encounters with routine screening for cannabis use among 203,489 patients seeing 1,274 clinicians. The validated NLP system identified 54% of documentation and NLP-assisted manual review the remainder. Language documenting reasons for cannabis use included 125 terms indicating medical use, 28 terms indicating non-medical use and 41 ambiguous terms. Implicit documentation of medical use (e.g., “edible THC nightly for lumbar pain”) was more common than explicit (e.g., “continues medical cannabis use”). Conclusions: Clinicians use diverse and often ambiguous language to document patients’ reasons for cannabis use. Automating extraction of documentation about patients’ cannabis use could facilitate clinical decision support and epidemiological investigation but will require large amounts of gold standard training data.
Authors: Carrell, David S; Campbell, Cynthia I; Lapham, Gwen T; et al.
Subst Abus. 2022;43(1):917-924.
Agreement between Youth Self-Report and Biospecimen-Confirmed Substance Use: A Systematic Review
ContextBiospecimen analysis may enhance confidence in the accuracy of self-reported substance use among adolescents and transitional age youth (TAY). Associations between biospecimen types and self-reported use, however, are poorly characterized in the existing literature. Objective: We performed a systematic review of associations between biospecimen-confirmed and self-reported substance use. Data sources: PubMed, Embase, and Web of Science. Study selection: We included studies documenting associations between self-reported and biospecimen-confirmed substance use among adolescents (12-18 years) and TAY (19-26 years) published 1990-2020. Data extraction: Three authors extracted relevant data using a template and assessed bias risk using a modified JBI Critical Appraisal Tool. Results: We screened 1523 titles and abstracts, evaluated 73 full texts for eligibility, and included 28 studies. Most studies examined urine (71.4%) and hair (32.1%) samples. Self-report retrospective recall period varied from past 24 h to lifetime use. Agreement between self-report and biospecimen results were low to moderate and were higher with rapidly metabolized substances (e.g., amphetamines) and when shorter retrospective recall periods were applied. Frequently encountered sources of potential bias included use of non-validated self-report measures and failure to account for confounding factors in the association between self-reported and biospecimen-confirmed use. Limitations: Study heterogeneity prevented a quantitative meta-analysis. Studies varied in retrospective recall periods, biospecimen processing, and use of validated self-report measures. Conclusions: Associations between self-reported and biospecimen-confirmed substance use are low to moderate and are higher for shorter recall periods and for substances with rapid metabolism. Future studies should employ validated self-report measures and include demographically diverse samples.
Authors: Folk, Johanna B; Hirschtritt, Matthew E; McCrary, Quincy D; Kalapatapu, Raj K
Subst Use Misuse. 2022;57(4):531-538. Epub 2022-01-04.
Parent-focused prevention of adolescent health risk behavior: Study protocol for a multisite cluster-randomized trial implemented in pediatric primary care
Evidence-based parenting interventions play a crucial role in the sustained reduction of adolescent behavioral health concerns. Guiding Good Choices (GGC) is a 5-session universal anticipatory guidance curriculum for parents of early adolescents that has been shown to reduce substance use, depression symptoms, and delinquent behavior. Although prior research has demonstrated the effectiveness of evidence-based parenting interventions at achieving sustained reductions in adolescent behavioral health concerns, public health impact has been limited by low rates of uptake in community and agency settings. Pediatric primary care is an ideal setting for implementing and scaling parent-focused prevention programs as these settings have a broad reach, and prevention programs implemented within them have the potential to achieve population-level impact. The current investigation, Guiding Good Choices for Health (GGC4H), tests the feasibility and effectiveness of implementing GGC in 3 geographically and socioeconomically diverse large integrated healthcare systems. This pragmatic, cluster randomized clinical trial will compare GGC parenting intervention to usual pediatric primary care practice, and will include approximately 3750 adolescents; n = 1875 GGC intervention and n = 1875 usual care. The study team hypothesizes that adolescents whose parents are randomized into the GGC intervention arm will show reductions in substance use initiation, the study’s primary outcomes, and other secondary (e.g., depression symptoms, substance use prevalence) and exploratory outcomes (e.g., health services utilization, anxiety symptoms). The investigative team anticipates that the implementation of GGC within pediatric primary care clinics will successfully fill an unmet need for effective preventive parenting interventions. Trial registration: Clinicaltrials.govNCT04040153.
Authors: Scheuer, Hannah; Sterling, Stacy A; Weisner, Constance; Quesenberry, Charles; Yoon, Tae; et al.
Contemp Clin Trials. 2022 01;112:106621. Epub 2021-11-14.
The Natural History of Large Abdominal Aortic Aneurysms in Patients without Timely Repair
Contemporary data on the natural history of large abdominal aortic aneurysms (AAAs) in patients undergoing delayed or no repair are lacking. In this study, we examine the impact of large AAA size on the incidence of rupture and mortality. From a prospectively maintained aneurysm surveillance registry, patients with an unrepaired, large AAA (≥5.5 cm in men and ≥5.0 cm in women) at baseline (ie, index imaging) or who progressed to a large size from 2003 to 2017 were included, with follow-up through March 2020. Outcomes of interest obtained by manual chart review included rupture (confirmed by imaging/autopsy), probable rupture (timing/findings consistent with rupture without more likely cause of death), repair, reasons for either no or delayed (>1 year after diagnosis of large AAA) repair and total mortality. Cumulative incidence of rupture was calculated using a nonparametric cumulative incidence function, accounting for the competing events of death and aneurysm repair and was stratified by patient sex. Of the 3248 eligible patients (mean age, 83.6 ± 9.1 years; 71.2% male; 78.1% white; and 32.0% current smokers), 1423 (43.8%) had large AAAs at index imaging, and 1825 progressed to large AAAs during the follow-up period, with a mean time to qualifying size of 4.3 ± 3.4 years. In total, 2215 (68%) patients underwent repair, of which 332 were delayed >1 year; 1033 (32%) did not undergo repair. The most common reasons for delayed repair were discrepancy in AAA measurement between surgeon and radiologist (34%) and comorbidity (20%), whereas the most common reasons for no repair were patient preference (48%) and comorbidity (30%). Among patients with delayed repair (mean time to repair, 2.6 ± 1.8 years), nine (2.7%) developed symptomatic aneurysms, and an additional 11 (3.3%) ruptured. Of patients with no repair, 94 (9.1%) ruptured. The 3-year cumulative incidence of rupture was 3.4% for initial AAA size 5.0 to 5.4 cm (women only), 2.2% for 5.5 to 6.0 cm, 6.0% for 6.1 to 7.0 cm, and 18.4% for >7.0 cm. Women with AAA size 6.1 to 7.0 cm had a 3-year cumulative incidence of rupture of 12.8% (95% confidence interval, 7.5%-19.6%) compared with 4.5% (95% confidence interval, 3.0%-6.5%) in men (P = .002). In this large cohort of AAA registry patients over 17 years, annual rupture rates for large AAAs were lower than previously reported, with possible increased risk in women. Further analyses are ongoing to identify those at increased risk for aneurysm rupture and may provide targeted surveillance regimens and improve patient counseling.
Authors: Lancaster, Elizabeth M; Gologorsky, Rebecca; Hull, Michaela M; Okuhn, Steven; Solomon, Matthew D; Avins, Andrew L; Adams, John L; Chang, Robert W
J Vasc Surg. 2022 01;75(1):109-117. Epub 2021-07-26.
Predicting adolescent alcohol and other drug problems using electronic health records data
Alcohol and other drug (AOD) use problems may cause significant burden on affected adolescents and their families, yet treatment providers often do not identify these problems early enough. To develop, and internally and externally validate a multivariable prediction model of adolescent AOD problems using child- and maternal-level predictors before age 12, and child-level predictors between ages 12 to 18, as recorded in the electronic health records (EHR). A retrospective cohort study conducted time-to-event analyses using Cox proportional hazards models. 41,172 children born between 1997 and 2000 at four health plans (Kaiser Permanente Hawaii, KPHI; Kaiser Permanente Northern California, KPNC; Geisinger Clinic, GC; and Henry Ford Health System, HFHS) who had continuous membership since birth and linkable maternal records in the health plan. AOD use problems between ages 12 to 18, defined as either: 1) having a contact with the AOD treatment program or 2) receiving a non-tobacco AOD diagnosis in an inpatient or outpatient encounter. Candidate predictor variables include demographics, socioeconomic status, and clinical diagnoses of the children and the mothers. Overall, 1400 (3.4%) adolescents had an AOD disorder between ages 12 to 18; the median follow-up time post-age 12 was 5.3 years. The research team developed two final prediction models: a “baseline” model of 10 child-level and 7 maternal-level predictors before age 12, and a more comprehensive “time-varying” model, which incorporated child risk factors after age 12 as time-varying covariates in addition to the baseline model predictors. Model performance evaluation showed good discrimination performance of the models, with the concordance index improved for the time-varying model, especially for prediction of AOD events in late adolescence. This study identified a number of child and maternal characteristics and diagnoses routinely available in EHR data as predictive of risk for developing AOD problems in adolescence. Further, we found that risk of developing problems varies significantly by the timing and persistence of the risk factors. Findings may have potential clinical implications for prevention and identification of adolescent AOD problems, but more research is needed, especially across additional health systems.
Authors: Chi, Felicia W; Alexeeff, Stacey; Ahmedani, Brian; Boscarino, Joseph A; Waitzfelder, Beth; Dugan, Ryan; Frankland, Timothy; Hu, Yong; Loree, Amy; Sterling, Stacy
J Subst Abuse Treat. 2022 Jan;132:108487. Epub 2021-05-21.
Predictors of Early and Sustained Cessation of Heavy Drinking Over 5 Years Among Adult Primary Care Patients
To identify factors asociated with early and sustained cessation of heavy drinking. Retrospective cohort study over 5 years. Kaiser Permanente Northern California, United States. Adults reporting heavy drinking during primary care-based alcohol screening between 1 June 2013 and 31 May 2014. The sample (n = 85 434) was 40.7% female and 33.8% non-white; mean age was 50.3 years (standard deviation = 18.1). Following US guidelines, early and sustained cessation of heavy drinking was defined as reporting lower-risk drinking or abstinence at 1 year and to 5 years after achieving early cessation, respectively. Associations between patient characteristics and service use and cessation outcomes were examined using logistic regression with inverse probability weights addressing attrition. Nearly two-thirds of participants achieved early cessation of heavy drinking. Women [odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.35, 1.44], middle-age (35-64 years: ORs = 1.16-1.19), non-white race/ethnicity (ORs = 1.03-1.57), medical conditions (OR = 1.05, 95% CI = 1.04, 1.06), psychiatric (OR = 1.10, 95% CI = 1.06, 1.15) and drug use disorders (OR = 1.35, 95% CI = 1.17, 1.56) and addiction treatment (OR = 1.19, 95% CI = 1.09, 1.30) were associated with higher odds of early cessation, while older age (≥ 65 years: OR = 0.91, 95% CI = 0.86, 0.96), smoking (OR = 0.81, 95% CI = 0.77, 0.84), higher index drinking levels (exceeding both daily and weekly limits: OR = 0.30, 95% CI = 0.29, 0.32) and psychiatric treatment (OR = 0.91, 95% CI = 0.84, 0.99) were associated with lower odds. Among those who achieved early cessation (n = 19 200), 60.0% sustained cessation. Associations between patient factors and sustained cessation paralleled those observed in analyses of early cessation. Additionally, routine primary care (OR = 1.57, 95% CI = 1.44, 1.71) and addiction treatment post-1 year (OR = 1.41, 95% CI = 1.19, 1.66) were associated with higher odds of sustained cessation. Lower-risk drinking versus abstinence at 1 year was associated with lower odds of sustained cessation (OR = 0.62, 95% CI = 0.57, 0.66). Nearly two-thirds of a large, diverse sample of patients who reported heavy drinking in a Californian health-care system achieved early and sustained cessation of heavy drinking. Vulnerable subgroups (i.e. non-white patients and those with psychiatric disorders), patients who received routine primary care and those who received addiction treatment were more likely to sustain cessation of heavy drinking than other participants.
Authors: Palzes, Vanessa A; Kline-Simon, Andrea H; Satre, Derek D; Sterling, Stacy; Weisner, Constance; Chi, Felicia W
Addiction. 2022 01;117(1):82-95. Epub 2021-07-12.
Engaging patients in population-based chronic disease management: A qualitative study of barriers and intervention opportunities
Cardiovascular disease (CVD) continues to be a leading cause of morbidity in the U.S. Managing CVD risk factors, such as diabetes or hypertension, can be challenging for many individuals. We investigated the barriers experienced by patients who persistently struggled to reach their CVD risk factor control goals. This qualitative study examined patient, clinician, and researcher observations of individuals’ experiences in a chronic disease management program. All participants (n = 332) were enrolled in a clinical trial testing a skills-based group intervention seeking to improve healthcare engagement. Data were analyzed through a general inductive approach and resulting themes were structured along the Capability-Opportunity-Motivation-Behavior framework. Analyses identified care engagement barriers related to participants’ communication skills and activation, care team relationship processes, and emotional factors. Although most participants reported benefitting from skills training, persistent barriers included distrust of their providers, shame about health challenges, and dissatisfaction with care team interactions that were described as impersonal or unresponsive. Efforts to support engagement in CVD risk factor management programs should address whether patients and their care team have the necessary skills, opportunities and confidence to proactively communicate health needs and engage in non-judgmental interactions for goal-setting, rapport-building, and shared decision-making.
Authors: Fang, Anya; Abdelgadir, Dana; Gopalan, Anjali; Ross, Thekla; Uratsu, Connie S; Sterling, Stacy A; Grant, Richard W; Iturralde, Esti
Patient Educ Couns. 2022 01;105(1):182-189. Epub 2021-05-04.
Association of Pregnancy Intentions With Substance Use During Early Pregnancy
The goal of this study was to evaluate the association between pregnancy intentions and substance use in early pregnancy among pregnant women receiving prenatal care in a large, integrated healthcare system. The sample comprised 29,787 Kaiser Permanente Northern California pregnant women (12.1% aged <25, 36.4% non-Hispanic White) screened for prenatal substance use in 2018 via a self-reported questionnaire and urine toxicology test given as part of standard prenatal care (at ∼8 weeks gestation). Multivariable logistic regression models tested for associations of pregnancy intentions with prenatal substance use (any use and specific substances) by self-report and/or a positive urine toxicology test. Adjusting for covariates, women with an unintended pregnancy (23.9% of the sample) had higher odds of any prenatal substance use than women with an intended pregnancy (28.8% vs 16.1%; adjusted odds ratio [aOR] = 1.80, 95% confidence interval [CI]:1.67-1.93). Having an unintended pregnancy was also associated with higher odds of using alcohol (14.4% vs 10.4%; aOR = 1.73, 95%CI:1.59-1.89), cannabis (15.6% vs 5.6%; aOR = 1.91, 95%CI:1.73-2.11), nicotine (3.8% vs 1.3%; aOR = 2.33, 95%CI:1.92-2.82), pain medication (2.3% vs 1.2%; aOR = 1.64, 95%CI:1.32-2.03), and stimulants (0.8% vs 0.3%; aOR = 1.85, 95%CI:1.23-2.79) early in pregnancy. Having an unintended pregnancy was associated with higher odds of substance use during early pregnancy. Connecting women of reproductive age with health education about pregnancy prevention and recognition of early signs of pregnancy, effective contraception, and early screening and interventions for prenatal substance use may help to reduce prenatal substance use and its associated consequences.
Authors: Young-Wolff, Kelly C; Slama, Natalie; Sarovar, Varada; Conway, Amy; Tucker, Lue-Yen; Goler, Nancy; Terplan, Mishka; Ansley, Deborah; Adams, Sara R; Armstrong, Mary Anne
J Addict Med. 2022 Jan-Feb 01;16(1):118-121.
Adult Suicide-Related emergency department encounters during the COVID-19 Pandemic: a Cross-Sectional study
Background: The coronavirus disease 2019 (COVID-19) pandemic resulted in widespread psychosocial disruption, which may impact suicidal thoughts and behaviours. This study characterizes adult suicide-related emergency department (ED) encounters and patient characteristics during the COVID-19 pandemic in 2020 compared to the year prior. Methods: Retrospective cross-sectional study in a large, integrated, community-based health system of adults (≥18-years-old) with suicide-related ED encounters (defined by the Centres for Disease Control-recommended International Statistical Classification of Diseases [ICD-10-CM] codes) during the COVID-19 pandemic compared to the same period in 2019. Population-level incidence rate ratios (IRRs) compared suicide-related ED encounters in 2020 to 2019. Patient characteristics for the first suicide-related ED visit for each period were used to calculate percent relative change comparing 2020 to 2019. Findings: Of 10,651 suicide-related ED encounters in 2020 and 11,476 in 2019, 49.6% and 51.6% were for females and the mean age was 38±17 and 38±16 years-old, respectively. Suicide-related ED encounters significantly declined in each month of 2020 (IRR 0.71-0.91, p<.05), but were equivalent to 2019 levels June-August. Adults in 2020 were more likely to have co-occurring substance use disorders (+15•7%; 95% CI 7•0-24•4%) or have no mental health or suicide diagnosis associated with an outpatient visit in the last year (+21•1%, 95% CI: 12•5-29•6) compared to 2019. Interpretation: Adults with suicidal thoughts and behaviours during the COVID-19 pandemic in 2020 had distinct social and psychiatric characteristics compared to patients in the prior year. These findings can help inform health system responses to mental health needs.
Authors: Ridout, Kathryn K; Alavi, Mubarika; Ridout, Samuel J; Koshy, Maria T; Awsare, Sameer; Harris, Brooke; Vinson, David R; Weisner, Constance M; Sterling, Stacy; Iturralde, Esti
Lancet Reg Health Am. 2021 Dec;4:100078. Epub 2021-09-21.
Adult Suicide-Related emergency department encounters during the COVID-19 Pandemic a Cross-Sectional study
Background: The coronavirus disease 2019 (COVID-19) pandemic resulted in widespread psychosocial disruption, which may impact suicidal thoughts and behaviours. This study characterizes adult suicide-related emergency department (ED) encounters and patient characteristics during the COVID-19 pandemic in 2020 compared to the year prior. Methods: Retrospective cross-sectional study in a large, integrated, community-based health system of adults (≥18-years-old) with suicide-related ED encounters (defined by the Centres for Disease Control-recommended International Statistical Classification of Diseases [ICD-10-CM] codes) during the COVID-19 pandemic compared to the same period in 2019. Population-level incidence rate ratios (IRRs) compared suicide-related ED encounters in 2020 to 2019. Patient characteristics for the first suicide-related ED visit for each period were used to calculate percent relative change comparing 2020 to 2019. Findings: Of 10,651 suicide-related ED encounters in 2020 and 11,476 in 2019, 49.6% and 51.6% were for females and the mean age was 38±17 and 38±16 years-old, respectively. Suicide-related ED encounters significantly declined in each month of 2020 (IRR 0.71-0.91, p<.05), but were equivalent to 2019 levels June-August. Adults in 2020 were more likely to have co-occurring substance use disorders (+15•7%; 95% CI 7•0-24•4%) or have no mental health or suicide diagnosis associated with an outpatient visit in the last year (+21•1%, 95% CI: 12•5-29•6) compared to 2019. Interpretation: Adults with suicidal thoughts and behaviours during the COVID-19 pandemic in 2020 had distinct social and psychiatric characteristics compared to patients in the prior year. These findings can help inform health system responses to mental health needs.
Authors: Ridout, Kathryn K; Alavi, Mubarika; Ridout, Samuel J; Koshy, Maria T; Awsare, Sameer; Harris, Brooke; Vinson, David R; Weisner, Constance M; Sterling, Stacy; Iturralde, Esti
Lancet Reg Health Am. 2021 Dec;4:100078. Epub 2021 Sep 21.
Cannabis Use and Patient-Centered Care During Pregnancy and Post Partum Among People Living With HIV
Authors: Young-Wolff, Kelly C; Marcus, Julia L; Satre, Derek D
JAMA Netw Open. 2021 12 01;4(12):e2137588. Epub 2021-12-01.
Treatment for alcohol use disorder among persons with and without HIV in a clinical care setting in the United States
Alcohol use disorders (AUD) can lead to poor health outcomes. Little is known about AUD treatment among persons with HIV (PWH). In an integrated health system in Northern California, 2014-2017, we compared AUD treatment rates between PWH with AUD and persons without HIV (PWoH) with AUD. Using Poisson regression with GEE, we estimated prevalence ratios (PRs) comparing the annual probability of receiving AUD treatment (behavioral intervention or dispensed medication), adjusted for sociodemographics, psychiatric comorbidities, insurance type, and calendar year. Among PWH, we examined independent AUD treatment predictors using PRs adjusted for calendar year only. PWH with AUD (N = 633; 93% men, median age 49) were likelier than PWoH with AUD (N = 7006; 95% men, median age 52) to have depression (38% vs. 21%) and a non-alcohol substance use disorder (SUD, 48% vs. 25%) (both P < 0.01). Annual probabilities of receiving AUD treatment were 45.4% for PWH and 34.4% for PWoH. After adjusting, there was no difference by HIV status (PR 1.02 [95% CI 0.94-1.11]; P = 0.61). Of treated PWH, 59% received only a behavioral intervention, 5% only a medication, and 36% both, vs. 67%, 4%, 30% for treated PWoH, respectively. Irrespective of HIV status, the most common medication was gabapentin. Among PWH, receiving AUD treatment was associated with having depression (PR 1.78 [1.51-2.10]; P < 0.01) and another SUD (PR 2.68 [2.20-3.27]; P < 0.01). PWH with AUD had higher AUD treatment rates than PWoH with AUD in unadjusted but not adjusted analyses, which may be explained by higher psychiatric comorbidity burden among PWH.
Authors: Davy-Mendez, Thibaut; Sarovar, Varada; Levine-Hall, Tory; Lea, Alexandra N; Sterling, Stacy A; Chi, Felicia W; Palzes, Vanessa A; Bryant, Kendall J; Weisner, Constance M; Silverberg, Michael J; Satre, Derek D
Drug Alcohol Depend. 2021 12 01;229(Pt A):109110. Epub 2021-09-28.
Stroke Belt Birth State and Late-life Cognition in The Study of Healthy Aging in African Americans (STAR)
We examined the association of Stroke Belt birth state with late-life cognition in The Study of Healthy Aging in African Americans (STAR). STAR enrolled 764 Black Americans ages 50+ who were long-term Kaiser Permanente Northern California members. Participants completed Multiphasic Health Check-ups (MHC; 1964-1985) where early-life overweight/obesity, hypertension, diabetes, and hyperlipidemia were measured. At STAR (2018), birth state, self-reported early-life socioeconomic status (SES), and executive function, verbal episodic memory, and semantic memory scores were collected. We used linear regression to examine the association between Stroke Belt birth and late-life cognition adjusting for birth year, gender, and parental education. We evaluated early-life SES and cardiovascular risk factors (CVRF) as potential mechanisms. Twenty-seven percent of participants were born in the Stroke Belt with a mean age of 69 (standard deviation = 9) at STAR. Stroke Belt birth was associated with worse late-life executive function (β [95% confidence interval]: -0.18 [-0.33, -0.02]) and semantic memory (-0.37 [-0.53, -0.21]), but not verbal episodic memory (-0.04 [-0.20, 0.12]). Adjustment for SES and CVRF attenuated associations of Stroke Belt birth with cognition (executive function [-0.05 {-0.25, 0.14}]; semantic memory [-0.28 {-0.49, -0.07}]). Black Americans born in the Stroke Belt had worse late-life cognition than those born elsewhere, underscoring the importance of early-life exposures on brain health.
Authors: George, Kristen M; Peterson, Rachel L; Gilsanz, Paola; Barnes, Lisa L; Mayeda, Elizabeth Rose; Glymour, M Maria; Mungas, Dan M; DeCarli, Charles S; Whitmer, Rachel A
Ann Epidemiol. 2021 12;64:26-32. Epub 2021-09-09.
Emergency Department Encounters Among Youth With Suicidal Thoughts or Behaviors During the COVID-19 Pandemic
Population-level reports of suicide-related emergency department (ED) encounters among youth during the COVID-19 pandemic are lacking, along with youth characteristics and preexisting psychiatric service use. To characterize population-level and relative change in suicide-related ED encounters among youth during the COVID-19 pandemic compared with 2019. This cross-sectional study evaluated ED encounters in 2019 and 2020 at Kaiser Permanente Northern California-a large, integrated, community-based health system. Youth aged 5 to 17 years who presented to the ED with suicidal thoughts or behaviors were included. The COVID-19 pandemic. Population-level incidence rate ratios (IRRs) and percent relative effects for suicide-related ED encounters as defined by the US Centers for Disease Control and Prevention-recommended International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes in 4 periods in 2020 compared with the same periods in 2019. There were 2123 youth with suicide-related ED encounters in 2020 compared with 2339 in 2019. In the 2020 group, 1483 individuals (69.9%) were female and 1798 (84.7%) were aged 13 to 17 years. In the 2019 group, 1542 (65.9%) were female, and 1998 (85.4%) were aged 13 to 17 years. Suicide-related ED encounter incidence rates were significantly lower in March through May 2020 compared with this period in 2019 (IRR, 0.57; 95% CI, 0.51-0.63; P < .001), then returned to prepandemic levels. However, suicide-related ED visits among female youth from June 1 to August 31, 2020, and September 1 through December 15, 2020, were significantly higher than in the corresponding months in 2019 (IRR, 1.19; 95% CI, 1.04-1.35; P = .04 and IRR, 1.22; 95% CI, 1.11-1.35; P < .001, respectively), while suicide-related ED visits for male youth decreased from September 1 through December 15, 2020 (IRR, 0.81; 95% CI, 0.69 to 0.94). Youth with no history of outpatient mental health or suicide encounters (129.4%; 95% CI, 41.0-217.8) and those with comorbid psychiatric conditions documented at the ED encounter (6.7%; 95% CI, 1.0-12.3) had a higher risk of presenting with suicide-related problems from September to December 2020 vs the same period in 2019. In this cross-sectional study of youth experiencing suicidal thoughts and behaviors, suicide-related presentations to the ED initially decreased during the COVID-19 pandemic, likely owing to shelter-in-place orders, then were similar to 2019 levels. However, a greater number of female youth, youth with no psychiatric history, and youth with psychiatric diagnoses at the time of the ED encounter presented for suicide-related concerns during the pandemic, suggesting these may be vulnerable groups in need of further interventions. Adjustments in care may be warranted to accommodate these groups during periods of crisis.
Authors: Ridout, Kathryn K; Alavi, Mubarika; Ridout, Samuel J; Koshy, Maria T; Awsare, Sameer; Harris, Brooke; Vinson, David R; Weisner, Constance M; Sterling, Stacy; Iturralde, Esti
JAMA Psychiatry. 2021 12 01;78(12):1319-1328.
Establishing a Carotid Artery Stenosis Disease Cohort for Comparative Effectiveness Research Using Natural Language Processing
Investigation of asymptomatic carotid stenosis treatment is hindered by the lack of a contemporary population-based disease cohort. We describe the use of natural language processing (NLP) to identify stenosis in patients undergoing carotid imaging. Adult patients with carotid imaging between 2008 and 2012 in a large integrated health care system were identified and followed through 2017. An NLP process was developed to characterize carotid stenosis according to the Society of Radiologists in Ultrasound (for ultrasounds) and North American Symptomatic Carotid Endarterectomy Trial (NASCET) (for axial imaging) guidelines. The resulting algorithm assessed text descriptors to categorize normal/non-hemodynamically significant stenosis, moderate or severe stenosis as well as occlusion in both carotid ultrasound (US) and axial imaging (computed tomography and magnetic resonance angiography [CTA/MRA]). For US reports, internal carotid artery systolic and diastolic velocities and velocity ratios were assessed and matched for laterality to supplement accuracy. To validate the NLP algorithm, positive predictive value (PPV or precision) and sensitivity (recall) were calculated from simple random samples from the population of all imaging studies. Lastly, all non-normal studies were manually reviewed for confirmation for prevalence estimates and disease cohort assembly. A total of 95,896 qualifying index studies (76,276 US and 19,620 CTA/MRA) were identified among 94,822 patients including 1059 patients who underwent multiple studies on the same day. For studies of normal/non-hemodynamically significant stenosis arteries, the NLP algorithm showed excellent performance with a PPV of 99% for US and 96.5% for CTA/MRA. PPV/sensitivity to identify a non-normal artery with correct laterality in the CTA/MRA and US samples were 76.9% (95% confidence interval [CI], 74.1%-79.5%)/93.1% (95% CI, 91.1%-94.8%) and 74.7% (95% CI, 69.3%-79.5%)/94% (95% CI, 90.2%-96.7%), respectively. Regarding cohort assembly, 15,522 patients were identified with diseased carotid artery, including 2674 exhibiting equal bilateral disease. This resulted in a laterality-specific cohort with 12,828 moderate, 5283 severe, and 1895 occluded arteries and 326 diseased arteries with unknown stenosis. During follow-up, 30.1% of these patients underwent 61,107 additional studies. Use of NLP to detect carotid stenosis or occlusion can result in accurate exclusion of normal/non-hemodynamically significant stenosis disease states with more moderate precision with lesion identification, which can substantially reduce the need for manual review. The resulting cohort allows for efficient research and holds promise for similar reporting in other vascular diseases.
Authors: Chang, Robert W; Tucker, Lue-Yen; Rothenberg, Kara A; Lancaster, Elizabeth M; Avins, Andrew L; Kuang, Hui C; Faruqi, Rishad M; Nguyen-Huynh, Mai N
J Vasc Surg. 2021 12;74(6):1937-1947.e3. Epub 2021-06-25.
Rates of Prenatal Cannabis Use Among Pregnant Women Before and During the COVID-19 Pandemic
Authors: Young-Wolff, Kelly C; Ray, G Thomas; Alexeeff, Stacey E; Adams, Sara R; Does, Monique B; Ansley, Deborah; Avalos, Lyndsay A
JAMA. 2021 11 02;326(17):1745-1747.
Non-fatal stimulant overdose among homeless and unstably housed women in San Francisco, California
US rates of overdose deaths involving stimulants (e.g., cocaine or methamphetamine) have increased, but little is known about non-fatal stimulant overdoses, particularly among vulnerable populations. We characterized rates of non-fatal stimulant overdose identified outside of health care settings among women at high risk. Homeless and unstably housed women in San Francisco, California using stimulants were administered questionnaires on drug use and outcomes (stimulant overdose, health care utilization) monthly for six months. Based on pilot interviews, stimulant overdose during follow-up was defined as acute toxicity from stimulant use (“over-amping”) resulting in “feeling sick, really scared, or like one’s life may be in danger”. Poisson regression estimated unadjusted incidence rate ratio (IRR) comparing participant characteristics. We included 160 women (41% Black, 26% White, 15% Latina, median age 54 years) using crack cocaine (81%), methamphetamine (48%), and powdered cocaine (36%). Participants reported 67 non-fatal stimulant overdoses over 685 person-months of observation, a rate of 117.4 per 100 person-years (95% CI 85.8-160.5). Rates were higher among participants who were Latina vs. White (IRR 4.18 [1.60-10.94]), used methamphetamine (IRR 1.80 [0.96-3.38]), or used any stimulant daily/almost daily (IRR 2.63 [1.41-4.91]). Among women reporting stimulant overdose, 4% received emergency and 3% inpatient care for overdose of any drug. Women in this setting, particularly those who used stimulants frequently or used methamphetamine, experienced high non-fatal stimulant overdose and rarely received health care for these events. Efforts should be made to increase awareness and reduce harms of stimulant toxicity in vulnerable populations.
Authors: Davy-Mendez, Thibaut; Vittinghoff, Eric; Dilworth, Samantha E; Suen, Leslie W; Braun, Carl; Coffin, Phillip O; Satre, Derek D; Riley, Elise D
Drug Alcohol Depend. 2021 11 01;228:109085. Epub 2021-09-22.
Opportunities to Integrate Mobile App-Based Interventions Into Mental Health and Substance Use Disorder Treatment Services in the Wake of COVID-19
The COVID-19 pandemic has heightened concerns about the impact of depression, anxiety, alcohol, and drug use on public health. Mobile apps to address these problems were increasingly popular even before the pandemic, and may help reach people who otherwise have limited treatment access. In this review, we describe pandemic-related substance use and mental health problems, the growing evidence for mobile app efficacy, how health systems can integrate apps into patient care, and future research directions. If equity in access and effective implementation can be addressed, mobile apps are likely to play an important role in mental health and substance use disorder treatment.
Authors: Satre, Derek D; Meacham, Meredith C; Asarnow, Lauren D; Fisher, Weston S; Fortuna, Lisa R; Iturralde, Esti
Am J Health Promot. 2021 11;35(8):1178-1183. Epub 2021-10-15.
Effectiveness of spironolactone dispensation in reducing weekly alcohol use: a retrospective high-dimensional propensity score-matched cohort study
There is a need to increase the armamentarium of pharmacotherapies for alcohol use disorder (AUD). Recent research suggests that mineralocorticoid receptor (MR) antagonism via spironolactone may represent a novel pharmacological treatment for AUD. We conducted a pharmacoepidemiologic retrospective cohort study (June 1, 2014 to May 31, 2018) to examine whether spironolactone dispensation (≥90 continuous days), for any indication, is associated with changes in weekly alcohol use about 6 months later. We compared 523 spironolactone-treated adults and 2305 untreated adults, matched on high-dimensional propensity scores created from a set of predefined (sociodemographic and health characteristics, diagnoses, and service utilization) and empirical electronic health record-derived covariates. The sample was 57% female and 27% non-White with a mean age of 59.2 years (SD = 19.3). Treated patients reduced their weekly alcohol use by 3.50 drinks (95% CI = -4.22, -2.79), while untreated patients reduced by 2.74 drinks (95% CI = -3.22, -2.26), yielding a significant difference of 0.76 fewer drinks (95% CI = -1.43, -0.11). Among those who drank >7 drinks/week at baseline, treated patients, compared to untreated patients, reported a greater reduction in weekly alcohol use by 4.18 drinks (95% CI = -5.38, -2.97), while there was no significant difference among those who drank less. There was a significant dose-response relationship between spironolactone dosage and change in drinks/week. Pending additional evidence on its safety and efficacy in individuals with AUD, spironolactone (and MR blockade, at large) may hold promise as a pharmacotherapy for AUD.
Authors: Palzes, Vanessa A; Farokhnia, Mehdi; Kline-Simon, Andrea H; Elson, Joseph; Sterling, Stacy; Leggio, Lorenzo; Weisner, Constance; Chi, Felicia W
Neuropsychopharmacology. 2021 11;46(12):2140-2147. Epub 2021-08-02.
Attention-Deficit/Hyperactivity Disorder Medication Adherence in the Transition to Adulthood: Associated Adverse Outcomes for Females and Other Disparities
The purpose of this study was to assess the association between attention-deficit/hyperactivity disorder (ADHD) medication adherence and adverse health outcomes in older adolescents transitioning to adulthood. In a cohort of 17-year-old adolescents with ADHD at Kaiser Permanente Northern California, we assessed medication adherence (medication possession ratio ≥70%) and any medication use and associations with adverse outcomes at 18 and 19 years of age. We conducted bivariate tests of association and multivariable logistic regression models. Adherence declined from 17 to 19 years of age (36.7%-19.1%, p < .001). Non-white race/ethnicity, lower estimated income, and male sex were associated with nonadherence. Model results show nonadherent females experienced several adverse outcomes: Adherence at 18 years of age (referent: nonadherence) was associated with lower odds of pregnancy (adjusted odds ratio [AOR]: .13, 95% confidence interval [CI]: .03-.54). Any use (referent: nonuse) at 18 years of age was associated with lower odds of sexually transmitted infections among females (AOR: .39, 95% CI: .19-.83), pregnancies (AOR: .26, 95% CI: .13-.50), emergency department visits (AOR: .69, 95% CI: .55-.85), and greater odds of injuries (AOR: 1.16, 95% CI: 1.02-1.32). Adherence at 19 years of age was associated with lower odds of pregnancy (AOR: .13, 95% CI: .02-.95). Any use at 19 years of age was associated with lower odds of injury in females (AOR: .77, 95% CI: .60-.99) pregnancy (AOR: .35, 95% CI: .16-.78), and, in both sexes, substance use (AOR: .71, 95% CI: .55-.92). Late adolescence is associated with decline in ADHD medication use and adherence. ADHD medication adherence and any ADHD medication use is associated with fewer adverse health outcomes, particularly in females.
Authors: Rao, Kavitha; Carpenter, Diane M; Campbell, Cynthia I
J Adolesc Health. 2021 11;69(5):806-814. Epub 2021-05-28.
Association of COA1 with Patellar Tendonitis: A Genome-wide Association Analysis
It is unknown why some athletes develop patellar tendinopathy and others do not, even when accounting for similar workloads between individuals. Genetic differences between these two populations may be a contributing factor. The purpose of this work was to screen the entire genome for genetic markers associated with patellar tendinopathy. Genome-wide association (GWA) analyses were performed utilizing data from the Kaiser Permanente Research Board (KPRB) and the UK Biobank. Patellar tendinopathy cases were identified based on electronic health records from KPRB and UK Biobank. GWA analyses from both cohorts were tested for patellar tendinopathy using a logistic regression model adjusting for sex, height, weight, age, and race/ethnicity using allele counts for single nucleotide polymorphisms. The data from the two GWA studies (KPRB and UK Biobank) were combined in a meta-analysis. There were a total of 1670 cases of patellar tendinopathy and 293,866 controls within the two cohorts. Two single nucleotide polymorphisms located in the intron of the cytochrome c oxidase assembly factor 1 (COA1) gene showed a genome-wide significant association in the meta-analysis. Genetic markers in COA1 seem to be associated with patellar tendinopathy and are potential risk factors for patellar tendinopathy that deserve further validation regarding molecular mechanisms.
Authors: Kim, Stuart K; Nguyen, Condor; Horton, Brandon H; Avins, Andrew L; Abrams, Geoffrey D
Med Sci Sports Exerc. 2021 11 01;53(11):2419-2424.
Prospective validation of the Kaiser Permanente prostate cancer risk calculator in a contemporary, racially diverse, referral population
To prospectively validate a new prostate cancer risk calculator in a racially diverse population. We recently developed, internally validated and published the Kaiser Permanente Prostate Cancer Risk Calculator. This study is a prospective validation of the calculator in a separate, referral population over a 21-month period. All patients were tested with a uniform PSA assay and a standardized systematic, ultrasound-guided biopsy scheme. We report on 3 calculator models: Model 1 included age, race, PSA, prior biopsy status, body mass index, and family history of prostate cancer; Model 2 added digital rectal exam to Model 1 variables; Model 3 added prostate volume to Model 2 variables. We considered three outcomes: high-grade disease (Gleason score ≥7), low-grade disease (Gleason score=6), and no cancer. Predictive discrimination and calibration were calculated. How each model might alter biopsy frequency and outcomes at various thresholds of risk was assessed. We compared the performance of our calculator with two other calculators. In 4178 patients (16.2% Asian, 11.3% African American, 13.5% Hispanic), cancer was found in 53%; 62% were Gleason score ≥7. Using a high-grade risk threshold for biopsy of ≥10%, Model 2 predictions would result in 9% of men avoiding a biopsy, while only missing 2% of high-grade cancers. At the same threshold, Model 3 predictions would result in 26% of men avoiding a biopsy, while only missing 5% of high-grade cancers. The c-statistics for Models 1, 2, and 3 to predict high-grade disease vs. low-grade or no cancer were 0.76, 0.79 and 0.85, respectively. The c-statistics for Models 1, 2, and 3 to predict any prostate cancer vs. no cancer were 0.70, 0.72 and 0.80, respectively. All models were well calibrated for all outcomes. Our Model 3 calculator had superior discrimination for high grade disease (c-statistic=0.85, 0.84-0.86) and any cancer (0.80, 0.79-0.82) compared to the PBCG calculator [(0.79, 0.78-0.80); 0.72 (0.70-0.73)] and the PCPT calculator [(0.75, 0.74-0.77); 0.69 (0.67-0.70)], respectively. In the high-grade cancer predicted risk range of 0-30%, our Model 2 was better calibrated than the PCPT and PBCG calculators. This validation of our calculator showed excellent performance characteristics.
Authors: Presti, Joseph C; Alexeeff, Stacey; Horton, Brandon; Prausnitz, Stephanie; Avins, Andrew L
Urol Oncol. 2021 11;39(11):783.e11-783.e19. Epub 2021-05-04.
Psychotropic medication prescribing during the COVID-19 pandemic
This study examined changes in psychotropic medication use associated with the early months of the coronavirus disease 2019 (COVID-19) pandemic. Using Kaiser Permanente Northern California electronic health records, the authors identified adult patients with fills for psychotropic medications and a non-psychotropic comparator (statins) in the 13 weeks before and after the first-known COVID-19-related death in California (March 4, 2020). Generalized estimating equations were used to derive relative risk ratios (RRR) for medication fills compared with the prior year. Analyses were stratified by new and continued fills and patient characteristics. Among 2,405,824 patients, the mean (SD) age was 49.8 (17.9) years; 52.9% were female; 47.9% identified as White; 8.0% and 7.9% had anxiety and depression disorder diagnoses, respectively. Accounting for secular trends, in the 13 weeks following March 4, 2020, there were increased fills for trazodone (RRR = 1.03, 95% CI = 1.02, 1.04), decreased fills for benzodiazepines (RRR = 0.95, 95% CI = 0.94, 0.96) and hypnotics (RRR = 0.97, 95% CI = 0.96, 0.99), and stable fills for antidepressants (RRR = 1.00, 95% CI = 0.99, 1.00). Relative rates of new fills decreased across most medication classes and continued fills either remained stable or demonstrated non-clinically significant decreases. Patients aged ≥65 years demonstrated decreased fills for most medication classes. In the first 13 weeks of the COVID-19 pandemic, fills for most psychotropic medications remained constant or showed small changes relative to the previous year. Continued (compared with new) fills accounted for observed increases in some medication classes. Older adults demonstrated decreased fills of most medications.
Authors: Hirschtritt, Matthew E; Slama, Natalie; Sterling, Stacy A; Olfson, Mark; Iturralde, Esti
Medicine (Baltimore). 2021 Oct 29;100(43):e27664.
Whole-genome sequencing in diverse subjects identifies genetic correlates of leukocyte traits: The NHLBI TOPMed program
Many common and rare variants associated with hematologic traits have been discovered through imputation on large-scale reference panels. However, the majority of genome-wide association studies (GWASs) have been conducted in Europeans, and determining causal variants has proved challenging. We performed a GWAS of total leukocyte, neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts generated from 109,563,748 variants in the autosomes and the X chromosome in the Trans-Omics for Precision Medicine (TOPMed) program, which included data from 61,802 individuals of diverse ancestry. We discovered and replicated 7 leukocyte trait associations, including (1) the association between a chromosome X, pseudo-autosomal region (PAR), noncoding variant located between cytokine receptor genes (CSF2RA and CLRF2) and lower eosinophil count; and (2) associations between single variants found predominantly among African Americans at the S1PR3 (9q22.1) and HBB (11p15.4) loci and monocyte and lymphocyte counts, respectively. We further provide evidence indicating that the newly discovered eosinophil-lowering chromosome X PAR variant might be associated with reduced susceptibility to common allergic diseases such as atopic dermatitis and asthma. Additionally, we found a burden of very rare FLT3 (13q12.2) variants associated with monocyte counts. Together, these results emphasize the utility of whole-genome sequencing in diverse samples in identifying associations missed by European-ancestry-driven GWASs.
Authors: Mikhaylova, Anna V; Choquet, Hélène; Auer, Paul L; et al.
Am J Hum Genet. 2021 10 07;108(10):1836-1851. Epub 2021-09-27.
Smoking reduction is associated with lower alcohol consumption and depressive symptoms among young adults over one year
This secondary analysis examined whether smoking reduction among young adults participating in a Facebook-based smoking cessation intervention study was associated with corresponding reductions in alcohol consumption and depressive symptoms. Participants were young adults who smoked and engaged in heavy episodic drinking (HED). Alcohol consumption (AUDIT-C, days of HED), depressive symptoms (PHQ-2), and past-month cigarettes per day (CPD) were self-reported at baseline and 12 months (N = 150). Linear regression estimated the relationship between the mean change in CPD and mean changes in alcohol consumption and depressive symptoms. CPD, alcohol consumption, and depressive symptoms decreased significantly between baseline and 12 months. The adjusted mean reduction in CPD was significantly associated with mean reductions in AUDIT-C (Beta [β] = 0.09, 95 % confidence interval [CI] = 0.04-0.14), days of HED (β = 0.17, 95 % CI = 0.04-0.29) and PHQ-2 (β = 0.05, 95 % CI = 0.01-0.08). Smoking abstinence (n = 48) was associated with a significantly larger mean reduction in AUDIT-C compared to a ≥50 % reduction (n = 45) (-2.9 vs -1.7 points, p = 0.03) or <50 % reduction in CPD (n = 57) (-2.9 vs -1.1 points, p < 0.01). The mean reduction in AUDIT-C did not differ between a ≥50 % reduction and <50 % reduction in CPD (-1.7 vs.-1.1 points, p = 0.18). Mean reductions in days of HED and the PHQ-2 did not differ according to the level of reduction in CPD. Smoking reduction was associated with reductions in alcohol consumption and depressive symptoms. Reductions appeared to be greater for those who achieved abstinence compared to a reduction in smoking.
Authors: Yonek, Juliet C; Meacham, Meredith C; Shumway, Martha; Tolou-Shams, Marina; Satre, Derek D
Drug Alcohol Depend. 2021 10 01;227:108922. Epub 2021-07-28.
Addressing cigarette smoking cessation treatment challenges during the COVID-19 pandemic with social media
This commentary reviews barriers to smoking cessation during the COVID-19 pandemic and the potential of social media-based smoking cessation programs. Several published randomized controlled trials are summarized and future directions for designing and evaluating social media-based smoking cessation programs are described.
Authors: Meacham, Meredith C; Vogel, Erin A; Thrul, Johannes; Ramo, Danielle E; Satre, Derek D
J Subst Abuse Treat. 2021 10;129:108379. Epub 2021-03-22.
Association of Timing of School Desegregation in the United States With Late-Life Cognition in the Study of Healthy Aging in African Americans (STAR) Cohort
Prior research suggests schooling differences for Black individuals in the US are associated with worse cognitive aging. It is unknown whether age when experiencing school desegregation is associated with differences in late-life cognition in this population. To examine patterns of association between age of school desegregation in grades 1 to 12 and late-life cognition. This cohort study analyzed baseline data from the Study of Healthy Aging in African Americans (STAR) cohort collected from 2018 through 2019 in Northern California, primarily in the cities of Richmond and Oakland. Participants were 699 self-identified Black individuals aged 50 years or older who were community-dwelling, long-term members of Kaiser Permanente Northern California and dementia free at baseline. Participants reported whether they attended a segregated school in grades 1, 6, 9, and 12 and were placed in 1 of 6 transition categories: (1) always attended integrated schools; (2) integrated between grades 1 through 5; (3) integrated between grades 6 through 8; (4) integrated between grades 9 through 12; (5) ever moved from integrated to segregated school; (6) never attended integrated schools. Executive function, semantic memory, and verbal episodic memory ascertained via the Spanish and English Neuropsychological Assessment Battery and z standardized for analyses. The mean (SD) age of the 699 participants was 68.5 (8.7) years, and 484 (69.2%) were female. Most participants transitioned from segregated to integrated schools owing to historical timing and cohort geography. Compared with 111 participants who never attended integrated schools (reference group), executive function was better among 50 participants who transitioned to integrated schools between grades 1 and 5 (β = 0.35; 95% CI, 0.08-0.61; P = .01). Semantic memory was better among 435 participants who only attended integrated schools (β = 0.34; 95% CI, 0.14-0.54; P = .001) or among 50 participants who transitioned to integrated schools between grades 1 and 5 (β = 0.43; 95% CI, 0.15-0.72; P = .003). However, no significant differences were found by group for verbal episodic memory function (eg, for 50 participants who transitioned to integrated schools between grades 1 and 5: β = 0.07; 95% CI, -0.22 to 0.35; P = .66). No significant differences were found when testing for potential interactions by sex, Southern birth, or baseline age. The STAR cohort data indicated that executive function and semantic memory were higher among Black individuals with some integrated school experience. These results suggest that racially segregated schooling experiences, including de facto segregation present today, may be associated with worse late-life cognition.
Authors: Peterson, Rachel L; George, Kristen M; Barnes, Lisa L; Gilsanz, Paola; Mayeda, Elizabeth Rose; Glymour, M Maria; Mungas, Dan M; Whitmer, Rachel A
JAMA Netw Open. 2021 10 01;4(10):e2129052. Epub 2021-10-01.
Patient and provider factors associated with receipt and delivery of brief interventions for unhealthy alcohol use in primary care
Unhealthy alcohol use is a serious and costly public health problem. Alcohol screening and brief interventions are effective in reducing unhealthy alcohol consumption. However, rates of receipt and delivery of brief interventions vary significantly across healthcare settings, and relatively little is known about the associated patient and provider factors. This study examines patient and provider factors associated with the receipt of brief interventions for unhealthy alcohol use in an integrated healthcare system, based on documented brief interventions in the electronic health record. Using multilevel logistic regression models, we retrospectively analyzed 287,551 adult primary care patients (and their 2952 providers) who screened positive for unhealthy drinking between 2014 and 2017. We found lower odds of receiving a brief intervention among patients exceeding daily or weekly drinking limits (vs. exceeding both limits), females, older age groups, those with higher medical complexity, and those already diagnosed with alcohol use disorders. Patients with other unhealthy lifestyle activities (e.g., smoking, no/insufficient exercise) were more likely to receive a brief intervention. We also found that female providers and those with longer tenure in the health system were more likely to deliver brief interventions. These findings point to characteristics that can be targeted to improve universal receipt of brief intervention.
Authors: Lu, Yun; Metz, Verena E; Weisner, Constance; Satre, Derek D; Campbell, Cynthia I; Sterling, Stacy A; et al.
Alcohol Clin Exp Res. 2021 10;45(10):2179-2189. Epub 2021-09-05.
Expected Organizational Costs for Inserting Prevalence Information Into Lumbar Spine Imaging Reports
Modifying physician behavior to more closely align with guideline-based care can be challenging. Few effective strategies resulting in appropriate spine-related health care have been reported. The Lumbar Imaging With Reporting of Epidemiology (LIRE) intervention did not result in reductions in spine care but did in opioid prescriptions written. To estimate organizational resource needs and costs associated with implementing a pragmatic, decision support-type intervention that inserted age- and modality-matched prevalence information for common lumbar spine imaging findings, using site-based resource use data from the LIRE trial. Time and cost estimation associated with implementing the LIRE intervention in a health organization. Providers and patients assessed in the LIRE trial. Expected personnel costs required to implement the LIRE intervention. Annual salaries were converted to daily average per person costs, ranging from $400 to $2,200 per day (base case) for personnel (range: $300-$2,600). Estimated total average cost for implementing LIRE was $5,009 (range: $2,651-$12,020), including conducting pilot testing with providers. Costs associated with a small amount of time for a radiologist (6-12 hours) and imaging-ordering providers (1-8 hours each) account for approximately 75% of the estimated total cost. The process of implementing an intervention for lumbar spine imaging reports containing age- and modality-appropriate epidemiological benchmarks for common imaging findings required radiologists, imaging-ordering providers, information technology specialists, and limited testing and monitoring. The LIRE intervention seems to be a relatively low-cost, evidence-based, complementary tool that can be easily integrated into the reporting of spine imaging.
Authors: Bresnahan, Brian W; Avins, Andrew L; Kessler, Larry G; et al.
J Am Coll Radiol. 2021 10;18(10):1415-1422. Epub 2021-06-30.
Investigating rare pathogenic/likely pathogenic exonic variation in bipolar disorder
Bipolar disorder (BD) is a serious mental illness with substantial common variant heritability. However, the role of rare coding variation in BD is not well established. We examined the protein-coding (exonic) sequences of 3,987 unrelated individuals with BD and 5,322 controls of predominantly European ancestry across four cohorts from the Bipolar Sequencing Consortium (BSC). We assessed the burden of rare, protein-altering, single nucleotide variants classified as pathogenic or likely pathogenic (P-LP) both exome-wide and within several groups of genes with phenotypic or biologic plausibility in BD. While we observed an increased burden of rare coding P-LP variants within 165 genes identified as BD GWAS regions in 3,987 BD cases (meta-analysis OR = 1.9, 95% CI = 1.3-2.8, one-sided p = 6.0 × 10-4), this enrichment did not replicate in an additional 9,929 BD cases and 14,018 controls (OR = 0.9, one-side p = 0.70). Although BD shares common variant heritability with schizophrenia, in the BSC sample we did not observe a significant enrichment of P-LP variants in SCZ GWAS genes, in two classes of neuronal synaptic genes (RBFOX2 and FMRP) associated with SCZ or in loss-of-function intolerant genes. In this study, the largest analysis of exonic variation in BD, individuals with BD do not carry a replicable enrichment of rare P-LP variants across the exome or in any of several groups of genes with biologic plausibility. Moreover, despite a strong shared susceptibility between BD and SCZ through common genetic variation, we do not observe an association between BD risk and rare P-LP coding variants in genes known to modulate risk for SCZ.
Authors: Jia, Xiaoming; Schaefer, Catherine; Scott, Laura J; et al.
Mol Psychiatry. 2021 09;26(9):5239-5250. Epub 2021-01-22.
The Relationship of E-Cigarette Use to Tobacco Use Outcomes Among Young Adults Who Smoke and Use Alcohol
E-cigarette use is increasing among young adults in the U.S. However, longitudinal research studies examining associations between e-cigarette use and combustible cigarette use among young adults are limited. This study assessed the relationship of e-cigarette use to smoking reduction and cessation among young adults. This is a secondary analysis of a randomized controlled social media-based smoking cessation trial comprising adults ages 18 to 25 who smoked cigarettes and engaged in heavy episodic drinking (N = 179). Over 12 months, participants reported past month e-cigarette use with nicotine or tetrahydrocannabinol, cigarette quantity in the past week, quit attempts, and cessation strategies including nicotine e-cigarettes. Longitudinal regression models estimated associations between e-cigarette use, smoking reduction, and 7-day abstinence. Past-month nicotine e-cigarette use prevalence ranged from 53.1% at baseline to 50.3% at 12 months. Over 70% of participants who reported past month nicotine e-cigarette use also smoked cigarettes (ie, dual use). Neither past month nicotine nor tetrahydrocannabinol e-cigarette use was associated with smoking reduction or cessation. However, use of nicotine e-cigarettes as a cessation strategy among participants attempting to quit (N = 137) was positively associated with abstinence (adjusted odds ratio = 2.47, 95% CI = 1.20-5.09) and ≥50% reduction in cigarettes per week from baseline (aOR = 2.36,95% CI = 1.08-5.18), relative to other strategies. Nicotine e-cigarettes were significantly associated with improved tobacco use outcomes when used as a cessation strategy, but not when used apart from trying to quit smoking. Dual use may not be an effective path to achieve smoking cessation.
Authors: Yonek, Juliet C; Meacham, Meredith C; Ramo, Danielle; Delucchi, Kevin; Tolou-Shams, Marina; Satre, Derek D
J Addict Med. 2021 Sep-Oct 01;15(5):421-424.
Patient, Provider, and Clinic Characteristics Associated with Opioid and Non-Opioid Pain Prescriptions for Patients Receiving Low Back Imaging in Primary Care
To describe characteristics of patients, providers, and clinics associated with opioid or non-opioid pain medication prescribing patterns for patients who received lower spine imaging in primary care clinics. In these secondary analyses of the Lumbar Imaging with Reporting of Epidemiology (LIRE) study, a randomized controlled trial conducted in 4 health systems in the United States, we evaluated characteristics associated with receipt of pain medication prescriptions. The outcomes were receipt of prescriptions for opioid or, separately, non-opioid pain medications within 90 days after imaging. Among patients who received opioid or non-opioid prescriptions, we evaluated receipt of multiple prescriptions in the year following imaging. Mixed models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Compared with whites, patients identified as Asian (OR, 0.53; 95% CI, 0.51-0.56), Native Hawaiian/Pacific Islander (OR, 0.73; 95% CI, 0.64-0.83), multiracial (OR, 0.84; 95% CI, 0.71-0.98) or Black (OR, 0.92; 95% CI, 0.89-0.96) had significantly reduced odds for receiving prescriptions for opioids within 90 days. Patients identified as Native American/Alaska Native had greater odds for receiving prescriptions for non-opioid pain medications within 90 days (OR, 1.12; 95% CI, 1.01-1.24). Receipt of pain prescriptions 120 days before imaging was strongly predictive of subsequent receipt of pain prescriptions across all categories. After adjusting for factors that could affect prescribing, the strongest differences observed in pain-medication prescribing were across racial categories and for patients with previous pain prescriptions. Further research is needed to understand these differences and to optimize prescribing.
Authors: Gold, Laura S; Avins, Andrew L; Jarvik, Jeffrey G; et al.
J Am Board Fam Med. 2021 Sep-Oct;34(5):950-963.
Steps per Day and All-Cause Mortality in Middle-aged Adults in the Coronary Artery Risk Development in Young Adults Study
Steps per day is a meaningful metric for physical activity promotion in clinical and population settings. To guide promotion strategies of step goals, it is important to understand the association of steps with clinical end points, including mortality. To estimate the association of steps per day with premature (age 41-65 years) all-cause mortality among Black and White men and women. This prospective cohort study was part of the Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants were aged 38 to 50 years and wore an accelerometer from 2005 to 2006. Participants were followed for a mean (SD) of 10.8 (0.9) years. Data were analyzed in 2020 and 2021. Daily steps volume, classified as low (<7000 steps/d), moderate (7000-9999 steps/d), and high (≥10 000 steps/d) and stepping intensity, classified as peak 30-minute stepping rate and time spent at 100 steps/min or more. All-cause mortality. A total of 2110 participants from the CARDIA study were included, with a mean (SD) age of 45.2 (3.6) years, 1205 (57.1%) women, 888 (42.1%) Black participants, and a median (interquartile range [IQR]) of 9146 (7307-11 162) steps/d. During 22 845 person years of follow-up, 72 participants (3.4%) died. Using multivariable adjusted Cox proportional hazards models, compared with participants in the low step group, there was significantly lower risk of mortality in the moderate (hazard ratio [HR], 0.28 [95% CI, 0.15-0.54]; risk difference [RD], 53 [95% CI, 27-78] events per 1000 people) and high (HR, 0.45 [95% CI, 0.25-0.81]; RD, 41 [95% CI, 15-68] events per 1000 people) step groups. Compared with the low step group, moderate/high step rate was associated with reduced risk of mortality in Black participants (HR, 0.30 [95% CI, 0.14-0.63]) and in White participants (HR, 0.37 [95% CI, 0.17-0.81]). Similarly, compared with the low step group, moderate/high step rate was associated with reduce risk of mortality in women (HR, 0.28 [95% CI, 0.12-0.63]) and men (HR, 0.42 [95% CI, 0.20-0.88]). There was no significant association between peak 30-minute intensity (lowest vs highest tertile: HR, 0.98 [95% CI, 0.54-1.77]) or time at 100 steps/min or more (lowest vs highest tertile: HR, 1.38 [95% CI, 0.73-2.61]) with risk of mortality. This cohort study found that among Black and White men and women in middle adulthood, participants who took approximately 7000 steps/d or more experienced lower mortality rates compared with participants taking fewer than 7000 steps/d. There was no association of step intensity with mortality.
Authors: Paluch, Amanda E; Gabriel, Kelley Pettee; Fulton, Janet E; Lewis, Cora E; Schreiner, Pamela J; Sternfeld, Barbara; Sidney, Stephen; Siddique, Juned; Whitaker, Kara M; Carnethon, Mercedes R
JAMA Netw Open. 2021 09 01;4(9):e2124516. Epub 2021-09-01.
Longitudinal bidirectional associations of physical activity and depressive symptoms: The CARDIA study
Depression affects many aspects of health and may be attenuated through increases in physical activity. While bidirectional associations between physical activity (PA) and depressive symptoms have been examined, few studies have examined these associations using both self-reported and accelerometer-estimated measures. Using data from Years 20 (2005-06, age 38-50) and 30 of the Coronary Artery Risk Development in Young Adults (CARDIA) study (N = 2,871), the bidirectional associations between moderate to vigorous intensity physical activity (MVPA) and depressive symptoms were examined using a cross-lagged panel model. Differences in the observed associations by physical activity assessment method were also examined. An inverse bidirectional association between self-reported MVPA and depressive symptoms was found. In subsequent analyses stratified by intensity category, higher levels of vigorous intensity physical activity at baseline, but not moderate intensity physical activity were associated with lower levels of depressive symptoms at the 10-year follow-up (ϕ = -0.04, p < 0.01; ϕ = -0.03, p = 0.15, respectively). A 10-year increase in self-reported MVPA was associated with a 10-year decrease in depressive symptoms. No associations were observed between accelerometer MVPA estimates and depressive symptoms. These findings may support the notion that each assessment method captures related, but also unique, aspects of physical activity behavior. When possible, future studies should explore measures of association by each physical activity assessment method to gain a better understanding of the complex relationship between physical activity and health.
Authors: Zhang, Dong; Pettee Gabriel, Kelley; Sidney, Stephen; Sternfeld, Barbara; Jacobs, David; Whitaker, Kara M
Prev Med Rep. 2021 Sep;23:101489. Epub 2021-07-12.
Impact of 2012 Prostate Cancer Screening Statement
Authors: Presti, Joseph; Alexeeff, Stacey; Avins, Andrew L
J Gen Intern Med. 2021 09;36(9):2854-2855. Epub 2021-07-13.
Why do Americans use marijuana?
Marijuana is the most commonly used illicit drug in the United States; yet, little is known about why adults use it. We examined the prevalence of past-month marijuana use by users’ reasons for use-medical, recreational, and both-and identified correlates of each group. Data from 20 states, which participated in the 2017-2019 Behavioral Risk Factor Surveillance System and fielded the marijuana use module, and multinomial logistic regression analysis were used to identify risk factors for past-month marijuana use by reason for use. User profiles were developed to illustrate how states’ policy environments influenced reported reasons for use. The average predicted probabilities of past-month marijuana use for medical, recreational, and both reasons were 28.6 %, 38.2 %, and 33.1 %, respectively. Age, gender, marital and employment status, income, mode and frequency of administration, and health status were associated with reasons for use. The reasons that young adult males who were infrequent marijuana users and binge drinkers gave for their marijuana use varied by state policy environment-in legal states, the average predicted probabilities were 5.3 % lower for recreational reasons and 5.0 % higher for both reasons. Reported reasons for past-month marijuana use did not significantly differ by state policy environment among daily users who were older women in poor mental and physical health. Significant differences existed in the characteristics of past-month marijuana users by reasons for use. Our estimates can serve as a baseline against which post-legalization marijuana users’ reasons for use can be compared as state policy environments shift.
Authors: Kurtzman, Ellen T; Young-Wolff, Kelly C
Drug Alcohol Depend. 2021 09 01;226:108880. Epub 2021-06-29.
Physical, Mental Health and Developmental Conditions, and Sociodemographic Characteristics Associated With Adverse Childhood Experiences Among Young Children in Pediatric Primary Care
To examine associations between patient characteristics and adverse childhood experiences (ACEs) in a population-based sample of pediatric primary care patients, using electronic health records and clinical, administrative data. An observational study was conducted in an integrated health care delivery system. Children ages 1-5 years (N = 13,370) were screened for ACEs at routine well-child visits between September 1, 2018 and May 31, 2019 in three pediatrics clinics. Multivariate models examined associations between patient characteristics (age, gender, race/ethnicity, insurance type, neighborhood income and education level, physical, mental health and developmental diagnoses, weight status) and any ACEs, and ≥ 3 ACEs exposure. Prevalence and severity of ACE exposure varied by race/ethnicity. Older age, Medicaid insurance, epilepsy/seizure disorder, sleeping disorders, adjustment disorders, and feeding disorders were associated with higher odds of ACEs exposure, higher-income with lower odds. Understanding relationships between ACEs and patient features can provide information to clinicians for early detection and appropriate interventions.
Authors: Sterling, Stacy; Iturralde, Esti; Young-Wolff, Kelly; Metz, Verena E; Espinas, Paul; et al.
J Pediatr Health Care. 2021 Sep-Oct;35(5):491-499. Epub 2021-07-03.
Associations of accelerometer-determined sedentary behavior and physical activity with physical performance outcomes by race/ethnicity in older women
To determine the cross-sectional associations of accelerometer-measured time spent in physical activity intensity categories (sedentary, low and high light intensity, or moderate to vigorous intensity physical activity (MVPA) with physical performance outcomes [stair climb ascent, 40 foot walk test, and short physical performance battery (SPPB)] in older women and examine differences by race/ethnicity. Data were from 1,256 Study of Women’s Health Across the Nation (SWAN) participants [aged 64.9 (2.7) years at Visit 15 (2015-16); 54.1% non-White]. Three sets of adjusted multivariable linear or logistic regression models were built to test the study objectives using the backward elimination approach to identify relevant covariates. In the full analytic sample, a 10 min increment in MVPA was related to faster performance on the stair climb [β = -0.023 (95% CI: -0.04, -0.005) seconds] and 40 foot walk test [β = -0.066 (95% CI: -0.133, -0.038) seconds], and a 9% lower odds [OR: 0.91; 95% CI: 0.87, 0.96; p = 0.004] of limitations based on the SPPB. Statistically significant differences by race/ethnicity were found for the stair climb ascent time as MVPA was associated with better performance for White, Chinese, and Japanese participants while high light intensity physical activity, but not MVPA, was deemed beneficial in Black women. Findings from the isotemporal substitution models were consistent. Findings further support the importance of MVPA on physical performance outcomes in older women. Further research is needed to examine the complex associations between physical (in)activity and physical performance outcomes by race/ethnicity to provide more targeted recommendations.
Authors: Pettee Gabriel, Kelley; Karvonen-Gutierrez, Carrie A; Colvin, Alicia B; Ylitalo, Kelly R; Whitaker, Kara M; Lange-Maia, Brittney S; Lucas, Alexander R; Dugan, Sheila A; Derby, Carol; Cauley, Jane A; Sternfeld, Barbara
Prev Med Rep. 2021 Sep;23:101408. Epub 2021-05-19.
Cardiovascular risk and functional burden at midlife: Prospective associations of isotemporal reallocations of accelerometer-measured physical activity and sedentary time in the CARDIA study
Cardiovascular risk and functional burden, or the accumulation of cardiovascular risk factors coupled with functional decline, may be an important risk state analogy to multimorbidity. We investigated prospective associations of sedentary time (ST), light intensity physical activity (LPA), and moderate to vigorous intensity physical activity (MVPA) with cardiovascular risk and functional burden at midlife. Participants were 1648 adults (mean ± SD age = 45 ± 4 years, 61% female, 39% Black) from Coronary Artery Risk Development in Young Adults (CARDIA) who wore accelerometers in 2005-2006 and 2015-2016. Cardiovascular risk and functional burden was defined as ≥2 cardiovascular risk factors (untreated/uncontrolled hypertension and hypercholesterolemia, type 2 diabetes, reduced kidney function) and/or functional decline conditions (reduced physical functioning and depressive symptoms). Prospective logistic regression models tested single activity, partition, and isotemporal substitution associations of accelerometer-measured ST, LPA, and MVPA with cardiovascular risk and functional burden 10 years later. In isotemporal models of baseline activity, reallocating 24 min of ST to MVPA was associated with 15% lower odds of cardiovascular risk and functional burden (OR: 0.85; CI: 0.75, 0.96). Reallocating 24 min of LPA to MVPA was associated with a 14% lower odds of cardiovascular risk and functional burden (OR: 0.86; CI: 0.75, 0.99). In longitudinal isotemporal models, similar beneficial associations were observed when 10-year increases in MVPA replaced time in ST or LPA. Findings suggest that maintaining an MVPA dose reflecting daily physical activity recommendations in early midlife is associated with lower odds of cardiovascular risk and functional burden later in midlife.
Authors: Full, Kelsie M; Whitaker, Kara M; Pettee Gabriel, Kelley; Lewis, Cora E; Sternfeld, Barbara; Sidney, Stephen; Reis, Jared P; Jacobs, David R; Gibbs, Bethany Barone; Schreiner, Pamela J
Prev Med. 2021 09;150:106626. Epub 2021-05-19.
Automated Extraction of Structured Data from Text Notes in the Electronic Medical Record
Authors: C Flint, Alexander; Melles, Ronald B; Klingman, Jeff G; Chan, Sheila L; Rao, Vivek A; Avins, Andrew L
J Gen Intern Med. 2021 09;36(9):2880-2882. Epub 2020-08-31.
Impact of Cardiovascular Risk Factors in Adolescence, Young Adulthood, and Midlife on Late-Life Cognition: Study of Healthy Aging in African Americans
Midlife cardiovascular risk factors (CVRFs) increase risk of dementia. Black Americans experience an elevated prevalence of CVRFs and dementia. However, little is known of how CVRFs prior to midlife affect late-life cognition. We examined CVRFs in adolescence, young adulthood, and midlife with late-life cognition in the Study of Healthy Aging in African Americans (STAR). STAR assesses cognitive aging among 764 Black Americans aged ≥50 (mean age = 69; SD = 9; range = 53-95). Participants’ body mass index, blood pressure, glucose, and total cholesterol were collected during Multiphasic Health Checkups (MHC; 1964-1985). At STAR baseline (2018-2019), executive function, verbal episodic memory, and semantic memory were measured using the Spanish and English Neuropsychological Assessment Scales. Linear regression models examined associations between CVRFs and cognition adjusting for demographics and years since MHC. At MHC, 36% of participants had 1 CVRF and 26% had ≥2. Twenty-two percent of participants were adolescents (age 12-20), 62% young adults (age 21-34), and 16% midlife adults (age 35-56). Overweight/obesity was not associated with cognition. Hypertension was associated with worse executive function (β [95% CI]: -0.14 [-0.28, -0.0003]) and verbal episodic memory (β [95% CI]: -0.22 [-0.37, -0.07]) compared to normotension. Diabetes was associated with worse executive function (β [95% CI]: -0.43 [-0.83, -0.03]). Having ≥2 CVRFs (vs 0) was associated with worse executive function (β [95% CI]: -0.19 [-0.34, -0.03]) and verbal episodic memory (β [95% CI]: -0.25 [-0.41, -0.08]). Adolescents with hypertension had lower late-life executive function compared to normotensive adolescents (β [95% CI]: -0.39 [-0.67, -0.11]). Young adulthood hypertension (β [95% CI]: -0.29 [-0.49, -0.09]) and midlife hyperlipidemia (β [95% CI]: -0.386 [-0.70, -0.02]) were associated with lower verbal episodic memory. Among Black Americans, life-course CVRFs were associated with poorer executive function and verbal episodic memory emphasizing the importance of cardiovascular health on the aging brain.
Authors: George, Kristen M; Gilsanz, Paola; Peterson, Rachel L; Barnes, Lisa L; DeCarli, Charles S; Mayeda, Elizabeth Rose; Mungas, Dan M; Whitmer, Rachel A
J Gerontol A Biol Sci Med Sci. 2021 08 13;76(9):1692-1698.
Associations between longitudinal trajectories of insomnia symptoms and sleep duration with objective physical function in postmenopausal women: the Study of Women’s Health Across the Nation
Examine the association between trajectories of self-reported insomnia symptoms and sleep duration over 13 years with objective physical function. We utilized data from 1,627 Study of Women’s Health Across the Nation participants, aged 61.9 ± 2.7 years at the end of the 13-year follow-up. Latent class growth models identified trajectories of insomnia symptoms (trouble falling asleep, frequent night-time awakenings, and/or early morning awakening) and sleep duration over 13 years. Physical function tests were performed at the end of the 13-year period: 40-ft walk, 4-m walk, repeated chair stand, grip strength, and balance. Multivariable regression analyses examined each physical function measure according to the insomnia symptom or sleep duration trajectory group. Five insomnia symptom trajectories and two sleep duration trajectories were identified. Women with a consistently high likelihood of insomnia symptoms and women with a decreased likelihood of insomnia symptoms (i.e. improving) had slower gait speed (3.5% slower 40-ft walk [consistently high], 3.7% slower 4-m walk [improving]; each p ≤ .05) than those with a consistently low likelihood of insomnia symptoms. In contrast, women with a steep increase in the likelihood of insomnia symptoms over time and women with persistent insufficient sleep duration had lower odds of having a balance problem (odds ratio [OR] = 0.36 and OR = 0.61, respectively; each p < .02) compared to those with a consistently low likelihood of insomnia symptoms and those with persistent sufficient sleep duration, respectively. These results suggest that women's sleep during midlife has important implications for maintaining physical function during the transition into older adulthood.
Authors: Kline, Christopher E; Colvin, Alicia B; Pettee Gabriel, Kelley; Karvonen-Gutierrez, Carrie A; Cauley, Jane A; Hall, Martica H; Matthews, Karen A; Ruppert, Kristine M; Neal-Perry, Genevieve S; Strotmeyer, Elsa S; Sternfeld, Barbara
Sleep. 2021 08 13;44(8).
GLIS1 regulates trabecular meshwork function and intraocular pressure and is associated with glaucoma in humans
Chronically elevated intraocular pressure (IOP) is the major risk factor of primary open-angle glaucoma, a leading cause of blindness. Dysfunction of the trabecular meshwork (TM), which controls the outflow of aqueous humor (AqH) from the anterior chamber, is the major cause of elevated IOP. Here, we demonstrate that mice deficient in the Krüppel-like zinc finger transcriptional factor GLI-similar-1 (GLIS1) develop chronically elevated IOP. Magnetic resonance imaging and histopathological analysis reveal that deficiency in GLIS1 expression induces progressive degeneration of the TM, leading to inefficient AqH drainage from the anterior chamber and elevated IOP. Transcriptome and cistrome analyses identified several glaucoma- and extracellular matrix-associated genes as direct transcriptional targets of GLIS1. We also identified a significant association between GLIS1 variant rs941125 and glaucoma in humans (P = 4.73 × 10-6), further supporting a role for GLIS1 into glaucoma etiology. Our study identifies GLIS1 as a critical regulator of TM function and maintenance, AqH dynamics, and IOP.
Authors: Nair, K Saidas; Choquet, H�l�ne; Jetten, Anton M; et al.
Nat Commun. 2021 08 12;12(1):4877. Epub 2021-08-12.
Trends in Ethnicity, Race, and Sex Among Psychiatry and Non-psychiatry Residency Applicants, 2008-2019
The objective of this study was to examine trends in racial/ethnic and gender representation among US psychiatry residency applicants compared with non-psychiatry applicants. Using publicly available applicant data, racial/ethnic and gender distributions of psychiatry residency applicants from 2008 to 2019 were examined and compared with non-psychiatry residency applicants. Both longitudinal trends within both cohorts and cross-sectional, between-group differences were examined. From 2008 to 2019, the percentage of female, American Indian/Alaskan Native (AIAN), Black, Hispanic, and Native Hawaiian/Other Pacific Islander (NHPI) psychiatry and non-psychiatry residency applicants increased (p<.001). Within each year, Black and Asian applicants comprised a larger percentage of psychiatry applicants compared with non-psychiatry applicants (p<.001). Between 2008 and 2019, Black psychiatry and non-psychiatry applicants increased from 9.1% to 11.6% and 6.6% to 7.6%, respectively; Asian psychiatry and non-psychiatry applicants decreased from 39.5% to 30.5% and 27.5% to 26.6%, respectively; White psychiatry and non-psychiatry applicants increased from 26.7% to 38.2% and 42.7% to 49.2%, respectively. Racial/ethnic and gender characteristics of US psychiatry residency applicants represent the future of the US psychiatric workforce. The US psychiatry residency applicant pool has become increasingly diverse from 2008 to 2019. Initiatives should work to enhance representation of psychiatry applicants from historically marginalized backgrounds, and simultaneously to recruit and retain a diverse psychiatric workforce following residency training.
Authors: Chen, Ingrid L; Koleilat, Issam; Choinski, Krystina; Phair, John; Hirschtritt, Matthew E
Acad Psychiatry. 2021 Aug;45(4):445-450. Epub 2021-04-06.
Cardiovascular risk and midlife cognitive decline in the Study of Women’s Health Across the Nation
Cardiovascular risk factors in midlife have been linked to late life risk for Alzheimer’s disease and related dementias (ADRD). The relation of vascular risk factors on cognitive decline within midlife has been less studied. Using data from the Study of Women’s Health Across the Nation, we examined associations of midlife hypertension, elevated lipid levels, diabetes, fasting glucose, central adiposity, and Framingham heart age with rates of cognitive decline in women who completed multiple cognitive assessments of processing speed, and working and verbal memory during midlife. Diabetes, elevated fasting glucose, central obesity, and heart age greater than chronological age were associated with rate of decline in processing speed during midlife. Vascular risk factors were not related to rate of decline in working or verbal memory. Midlife may be a critical period for intervening on cardiovascular risk factors to prevent or delay later life cognitive impairment and ADRD.
Authors: Derby, Carol A; Hutchins, Franya; Greendale, Gail A; Matthews, Karen A; Sternfeld, Barbara; Everson-Rose, Susan A; Kazlauskaite, Rasa; Whitmer, Rachel A; Brooks, Maria M
Alzheimers Dement. 2021 08;17(8):1342-1352. Epub 2021-03-12.
Validation of Natural Language Processing to Determine the Presence and Size of Abdominal Aortic Aneurysms in a Large Integrated Health System
Previous studies of the natural history of abdominal aortic aneurysms (AAAs) have been limited by small cohort sizes or heterogeneous analyses of pooled data. By quickly and efficiently extracting imaging data from the health records, natural language processing (NLP) has the potential to substantially improve how we study and care for patients with AAAs. The aim of the present study was to test the ability of an NLP tool to accurately identify the presence or absence of AAAs and detect the maximal abdominal aortic diameter in a large dataset of imaging study reports. Relevant imaging study reports (n = 230,660) from 2003 to 2017 were obtained for 32,778 patients followed up in a prospective aneurysm surveillance registry within a large, diverse, integrated healthcare system. A commercially available NLP algorithm was used to assess the presence of AAAs, confirm the absence of AAAs, and extract the maximal diameter of the abdominal aorta, if stated. A blinded expert manual review of 18,000 randomly selected imaging reports was used as the reference standard. The positive predictive value (PPV or precision), sensitivity (recall), and the kappa statistics were calculated. Of the randomly selected 18,000 studies that underwent expert manual review, 48.7% were positive for AAAs. In confirming the presence of an AAA, the interrater reliability of the NLP compared with the expert review showed a kappa value of 0.84 (95% confidence interval [CI], 0.83-0.85), with a PPV of 95% and sensitivity of 88.5%. The NLP algorithm showed similar results for confirming the absence of an AAA, with a kappa of 0.79 (95% CI, 0.799-0.80), PPV of 77.7%, and sensitivity of 91.9%. The kappa, PPV, and sensitivity of the NLP for correctly identifying the maximal aortic diameter was 0.88 (95% CI, 0.87-0.89), 88.8%, and 88.2% respectively. The use of NLP software can accurately analyze large volumes of radiology report data to detect AAA disease and assemble a contemporary aortic diameter-based cohort of patients for longitudinal analysis to guide surveillance, medical management, and operative decision making. It can also potentially be used to identify from the electronic medical records pre- and postoperative AAA patients “lost to follow-up,” leverage human resources engaged in the ongoing surveillance of patients with AAAs, and facilitate the construction and implementation of AAA screening programs.
Authors: McLenon, Myra; Okuhn, Steven; Lancaster, Elizabeth M; Hull, Michaela M; Adams, John L; McGlynn, Elizabeth; Avins, Andrew L; Chang, Robert W
J Vasc Surg. 2021 08;74(2):459-466.e3. Epub 2021-02-04.
New and sex-specific migraine susceptibility loci identified from a multiethnic genome-wide meta-analysis
Migraine is a common disabling primary headache disorder that is ranked as the most common neurological cause of disability worldwide. Women present with migraine much more frequently than men, but the reasons for this difference are unknown. Migraine heritability is estimated to up to 57%, yet much of the genetic risk remains unaccounted for, especially in non-European ancestry populations. To elucidate the etiology of this common disorder, we conduct a multiethnic genome-wide association meta-analysis of migraine, combining results from the GERA and UK Biobank cohorts, followed by a European-ancestry meta-analysis using public summary statistics. We report 79 loci associated with migraine, of which 45 were novel. Sex-stratified analyses identify three additional novel loci (CPS1, PBRM1, and SLC25A21) specific to women. This large multiethnic migraine study provides important information that may substantially improve our understanding of the etiology of migraine susceptibility.
Authors: Choquet, Hélène; Yin, Jie; Jacobson, Alice S; Horton, Brandon H; Hoffmann, Thomas J; Jorgenson, Eric; Avins, Andrew L; Pressman, Alice R
Commun Biol. 2021 07 22;4(1):864. Epub 2021-07-22.
Relative-Intensity Physical Activity and Its Association With Cardiometabolic Disease
Authors: Siddique, Juned; Welch, Whitney A; Aaby, David; Sternfeld, Barbara; Pettee Gabriel, Kelley; Carnethon, Mercedes R; Rana, Jamal S; Sidney, Stephen
J Am Heart Assoc. 2021 07 20;10(14):e019174. Epub 2021-07-14.
Engagement in perinatal depression treatment: a qualitative study of barriers across and within racial/ethnic groups
To better understand previously observed racial/ethnic disparities in perinatal depression treatment rates we examined care engagement factors across and within race/ethnicity. Obstetric patients and women’s health clinician experts from a large healthcare system participated in this qualitative study. We conducted focus groups with 30 pregnant or postpartum women of Asian, Black, Latina, and White race/ethnicity with positive depression screens. Nine clinician experts in perinatal depression (obstetric, mental health, and primary care providers) were interviewed. A semi-structured format elicited treatment barriers, cultural factors, and helpful strategies. Discussion transcripts were coded using a general inductive approach with themes mapped to the Capability-Opportunity-Motivation-Behavior (COM-B) theoretical framework. Treatment barriers included social stigma, difficulties recognizing one’s own depression, low understanding of treatment options, and lack of time for treatment. Distinct factors emerged for non-White women including culturally specific messages discouraging treatment, low social support, trauma history, and difficulty taking time off from work for treatment. Clinician factors included knowledge and skill handling perinatal depression, cultural competencies, and language barriers. Participants recommended better integration of mental health treatment with obstetric care, greater treatment convenience (e.g., telemedicine), and programmatic attention to cultural factors and social determinants of health. Women from diverse backgrounds with perinatal depression encounter individual-level, social, and clinician-related barriers to treatment engagement, necessitating care strategies that reduce stigma, offer convenience, and attend to cultural and economic factors. Our findings suggest the importance of intervention and policy approaches effecting change at multiple levels to increase perinatal depression treatment engagement.
Authors: Iturralde, Esti; Hsiao, Crystal A; Nkemere, Linda; Kubo, Ai; Sterling, Stacy A; Flanagan, Tracy; Avalos, Lyndsay A
BMC Pregnancy Childbirth. 2021 Jul 16;21(1):512. Epub 2021-07-16.
Transcriptome-Wide Association Study of Blood Cell Traits in African Ancestry and Hispanic/Latino Populations
Thousands of genetic variants have been associated with hematological traits, though target genes remain unknown at most loci. Moreover, limited analyses have been conducted in African ancestry and Hispanic/Latino populations; hematological trait associated variants more common in these populations have likely been missed. To derive gene expression prediction models, we used ancestry-stratified datasets from the Multi-Ethnic Study of Atherosclerosis (MESA, including n = 229 African American and n = 381 Hispanic/Latino participants, monocytes) and the Depression Genes and Networks study (DGN, n = 922 European ancestry participants, whole blood). We then performed a transcriptome-wide association study (TWAS) for platelet count, hemoglobin, hematocrit, and white blood cell count in African (n = 27,955) and Hispanic/Latino (n = 28,324) ancestry participants. Our results revealed 24 suggestive signals (p < 1 × 10-4) that were conditionally distinct from known GWAS identified variants and successfully replicated these signals in European ancestry subjects from UK Biobank. We found modestly improved correlation of predicted and measured gene expression in an independent African American cohort (the Genetic Epidemiology Network of Arteriopathy (GENOA) study (n = 802), lymphoblastoid cell lines) using the larger DGN reference panel; however, some genes were well predicted using MESA but not DGN. These analyses demonstrate the importance of performing TWAS and other genetic analyses across diverse populations and of balancing sample size and ancestry background matching when selecting a TWAS reference panel.
Authors: Wen, Jia; Fornage, Myriam; Li, Yun; et al.
Genes (Basel). 2021 07 08;12(7). Epub 2021-07-08.
Receipt of medications for opioid use disorder among youth engaged in primary care: data from 6 health systems
Little is known about prevalence and treatment of OUD among youth engaged in primary care (PC). Medications are the recommended treatment of opioid use disorder (OUD) for adolescents and young adults (youth). This study describes the prevalence of OUD, the prevalence of medication treatment for OUD, and patient characteristics associated with OUD treatment among youth engaged in PC. This cross-sectional study includes youth aged 16-25 years engaged in PC. Eligible patients had ≥ 1 PC visit during fiscal years (FY) 2014-2016 in one of 6 health systems across 6 states. Data from electronic health records and insurance claims were used to identify OUD diagnoses, office-based OUD medication treatment, and patient demographic and clinical characteristics in the FY of the first PC visit during the study period. Descriptive analyses were conducted in all youth, and stratified by age (16-17, 18-21, 22-25 years). Among 303,262 eligible youth, 2131 (0.7%) had a documented OUD diagnosis. The prevalence of OUD increased by ascending age groups. About half of youth with OUD had documented depression or anxiety and one third had co-occurring substance use disorders. Receipt of medication for OUD was lowest among youth 16-17 years old (14%) and highest among those aged 22-25 (39%). In this study of youth engaged in 6 health systems across 6 states, there was low receipt of medication treatment, and high prevalence of other substance use disorders and mental health disorders. These findings indicate an urgent need to increase medication treatment for OUD and to integrate treatment for other substance use and mental health disorders.
Authors: Bagley, Sarah M; Campbell, Cynthia I; PROUD Collaborative,; et al.
Addict Sci Clin Pract. 2021 07 07;16(1):46. Epub 2021-07-07.
Operationalizing Social Environments in Cognitive Aging and Dementia Research: A Scoping Review
Social environments are a contributing determinant of health and disparities. This scoping review details how social environments have been operationalized in observational studies of cognitive aging and dementia. A systematic search in PubMed and Web of Science identified studies of social environment exposures and late-life cognition/dementia outcomes. Data were extracted on (1) study design; (2) population; (3) social environment(s); (4) cognitive outcome(s); (5) analytic approach; and (6) theorized causal pathways. Studies were organized using a 3-tiered social ecological model at interpersonal, community, or policy levels. Of 7802 non-duplicated articles, 123 studies met inclusion criteria. Eighty-four studies were longitudinal (range 1-28 years) and 16 examined time-varying social environments. When sorted into social ecological levels, 91 studies examined the interpersonal level; 37 examined the community/neighborhood level; 3 examined policy level social environments; and 7 studies examined more than one level. Most studies of social environments and cognitive aging and dementia examined interpersonal factors measured at a single point in time. Few assessed time-varying social environmental factors or considered multiple social ecological levels. Future studies can help clarify opportunities for intervention by delineating if, when, and how social environments shape late-life cognitive aging and dementia outcomes.
Authors: Peterson, Rachel L; George, Kristen M; Tran, Duyen; Malladi, Pallavi; Gilsanz, Paola; Kind, Amy J H; Whitmer, Rachel A; Besser, Lilah M; Meyer, Oanh L
Int J Environ Res Public Health. 2021 07 04;18(13). Epub 2021-07-04.
Perceived Barriers and Motivators for Physical Activity in Women With Perinatal Depression
Physical activity (PA) can help reduce depression symptom severity in women with perinatal depression. However, PA is low, and barriers and motivators for PA among women with perinatal depression are not well understood. An ethnically diverse sample of women with perinatal depression was identified using a universal perinatal depression screening program. The authors conducted 8 focus groups (4 in pregnant women [n = 15] and 4 in postpartum women [n = 20]). Depression symptoms were measured using the Patient Health Questionnaire-8 at recruitment. Focus groups were analyzed using an inductive approach. Pregnant participants were 27 weeks gestation, and postpartum participants were 11.5 months postpartum, on average. Depression symptoms were moderately severe (mean Patient Health Questionnaire-8 score: 16). Women identified practical barriers and motivators for PA common to perinatal women (physical health, parental responsibilities, PA tracking tools, and environmental factors) and described emotional and social factors influencing PA. Motivators included using PA to improve mood, relieve stress, boost self-image, and spend time with others. Bad mood, fear of social judgment, and feeling discouraged made it difficult to be active. PA interventions in women with perinatal depression should include components addressing emotional and social barriers to PA in addition to addressing additional common practical barriers to PA.
Authors: Badon, Sylvia E; Iturralde, Esti; Nkemere, Linda; Nance, Nerissa; Avalos, Lyndsay A
J Phys Act Health. 2021 07 01;18(7):801-810. Epub 2021-05-12.
Participant education, spousal education and dementia risk in a diverse cohort of members of an integrated health care delivery system in Northern California
The role of spousal education on dementia risk and how it may differ by gender or race/ethnicity is unknown. This study examines the association between one’s own education separate from and in conjunction with spousal education and risk of dementia. Cohort. Kaiser Permanente Northern California (KPNC), an integrated health care delivery system. 8835 members of KPNC who were aged 40-55, married and reported own and spousal education in 1964-1973. Dementia cases were identified through medical records from 1 January 1996 to 30 September 2017. Own and spousal education was self-reported in 1964-1973 and each was classified as four indicator variables (≤high school, trade school/some college, college degree and postgraduate) and as ≥college degree versus college degree. Age as timescale weighted Cox proportional hazard models adjusted for demographics and health indicators evaluated associations between participant education, spousal education and dementia risk overall and by gender and race/ethnicity. The cohort was 37% non-white, 46% men and 30% were diagnosed with dementia during follow-up from 1996 to 2017 (mean follow-up=12.7 years). Greater participant education was associated with lower dementia risk independent of spousal education, demographics and health indicators. Greater spousal education was associated with lower dementia adjusting for demographics but became non-significant after further adjustment for participant education. The same pattern was seen for spousal education ≥college degree (not adjusting for participant education HRspousal education≥college degree=0.83 (95% CI: 0.76 to 0.90); adjusting for participant education HRspousal education≥college degree=0.92 (95% CI: 0.83 to 1.01)). These associations did not vary by gender or race/ethnicity. In a large diverse cohort, we found that higher levels of participant’s own education were associated with lower dementia risk regardless of spousal education. An inverse association between spousal education and dementia risk was also present, however, the effects became non-significant after adjusting for participant education.
Authors: Gilsanz, Paola; Mayeda, Elizabeth Rose; Eng, Chloe W; Meyer, Oanh L; Glymour, M Maria; Quesenberry, Charles P; Whitmer, Rachel A
BMJ Open. 2021 06 18;11(6):e040233. Epub 2021-06-18.
A large multiethnic GWAS meta-analysis of cataract identifies new risk loci and sex-specific effects
Cataract is the leading cause of blindness among the elderly worldwide and cataract surgery is one of the most common operations performed in the United States. As the genetic etiology of cataract formation remains unclear, we conducted a multiethnic genome-wide association meta-analysis, combining results from the GERA and UK Biobank cohorts, and tested for replication in the 23andMe research cohort. We report 54 genome-wide significant loci, 37 of which were novel. Sex-stratified analyses identified CASP7 as an additional novel locus specific to women. We show that genes within or near 80% of the cataract-associated loci are significantly expressed and/or enriched-expressed in the mouse lens across various spatiotemporal stages as per iSyTE analysis. Furthermore, iSyTE shows 32 candidate genes in the associated loci have altered gene expression in 9 different gene perturbation mouse models of lens defects/cataract, suggesting their relevance to lens biology. Our work provides further insight into the complex genetic architecture of cataract susceptibility.
Authors: Choquet, Hélène; Jorgenson, Eric; et al.
Nat Commun. 2021 06 14;12(1):3595. Epub 2021-06-14.
Bidirectional associations of accelerometer-derived physical activity and stationary behavior with self-reported mental and physical health during midlife
Moderate-to-vigorous intensity physical activity (MVPA) is associated with favorable self-rated mental and physical health. Conversely, poor self-rated health in these domains could precede unfavorable shifts in activity. We evaluated bidirectional associations of accelerometer-estimated time spent in stationary behavior (SB), light intensity physical activity (LPA), and MVPA with self-rated health over 10 years in in the CARDIA longitudinal cohort study. Participants (n = 894, age: 45.1 ± 3.5; 63% female; 38% black) with valid accelerometry wear and self-rated health at baseline (2005-6) and 10-year follow-up (2015-6) were included. Accelerometry data were harmonized between exams and measured mean total activity and duration (min/day) in SB, LPA, and MVPA; duration (min/day) in long-bout and short-bout SB (≥30 min vs. < 30 min) and MVPA (≥10 min vs. < 10 min) were also quantified. The Short-Form 12 Questionnaire measured both a mental component score (MCS) and physical component score (PCS) of self-rated health (points). Multivariable linear regression associated baseline accelerometry variables with 10-year changes in MCS and PCS. Similar models associated baseline MCS and PCS with 10-year changes in accelerometry measures. Over 10-years, average (SD) MCS increased 1.05 (9.07) points, PCS decreased by 1.54 (7.30) points, and activity shifted toward greater SB and less mean total activity, LPA, and MVPA (all p < 0.001). Only baseline short-bout MVPA was associated with greater 10-year increases in MCS (+ 0.92 points, p = 0.021), while baseline mean total activity, MVPA, and long-bout MVPA were associated with greater 10-year changes in PCS (+ 0.53 to + 1.47 points, all p < 0.005). In the reverse direction, higher baseline MCS and PCS were associated with favorable 10-year changes in mean total activity (+ 9.75 cpm, p = 0.040, and + 15.66 cpm, p < 0.001, respectively) and other accelerometry measures; for example, higher baseline MCS was associated with - 13.57 min/day of long-bout SB (p < 0.001) and higher baseline PCS was associated with + 2.83 min/day of MVPA (p < 0.001) in fully adjusted models. The presence of bidirectional associations between SB and activity with self-rated health suggests that individuals with low overall activity levels and poor self-rated health are at high risk for further declines and supports intervention programming that aims to dually increase activity levels and improve self-rated health.
Authors: Barone Gibbs, Bethany; Sternfeld, Barbara; Whitaker, Kara M; Brach, Jennifer S; Hergenroeder, Andrea L; Jacobs, David R; Reis, Jared P; Sidney, Stephen; White, Daniel; Pettee Gabriel, Kelley
Int J Behav Nutr Phys Act. 2021 06 06;18(1):74. Epub 2021-06-06.
Providing Epidemiologic Data in Lumbar Spine Imaging Reports Did Not Affect Subsequent Utilization of Spine Procedures: Secondary Outcomes from a Stepped-Wedge Randomized Controlled Trial
To evaluate the effect of inserting epidemiological information into lumbar spine imaging reports on subsequent nonsurgical and surgical procedures involving the thoracolumbosacral spine and sacroiliac joints. Analysis of secondary outcomes from the Lumbar Imaging with Reporting of Epidemiology (LIRE) pragmatic stepped-wedge randomized trial. Primary care clinics within four integrated health care systems in the United States. 238,886 patients ≥18 years of age who received lumbar diagnostic imaging between 2013 and 2016. Clinics were randomized to receive text containing age- and modality-specific epidemiological benchmarks indicating the prevalence of common spine imaging findings in people without low back pain, inserted into lumbar spine imaging reports (the “LIRE intervention”). The study outcomes were receiving 1) any nonsurgical lumbosacral or sacroiliac spine procedure (lumbosacral epidural steroid injection, facet joint injection, or facet joint radiofrequency ablation; or sacroiliac joint injection) or 2) any surgical procedure involving the lumbar, sacral, or thoracic spine (decompression surgery or spinal fusion or other spine surgery). The LIRE intervention was not significantly associated with subsequent utilization of nonsurgical lumbosacral or sacroiliac spine procedures (odds ratio [OR] = 1.01, 95% confidence interval [CI] 0.93-1.09; P = 0.79) or any surgical procedure (OR = 0.99, 95 CI 0.91-1.07; P = 0.74) involving the lumbar, sacral, or thoracic spine. The intervention was also not significantly associated with any individual spine procedure. Inserting epidemiological text into spine imaging reports had no effect on nonsurgical or surgical procedure utilization among patients receiving lumbar diagnostic imaging.
Authors: Suri, Pradeep; Avins, Andrew L; Friedly, Janna L; et al.
Pain Med. 2021 06 04;22(6):1272-1280.
Accelerated DNA methylation age and medication use among African Americans.
DNA methylation age acceleration, the discrepancy between epigenetic age and chronological age, is associated with mortality and chronic diseases, including diabetes, hypertension, and hyperlipidemia. In this study, we investigate whether medications commonly used to treat these diseases in 15 drug categories are associated with four epigenetic age acceleration measures: HorvathAge acceleration (HorvathAA), HannumAge acceleration (HannumAA), PhenoAge acceleration, and GrimAge acceleration (GrimAA) using cross-sectional (Phase 1, N=1,100) and longitudinal (Phases 1 and 2, N=266) data from African Americans in the Genetic Epidemiology Network of Arteriopathy (GENOA) study. In cross-sectional analyses, the use of calcium channel blockers was associated with 1.27 years lower HannumAA after adjusting for covariates including hypertension (p=0.001). Longitudinal analyses showed that, compared to those who never used antihypertensives, those who started to take antihypertensives after Phase 1 had a 0.97-year decrease in GrimAA (p=0.007). In addition, compared to those who never used NSAID analgesics, those who started to take them after Phase 1 had a 2.61-year increase in HorvathAA (p=0.0005). Our study demonstrates that three commonly used medications are associated with DNAm age acceleration in African Americans and sheds light on the potential epigenetic effects of pharmaceuticals on aging at the cellular level.
Authors: Kho, Minjung;Wang, Yi Zhe;Chaar, Dima;Zhao, Wei;Ratliff, Scott M;Mosley, Thomas H;Peyser, Patricia A;Kardia, Sharon L R;Smith, Jennifer A
Aging (Albany NY). 2021 Jun 03;13(11):14604-14629. doi: 10.18632/aging.203115..
Association of Type 1 Diabetes and Hypoglycemic and Hyperglycemic Events and Risk of Dementia
To determine whether severe hypoglycemic and hyperglycemic events are associated with longitudinal dementia risk in older adults with type 1 diabetes. A longitudinal cohort study followed 2,821 members of an integrated healthcare delivery system with type 1 diabetes from 1997-2015. Hypoglycemic and hyperglycemic events requiring emergency room or hospitalization were abstracted from medical records beginning 1/1/1996 through cohort entry. Participants were followed for dementia diagnosis through 9/30/2015. Dementia risk was examined using Cox proportional hazard models adjusted for age (as timescale), sex, race/ethnicity, HbA1c, depression, stroke, and nephropathy. Among 2,821 older adults (mean age 56) with type 1 diabetes, 398 (14%) had a history of severe hypoglycemia, 335 (12%) severe hyperglycemia and 87 (3%) both. Over a mean 6.9 years of follow-up, 153 individuals (5.4%) developed dementia. In fully adjusted models, individuals with hypoglycemic events had 66% greater risk of dementia than those without a hypoglycemic event (HR=1.66; 95% CI: 1.09, 2.53), while those with hyperglycemic events had >2 times the risk (HR=2.11; 95% CI: 1.24, 3.59) than those without a hyperglycemic event. There was a 6-fold greater risk of dementia in individuals with both severe hypoglycemia and hyperglycemia versus those with neither (HR=6.20; 95% CI: 3.02, 12.70). For older individuals with type 1 diabetes, severe hypoglycemic and hyperglycemic events are associated with increased future risk of dementia.
Authors: Whitmer, Rachel A; Gilsanz, Paola; Quesenberry, Charles P; Karter, Andrew J; Lacy, Mary E
Neurology. 2021 Jun 02.
Improvements in Functional Disability After Psychotherapy for Depression Are Associated With Reduced Suicide Ideation Among Older Adults
To evaluate the association between changes in functional disability and suicide ideation among older adults following psychotherapy for depression. Sixty-five participants (65-91 years old, 72% White, and 66% female) with depression completed 12 sessions of problem solving therapy (PST) and completed measures of disability (WHO Disability Assessment Schedule 2.0) and suicide ideation (Geriatric Suicide Ideation Scale [GSIS]) at baseline and post-treatment. Hierarchical linear regressions found that reductions in functional disability were associated with overall reductions in suicide ideation on the GSIS (F[4,60] = 4.06, p < 0.01), particularly with the Loss of Worth GSIS subscale (F[4,60] = 7.86, p < 0.001, ΔR2 = 0.140). Results suggest decreased functional disability following depression treatment is associated with decreased suicide ideation, especially thoughts regarding loss of worth. These results highlight the potential for treatments that reduce functional disability (e.g., PST) to reduce risk of suicide among older adults.
Authors: Lutz, Julie; Mackin, R Scott; Otero, Marcela C; Morin, Ruth; Bickford, David; Tosun, Duygu; Satre, Derek D; Gould, Christine E; Nelson, J Craig; Beaudreau, Sherry A
Am J Geriatr Psychiatry. 2021 06;29(6):557-561. Epub 2020-10-07.
Accounting for quality improvement during the conduct of embedded pragmatic clinical trials within healthcare systems: NIH Collaboratory case studies
Embedded pragmatic clinical trials (ePCTs) and quality improvement (QI) activities often occur simultaneously within healthcare systems (HCSs). Embedded PCTs within HCSs are conducted to test interventions and provide evidence that may impact public health, health system operations, and quality of care. They are larger and more broadly generalizable than QI initiatives, and may generate what is considered high-quality evidence for potential use in care and clinical practice guidelines. QI initiatives often co-occur with ePCTs and address the same high-impact health questions, and this co-occurrence may dilute or confound the ability to detect change as a result of the ePCT intervention. During the design, pilot, and conduct phases of the large-scale NIH Collaboratory Demonstration ePCTs, many QI initiatives occurred at the same time within the HCSs. Although the challenges varied across the projects, some common, generalizable strategies and solutions emerged, and we share these as case studies. KEY LESSONS: Study teams often need to monitor, adapt, and respond to QI during design and the course of the trial. Routine collaboration between ePCT researchers and health systems stakeholders throughout the trial can help ensure research and QI are optimally aligned to support high-quality patient-centered care.
Authors: Tuzzio, Leah; Sterling, Stacy A; Larson, Eric B; et al.
Healthc (Amst). 2021 Jun;8 Suppl 1:100432. Epub 2021-06-23.
Three genes associated with anterior and posterior cruciate ligament injury : a genome-wide association analysis
The aim of this study was to screen the entire genome for genetic markers associated with risk for anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) injury. Genome-wide association (GWA) analyses were performed using data from the Kaiser Permanente Research Board (KPRB) and the UK Biobank. ACL and PCL injury cases were identified based on electronic health records from KPRB and the UK Biobank. GWA analyses from both cohorts were tested for ACL and PCL injury using a logistic regression model adjusting for sex, height, weight, age at enrolment, and race/ethnicity using allele counts for single nucleotide polymorphisms (SNPs). The data from the two GWA studies were combined in a meta-analysis. Candidate genes previously reported to show an association with ACL injury in athletes were also tested for association from the meta-analysis data from the KPRB and the UK Biobank GWA studies. There was a total of 2,214 cases of ACL and PCL injury and 519,869 controls within the two cohorts, with three loci demonstrating a genome-wide significant association in the meta-analysis: INHBA, AEBP2, and LOC101927869. Of the eight candidate genes previously studied in the literature, six were present in the current dataset, and only COL3A1 (rs1800255) showed a significant association (p = 0.006). Genetic markers in three novel loci in this study and one previously-studied candidate gene were identified as potential risk factors for ACL and PCL injury and deserve further validation and investigation of molecular mechanisms. Cite this article: Bone Jt Open 2021;2(6):414-421.
Authors: Kim SK; Nguyen C; Avins AL; Abrams GD
Bone Jt Open. 2021 Jun;2(6):414-421.
Nicotine and cannabis vaping among adolescents in treatment for substance use disorders
This study examined nicotine and cannabis vaping among adolescents in treatment for substance use disorders. Participants were 363 adolescents aged 12-17 (66% male, mean age = 15.5 [SD = 1.3], 46% non-Hispanic white) seen for a specialty addiction intake evaluation between 2017 and 2019 at one of six medical offices of a large, integrated health care system in Northern California. Multivariable logistic regression models tested for associations of sociodemographics, cigarette smoking, and substance use disorders with vaping behaviors. A majority of adolescents reported ever (68%) or current vaping (60%) of nicotine and/or cannabis; current vaping was similar for nicotine (50%) and cannabis (51%); 40% reported current vaping of both. Current smokers (6% of the sample) had higher odds of ever vaping (aOR = 3.95, 95%CI: 1.04-14.95). Black (versus non-Hispanic white) adolescents had lower odds of current nicotine vaping (aOR = 0.08, 95%CI: 0.02-0.37) and current vaping of both nicotine and cannabis (aOR = 0.12, 95%CI: 0.03-0.60). Having an alcohol use disorder was associated with current vaping (aOR = 2.14, 95%CI: 1.06-4.33). Those who endorsed that most friends get drunk/high (aOR = 1.87, 95%CI: 1.02-3.42) or that cannabis was their substance of choice (aOR = 2.36, 95%CI: 1.16-4.81) had higher odds of current cannabis vaping. Higher neighborhood household income ($80,000-$120,000 and >$120,000 vs. <$80,000, aORs = 2.05-9.48), never versus ever blunt use (aORs = 2.47-8.68), and intakes in 2018 and 2019 versus 2017 (aORs = 2.18-5.38) were associated with higher odds of all vaping outcomes. Vaping was common among adolescents in addiction treatment and varied with sociodemographics and substance-related factors. Research should assess how vaping impacts the development of substance use disorders and whether it interferes with addiction treatment.
Authors: Young-Wolff, Kelly C; Adams, Sara R; Sterling, Stacy A; Tan, Andy S L; Salloum, Ramzi G; Torre, Kira; Carter-Harris, Lisa; Prochaska, Judith J
J Subst Abuse Treat. 2021 06;125:108304. Epub 2021-01-27.
Bidirectional associations of accelerometer measured sedentary behavior and physical activity with knee pain, stiffness, and physical function: The CARDIA study
The objective was to examine bidirectional associations of accelerometer estimated sedentary time and physical activity with reported knee symptoms. Participants were 2,034 adults (mean age 45.3 ± 3.6 years, 58.7% female) from CARDIA. Generalized estimating equations for logistic regression and linear mixed regression models examined associations of accelerometer estimated sedentary time, light-intensity physical activity (LPA), and moderate-to-vigorous intensity physical activity (MVPA) at baseline (2005-06) with knee discomfort, pain, stiffness, and physical function (yes/no and continuous scores from short-form WOMAC function scale) at the 5- and 10-year follow-up exams. Linear regression models examined associations between knee symptoms at the 5-year follow-up with accelerometer estimates at the 10-year follow-up. Models were adjusted for confounders; individuals with comorbidities were excluded in sensitivity analyses. A 30 min/day increment in sedentary time at baseline was associated with lower odds of knee symptoms at the 5- and 10-year follow-up (OR: 0.95, 95% CI range: 0.92-0.98), while LPA and MVPA were associated with greater odds of knee symptoms (LPA OR range: 1.04-1.05, 95% CI range: 1.01-1.09; MVPA OR range: 1.17-1.19, 95% CI range: 1.06-1.32). Report of knee symptoms at the 5-year follow-up was associated with 13.52-17.51 (95% CI range: -29.90, -0.56) fewer minutes/day of sedentary time and 14.58-17.51 (95% CI range: 2.48, 29.38) more minutes/day of LPA at the 10-year follow-up, compared to those reporting no symptoms. Many associations were no longer statistically significant when excluding individuals with comorbidities. Findings support a bidirectional association of accelerometer estimated sedentary time and physical activity with knee symptoms across midlife.
Authors: Whitaker, Kara M; Pettee Gabriel, Kelley; Laddu, Deepika; White, Daniel K; Sidney, Stephen; Sternfeld, Barbara; Lewis, Cora E; Jacobs, David R
Prev Med Rep. 2021 Jun;22:101348. Epub 2021-03-09.
Screening for Gender Identity in Adolescent Well Visits: Is It Feasible and Acceptable?
This study aimed to pilot systematic gender identity screening during adolescent well checks and examine perceptions of feasibility and acceptability of screening from adolescents, parents/guardians, and clinicians. Adolescents aged 12-18 years with a well visit between July 1, 2018, and June 30, 2019 (n = 134,114; 817 pilot and 133,297 usual care) in Kaiser Permanente Northern California (KPNC) pediatric primary care clinics. “What is your gender?” was added to the previsit questionnaire in pilot clinics; all other KPNC clinics provided usual care. Additional anonymous surveys were administered to adolescents and parents/guardians in the pilot clinics and to all KPNC pediatric clinicians. Multivariable logistic regression examined associations between clinics and patients reporting as transgender and gender diverse (TGD). Descriptive statistics summarized patient, parent/guardian, and clinician perceptions of gender identity screening. Adjusting for age and race/ethnicity, adolescents had higher odds of reporting as TGD in pilot clinics than in usual care (odds ratio = 6.91, 95% confidence interval = 3.76-12.74). Two thirds of adolescents, 75.5% of parents/guardians, and 92.5% of clinicians felt it was important to screen for gender identity in primary care. Less than 2% of adolescents found the question confusing, offensive, or uncomfortable, and 2.8% of parents/guardians felt it was offensive. In addition, 36.4% of clinicians and 3.6% of parents/guardians were concerned it would affect visit workflow/time. Most adolescents, parents/guardians, and pediatric clinicians viewed systematic gender identity screening as both feasible and acceptable. Standardized gender identity screening during adolescent well checks could facilitate and increase identification of TGD adolescents and the delivery of gender-affirming care for adolescents and families in need.
Authors: Lau, Josephine S; Kline-Simon, Andrea; Sterling, Stacy; Hojilla, J Carlo; Hartman, Lauren
J Adolesc Health. 2021 06;68(6):1089-1095. Epub 2020-09-15.
Impact of Cardiovascular Risk Factors in Adolescence, Young Adulthood, and Midlife on Late-life Cognition: Study of Healthy Aging in African Americans (STAR)
Midlife cardiovascular risk factors (CVRF) increase risk of dementia. Black Americans experience an elevated prevalence of CVRF and dementia. However, little is known of how CVRF prior to midlife affect late-life cognition. We examined CVRF in adolescence, young adulthood, and midlife with late-life cognition in The Study of Healthy Aging in African Americans (STAR). STAR assesses cognitive aging among 764 Black Americans ages ≥50 (mean age=69;SD=9;range 53-95). Participants’ body mass index, blood pressure, glucose, and total cholesterol were collected during Multiphasic Health Check-ups (MHC;1964-1985). At STAR baseline (2018-2019), executive function, verbal episodic memory, and semantic memory were measured using the Spanish and English Neuropsychological Assessment Scales. Linear regression models examined associations between CVRF and cognition adjusting for demographics and years since MHC. At MHC, 36% of participants had 1 CVRF and 26% had ≥2. Twenty-two percent of participants were adolescents (ages:12-20), 62% young adults (ages:21-34), and 16% midlife adults (ages:35-56). Overweight/obesity was not associated with cognition. Hypertension was associated with worse executive function [β(95%CI):-0.14(-0.28,-0.0003)] and verbal episodic memory [β(95%CI):-0.22(-0.37,-0.07)] compared to normotension. Diabetes was associated with worse executive function [β(95%CI):-0.43(-0.83,-0.03)]. Having ≥2 CVRF (versus 0) was associated with worse executive function [β(95%CI):-0.19(-0.34,-0.03)] and verbal episodic memory [β(95%CI):-0.25(-0.41,-0.08)]. Adolescents with hypertension had lower late-life executive function compared to normotensive adolescents [β(95%CI):-0.39(-0.67,-0.11)]. Young adulthood hypertension [β(95%CI):-0.29(-0.49,-0.09)] and midlife hyperlipidemia [β(95%CI):-0.386(-0.70,-0.02)] were associated with lower verbal episodic memory. Among Black Americans, lifecourse CVRF were associated with poorer executive function and verbal episodic memory emphasizing the importance of cardiovascular health on the aging brain.
Authors: George, Kristen M; Gilsanz, Paola; Peterson, Rachel L; Barnes, Lisa L; DeCarli, Charles S; Mayeda, Elizabeth Rose; Mungas, Dan M; Whitmer, Rachel A
J Gerontol A Biol Sci Med Sci. 2021 May 18.
Association Between Social Media Use and Vaping Among Florida Adolescents, 2019
With the growing popularity of vaping, evidence has emerged about the association between social media use and vaping among adolescents, possibly because of the proliferation of e-cigarette advertisements and other related content on social media. Our study examined the association between social media use and vaping among adolescents. Using data from the 2019 Florida Youth Tobacco Survey (N = 10,776), we conducted logistic regression models on adolescent vaping status (experimental and current vaping) by nondaily and daily use of social media platforms – Facebook, Instagram, Twitter and Snapchat, controlling for other confounders. Use of all 4 selected social media platforms was significantly associated with vaping status (P <.001 for all). Once jointly analyzed, daily use of Instagram was significantly associated with increased relative risks of experimental (adjusted relative risk ratio [aRRR] = 1.76; 95% CI, 1.38-2.25) and current vaping (aRRR = 1.51; 95% CI, 1.16-1.95); nondaily use of Snapchat was significantly associated with increased relative risk of experimental (aRRR = 1.57; 95% CI, 1.17-2.10) and current vaping (aRRR = 1.87; 95% CI, 1.31-2.66); daily use of Snapchat was associated with increased relative risk of experimental (aRRR = 2.38; 95% CI, 1.85-3.08) and current vaping (aRRR = 5.09; 95% CI, 3.78-6.86); nondaily use of Facebook was associated with increased relative risk of current vaping (aRRR = 1.20; 95% CI, 1.00-1.43), and nondaily use of Twitter was associated with increased relative risk of current vaping (aRRR = 1.29; 95% CI, 1.07-1.56). Multilevel efforts are warranted to monitor social media use and vaping status among adolescents, including media use monitoring plans, developing counter-marketing campaigns, and strict regulatory action on social media.
Authors: Lee, Juhan; Tan, Andy S L; Porter, Lauren; Young-Wolff, Kelly C; Carter-Harris, Lisa; Salloum, Ramzi G
Prev Chronic Dis. 2021 05 13;18:E49. Epub 2021-05-13.
Lifecourse socioeconomic changes and late-life cognition in a cohort of U.S.-born and U.S. immigrants: findings from the KHANDLE study
Low socioeconomic status (SES) in early and late life has been associated with lower late-life cognition. Less is known about how changes in SES from childhood to late life are associated with late-life cognition, especially among diverse populations of older adults. In a multi-ethnic sample (n = 1353) of older adults, we used linear regression to test associations of change in comprehensive measures of SES (financial, cultural, and social domains) from childhood to late life with semantic memory, episodic memory, and executive function. We tested whether the association between SES trajectory and late-life cognition differed by populations who resided in the U.S. during childhood or immigrated to the U.S. as adults. Participants with low childhood/high late-life financial capital had better semantic memory (β = 0.18; 95% CI: 0.04, 0.32) versus those with low financial capital in both childhood and late life, regardless of childhood residence. We observed a significant interaction in the association of verbal episodic memory and cultural capital by childhood residence (p = 0.08). Participants with a foreign childhood residence had higher verbal episodic memory if they had low childhood/high late-life cultural capital (β = 0.32; 95% CI: 0.01, 0.63), but lower verbal episodic memory if they had high childhood/low late-life cultural capital (β = - 0.40; 95% CI: - 0.94, 0.13). Having high lifecourse social capital was associated with better verbal episodic memory scores among those with a U.S. childhood (β = 0.34; 95% CI: 0.14, 0.55), but lower verbal episodic memory among those with a foreign childhood (β = - 0.10; 95% CI: - 0.51, 0.31). High financial and cultural capital in late life is associated with better cognition, regardless of early childhood SES or childhood residence.
Authors: Peterson, Rachel L; George, Kristen M; Gilsanz, Paola; Mayeda, Elizabeth Rose; Glymour, M Maria; Meyer, Oanh L; Mungas, Dan M; DeCarli, Charles; Whitmer, Rachel A
BMC Public Health. 2021 05 13;21(1):920. Epub 2021-05-13.
Cannabis Use Among Patients With Psychotic Disorders
Amidst a rapidly changing legal landscape, cannabis use in the United States has become increasingly common in the past several years. There is strong evidence to suggest that chronic and early cannabis use increases the risk of developing a psychotic disorder, and there is at least moderate evidence that suggests ongoing cannabis use among individuals with a psychotic disorder worsens clinical outcomes (eg, decreased psychiatric medication adherence, more frequent psychiatric hospitalizations). In this Review Article, we provide a focused, clinically oriented overview of the epidemiology and characteristics of cannabis use among individuals with first-episode psychosis; evaluation of cannabis use; and treatment modalities, focusing on behavioral interventions suitable for outpatient primary care settings. We discuss the limited data supporting pharmacologic interventions for cannabis use disorder, specifically among individuals with first-episode psychosis, and the unique potential of cannabidiol to serve as a harm-reduction strategy for individuals who are not able or willing to achieve abstinence for cannabis.
Authors: Hirschtritt, Matthew E; Young-Wolff, Kelly C; Mathalon, Daniel H; Satre, Derek D
Perm J. 2021 05 12;25. Epub 2021-05-12.
A Change in Blood Carbamazepine Levels Associated With Cannabis Use: Implications for Clinical Practice
Authors: Ridout, Kathryn K; Young-Wolff, Kelly C; Ridout, Samuel J
J Clin Psychiatry. 2021 05 11;82(3). Epub 2021-05-11.
Whole-genome sequencing association analysis of quantitative red blood cell phenotypes: The NHLBI TOPMed program
Whole-genome sequencing (WGS), a powerful tool for detecting novel coding and non-coding disease-causing variants, has largely been applied to clinical diagnosis of inherited disorders. Here we leveraged WGS data in up to 62,653 ethnically diverse participants from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program and assessed statistical association of variants with seven red blood cell (RBC) quantitative traits. We discovered 14 single variant-RBC trait associations at 12 genomic loci, which have not been reported previously. Several of the RBC trait-variant associations (RPN1, ELL2, MIDN, HBB, HBA1, PIEZO1, and G6PD) were replicated in independent GWAS datasets imputed to the TOPMed reference panel. Most of these discovered variants are rare/low frequency, and several are observed disproportionately among non-European Ancestry (African, Hispanic/Latino, or East Asian) populations. We identified a 3 bp indel p.Lys2169del (g.88717175_88717177TCT[4]) (common only in the Ashkenazi Jewish population) of PIEZO1, a gene responsible for the Mendelian red cell disorder hereditary xerocytosis (MIM: 194380), associated with higher mean corpuscular hemoglobin concentration (MCHC). In stepwise conditional analysis and in gene-based rare variant aggregated association analysis, we identified several of the variants in HBB, HBA1, TMPRSS6, and G6PD that represent the carrier state for known coding, promoter, or splice site loss-of-function variants that cause inherited RBC disorders. Finally, we applied base and nuclease editing to demonstrate that the sentinel variant rs112097551 (nearest gene RPN1) acts through a cis-regulatory element that exerts long-range control of the gene RUVBL1 which is essential for hematopoiesis. Together, these results demonstrate the utility of WGS in ethnically diverse population-based samples and gene editing for expanding knowledge of the genetic architecture of quantitative hematologic traits and suggest a continuum between complex trait and Mendelian red cell disorders.
Authors: Hu, Yao; Choquet, Hélène; NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium,; et al.
Am J Hum Genet. 2021 05 06;108(5):874-893. Epub 2021-04-21.
Prevalence of Medical Cannabis Use and Associated Health Conditions Documented in Electronic Health Records Among Primary Care Patients in Washington State
Many people use cannabis for medical reasons despite limited evidence of therapeutic benefit and potential risks. Little is known about medical practitioners’ documentation of medical cannabis use or clinical characteristics of patients with documented medical cannabis use. To estimate the prevalence of past-year medical cannabis use documented in electronic health records (EHRs) and to describe patients with EHR-documented medical cannabis use, EHR-documented cannabis use without evidence of medical use (other cannabis use), and no EHR-documented cannabis use. This cross-sectional study assessed adult primary care patients who completed a cannabis screen during a visit between November 1, 2017, and October 31, 2018, at a large health system that conducts routine cannabis screening in a US state with legal medical and recreational cannabis use. Three mutually exclusive categories of EHR-documented cannabis use (medical, other, and no use) based on practitioner documentation of medical cannabis use in the EHR and patient report of past-year cannabis use at screening. Health conditions for which cannabis use has potential benefits or risks were defined based on National Academies of Sciences, Engineering, and Medicine’s review. The adjusted prevalence of conditions diagnosed in the prior year were estimated across 3 categories of EHR-documented cannabis use with logistic regression. A total of 185 565 patients (mean [SD] age, 52.0 [18.1] years; 59% female, 73% White, 94% non-Hispanic, and 61% commercially insured) were screened for cannabis use in a primary care visit during the study period. Among these patients, 3551 (2%) had EHR-documented medical cannabis use, 36 599 (20%) had EHR-documented other cannabis use, and 145 415 (78%) had no documented cannabis use. Patients with medical cannabis use had a higher prevalence of health conditions for which cannabis has potential benefits (49.8%; 95% CI, 48.3%-51.3%) compared with patients with other cannabis use (39.9%; 95% CI, 39.4%-40.3%) or no cannabis use (40.0%; 95% CI, 39.8%-40.2%). In addition, patients with medical cannabis use had a higher prevalence of health conditions for which cannabis has potential risks (60.7%; 95% CI, 59.0%-62.3%) compared with patients with other cannabis use (50.5%; 95% CI, 50.0%-51.0%) or no cannabis use (42.7%; 95% CI, 42.4%-42.9%). In this cross-sectional study, primary care patients with documented medical cannabis use had a high prevalence of health conditions for which cannabis use has potential benefits, yet a higher prevalence of conditions with potential risks from cannabis use. These findings suggest that practitioners should be prepared to discuss potential risks and benefits of cannabis use with patients.
Authors: Matson, Theresa E; Campbell, Cynthia I; Lapham, Gwen T; et al.
JAMA Netw Open. 2021 05 03;4(5):e219375. Epub 2021-05-03.
Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images
Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is used to diagnose and manage ophthalmic diseases including glaucoma. We present the first large-scale genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has been associated with glaucoma, and despite its clear role as a biomarker for the disease, Mendelian randomisation does not support inner retinal thickness being on the same genetic causal pathway as glaucoma. We extracted overall retinal thickness at the fovea, representative of foveal hypoplasia, with which three of the 46 SNPs were associated. We additionally associate these three loci with visual acuity. In contrast to the Mendelian causes of severe foveal hypoplasia, our results suggest a spectrum of foveal hypoplasia, in part genetically determined, with consequences on visual function.
Authors: Currant, Hannah; Choquet, Hélène; Khawaja, Anthony P; et al.
PLoS Genet. 2021 05;17(5):e1009497. Epub 2021-05-12.
Temporal Trends in Stroke-Related Memory Change: Results From a US National Cohort 1998-2016
Findings from the Framingham Heart Study suggest that declines in dementia incidence rates over recent decades are partially due to decreases in stroke incidence and mortality; however, whether trends of declining dementia rates extend to survivors of incident stroke remains unclear. We investigated evidence for temporal trends in memory change related to incident stroke in a nationally representative cohort. Adults age 50+ in the HRS (Health and Retirement Study) were followed across three successive 6-year epochs (epoch 1: 1998-2004, n=16 781; epoch 2: 2004-2010, n=15 345; and epoch 3: 2010-2016; n=15 949). Participants were included in an epoch if they were stroke-free at the start of that epoch. Annual rates of change in a composite z-standardized memory score were compared using demographic-adjusted linear regression models for stroke-free participants, those who survived after stroke, and those who died after stroke, considering memory change before stroke, at the time of stroke, and for years following stroke. Crude stroke incidence rates decreased from 8.5 per 1000 person-years in epoch 1 to 6.8 per 1000 person-years in epoch 3. Rates of memory change before and following stroke onset were similar across epochs. Memory decrement immediately after stroke onset attenuated from -0.37 points (95% CI, -0.44 to -0.29) in epoch 1 to -0.26 (95% CI, -0.33 to -0.18) points in epoch 2 and -0.25 (95% CI, -0.33 to -0.17) points in epoch 3 (P value for linear trend=0.02). Decreases in stroke-related dementia in recent years may be partially attributable to smaller memory decrements immediately after stroke onset. Findings suggest reductions in stroke incidence and improvements in stroke care may also reduce population burden of dementia. Further investigations into whether temporal trends are attributable to improvements in stroke care are needed.
Authors: Eng, Chloe W; Mayeda, Elizabeth R; Gilsanz, Paola; Whitmer, Rachel A; Kim, Anthony S; Glymour, M Maria
Stroke. 2021 05;52(5):1702-1711. Epub 2021-03-16.
A validation study for remote testing of cognitive function in multiple sclerosis
Determine the validity and reliability of a remote, technician-guided cognitive assessment for multiple sclerosis (MS), incorporating the Symbol Digit Modalities Test (SDMT) and the California Verbal Learning Test, Second Edition (CVLT-II). In 100 patients, we compared conventional in-person testing to remote, web-assisted assessments, and in 36 patients, we assessed test-retest reliability using two equivalent, alternative forms. In-person and remote-administered SDMT (r = 0.85) and CVLT-II (r = 0.71) results were very similar. Reliability was adequate and alternative forms of SDMT (r = 0.92) and CVLT-II (r = 0.81) produced similar results. Findings indicate remote assessment can provide valid, reliable measures of cognitive function in MS.
Authors: Barcellos LF; Horton M; Shao X; Bellesis KH; Chinn T; Waubant E; Bakshi N; Marcus J; Benedict RH; Schaefer C
Mult Scler. 2021 04;27(5):795-798. Epub 2020-07-14.
A large-scale association study detects novel rare variants, risk genes, functional elements, and polygenic architecture of prostate cancer susceptibility
To identify rare variants associated with prostate cancer susceptibility and better characterize the mechanisms and cumulative disease risk associated with common risk variants, we conducted an integrated study of prostate cancer genetic etiology in two cohorts using custom genotyping microarrays, large imputation reference panels, and functional annotation approaches. Specifically, 11,984 men (6,196 prostate cancer cases and 5,788 controls) of European ancestry from Northern California Kaiser Permanente were genotyped and meta-analyzed with 196,269 men of European ancestry (7,917 prostate cancer cases and 188,352 controls) from the UK Biobank. Three novel loci, including two rare variants (European ancestry minor allele frequency < 0.01, at 3p21.31 and 8p12), were significant genome wide in a meta-analysis. Gene-based rare variant tests implicated a known prostate cancer gene (HOXB13), as well as a novel candidate gene (ILDR1), which encodes a receptor highly expressed in prostate tissue and is related to the B7/CD28 family of T-cell immune checkpoint markers. Haplotypic patterns of long-range linkage disequilibrium were observed for rare genetic variants at HOXB13 and other loci, reflecting their evolutionary history. In addition, a polygenic risk score (PRS) of 188 prostate cancer variants was strongly associated with risk (90th vs. 40th-60th percentile OR = 2.62, P = 2.55 × 10-191). Many of the 188 variants exhibited functional signatures of gene expression regulation or transcription factor binding, including a 6-fold difference in log-probability of androgen receptor binding at the variant rs2680708 (17q22). Rare variant and PRS associations, with concomitant functional interpretation of risk mechanisms, can help clarify the full genetic architecture of prostate cancer and other complex traits. SIGNIFICANCE: This study maps the biological relationships between diverse risk factors for prostate cancer, integrating different functional datasets to interpret and model genome-wide data from over 200,000 men with and without prostate cancer.See related commentary by Lachance, p. 1637.
Authors: Emami, Nima C; Presti, Joseph; Habel, Laurel A; Sakoda, Lori C; Schaefer, Catherine; Van Den Eeden, Stephen K; Witte, John S; et al.
Cancer Res. 2021 04 01;81(7):1695-1703. Epub 2020-12-08.
Comparison of dementia risk after age 50 between individuals with and without HIV infection
To compare risk of dementia after age 50 by HIV status among individuals in a primary care setting. Observational cohort study; participants were identified from 2013 to 2017 and followed through 2019. Participants were people with HIV (PWH) on antiretroviral therapy (ART) and demographically similar people without HIV (PWOH), all at least 50 years old and with no prior diagnosis of dementia. The study setting was Kaiser Permanente Northern California, an integrated healthcare delivery system in the United States. Incident dementia diagnoses and baseline data on sociodemographics, smoking, alcohol use, other substance use, and clinical factors were gathered from the electronic health record. Cumulative proportion of incident dementia by HIV status was assessed using Kaplan–Meier curves. Unadjusted and adjusted hazard ratios for incident dementia by HIV status were generated using Cox proportional hazards models with age as the time scale. The study included 5381 PWH and 119 022 PWOH (average age at baseline: 57 and 58 years, respectively). Incident dementia was diagnosed in 117 PWH and 2427 PWOH. By age 80, 25.8% of PWH and 13.8% of PWOH had been diagnosed with dementia, corresponding with an unadjusted hazard ratio of 1.98 (95% CI 1.64-2.39). After adjustment for sociodemographic, substance use, and clinical factors, including frequency of outpatient visits, the risk of dementia among PWH remained elevated (vs. PWOH, adjusted hazard ratio = 1.58, 95% CI 1.31-1.92). Compared with PWOH, PWH were at 58% higher risk for dementia despite HIV treatment with ART. Research is needed to investigate the potential benefits of targeted risk factor management or earlier cognitive screening in this population.
Authors: Lam, Jennifer O; Hou, Craig E; Hojilla, J Carlo; Anderson, Alexandra N; Gilsanz, Paola; Alexeeff, Stacey E; Levine-Hall, Tory; Hood, Nicole; Lee, Catherine; Satre, Derek D; Silverberg, Michael J
AIDS. 2021 04 01;35(5):821-828.
Mental Health Services in a U.S. Prison During the COVID-19 Pandemic
Pandemics pose unique risks to people in correctional facilities. Among other vulnerabilities, incarcerated populations often have high rates of mental disorders and substance use disorders, which may increase risks for morbidity and mortality during a pandemic. California’s San Quentin State Prison (SQSP) experienced multiple outbreaks during the 1918 influenza pandemic, and, a century later, the prison faces a new pandemic. This Open Forum describes the modification of mental health services in SQSP during the early stages of the COVID-19 pandemic. The authors explore the challenges of reducing risks of viral contagion while maintaining high-quality mental health care in a correctional setting.
Authors: Burton, Paul R S; Morris, Nathaniel P; Hirschtritt, Matthew E
Psychiatr Serv. 2021 04 01;72(4):458-460. Epub 2021-01-05.
Racial/Ethnic Disparities in Young Adulthood and Midlife Cardiovascular Risk Factors and Late-life Cognitive Domains: The Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study
Midlife cardiovascular risk factors (CVRF) increase dementia risk. Less is known about whether CVRF identified before midlife impact late-life cognition in diverse populations. Linear regression models examined hypertension, hyperlipidemia, and overweight/obesity at ages 30 to 59 with late-life executive function, semantic memory, verbal episodic memory, and global cognition in a cohort of Asians, blacks, Latinos, and whites (n=1127; mean age=75.8, range=65 to 98). Models adjusted for age at CVRF, age at cognitive assessment, sex, race/ethnicity, participant education, and parental education. Overall, 34% had 1 CVRF at ages 30 to 59; 19% had 2+. Blacks (26%) and Latinos (23%) were more likely to have 2+ CVRF than Asians (14%) or whites (13%). Having 2+ CVRF was associated with lower global cognition [β=-0.33; 95% confidence interval (CI)=-0.45, -0.21], executive function (β=-0.26; 95% CI=-0.39, -0.13), verbal episodic memory (β=-0.34; 95% CI=-0.48, -0.20), and semantic memory (β=-0.20; 95% CI=-0.33, -0.07). Interaction by age (P=0.06) indicated overweight/obesity was negatively associated with executive function at ages 30 to 39 but not at ages 40 to 59. Race/ethnic-specific effects showed disparities in CVRF prevalence impact population disparities in late-life cognition. Being overweight/obese in early adulthood and having 2+ CVRF in early adulthood/midlife are modifiable targets to redress racial/ethnic disparities in cognitive impairment and dementia.
Authors: Peterson, Rachel L; George, Kristen M; Gilsanz, Paola; Ackley, Sarah; Mayeda, Elizabeth R; Glymour, M M; Mungas, Dan M; DeCarli, Charles; Whitmer, Rachel A
Alzheimer Dis Assoc Disord. 2021 Apr-Jun 01;35(2):99-105.
Coronavirus Disease 2019 (COVID-19) and the Incidence of Obstetric and Gynecologic Emergency Department Visits in an Integrated Health Care System
Authors: Abel, Mary Kathryn; Alavi, Mubarika X; Tierney, Cassidy; Weintraub, Miranda Ritterman; Avins, Andrew; Zaritsky, Eve
Obstet Gynecol. 2021 04 01;137(4):581-583.
Prevalence and Medication Treatment of Opioid Use Disorder Among Primary Care Patients with Hepatitis C and HIV
Hepatitis C and HIV are associated with opioid use disorders (OUD) and injection drug use. Medications for OUD can prevent the spread of HCV and HIV. To describe the prevalence of documented OUD, as well as receipt of office-based medication treatment, among primary care patients with HCV or HIV. Retrospective observational cohort study using electronic health record and insurance data. Adults ≥ 18 years with ≥ 2 visits to primary care during the study (2014-2016) at 6 healthcare systems across five states (CO, CA, OR, WA, and MN). The primary outcome was the diagnosis of OUD; the secondary outcome was OUD treatment with buprenorphine or oral/injectable naltrexone. Prevalence of OUD and OUD treatment was calculated across four groups: HCV only; HIV only; HCV and HIV; and neither HCV nor HIV. In addition, adjusted odds ratios (AOR) of OUD treatment associated with HCV and HIV (separately) were estimated, adjusting for age, gender, race/ethnicity, and site. The sample included 1,368,604 persons, of whom 10,042 had HCV, 5821 HIV, and 422 both. The prevalence of diagnosed OUD varied across groups: 11.9% (95% CI: 11.3%, 12.5%) for those with HCV; 1.6% (1.3%, 2.0%) for those with HIV; 8.8% (6.2%, 11.9%) for those with both; and 0.92% (0.91%, 0.94%) among those with neither. Among those with diagnosed OUD, the prevalence of OUD medication treatment was 20.9%, 16.0%, 10.8%, and 22.3%, for those with HCV, HIV, both, and neither, respectively. HCV was not associated with OUD treatment (AOR = 1.03; 0.88, 1.21), whereas patients with HIV had a lower probability of OUD treatment (AOR = 0.43; 0.26, 0.72). Among patients receiving primary care, those diagnosed with HCV and HIV were more likely to have documented OUD than those without. Patients with HIV were less likely to have documented medication treatment for OUD.
Authors: Tsui, Judith I; Campbell, Cynthia I; Bradley, Katharine A; et al.
J Gen Intern Med. 2021 04;36(4):930-937. Epub 2021-02-10.
A Genome-wide Association Study for Concussion Risk
This study aimed to screen the entire genome for genetic markers associated with risk for concussion. A genome-wide association analyses was performed using data from the Kaiser Permanente Research Bank and the UK Biobank. Concussion cases were identified based on electronic health records from the Kaiser Permanente Research Bank and the UK Biobank from individuals of European ancestry. Genome-wide association analyses from both cohorts were tested for concussion using a logistic regression model adjusting for sex, height, weight, and race/ethnicity using allele counts for single nucleotide polymorphisms. Previously identified genes within the literature were also tested for association with concussion. There were a total of 4064 cases of concussion and 291,472 controls within the databases, with two single nucleotide polymorphisms demonstrating a genome-wide significant association with concussion. The first polymorphism, rs144663795 (P = 9.7 × 10-11; OR = 2.91 per allele copy), is located within the intron of SPATA5. Strong, deleterious mutations in SPATA5 cause intellectual disability, hearing loss, and vision loss. The second polymorphism, rs117985931 (P = 3.97 × 10-9; OR = 3.59 per allele copy), is located within PLXNA4. PLXNA4 plays a key role is axon outgrowth during neural development, and DNA variants in PLXNA4 are associated with risk for Alzheimer’s disease. Previous investigations have identified five candidate genes that may be associated with concussion, but none showed a significant association in the current model (P < 0.05). Two genetic markers were identified as potential risk factors for concussion and deserve further validation and investigation of molecular mechanisms.
Authors: Kim, Stuart K; Roche, Megan D; Fredericson, Michael; Dragoo, Jason L; Horton, Brandon H; Avins, Andy L; Belanger, Heather G; Ioannidis, John P A; Abrams, Geoffrey D
Med Sci Sports Exerc. 2021 04 01;53(4):704-711.
Do the Benefits of Educational Attainment for Late-life Cognition Differ by Racial/Ethnic Group?: Evidence for Heterogenous Treatment Effects in the Kaiser Healthy Aging and Diverse Life Experience (KHANDLE) Study
Educational attainment is associated with late-life cognitive performance and dementia; few studies have examined diverse racial/ethnic groups to assess whether the association differs by race/ethnicity. We investigated whether the association between educational attainment and cognition differed between White, Black, Asian, and Latino participants in the Kaiser Healthy Aging and Diverse Life Experiences study (n=1348). Covariate-adjusted multivariable linear regression models examined domains of verbal episodic memory, semantic memory, and executive functioning. We observed significant effect heterogeneity by race/ethnicity only for verbal episodic memory (P=0.0198), for which any schooling between high school and college was beneficial for White, Asian, and Black participants, but not Latino participants. We found no evidence of heterogeneity for semantic memory or executive function. With the exception of Latino performance on verbal episodic memory, more education consistently predicted better cognitive scores to a similar extent across racial/ethnic groups, despite likely heterogenous educational and social experiences.
Authors: Eng, Chloe W; Glymour, Medellena Maria; Gilsanz, Paola; Mungas, Dan M; Mayeda, Elizabeth R; Meyer, Oanh L; Whitmer, Rachel A
Alzheimer Dis Assoc Disord. 2021 Apr-Jun 01;35(2):106-113.
Do Youth Want Psychosocial Screenings in Diabetes Clinic? Profiles of Acceptability
Psychosocial screenings are recommended and increasingly common in pediatric subspecialty clinics, though little is known about their acceptability. This study seeks to uncover profiles of acceptability and assess demographic and clinical correlates among adolescents with diabetes. A sample of 124 adolescents (57.7% female) ages 12-21 years (M = 16.2 ± 2.3) completed screenings during routine diabetes appointments. K-means clustering of responses to acceptability items derived profiles; Analysis of Variance (ANOVA) and Chi-square tests assessed correlates. Adolescents with the most common profile (72.6%) placed high importance on medical providers’ awareness of their emotions and reported no difficulties/discomfort with the screener. These youth had moderate depressive symptoms, low diabetes distress, and low A1c. Those who fit a less common profile (18.5%) were uncomfortable with the screener and had the highest depressive symptoms and lowest A1c. Youth who fit a smaller profile (6.5%) endorsed technical difficulties and had high depressive symptoms and lowest diabetes distress. The smallest profile (2.4%, N = 3) had difficulty understanding and experienced discomfort with the screening and had the lowest depressive symptoms and the highest diabetes distress and A1c. These differences in depressive symptoms (F = 3.54, p = .017), A1c values (F = 4.03, p = .009), and diabetes distress (F = 3.27, p = .036) were significant though differences in age, gender, and diabetes duration were not. Most youth responded favorably to in-clinic psychosocial screenings. Youth who were less satisfied were at increased risk for psychosocial and medical complications. Findings highlight areas of need, such as enhanced support with and an emphasized rationale for screenings, which may improve patient experience in subspecialty care.
Authors: Wong, Jessie J; Hanes, Sarah; Iturralde, Esti; Lanning, Monica S; Naranjo, Diana; Tanenbaum, Molly; Hood, Korey K
J Pediatr Psychol. 2021 03 18;46(3):332-340.
Changes in Diagnostic and Demographic Characteristics of Patients Seeking Mental Health Care During the Early COVID-19 Pandemic in a Large, Community-Based Health Care System
The early COVID-19 pandemic resulted in great psychosocial disruption and stress, raising speculation that psychiatric disorders may worsen. This study aimed to identify patients vulnerable to worsening mental health during the COVID-19 pandemic. This retrospective observational study used electronic health records from March 9 to May 31 in 2019 (n = 94,720) and 2020 (n = 94,589) in a large, community-based health care system. Percent change analysis compared variables standardized to the average patient population for the respective time periods. Compared to 2019, psychiatric visits increased significantly (P < .0001) in 2020, with the majority being telephone/video-based (+264%). Psychiatric care volume increased overall (7%), with the greatest increases in addiction (+42%), behavioral health in primary care (+17%), and adult psychiatry (+5%) clinics. While patients seeking care with preexisting psychiatric diagnoses were mainly stable (−2%), new patients declined (−42%). Visits for substance use (+51%), adjustment (+15%), anxiety (+12%), bipolar (+9%), and psychotic (+6%) disorder diagnoses, and for patients aged 18–25 years (+4%) and 26–39 years (+4%), increased. Child/adolescent and older adult patient visits decreased (−22.7% and −5.5%, respectively), and fewer patients identifying as White (−3.8%) or male (−5.0) or with depression (−3%) or disorders of childhood (−2%) sought care. The early COVID-19 pandemic was associated with dramatic changes in psychiatric care facilitated by a rapid telehealth care transition. Patient volume, demographic, and diagnostic changes may reflect comfort with telehealth or navigating the psychiatric care system. These data can inform health system resource management and guide future work examining how care delivery changes impact psychiatric care quality and access.
Authors: Ridout, Kathryn K; Alavi, Mubarika; Ridout, Samuel J; Koshy, Maria T; Harris, Brooke; Dhillon, Inderpreet; Awsare, Sameer; Weisner, Constance M; Campbell, Cynthia I; Iturralde, Esti
J Clin Psychiatry. 2021 03 03;82(2). Epub 2021-03-03.
A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus
Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease.
Authors: Hardcastle, Alison J; Choquet, Hélène; Hysi, Pirro G; et al.
Commun Biol. 2021 03 01;4(1):266. Epub 2021-03-01.
Smoking cessation treatment for individuals with comorbid diabetes and serious mental illness in an integrated health care delivery system
Smoking is a significant modifiable risk factor for mortality for persons with serious mental illness (SMI), who have a life expectancy 15-20 years shorter than the general population. Individuals with SMI and comorbid diabetes who are smokers face an even higher risk of cardiovascular complications and early death. Yet despite high rates of smoking among people with SMI, tobacco cessation interventions have not been broadly offered to this population. We conducted a retrospective cohort study using electronic health records from 2014 in a large integrated care delivery system to examine whether use of smoking cessation pharmacotherapy among smokers with type 2 diabetes varies by serious mental illness (SMI) diagnosis. We analyzed smoking cessation medication prescription fills among adult smokers with diabetes, comparing those with SMI (N = 634) and without SMI (N = 18,021). Risk ratios were adjusted for age, gender, race, urban area type, and medical facility. Of the SMI group, 19.09% filled at least one smoking cessation prescription compared to 9.73% of the non-SMI group (adjusted risk ratio 1.80 [95% CI 1.52-2.13]; p < .001). For the SMI group, primary care providers wrote 80.24% of prescriptions, while psychiatrists wrote 8.81% of prescriptions. These findings offer an example of a delivery system with higher uptake of smoking cessation pharmacotherapy among people with SMI than without SMI, and highlight the opportunity to provide more smoking cessation interventions in mental health care settings.
Authors: Hwong AR; Schmittdiel J; Schillinger D; Newcomer JW; Essock S; Zhu Z; Dyer W; Young-Wolff KC; Mangurian C
Addict Behav. 2021 03;114:106697. Epub 2020-10-14.
A Facebook intervention to address cigarette smoking and heavy episodic drinking: A pilot randomized controlled trial
Co-occurrence of tobacco use and heavy episodic drinking (HED; 5+ drinks for men and 4+ drinks for women per occasion) is common among young adults; both warrant attention and intervention. In a two-group randomized pilot trial, we investigated whether a Facebook-based smoking cessation intervention addressing both alcohol and tobacco use would increase smoking abstinence and reduce HED compared to a similar intervention addressing only tobacco. Participants were 179 young adults (age 18-25; 49.7% male; 80.4% non-Hispanic white) recruited from Facebook and Instagram who reported smoking 4+ days/week and past-month HED. The Smoking Tobacco and Drinking (STAND) intervention (N = 84) and the Tobacco Status Project (TSP), a tobacco-only intervention (N = 95), both included daily Facebook posts for 90 days and weekly live counseling sessions in private “secret” groups. We verified self-reported 7-day smoking abstinence via remote salivary cotinine tests at 3, 6, and 12 months (with retention at 83%, 66%, and 84%, respectively). Participants self-reported alcohol use. At baseline, the participants averaged 10.4 cigarettes per day (SD = 6.9) and 8.9 HED occasions in the past month (SD = 8.1), with 27.4% in a preparation stage of change for quitting smoking cigarettes. Participants reported significant improvements in cigarette smoking and alcohol use outcomes over time, with no significant differences by condition. At 12 months, intent-to-treat smoking abstinence rates were 3.5% in STAND vs. 0% in TSP (biochemically verified) and 29.4% in STAND vs. 25.5% in TSP (self-reported). Compared to TSP, participants rated the STAND intervention more favorably for supporting health and providing useful information. Adding an alcohol treatment component to a tobacco cessation social media intervention was acceptable and engaging but did not result in significant differences by treatment condition in smoking or alcohol use outcomes. Participants in both conditions reported smoking and drinking less over time, suggesting covariation in behavioral changes.
Authors: Meacham, Meredith C; Ramo, Danielle E; Prochaska, Judith J; Maier, Larissa J; Delucchi, Kevin L; Kaur, Manpreet; Satre, Derek D
J Subst Abuse Treat. 2021 03;122:108211. Epub 2020-11-23.
Association of Cannabis Retailer Proximity and Density With Cannabis Use Among Pregnant Women in Northern California After Legalization of Cannabis for Recreational Use
Authors: Young-Wolff, Kelly C; Adams, Sara R; Padon, Alisa; Silver, Lynn D; Alexeeff, Stacey E; Van Den Eeden, Stephen K; Avalos, Lyndsay A
JAMA Netw Open. 2021 03 01;4(3):e210694. Epub 2021-03-01.
Closing the gap: Identification and management of familial hypercholesterolemia in an integrated healthcare delivery system
Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder that causes markedly elevated risk for early onset coronary artery disease. Despite availability of effective therapy, only 5-10% of affected individuals worldwide are diagnosed. To develop and evaluate a novel approach for identifying and managing patients with FH in a large integrated health system with a diverse patient population, using inexpensive methods. Using Make Early Diagnosis/Prevent Early Death (MEDPED) criteria, we created a method for identifying patients at high risk for FH within the Kaiser Permanente Northern California electronic medical record. This led to a pragmatic workflow for contacting patients, establishing a diagnosis in a dedicated FH clinic, and initiating management. We prospectively collected data on the first 100 patients to assess implementation effectiveness. Ninety-three (93.0%, 95%CI: 86.1%-97.1%) of the first 100 evaluated patients were diagnosed with FH (median age = 38 years) of whom only 5% were previously recognized; 48% were taking no lipid-lowering therapy, and 7% had acute coronary symptoms. 82 underwent successful genetic testing of whom 55 (67.1%; 95%CI: 55.8%-77.1%) had a pathogenic mutation. Following clinic evaluation, 83 of 85 (97.6%) medication-eligible patients were prescribed combination lipid-lowering therapy. 20 family members in the healthcare system were diagnosed with FH through cascade testing. This novel approach was effective for identifying and managing patients with undiagnosed FH. Care gaps in providing appropriate lipid-lowering therapy were successfully addressed. Further development and dissemination of integrated approaches to FH care are warranted.
Authors: Birnbaum, Richard A; Horton, Brandon H; Gidding, Samuel S; Brenman, Leslie Manace; Macapinlac, Brian A; Avins, Andrew L
J Clin Lipidol. 2021 Mar-Apr;15(2):347-357. Epub 2021-02-02.
Adverse Childhood Experiences and Early and Continued Breastfeeding: Findings from an Integrated Health Care Delivery System
Purpose: To examine whether adverse childhood experiences (ACEs) are associated with breastfeeding behaviors. Methods: Women in three Kaiser Permanente Northern California medical centers were screened for ACEs during standard prenatal care (N = 926). Multivariable binary and multinomial logistic regression was used to test whether ACEs (count and type) were associated with early breastfeeding at the 2-week newborn pediatric visit and continued breastfeeding at the 2-month pediatric visit, adjusting for covariates. Results: Overall, 58.2% of women reported 0 ACEs, 19.2% reported 1 ACE, and 22.6% reported 2+ ACEs. Two weeks postpartum, 92.2% reported any breastfeeding (62.9% exclusive, 29.4% mixed breastfeeding/formula). Compared with women with 0 ACEs, those with 2+ ACEs had increased odds of any breastfeeding (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.3-5.6) and exclusive breastfeeding 2 weeks postpartum (OR = 3.0, 95% CI = 1.4-6.3). Among those who breastfed 2 weeks postpartum, 86.4% reported continued breastfeeding (57.5% exclusive, 28.9% mixed breastfeeding/formula) 2 months postpartum. ACE count was not associated with continued breastfeeding 2 months postpartum. Individual ACEs were not related to breastfeeding outcomes, with the exception that living with someone who went to jail or prison was associated with lower odds of continued breastfeeding 2 months postpartum. Conclusions: ACE count was associated with greater early breastfeeding, but not continued breastfeeding, among women screened for ACEs as part of standard prenatal care. Results reiterate the need to educate and assist all women to meet their breastfeeding goals, regardless of ACE score.
Authors: Watson, Carey; Wei, Julia; Varnado, Nicole; Rios, Normelena; Flanagan, Tracy; Alabaster, Amy; Staunton, Mary; Sterling, Stacy A; Gunderson, Erica P; Young-Wolff, Kelly C
J Womens Health (Larchmt). 2021 03;30(3):367-376. Epub 2021-02-04.
Gestational weight gain and adverse pregnancy outcomes by pre-pregnancy BMI category in women with chronic hypertension: A cohort study
It is important to understand relationships of gestational weight gain with adverse pregnancy outcomes in women with chronic hypertension, given their high baseline risk of adverse outcomes. We assessed associations of gestational weight gain with adverse pregnancy outcomes in women with chronic hypertension by pre-pregnancy body mass index categories. We identified 14,369 women with chronic hypertension using electronic health records from 3 integrated health care delivery systems (2005-2014). Gestational weight gain-for-gestational age charts were used to calculate gestational weight gain z-scores, which account for gestational age. Modified Poisson regression models using generalized estimating equations were used to calculate relative risks and 95% confidence intervals, adjusted for sociodemographic and medical characteristics. Preeclampsia, preterm delivery, cesarean delivery, neonatal intensive care unit admission, birthweight (extracted from the electronic health record). In women with normal weight or overweight, low gestational weight gain (z-score < -1) was associated with 27-28% greater risk of preterm delivery and 48-82% greater risk of small-for-gestational age birthweight, while high gestational weight gain (z-score > 1) was associated with 40-90% greater risk of preeclampsia and 59-113% greater risk of large-for-gestational age birthweight. In women with obesity, low gestational weight gain was associated with 27-54% lower risk of several adverse pregnancy outcomes, including preeclampsia and cesarean delivery. In women with chronic hypertension and normal weight or overweight, moderate gestational weight gain may confer the lowest risk of adverse outcomes. In women with chronic hypertension and obesity, low gestational weight gain may be necessary for the lowest risk of adverse pregnancy outcomes.
Authors: Badon, Sylvia E; Dublin, Sascha; Nance, Nerissa; Hedderson, Monique M; Neugebauer, Romain; Easterling, Thomas; Cheetham, T Craig; Chen, Lu; Holt, Victoria L; Avalos, Lyndsay A
Pregnancy Hypertens. 2021 Mar;23:27-33. Epub 2020-10-24.
Adverse Childhood Experiences and Pregnancy Intentions among Pregnant Women Seeking Prenatal Care
This study examined whether adverse childhood experiences (ACEs) are associated with increased risk of having an unwanted or mistimed pregnancy. Women in two medical centers within an integrated health system were screened for ACEs during standard prenatal care (N = 745). Multinomial multivariable logistic regression analyses examined the associations of ACEs (count and type) with pregnancy intentions, adjusting for covariates. Overall, 58.3% of pregnant women reported no ACEs, 19.1% reported one ACE, and 22.7% reported two or more ACEs; 76.2% reported wanting to get pregnant, 18.5% reported wanting to get pregnant but not at this time (i.e., mistimed pregnancy), and 5.2% reported not wanting to get pregnant at all (i.e., unwanted pregnancy). Having two or more (vs. 0) ACEs was associated with higher odds of an unwanted pregnancy (odds ratio, 2.60; 95% confidence interval, 1.19-5.68). Further, childhood loss of parent (odds ratio, 2.20; 95% confidence interval, 1.03-4.71) and neglect (odds ratio, 5.67; 95% confidence interval, 1.72-18.72) were each associated with higher odds of an unwanted pregnancy in separate analyses. ACEs count and type were not significantly associated with having a mistimed pregnancy. Among women screened for ACEs during standard prenatal care, ACEs were associated with increased odds of having an unwanted pregnancy, but not a mistimed pregnancy. Additional research is needed to better understand the mechanisms through which ACEs and other individual, social, and contextual factors impact pregnancy intentions to better support women and provide appropriate resources to help prevent unintended pregnancies.
Authors: Young-Wolff, Kelly C; Wei, Julia; Varnado, Nicole; Rios, Normelena; Staunton, Mary; Watson, Carey
Womens Health Issues. 2021 Mar-Apr;31(2):100-106. Epub 2020-10-05.
Long-term Stroke Risk with Carotid Endarterectomy in Patients with Severe Carotid Stenosis
Informed debate regarding the optimal use of carotid endarterectomy (CEA) for stroke risk reduction requires contemporary assessment of both long-term risk and periprocedural risk. In this study, we report long-term stroke and death risk after CEA in a large integrated health care system. All patients with documented severe (70%-99%) stenosis from 2008 to 2012 who underwent CEA were identified and stratified by asymptomatic or symptomatic indication. Those with prior ipsilateral interventions were excluded. Patients were followed up through 2017 for the primary outcomes of any stroke/death within 30 days of intervention and long-term ipsilateral ischemic stroke; secondary outcomes were any stroke and overall survival. Overall, 1949 patients (63.2% male; mean age, 71.3 ± 8.9 years) underwent 2078 primary CEAs, 1196 (58%) for asymptomatic stenosis and 882 (42%) for symptomatic stenosis. Mean follow-up was 5.5 ± 2.7 years. Median time to surgery was 72.0 (interquartile range, 38.5-198.0) days for asymptomatic patients and 21.0 (interquartile range, 5.0-55.0) days for symptomatic patients (P < .001). Most of the patients' demographics and characteristics were similar in both groups. Controlled blood pressure rates were similar at the time of CEA. Baseline statin use was seen in 60.5% of the asymptomatic group compared with 39.9% in the symptomatic group (P < .001), and statin adherence by 80% medication possession ratio was 19.3% asymptomatic vs 12.4% symptomatic (P < .001). The crude overall 30-day any stroke/death rates were 0.9% and 1.5% for the asymptomatic group and the symptomatic group, respectively. The 5-year risk of ipsilateral stroke and a combined end point of any stroke/death by Kaplan-Meier survival analysis were 2.5% and 28.7% for the asymptomatic group and 4.0% and 31.4% for the symptomatic group, respectively. Unadjusted cumulative all-cause survival was 74.2% for the asymptomatic group and 71.8% for the symptomatic group at 5 years. In a contemporary review of CEA, outcomes for either operative indication show low adverse events perioperatively and low long-term stroke risk up to 5 years. These results are well within consensus guidelines and published trial outcomes and should help inform the discussion around optimal CEA use for severe carotid stenosis.
Authors: Rothenberg KA; Tucker LY; Gologorsky RC; Avins AL; Kuang HC; Faruqi RM; Flint AC; Nguyen-Huynh MN; Chang RW
J Vasc Surg. 2021 03;73(3):983-991. Epub 2020-07-21.
Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries
Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.
Authors: Gharahkhani, Puya; Qassim, Ayub; Wiggs, Janey L; et al.
Nat Commun. 2021 02 24;12(1):1258. Epub 2021-02-24.
Cigarette smoking behaviors and the importance of ethnicity and genetic ancestry
Cigarette smoking contributes to numerous diseases and is one of the leading causes of death in the United States. Smoking behaviors vary widely across race/ethnicity, but it is not clear why. Here, we examine the contribution of genetic ancestry to variation in two smoking-related traits in 43,485 individuals from four race/ethnicity groups (non-Hispanic white, Hispanic/Latino, East Asian, and African American) from a single U.S. healthcare plan. Smoking prevalence was the lowest among East Asians (22.7%) and the highest among non-Hispanic whites (38.5%). We observed significant associations between genetic ancestry and smoking-related traits. Within East Asians, we observed higher smoking prevalence with greater European (versus Asian) ancestry (P = 9.95 × 10-12). Within Hispanic/Latinos, higher cigarettes per day (CPD) was associated with greater European ancestry (P = 3.34 × 10-25). Within non-Hispanic whites, the lowest number of CPD was observed for individuals of southeastern European ancestry (P = 9.06 × 10-5). These associations remained after considering known smoking-associated loci, education, socioeconomic factors, and marital status. Our findings support the role of genetic ancestry and socioeconomic factors in cigarette smoking behaviors in non-Hispanic whites, Hispanic/Latinos, and East Asians.
Authors: Choquet, Hélène; Yin, Jie; Jorgenson, Eric
Transl Psychiatry. 2021 02 11;11(1):120. Epub 2021-02-11.
Are adverse childhood experiences associated with late-life cognitive performance across racial/ethnic groups: results from the Kaiser Healthy Aging and Diverse Life Experiences study baseline
Evidence on adverse childhood experiences (ACEs) and late-life cognitive outcomes is inconsistent, with little research among diverse racial/ethnic groups. We investigated whether ACE exposures were associated with worse late-life cognition for all racial/ethnic groups and at different ages of exposure. Covariate-adjusted mixed-effects linear regression models estimated associations of: (1) total number of ACEs experienced, (2) earliest age when ACE occurred and (3) type of ACE with overall cognition. Kaiser Permanente Northern California members aged 65 years and older, living in Northern California. Kaiser Healthy Aging and Diverse Life Experiences study baseline participants, aged 65 years and older (n=1661; including 403 Asian-American, 338 Latino, 427 Black and 493 white participants). Most respondents (69%) reported one or more ACE, most frequently family illness (36%), domestic violence (23%) and parental divorce (22%). ACE count was not adversely associated with cognition overall (β=0.01; 95% CI -0.01 to 0.03), in any racial/ethnic group or for any age category of exposure. Pooling across all race/ethnicities, parent’s remarriage (β=-0.11; 95% CI -0.20 to -0.03), mother’s death (β=-0.18; 95% CI -0.30 to -0.07) and father’s death (β=-0.11; 95% CI -0.20 to -0.01) were associated with worse cognition. Adverse childhood exposures overall were not associated with worse cognition in older adults in a diverse sample, although three ACEs were associated with worse cognitive outcomes.
Authors: Gold, Audra L; Meza, Erika; Ackley, Sarah F; Mungas, Dan M; Whitmer, Rachel A; Mayeda, Elizabeth Rose; Miles, Sunita; Eng, Chloe W; Gilsanz, Paola; Glymour, M Maria
BMJ Open. 2021 02 05;11(2):e042125. Epub 2021-02-05.
Longitudinal Associations of Midlife Accelerometer Determined Sedentary Behavior and Physical Activity With Cognitive Function: The CARDIA Study
Background To determine if accelerometer measured sedentary behavior (SED), light-intensity physical activity (LPA), and moderate-to-vigorous-intensity physical activity (MVPA) in midlife is prospectively associated with cognitive function. Methods and Results Participants were 1970 adults enrolled in the CARDIA (Coronary Artery Risk Development in Young Adults) study who wore an accelerometer in 2005 to 2006 (ages 38-50 years) and had cognitive function assessments completed 5 and/or 10 years later. SED, LPA, and MVPA were measured by an ActiGraph 7164 accelerometer. Cognitive function tests included the Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, and Stroop Test. Compositional isotemporal substitution analysis examined associations of SED, LPA, and MVPA with repeated measures of the cognitive function standardized scores. In men, statistical reallocation of 30 minutes of LPA with 30 minutes of MVPA resulted in an estimated difference of SD 0.07 (95% CI, 0.01-0.14), SD 0.09 (95% CI, 0.02-0.17), and SD -0.11 (95% CI, -0.19 to -0.04) in the Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, and Stroop scores, respectively, indicating better performance. Associations were similar when reallocating time in SED with MVPA, but results were less robust. Reallocation of time in SED with LPA resulted in an estimated difference of SD -0.05 (95% CI, -0.06 to -0.03), SD -0.03 (95% CI, -0.05 to -0.01), and SD 0.05 (95% CI, 0.03- 0.07) in the Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, and Stroop scores, respectively, indicating worse performance. Associations were largely nonsignificant among women. Conclusions Our findings support the idea that for men, higher-intensity activities (MVPA) may be necessary in midlife to observe beneficial associations with cognition.
Authors: Whitaker, Kara M; Zhang, Dong; Pettee Gabriel, Kelley; Ahrens, Monica; Sternfeld, Barbara; Sidney, Stephen; Jacobs, David R; Palta, Priya; Yaffe, Kristine
J Am Heart Assoc. 2021 02 02;10(3):e018350. Epub 2021-01-20.
Comparison of eating disorder characteristics and depression comorbidity in adolescent males and females: An observational study
Depression comorbid with eating disorders is common and can worsen the severity of both disorders. Little is published regarding depression and eating disorders in male adolescents. This retrospective observational study compared eating disorder presentation and depression comorbidity between medically-hospitalized male and female adolescents. Standardized chart abstraction was performed for 148 subjects (n=127 females, =21 males). Male adolescents had significantly greater pre-hospitalization weight loss and longer eating disorder duration, and were 1.6 times more likely to have comorbid depression compared to female patients. These findings suggest increased detection and treatment of both disorders in adolescent males is warranted.
Authors: Ridout, Samuel J; Ridout, Kathryn K; Kole, Jonathan; Fitzgerald, Kelly L; Donaldson, Abigail A; Alverson, Brian
Psychiatry Res. 2021 02;296:113650. Epub 2020-12-15.
Moving Toward Health and Social Equity for Women Who Use Cannabis During Preconception, Pregnancy, and Lactation
Authors: Young-Wolff, Kelly C; Silver, Lynn D; Brown, Qiana L
JAMA Netw Open. 2021 02 01;4(2):e210148. Epub 2021-02-01.
The relationship of smoking and unhealthy alcohol use to the HIV care continuum among people with HIV in an integrated health care system
Smoking tobacco and unhealthy alcohol use may negatively influence HIV care continuum outcomes but have not been examined in combination. Participants were people with HIV (PWH) in Kaiser Permanente Northern California. Predictors included smoking status and unhealthy alcohol use (exceeding daily and/or weekly limits) reported by patients during primary care screening (index date). Outcomes were based on not achieving the following steps in the care continuum: linkage to HIV care (≥1 visit within 90 days of newly identified HIV diagnosis), retention (2+ in-person visits, 60+ days apart) and HIV RNA control (<75 copies/mL). Adjusted odds ratios (ORs) were obtained from separate logistic regression models for each outcome associated with smoking and unhealthy alcohol use independently and combined. The overall sample (N = 8958) had a mean age of 48.0 years; was 91.3 % male; 54.0 % white, 17.6 % Latino, 15.1 % black, and 9.6 % other race/ethnicity. Smoking was associated with higher odds of not being linked to HIV care (OR = 1.60 [95 % CI 1.03-2.48]), not retained (OR = 1.30 [95 % CI 1.13-1.50]), and HIV RNA not in control (OR = 1.91 [95 % CI 1.60-2.27]). Alcohol measures were not independently associated with outcomes. The combination of unhealthy alcohol use and smoking (versus neither) was associated with higher odds of not being linked to care (OR = 2.83 [95 % CI 1.40-5.71]), although the interaction did not reach significance (p = 0.18). In this large sample of PWH in an integrated health care system, smoking, both independently and in combination with unhealthy alcohol use, was associated with worse HIV care continuum outcomes.
Authors: Satre, Derek D; Sterling, Stacy A; Young-Wolff, Kelly C; Lam, Jennifer O; Alexeeff, Stacey; Weisner, Constance; Silverberg, Michael J; et al.
Drug Alcohol Depend. 2021 02 01;219:108481. Epub 2021-01-08.
PRimary Care Opioid Use Disorders treatment (PROUD) trial protocol: a pragmatic, cluster-randomized implementation trial in primary care for opioid use disorder treatment
Most people with opioid use disorder (OUD) never receive treatment. Medication treatment of OUD in primary care is recommended as an approach to increase access to care. The PRimary Care Opioid Use Disorders treatment (PROUD) trial tests whether implementation of a collaborative care model (Massachusetts Model) using a nurse care manager (NCM) to support medication treatment of OUD in primary care increases OUD treatment and improves outcomes. Specifically, it tests whether implementation of collaborative care, compared to usual primary care, increases the number of days of medication for OUD (implementation objective) and reduces acute health care utilization (effectiveness objective). The protocol for the PROUD trial is presented here. PROUD is a hybrid type III cluster-randomized implementation trial in six health care systems. The intervention consists of three implementation strategies: salary for a full-time NCM, training and technical assistance for the NCM, and requiring that three primary care providers have DEA waivers to prescribe buprenorphine. Within each health system, two primary care clinics are randomized: one to the intervention and one to Usual Primary Care. The sample includes all patients age 16-90 who visited the randomized primary care clinics from 3 years before to 2 years after randomization (anticipated to be > 170,000). Quantitative data are derived from existing health system administrative data, electronic medical records, and/or health insurance claims (“electronic health records,” [EHRs]). Anonymous staff surveys, stakeholder debriefs, and observations from site visits, trainings and technical assistance provide qualitative data to assess barriers and facilitators to implementation. The outcome for the implementation objective (primary outcome) is a clinic-level measure of the number of patient days of medication treatment of OUD over the 2 years post-randomization. The patient-level outcome for the effectiveness objective (secondary outcome) is days of acute care utilization [e.g. urgent care, emergency department (ED) and/or hospitalizations] over 2 years post-randomization among patients with documented OUD prior to randomization. The PROUD trial provides information for clinical leaders and policy makers regarding potential benefits for patients and health systems of a collaborative care model for management of OUD in primary care, tested in real-world diverse primary care settings. Trial registration # NCT03407638 (February 28, 2018); CTN-0074 https://clinicaltrials.gov/ct2/show/NCT03407638?term=CTN-0074&draw=2&rank=1.
Authors: Campbell, Cynthia I; Bradley, Katharine A; et al.
Addict Sci Clin Pract. 2021 01 31;16(1):9. Epub 2021-01-31.
Core outcomes set for research on the treatment of opioid use disorder (COS-OUD): the National Institute on Drug Abuse Clinical Trials Network protocol for an e-Delphi consensus study
A lack of consensus on the optimal outcome measures to assess the efficacy and effectiveness of interventions for the treatment of opioid use disorder (OUD) has hampered the pooling of research data for evidence synthesis and clinical guidelines. A core outcome set (COS) is a minimum set of outcome measures that are recommended for all studies of a particular condition. The National Drug Abuse Treatment Clinical Trials Network (CTN) Core Outcome Set for OUD (COS-OUD) is a development study to identify core constructs, meaningful outcomes, and their optimal measurement for all efficacy and effectiveness studies of OUD treatment and service delivery. Overseen by an expert workgroup, a modified, stepwise, e-Delphi methodology will be used to gain consensus among a panel of clinical practitioners and researchers involved in the treatment of OUD, who are members of the CTN. Sequential rounds of anonymous, online questionnaires will be used to identify, rate the importance of, and refine a core outcome set. A consensus threshold will be achieved if at least 70% of the panel rate the measure as critical for inclusion in the COS-OUD. Where consensus is not reached or there are suggestions for new measures, these will be brought forward to a further round of review prior to a consensus meeting. Products from this study will be communicated via peer-reviewed scientific journals and conferences. This initiative will develop a COS for OUD intervention trials, treatment studies, and service delivery and will support the pooling of research and clinical practice data and efforts to develop measurement-based care within the OUD treatment cascade. https://www.comet-initiative.org/Studies/Details/1579.
Authors: Karnik, Niranjan S; Campbell, Cynthia I; Marsden, John; et al.
Trials. 2021 Jan 28;22(1):102. Epub 2021-01-28.
The impact of adjusting for baseline in pharmacogenomic genome-wide association studies of quantitative change
In pharmacogenomic studies of quantitative change, any association between genetic variants and the pretreatment (baseline) measurement can bias the estimate of effect between those variants and drug response. A putative solution is to adjust for baseline. We conducted a series of genome-wide association studies (GWASs) for low-density lipoprotein cholesterol (LDL-C) response to statin therapy in 34,874 participants of the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort as a case study to investigate the impact of baseline adjustment on results generated from pharmacogenomic studies of quantitative change. Across phenotypes of statin-induced LDL-C change, baseline adjustment identified variants from six loci meeting genome-wide significance (SORT/CELSR2/PSRC1, LPA, SLCO1B1, APOE, APOB, and SMARCA4/LDLR). In contrast, baseline-unadjusted analyses yielded variants from three loci meeting the criteria for genome-wide significance (LPA, APOE, and SLCO1B1). A genome-wide heterogeneity test of baseline versus statin on-treatment LDL-C levels was performed as the definitive test for the true effect of genetic variants on statin-induced LDL-C change. These findings were generally consistent with the models not adjusting for baseline signifying that genome-wide significant hits generated only from baseline-adjusted analyses (SORT/CELSR2/PSRC1, APOB, SMARCA4/LDLR) were likely biased. We then comprehensively reviewed published GWASs of drug-induced quantitative change and discovered that more than half (59%) inappropriately adjusted for baseline. Altogether, we demonstrate that (1) baseline adjustment introduces bias in pharmacogenomic studies of quantitative change and (2) this erroneous methodology is highly prevalent. We conclude that it is critical to avoid this common statistical approach in future pharmacogenomic studies of quantitative change.
Authors: Oni-Orisan A; Haldar T; Ranatunga DK; Medina MW; Schaefer C; Krauss RM; Iribarren C; Risch N; Hoffmann TJ
NPJ Genom Med. 2020 Jan 16;5(1):1. Epub 2020-01-16.
Fitting a shared frailty illness-death model to left-truncated semi-competing risks data to examine the impact of education level on incident dementia
Semi-competing risks arise when interest lies in the time-to-event for some non-terminal event, the observation of which is subject to some terminal event. One approach to assessing the impact of covariates on semi-competing risks data is through the illness-death model with shared frailty, where hazard regression models are used to model the effect of covariates on the endpoints. The shared frailty term, which can be viewed as an individual-specific random effect, acknowledges dependence between the events that is not accounted for by covariates. Although methods exist for fitting such a model to right-censored semi-competing risks data, there is currently a gap in the literature for fitting such models when a flexible baseline hazard specification is desired and the data are left-truncated, for example when time is on the age scale. We provide a modeling framework and openly available code for implementation. We specified the model and the likelihood function that accounts for left-truncated data, and provided an approach to estimation and inference via maximum likelihood. Our model was fully parametric, specifying baseline hazards via Weibull or B-splines. Using simulated data we examined the operating characteristics of the implementation in terms of bias and coverage. We applied our methods to a dataset of 33,117 Kaiser Permanente Northern California members aged 65 or older examining the relationship between educational level (categorized as: high school or less; trade school, some college or college graduate; post-graduate) and incident dementia and death. A simulation study showed that our implementation provided regression parameter estimates with negligible bias and good coverage. In our data application, we found higher levels of education are associated with a lower risk of incident dementia, after adjusting for sex and race/ethnicity. As illustrated by our analysis of Kaiser data, our proposed modeling framework allows the analyst to assess the impact of covariates on semi-competing risks data, such as incident dementia and death, while accounting for dependence between the outcomes when data are left-truncated, as is common in studies of aging and dementia.
Authors: Lee, Catherine; Gilsanz, Paola; Haneuse, Sebastien
BMC Med Res Methodol. 2021 01 11;21(1):18. Epub 2021-01-11.
Physical Performance and Cognition in a Diverse Cohort: Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study
The authors assessed the cross-sectional association of physical function measures with cognition in the Kaiser Healthy Aging and Diverse Life Experiences Cohort. Analyses included 1369 participants (24% Asian, 26% Black, 18% Latino, 32% White). Grip strength was measured using a hand-held dynamometer (kilograms) and gait speed was measured over a 4-m walk (seconds/meter). The Spanish and English Neuropsychological Assessment Scales was used to evaluate cognitive domains of executive function, semantic memory, and verbal episodic memory. Physical function measures (per SD) were associated with cognitive test z-scores in linear regression models adjusted for demographic, behavioral, and clinical factors. Racial/ethnic differences were tested using interaction terms and stratification. Stronger grip was associated with better executive function [β=0.10 (95% confidence interval, 0.05-0.15)], semantic memory [β=0.13 (0.09-0.18)] and verbal episodic memory [β=0.07 (0.02-0.13)] with no racial/ethnic differences. Faster gait was associated with better executive function [β=0.29 (0.22-0.36)], semantic memory [β=0.23 (0.16-0.30)], and verbal episodic memory [β=0.20 (0.13-0.27)]; however, the association between gait speed and executive function varied by race/ethnicity with the strongest associations in Asians and Whites. Across race/ethnicity, grip strength and gait speed were associated with cognition with racial/ethnic differences in the association of gait speed and executive function.
Authors: George KM; Gilsanz P; Peterson RL; Glymour MM; Mayeda ER; Mungas DM; Miles SQ; Whitmer RA
Alzheimer Dis Assoc Disord. 2021 Jan 11.
Associations of diet, physical activity and polycystic ovary syndrome in the Coronary Artery Risk Development in Young Adults Women’s Study
Current evidence supports the adoption of healthy diet and physical activity (PA) behaviors in patients with polycystic ovary syndrome (PCOS), given the positive effects of those behaviors on physical well-being. An improved understanding of the associations between diet and PA with PCOS is needed to ascertain whether tailored dietary and PA recommendations are needed for this population. Thus, we investigated the associations of diet and PA with PCOS and its isolated features. Cross-sectional study. Of the 748 women who were included in this study from the Coronary Artery Risk Development in Young Adults (CARDIA) Women’s Study, 40 were classified as having PCOS, 104 had isolated hyperandrogenism (HA) and 75 had isolated oligomenorrhea (OA). Dietary intake was measured using the CARDIA diet history questionnaire and diet quality was scored using the Alternative Healthy Eating Index 2010; a higher score indicated a better quality diet. Self-reported PA was measured using a validated interviewer-administered questionnaire. Polytomous logistic regression analyses examined the associations between diet and PA with PCOS, HA, and OA status (outcomes), adjusting for age, race, total energy intake, education, and/or body mass index. The threshold for statistical significance was set at p < 0.05. Mean age of the participants was 25.4 years (SD 3.6) and 46.8% of participants were Black women. There was little to no association of total energy intake, nutrients, diet quality, and PA with PCOS, HA or OA status. Energy intake, nutrient composition, diet quality, and PA were not associated with PCOS, supporting recent PCOS guidelines of using national recommendations for the general population to encourage health-promoting behaviors among women with PCOS. However, longitudinal studies evaluating changes in diet and physical activity in relation to the development and/or the progression of PCOS are needed to establish a causal association.
Authors: Lin, Annie W; Sternfeld, Barbara; Lujan, Marla E; et al.
BMC Public Health. 2021 01 06;21(1):35. Epub 2021-01-06.
Alcohol Use and Antiretroviral Adherence Among Patients Living with HIV: Is Change in Alcohol Use Associated with Change in Adherence?
Alcohol use increases non-adherence to antiretroviral therapy (ART) among persons living with HIV (PLWH). Dynamic longitudinal associations are understudied. Veterans Aging Cohort Study (VACS) data 2/1/2008-7/31/16 were used to fit linear regression models estimating changes in adherence (% days with ART medication fill) associated with changes in alcohol use based on annual clinically-ascertained AUDIT-C screening scores (range – 12 to + 12, 0 = no change) adjusting for demographics and initial adherence. Among 21,275 PLWH (67,330 observations), most reported no (48%) or low-level (39%) alcohol use initially, with no (55%) or small (39% ≤ 3 points) annual change. Mean initial adherence was 86% (SD 21%), mean annual change was – 3.1% (SD 21%). An inverted V-shaped association was observed: both increases and decreases in AUDIT-C were associated with greater adherence decreases relative to stable scores [p < 0.001, F (4, 21,274)]. PLWH with dynamic alcohol use (potentially indicative of alcohol use disorder) should be considered for adherence interventions. El consumo de alcohol aumenta el no-cumplimiento a la terapia antirretroviral (TARV) entre las personas que viven con VIH. No se han estudiado lo suficiente las dinámicas asociaciones longitudinales. Los datos del Estudio de la Envejecimiento de Cohorte de Veteranos (EECV) (1/2/2008–31/7/2016) fueron usados para encajar modelos de regresión lineal estimando los cambios en cumplimiento (% de días con medicaciones TARV surtidas) asociados con los cambios en el consumo de alcohol basado en los resultados anuales de las evaluaciones AUDIT-C, determinadas clínicamente, (una gama de -12 a + 12, 0 = cero cambio) adaptándose a las estadísticas demográficas y cumplimiento inicial. Entre 21,275 personas que viven con VIH (67,330 observaciones), la mayoría reportó ningún (48%) o bajos niveles del (39%) consumo de alcohol inicialmente, con ningún (55%) o muy pequeño (39% ≤ 3 puntos) cambio anual. la media inicial de cumplimiento fue 86% (DE 21%). La media de cambio anual fue -3.1% (DE 21%). Se observó una asociación de forma V invertida: tanto los aumentos como las disminuciones en AUDIT-C fueron asociados con mayor disminuciones de cumplimiento en comparación con resultados estables (p < 0.001, F (4, 21,274)). Personas que viven con VIH con el consumo dinámico de alcohol (potencialmente indicativo de un trastorno por consumo de alcohol) deben ser considerados por intervenciones de cumplimiento.
Authors: Williams EC; Satre DD; Bradley KA; et al.
AIDS Behav. 2021 Jan;25(1):203-214.
Chapter 26 – Telomeres and Early-Life Stress
Telomere biology may be important in understanding the mental and physical health consequences of early adversity and for assessing the therapeutic effects of interventions aimed at alleviating these consequences. Telomeres are nucleoprotein structures at the ends of chromosomes that preserve coding deoxyribonucleic acid during chromosome replication. Telomeres shorten with each cell division, reflecting the age of a cell and the time until senescence. Telomere shortening and changes in levels of telomerase, the enzyme that maintains telomeres, occur in the context of certain somatic and psychiatric diseases. Emerging evidence indicates that telomeres shorten with exposure to multiple forms of stress experienced early in life. These findings suggest that telomere shortening might be a useful biomarker for indicating the stress response of an organism to various conditions. The possibility that telomere shortening can be slowed or reversed by psychiatric and psychosocial interventions represents an opportunity for developing novel preventative and therapeutic approaches.
Authors: Mayer, Stefanie; Conklin, Quinn; Ridout, Samuel J; Ridout, Kathryn K
In: Fink G, editor. Stress: Genetics, Epigenetics and Genomics (Handbook of Stress Series, Volume 4). Cambridge (MA): Academic Press; 2021.
Cognitive impairment in racially/ethnically diverse older adults: Accounting for sources of diagnostic bias
The Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study enrolled Asian, Black, Latino, and White adults ages 65+ without prior dementia diagnosis (N = 1709). We evaluated the prevalence of cognitive impairment (mild cognitive impairment or dementia) accounting for potential biases. A random subgroup (N = 541) received clinical evaluation and others were evaluated if they failed a cognitive screen. Diagnoses were made under two conditions: (1) demographics-blind, based on clinical exam and demographically adjusted neuropsychological test scores; and (2) all available information (clinical exam, demographics, and adjusted and unadjusted test scores). Cognitive impairment prevalence was 28% for blinded-adjusted diagnosis and 25% using all available information. Black participants had higher impairment rates than White (both conditions) and Latino (blinded-adjusted diagnosis) participants. Incomplete assessments negatively biased prevalence estimates for White participants. Racial/ethnic disparities in cognitive impairment were amplified by attrition bias in White participants but were unaffected by type of test norms and diagnosticians’ knowledge of demographics.
Authors: Mungas, Dan; Shaw, Crystal; Hayes-Larson, Eleanor; DeCarli, Charles; Farias, Sarah Tomaszewski; Olichney, John; Saucedo, Hector Hernandez; Gilsanz, Paola; Glymour, M Maria; Whitmer, Rachel A; Mayeda, Elizabeth Rose
Alzheimers Dement (Amst). 2021;13(1):e12265. Epub 2021-12-31.
COVID-19 prevalence, symptoms, and sociodemographic disparities in infection among insured pregnant women in Northern California
Research on COVID-19 during pregnancy has mainly focused on women hospitalized for COVID-19 or other reasons during their pregnancy. Little is known about COVID-19 in the general population of pregnant women. To describe the prevalence of COVID-19, symptoms, consequent healthcare use, and possible sources of COVID-19 exposure among a population-based sample of pregnant women residing in Northern California. We analyzed data from 19,458 members of Kaiser Permanente Northern California who were pregnant between January 2020 and April 2021 and responded to an online survey about COVID-19 testing, diagnosis, symptoms, and their experiences during the COVID-19 pandemic. Medical diagnosis of COVID-19 during pregnancy was defined separately by self-report and by documentation in electronic health records (EHR). We examined relationships of COVID-19 with sociodemographic factors, underlying comorbidities, and survey measures of COVID-19-like symptoms, consequent healthcare utilization, and possible COVID-19 exposures. Among 19,458 respondents, the crude prevalence of COVID-19 was 2.5% (n = 494) according to self-report and 1.4% (n = 276) according to EHR. After adjustment, the prevalence of self-reported COVID-19 was higher among women aged <25 years compared with women aged ≥35 years (prevalence ratio [PR], 1.75, 95% CI: 1.23, 2.49) and among Hispanic women compared with White women (PR, 1.91, 95% CI: 1.53, 2.37). Prevalence of self-reported COVID-19 was higher among women affected by personal or partner job loss during the pandemic (PR, 1.23, 95% CI: 1.02, 1.47) and among women living in areas of high vs. low neighborhood deprivation (PR, 1.74, 95% CI: 1.33, 2.27). We did not observe differences in self-reported COVID-19 between women with and without underlying comorbidities. Results were similar for EHR-documented COVID-19. Loss of smell or taste was a unique and common symptom reported among women with COVID-19 (42.3% in self-reported; 54.0% in EHR-documented). Among women with symptomatic COVID-19, approximately 2% were hospitalized, 71% had a telehealth visit, and 75% quarantined at home. Over a third of women with COVID-19 reported no known exposure to someone with COVID-19. Observed COVID-19 prevalence differences by sociodemographic and socioeconomic factors underscore social and health inequities among reproductive-aged women. Women with COVID-19 reported unique symptoms and low frequency of hospitalization. Many were not aware of an exposure to someone with COVID-19.
Authors: Ames, Jennifer L; Ferrara, Assiamira; Avalos, Lyndsay A; Badon, Sylvia E; Greenberg, Mara B; Hedderson, Monique M; Kuzniewicz, Michael W; Young-Wolff, Kelly C; Zerbo, Ousseny; Zhu, Yeyi; Croen, Lisa A; et al.
PLoS One. 2021;16(9):e0256891. Epub 2021-09-03.
An implementation evaluation of “Zero Suicide” using normalization process theory to support high-quality care for patients at risk of suicide
Suicide rates continue to rise across the United States, galvanizing the need for increased suicide prevention and intervention efforts. The Zero Suicide (ZS) model was developed in response to this need and highlights four key clinical functions of high-quality health care for patients at risk of suicide. The goal of this quality improvement study was to understand how six large health care systems operationalized practices to support these functions-identification, engagement, treatment and care transitions. Using a key informant interview guide and data collection template, researchers who were embedded in each health care system cataloged and summarized current and future practices supporting ZS, including, (1) the function addressed; (2) a description of practice intent and mechanism of intervention; (3) the target patient population and service setting; (4) when/how the practice was (or will be) implemented; and (5) whether/how the practice was documented and/or measured. Normalization process theory (NPT), an implementation evaluation framework, was applied to help understand how ZS had been operationalized in routine clinical practices and, specifically, what ZS practices were described by key informants (coherence), the current state of norms/conventions supporting these practices (cognitive participation), how health care teams performed these practices (collective action), and whether/how practices were measured when they occurred (reflexive monitoring). The most well-defined and consistently measured ZS practices (current and future) focused on the identification of patients at high risk of suicide. Stakeholders also described numerous engagement and treatment practices, and some practices intended to support care transitions. However, few engagement and transition practices were systematically measured, and few treatment practices were designed specifically for patients at risk of suicide. The findings from this study will support large-scale evaluation of the effectiveness of ZS implementation and inform recommendations for implementation of high-quality suicide-related care in health care systems nationwide.
Authors: Richards, Julie E; Sterling, Stacy A; Ahmedani, Brian K; et al.
Implement Res Pract. 2021 Jan 01;2. Epub 2021-05-24.
Physical Performance and Cognition in a Diverse Cohort: Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study
The authors assessed the cross-sectional association of physical function measures with cognition in the Kaiser Healthy Aging and Diverse Life Experiences Cohort. Analyses included 1369 participants (24% Asian, 26% Black, 18% Latino, 32% White). Grip strength was measured using a hand-held dynamometer (kilograms) and gait speed was measured over a 4-m walk (seconds/meter). The Spanish and English Neuropsychological Assessment Scales was used to evaluate cognitive domains of executive function, semantic memory, and verbal episodic memory. Physical function measures (per SD) were associated with cognitive test z-scores in linear regression models adjusted for demographic, behavioral, and clinical factors. Racial/ethnic differences were tested using interaction terms and stratification. Stronger grip was associated with better executive function [β=0.10 (95% confidence interval, 0.05-0.15)], semantic memory [β=0.13 (0.09-0.18)] and verbal episodic memory [β=0.07 (0.02-0.13)] with no racial/ethnic differences. Faster gait was associated with better executive function [β=0.29 (0.22-0.36)], semantic memory [β=0.23 (0.16-0.30)], and verbal episodic memory [β=0.20 (0.13-0.27)]; however, the association between gait speed and executive function varied by race/ethnicity with the strongest associations in Asians and Whites. Across race/ethnicity, grip strength and gait speed were associated with cognition with racial/ethnic differences in the association of gait speed and executive function.
Authors: George, Kristen M; Gilsanz, Paola; Peterson, Rachel L; Glymour, Medellena Maria; Mayeda, Elizabeth Rose; Mungas, Dan M; Miles, Sunita Q; Whitmer, Rachel A
Alzheimer Dis Assoc Disord. 2021 Jan-Mar 01;35(1):23-29.
Sex, diabetes status and cognition: findings from the study of longevity in diabetes
Women comprise two-thirds of people with dementia, making female sex a significant dementia risk factor. Both type 1 diabetes (T1D) and type 2 diabetes (T2D) are known dementia risk factors with an increasing global incidence. Understanding whether subtle sex differences persist in cognitive function prior to dementia in the context of diabetes may help elucidate the magnitude of sex effects on dementia risk. We examined cross-sectional data from the Study of Longevity in Diabetes (SOLID), a prospective cohort study of members of Kaiser Permanente Northern California aged 60 years and older with T1D (n=758), T2D (n=232) and without either T1D or T2D (n=247). We used factor analysis to generate summary scores of cognitive domains and used regression analyses to examine the associations between sex and cognition adjusting for sociodemographic and cardiovascular confounders. We included 1237 participants (630 women and 607 men) with mean age 68 years. By design, the distribution of men and women in T1D, T2D and no diabetes was similar. Women had better cognitive performance than men in global cognition (β=0.21, 95% CI 0.16 to 0.26), language (β=0.08, 95% CI 0.004 to 0.15), executive function (β=0.13, 95% CI 0.05 to 0.20), episodic verbal memory (β=0.68, 95% CI 0.59 to 0.77) and attention (β=0.20, 95% CI 0.11 to 0.28) but not in episodic visual memory (β=0.006, 95% CI -0.07 to 0.09) adjusting for age and education independent of diabetes status. We did not find an interaction between sex and diabetes status for any of the cognitive outcomes. Women in late mid-life have better cognitive performance than men in many cognitive domains independent of the presence of T1D or T2D. Further work is required to understand whether these differences change over time or in older cohorts and to understand their relationship to subsequent dementia.
Authors: Moran, Chris; Gilsanz, Paola; Beeri, Michal S; Whitmer, Rachel A; Lacy, Mary E
BMJ Open Diabetes Res Care. 2021 01;9(1).
Three-Year Outcomes After Brief Treatment of Substance Use and Mood Symptoms
Screening, brief intervention, and referral to treatment (SBIRT) for adolescents exhibiting co-occurring substance use and mental health problems may improve outcomes and have long-lasting effects. This study examined the relationship between access to SBIRT and substance use, depression and medical diagnoses, and health services use at 1 and 3 years postscreening for such adolescents. The study draws from a cluster-randomized trial comparing SBIRT to usual care (UC) for adolescents endorsing past-year substance use and recent mood symptoms during visits to a general pediatrics clinic between November 1, 2011, and October 31, 2013, in a large, integrated health system (N = 1851); this sample examined the subset of adolescents endorsing both problems (n = 289). Outcomes included depression, substance use and medical diagnoses, and emergency department and outpatient visits 1 and 3 years later. The SBIRT group had lower odds of depression diagnoses at 1 (odds ratio [OR] = 0.31; confidence interval [CI] = 0.11-0.87) and 3 years (OR = 0.51; CI = 0.28-0.94) compared with the UC group. At 3 years, the SBIRT group had lower odds of a substance use diagnosis (OR = 0.46; CI = 0.23-0.92), and fewer emergency department visits (rate ratio = 0.65; CI = 0.44-0.97) than UC group. The findings suggest that SBIRT may prevent health complications and avert costly services use among adolescents with both mental health and substance use problems. As SBIRT is implemented widely in pediatric primary care, training pediatricians to discuss substance use and mental health problems can translate to positive outcomes for these vulnerable adolescents.
Authors: Parthasarathy, Sujaya; Kline-Simon, Andrea H; Jones, Ashley; Hartman, Lauren; Saba, Katrina; Weisner, Constance; Sterling, Stacy
Pediatrics. 2021 01;147(1).
Premature mortality associated with severe mental illness or substance use disorder in an integrated health care system
Research has reported shortened lifespans (by 15-30 years) for those with severe mental illness (SMI) or substance use disorder (SUD), particularly among public mental health treatment consumers. We assessed SMI- and SUD-associated mortality in the understudied setting of a large, nonprofit integrated health care system. This retrospective cohort study examined 2010-2017 health system and death records for 564,592 adult patients. Half had SMI/SUD diagnosis; half were a demographically matched comparison group without SMI, other mental health, or SUD diagnoses. We estimated mortality risks, adjusting for demographic and physical health factors. Having SMI or SUD was associated with higher odds of death (adjusted odds ratio = 1.87) and an average 6.3 years of earlier death relative to comparison individuals. Co-occurring SMI and SUD conferred higher mortality risk from major natural and unnatural causes than did SMI with no SUD. Some indicators of premature mortality were lower than those reported for U.S. public mental health consumers, but risk level varied widely by diagnosis. While patients’ having insurance and broad access to care may lower risk, access to care may be insufficient to overcome the many patient-, provider-, and system-level factors contributing to poor physical health in SMI and SUD.
Authors: Iturralde, Esti; Slama, Natalie; Kline-Simon, Andrea H; Young-Wolff, Kelly C; Mordecai, Don; Sterling, Stacy A
Gen Hosp Psychiatry. 2021 Jan-Feb;68:1-6. Epub 2020-11-10.
HIV Stigma and Its Associations with Longitudinal Health Outcomes Among Persons Living with HIV with a History of Unhealthy Alcohol Use
This study examined the demographic and clinical correlates of HIV stigma and evaluated how HIV stigma was associated with physical and mental health outcomes one year later in a primary-care based cohort of persons living with HIV (PLHIV; N = 584). HIV stigma was measured using a modified Berger HIV stigma scale, which includes four subscales: (1) personalized stigma; (2) disclosure concerns; (3) negative self-image; and (4) concerns around public attitudes towards PLHIV. Physical and mental health were assessed using the 12-item short form survey (SF-12). Compared to whites, African Americans were more likely to have higher personalized stigma scores (adjusted prevalence ratio [aPR] 1.54 [95% confidence interval 1.10-2.15]), disclosure concerns (aPR 1.40 [1.03-1.92]), and concerns with public attitudes about PLHIV (aPR 1.61 [1.11-2.34]). Hispanic/Latinx participants were more likely to have concerns around public attitudes towards PLHIV (aPR 1.50 [1.11-2.02]) than whites. Compared to men, women were more likely to have higher negative self-image scores (aPR 1.50 [1.08-2.08]). Higher stigma scores were associated with poorer subsequent self-reported physical and mental health functional status. Our findings highlight the substantial need for addressing HIV stigma, particularly among minority subgroups. El objetivo de este estudio era examinar la correlación del estigma del VIH con aspectos demográficos y clínicos. Se buscaba evaluar la asociación del estigma del VIH con los efectos de la salud física y mental luego de un año en un cohorte de personas viviendo con VIH (PVV; N = 584) provenientes de una clínica de servicios primarios. El estigma del VIH se midió utilizando la escala modificada de estigma del VIH de Berger que incluye cuatro sub-escalas: (1) estigma personalizado; (2) preocupaciones por revelación de diagnóstico; (3) auto-imagen negativa; y (4) preocupaciones acerca de actitudes hacia PVV. La salud física y mental fue evaluada utilizando una encuesta corta de 12 ítems. En comparación con las personas blancas, entre las personas Afroamericanas había más probabilidad de obtener una mayor puntuación en las escalas de estigma personalizado (razón de prevalencia ajustada [aRP] 1.54 [95% intervalo de confianza 1.10–2.15]), preocupaciones por revelación de diagnóstico (aRP 1.40 [1.03–1.92]), y preocupacionespor actitudes negativas hacia PVV (aRP 1.61 [1.11–2.34]). Participantes Hispanos/Latinos tenían más probabilidad de tener preocupaciones por las actitudes negativas hacia PVV (aRP 1.50 [1.11–2.02]) en comparación con personas blancas. En comparación con los hombres, las mujeres tenían mayor probabilidad de tener un resultado más alto en la escala de auto-imagen negativa (aRP 1.50 [1.08–2.08]). Resultados mayores estuvieron asociados a estatus más pobres de funcionalidad de salud física y mental. Nuestros resultados destacan la necesidad substancial de atender asuntos de estigma por el VIH, particularmente en grupos minoritarios.
Authors: Hojilla JC; Santiago-Rodriguez EI; Sterling S; Williams EC; Leyden W; Hare CB; Silverberg MJ; Satre DD
AIDS Behav. 2021 Jan;25(1):215-224.
A Telemedicine Approach to Increase Treatment of Alcohol Use Disorder in Primary Care: A Pilot Feasibility Study
Unhealthy drinking is a leading threat to health, yet few people with alcohol use disorder (AUD) receive treatment. This pilot tested the feasibility of addiction medicine video consultations in primary care for improving AUD medication adoption and specialty treatment initiation. Primary care providers (PCPs) received training and access to on-call addiction medicine consultations. Feasibility measures were training attendance, intention to use the service and/or AUD pharmacotherapy, and user feedback. Secondary outcomes were utilization, prescription and treatment initiation rates, and case reports. χ2 tests were used to compare prescription and treatment initiation rates for consult recipients and non-recipients. Ninety-one PCPs (71.1%) attended a training, and 60 (65.9%) provided feedback. Of those, 37 (64.9%) mentioned pharmacotherapy and 41 (71.9%) intended to use the video consult service. Of 27 users, 19 provided feedback; 12 (63.1%) rated its value at 8 or above, on a scale of 1 to 10 (average 6.9). The most useful aspect was immediacy, and users wanted an easier workflow and increased consultant availability. Of 32 patients who received a consult, 11 (34.4%) were prescribed naltrexone, versus 43 (6.4%) of non-recipients (P < 0.0001); 11 (34.4%) initiated specialty treatment, versus 105 (19.7%) of non-recipients (P < 0.05). PCP training attendance and feedback suggest that an addiction telemedicine consult service would be valuable to PCPs and might increase AUD medication uptake and specialty addiction treatment initiation. However, future research should include significant modifications to the piloted telemedicine model: robust staffing and simpler, more flexible methods for PCPs to obtain consults.
Authors: Leibowitz A; Satre DD; Lu W; Weisner C; Corriveau C; Gizzi E; Sterling S
J Addict Med. 2021 Jan-Feb 01;15(1):27-33.
Functional deficit in hippocampal activity during fear extinction recall in the single prolonged-stress model of PTSD in male rats.
To interrogate whether altered function of the hippocampal-mPFC circuit underlies the deficit in fear extinction recall in rats subjected to single-prolonged stress (SPS), changes in brain region-specific metabolic rate were measured in male rats (control and SPS treated). Brain region metabolic rates were quantified using uptake of
Authors: Winters, Jesse J;Rodriguez, Elizabeth;Liberzon, Israel;et al.
Behav Brain Res. 2021 Jan 01;396:112902. doi: 10.1016/j.bbr.2020.112902. Epub 2020 Sep 11.
Response by Flint et al to Letter Regarding Article, “Risk of Distal Embolization From tPA (Tissue-Type Plasminogen Activator) Administration Prior to Endovascular Stroke Treatment”
Authors: Flint AC; Avins AL; Nguyen-Huynh MN
Stroke. 2021 Jan;52(1):e39-e40. Epub 2020-12-28.
Genetic ancestry, skin pigmentation, and the risk of cutaneous squamous cell carcinoma in Hispanic/Latino and non-Hispanic white populations
Although cutaneous squamous cell carcinoma (cSCC) is one of the most common malignancies in individuals of European ancestry, the incidence of cSCC in Hispanic/Latinos is also increasing. cSCC has both a genetic and environmental etiology. Here, we examine the role of genetic ancestry, skin pigmentation, and sun exposure in Hispanic/Latinos and non-Hispanic whites on cSCC risk. We observe an increased cSCC risk with greater European ancestry (P = 1.27 × 10-42) within Hispanic/Latinos and with greater northern (P = 2.38 × 10-65) and western (P = 2.28 × 10-49) European ancestry within non-Hispanic whites. These associations are significantly, but not completely, attenuated after considering skin pigmentation-associated loci, history of actinic keratosis, and sun-protected versus sun-exposed anatomical sites. We also report an association of the well-known pigment variant Ala111Thr (rs1426654) at SLC24A5 with cSCC in Hispanic/Latinos. These findings demonstrate a strong correlation of northwestern European genetic ancestry with cSCC risk in both Hispanic/Latinos and non-Hispanic whites, largely but not entirely mediated through its impact on skin pigmentation.
Authors: Jorgenson, Eric; Choquet, Hélène; Yin, Jie; Hoffmann, Thomas J; Banda, Yambazi; Kvale, Mark N; Risch, Neil; Schaefer, Catherine; Asgari, Maryam M
Commun Biol. 2020 12 14;3(1):765. Epub 2020-12-14.
Factors associated with readiness to quit smoking among young adults enrolled in a Facebook-based tobacco and alcohol intervention study
Young adults who smoke cigarettes often report heavy episodic drinking (HED) and co-use of other psychoactive substances which may complicate efforts to quit cigarette smoking. The current study examined factors associated with readiness to quit cigarette smoking among young adults who smoke and engage in HED. One hundred seventy-nine young adults aged 18 to 25 who reported regular cigarette smoking and past month HED enrolled in the 90-day Facebook-based Smoking Tobacco and Drinking (STAND) intervention study. Analyses compared baseline differences in patterns of cigarette smoking and alcohol and cannabis use, thoughts about abstinence, use of nicotine replacement therapy (NRT), sociodemographic characteristics, and other health behaviors between participants who were ready to quit cigarette smoking in the next 30 days and those who were not. Participants were 40.2% female, 49.7% male, 10.1% non-binary, and 80.4% Non-Hispanic White. They reported on average moderate nicotine dependence (FTCD), moderate risk for alcohol use disorder (AUDIT), and occasional or regular cannabis use. Readiness to quit cigarette smoking in the next 30 days (33.5%) was positively associated with age (p = .021), NRT use in the past 30 days (p = .037) and perceived importance to also reduce alcohol use (p = .033). Findings indicate that readiness to quit cigarette smoking among young adults who drink is positively associated with importance to reduce alcohol use, but not with use patterns or levels of dependence. Interventions addressing polysubstance use may be better suited to help young adults reduce or quit cigarette smoking once they signal readiness for behavior change.
Authors: Maier, Larissa J; Ramo, Danielle E; Kaur, Manpreet; Meacham, Meredith C; Satre, Derek D
Addict Behav. 2020 12;111:106524. Epub 2020-06-27.
Telepsychiatry, Hospitals, and the COVID-19 Pandemic
Calls for social distancing amid the COVID-19 pandemic have renewed attention on the utility of telepsychiatry. Although considerable evidence supports use of telepsychiatry in outpatient settings, telepsychiatry in hospitals is less studied and less developed. The COVID-19 pandemic may lead to rapid adoption of telepsychiatry by hospitals, and this column explores opportunities hospital-based telepsychiatry offers for staffing, patient and staff safety, social connection, and real-time responsiveness. Because hospital-based telepsychiatry brings unique challenges compared with outpatient telepsychiatry, this column also proposes a research agenda for studying and supporting adoption of these technologies in hospital settings.
Authors: Morris, Nathaniel P; Hirschtritt, Matthew E
Psychiatr Serv. 2020 12 01;71(12):1309-1312. Epub 2020-09-16.
Treatment for Anxiety and Substance Use Disorders During the COVID-19 Pandemic: Challenges and Strategies
: The COVID-19 pandemic is likely to exacerbate existing anxiety and substance use disorders (SUDs) and increase vulnerability among individuals previously free of these conditions. Numerous pandemic-related stressors-coronavirus infection fears, social distancing and isolation, activity restrictions, financial insecurity and unemployment, caregiving or childcare responsibilities-place a substantial burden both on the general population and on many health care providers. Anxiety symptoms such as worry, tension, irritability, difficulty concentrating, and sleep disruption are increasingly prevalent. For individuals in SUD treatment, anxiety can complicate efforts to achieve treatment goals. In this commentary, we outline the potential impact of anxiety on substance use problems during the COVID-19 crisis and describe key behavioral, pharmacological, and digital health treatment considerations. We highlight populations of special concern due to heightened vulnerability and challenges accessing services, strategies to support health care providers, and directions for future research.
Authors: Satre, Derek D; Iturralde, Esti; Ghadiali, Murtuza; Young-Wolff, Kelly C; Campbell, Cynthia I; Leibowitz, Amy S; Sterling, Stacy A
J Addict Med. 2020 12;14(6):e293-e296.
Recruitment, retention, and adherence in a randomized feasibility trial of mindfulness-based stress reduction for patients with migraine
Increasing evidence demonstrates effectiveness of Mindfulness-Based Stress Reduction (MBSR) for pain-related and functional disorders. In order to conduct successful and efficient trials of MBSR, evidence regarding the relative performance of strategies to improve recruitment, retention, and adherence is required, but few studies have examined these issues specifically. In preparation for a fully powered trial, we conducted a 2-arm, parallel comparison randomized controlled feasibility trial of MBSR vs. usual-care for 60 patients with migraine headache. Two large U.S. health systems in Northern California. MBSR is an 8-week classroom-based intervention that combines mindfulness meditation and yoga, with didactic presentations about stress psychology and group process/experiential education. Participants received the intervention at their choice of one of several existing, vetted community-based classes. Successful recruitment was defined a priori as 18 participants within any 9-week period or 60 participants enrolled within a 36-week period. We considered participants adherent to the intervention if they attended at least 5 of the 8 weekly classes and the day-long retreat. We successfully enrolled 18 participants within a 7-week period, however, we did not attain our second goal of recruiting 60 participants within a 36-week period. Sixty-eight percent of our participants were adherent to the intervention. We found that close monitoring of recruitment activities, flexibility in protocol modifications, and integration within the delivery system were crucial factors for successful participant recruitment, retention, and adherence in mindfulness research.
Authors: Law, Heather; Avins, Andrew; Stahl, Robert; Goodreau, Michelle; Jacobson, Alice; Sudat, Sylvia; Pressman, Alice
Complement Ther Med. 2020 Dec;55:102610. Epub 2020-11-04.
Associations Between Psychiatric Disorders and Alcohol Consumption Levels in an Adult Primary Care Population
Unhealthy alcohol use frequently co-occurs with psychiatric disorders; however, little is known about the relationship between psychiatric disorders and alcohol consumption levels. Understanding varying levels of unhealthy alcohol use among individuals with a variety of psychiatric disorders in primary care would provide valuable insight for tailoring interventions. We conducted a cross-sectional study of 2,720,231 adult primary care patients screened for unhealthy alcohol use between 2014 and 2017 at Kaiser Permanente Northern California, using electronic health record data. Alcohol consumption level was classified as no reported use, low-risk use, and unhealthy use, per National Institute on Alcohol Abuse and Alcoholism guidelines. Unhealthy use was further differentiated into mutually exclusive groups: exceeding only daily limits, exceeding only weekly limits, or exceeding both daily and weekly limits. Multivariable multinomial logistic regression models were fit to examine associations between 8 past-year psychiatric disorders (depression, bipolar disorder, anxiety disorder, obsessive-compulsive disorder, schizophrenia, schizoaffective disorder, anorexia nervosa, and bulimia nervosa) and alcohol consumption levels, adjusting for sociodemographic and health characteristics. In the full sample [53% female, 48% White, mean (SD) age = 46 (18) years], patients with psychiatric disorders (except eating disorders), compared to those without, had lower odds of reporting low-risk and unhealthy alcohol use relative to no use. Among patients who reported any alcohol use (n = 861,427), patients with depression and anxiety disorder, compared to those without, had higher odds of exceeding only weekly limits and both limits; patients with bulimia nervosa were also more likely to exceed both limits. Findings suggest that patients with anxiety disorder, depression, and bulimia nervosa who drink alcohol are more likely to exceed recommended limits, increasing risk of developing more serious problems. Health systems and clinicians may wish to consider implementing more robust screening, assessment, and intervention approaches to support these vulnerable subgroups in limiting their drinking.
Authors: Palzes, Vanessa A; Parthasarathy, Sujaya; Chi, Felicia W; Kline-Simon, Andrea H; Lu, Yun; Weisner, Constance; Ross, Thekla B; Elson, Joseph; Sterling, Stacy A
Alcohol Clin Exp Res. 2020 12;44(12):2536-2544. Epub 2020-11-05.
Health System-Based Unhealthy Alcohol Use Screening and Treatment Comparing Demographically-Matched Participants With and Without HIV
Unhealthy alcohol use among persons living with HIV (PLWH) is linked to significant morbidity, and use of alcohol services may differ by HIV status. Our objective was to compare unhealthy alcohol use screening and treatment by HIV status in primary care. Cohort study of adult (≥18 years) PLWH and HIV-uninfected participants frequency matched 20:1 to PLWH by age, sex, and race/ethnicity who were enrolled in a large integrated healthcare system in the United States, with information ascertained from an electronic health record. Outcomes included unhealthy alcohol screening, prevalence, provider-delivered brief interventions, and addiction specialty care visits. Other predictors included age, sex, race/ethnicity, neighborhood deprivation index, depression, smoking, substance use disorders, Charlson comorbidity index, prior outpatient visits, insurance type, and medical facility. Cox proportional hazards models were used to compute hazard ratios (HR) for the outcomes of time to unhealthy alcohol use screening and time to first addiction specialty visit. Poisson regression with robust standard errors was used to compute prevalence ratios (PR) for other outcomes. 11,235 PLWH and 227,320 HIV-uninfected participants were included. By 4.5 years after baseline, most participants were screened for unhealthy alcohol use (85% of PLWH and 93% of HIV-uninfected), but with a lower rate among PLWH (adjusted HR 0.84, 95% CI 0.82 to 0.85). PLWH were less likely, compared with HIV-uninfected participants, to report unhealthy drinking among those screened (adjusted PR 0.74, 95% CI 0.69 to 0.79), and among those who screened positive, less likely to receive brief interventions (adjusted PR 0.82, 95% CI 0.75 to 0.90), but more likely (adjusted HR 1.7, 95% CI 1.2 to 2.4) to have an addiction specialty visit within 1 year. Unhealthy alcohol use was lower in PLWH, but the treatment approach by HIV status differed. PLWH reporting unhealthy alcohol use received less brief interventions and more addiction specialty care than HIV-uninfected participants.
Authors: Silverberg, Michael J; Alexeeff, Stacey E; Lam, Jennifer O; Weisner, Constance M; Sterling, Stacy A; Satre, Derek D; et al.
Alcohol Clin Exp Res. 2020 12;44(12):2545-2554. Epub 2020-11-10.
Health care utilization and HIV clinical outcomes among newly enrolled patients following Affordable Care Act implementation in a California integrated health system: a longitudinal study
The Affordable Care Act (ACA) has increased insurance coverage for people with HIV (PWH) in the United States. To inform health policy, it is useful to investigate how enrollment through ACA Exchanges, deductible levels, and demographic factors are associated with health care utilization and HIV clinical outcomes among individuals newly enrolled in insurance coverage following implementation of the ACA. Among PWH newly enrolled in an integrated health care system (Kaiser Permanente Northern California) in 2014 (N = 880), we examined use of health care and modeled associations between enrollment mechanisms (enrolled in a Qualified Health Plan through the California Exchange vs. other sources), deductibles (none, $1-$999 and > = $1000), receipt of benefits from the California AIDS Drug Assistance Program (ADAP), demographic factors, and three-year patterns of health service utilization (primary care, psychiatry, substance treatment, emergency, inpatient) and HIV outcomes (CD4 counts; viral suppression at HIV RNA < 75 copies/mL). Health care use was greatest immediately after enrollment and decreased over 3 years. Those with high deductibles were less likely to use primary care (OR = 0.64, 95% CI = 0.49-0.84, p < 0.01) or psychiatry OR = 0.59, 95% CI = 0.37, 0.94, p = 0.03) than those with no deductible. Enrollment via the Exchange was associated with fewer psychiatry visits (rate ratio [RR] = 0.40, 95% CI = 0.18-0.86; p = 0.02), but ADAP was associated with more psychiatry visits (RR = 2.22, 95% CI = 1.24-4.71; p = 0.01). Those with high deductibles were less likely to have viral suppression (OR = 0.65, 95% CI = 0.42-1.00; p = 0.05), but ADAP enrollment was associated with viral suppression (OR = 2.20, 95% CI = 1.32-3.66, p < 0.01). Black (OR = 0.35, 95% CI = 0.21-0.58, p < 0.01) and Hispanic (OR = 0.50, 95% CI = 0.29-0.85, p = 0.01) PWH were less likely to be virally suppressed. In this sample of PWH newly enrolled in an integrated health care system in California, findings suggest that enrollment via the Exchange and higher deductibles were negatively associated with some aspects of service utilization, high deductibles were associated with worse HIV outcomes, but support from ADAP appeared to help patients achieve viral suppression. Race/ethnic disparities remain important to address even among those with access to insurance coverage.
Authors: Satre, Derek D; Parthasarathy, Sujaya; Silverberg, Michael J; Horberg, Michael; Young-Wolff, Kelly C; Williams, Emily C; Volberding, Paul; Campbell, Cynthia I
BMC Health Serv Res. 2020 Nov 11;20(1):1030. Epub 2020-11-11.
Pregnancy does not modify the risk of MS in genetically susceptible women
To use the case-only gene-environment (G [Formula: see text] E) interaction study design to estimate interaction between pregnancy before onset of MS symptoms and established genetic risk factors for MS among White adult females. We studied 2,497 female MS cases from 4 cohorts in the United States, Sweden, and Norway with clinical, reproductive, and genetic data. Pregnancy exposure was defined in 2 ways: (1) [Formula: see text] live birth pregnancy before onset of MS symptoms and (2) parity before onset of MS symptoms. We estimated interaction between pregnancy exposure and established genetic risk variants, including a weighted genetic risk score and both HLA and non-HLA variants, using logistic regression and proportional odds regression within each cohort. Within-cohort associations were combined using inverse variance meta-analyses with random effects. The case-only G × E independence assumption was tested in 7,067 individuals without MS. Evidence for interaction between pregnancy exposure and established genetic risk variants, including the strongly associated HLA-DRB1*15:01 allele and a weighted genetic risk score, was not observed. Results from sensitivity analyses were consistent with observed results. Our findings indicate that pregnancy before symptom onset does not modify the risk of MS in genetically susceptible White females.
Authors: Adams, Cameron J; Schaefer, Catherine; Barcellos, Lisa F; et al.
Neurol Neuroimmunol Neuroinflamm. 2020 11;7(6). Epub 2020-10-09.
Changing Provider PSA Screening Behavior Using Best Practice Advisories: Interventional Study in a Multispecialty Group Practice
Most guidelines recommend against PSA-based screening for prostate cancer in men ≥ 70 years of age. Adherence to these guidelines is variable. To determine whether the use of a “Best Practice Advisory” (BPA) intervention within the electronic medical record (EMR) system can alter the rate of PSA screening in men ≥ 70 years of age. This is an interventional study spanning the years 2013 through 2017, in men ≥ 70 years of age in Kaiser Permanente Northern California with no prior history of prostate cancer. The BPA intervention was activated in the EMR system on October 15, 2015, with no prior notice or education. Integrated healthcare system including all Kaiser Permanente Northern California facilities. A population-based sample that included all male members ≥ 70 years of age without a history of prostate cancer. The main outcome was the rate of PSA testing in men ≥ 70 years of age. We compared the rates of PSA testing between the pre-BPA period (January 1, 2013-October 14, 2015) and the post-BPA period (October 15, 2015-December 31, 2017). An interrupted time series analysis of PSA ordering rates was performed. Following the 2015 BPA intervention, screening rates substantially declined from 36.0 per 100 person-years to 14.9 per 100 person-years (rate ratio = 0.415; 95% CI: 0.410-0.419). The effect of the BPA was comparable among all patient races and ordering provider specialties. The interrupted time series analysis showed a rapid, large, and sustained drop in the rate of PSA ordering, and much less temporal variation in test ordering after activation of the BPA. Following activation of a BPA within the EMR, the rates of inappropriate PSA testing significantly declined by 58.5% in men ≥ 70 years of age and temporal variation was reduced.
Authors: Presti, Joseph; Alexeeff, Stacey; Horton, Brandon; Prausnitz, Stephanie; Avins, Andrew L
J Gen Intern Med. 2020 11;35(Suppl 2):796-801. Epub 2020-10-26.
Healthcare utilization of individuals with substance use disorders following Affordable Care Act implementation in a California healthcare system
Practitioners expected the Affordable Care Act (ACA) to increase availability of health services and access to treatment for Americans with substance use disorders (SUDs). Yet research has not examined the associations among ACA enrollment mechanisms, deductibles, and the use of SUD treatment and other healthcare services. Understanding these relationships can inform future healthcare policy. We conducted a longitudinal analysis of patients with SUDs newly enrolled in the Kaiser Permanente Northern California health system in 2014 (N = 6957). Analyses examined the likelihood of service utilization (primary care, specialty SUD treatment, psychiatry, inpatient, and emergency department [ED]) over three years after SUD diagnosis, and associations with enrollment mechanisms (ACA Exchange vs. other), deductibles (none, $1-$999 [low] and ≥$1000 [high]), membership duration, psychiatric comorbidity, and demographic characteristics. We also evaluated whether the enrollment mechanism moderated the associations between deductible limits and utilization likelihood. Service utilization was highest in the 6 months after SUD diagnosis, decreased in the following 6 months, and remained stable in years 2-3. Relative to patients with no deductible, those with a high deductible had lower odds of using all health services except SUD treatment; associations with primary care and psychiatry were strongly negative among Exchange enrollees. Among non-Exchange enrollees, patients with deductibles were more likely than those without deductibles to receive SUD treatment. Exchange enrollment compared to other mechanisms was associated with less ED use. Psychiatric comorbidity was associated with greater use of all services. Nonwhite patients were less likely to initiate SUD and psychiatry treatment. Higher deductibles generally were associated with use of fewer health services, especially in combination with enrollment through the Exchange. The role of insurance factors, psychiatric comorbidity and race/ethnicity in health services for people with SUDs are important to consider as health policy evolves.
Authors: Satre, Derek D; Palzes, Vanessa A; Young-Wolff, Kelly C; Parthasarathy, Sujaya; Weisner, Constance; Guydish, Joseph; Campbell, Cynthia I
J Subst Abuse Treat. 2020 11;118:108097. Epub 2020-08-04.
Elevated Depressive Symptoms and the Risk of Stroke among the Mexican Older Population
Several longitudinal studies in high-income countries suggest that depression increases stroke risk. However, few prior studies have evaluated this association in low- and middle-income countries (LMICs), where rapidly aging populations may have markedly different vascular risk profiles. Prospective cohort study. The Mexican Health and Aging Study is a national population-based study of older adults in Mexico. A total of 10,693 Mexican adults aged 50 and older enrolled in 2001 with no history of prior stroke. Depressive symptoms were assessed with a modified 9-item Centers for Epidemiologic Studies Depression Scale (elevated depressive symptom cutoff ≥5) in 2001 and 2003. We evaluated associations between baseline and short-term (2-year) changes in elevated depressive symptoms (categorized as stable low, recently remitted, recent-onset, or stable high symptoms) with incident self-reported or next-of-kin reported doctor-diagnosed stroke through 2015 using Cox proportional hazards models and sensitivity analyses applying inverse probability weights. Over an average follow-up of 11.4 years (standard deviation = 4.2), 10,693 respondents reported 546 incident strokes. Individuals with elevated baseline depressive symptoms experienced a moderately higher hazard of incident stroke (hazard ratio [HR] = 1.13; 95% confidence interval [CI] = .95-1.36) compared with those without elevated baseline depressive symptoms. In analyses of short-term changes in elevated depressive symptoms (n = 8,808; 414 incident stokes), participants with recent-onset (HR = 1.38; 95% CI = 1.06-1.81) or stable high (HR = 1.42; 95% CI = 1.10-1.84) elevated depressive symptoms had a greater hazard of incident stroke compared to those with stable low/no depressive symptoms, whereas recently remitted (HR = 1.01; 95% CI = .74-1.37) symptoms was not associated with stroke hazard. Strategies to reduce depressive symptoms merit evaluation as approaches to prevent stroke in middle-income countries. Findings are similar to those in high-income countries but should be replicated in other LMICs.
Authors: Meza, Erika; Eng, Chloe W; Sáenz, Joseph L; Gilsanz, Paola; Glymour, Medellena Maria; Torres, Jacqueline M
J Am Geriatr Soc. 2020 11;68(11):2579-2586. Epub 2020-09-02.
Natural history of achondroplasia: A retrospective review of longitudinal clinical data
There are limited data on the longitudinal frequency and severity of the symptoms and complications of achondroplasia. We undertook a retrospective electronic chart review of 114 patients to develop a more thorough understanding of the lifetime impact of achondroplasia. Craniocervical stenosis (involving the foramen magnum with or without cervical vertebrae C1 and/or C2) was noted in nearly 50% of patients with craniovertebral junction imaging; however, corrective decompression surgery was only needed in 6% of patients. No children in our cohort died at 4 years of age or under. Kyphosis was present in most patients but usually resolved in early childhood. Cervical and lumbar stenosis were diagnosed in children and adults while, genu varum, elbow contractures, and radial head dislocations were identified during childhood. Central sleep apnea and obstructive sleep apnea were present in children, while the diagnosis of obstructive sleep apnea was shown to recur in adulthood. Cardiovascular risk factors were present in only 7% of patients. A range of mental health disorders were identified, with most diagnoses being made before 18 years of age. Our data show that achondroplasia has a significant impact on patients’ physical health, and complications continue to be reported and require intervention throughout patients’ lifetimes. This highlights the need for continuous support beyond pediatric care, by adult care clinicians experienced with managing the long-term complications of achondroplasia.
Authors: Okenfuss, Ericka; Moghaddam, Billur; Avins, Andrew L
Am J Med Genet A. 2020 11;182(11):2540-2551. Epub 2020-08-31.
Prospective development of a prostate cancer risk calculator in a racially diverse population: The Kaiser Permanente Prostate Cancer Risk Calculator
To prospectively develop a prostate cancer (CaP) risk calculator in a racially diverse population. All patients referred for prostate biopsy due to an elevated prostate-specific antigen or abnormal digital rectal exam in a 19-months period at Kaiser Permanente Northern California underwent a standardized systematic, ultrasound-guided biopsy scheme (14-cores for initial biopsy, 18-20 cores for repeat biopsy). All pertinent clinical variables were prospectively collected. The highest Gleason score for each patient was recorded for all positive biopsies. We used a split sample design to develop and validate 3 multivariable prediction models using multinomial logistic regression with the least absolute shrinkage and selection operator. All models included these core variables: age, race, prostate-specific antigen, prior biopsy status, body mass index, and family history of CaP. Model 1 included only the core variables, Model 2 added digital rectal exam, and Model 3 added digital rectal exam and prostate volume. We considered 3 outcomes: high-grade disease (Gleason score ≥7), low-grade disease (Gleason score = 6), and no cancer. Predictive discrimination was quantified using the c-statistic. Complete data were available for 2,967 patients. Cancer was found in 50% of patients: of these, 58% were Gleason score ≥7 and 42% were low grade. Compared to Caucasians, African Americans were at a higher risk while Asians and Hispanics were at a lower risk for overall and high-grade cancer detection. The number of prior negative biopsies was also protective for these outcomes. The c-statistics for Model 1, 2, and 3 to predict high-grade disease vs. low-grade or no cancer were 0.76, 0.79, and 0.85, respectively. The c-statistics for Model 1, 2, and 3 to predict any CaP vs. no cancer were 0.69, 0.70, and 0.79, respectively. All models were well calibrated for all outcomes. In men with elevated PSA levels, our calculator provides useful information that may enhance the shared decision-making process regarding the need for biopsy.
Authors: Presti J; Alexeeff S; Horton B; Prausnitz S; Avins AL
Urol Oncol. 2020 11;38(11):847.e1-847.e8. Epub 2020-06-12.
Understanding Racial/Ethnic Disparities in Physical Performance in Mid-Life Women: Findings from SWAN (Study of Women’s Health Across the Nation)
Evaluate degree to which racial/ethnic differences in physical performance are mediated by sociodemographic, health, behavioral, and psychosocial factors. Physical performance was evaluated using a decile score derived from grip strength, timed 4 m walk, and timed repeat chair stand in 1,855 African American, Caucasian, Chinese, Hispanic, and Japanese women, mean age = 61.8 (SD = 2.7) in the Study of Women’s Health Across the Nation. Mediators included education, financial strain, comorbidities, pain, body mass index (BMI), physical activity, and perceived stress. Structural equation models provided estimates of the total difference in physical performance between Caucasians and each race/ethnic groups and differences due to direct effects of race/ethnicity and indirect effects through mediators. The mean decile score for Caucasian women was 16.9 (SD = 5.6), 1.8, 2.6, and 2.1 points higher than the model-estimated scores in African Americans, Hispanics and Chinese, respectively, and 1.3 points lower than the Japanese. Differences between Caucasians and the Chinese and Japanese were direct effects of race/ethnicity whereas in African Americans and Hispanics 75% or more of that disparity was through mediators, particularly education, financial strain, BMI, physical activity, and pain. Addressing issues of poverty, racial inequality, pain, and obesity could reduce some racial/ethnic disparity in functional limitations as women age.
Authors: Sternfeld B; Colvin A; Stewart A; Appelhans BM; Cauley JA; Dugan SA; El Khoudary SR; Greendale GA; Strotmeyer E; Karvonen-Gutierrez C
J Gerontol B Psychol Sci Soc Sci. 2020 10 16;75(9):1961-1971.
Smoking cessation treatment for individuals with comorbid diabetes and serious mental illness in an integrated health care delivery system
Smoking is a significant modifiable risk factor for mortality for persons with serious mental illness (SMI), who have a life expectancy 15-20 years shorter than the general population. Individuals with SMI and comorbid diabetes who are smokers face an even higher risk of cardiovascular complications and early death. Yet despite high rates of smoking among people with SMI, tobacco cessation interventions have not been broadly offered to this population. We conducted a retrospective cohort study using electronic health records from 2014 in a large integrated care delivery system to examine whether use of smoking cessation pharmacotherapy among smokers with type 2 diabetes varies by serious mental illness (SMI) diagnosis. We analyzed smoking cessation medication prescription fills among adult smokers with diabetes, comparing those with SMI (N = 634) and without SMI (N = 18,021). Risk ratios were adjusted for age, gender, race, urban area type, and medical facility. Of the SMI group, 19.09% filled at least one smoking cessation prescription compared to 9.73% of the non-SMI group (adjusted risk ratio 1.80 [95% CI 1.52-2.13]; p < .001). For the SMI group, primary care providers wrote 80.24% of prescriptions, while psychiatrists wrote 8.81% of prescriptions. These findings offer an example of a delivery system with higher uptake of smoking cessation pharmacotherapy among people with SMI than without SMI, and highlight the opportunity to provide more smoking cessation interventions in mental health care settings.
Authors: Hwong AR; Schmittdiel J; Schillinger D; Newcomer JW; Essock S; Zhu Z; Dyer W; Young-Wolff KC; Mangurian C
Addict Behav. 2020 Oct 14:106697.
Identification of 31 loci for mammographic density phenotypes and their associations with breast cancer risk
Mammographic density (MD) phenotypes are strongly associated with breast cancer risk and highly heritable. In this GWAS meta-analysis of 24,192 women, we identify 31 MD loci at P < 5 × 10-8, tripling the number known to 46. Seventeen identified MD loci also are associated with breast cancer risk in an independent meta-analysis (P < 0.05). Mendelian randomization analyses show that genetic estimates of dense area (DA), nondense area (NDA), and percent density (PD) are all significantly associated with breast cancer risk (P < 0.05). Pathway analyses reveal distinct biological processes involving DA, NDA and PD loci. These findings provide additional insights into the genetic basis of MD phenotypes and their associations with breast cancer risk.
Authors: Sieh, Weiva; Alexeeff, Stacey E; Sakoda, Lori C; Risch, Neil; Habel, Laurel A; et al.
Nat Commun. 2020 10 09;11(1):5116. Epub 2020-10-09.
Risk Factors for Conversion of Hip Arthroscopy to Total Hip Arthroplasty: A Large Closed-Cohort Study
To evaluate risk factors for conversion of hip arthroscopy to total hip arthroplasty (THA) within 2 years in a closed patient cohort. This study was a case series of consecutive hip arthroscopy procedures from September 2008 to November 2018 in the electronic medical record of Kaiser Permanente Northern California. Patients were included with minimum 2-year follow-up or if they had conversion to THA within 2 years (the primary outcome) regardless of follow-up time. Patient characteristics at the time of the index arthroscopy were extracted; characteristics of patients who experienced the outcome event versus those who did not were compared by use of multivariable logistic regression models and receiver operating characteristic (ROC) curves. The mean follow-up time was 4.9 years (median 4.6, range 0.6 to 11.6). The mean age was 37.2 years (range 10 to 88), and 57% were female. During the follow-up period, 82 patients underwent a THA within 2 years of their arthroscopies (5.3%, 95% confidence interval 4.3% to 6.5%) after a median time of 9 months (interquartile range 5.9 to 14.4) after the initial arthroscopy. Increasing age was highly predictive of early THA conversion (area under the ROC curve = 0.78, P < .001). Although other predictors showed significant bivariable associations with early failure, body mass index (BMI), race, sex, and prior arthroscopy did not add meaningful independent predictive information. The risk of conversion to THA within 2 years after hip arthroscopy increased substantially with patient age at the time of the procedure. BMI, race, sex, and prior arthroscopy were not important independent predictors of conversion beyond the information contained in patient age. Level IV, therapeutic case series.
Authors: Allahabadi, Sachin; Hinman, Adrian D; Horton, Brandon H; Avins, Andrew L; Coughlan, Monica J; Ding, David Y
Arthrosc Sports Med Rehabil. 2020 Oct;2(5):e599-e605. Epub 2020-10-15.
Estimates of Workload Associated With Suicide Risk Alerts After Implementation of Risk-Prediction Model
Authors: Kline-Simon, Andrea H; Sterling, Stacy; Young-Wolff, Kelly; Simon, Gregory; Lu, Yun; Does, Monique; Liu, Vincent
JAMA Netw Open. 2020 10 01;3(10):e2021189. Epub 2020-10-01.
Pilot pragmatic randomized trial of mHealth mindfulness-based intervention for advanced cancer patients and their informal caregivers
Assess the feasibility of conducting a cluster randomized trial (RCT) comparing technology-delivered mindfulness-based intervention (MBI) programs against a waitlist control arm targeting advanced cancer patients and their informal caregivers. Two-arm cluster RCT within Kaiser Permanente Northern California (KPNC). We recruited patients with metastatic solid malignancies or hematological cancers and their informal caregivers. Intervention-group participants chose to use either a commercially available mindfulness app (10-20 minutes/day) or a webinar-based mindfulness course for 6 weeks. The waitlist control group received usual care. We assessed feasibility measures and obtained participant-reported data on quality-of-life (primary outcome) and distress outcomes (secondary) pre- and post-intervention. 103 patients (median age 67 years; 70% female; 81% White) and 39 caregivers (median age 66 years; 79% female; 69% White) were enrolled. Nearly all participants chose the mindfulness app over the webinar-based program. Among the participants in the intervention arm who chose the mobile-app program and completed the postintervention (6-week) survey, 21 (68%) patients and 7 (47%) caregivers practiced mindfulness at least 50% of the days during the 6-week study period. Seventy-four percent of intervention participants were “very” or “extremely” satisfied with the mindfulness program. We observed improvements in anxiety, quality of life, and mindfulness among patients in the intervention arm compared to those in the control group. We demonstrated the feasibility of conducting a cluster RCT of mHealth MBI for advanced cancer patients and their caregivers. Such remote interventions can be helpful particularly during the COVID-19 pandemic. This article is protected by copyright. All rights reserved.
Authors: Kubo, Ai; Kurtovich, Elaine; McGinnis, MegAnn; Aghaee, Sara; Altschuler, Andrea; Quesenberry, Charles; Kolevska, Tatjana; Liu, Raymond; Greyz-Yusupov, Natalya; Avins, Andrew
Psychooncology. 2020 Sep 26.
Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations
Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p < 5 × 10-9, including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 secretion levels in vitro. Fine-mapping prioritized variants annotated as functional and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EUR-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations and compared genetic architecture and the effect of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies.
Authors: Chen, Ming-Huei; Choquet, Hélène; Lettre, Guillaume; et al.
Cell. 2020 09 03;182(5):1198-1213.e14.
The Polygenic and Monogenic Basis of Blood Traits and Diseases
Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation.
Authors: Vuckovic, Dragana; Danesh, John; Soranzo, Nicole; et al.
Cell. 2020 09 03;182(5):1214-1231.e11.
Association of genetic risk for Alzheimer disease and hearing impairment
To test the hypothesis that incipient AD may adversely affect hearing and that hearing loss may adversely affect cognition we evaluated whether (1) genetic variants that increase AD risk also increase problem hearing and (2) genetic variants that increase hearing impairment risk do not influence cognition. UK Biobank participants without dementia aged 56+ with Caucasian genetic ancestry completed a Digit Triplets Test of speech-in-noise hearing (n = 80,074), self-reported problem hearing and hearing with background noise (n = 244,915) and completed brief cognitive assessments. A genetic risk score for AD (AD-GRS) was calculated as a weighted sum of 23 previously identified AD-related polymorphisms. A genetic risk score for hearing (hearing-GRS) was calculated using 3 previously identified polymorphisms related to hearing impairment. Using age-, sex-, and genetic ancestry-adjusted logistic and linear regression models, we evaluated (1) whether the AD-GRS predicted poor hearing and (2) whether the hearing-GRS predicted worse cognition. Poor speech-in-noise hearing (>-5.5 dB speech reception threshold; prevalence = 14%) was associated with lower cognitive scores (ß = -1.28; 95% CI: -1.54, -1.03). Higher AD-GRS was significantly associated with poor speech-in-noise hearing (OR = 1.06; 95% CI: 1.01, 1.11) and self-reported problems hearing with background noise (OR = 1.03; 95% CI: 1.00, 1.05). Hearing-GRS was not significantly associated with cognitive scores (ß = -0.05; 95% CI: -0.17, 0.07). Genetic risk for AD also influences speech-in-noise hearing. We failed to find evidence that genetic risk for hearing impairment affects cognition. AD disease processes or a shared etiology may cause speech-in-noise difficulty prior to dementia onset.
Authors: Brenowitz WD; Filshtein TJ; Yaffe K; Walter S; Ackley SF; Hoffmann TJ; Jorgenson E; Whitmer RA; Glymour MM
Neurology. 2020 Sep 02.
Associations of CYP2C9 and CYP2C19 pharmacogenetic variation with phenytoin-induced cutaneous adverse drug reactions
The role of cytochrome P450 (CYP)2C9 and CYP2C19 genetic variation in risk for phenytoin-induced cutaneous adverse drug events is not well understood independently of the human leukocyte antigen B (HLA-B)*15:02 risk allele. In the multi-ethnic resource for Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort, we identified 382 participants who filled a phenytoin prescription between 2005 and 2017. These participants included 21 people (5%) who self-identified as Asian, 18 (5%) as black, 29 (8%) as white Hispanic, and 308 (81%) as white non-Hispanic. We identified 264 (69%) CYP2C9*1/*1, 77 (20%) CYP2C9*1/*2, and 29 (8%) CYP2C9*1/*3. We also determined CYP2C19 genotypes, including 112 with the increased activity CYP2C19*17 allele. Using electronic clinical notes, we identified 32 participants (8%) with phenytoin-induced cutaneous adverse events recorded within 100 days of first phenytoin dispensing. Adjusting for age, sex, daily dose, and race/ethnicity, participants with CYP2C9*1/*3 or CYP2C9*2/*2 genotypes were more likely to develop cutaneous adverse events compared with CYP2C9*1/*1 participants (odds ratio 4.47; 95% confidence interval 1.64-11.69; P < 0.01). Among participants with low-intermediate and poor CYP2C9 metabolizer genotypes, eight (22%) who also had extensive and rapid CYP2C19 metabolizer genotypes experienced cutaneous adverse events, compared with none of those who also had intermediate CYP2C19 metabolizer genotypes (P = 0.17). Genetic variation reducing CYP2C9 metabolic activity may increase risk for phenytoin-induced cutaneous adverse events in the absence of the HLA-B*15:02 risk allele.
Authors: Fohner AE; Rettie AE; Thai KK; Ranatunga DK; Lawson BL; Liu VX; Schaefer CA
Clin Transl Sci. 2020 09;13(5):1004-1009. Epub 2020-04-18.
Are Substance Use and Bullying Perpetration Two Sides of the Same Coin?
Authors: Hirschtritt, Matthew E
J Adolesc Health. 2020 09;67(3):311-312.
Risk of Distal Embolization From tPA (Tissue-Type Plasminogen Activator) Administration Prior to Endovascular Stroke Treatment
In large artery occlusion stroke, both intravenous (IV) tPA (tissue-type plasminogen activator) and endovascular stroke treatment (EST) are standard-of-care. It is unknown how often tPA causes distal embolization, in which a procedurally accessible large artery occlusion is converted to a more distal and potentially inaccessible occlusion. We analyzed data from a decentralized stroke telemedicine program in an integrated healthcare delivery system covering 21 hospitals, with 2 high-volume EST centers. We captured all cases sent for EST and examined the relationship between IV tPA administration and the rate of distal embolization, the rate of target recanalization (modified Treatment in Cerebral Infarction scale 2b/3), clinical improvement before EST, and short-term and long-term clinical outcomes. Distal embolization before EST was quite common (63/314 [20.1%]) and occurred more often after IV tPA before EST (57/229 [24.9%]) than among those not receiving IV tPA (6/85 [7.1%]; P<0.001). Distal embolization was associated with an inability to attempt EST: after distal embolization, 26/63 (41.3%) could not have attempted EST because of the new clot location, while in cases without distal embolization, only 8/249 (3.2%) were unable to have attempted EST (P<0.001). Among patients who received IV tPA, 13/242 (5.4%) had sufficient symptom improvement that a catheter angiogram was not performed; 6/342 (2.5%) had improvement to within 2 points of their baseline NIHSS. At catheter angiogram, 2/229 (0.9%) of patients who had received tPA had complete recanalization without distal embolization. Both IV tPA and EST recanalization were associated with improved long-term outcome. IV tPA administration before EST for large artery occlusion is associated with distal embolization, which in turn may reduce the chance that EST can be attempted and recanalization achieved. At the same time, some IV tPA-treated patients show symptomatic improvement and complete recanalization. Because IV tPA is associated with both distal embolization and improved long-term clinical outcome, there is a need for prospective clinical trials testing the net benefit or harm of IV tPA before EST.
Authors: Flint, Alexander C; Avins, Andrew L; Nguyen-Huynh, Mai N; et al.
Stroke. 2020 09;51(9):2697-2704. Epub 2020-08-06.
Trends and correlates of self-reported alcohol and nicotine use among women before and during pregnancy, 2009-2017
To examine trends and correlates of frequency of self-reported alcohol and nicotine use among pregnant women. Cross-sectional study of 363,240 pregnancies from 2009 to 2017 screened for self-reported substance use at their first prenatal visit in Kaiser Permanente Northern California. Poisson regression with a log link function was used to estimate the annual prevalences of self-reported daily, weekly, and ≤ monthly alcohol and nicotine use, adjusting for socio-demographics. Generalized estimating equation models were used to estimate the adjusted odds ratios (aOR) of any self-reported prenatal alcohol or nicotine use among those who self-reported use in the year prior to pregnancy, by frequency of pre-pregnancy substance use and socio-demographics. The sample was 64 % non-White [mean (SD) age = 30.1 (5.6)]. From 2009-2017, alcohol use before pregnancy increased from 63.4%-65.9% (trend p-value = .008), and prenatal alcohol use decreased from 11.6%-8.8% (trend p-value<.0001). Nicotine use before pregnancy decreased from 12.7 % to 7.7 % (trend p-value<.0001), and prenatal use decreased from 4.3 % to 2.0 % (trend p-value<.0001). Trends by use frequency were similar to overall trends. The odds of continued use of alcohol and nicotine during pregnancy were higher among those who used daily or weekly (versus monthly or less) in the year before pregnancy and varied with socio-demographics. Prenatal alcohol and nicotine use decreased from 2009 to 2017. More frequent pre-pregnancy use predicted higher odds of prenatal use. Results suggest that interventions and education about the harms of prenatal substance use for frequent users prior to conception may reduce substance use during pregnancy.
Authors: Young-Wolff, Kelly C; Sarovar, Varada; Alexeeff, Stacey E; Adams, Sara R; Tucker, Lue-Yen; Conway, Amy; Ansley, Deborah; Goler, Nancy; Armstrong, Mary Anne; Weisner, Constance
Drug Alcohol Depend. 2020 09 01;214:108168. Epub 2020-07-15.
Body mass index versus bioelectrical impedance analysis for classifying physical function impairment in a racially diverse cohort of midlife women: the Study of Women’s Health Across the Nation (SWAN)
Body composition strongly influences physical function in older adults. Bioelectrical impedance analysis (BIA) differentiates fat mass from skeletal muscle mass, and may be more useful than body mass index (BMI) for classifying women on their likelihood of physical function impairment. This study tested whether BIA-derived estimates of percentage body fat (%BF) and height-normalized skeletal muscle mass (skeletal muscle mass index; SMI) enhance classification of physical function impairment relative to BMI. Black, White, Chinese, and Japanese midlife women (N = 1482) in the Study of Women’s Health Across the Nation (SWAN) completed performance-based measures of physical function. BMI (kg/m2) was calculated. %BF and SMI were derived through BIA. Receiver-operating characteristic (ROC) curve analysis, conducted in the overall sample and stratified by racial group, evaluated optimal cutpoints of BMI, %BF, and SMI for classifying women on moderate-severe physical function impairment. In the overall sample, a BMI cutpoint of ≥ 30.1 kg/m2 correctly classified 71.1% of women on physical function impairment, and optimal cutpoints for %BF (≥ 43.4%) and SMI (≥ 8.1 kg/m2) correctly classified 69% and 62% of women, respectively. SMI did not meaningfully enhanced classification relative to BMI (change in area under the ROC curve = 0.002; net reclassification improvement = 0.021; integrated discrimination improvement = - 0.003). Optimal cutpoints for BMI, %BF, and SMI varied substantially across race. Among Black women, a %BF cutpoint of 43.9% performed somewhat better than BMI (change in area under the ROC curve = 0.017; sensitivity = 0.69, specificity = 0.64). Some race-specific BMI and %BF cutpoints have moderate utility for identifying impaired physical function among midlife women.
Authors: Appelhans BM; Lange-Maia BS; Pettee Gabriel K; Karvonen-Gutierrez C; Karavolos K; Dugan SA; Greendale GA; Avery EF; Sternfeld B; Janssen I; Kravitz HM
Aging Clin Exp Res. 2020 Sep;32(9):1739-1747. Epub 2019-10-04.
Meta-analysis of 26,638 Individuals Identifies Two Genetic Loci Associated with Left Ventricular Ejection Fraction
Left ventricular ejection fraction (EF) is an indicator of cardiac function, usually assessed in individuals with heart failure and other cardiac conditions. Although family studies indicate that EF has an important genetic component with heritability estimates up to 0.61, to date only 6 EF-associated loci have been reported. Here, we conducted a genome-wide association study (GWAS) of EF in 26 638 adults from the Genetic Epidemiology Research on Adult Health and Aging and the UK Biobank cohorts. A meta-analysis combining results from Genetic Epidemiology Research on Adult Health and Aging and UK Biobank identified a novel locus: TMEM40 on chromosome 3p25 (rs11719526; β=0.47 and P=3.10×10-8) that replicated in Biobank Japan and confirmed recent findings implicating the BAG3 locus on chromosome 10q26 in EF variation, with the strongest association observed for rs17617337 (β=-0.83 and P=8.24×10-17). Although the minor allele frequencies of TMEM40 rs11719526 were generally common (between 0.13 and 0.44) in different ethnic groups, BAG3 rs17617337 was rare (minor allele frequencies<0.05) in Asian and African ancestry populations. These associations were slightly attenuated, after considering antecedent cardiac conditions (ie, heart failure/cardiomyopathy, hypertension, myocardial infarction, atrial fibrillation, valvular disease, and revascularization procedures). This suggests that the effects of the lead variants at TMEM40 or BAG3 on EF are largely independent of these conditions. In this large and multiethnic study, we identified 2 loci, TMEM40 and BAG3, associated with EF at a genome-wide significance level. Identifying and understanding the genetic determinants of EF is important to better understand the pathophysiology of this strong correlate of cardiac outcomes and to help target the development of future therapies.
Authors: Choquet H; Thai KK; Jiang C; Ranatunga DK; Hoffmann TJ; Go AS; Lindsay AC; Ehm MG; Waterworth DM; Risch N; Schaefer C
Circ Genom Precis Med. 2020 08;13(4):e002804. Epub 2020-06-30.
Smoking and cessation treatment among persons with and without HIV in a U.S. integrated health system
Persons with HIV (PWH) are more likely to smoke and are more susceptible to the harmful effects of smoking than persons without HIV. We examined smoking patterns and use of cessation treatment among PWH and persons without HIV in a U.S. integrated health system. We identified adults (≥18 years) with HIV and demographically-matched persons without HIV between July 2013 and December 2017. Smoking status and cessation treatment were ascertained from health records. We calculated age-standardized annual prevalence of smoking and evaluated trends using Cochran-Armitage tests and Poisson regression. Factors associated with cessation treatment during the study period, and smoking in the last year of the study, were evaluated by HIV status using multivariable Poisson models. The study included 11,235 PWH and 227,320 persons without HIV. Smoking prevalence was higher among PWH across all years but declined for both groups (from 16.6% to 14.6% in PWH and 11.6% to 10.5% in persons without HIV). Among smokers, PWH were more likely to initiate cessation treatment compared to persons without HIV (17.9% vs. 13.3%, covariate-adjusted prevalence ratio of 1.31, 95% CI = 1.15-1.50), with few differences in cessation treatment across subgroups of PWH. In 2017, smoking prevalence remained higher in PWH, especially among those who were younger or who had diagnoses of depression or substance use disorder. In a setting with access to cessation resources, smoking prevalence decreased both in PWH and persons without HIV. PWH had greater uptake of cessation treatment, which is encouraging for smoking reduction and improved health.
Authors: Lam JO; Levine-Hall T; Hood N; Alexeeff SE; Horberg MA; Young-Wolff KC; Sterling SA; Williams A; Weisner C; Satre DD; Silverberg MJ
Drug Alcohol Depend. 2020 08 01;213:108128. Epub 2020-06-18.
The Kaiser Permanente Northern California Adult Alcohol Registry, an Electronic Health Records-Based Registry of Patients With Alcohol Problems: Development and Implementation
Electronic health record (EHR)-based disease registries have aided health care professionals and researchers in increasing their understanding of chronic illnesses, including identifying patients with (or at risk of developing) conditions and tracking treatment progress and recovery. Despite excessive alcohol use being a major contributor to the global burden of disease and disability, no registries of alcohol problems exist. EHR-based data in Kaiser Permanente Northern California (KPNC), an integrated health system that conducts systematic alcohol screening, which provides specialty addiction medicine treatment internally and has a membership of over 4 million members that are highly representative of the US population with access to care, provide a unique opportunity to develop such a registry. Our objectives were to describe the development and implementation of a protocol for assembling the KPNC Adult Alcohol Registry, which may be useful to other researchers and health systems, and to characterize the registry cohort descriptively, including underlying health conditions. Inclusion criteria were adult members with unhealthy alcohol use (using National Institute on Alcohol Abuse and Alcoholism guidelines), an alcohol use disorder (AUD) diagnosis, or an alcohol-related health problem between June 1, 2013, and May 31, 2019. We extracted patients’ longitudinal, multidimensional EHR data from 1 year before their date of eligibility through May 31, 2019, and conducted descriptive analyses. We identified 723,604 adult patients who met the registry inclusion criteria at any time during the study period: 631,780 with unhealthy alcohol use, 143,690 with an AUD diagnosis, and 18,985 with an alcohol-related health problem. We identified 65,064 patients who met two or more criteria. Of the 4,973,195 adult patients with at least one encounter with the health system during the study period, the prevalence of unhealthy alcohol use was 13% (631,780/4,973,195), the prevalence of AUD diagnoses was 3% (143,690/4,973,195), and the prevalence of alcohol-related health problems was 0.4% (18,985/4,973,195). The registry cohort was 60% male (n=432,847) and 41% non-White (n=295,998) and had a median age of 41 years (IQR=27). About 48% (n=346,408) had a chronic medical condition, 18% (n=130,031) had a mental health condition, and 4% (n=30,429) had a drug use disorder diagnosis. We demonstrated that EHR-based data collected during clinical care within an integrated health system could be leveraged to develop a registry of patients with alcohol problems that is flexible and can be easily updated. The registry’s comprehensive patient-level data over multiyear periods provides a strong foundation for robust research addressing critical public health questions related to the full course and spectrum of alcohol problems, including recovery, which would complement other methods used in alcohol research (eg, population-based surveys, clinical trials).
Authors: Palzes VA; Weisner C; Chi FW; Kline-Simon AH; Satre DD; Hirschtritt ME; Ghadiali M; Sterling S
JMIR Med Inform. 2020 Jul 22;8(7):e19081. Epub 2020-07-22.
Analysis of putative cis-regulatory elements regulating blood pressure variation
Hundreds of loci have been associated with blood pressure (BP) traits from many genome-wide association studies. We identified an enrichment of these loci in aorta and tibial artery expression quantitative trait loci in our previous work in ~100 000 Genetic Epidemiology Research on Aging study participants. In the present study, we sought to fine-map known loci and identify novel genes by determining putative regulatory regions for these and other tissues relevant to BP. We constructed maps of putative cis-regulatory elements (CREs) using publicly available open chromatin data for the heart, aorta and tibial arteries, and multiple kidney cell types. Variants within these regions may be evaluated quantitatively for their tissue- or cell-type-specific regulatory impact using deltaSVM functional scores, as described in our previous work. We aggregate variants within these putative CREs within 50 Kb of the start or end of ‘expressed’ genes in these tissues or cell types using public expression data and use deltaSVM scores as weights in the group-wise sequence kernel association test to identify candidates. We test for association with both BP traits and expression within these tissues or cell types of interest and identify the candidates MTHFR, C10orf32, CSK, NOV, ULK4, SDCCAG8, SCAMP5, RPP25, HDGFRP3, VPS37B and PPCDC. Additionally, we examined two known QT interval genes, SCN5A and NOS1AP, in the Atherosclerosis Risk in Communities Study, as a positive control, and observed the expected heart-specific effect. Thus, our method identifies variants and genes for further functional testing using tissue- or cell-type-specific putative regulatory information.
Authors: Nandakumar P; Kwok PY; Risch N; Chakravarti A; Chakravarti A; et al.
Hum Mol Genet. 2020 07 21;29(11):1922-1932.
Remission From Unhealthy Drinking Among Patients With an Alcohol Use Disorder: A Longitudinal Study Using Systematic, Primary Care-Based Alcohol Screening Data
Using electronic health record (EHR) data from a systematic, primary care-based alcohol screening, brief intervention, and referral to treatment (SBIRT) initiative within a health system, we examined correlates of remission from unhealthy drinking among patients with an alcohol use disorder (AUD). We conducted a longitudinal study of 4,078 adults with AUD who screened positive for unhealthy drinking between October 1, 2015, and September 30, 2016. We extracted EHR data up to 3 years after screening until October 1, 2018. We used survival analysis to examine associations between remission (i.e., reporting abstinence or low-risk drinking at a subsequent screening) and patient characteristics, comorbidities, and treatment utilization. The median time to remission from unhealthy drinking was 1.7 years. Factors significantly associated with greater odds of remitting from unhealthy drinking during follow-up were female gender; older age (50-64 years); Black or Latino/Hispanic race/ethnicity; having more medical comorbidities; not having a comorbid drug use disorder; lower alcohol consumption levels; and receiving addiction medicine treatment before the index screening. In the first follow-up year, individuals with mental health comorbidities were more likely to remit, but those in psychiatric treatment were less likely. Receiving addiction treatment during follow-up was not associated with remission. Ethnic minorities and individuals with mental illness were more likely to remit, which is encouraging given the health disparities observed among these clinically important subgroups and warrants further research. Our findings may inform research on AUD recovery and clinical practice, as remission from unhealthy drinking is a crucial component of the early stages of recovery.
Authors: Palzes, Vanessa A; Kline-Simon, Andrea H; Satre, Derek D; Sterling, Stacy; Weisner, Constance; Chi, Felicia W
J Stud Alcohol Drugs. 2020 07;81(4):436-445.
Women’s Questions About Perinatal Cannabis Use and Health Care Providers’ Responses
Background: Cannabis use is common among individuals of reproductive age. We examined publicly posted questions about perinatal cannabis use and licensed United States health care provider responses. Materials and Methods: Data were medical questions on perinatal cannabis use posted online from March 2011 to January 2017 on an anonymous digital health platform. Posters were able to “thank” health care providers for their responses and providers could “agree” with other provider responses. We characterized 364 user questions and 596 responses from 277 unique providers and examined endorsement of responses through provider “agrees” and user “thanks.” Results: The most frequent questions concerned prenatal cannabis use detection (24.7%), effects on fertility (22.6%), harms of prenatal use to the fetus (21.3%), and risks of baby exposure to cannabis through breast milk (14.4%). Provider sentiment in responses regarding the safety of perinatal cannabis use were coded as 55.6% harmful, 8.8% safe, 8.8% mixed/unsure, and 26.8% safety unaddressed. Half of providers (49.6%) discouraged perinatal cannabis use, 0.5% encouraged use, and 49.9% neither encouraged nor discouraged use. Provider responses received 1,004 provider “agrees” and 583 user “thanks.” Provider responses indicating that perinatal cannabis use is unsafe received more provider “agrees” than responses indicating that use is safe (B = 0.42, 95% CI 0.02-0.82, p = 0.04). User “thanks” did not differ by provider responses regarding safety or dis/encouragement. Conclusion: The data indicate public interest in cannabis use effects before, during, and after pregnancy. While most health care providers indicated cannabis use during pregnancy and breastfeeding is not safe, many did not address safety or discourage use, suggesting a missed educational opportunity.
Authors: Young-Wolff KC; Gali K; Sarovar V; Rutledge GW; Prochaska JJ
J Womens Health (Larchmt). 2020 07;29(7):919-926. Epub 2020-01-30.
Age-of-onset information helps identify 76 genetic variants associated with allergic disease
Risk factors that contribute to inter-individual differences in the age-of-onset of allergic diseases are poorly understood. The aim of this study was to identify genetic risk variants associated with the age at which symptoms of allergic disease first develop, considering information from asthma, hay fever and eczema. Self-reported age-of-onset information was available for 117,130 genotyped individuals of European ancestry from the UK Biobank study. For each individual, we identified the earliest age at which asthma, hay fever and/or eczema was first diagnosed and performed a genome-wide association study (GWAS) of this combined age-of-onset phenotype. We identified 50 variants with a significant independent association (P
Authors: Ferreira MAR; 23andMe Research Team; collaborators of the SHARE study; Jorgenson E; Koppelman GH; et al.
PLoS Genet. 2020 Jun;16(6):e1008725. Epub 2020-06-30.
A multiethnic genome-wide analysis of 44,039 individuals identifies 41 new loci associated with central corneal thickness
Central corneal thickness (CCT) is one of the most heritable human traits, with broad-sense heritability estimates ranging between 0.68 to 0.95. Despite the high heritability and numerous previous association studies, only 8.5% of CCT variance is currently explained. Here, we report the results of a multiethnic meta-analysis of available genome-wide association studies in which we find association between CCT and 98 genomic loci, of which 41 are novel. Among these loci, 20 were significantly associated with keratoconus, and one (RAPSN rs3740685) was significantly associated with glaucoma after Bonferroni correction. Two-sample Mendelian randomization analysis suggests that thinner CCT does not causally increase the risk of primary open-angle glaucoma. This large CCT study explains up to 14.2% of CCT variance and increases substantially our understanding of the etiology of CCT variation. This may open new avenues of investigation into human ocular traits and their relationship to the risk of vision disorders.
Authors: Choquet H; Schaefer C; Risch N; Jorgenson E; et al.
Commun Biol. 2020 06 11;3(1):301. Epub 2020-06-11.
Molecular markers of neuroendocrine function and mitochondrial biogenesis associated with early life stress
Glucocorticoid receptor gene (NR3C1) promoter methylation influences cellular expression of the glucocorticoid receptor and is a proposed mechanism by which early life stress impacts neuroendocrine function. Mitochondria are sensitive and responsive to neuroendocrine stress signaling through the glucocorticoid receptor, and recent evidence with this sample and others shows that mitochondrial DNA copy number (mtDNAcn) is increased in adults with a history of early stress. No prior work has examined the role of NR3C1 methylation in the association between early life stress and mtDNAcn alterations. Adult participants (n = 290) completed diagnostic interviews and questionnaires characterizing early stress and lifetime psychiatric symptoms. Medical conditions, active substance abuse, and prescription medications other than oral contraceptives were exclusionary. Subjects with a history of lifetime bipolar, obsessive-compulsive, or psychotic disorders were excluded; individuals with other forms of major psychopathology were included. Whole blood mtDNAcn was measured using qPCR; NR3C1 methylation was measured via pyrosequencing. Multiple regression and bootstrapping procedures tested NR3C1 methylation as a mediator of effects of early stress on mtDNAcn. The positive association between early adversity and mtDNAcn (p = .02) was mediated by negative associations of early adversity with NR3C1 methylation (p = .02) and NR3C1 methylation with mtDNAcn (p < .001). The indirect effect involving early adversity, NR3C1 methylation, and mtDNAcn was significant (95 % CI [.002, .030]). NR3C1 methylation significantly mediates the association between early stress and mtDNAcn, suggesting that glucocorticoid receptor signaling may be a mechanistic pathway underlying mtDNAcn alterations of interest for future longitudinal work.
Authors: Ridout KK; Coe JL; Parade SH; Marsit CJ; Kao HT; Porton B; Carpenter LL; Price LH; Tyrka AR
Psychoneuroendocrinology. 2020 06;116:104632. Epub 2020-02-20.
A Novel Experiential Quality Improvement Training Program During Residency Improves Quality Improvement Confidence and Knowledge: a Prospective Cohort Study
The Accreditation Council for Graduate Medical Education (ACGME) mandates resident quality improvement (QI) training to improve patient safety, cost control, and efficiency. Thus, understanding this topic is crucial for early career physicians. This manuscript describes an enhanced, experiential QI curriculum for psychiatry residents and its outcomes. Two cohorts of 12 third-year residents completed the curriculum, which included didactics, external resources, and expert guidance through small group project design, implementation, and analysis/presentation. A survey on resident confidence in QI principles and the quality improvement knowledge assessment tool-revised (QIKAT-R) was used before and after curriculum participation. Data were analyzed using parametric descriptive tests and repeated measures general linear models with Benjamini-Hochberg correction for multiple comparisons. Resident confidence in performing seven of the ten steps of QI and QIKAT-R scores significantly improved for both cohorts (p = .011). Eighty-nine percent of residents felt that the curriculum met their goals. The QI curriculum effectively improved resident QI confidence and knowledge. Residents reported that experiential engagement in the design, implementation, and analysis/presentation of their project was crucial to these achievements. This experiential QI curriculum with resident-generated QI projects addressed ACGME training requirements while integrating QI training directly into the residents’ clinical activities, making the QI efforts relevant and meaningful while also achieving ACGME goals.
Authors: Ridout SJ; Ridout KK; Theyel B; Shea LM; Weinstock L; Uebelacker LA; Epstein-Lubow G
Acad Psychiatry. 2020 Jun;44(3):267-271. Epub 2020-01-21.
Behavioural and psychosocial factors associated with 5-year weight trajectories within the PORTAL Overweight/Obesity Cohort
The purpose of this study was to model weight trajectories over a 5-year time period (2012-2016) and their association with behavioural and psychosocial characteristics and health care-related experiences using data from the Patient Outcomes Research to Advance Learning (PORTAL) overweight/obesity cohort. Weight trajectories for each eligible patient in the PORTAL overweight/obesity cohort (n = 2864) were identified first using growth modelling; trajectories were then grouped using a hierarchical cluster analysis. Weight trajectory clusters that emerged were compared on demographics, and predictors of cluster membership were examined. Clusters were also compared on responses to a survey assessing health behaviours, quality of life, and health care experience completed in 2015 by 49% of the total sample (n = 1391). Seven distinct weight trajectory clusters were identified: (a) significant weight loss then maintenance; (b) higher stable weight; (c) moderate stable weight; (d) steady weight loss then relapse; (e) weight gain then weight loss; (f) steady weight gain then maintenance; and (g) lower stable weight. Age, sex, race/ethnicity, and body mass index at baseline predicted patient’s weight trajectory (P < .001). Over two thirds of patients maintained their weight over the 5-year period. Significant weight loss then maintenance, weight gain then weight loss, and higher stable weight patients were more likely to report receiving weight counselling from their provider. Patients in the significant weight loss then maintenance and lower stable weight clusters were more likely to be physically active than the other clusters. Findings suggest variability in patterns of weight change among adults with overweight or obesity who have access to health care and that these patterns differ on demographic, behavioural and psychosocial factors, and health care experience.
Authors: Fitzpatrick SL; Rosales AG; Brown SD; Arterburn DE; Daley MF; Horberg M; Koebnick C; Oshiro C; Young DR
Obes Sci Pract. 2020 Jun;6(3):272-281. Epub 2020-02-27.
Recurrent diabetic ketoacidosis and cognitive function among older adults with type 1 diabetes: findings from the Study of Longevity in Diabetes
Diabetic ketoacidosis (DKA) is a serious complication of diabetes. DKA is associated with poorer cognition in children with type 1 diabetes (T1D), but whether this is the case in older adults with T1D is unknown. Given the increasing life expectancy in T1D, understanding the role of DKA on brain health in older adults is crucial. We examined the association of DKA with cognitive function in 714 older adults with T1D from the Study of Longevity in Diabetes. Participants self-reported lifetime exposure to DKA resulting in hospitalization; DKA was categorized into 0 hospitalization, 1 hospitalization or ≥2 hospitalizations (recurrent DKA). Global and domain-specific cognition (language, executive function/psychomotor speed, episodic memory and simple attention) were assessed. The association of DKA with cognitive function was evaluated via linear and logistic regression models. Twenty-eight percent of participants (mean age=67 years; mean age at diagnosis=28 years; average duration of diabetes=39 years) reported a lifetime history of DKA resulting in hospitalization (18.5% single DKA; 9.7% recurrent DKA). In fully adjusted models, those with recurrent DKA had lower global cognitive function (β=-0.13; 95% CI -0.22 to 0.02) and lower scores on the executive function/psychomotor speed domain (β=-0.34; 95% CI -0.51 to 0.17). Individuals with recurrent DKA were also more likely to have the lowest level of cognitive function on the executive function/psychomotor speed domain (defined as 1.5 SD below the population mean; OR=3.26, 95% CI 1.43 to 7.42). Among 714 older adults with T1D, recurrent DKA was associated with lower global cognitive function, lower scores on the executive function/psychomotor speed domain and 3.3 times greater risk of having the lowest level of cognitive function in our sample on the executive function/psychomotor speed domain. These findings suggest that recurrent DKA may negatively impact the brain health of older patients with T1D and highlight the importance of DKA prevention.
Authors: Lacy ME; Gilsanz P; Eng CW; Beeri MS; Karter AJ; Whitmer RA
BMJ Open Diabetes Res Care. 2020 06;8(1).
Association between Objective Activity Intensity and Heart Rate Variability: Cardiovascular Disease Risk Factor Mediation (CARDIA)
We evaluated the associations between accelerometer-estimated physical activity (PA) intensity and heart rate variability (HRV) and examined mediation of these associations by glycemic control indices and other cardiovascular disease risk factors. Data were from 1668 participants (X[Combining Overline]age = 45.9 ± 3.5 yr, 58.0% female, 39.9% black) who participated in year 20 (2005-2006) of the Coronary Artery Risk Development in Young Adults Fitness Study. The ActiGraph 7164 estimated participants’ mean minutes per day of vigorous-intensity PA (VPA), moderate-intensity PA (MPA), and light-intensity PA (LPA) over 7 d. Three sequential 10-s 12-lead ECG strips were used to derive standard deviation of all normal RR intervals (SDNN) and root mean square of all successive RR intervals (rMSSD) HRV. Mediators representing glycemic control indices included fasting glucose, fasting insulin, and 2-h oral glucose tolerance, with other mediators being traditional cardiovascular disease risk factors. Multiple linear regression assessed independent associations of PA intensity with HRV per 1-SD. Mediation analyses computed the proportion of the PA-HRV association attributable to physiological mediators. Participants averaged 2.7 ± 6.2 min·d, 33.0 ± 22.0 min·d, and 360.2 ± 83.8 min·d of VPA, MPA, and LPA, respectively, with mean values for SDNN (32.6 ± 22.4 ms) and rMSSD (34.0 ± 24.8 ms) similar. After adjustment for demographic and lifestyle behaviors, VPA was associated with both HRV metrics (SDNN: std beta = 0.06 [0.03, 0.10]; rMSSD: std beta = 0.08 [0.05, 0.12]) and LPA with rMSSD only (std beta = 0.05 [0.01, 0.08]). Fasting insulin and glucose mediated 11.6% to 20.7% of the association of VPA and LPA with HRV, with triglycerides also potentially mediating these associations (range, 9.6%-13.4%). Accelerometer-estimated VPA was associated with higher (i.e., improved) HRV. Light-intensity PA also demonstrated a positive association. Mediation analyses suggested these associations may be most attributable to glucose-insulin dynamics.
Authors: Pope ZC; Gabriel KP; Whitaker KM; Chen LY; Schreiner PJ; Jacobs DR; Sternfeld B; Carr JJ; Lloyd-Jones DM; Pereira MA
Med Sci Sports Exerc. 2020 06;52(6):1314-1321.
Tobacco-related counseling and documentation in adolescent primary care practice: Challenges and opportunities
Primary care visits present an opportunity to reduce tobacco use and tobacco smoke exposure (TSE) among adolescents. To date, few studies have examined tobacco-related electronic health record (EHR) documentation in adolescent visits. The purpose of this study was to (1) describe tobacco-related EHR documentation practices in adolescent care clinics, including whether alternative tobacco products, parental use, and TSE were addressed; and (2) identify aspects of adolescent tobacco use that may inform EHR updates and counseling and documentation practices. Following a convergent mixed-methods design, we conducted an EHR review of 508 adolescent well-child visits, performed focus groups with pediatric providers and staff, and conducted in-depth interviews with adolescent patients. Record review data and interview transcripts were analyzed and interpreted concurrently. In the EHR review, cigarette screening was documented in 92.3% of visits, smokeless tobacco screening in 51.4%, parental tobacco use in 23.2%, and home TSE in 33.1% of visits. Smoking status options were not mutually exclusive and did not include noncigarette products. No records documented assessment of e-cigarette use, despite nearly half of adolescent interview respondents citing these as the most popular products among adolescents. In interviews, adolescents discussed their experiences with alternative tobacco/nicotine products more than cigarettes. Tobacco use status prompts should be revised for clarity and include noncigarette tobacco products and TSE. Provider education on noncigarette products and TSE assessment is needed. Improvements in EHR systems, resources, and tools can lead to better tobacco screening, prevention, and treatment practices among primary care providers. Clinical guidelines call for pediatricians to assess and treat adolescent and parental tobacco use during primary care visits. The use of electronic health records (EHRs) can improve screening and counseling practices; however, few studies have examined tobacco-related EHR documentation practices in adolescent care settings. This mixed-methods study found low rates of EHR documentation related to noncigarette nicotine/tobacco products, parental tobacco use, and tobacco smoke exposure. These results demonstrate the need for increased provider training and EHR modifications to facilitate comprehensive tobacco control efforts in the adolescent population.
Authors: LeLaurin JH; Theis RP; Thompson LA; Tan ASL; Young-Wolff KC; Carter-Harris L; Shenkman EA; Salloum RG
Nicotine Tob Res. 2020 05 26;22(6):1023-1029.
Genetic and environmental factors underlying keratinocyte carcinoma risk
Recent large-scale GWAS and large epidemiologic studies have accelerated the discovery of genes and environmental factors that contribute to the risk of keratinocyte carcinoma (KC), which includes basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). This Review summarizes the genomic regions associated with SCC and BCC risk, examines the genetic overlap between SCC and BCC, and discusses biological pathways involved in SCC and BCC development. Next, we review environmental factors that are associated with KC risk, including those that are shared between SCC and BCC as well as others that associated with only one type of KC. We conclude with a critical appraisal of current research and potential directions for future research.
Authors: Choquet H; Ashrafzadeh S; Kim Y; Asgari MM; Jorgenson E
JCI Insight. 2020 05 21;5(10). Epub 2020-05-21.
Developing a risk prediction model for keratinocyte carcinoma in patients with actinic keratosis
Authors: Kim Y; Jorgenson E; Asgari MM
Br J Dermatol. 2020 May 10.
Associations Between Medical Conditions and Alcohol Consumption Levels in an Adult Primary Care Population
Excessive alcohol consumption is associated with increased incidence of several medical conditions, but few nonveteran, population-based studies have assessed levels of alcohol use across medical conditions. To examine associations between medical conditions and alcohol consumption levels in a population-based sample of primary care patients using electronic health record data. This cross-sectional study used separate multinomial logistic regression models to estimate adjusted associations between 26 medical conditions and alcohol consumption levels in a sample of 2 720 231 adult primary care patients screened for unhealthy drinking between January 1, 2014, and December 31, 2017, then only among those reporting alcohol use. The study was conducted at Kaiser Permanente Northern California, a large, integrated health care delivery system that incorporated alcohol screening into its adult primary care workflow. Data were analyzed from June 29, 2018, to February 7, 2020. The main outcome was level of alcohol use, classified as no reported use, low-risk use, exceeding daily limits only, exceeding weekly limits only, or exceeding daily and weekly limits, per National Institute on Alcohol Abuse and Alcoholism guidelines. Other measures included sociodemographic, body mass index, smoking, inpatient and emergency department use, and a dichotomous indicator for the presence of 26 medical conditions in the year prior to the alcohol screening identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and ICD-10-CM diagnosis codes. Among the 2 720 231 included patients, 1 439 361 (52.9%) were female, 1 308 659 (48.1%) were white, and 883 276 (32.5%) were aged 18 to 34 years. Patients with any of the conditions (except injury or poisoning) had lower odds of drinking at low-risk and unhealthy levels relative to no reported use compared with those without the condition. Among 861 427 patients reporting alcohol use, patients with diabetes (odds ratio [OR], 1.11; 95% CI, 1.08-1.15), hypertension (OR, 1.11; 95% CI, 1.09-1.13), chronic obstructive pulmonary disease (COPD; OR, 1.16; 95% CI, 1.10-1.22), or injury or poisoning (OR, 1.06; 95% CI, 1.04-1.07) had higher odds of exceeding daily limits only; those with atrial fibrillation (OR, 1.12; 95% CI, 1.06-1.18), cancer (OR, 1.06; 95% CI, 1.03-1.10), COPD (OR, 1.15; 95% CI, 1.09-1.20), or hypertension (OR, 1.37; 95% CI, 1.34-1.40) had higher odds of exceeding weekly limits only; and those with COPD (OR, 1.15; 95% CI, 1.07-1.23), chronic liver disease (OR, 1.42; 95% CI, 1.32-1.53), or hypertension (OR, 1.48; 95% CI, 1.44-1.52) had higher odds of exceeding both daily and weekly limits. Findings suggest that patients with certain medical conditions are more likely to have elevated levels of alcohol use. Health systems and clinicians may want to consider approaches to help targeted patient subgroups limit unhealthy alcohol use and reduce health risks.
Authors: Sterling SA; Palzes VA; Lu Y; Kline-Simon AH; Parthasarathy S; Ross T; Elson J; Weisner C; Maxim C; Chi FW
JAMA Netw Open. 2020 May 01;3(5):e204687. Epub 2020-05-01.
Chronic psychosocial and financial burden accelerates 5-year telomere shortening: findings from the Coronary Artery Risk Development in Young Adults Study
Leukocyte telomere length, a marker of immune system function, is sensitive to exposures such as psychosocial stressors and health-maintaining behaviors. Past research has determined that stress experienced in adulthood is associated with shorter telomere length, but is limited to mostly cross-sectional reports. We test whether repeated reports of chronic psychosocial and financial burden is associated with telomere length change over a 5-year period (years 15 and 20) from 969 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a longitudinal, population-based cohort, ages 18-30 at time of recruitment in 1985. We further examine whether multisystem resiliency, comprised of social connections, health-maintaining behaviors, and psychological resources, mitigates the effects of repeated burden on telomere attrition over 5 years. Our results indicate that adults with high chronic burden do not show decreased telomere length over the 5-year period. However, these effects do vary by level of resiliency, as regression results revealed a significant interaction between chronic burden and multisystem resiliency. For individuals with high repeated chronic burden and low multisystem resiliency (1 SD below the mean), there was a significant 5-year shortening in telomere length, whereas no significant relationships between chronic burden and attrition were evident for those at moderate and higher levels of resiliency. These effects apply similarly across the three components of resiliency. Results imply that interventions should focus on establishing strong social connections, psychological resources, and health-maintaining behaviors when attempting to ameliorate stress-related decline in telomere length among at-risk individuals.
Authors: Cabeza de Baca T; Prather AA; Lin J; Sternfeld B; Adler N; Epel ES; Puterman E
Mol Psychiatry. 2020 05;25(5):1141-1153. Epub 2019-08-27.
Addressing Problems With Alcohol and Other Substances Among Older Adults During the COVID-19 Pandemic
Authors: Satre DD; Hirschtritt ME; Silverberg MJ; Sterling SA
Am J Geriatr Psychiatry. 2020 Apr 22.
Associations of maternal diet and placenta leptin methylation
Maternal diet is an important factor in prenatal development that also has implications for disease risk later in life. The adipokine leptin is a key regulator of energy homeostasis and may be involved in the association between maternal nutrition, maternal obesity, and infant outcomes. DNA methylation of placenta genes may occur in response to exposures and may program subsequent infant development. This study examined maternal diet, placenta leptin gene DNA methylation, and neonatal growth in a sample of healthy neonates and their mothers. Mothers and their healthy neonates (N = 135) were recruited within 1-2 days following delivery at Women and Infants Hospital in Providence, RI. A structured interview was conducted to assess maternal dietary intake. Maternal pre-pregnancy weight, weight gain during pregnancy, maternal health, medications, and vitamin use were obtained from medical records. Bisulfite pyrosequencing was used to measure methylation of CpG sites in the promoter region of the placenta leptin gene and determine genotype of the leptin single nucleotide polymorphism (SNP) rs2167270, which is known to influence leptin methylation. Bivariate analyses and linear regression models were used to evaluate associations of demographics, diet, and mean leptin methylation. Genotype was a significant predictor of placenta leptin DNA methylation (p < .01), and after controlling for this and other relevant maternal and infant covariates, lower levels of leptin methylation were significantly associated with greater intake of carbohydrates (p < .05), in particular added sugars (p < .05) and white/refined carbohydrates (p < .05). Total caloric intake was also associated with placenta leptin methylation (p < .05), however after controlling for relevant covariates, significance diminished to trend-level. There were no significant associations of placenta leptin methylation and intake of protein (p > .05) or fat (p > .05). These findings underline the importance of intake of carbohydrate consumption for methylation of the placenta leptin gene. Because methylation reduces gene transcription, lower methylation may indicate a placenta response to high caloric intake and carbohydrate food that would result in higher levels of this hormone during fetal development. Further investigation of the developmental ramifications of epigenetic changes to placenta leptin methylation should be pursued.
Authors: Daniels TE; Sadovnikoff AI; Ridout KK; Lesseur C; Marsit CJ; Tyrka AR
Mol Cell Endocrinol. 2020 04 05;505:110739. Epub 2020-01-29.
Breastfeeding is associated with reduced risk of multiple sclerosis in males, predominantly among HLA-DRB1*15:01 carriers
Breastfeeding as an infant appears protective against later development of some autoimmune diseases, but research into its influence on multiple sclerosis (MS) risk has yielded inconclusive results. We investigated the possible impact of breastfeeding on MS risk. We used two population-based case-control studies comprising 3670 cases and 6737 matched controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between MS and exposure to prolonged breastfeeding (4 months or longer) versus reduced breastfeeding (less than 4 months). A meta-analysis of case-control studies that assessed the impact of breastfeeding on MS risk among women and men was conducted. Prolonged breastfeeding was associated with reduced MS risk among men (OR 0.7, 95% CI 0.5-0.9) but not among women (OR 0.9, 95% CI 0.8-1.1). Among men, a synergistic effect was observed between HLA-DRB1*15:01 carrier status and reduced breastfeeding. Findings from the current study add to accumulating evidence that breastfeeding may be a modifiable protective factor for reducing the risk of MS in offspring. When possible, mothers should be supported to breastfeed their infants; however, the mechanism of a sex-specific biologic effect of breastfeeding on MS risk is unclear.
Authors: Hedström AK; Adams C; Shao X; Schaefer C; Olsson T; Barcellos LF; Alfredsson L
Mult Scler J Exp Transl Clin. 2020 Apr-Jun;6(2):2055217320928101. Epub 2020-06-01.
Meta-analysis of 542,934 subjects of European ancestry identifies new genes and mechanisms predisposing to refractive error and myopia
Refractive errors, in particular myopia, are a leading cause of morbidity and disability worldwide. Genetic investigation can improve understanding of the molecular mechanisms that underlie abnormal eye development and impaired vision. We conducted a meta-analysis of genome-wide association studies (GWAS) that involved 542,934 European participants and identified 336 novel genetic loci associated with refractive error. Collectively, all associated genetic variants explain 18.4% of heritability and improve the accuracy of myopia prediction (area under the curve (AUC) = 0.75). Our results suggest that refractive error is genetically heterogeneous, driven by genes that participate in the development of every anatomical component of the eye. In addition, our analyses suggest that genetic factors controlling circadian rhythm and pigmentation are also involved in the development of myopia and refractive error. These results may enable the prediction of refractive error and the development of personalized myopia prevention strategies in the future.
Authors: Hysi PG; Khawaja AP; Hammond CJ; et al.
Nat Genet. 2020 04;52(4):401-407. Epub 2020-03-30.
The role of substance use disorders in experiencing a repeat opioid overdose, and substance use treatment patterns among patients with a non-fatal opioid overdose
A non-fatal opioid overdose (NFOO) increases the risk of another overdose and identifies high-risk patients. We estimated the risk of repeat opioid overdose for patients with and without substance use disorder (SUD) diagnoses and the change in substance use treatment utilization rates associated with the first NFOO. We selected patients (>18 years of age) from Kaiser Permanente Northern California with a NFOO between 2009-2016 (n = 3,992). Cox proportional hazards models estimated the 1-year risk of opioid overdose associated with SUD diagnoses (opioid, alcohol, cannabis, amphetamine, sedative, and cocaine), controlling for patient characteristics. Among patients with an index NFOO, we calculated monthly utilization rates for outpatient substance use services and buprenorphine before and after the index overdose. Interrupted time series models estimated the change in level and trend in utilization rates associated with the index overdose. Approximately 7.2 % of patients had a repeat opioid overdose during the year after the index NFOO. The only SUD diagnosis significantly associated with greater risk of repeat overdose was opioid use disorder (OUD) (aHR: 1.51; 95 % CI: 1.13-2.01). Before the index overdose, 4.16 % of patients received outpatient substance use services and 1.32 % received buprenorphine. The index overdose was associated with a 5.94 % (standard error: 0.77 %) absolute increase in outpatient substance use services and a 1.29 % (standard error: 0.15 %) increase in buprenorphine. Patients with a NFOO and OUD are vulnerable to another overdose. Low initiation rates for substance use treatment after a NFOO indicate a need to address patient, provider, and system barriers.
Authors: Karmali RN; Ray GT; Rubinstein AL; Sterling SA; Weisner CM; Campbell CI
Drug Alcohol Depend. 2020 04 01;209:107923. Epub 2020-02-20.
Correlates of Pregnant Women’s Participation in a Substance Use Assessment and Counseling Intervention Integrated into Prenatal Care
Screening and referral for substance use are essential components of prenatal care. However, little is known about barriers to participation in substance use interventions that are integrated within prenatal care. Our study examines demographic and clinical correlates of participation in an initial assessment and counseling intervention integrated into prenatal care in a large healthcare system. The sample comprised Kaiser Permanente Northern California pregnant women with a live birth in 2014 or 2015 who screened positive for prenatal substance use via a self-reported questionnaire and/or urine toxicology test given as part of standard prenatal care (at ~ 8 weeks gestation). Of the 11,843 women who screened positive for prenatal substance use (median age = 30 years; 42% white; 38% screened positive for alcohol only, 20% for cannabis only, 5% nicotine only, 17% other drugs only, and 19% ≥ 2 substance categories), 9836 (83%) completed the initial substance use assessment and counseling intervention. Results from multivariable logistic regression analyses indicated that younger age, lower income, single marital status, and a positive urine toxicology test predicted higher odds of participation, while other/unknown race/ethnicity, greater parity, receiving the screening later in pregnancy, and screening positive for alcohol only or other drugs only predicted lower odds of participation (all Ps < .05). Findings suggest that integrated substance use interventions can successfully reach vulnerable populations of pregnant women (e.g., younger, lower income, racial/ethnic minorities). Future research should address whether differences in participation are due to patient (e.g., type of substance used, perceived stigma) or provider factors (e.g., working harder to engage traditionally underserved patients).
Authors: Young-Wolff KC; Tucker LY; Armstrong MA; Conway A; Weisner C; Goler N
Matern Child Health J. 2020 Apr;24(4):423-431.
PROMIS® Pediatric Depressive Symptoms as a Harmonized Score Metric
To conduct an evidence-based review of adolescent self-report depression measures and to demonstrate how various measures can be rescored onto a harmonized metric. Six widely used person-reported outcome measures (PROMs) were reviewed. Psychometric properties were evaluated using previously published guidance for PROMs. Next, two secondary data sources (from an outpatient behavioral health clinic and from the general population) were evaluated to harmonize scores across three of the measures. Both item response theory and equipercentile linking methods were used and compared. All six PROMs demonstrated a high evidence base for widespread use depending on the purpose of the assessments. Adolescent involvement when developing the PROM for content validity and floor or ceiling effects were the least frequent available evidence. Three of the PROMs were linked to the PROMIS® Pediatric Depressive Symptoms v2.0 (PROMIS-PedDepSx) metric. The scales were highly correlated and essentially unidimensional when aggregated. All linking methods were broadly comparable. Group-level score conversions are recommended to minimize linking bias. There are a number of strong, widely used PROMs for the evidence-based assessment (EBD) of adolescent depression. However, score comparability is a concern whenever there is a proliferation of measures. Harmonized score metrics support data aggregation and re-analysis. Using four PROMs, one of which served as the scoring metric, we demonstrated the possibility of harmonized depression scores. Future directions for EBD should evaluate whether harmonized PROMs for other pediatric health domains would be useful.
Authors: Kaat AJ; Kallen MA; Nowinski CJ; Sterling SA; Westbrook SR; Peters JT
J Pediatr Psychol. 2020 04 01;45(3):271-280.
The impact of breast cancer on physical activity from midlife to early older adulthood and predictors of change post-diagnosis
To examine physical activity (PA) patterns from pre- to post-diagnosis, and compare these changes to women without breast cancer. To determine pre-diagnosis predictors of PA change, post-diagnosis, in breast cancer survivors (BCS). Data were from 2314 Study of Women’s Health Across the Nation (SWAN) participants, average age of 46.4 ± 2.7 years at baseline (1996-1997). In Pink SWAN, 151 women who reported an incident breast cancer diagnosis over 20 years were classified as BCS; the remaining 2163 women were controls. LOESS plots and linear mixed models were used to illustrate and compare PA changes (sports/exercise [primary measure] and total PA) from pre- to post-diagnosis (or corresponding period) in BCS versus controls. Adjusted linear regression models were used to determine pre-diagnosis predictors of at-risk post-diagnosis PA change patterns (consistently low and decreased PA). No differences in pre- to post-diagnosis PA (or corresponding period) were observed in BCS versus controls. Among BCS, the odds of at-risk post-diagnosis PA change patterns was 2.50 (95% CI 0.96-6.48) times higher for those who reported sleep problems at ≥ 50% (compared to 0%) of pre-diagnosis visits and 3.49 (95% CI 1.26-9.65) times higher for those who were overweight or obese at all (compared to no) pre-diagnosis visits. No other statistically significant predictors were noted. Age-related declines in PA were not amplified by a breast cancer diagnosis. Given the beneficial role of PA across the cancer control continuum, efforts to increase or maintain adequate PA, post-diagnosis, should be continued. While age-related physical activity declines were not amplified breast cancer diagnosis, efforts to identify breast cancer survivors at increased risk for post-diagnosis physical activity declines (or maintenance of low activity) may be a high-yield strategy to improve prognosis and quality of life.
Authors: Pettee Gabriel K; Sternfeld B; Colvin AB; Lucas AR; Karvonen-Gutierrez CA; Gold EB; Crawford S; Greendale GA; Avis NE
J Cancer Surviv. 2020 Mar 30.
Drug Formularies in Correctional Settings
Authors: Morris NP; Hirschtritt ME; Tamburello AC
J Am Acad Psychiatry Law. 2020 03;48(1):2-6.
Documented opioid use disorder and its treatment in primary care patients across six U.S. health systems
The United States is in the middle of an opioid overdose epidemic, and experts are calling for improved detection of opioid use disorders (OUDs) and treatment with buprenorphine or extended release (XR) injectable naltrexone, which can be prescribed in general medical settings. To better understand the magnitude of opportunities for treatment among primary care (PC) patients, we estimated the prevalence of documented OUD and medication treatment of OUD among PC patients. This cross-sectional study included patients with ≥2 visits to PC clinics across 6 healthcare delivery systems who were ≥16 years of age during the study period (fiscal years 2014-2016). Diagnoses, prescriptions, and healthcare utilization were ascertained from electronic health records and insurance claims (5 systems that also offer health insurance). Documented OUDs were defined as ≥1 International Classification of Diseases code for OUDs (active or remission), and OUD treatment was defined as ≥1 prescription(s) for buprenorphine formulations indicated for OUD or naltrexone XR, during the 3-year study period. The prevalence of documented OUD and treatment (95% confidence intervals) across health systems were estimated, and characteristics of patients by treatment status were compared. Prevalence of OUD and OUD treatment were adjusted for age, gender, and race/ethnicity. Combined results were also adjusted for site. Among 1,403,327 eligible PC patients, 54-62% were female and mean age ranged from 46 to 51 years across health systems. The 3-year prevalence of documented OUD ranged from 0.7-1.4% across the health systems. Among patients with documented OUD, the prevalence of medication treatment (primarily buprenorphine) varied across health systems: 3%, 12%, 16%, 20%, 22%, and 36%. The prevalence of documented OUD and OUD treatment among PC patients varied widely across health systems. The majority of PC patients with OUD did not have evidence of treatment with buprenorphine or naltrexone XR, highlighting opportunities for improved identification and treatment in medical settings. These results can inform initiatives aimed at improving treatment of OUD in PC. Future research should focus on why there is such variation and how much of the variation can be addressed by improving access to medication treatment.
Authors: Boudreau DM; Campbell CI; Bradley KA; et al.
J Subst Abuse Treat. 2020 03;112S:41-48.
The application of digital health to the assessment and treatment of substance use disorders: The past, current, and future role of the National Drug Abuse Treatment Clinical Trials Network
The application of digital technologies to better assess, understand, and treat substance use disorders (SUDs) is a particularly promising and vibrant area of scientific research. The National Drug Abuse Treatment Clinical Trials Network (CTN), launched in 1999 by the U.S. National Institute on Drug Abuse, has supported a growing line of research that leverages digital technologies to glean new insights into SUDs and provide science-based therapeutic tools to a diverse array of persons with SUDs. This manuscript provides an overview of the breadth and impact of research conducted in the realm of digital health within the CTN. This work has included the CTN’s efforts to systematically embed digital screeners for SUDs into general medical settings to impact care models across the nation. This work has also included a pivotal multi-site clinical trial conducted on the CTN platform, whose data led to the very first “prescription digital therapeutic” authorized by the U.S. Food and Drug Administration (FDA) for the treatment of SUDs. Further CTN research includes the study of telehealth to increase capacity for science-based SUD treatment in rural and under-resourced communities. In addition, the CTN has supported an assessment of the feasibility of detecting cocaine-taking behavior via smartwatch sensing. And, the CTN has supported the conduct of clinical trials entirely online (including the recruitment of national and hard-to-reach/under-served participant samples online, with remote intervention delivery and data collection). Further, the CTN is supporting innovative work focused on the use of digital health technologies and data analytics to identify digital biomarkers and understand the clinical trajectories of individuals receiving medications for opioid use disorder (OUD). This manuscript concludes by outlining the many potential future opportunities to leverage the unique national CTN research network to scale-up the science on digital health to examine optimal strategies to increase the reach of science-based SUD service delivery models both within and outside of healthcare.
Authors: Marsch LA; Campbell A; Young S; et al.
J Subst Abuse Treat. 2020 03;112S:4-11.
Online patient-provider cannabis consultations
Cannabis has been legalized, decriminalized, or medicalized in over half the U.S. states. With restrictions on cannabis research, accepted standards to guide clinical practice are lacking. Analyzing online communications through a digital health platform, we characterized patient questions about cannabis use and provider responses. Coded for content were 4579 questions posted anonymously online between March 2011 through January 2017, and the responses from 1439 U.S. licensed clinicians. Provider responses to medical cannabis use questions were coded for sentiment: “negative”, “positive”, and “mixed.” Responses could be “thanked” by patients and receive “agrees” from providers. The most frequent themes were detection of cannabis use (25.3%), health harms (19.9%), co-use with other substances (9.1%), and medical use (8.2%). The 425 medical cannabis use questions most frequently related to treatment of mental illness (20.3%), pain (20.0%), and cancer care (6.7%). The 762 provider responses regarding medical cannabis use were coded for sentiment as 59.6% negative, 28.6% mixed, and 11.8% positive. Provider sentiment was most positive regarding cannabis use for palliative care and most negative for treating respiratory conditions, poor appetite, and mental illness. The proportion of positive sentiment responses increased from 17.6% to 32.4%. Provider responses coded as negative sentiment received more provider “Agrees” (mean rank = 280) than those coded as positive (mean rank = 215), beta coefficient = 0.33; 95% CI: 0.05, 0.62; p = .02. Cannabis use is a health topic of public interest. Variability in provider responses reflects the need for more research and consensus building to inform evidence-based clinical guidelines for cannabis use in medicine.
Authors: Gali K; Narode R; Young-Wolff KC; Rubinstein ML; Rutledge G; Prochaska JJ
Prev Med. 2020 03;132:105987. Epub 2020-01-15.
Severe Hypoglycemia and Cognitive Function in Older Adults With Type 1 Diabetes: The Study of Longevity in Diabetes (SOLID)
In children with type 1 diabetes (T1D), severe hypoglycemia (SH) is associated with poorer cognition, but the association of SH with cognitive function in late life is unknown. Given the increasing life expectancy in people with T1D, understanding the role of SH in brain health is crucial. We examined the association between SH and cognitive function in 718 older adults with T1D from the Study of Longevity in Diabetes (SOLID). Subjects self-reported recent SH (previous 12 months) and lifetime history of SH resulting in inpatient/emergency department utilization. Global and domain-specific cognition (language, executive function, episodic memory, and simple attention) were assessed. The associations of SH with cognitive function and impaired cognition were evaluated via linear and logistic regression models, respectively. Thirty-two percent of participants (mean age 67.2 years) reported recent SH and 50% reported lifetime SH. Compared with those with no SH, subjects with a recent SH history had significantly lower global cognition scores. Domain-specific analyses revealed significantly lower scores on language, executive function, and episodic memory with recent SH exposure and significantly lower executive function with lifetime SH exposure. Recent SH was associated with impaired global cognition (odds ratio [OR] 3.22, 95% CI 1.30, 7.94) and cognitive impairment on the language domain (OR 3.15, 95% CI 1.19, 8.29). Among older adults with T1D, recent SH and lifetime SH were associated with worse cognition. Recent SH was associated with impaired global cognition. These findings suggest a deleterious role of SH on the brain health of older patients with T1D and highlight the importance of SH prevention.
Authors: Lacy ME; Gilsanz P; Eng C; Beeri MS; Karter AJ; Whitmer RA
Diabetes Care. 2020 03;43(3):541-548. Epub 2019-12-27.
Association of Depression, Anxiety, and Trauma With Cannabis Use During Pregnancy
Authors: Young-Wolff KC; Sarovar V; Tucker LY; Goler NC; Alexeeff SE; Ridout KK; Avalos LA
JAMA Netw Open. 2020 02 05;3(2):e1921333. Epub 2020-02-05.
Prevalence and treatment of opioid use disorders among primary care patients in six health systems
The U.S. experienced nearly 48,000 opioid overdose deaths in 2017. Treatment of opioid use disorder (OUD) with buprenorphine is a recommended part of primary care, yet little is known about current U.S. practices in this setting. This observational study reports the prevalence of documented OUD and OUD treatment with buprenorphine among primary care patients in six large health systems. Adults with ≥2 primary care visits during a three-year period (10/1/2013-9/30/2016) in six health systems were included. Data were obtained from electronic health record and claims data, with measures, assessed over the three-year period, including indicators for documented OUD from ICD 9 and 10 codes and OUD treatment with buprenorphine. The prevalence of OUD treatment was adjusted for age, gender, race/ethnicity, and health system. Among 1,368,604 primary care patients, 13,942 (1.0 %) had documented OUD, and among these, 21.0 % had OUD treatment with buprenorphine. For those with documented OUD, the adjusted prevalence of OUD treatment with buprenorphine varied across demographic and clinical subgroups. OUD treatment was lower among patients who were older, women, Black/African American and Hispanic (compared to white), non-commercially insured, and those with non-cancer pain, mental health disorders, greater comorbidity, and more opioid prescriptions, emergency department visits or hospitalizations. Among primary care patients in six health systems, one in five with an OUD were treated with buprenorphine, with disparities across demographic and clinical characteristics. Less buprenorphine treatment among those with greater acute care utilization highlights an opportunity for systems-level changes to increase OUD treatment.
Authors: Lapham G; Campbell CI; PROUD Collaborative Investigators; et al.
Drug Alcohol Depend. 2020 02 01;207:107732. Epub 2019-11-15.
The Effect of Gestational Weight Gain Across Reproductive History on Maternal Body Mass Index in Midlife: The Study of Women’s Health Across the Nation
Background: Excessive weight gain during pregnancy is common and has been shown to be associated with increased long-term maternal weight. However, less is known on whether there is a cumulative effect of excessive gestational weight gain (GWG) over multiple pregnancies. Methods: Data from the Study of Women’s Health Across the Nation were used, restricted to parous women with no history of stillbirth or premature birth. The effect of the number of excessive GWG pregnancies on body mass index (BMI) in midlife (age 42-53) was analyzed using multivariable linear regression. Fully adjusted models included parity, inadequate GWG, demographic, and behavioral characteristics. Results: The 1181 women included in this analysis reported a total of 2693 births. Overall, 466 (39.5%) were categorized as having at least one pregnancy with excessive GWG. The median BMI at midlife was 26.0 kg/m2 (interquartile range 22.5-31.1). In fully adjusted models, each additional pregnancy with excessive GWG was associated with 0.021 higher estimated log BMI (p = 0.031). Among women with 1-3 births, adjusted mean (95% confidence interval) BMI for those with 0, 1, 2, and 3 excessive GWG pregnancies was 25.4 (24.9-25.9), 26.8 (26.1-27.5), 27.5 (26.6-28.4), and 28.8 (27.3-30.5), respectively. Conclusions: In this multiethnic study of women with a history of term live births, the number of pregnancies with excessive GWG was associated with increased maternal BMI in midlife. Our findings suggest that prevention of excessive GWG at any point in a woman’s reproductive history can have an impact on long-term maternal health.
Authors: Hutchins F; Abrams B; Brooks M; Colvin A; Moore Simas T; Rosal M; Sternfeld B; Crawford S
J Womens Health (Larchmt). 2020 02;29(2):148-157. Epub 2019-11-27.
Management of Cannabis Use in Breastfeeding Women: The Untapped Potential of Certified Lactation Consultants
Recent increases in maternal cannabis use, in combination with rapidly changing cannabis policies in the United States, pose a unique threat to maternal and child health. To date, 33 states and the District of Columbia (D.C.) have legalized medicinal cannabis, and 11 states and D.C. have legalized recreational cannabis. Many other states have decriminalized cannabis and are considering legalization. Recent data suggest that maternal cannabis use is increasing. Maternal cannabis use in the postpartum period, including breastfeeding women, may contribute to negative health outcomes in young children. Perinatal health professionals should work collaboratively to safeguard maternal and child health outcomes from potential adverse health effects of cannabis use. To that end, we highlight the critical role International Board Certified Lactation Consultants® (IBCLCs®) could play in postpartum management of cannabis use. IBCLCs have direct access to a large number of women shortly after delivery and throughout the postpartum period. They are an extremely well-positioned, but arguably underutilized, and are potential partners for postpartum management of cannabis use. Given the rapport IBCLCs frequently develop with their patients, these mothers may be especially willing to disclose cannabis use and be receptive to education and advice to quit cannabis use while breastfeeding. As such, we propose that the role of IBCLCs be promoted to support families with nonpunitive education about the potential risks, advice to not use cannabis while breastfeeding, and timely referral for treatment, when needed. This approach holds promise for improving the health and quality of life for breastfeeding women and their infants.
Authors: Skelton KR; Young-Wolff KC; Benjamin-Neelon SE
Breastfeed Med. 2020 02;15(2):117-120. Epub 2019-12-20.
Individualized Relative Intensity Physical Activity Accelerometer Cut-points
Physical activity (PA) intensity is expressed as either absolute or relative intensity. Absolute intensity refers to the energy required to perform an activity. Relative intensity refers to a level of effort that takes into account how hard an individual is working relative to their maximum capacity. We sought to develop methods for obtaining individualized relative-intensity accelerometer cut points using data from a maximal graded exercise treadmill test (GXT) so that each individual has their own cut point. A total of 2363 men and women 38 to 50 yr old from the CARDIA fitness study wore ActiGraph 7164 accelerometers during a maximal GXT and for seven consecutive days in 2005-2006. Using mixed-effects regression models, we regressed accelerometer counts on heart rate as a percentage of maximum (%HRmax) and on RPE. Based on these two models, we obtained a moderate-intensity (%HRmax = 64% or RPE = 12) count cut point that is specific to each participant. We applied these subject-specific cut points to the available CARDIA accelerometer data. Using RPE, the mean moderate-intensity accelerometer cut point was 4004 (SD = 1120) counts per minute. On average, cut points were higher for men (4189 counts per minute) versus women (3865 counts per minute) and were higher for Whites (4088 counts per minute) versus African Americans (3896 counts per minute). Cut points were correlated with body mass index (rho = -0.11) and GXT duration (rho = 0.33). Mean daily minutes of absolute- and relative-intensity moderate to vigorous PA were 34.1 (SD = 31.1) min·d and 9.1 (SD = 18.2) min·d, respectively. RPE cut points were higher than those based on %HRmax. This is likely due to some participants ending the GXT before achieving their HRmax. Accelerometer-based relative-intensity PA may be a useful measure of intensity relative to maximal capacity.
Authors: Siddique J; Sternfeld B; Freedson P; et al.
Med Sci Sports Exerc. 2020 02;52(2):398-407.
Chronic pain diagnoses and opioid dispensings among insured individuals with serious mental illness
Individuals with major depressive disorder (MDD) and bipolar disorder (BD) have particularly high rates of chronic non-cancer pain (CNCP) and are also more likely to receive prescription opioids for their pain. However, there have been no known studies published to date that have examined opioid treatment patterns among individuals with schizophrenia. Using electronic medical record data across 13 Mental Health Research Network sites, individuals with diagnoses of MDD (N = 65,750), BD (N = 38,117) or schizophrenia or schizoaffective disorder (N = 12,916) were identified and matched on age, sex and Medicare status to controls with no documented mental illness. CNCP diagnoses and prescription opioid medication dispensings were extracted for the matched samples. Multivariate analyses were conducted to evaluate (1) the odds of receiving a pain-related diagnosis and (2) the odds of receiving opioids, by separate mental illness diagnosis category compared with matched controls, controlling for age, sex, Medicare status, race/ethnicity, income, medical comorbidities, healthcare utilization and chronic pain diagnoses. Multivariable models indicated that having a MDD (OR = 1.90; 95% CI = 1.85-1.95) or BD (OR = 1.71; 95% CI = 1.66-1.77) diagnosis was associated with increased odds of a CNCP diagnosis after controlling for age, sex, race, income, medical comorbidities and healthcare utilization. By contrast, having a schizophrenia diagnosis was associated with decreased odds of receiving a chronic pain diagnosis (OR = 0.86; 95% CI = 0.82-0.90). Having a MDD (OR = 2.59; 95% CI = 2.44-2.75) or BD (OR = 2.12; 95% CI =
Authors: Owen-Smith A; Sterling SA; Campbell CI; Simon G; et al.
BMC Psychiatry. 2020 01 31;20(1):40. Epub 2020-01-31.
Development of a National Caregiver Health Survey for Hematopoietic Stem Cell Transplant: Qualitative Study of Cognitive Interviews and Verbal Probing.
BACKGROUND: Roadmap 1.0 is a mobile health app that was previously developed for caregivers of patients who have undergone hematopoietic stem cell transplantation (HSCT). Formative research targeted toward its end users (caregivers) can help inform app design and development, allowing additional components to be incorporated into the app, which can then be tested in a future randomized controlled trial. n OBJECTIVE: This study aimed to create a methodologically rigorous national survey that would help inform the development of Roadmap 2.0. n METHODS: We conducted a prospective, qualitative research study that took place between November 18, 2018, and February 7, 2019, in a blood and marrow transplant unit within a large academic medical institution in the midwestern part of the United States. Cognitive interviews, including think-aloud and verbal probing techniques, were conducted in 10 adult caregivers (≥18 years) of patients who had undergone HSCT. n RESULTS: Most participants were female (9/10, 90%), white (9/10, 90%), married (9/10, 90%), employed at least part time (6/10, 60%), caregivers of adult patients (7/10, 70%), and had some college education (9/10, 90%) and an annual household income of $60,000 or higher (6/10, 60%). All but one interview was audio-recorded, with permission. Overall, participants were engaged in the cognitive interview process of the draft survey, which included 7 topics. The interviews highlighted areas wherein survey items could be further refined, such as offering more response choices (eg, “NA”) or clarifying the type of transplant (eg, autologous or allogeneic) or context of transplant care (eg, pre-HSCT, during HSCT, post-HSCT, inpatient, and outpatient). Apart from these findings, the items in demographics, caregiving experiences, technology, positive activities, and mood were generally interpreted as intended. On the basis of the transcript data and field notes by the interviewer, items within self-efficacy (Caregiver Self-Efficacy Scale) and coping (Brief Coping Orientation to Problems Experienced inventory) questionnaires generated more confusion among interviewer and participants, reflecting difficulties in interpreting the meaning of some survey items. n CONCLUSIONS: This study incorporated the four cognitive aspects of survey methodology that describe the question-answering process-(1) comprehension, (2) information retrieval, (3) judgment and decision making, and (4) responding-by using the think-aloud and probing techniques in cognitive interviews. We conclude that this methodologically rigorous process informed revisions and improved our final questionnaire design. n INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/resprot.49188.
Authors: Kedroske, Jacob;Koblick, Sarah;Chaar, Dima;Mazzoli, Amanda;O'Brien, Maureen;Yahng, Lilian;Vue, Rebecca;Chappell, Grant;Shin, Ji Youn;Hanauer, David A;Choi, Sung Won
JMIR Form Res. 2020 Jan 23;4(1):e17077. doi: 10.2196/17077..
Functional validity, role, and implications of heavy alcohol consumption genetic loci
High alcohol consumption is a risk factor for morbidity and mortality, yet few genetic loci have been robustly associated with alcohol intake. Here, we use U.K. Biobank (n = 125,249) and GERA (n = 47,967) datasets to determine genetic factors associated with extreme population-level alcohol consumption and examine the functional validity of outcomes using model organisms and in silico techniques. We identified six loci attaining genome-wide significant association with alcohol consumption after meta-analysis and meeting our criteria for replication: ADH1B (lead SNP: rs1229984), KLB (rs13130794), BTF3P13 (rs144198753), GCKR (rs1260326), SLC39A8 (rs13107325), and DRD2 (rs11214609). A conserved role in phenotypic responses to alcohol was observed for all genetic targets available for investigation (ADH1B, GCKR, SLC39A8, and KLB) in Caenorhabditis elegans. Evidence of causal links to lung cancer, and shared genetic architecture with gout and hypertension was also found. These findings offer insight into genes, pathways, and relationships for disease risk associated with high alcohol consumption.
Authors: Thompson A; Cook J; Choquet H; Jorgenson E; Yin J; Kinnunen T; Barclay J; Morris AP; Pirmohamed M
Sci Adv. 2020 Jan;6(3):eaay5034. Epub 2020-01-15.
Association Between Objective Activity Intensity & Heart Rate Variability: CVD Risk Factor Mediation (CARDIA)
We evaluated the associations between accelerometer-estimated physical activity (PA) intensity and heart rate variability (HRV) and examined mediation of these associations by glycemic control indices and other cardiovascular disease (CVD) risk factors. Data were from 1,668 participants (X[Combining Overline]age=45.9±3.5 years, 58.0% female, 39.9% black) who participated in Year 20 (2005-06) of the Coronary Artery Risk Development in Young Adults (CARDIA) Fitness Study. The ActiGraph 7164 estimated participants’ mean min/day of vigorous-intensity PA (VPA), moderate-intensity PA (MPA), and light-intensity PA (LPA) over seven days. Three sequential 10-sec 12-lead ECG strips were used to derive standard deviation of all normal RR intervals (SDNN) and root mean square of all successive RR intervals (rMSSD) HRV. Mediators representing glycemic control indices included fasting glucose, fasting insulin, and 2-hour oral glucose tolerance, with other mediators being traditional CVD risk factors. Multiple linear regression assessed independent associations of PA intensity with HRV per 1-SD. Mediation analyses computed the proportion of the PA-HRV association attributable to physiological mediators. Participants averaged 2.7±6.2, 33.0±22.0, and 360.2±83.8 min/day of VPA, MPA, and LPA, respectively, with mean values for SDNN (32.6±22.4 ms) and rMSSD (34.0±24.8 ms) similar. After adjustment for demographic and lifestyle behaviors, VPA was associated with both HRV metrics (SDNN: std beta=0.06 [0.03, 0.10]; rMSSD: std beta=0.08, [0.05, 0.12]) and LPA with rMSSD only (std beta=0.05, [0.01, 0.08]). Fasting insulin and glucose mediated 11.6%-20.7% of the association of VPA and LPA with HRV, with triglycerides also potentially mediating these associations (range: 9.6%-13.4%). Accelerometer-estimated VPA was associated with higher (i.e., improved) HRV. LPA also demonstrated a positive association. Mediation analyses suggested these associations may be most attributable to glucose-insulin dynamics.
Authors: Pope ZC; Gabriel KP; Whitaker KM; Chen LY; Schreiner PJ; Jacobs DR; Sternfeld B; Carr JJ; Lloyd-Jones DM; Pereira MA
Med Sci Sports Exerc. 2020 Jan 06.
Genome-wide Genotyping of Cerebral Cavernous Malformation Type 1 Individuals to Identify Genetic Modifiers of Disease Severity
Familial cerebral cavernous malformation type 1 (CCM1) is an autosomal dominant disease caused by mutations in the Krev Interaction Trapped 1 (KRIT1/CCM1) gene, and characterized by brain lesions that can cause hemorrhagic strokes, seizures, and neurological deficits. Carriers of the same genetic mutation can present with variable symptoms and severity of disease, suggesting the influence of modifier factors. Genetic modifiers of CCM1 disease severity have been recently identified and included common genetic variants in inflammatory, immune response, and oxidative stress genes and pathways. Here, we describe the genotyping of CCM1 patients with the same gene mutation (Q455X) using a high-throughput genotyping array optimized for individuals of Hispanic/Latino ancestry. We then review the quality control steps following the genome-wide genotyping. Genome-wide genotyping of larger cohorts of CCM1 patients might reveal additional genetic variants contributing to the disease severity of CCM1.
Authors: Choquet H; Kim H
Methods Mol Biol. 2020;2152:77-84.
The impact of adjusting for baseline in pharmacogenomic genome-wide association studies of quantitative change
In pharmacogenomic studies of quantitative change, any association between genetic variants and the pretreatment (baseline) measurement can bias the estimate of effect between those variants and drug response. A putative solution is to adjust for baseline. We conducted a series of genome-wide association studies (GWASs) for low-density lipoprotein cholesterol (LDL-C) response to statin therapy in 34,874 participants of the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort as a case study to investigate the impact of baseline adjustment on results generated from pharmacogenomic studies of quantitative change. Across phenotypes of statin-induced LDL-C change, baseline adjustment identified variants from six loci meeting genome-wide significance (SORT/CELSR2/PSRC1, LPA, SLCO1B1, APOE, APOB, and SMARCA4/LDLR). In contrast, baseline-unadjusted analyses yielded variants from three loci meeting the criteria for genome-wide significance (LPA, APOE, and SLCO1B1). A genome-wide heterogeneity test of baseline versus statin on-treatment LDL-C levels was performed as the definitive test for the true effect of genetic variants on statin-induced LDL-C change. These findings were generally consistent with the models not adjusting for baseline signifying that genome-wide significant hits generated only from baseline-adjusted analyses (SORT/CELSR2/PSRC1, APOB, SMARCA4/LDLR) were likely biased. We then comprehensively reviewed published GWASs of drug-induced quantitative change and discovered that more than half (59%) inappropriately adjusted for baseline. Altogether, we demonstrate that (1) baseline adjustment introduces bias in pharmacogenomic studies of quantitative change and (2) this erroneous methodology is highly prevalent. We conclude that it is critical to avoid this common statistical approach in future pharmacogenomic studies of quantitative change.
Authors: Oni-Orisan A; Haldar T; Ranatunga DK; Medina MW; Schaefer C; Krauss RM; Iribarren C; Risch N; Hoffmann TJ
NPJ Genom Med. 2020;5:1. Epub 2020-01-16.
Clinical implications of recent advances in primary open-angle glaucoma genetics
Over the last decade, genetic studies, including genome-wide association studies (GWAS), have accelerated the discovery of genes and genomic regions contributing to primary open-angle glaucoma (POAG), a leading cause of irreversible vision loss. Here, we review the findings of genetic studies of POAG published in English prior to September 2019. In total, 74 genomic regions have been associated at a genome-wide level of significance with POAG susceptibility. Recent POAG GWAS provide not only insight into global and ethnic-specific genetic risk factors for POAG susceptibility across populations of diverse ancestry, but also important functional insights underlying biological mechanisms of glaucoma pathogenesis. In this review, we also summarize the genetic overlap between POAG, glaucoma endophenotypes, such as intraocular pressure and vertical cup-disc ratio (VCDR), and other eye disorders. We also discuss approaches recently developed to increase power for POAG locus discovery and to predict POAG risk. Finally, we discuss the recent development of POAG gene-based therapies and future strategies to treat glaucoma effectively. Understanding the genetic architecture of POAG is essential for an earlier diagnosis of this common eye disorder, predictive testing of at-risk patients, and design of gene-based targeted medical therapies none of which are currently available. ??: ?????????(POAG)???????????????, ??????, ?????????, ??????????, ???POAG??????????????????2019?9??????????POAG?????????????????, ??74???????POAG???????????POAG? GWAS????????????????POAG????????????, ?????????????????????????????????, ?????POAG???????????, ??????? (??????????) ??????????????????????????????POAG??????????POAG????????, ???????POAG??????????????????????????POAG????????????????????, ??????????????????????????????????????.
Authors: Choquet H; Wiggs JL; Khawaja AP
Eye (Lond). 2020 01;34(1):29-39. Epub 2019-10-23.
Pharmacist Medication Management of Adults with Attention Deficit: An Alternative Clinical Structure
Attention-deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric conditions in youth. This disorder can persist into adulthood, with an estimated prevalence of 4.4% to 5.2% in the US. To review adult ADHD diagnostic criteria, adult clinical presentation, and resulting impairments in function and to describe our adult psychiatry clinic’s pharmacist-comanaged ADHD medication management program as a model to provide safe and effective care that is accessible, efficient, and well monitored. The program consists of 1) screening (urine toxicology, diagnostic evaluation, data collection) by physicians, 2) program participation and treatment agreement with establishment of care goals, and 3) patient maintenance and monitoring. Pharmacists in the Department of Psychiatry manage refills, distributing the clinical caseload among a broader clinician base. This program created a standardized protocol for assessment, referral, and follow-up of adult patients with ADHD, with close monitoring and titration of controlled medications, systematic use of screening measures, and a stimulant treatment contract. Development of this program and workflow model could increase care delivery efficiency, potentially improving patient satisfaction and outcomes. There is a great need to use alternative patient management strategies such as this to maintain access to high-quality care while there is a nationwide need for more psychiatric clinicians. We believe this program offers a solution to a component of this growing problem, and other clinical sites would benefit from such a program. Next steps include analysis and publication of results of implementation, including patient outcomes, engagement in treatment, and satisfaction.
Authors: Huang R; Ridout SJ; Harris B; Ridout KK; Raja K
Perm J. 2020;24. Epub 2020-03-18.
Racial/Ethnic Differences in Sleep Quality among Older Adults: Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study
We assessed cross-sectional differences in sleep quality and risk factors among Asian, Black, Latino, and White participants in the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study. KHANDLE enrolled community-dwelling adults aged ≥65 years living in northern California. Participants completed a modified Pittsburgh Sleep Quality Index to measure six sleep components and a global sleep score (scored 0-24). Covariates included age, sex, central adiposity, education, income, alcohol consumption, ever smoking, physical activity, and depression. Ordinal logistic regression was used to model sleep component scores across race/ethnic groups. Linear regression was used to assess racial/ethnic differences in global sleep score and the association between risk factors and global sleep score. 1,664 participants with a mean age of 76 (SD=7) and mean global sleep score of 6 (SD=4) were analyzed. Using Latinos as reference (highest average sleep score), Blacks had an average .96 (.37, 1.54) unit higher global sleep score (worse sleep) while Asians [β: .04 (-.56, .63)] and Whites [β: .28 (-.29, .84)] did not significantly differ. Compared with Latinos, Blacks and Asians had greater odds of a worse score on the sleep duration component; Blacks and Whites had greater odds of a worse score on the sleep disturbances component; and, Whites had greater odds of a worse score on the medication component. Risk factors for poor sleep did not differ by race/ethnicity except alcohol consumption (interaction P=.04), which was associated with poor sleep in Blacks only. In this cohort, racial/ethnic differences in sleep quality were common.
Authors: George, Kristen M; Peterson, Rachel L; Gilsanz, Paola; Mungas, Dan M; Glymour, M Maria; Mayeda, Elizabeth Rose; Whitmer, Rachel A
Ethn Dis. 2020 Summer;30(3):469-478. Epub 2020-07-09.
Differences in association of leisure time activities and cognition in a racially/ethnically diverse cohort of older adults: Findings from the KHANDLE study
Leisure time activity is associated with better cognitive function but has not been well studied in racially/ethnically diverse cohorts, who may have different access to activities. Frequency of participation in 10 leisure time activities (eg, reading, attending cultural events) and cognition (executive function, semantic memory, and verbal episodic memory) were assessed at Wave 1 in the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study, a prospective cohort initiated in 2017. Linear regression models adjusted for sociodemographics and depression estimated cross-sectional associations between leisure time activity variety and frequency and cognitive domains overall and by race/ethnicity. Logistic regression models estimated odds of cognitive impairment among those in the lowest quartiles of activity variety and frequency. All models controlled for age, sex, education, income, retirement status, and depression. Higher leisure time activity variety was significantly associated with better cognition for all, except for verbal episodic memory among Asians (β = 0.05, 95% confidence interval [CI]: -0.004, 0.11) and semantic memory among Latinos (β = 0.04, 95% CI: -0.01, 0.08). Low activity variety was associated with nearly three-fold increased odds of cognitive impairment (adjusted odds ratio [OR] = 2.87, 95% CI: 1.77, 4.64). Activity frequency was associated with higher executive function only among whites (β = 0.10, 95% CI: 0.02, 0.18). Patterns by race/ethnicity were not explained by education. Engaging in a wider variety of leisure time activities may be more important than frequently participating in fewer activities for cognitive aging in racially/ethnically diverse cohorts.
Authors: Peterson RL; Gilsanz P; George KM; Ackley S; Glymour MM; Mungas DM; Whitmer RA
Alzheimers Dement (N Y). 2020;6(1):e12047. Epub 2020-06-26.
Comparing three approaches for involving patients in research prioritization: a qualitative study of participant experiences
By participating in priority-setting activities in research, patients and members of the public help ensure that important questions are incorporated into future research agendas. Surveys, focus groups, and online crowdsourcing are increasingly used to obtain input, yet little is known about how they compare for prioritizing research topics. To address this gap, the Study of Methods for Assessing Research Topic Elicitation and pRioritization (SMARTER) evaluated participant satisfaction with the engagement experience across three prioritization activities. Respondents from Back pain Outcomes using Longitudinal Data (BOLD), a registry of patients 65 years and older with low back pain (LBP), were randomly assigned to one of three interactive prioritization activities: online crowd-voting, in-person focus groups using nominal group technique, and two rounds of a mailed survey (Delphi). To assess quality of experience, participants completed a brief survey; a subset were subsequently interviewed. We used descriptive statistics to characterize participants, and we analyzed responses to the evaluation using a mixed-methods approach, tabulating responses to Likert-scale questions and using thematic analysis of interviews to explore participant understanding of the activity and perceptions of experience. The crowd-voting activity had 38 participants, focus groups 39, and the Delphi survey 74. Women outnumbered men in the focus groups and Delphi survey; otherwise, demographics among groups were similar, with participants being predominantly white, non-Hispanic, and college educated. Activities generated similar lists of research priorities, including causes of LBP, improving physician-patient communication, and self-care strategies. The evaluation survey was completed by 123 participants. Of these, 31 across all activities were interviewed about motivations to participate, understanding of activity goals, logistics, clarity of instructions, and the role of patients in research. Focus group participants rated their experience highest, in both the evaluation and interviews. Common methods for research prioritization yielded similar priorities but differing perceptions of experience. Such comparative studies are rare but important in understanding methods to involve patients and the public in research. Preferences for different methods may vary across stakeholder groups; this warrants future study. NICHSR, HSRP20152274. Registered 19 February 2015.
Authors: Lavallee DC; Lawrence SO; Avins AL; Nerenz DR; Edwards TC; Patrick DL; Bauer Z; Truitt AR; Monsell SE; Scott MR; Jarvik JG
Res Involv Engagem. 2020;6:18. Epub 2020-05-01.
Routes of cannabis administration among females in the year before and during pregnancy: Results from a pilot project
Use of cannabis during pregnancy is on the rise, yet little is known about how women administer cannabis during the perinatal period. This study examined self-reported modes of cannabis administration among women in the year before and during pregnancy, and their association with self-reported cannabis use frequency using data from 585 women screened in 2018-2019 for cannabis use during standard prenatal care in two medical centers in Northern California. The prevalence of cannabis use was 12% before pregnancy and 3% during pregnancy. Among the 71 women who reported cannabis use before pregnancy and the 19 women who reported cannabis use during pregnancy, smoking was the most common mode of administration (58% and 42%), followed by edibles (27% and 16%), vaping (23% and 16%), lotions (11% and 5%), and other (10% and 0%). In the year before pregnancy and during pregnancy, monthly or less use was most common (56% and 58%), followed by weekly use (24% and 26%) and daily use (20% and 16%). Among cannabis users, 43% used more than one mode before pregnancy compared to 15% during pregnancy. Daily cannabis use was most common among women who reported smoking only or smoking in combination with other modes. These novel results indicate that while smoking is the most common mode of cannabis administration during the perinatal period, there is variation in use and co-use of alternative modes. Future studies are needed to understand the relative health effects associated with individual and combined modes of cannabis administration during pregnancy.
Authors: Young-Wolff KC; Adams SR; Wi S; Weisner C; Conway A
Addict Behav. 2020 01;100:106125. Epub 2019-09-09.
Sleep Quality and Cognitive Function in Type 1 Diabetes: Findings From the Study of Longevity in Diabetes (SOLID)
The objective was to examine the association between sleep quality and global and domain-specific cognitive function among older individuals with type 1 diabetes (T1D). We evaluated 695 individuals with T1D aged 60 years or above who participated in the baseline assessment of the Study of Longevity in Diabetes (SOLID), which captured subjective sleep quality (Pittsburgh Sleep Quality Index) and global and domain-specific (language, executive function, episodic memory, and simple attention) cognitive function. Multivariable linear regressions estimated the associations between sleep quality quartiles and overall and domain-specific cognitive function adjusting for age, sex, race/ethnicity, education, depressive symptoms, and severe hypoglycemic episodes. Sensitivity analyses examined the associations between aspects of sleep quality and global cognitive function. The worst sleep quality quartile was associated with lower global cognition (β=-0.08; 95% confidence interval: -0.17, -0.01) and lower executive function (β=-0.17, 95% confidence interval: -0.30, -0.03) compared with the best quartile of sleep quality adjusting for demographics and comorbidities. Sleep quality was not associated with language, episodic memory, or simple attention. Sleep medications and daytime dysfunction were most strongly associated with global cognition. Our results suggest that sleep quality may be a modifiable risk factor for global cognitive function and executive function among elderly individuals with T1D.
Authors: Gilsanz P; Lacy ME; Beeri MS; Karter AJ; Eng CW; Whitmer RA
Alzheimer Dis Assoc Disord. 2020 Jan-Mar;34(1):18-24.
Genetic ancestry does not explain increased atopic dermatitis susceptibility or worse disease control among African American subjects in 2 large US cohorts
Atopic dermatitis (AD) is more common among African American children. Whether there are racial/ethnic difference among adults with AD and the causes for those disparities are unclear. We sought to examine the relationship between self-reported race/ethnicity and AD and determine whether African genetic ancestry is predictive of these outcomes among African American subjects. We analyzed data from 2 independent multiethnic longitudinal studies: 86,893 subjects aged 18 to 100 years from the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort and 5467 subjects aged 2 to 26 years from the national Pediatric Eczema Elective Registry (PEER) cohort. The primary outcomes were physician-diagnosed AD in GERA and repeated measures of self-reported disease control among patients with physician-diagnosed AD at 6-month intervals in PEER. We examined whether self-identified African American race/ethnicity was predictive of these outcomes and then tested whether a continuous measure of African genetic ancestry was associated with outcomes within the African American group. AD was more common among self-identified African American subjects than non-Hispanic white subjects in GERA (4.4% vs 2.1%; odds ratio, 2.06; 95% CI, 1.70-2.48) and less well-controlled in PEER subjects (odds of 1-level worse control, 1.91; 95% CI, 1.64-2.22). However, African genetic ancestry was not associated with AD risk or control among self-identified African American subjects in either cohort, nor did an AD polygenic risk score or genetic skin pigment score explain the AD disparities in patients with AD. Ancestry-related genetic effects do not explain increased AD prevalence or poorer disease control among African American subjects.
Authors: Abuabara K; You Y; Margolis DJ; Hoffmann TJ; Risch N; Jorgenson E
J Allergy Clin Immunol. 2020 01;145(1):192-198.e11. Epub 2019-07-29.
Long-term opioid therapy definitions and predictors: A systematic review
This review sought to (a) describe definitions of long-term opioid therapy (LTOT) outcome measures, and (b) identify the predictors associated with the transition from short-term opioid use to LTOT for opioid-naïve individuals. We conducted a systematic review of the peer-reviewed literature (January 2007 to July 2018). We included studies examining opioid use for more than 30 days. We classified operationalization of LTOT based on criteria used in the definitions. We extracted LTOT predictors from multivariate models in studies of opioid-naïve individuals. The search retrieved 5,221 studies, and 34 studies were included. We extracted 41 unique variations of LTOT definitions. About 36% of definitions required a cumulative duration of opioid use of 3 months. Only 17% of definitions considered consecutive observation periods, 27% used days’ supply, and no definitions considered dose. We extracted 76 unique predictors of LTOT from seven studies of opioid-naïve patients. Common predictors included pre-existing comorbidities (21.1%), non-opioid prescription medication use (13.2%), substance use disorders (10.5%), and mental health disorders (10.5%). Most LTOT definitions aligned with the chronic pain definition (pain more than 3 months), and used cumulative duration of opioid use as a criterion, although most did not account for consistent use. Definitions were varied and rarely accounted for prescription characteristics, such as days’ supply. Predictors of LTOT were similar to known risk factors of opioid abuse, misuse, and overdose. As LTOT becomes a central component of quality improvement efforts, researchers should incorporate criteria to identify consistent opioid use to build the evidence for safe and appropriate use of prescription opioids.
Authors: Karmali RN; Bush C; Raman SR; Campbell CI; Skinner AC; Roberts AW
Pharmacoepidemiol Drug Saf. 2019 Dec 18.
The associations of anthropometric, behavioural and sociodemographic factors with circulating concentrations of IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3 in a pooled analysis of 16,024 men from 22 studies
Insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross-sectional associations of these exposures with circulating concentrations of IGFs (IGF-I and IGF-II) and IGFBPs (IGFBP-1, IGFBP-2 and IGFBP-3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22-89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGF-I, IGF-II and IGFBP-3. Higher body mass index was associated with lower concentrations of IGFBP-1 and IGFBP-2. Taller height was associated with higher concentrations of IGF-I and IGFBP-3 and lower concentrations of IGFBP-1. Smokers had higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGFBP-3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF-II and lower concentrations of IGF-I and IGFBP-2. African Americans had lower concentrations of IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 and Hispanics had lower IGF-I, IGF-II and IGFBP-3 than non-Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk.
Authors: Watts EL; Habel LA; Schaefer CA; Van Den Eeden SK; Travis RC; et al.
Int J Cancer. 2019 12 15;145(12):3244-3256. Epub 2019-04-04.
Changes in Prostate Cancer Presentation Following the 2012 USPSTF Screening Statement: Observational Study in a Multispecialty Group Practice
In 2012, the US Preventive Services Task Force (USPSTF) recommended against PSA-based screening for prostate cancer in men of all ages. Following this change, screening declined yet the complete impact on clinical presentation is not well defined in the screen-eligible population. To determine if the rates of PSA screening, prostate biopsy, incident prostate cancer detection, and stage IV at presentation in screen-eligible men in Kaiser Permanente Northern California changed following the 2012 USPSTF Prostate Cancer Screening recommendations. Retrospective study spanning the years 2010 to 2015, in screen-eligible Kaiser Permanente Northern California members (African American men ages 45-69 and all other men ages 50-69) with no prior history of prostate cancer. Participants All screen-eligible, male members during 2010 (n = 403,931) to 2015 (n = 483,286) without a history of prostate cancer within all Kaiser Permanente Northern California facilities. Annual rates of PSA testing, prostate biopsy, incident prostate cancer detection, and stage IV cancer at presentation were compared between the pre-guideline period, 2010 and 2011, and the post-guideline period, 2014 and 2015, in men under the age of 70. Following the 2012 USPSTF guideline change, screening rates declined 23.4% (95% CI 23.0-23.8%), biopsy rates declined 64.3% (95% CI 62.9-65.6%), and incident prostate cancer detection rates declined 53.5% (95% CI 50.1-56.7%) resulting in 1871 fewer incident cancers detected, and metastatic cancer rates increased 36.9% (95% CI 9.5-71.0%) resulting in 75 more stage IV cancers detected. Less screening resulted in a large decrease in cancer detection, some of which may be beneficial as many cancers may be indolent, yet this decrease occurred at the expense of an increase in metastatic cancer rates. For every 25 fewer cancers detected, one metastatic cancer was diagnosed. This information may be valuable in the shared decision-making process around prostate cancer screening.
Authors: Presti J; Alexeeff S; Horton B; Prausnitz S; Avins AL
J Gen Intern Med. 2019 Dec 09.
Changing Results-Engage and Activate to Enhance Wellness: A Randomized Clinical Trial to Improve Cardiovascular Risk Management
Background Despite the success of current cardiovascular disease (CVD) management programs, many patients do not achieve optimal control of CVD-related risk factors. New strategies are needed to better activate and engage these patients. Methods and Results We conducted a parallel, 2-arm, randomized controlled trial, CREATE Wellness (Changing Results-Engage and Activate to Enhance Wellness) from February 2015 to September 2017 with 12-month follow-up to September 2018. Eligible participants had ≥1 uncontrolled CVD risk factors (hyperlipidemia, hypertension, or diabetes mellitus) for at least 2 years before study enrollment. The control group (n=315) received usual care within an existing CVD population-based disease management program. The intervention group (n=332) received usual care plus a group-based behavioral intervention focused on patient activation and engagement. Study outcomes included patient activation and patient-centered care processes (6 months) and healthcare system engagement, medication adherence, and control of CVD risk factors (12 months). Compared with the control group at follow-up, the intervention group had greater improvement in patient activation (adjusted mean difference=2.8, P=0.01), patient-centered care (adjusted mean difference=0.19, P=0.003), and 2 out of 3 measures of healthcare system engagement (eg, secure messages exchanged with a population health manager; adjusted incidence rate ratio=1.7, P=0.01). Intervention and control arms did not differ on improvement in 1-year CVD risk factor control. Conclusions Further work is needed to more effectively connect increased patient activation and engagement to downstream changes in risk factor control. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02302612.
Authors: Iturralde E; Sterling SA; Uratsu CS; Mishra P; Ross TB; Grant RW
J Am Heart Assoc. 2019 12 03;8(23):e014021. Epub 2019-11-30.
Use of >100,000 NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium whole genome sequences improves imputation quality and detection of rare variant associations in admixed African and Hispanic/Latino populations
Most genome-wide association and fine-mapping studies to date have been conducted in individuals of European descent, and genetic studies of populations of Hispanic/Latino and African ancestry are limited. In addition, these populations have more complex linkage disequilibrium structure. In order to better define the genetic architecture of these understudied populations, we leveraged >100,000 phased sequences available from deep-coverage whole genome sequencing through the multi-ethnic NHLBI Trans-Omics for Precision Medicine (TOPMed) program to impute genotypes into admixed African and Hispanic/Latino samples with genome-wide genotyping array data. We demonstrated that using TOPMed sequencing data as the imputation reference panel improves genotype imputation quality in these populations, which subsequently enhanced gene-mapping power for complex traits. For rare variants with minor allele frequency (MAF) < 0.5%, we observed a 2.3- to 6.1-fold increase in the number of well-imputed variants, with 11-34% improvement in average imputation quality, compared to the state-of-the-art 1000 Genomes Project Phase 3 and Haplotype Reference Consortium reference panels. Impressively, even for extremely rare variants with minor allele count <10 (including singletons) in the imputation target samples, average information content rescued was >86%. Subsequent association analyses of TOPMed reference panel-imputed genotype data with hematological traits (hemoglobin (HGB), hematocrit (HCT), and white blood cell count (WBC)) in ~21,600 African-ancestry and ~21,700 Hispanic/Latino individuals identified associations with two rare variants in the HBB gene (rs33930165 with higher WBC [p = 8.8×10-15] in African populations, rs11549407 with lower HGB [p = 1.5×10-12] and HCT [p = 8.8×10-10] in Hispanics/Latinos). By comparison, neither variant would have been genome-wide significant if either 1000 Genomes Project Phase 3 or Haplotype Reference Consortium reference panels had been used for imputation. Our findings highlight the utility of the TOPMed imputation reference panel for identification of novel rare variant associations not previously detected in similarly sized genome-wide studies of under-represented African and Hispanic/Latino populations.
Authors: Kowalski MH; Choquet H; Li Y; et al.
PLoS Genet. 2019 12;15(12):e1008500. Epub 2019-12-23.
Postoperative Opioid Use Before and After Enhanced Recovery After Surgery Program Implementation
Authors: Liu VX; Eaton A; Lee DC; Reyes VM; Paulson SS; Campbell CI; Avins AL; Parodi SM
Ann Surg. 2019 12;270(6):e69-e71.
Contribution of rare coding mutations in CD36 to type 2 diabetes and cardio-metabolic complications
We sequenced coding regions of the cluster of differentiation 36 (CD36) gene in 184 French individuals of European ancestry presenting simultaneously with type 2 diabetes (T2D), arterial hypertension, dyslipidemia, and coronary heart disease. We identified rare missense mutations (p.Pro191Leu/rs143150225 and p.Ala252Val/rs147624636) in two heterozygous cases. The two CD36 mutation carriers had no family history of T2D and no clustering of cardio-metabolic complications. While the p.Pro191Leu mutation was found in 84 heterozygous carriers from five ethnic groups from the genome aggregation database (global frequency: 0.0297%, N = 141,321), only one European carrier of the p.Ala252Val mutation was identified (global frequency: 0.00040%, N = 125,523). The Pro191 and Ala252 amino acids were not conserved (74.8% and 68.9% across 131 animal species, respectively). In vitro experiments showed that the two CD36 mutant proteins are expressed and trafficked to the plasma membrane where they bind modified low-density-lipoprotein (LDL) cholesterol as normal. However, molecular modelling of the recent CD36 crystal structure showed that Pro191 was located at the exit/entrance gate of the lipid binding chamber and Ala252 was in line with the chamber. Overall, our data do not support a major contribution of CD36 rare coding mutations to T2D and its cardio-metabolic complications in the French population.
Authors: Meyre D; Choquet H; Linton KJ; et al.
Sci Rep. 2019 11 20;9(1):17123. Epub 2019-11-20.
Comorbid Diabetes and Severe Mental Illness: Outcomes in an Integrated Health Care Delivery System
Diabetes prevalence is twice as high among people with severe mental illness (SMI) when compared to the general population. Despite high prevalence, care outcomes are not well understood. To compare diabetes health outcomes received by people with and without comorbid SMI, and to understand demographic factors associated with poor diabetes control among those with SMI. Retrospective cohort study PARTICIPANTS: 269,243 adults with diabetes MAIN MEASURES: Primary outcomes included optimal glycemic control (A1c < 7) or poor diabetes control (A1c > 9) in 2014. Secondary outcomes included control of other cardiometabolic risk factors (hypertension, dyslipidemia, smoking) and recommended diabetes monitoring. Among this cohort, people with SMI (N = 4,399), compared to those without SMI (N = 264,844), were more likely to have optimal glycemic control, adjusting for various covariates (adjusted relative risk (aRR) 1.25, 95% CI 1.21-1.28, p < .001) and less likely to have poor control (aRR 0.92, 95% CI 0.87-0.98, p = 0.012). Better blood pressure and lipid control was more prevalent among people with SMI when compared to those without SMI (aRR 1.03; 95% CI 1.02-1.05, p < .001; aRR 1.02; 95% CI 1.00-1.05, p = 0.044, respectively). No differences were observed in recommended A1c or LDL testing, but people with SMI were more likely to have blood pressure checked (aRR 1.02, 95% CI 1.02-1.03, p < .001) and less likely to receive retinopathy screening (aRR 0.80, 95% CI 0.71-0.91, p < .001) than those without SMI. Among people with diabetes and comorbid SMI, younger adults and Hispanics were more likely to have poor diabetes control. Adults with diabetes and comorbid SMI had better cardiometabolic control than people with diabetes who did not have SMI, despite lower rates of retinopathy screening. Among those with comorbid SMI, younger adults and Hispanics were more vulnerable to poor A1c control.
Authors: Mangurian C; Schillinger D; Newcomer JW; Vittinghoff E; Essock S; Zhu Z; Dyer W; Young-Wolff KC; Schmittdiel J
J Gen Intern Med. 2019 Nov 08.
Validity of Self-reported Cannabis Use Among Pregnant Females in Northern California
Most clinical and epidemiologic estimates of prenatal cannabis use are based on self-report, and the validity of self-reported cannabis use has not been examined in a large, representative population of pregnant women. We determined the validity of self-reported prenatal cannabis use and predictors of nondisclosure using data from Kaiser Permanente Northern California’s (KPNC) healthcare system with universal prenatal cannabis screening during prenatal care. Validation study using data from 281,025 pregnancies in KPNC among females aged ≥11 years who completed a self-administered questionnaire on prenatal cannabis use and a cannabis urine toxicology test from 2009 to 2017. We calculated sensitivity, specificity, positive predictive value, and negative predictive value of self-reported prenatal cannabis use using urine toxicology testing as the criterion standard, and sensitivity of urine toxicology testing using self-reported use as the criterion standard. We compared sociodemographics of those who disclosed versus did not disclose prenatal cannabis use. Urine toxicology testing identified more instances of prenatal cannabis use than self-report (4.9% vs 2.5%). Sensitivity of self-reported use was low (33.9%). Sensitivity of the toxicology test was higher (65.8%), with greater detection of self-reported daily (83.9%) and weekly (77.4%) than monthly or less use (54.1%). Older women, those of Hispanic race/ethnicity, and those with lower median neighborhood incomes were most likely to be misclassified as not using cannabis by self-reported screening. Given that many women choose not to disclose prenatal cannabis use, clinicians should educate all prenatal patients about the potential risks and advise them to quit cannabis use during pregnancy.
Authors: Young-Wolff KC; Sarovar V; Tucker LY; Goler N; Conway A; Weisner C; Armstrong MA; Alexeeff S
J Addict Med. 2019 Nov 04.
Maternal cortisol during pregnancy and offspring schizophrenia: Influence of fetal sex and timing of exposure
Maternal stress during pregnancy has been repeatedly linked to increased risk for schizophrenia; however, no study has examined maternal cortisol during pregnancy and risk for the disorder. Study aims were to determine whether prenatal cortisol was associated with risk for schizophrenia and risk for an intermediate phenotype-decreased fetal growth-previously linked to prenatal cortisol and schizophrenia. Timing of exposure and fetal sex also were examined given previous findings. Participants were 64 cases diagnosed with schizophrenia spectrum disorders (SSD) and 117 controls from a prospective birth cohort study. Maternal cortisol was determined from stored sera from each trimester and psychiatric diagnoses were assessed from offspring using semi-structured interviews and medical records review. Maternal cortisol during pregnancy was not associated with risk for offspring schizophrenia. There was a significant interaction between 3rd trimester cortisol and case status on fetal growth. Specifically, cases exposed to higher 3rd trimester maternal cortisol had significantly decreased fetal growth compared to controls. In addition, these findings were restricted to male offspring. Our results indicate that higher prenatal cortisol is associated with an intermediate phenotype linked to schizophrenia, fetal growth, but only among male offspring who developed schizophrenia. Findings were consistent with evidence that schizophrenia genes may disrupt placental functioning specifically for male fetuses, as well as findings that males are more vulnerable to maternal cortisol during pregnancy. Finally, results suggest that examining fetal sex and intermediate phenotypes may be important in understanding the mechanisms involved in prenatal contributors to schizophrenia.
Authors: Ellman LM; Murphy SK; Maxwell SD; Calvo EM; Cooper T; Schaefer CA; Bresnahan MA; Susser ES; Brown AS
Schizophr Res. 2019 11;213:15-22. Epub 2019-07-22.
Assessing strengths of children with type 1 diabetes: Validation of the Diabetes Strengths and Resilience (DSTAR) measure for ages 9 to 13
Adaptive diabetes-specific attitudes and behaviors, known as diabetes strengths, relate to positive self-management and quality of life outcomes in type 1 diabetes (T1D), but have not been studied in preadolescence. To facilitate strengths-based care and research on this topic, we developed and evaluated the psychometric properties of a measure of diabetes strengths for children age 9 to 13. Participants were 187 children receiving care for T1D at a tertiary care children’s hospital. They completed the 12-item self-report Diabetes Strengths and Resilience scale for children (DSTAR-Child), which we adapted from a measure validated for adolescents. Youth completed the DSTAR-Child twice, and measures of relevant constructs at baseline: general and diabetes-related quality of life, depressive symptoms, and diabetes distress. Parents rated children’s engagement in self-management behaviors and general resilience. We extracted HbA1c from the medical record. The DSTAR-Child total score demonstrated reliability, including internal consistency and stability across two time points. The total score was significantly associated in expected directions with psychosocial measures and glycemic control but not self-management behaviors. In confirmatory factor analyses, the best-fitting structure contained two latent factors tapping intrapersonal and interpersonal strengths. Resulting subscale scores also appeared reliable and valid. This brief, practical measure of diabetes strengths demonstrated sound psychometric properties. Diabetes strengths appeared unrelated to self-management behaviors, perhaps because of the primary role of adult caregivers in T1D management for preadolescents. As a research and clinical tool, the DSTAR-Child can facilitate greater understanding of diabetes strengths and inform strengths-based strategies to foster resilient T1D outcomes.
Authors: Iturralde E; Hood KK; Weissberg-Benchell J; Anderson BJ; Hilliard ME
Pediatr Diabetes. 2019 11;20(7):1007-1015. Epub 2019-07-29.
Physician-Training Stress and Accelerated Cellular Aging
Stress is a key precipitant for many common diseases, but established biological markers to track stress and guide investigations into mechanisms linking stress and disease are lacking. Cross-sectional studies have identified correlations between stress and telomere attrition, but no large, longitudinal studies examining the impacts of chronic stress on telomere length exist. Residency training for physicians is a well-established stressful experience and can be used as a prospective stress model. In a longitudinal cohort study of 250 interns (first-year residents) at 55 United States hospital systems serving during the 2015-2016 academic year, we examined associations between measures of the residency experience and saliva-measured telomere attrition. Telomere length shortened significantly over the course of internship year, from mean ± SD of 6465.1 ± 876.8 base pairs before internship to 6321.5 ± 630.6 base pairs at the end of internship (t246 = 2.69; p = .008). Stressful early family environments and neuroticism were significantly associated with shorter preinternship telomere length. Longer work hours were associated with greater telomere intern telomere loss over the year (p = .002). Of note, the mean telomere attrition during internship year was six times greater than the typical annual attrition rate identified in a recent meta-analysis. This work implicates telomere attrition as a biologically measurable consequence of physician training, with the magnitude of attrition associated with workload. Identification of an objective, biological sequela of residency stress may help to facilitate the development of effective interventions. Further, the findings implicate telomere attrition as an objective biomarker to follow the pathologic effects of stress, in general.
Authors: Ridout KK; Ridout SJ; Guille C; Mata DA; Akil H; Sen S
Biol Psychiatry. 2019 11 01;86(9):725-730. Epub 2019-05-09.
A Mobile Health App (Roadmap 2.0) for Patients Undergoing Hematopoietic Stem Cell Transplant: Qualitative Study on Family Caregivers’ Perspectives and Design Considerations.
BACKGROUND: Hematopoietic stem cell transplantation (HCT), also referred to as blood and marrow transplantation (BMT), is a high-risk, but potentially curative therapy for a number of cancer and noncancer conditions. BMT Roadmap (Roadmap 1.0) is a mobile health app that was developed as a family caregiver-facing tool to provide informational needs about the health status of patients undergoing inpatient HCT. n OBJECTIVE: This study explored the views and perceptions of family caregivers of patients undergoing HCT and their input regarding further technology development and expansion of BMT Roadmap into the outpatient setting (referred to as Roadmap 2.0). n METHODS: Semistructured qualitative interviews were conducted among 24 family caregivers. Questions were developed from existing literature coupled with prior in-depth observations and interviews in hospital-based settings to explore the study objectives. Participants were recruited during routine outpatient clinic appointments of HCT patients, and all interviews were conducted in the participants’ homes, the setting in which Roadmap 2.0 is intended for use. A thematic analysis was performed using a consistent set of codes derived from our prior research. New emerging codes were also included, and the coding structure was refined with iterative cycles of coding and data collection. n RESULTS: Four major themes emerged through our qualitative analysis: (1) stress related to balancing caregiving duties; (2) learning and adapting to new routines (resilience); (3) balancing one’s own needs with the patient’s needs (insight); and (4) benefits of caregiving. When caregivers were further probed about their views on engagement with positive activity interventions (ie, pleasant activities that promote positive emotions and well-being such as expressing gratitude or engaging in activities that promote positive thoughts, emotions, and behaviors), they preferred a “menu” of positive activities to help support caregiver health and well-being. n CONCLUSIONS: This study involved family caregivers as participants in the development of new components for Roadmap 2.0. Our research provided a further understanding of the many priorities that hematopoietic stem cell transplant family caregivers face while maintaining balance in their lives. Their schedules can often be unpredictable, even more so once the patient is discharged from the hospital. Our findings suggest that expanding Roadmap 2.0 into the outpatient setting may provide critical caregiver support and that HCT caregivers are interested in and willing to engage in positive activities that may enhance well-being and attenuate the stress associated with caregiving. n INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/resprot.4918.
Authors: Chaar, Dima;Shin, Ji Youn;Mazzoli, Amanda;Vue, Rebecca;Kedroske, Jacob;Chappell, Grant;Hanauer, David A;Barton, Debra;Hassett, Afton L;Choi, Sung Won
JMIR Mhealth Uhealth. 2019 Oct 24;7(10):e15775. doi: 10.2196/15775..
Locus of Control and Cognition in Older Adults With Type I Diabetes: Evidence For Sex Differences From the Study of Longevity in Diabetes (SOLID)
Life expectancy for individuals with type 1 diabetes mellitus (T1DM) has increased recently; however, it is unknown how diabetes care attitudes affect late-life brain health. The Study of Longevity in Diabetes (SOLID) consists of 734 older adults with T1DM, reporting diabetes locus of control (dLOC), age of diabetes diagnosis and other demographics, history of hypoglycemic episodes, and depressive symptoms. Global and domain-specific (language, executive function, episodic memory, simple attention) cognitive functioning was assessed at in-person interviews. Cross-sectional associations between dLOC and cognition were estimated using covariate-adjusted linear regression models in pooled and sex-stratified models. In pooled analyses, a 1-point increase in dLOC (more internal) was positively associated with global cognition [β=0.05, 95% confidence interval (CI): 0.02, 0.07], language (β=0.04, 95% CI: 0.01, 0.07), and executive function (β=0.04, 95% CI: 0.01, 0.07), but not episodic memory or simple attention. However, in sex-stratified analyses, this effect was seen only in males and not females. In elderly individuals with T1DM, we found associations between dLOC and cognition overall and in men but not women. Underlying sex differences should be considered in future research or interventions on psychosocial characteristics for cognition.
Authors: Eng CW; Gilsanz P; Lacy ME; Beeri M; Whitmer RA
Alzheimer Dis Assoc Disord. 2019 Oct 17.
Assessing the clinical impact of CYP2C9 pharmacogenetic variation on phenytoin prescribing practice and patient response in an integrated health system
To assess the impact of CYP2C9 variation on phenytoin patient response and clinician prescribing practice where genotype was unknown during treatment. A retrospective analysis of Resource on Genetic Epidemiology Research on Adult Health and Aging cohort participants who filled a phenytoin prescription between 1996 and 2017. We used laboratory test results, medication dispensing records, and medical notes to identify associations of CYP2C9 genotype with phenytoin blood concentration, neurologic side effects, and medication dispensing patterns reflecting clinician prescribing practice and patient response. Among 993 participants, we identified 69% extensive, 20% high-intermediate, 10% low-intermediate, and 2% poor metabolizers based on CYP2C9 genotypes. Compared with extensive metabolizer genotype, low-intermediate/poor metabolizer genotype was associated with increased dose-adjusted phenytoin blood concentration [21.3 pg/mL, 95% confidence interval (CI): 13.6-29.0 pg/mL; P < 0.01] and increased risk of neurologic side effects (hazard ratio: 2.40, 95% CI: 1.24-4.64; P < 0.01). Decreased function CYP2C9 genotypes were associated with medication dispensing patterns indicating dose decrease, use of alternative anticonvulsants, and worse adherence, although these associations varied by treatment indication for phenytoin. CYP2C9 variation was associated with clinically meaningful differences in clinician prescribing practice and patient response, with potential implications for healthcare utilization and treatment efficacy.
Authors: Fohner AE; Ranatunga DK; Thai KK; Lawson BL; Risch N; Oni-Orisan A; Jelalian AT; Rettie AE; Liu VX; Schaefer CA
Pharmacogenet Genomics. 2019 10;29(8):192-199.
Interventions to Reduce Unhealthy Alcohol Use among Primary Care Patients with HIV: the Health and Motivation Randomized Clinical Trial
Unhealthy alcohol use has adverse effects on HIV treatment. Screening, brief intervention, and referral to treatment (SBIRT) has some evidence of efficacy but may not be sufficient for those with low motivation or comorbid substance use. To examine the effectiveness of motivational interviewing (MI) and emailed feedback (EF) among primary care HIV-positive patients, compared with treatment as usual care (UC) only, which included SBIRT. Randomized clinical trial. Six hundred fourteen adult HIV-positive patients in Kaiser Permanente Northern California who reported prior-year unhealthy alcohol use. Participants were randomized to either three sessions of MI (one in person and two by phone), information regarding alcohol risks via EF through a patient portal, or UC alone. MI and EF participants who reported unhealthy alcohol use at 6 months were offered additional MI and EF treatment, respectively. Participant-reported unhealthy alcohol use (defined as ≥ 4/≥ 5 drinks per day for women/men), alcohol problems at 12 months, based on blinded telephone interviews. Secondary outcomes included drug use and antiretroviral (ART) adherence. At 12 months, there were no overall group differences, but in all three arms, there were declines in unhealthy alcohol use and alcohol-related problems (p < 0.001). Participants reporting low motivation to reduce drinking at baseline were less likely to report unhealthy alcohol use if they received MI vs. EF and UC (p = 0.013). At 6 months, reported illegal drug use/misuse of prescription drugs other than marijuana was lower in the MI arm than EF or UC (p = 0.012). There were no differences in ART adherence between groups. In a randomized trial of HIV-positive patients using two behavioral interventions compared with SBIRT alone, participants in all three conditions reduced unhealthy alcohol use. MI may provide added benefit for patients with low motivation or who report illegal drug use/misuse of prescription drugs. NCT01671501 ( ClinicalTrials.gov ).
Authors: Satre DD; Lam JO; Weisner CM; Sterling SA; Silverberg MJ; et al.
J Gen Intern Med. 2019 10;34(10):2054-2061. Epub 2019-06-11.
Multisite Pain Is Associated with Long-term Patient-Reported Outcomes in Older Adults with Persistent Back Pain
To estimate the prevalence of co-occurring pain sites among older adults with persistent back pain and associations of multisite pain with longitudinal outcomes. Secondary analysis of a cohort study. Three integrated health systems in the United States. Eight hundred ninety-nine older adults with persistent back pain. Participants reported pain in the following sites: stomach, arms/legs/joints, headaches, neck, pelvis/groin, and widespread pain. Over 18 months, we measured back-related disability (Roland Morris, scored 0-24), pain intensity (11-point numerical rating scale), health-related quality of life (EuroQol-5D [EQ-5D], utility from 0-1), and falls in the past three weeks. We used mixed-effects models to test the association of number and type of pain sites with each outcome. Nearly all (N = 839, 93%) respondents reported at least one additional pain site. There were 216 (24%) with one additional site and 623 (69%) with multiple additional sites. The most prevalent comorbid pain site was the arms/legs/joints (N = 801, 89.1%). Adjusted mixed-effects models showed that for every additional pain site, RMDQ worsened by 0.65 points (95% confidence interval [CI] = 0.43 to 0.86), back pain intensity increased by 0.14 points (95% CI = 0.07 to 0.22), EQ-5D worsened by 0.012 points (95% CI = -0.018 to -0.006), and the odds of falling increased by 27% (odds ratio = 1.27, 95% CI = 1.12 to 1.43). Some specific pain sites (extremity pain, widespread pain, and pelvis/groin pain) were associated with greater long-term disability. Multisite pain is common among older adults with persistent back pain. Number of pain sites was associated with all outcomes; individual pain sites were less consistently associated with outcomes.
Authors: Rundell SD; Avins AL; Jarvik JG; et al.
Pain Med. 2019 10 01;20(10):1898-1906.
Is it possible to overcome the ‘long arm’ of childhood socioeconomic disadvantage through upward socioeconomic mobility?
Socioeconomically disadvantaged children have worse adult health; we test if this ‘long arm’ of childhood disadvantage can be overcome through upward socioeconomic mobility in adulthood. Four SES trajectories (stable low, upwardly mobile, downwardly mobile and stable high) were created from median dichotomized childhood socioeconomic status (SES; childhood human and financial capital) and adult SES (wealth at age 67) from Health and Retirement Study respondents (N = 6669). Healthy ageing markers, in tertiles, were walking speed, peak expiratory flow (PEF), and grip strength measured in 2008 and 2010. Multinomial logistic regression models, weighted to be nationally representative, controlled for age, gender, race, birthplace, outcome year and childhood health and social capital. Upwardly mobile individuals were as likely as the stable high SES group to be in the best health tertile for walking speed (OR = 0.81; 95% CI: 0.63, 1.05; P = 0.114), PEF (OR = 0.97; 95% CI: 0.78, 1.21; P = 0.810) and grip strength (OR = 0.97; 95%CI: 0.74, 1.27; P = 0.980). Findings suggest the ‘long arm’ of childhood socioeconomic disadvantage can be overcome for these markers of healthy ageing through upward socioeconomic mobility.
Authors: Vable AM; Gilsanz P; Kawachi I
J Public Health (Oxf). 2019 09 30;41(3):566-574.
Enhanced Recovery After Surgery to Change Process Measures and Reduce Opioid Use After Cesarean Delivery: A Quality Improvement Initiative
To evaluate implementation of an enhanced recovery after surgery (ERAS) program for patients undergoing elective cesarean delivery by comparing opioid exposure, multimodal analgesia use, and other process and outcome measures before and after implementation. An ERAS program was implemented among patients undergoing elective cesarean delivery in a large integrated health care delivery system. We conducted a pre-post study of ERAS implementation to compare changes in process and outcome measures during the 12 months before and 12 months after implementation. The study included 4,689 patients who underwent an elective cesarean delivery in the 12 months before (pilot sites: March 1, 2015-February 29, 2016, all other sites: October 1, 2015-September 30, 2016), and 4,624 patients in the 12 months after (pilot sites: April 1, 2016-March 31, 2017, all other sites: November 1, 2016-October 31, 2017) ERAS program implementation. After ERAS implementation mean inpatient opioid exposure (average daily morphine equivalents) decreased from 10.7 equivalents (95% CI 10.2-11.3) to 5.4 equivalents (95% CI 4.8-5.9) controlling for age, race-ethnicity, prepregnancy body mass index, patient reported pain score, and medical center. The use of multimodal analgesia (ie, acetaminophen and neuraxial anesthesia) increased from 9.7% to 88.8%, the adjusted risk ratio (RR) for meeting multimodal analgesic goals was 9.13 (RR comparing post-ERAS with pre-ERAS; 95% CI 8.35-10.0) and the proportion of time patients reported acceptable pain scores increased from 82.1% to 86.4% (P<.001). Outpatient opioids dispensed at hospital discharge decreased from 85.9% to 82.2% post-ERAS (P<.001) and the average number of dispensed pills decreased from 38 to 26 (P<.001). The hours to first postsurgical ambulation decreased by 2.7 hours (95% CI -3.1 to -2.4) and the hours to first postsurgical solid intake decreased by 11.1 hours (95% CI -11.5 to -10.7). There were no significant changes in hospital length of stay, surgical site infections, hospital readmissions, or breastfeeding rates. Implementation of an ERAS program in patients undergoing elective cesarean delivery was associated with a reduction in opioid inpatient and outpatient exposure and with changes in surgical process measures of care without worsened surgical outcomes.
Authors: Hedderson M; Campbell C; Quesenberry C; Liu V; et al.
Obstet Gynecol. 2019 09;134(3):511-519.
Implementing electronic substance use disorder and depression and anxiety screening and behavioral interventions in primary care clinics serving people with HIV: Protocol for the Promoting Access to Care Engagement (PACE) trial
Substance use disorders (SUDs) and psychiatric disorders are common among people with HIV (PWH) and lead to poor outcomes. Yet these conditions often go unrecognized and untreated in primary care. The Promoting Access to Care Engagement (PACE) trial currently in process examines the impact of self-administered electronic screening for SUD risk, depression and anxiety in three large Kaiser Permanente Northern California primary care clinics serving over 5000 PWH. Screening uses validated measures (Tobacco, Alcohol, Prescription medication, and other Substance use [TAPS]; and the Adult Outcomes Questionnaire [AOQ], which includes the Patient Health Questionnaire [PHQ-9] and Generalized Anxiety Disorder [GAD-2]) delivered via three modalities (secure messaging, tablets in waiting rooms, and desktop computers in exam rooms). Results are integrated automatically into the electronic health record. Based on screening results and physician referrals, behavioral health specialists embedded in primary care initiate motivational interviewing- and cognitive behavioral therapy-based brief treatment and link patients to addiction and psychiatry clinics as needed. Analyses examine implementation (screening and treatment rates) and effectiveness (SUD, depression and anxiety symptoms; HIV viral control) outcomes using a stepped-wedge design, with a 12-month intervention phase implemented sequentially in the clinics, and a 24-month usual care period prior to implementation in each clinic functioning as sequential observational phases for comparison. We also evaluate screening and treatment costs and implementation barriers and facilitators. The study examines innovative, technology-facilitated strategies for improving assessment and treatment in primary care. Results may help to inform substance use, mental health, and HIV services. NCT03217058.
Authors: Satre DD; Weisner CM; Silverberg MJ; et al.
Contemp Clin Trials. 2019 09;84:105833. Epub 2019-08-22.
Association of Anxiety With High-Cost Health Care Use Among Individuals With Type 2 Diabetes
People with type 2 diabetes vary greatly in their use of high-cost health care resources. We examined the association of anxiety with high-cost use after accounting for depression and medical comorbidity. Using electronic health record data, we assessed past anxiety diagnosis, health care use and costs, demographics, comorbidities, and diabetes control status and complications during 2008-2012 for 143,573 adult members of an integrated health care system with type 2 diabetes. Multivariable regression models estimated associations between anxiety and emergency department (ED) use, total hospitalization costs, and high-cost status (i.e., incurring total health care costs in the top 20% among all system members). During 2008-2011, 12.9% of participants received a diagnosis of anxiety, of whom 52.9% also had received a depression diagnosis. After adjustment for covariates including depression, anxiety was positively related to the number of ED visits in 2012 (incidence rate ratio 1.27; 95% CI 1.21, 1.34), the likelihood of visiting the ED on a chronic, frequent basis during 2010-2012 (odds ratio 2.55; 95% CI 1.90, 3.44), and high-cost status in 2012 (odds ratio 1.29; 95% CI 1.23, 1.36), but anxiety was not related to total hospitalization costs in 2012 (relative cost ratio 1.06; 95% CI 0.94, 1.21; P = 0.33). Anxiety is highly comorbid with depression among individuals with type 2 diabetes and is independently associated with high-cost resource use. Strategies to improve anxiety management among people with diabetes hold the potential to also reduce health care costs.
Authors: Iturralde E; Chi FW; Grant RW; Weisner C; Van Dyke L; Pruzansky A; Bui S; Madvig P; Pearl R; Sterling SA
Diabetes Care. 2019 09;42(9):1669-1674. Epub 2019-06-18.
Bidirectional 10-year associations of accelerometer-measured sedentary behavior and activity categories with weight among middle-aged adults
Although higher sedentary behavior (SB) with low light intensity (LPA) and moderate-to-vigorous intensity physical activity (MVPA) are thought to increase risk for obesity, other data suggest excess weight may precede these behaviors in the causal pathway. We aimed to investigate 10-year bidirectional associations between SB and activity with weight. Analysis included 886 CARDIA participants (aged 38-50 years, 62% female, 38% black) with weight and accelerometry ( ≥ 4 days with ≥ 10 h/day) collected in 2005-6 (ActiGraph 7164) and 2015-6 (ActiGraph wGT3X-BT). Accelerometer data were calibrated, harmonized, and expressed as counts per minute (cpm) and time-dependent intensity categories (min/day of SB, LPA, and MVPA; SB and MVPA were also separated into long-bout and short-bout categories). Linear regression models were constructed to estimate adjusted associations of baseline activity with 10-year change in weight and vice versa. When activity categories were the independent variables, standardized regression coefficients (βstd.) estimated associations of replacing SB with a one SD increase in other categories, adjusted for accelerometer wear time. Over 10-years, weight increased by a mean 2.55 ± 8.05 kg and mean total activity decreased by 50 ± 153 cpm. In adjusted models, one SD higher baseline mean total activity (βstd. = -1.4 kg, p
Authors: Barone Gibbs B; Aaby D; Siddique J; Reis JP; Sternfeld B; Whitaker K; Pettee Gabriel K
Int J Obes (Lond). 2019 Aug 28.
HIV Disease Severity is Sensitive to Temporal Changes in Alcohol Use: A National Study of VA Patients with HIV
Alcohol use influences HIV disease severity through multiple mechanisms. Whether HIV disease severity is sensitive to changes in alcohol use among people with HIV (PWH) is understudied. National Veterans Health Administration. Pairs of AUDIT-C screens within 9-15 months (February 1, 2008-September 30, 2014) were identified among PWH from the Veterans Aging Cohort Study (VACS). Initial and follow-up VACS Index 2.0 pairs obtained 0-270 days after initial and follow-up AUDIT-Cs, respectively, determined change in VACS Index 2.0, a composite HIV severity measure. Change in VACS Index 2.0 was regressed on AUDIT-C change scores (-12 to +12) adjusted for demographics, initial VACS Index 2.0, and days between VACS Index measures. Among 23,297 PWH (76,202 observations), most had no (51%) or low-level (38%) alcohol use initially. Most (54%) had no subsequent change; 21% increased and 24% decreased drinking. Initial VACS Index 2.0 scores ranged from 0 to 134, change scores ranged from -65 to +73, with average improvement of 0.76 points (SD 9.48). AUDIT-C change was associated with VACS Index 2.0 change (P < 0.001). Among those with stable alcohol use (AUDIT-C change ≤ │1│ point), VACS Index 2.0 improvements ranged 0.36-0.60 points. For those with maximum AUDIT-C increase (change from 0 to 12), VACS Index 2.0 worsened 3.74 points (95% CI: -4.71 to -2.78); for those with maximum AUDIT-C decrease (change from 12 to 0), VACS Index 2.0 changed minimally [-0.60 (95% CI: -1.43 to 0.23)]. In this national sample, improvement in HIV severity was generally greatest among those with stable alcohol use (primarily those with no use).
Authors: Williams EC; Satre DD; Bradley KA; et al.
J Acquir Immune Defic Syndr. 2019 08 01;81(4):448-455.
Intimate Partner Violence and Psychological Distress: Opportunities for Prevention and Early Intervention Among Emerging Adult Women
Authors: Young-Wolff KC; McCaw B
J Womens Health (Larchmt). 2019 08;28(8):1013-1014. Epub 2019-07-16.
A Seat at the Table: Strategic Engagement in Service Activities for Early Career Faculty From Underrepresented Groups in the Academy
Many academic institutions strive to promote more diverse and inclusive campuses for faculty, staff, and students. As part of this effort, these institutions seek to include individuals from historically underrepresented groups (URGs)-such as women, people from racial/ethnic minority populations, persons with disabilities-on committees and in other service activities. However, given the low number of faculty members from URGs at many institutions, these faculty members tend to receive more requests to provide service to the institution or department (e.g., serving on committees, mentoring) than their counterparts from majority groups. Faculty members from URGs, especially early-career faculty, thus risk becoming overburdened with providing service at the expense of working on other scholarly activities required for promotion and tenure (i.e., conducting research, publishing). Although many scholars and others have written about this “minority tax” and its implications for early-career faculty from underrepresented racial/ethnic minority groups, fewer have published about how this tax extends beyond racial/ethnic minorities to women and persons with disabilities. Further, the literature provides scant practical advice on how to avoid overburdening early-career faculty from URGs. Here, a group of multidisciplinary early- and mid-career faculty members from URGs seek to provide their peers from URGs with practical strategies for both evaluating the appropriateness of service requests and declining those that are not a good fit. The authors also provide institutional leaders with actionable recommendations to prevent early-career faculty from URGs from becoming overburdened with service.
Authors: Carson TL; Aguilera A; Brown SD; Peña J; Butler A; Dulin A; Jonassaint CR; Riley I; Vanderbom K; Molina KM; Cené CW
Acad Med. 2019 08;94(8):1089-1093.
Self-reported Daily, Weekly, and Monthly Cannabis Use Among Women Before and During Pregnancy
As the overall prevalence of prenatal cannabis use rises, it is vital to also monitor trends in the frequency of cannabis use in the period leading up to and during pregnancy because more frequent use may confer greater health risks for mothers and their children. To examine trends in the frequency of self-reported cannabis use among pregnant women in the year before and during pregnancy. Cross-sectional study using data from 367 403 pregnancies among 276 991 women 11 years or older who completed a self-administered questionnaire on cannabis use during standard prenatal care in Kaiser Permanente Northern California from January 1, 2009, to December 31, 2017. The annual prevalence of self-reported daily, weekly, and monthly cannabis use among women before and during pregnancy was estimated using Poisson regression with a log link function, adjusting for sociodemographics. Data analyses were conducted from February to May 2019. Calendar year. Self-reported frequency of cannabis use in the year before pregnancy and during pregnancy assessed as part of standard prenatal care (at approximately 8 weeks’ gestation). Among the overall sample of 367 403 pregnancies among 276 991 women, 35.9% of the women self-reported white race/ethnicity; 28.0%, Hispanic; 16.6%, Asian; 6.0%, African American; and 13.5%, other. In the sample, 1.2% of the women were aged 11 to 17 years; 15.3%, 18 to 24 years; 61.4%, 25 to 34 years; and 22.0%, older than 34 years. Median (interquartile range) neighborhood household income was $70 472 ($51 583-$92 643). From 2009 to 2017, the adjusted prevalence of cannabis use in the year before pregnancy increased from 6.80% (95% CI, 6.42%-7.18%) to 12.50% (95% CI, 12.01%-12.99%), and the adjusted prevalence of cannabis use during pregnancy increased from 1.95% (95% CI, 1.78%-2.13%) to 3.38% (95% CI, 3.15%-3.60%). Annual relative rates of change in self-reported daily cannabis use (1.115; 95% CI, 1.103-1.128), weekly cannabis use (1.083; 95% CI, 1.071-1.095), and monthly or less cannabis use (1.050; 95% CI, 1.043-1.057) in the year before pregnancy increased significantly, with daily use increasing most rapidly (from 1.17% to 3.05%). Similarly, annual relative rates of change in self-reported daily cannabis use (1.110; 95% CI, 1.089-1.132), weekly cannabis use (1.075; 95% CI, 1.059-1.092) and monthly or less cannabis use (1.044; 95% CI, 1.032-1.057) during pregnancy increased significantly from 2009 to 2017, with daily use increasing most rapidly (from 0.28% to 0.69%). Results of this study demonstrate that frequency of cannabis use in the year before pregnancy and during pregnancy has increased in recent years among pregnant women in Northern California, potentially associated with increasing acceptance of cannabis use and decreasing perceptions of cannabis-associated harms.
Authors: Young-Wolff KC; Sarovar V; Tucker LY; Conway A; Alexeeff S; Weisner C; Armstrong MA; Goler N
JAMA Netw Open. 2019 07 03;2(7):e196471. Epub 2019-07-03.
Barriers and facilitators to healthy eating among low-income Latino adolescents
The objective of this study was to explore barriers and facilitators to healthy eating among low-income Latino adolescents using an intervention development framework. Semi-structured interviews (n = 30) were conducted with Latino youth ages 13-17 who had overweight or obesity at a safety-net clinic in San Francisco, CA. Adolescent beliefs and attitudes regarding healthy eating and individual, family, and community level barriers and facilitators were elicited. Interviews were analyzed using an inductive approach and the Capability-Opportunity-Motivation (COM-B) model. Participants had capability gaps; while they demonstrated basic nutrition knowledge, they also held significant misconceptions about healthy eating, equating “organic” with healthy and failing to recognize sugar in a number of beverages and foods. Families were a source of support through role modeling and purchasing fresh produce, yet in many cases also undermined adolescents’ healthy eating goals through purchases of high calorie low nutrient food, an opportunity facilitator and challenge. By contrast, peers were mostly a negative influence due to frequent consumption of high calorie low nutrient food. The school environment posed opportunity challenges as participants found school lunch unpalatable and had ready access to unhealthy options nearby. Participants were motivated to improve their eating habits but often not resilient in the face of obstacles. Interventions to promote healthy eating among low-income Latino adolescents should address common nutritional misconceptions, target families as well as teens, consider peer influences, and advocate for policy approaches that improve the school food environment.
Authors: Beck AL; Iturralde E; Haya-Fisher J; Kim S; Keeton V; Fernandez A
Appetite. 2019 07 01;138:215-222. Epub 2019-04-04.
Optimizing the use of continuous glucose monitoring in young children with type 1 diabetes with an adaptive study design and multiple randomizations
Parents of young children with type 1 diabetes (T1D) experience unique, developmental challenges in managing their child’s T1D, resulting in psychosocial distress. Only a small portion of young children reach glucose goals and adherence to diabetes devices that help improve T1D management have historically been low in this population. The purpose of this study is to test four interventions that couple developmentally tailored behavioral supports with education to optimize use of diabetes devices, improve glucose control, and reduce psychosocial distress for parents of young children with T1D. The study team designed four behavioral interventions, two aimed at improving glucose control and two aimed at optimizing use of diabetes devices. The goal of this paper is to describe the behavioral interventions developed for this study, including the results of a pilot test, and describe the methods and analysis plan to test this intervention strategy with ninety participants in a large-scale, randomized trial using a sequential multiple assignment randomization trial (SMART) design. A SMART design will permit a clinically relevant evaluation of the intervention strategy, as it allows multiple randomizations based on individualized assessments throughout the study instead of a fixed intervention dose seen in most traditional randomized controlled trials.
Authors: Berget, Cari; Iturralde, Esti; Toddler Diabetes Technology Study Group,; et al.
Contemp Clin Trials. 2019 07;82:60-65. Epub 2019-05-23.
Initiation of antidepressant medication and risk of incident stroke: using the Adult Changes in Thought cohort to address time-varying confounding
Depression strongly predicts stroke incidence, suggesting that treating depression may reduce stroke risk. Antidepressant medications, however, may increase stroke risk via direct pathways. Previous evidence on antidepressant medication and stroke incidence is mixed. We evaluated associations between antidepressant use and incident stroke. For 2302 Adult Changes in Thought cohort participants with no stroke at study entry, we characterized antidepressant use from pharmacy records, biennial depressive symptoms with a 10-item Centers for Epidemiologic Study-Depression scale, and incident strokes from ICD codes. We used discrete-time survival models with inverse probability weighting to compare stroke risk associated with filling antidepressant prescriptions and by medication category: tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors, or other. Over an average 8.4-year follow-up, 441 incident strokes occurred. Filling antidepressant medications 3+ times versus 0-2 times predicted 35% increased odds of stroke (OR = 1.35; 95% CI: 0.98, 1.66). Use of TCAs was associated with stroke onset (OR per 10 fills = 1.28; CI: 1.04, 1.57), but use of selective serotonin reuptake inhibitors (OR = 0.98; CI: 0.80, 1.20) or other antidepressants (OR = 0.99; CI: 0.67, 1.45) was not. Although patients who received antidepressant medication were at higher risk of stroke, this association appeared specific to TCA prescriptions.
Authors: Glymour MM; Gilsanz P; Crane PK; et al.
Ann Epidemiol. 2019 07;35:42-47.e1. Epub 2019-05-11.
Stressors in Midlife and Risk of Dementia: The Role of Race and Education
Posttraumatic stress disorder is associated with increased dementia risk but less is known about stress because of everyday problems in diverse populations. A total of 9605 health care plan members who provided information regarding midlife stressors in 1972 to 1973 (ages, 40 to 55 y) were followed for dementia diagnosis between 1996 and 2017. Cox proportional hazard models evaluated associations between midlife stressors and dementia adjusting for demographics and lifecourse health indicators. Reporting at least 1 midlife stressor was associated with 17% greater dementia risk [hazard ratio (HR), 1.17; 95% confidence interval (CI),1.07-1.27] versus 0 midlife stressors and 26% increased risk among those with less than equal to high school education (HR, 1.26; 95% CI,1.09-1.44) adjusting for demographics. Compared with whites without stressors, whites with ≥1 stressor had 13% greater dementia risk (HR, 1.13; 95% CI, 1.02-1.24), blacks without stressors 19% greater risk (HR, 1.19; 95% CI,1.08-1.32), and blacks with ≥1 stressors 47% greater risk (HR, 1.47; 95% CI,1.27-1.69) in fully adjusted models. Resource problems were associated with 20% greater risk (HR, 1.20; 95% CI, 1.01-1.42) than interpersonal problems. Reporting ≥1 serious midlife stressor was associated with elevated dementia risk, especially stressors related to resources problems and for those with less than equal to high school education. Everyday stressors can impact brain health over the long term and may contribute to racial inequities in dementia rates, though education can be a mitigating factor.
Authors: Gilsanz P; Quesenberry CP; Mayeda ER; Glymour MM; Farias ST; Whitmer RA
Alzheimer Dis Assoc Disord. 2019 Jul-Sep;33(3):200-205.
Multiple Stakeholder Views on Data Sharing in a Biobank in an Integrated Healthcare Delivery System: Implications for Biobank Governance
Beginning in 2005, researchers at Kaiser Permanente Northern California (KPNC) Division of Research developed the Research Program on Genes, Environment, and Health (RPGEH), a research resource of linked biospecimens, health surveys, and electronic health records on more than 200,000 adult KPNC members. This study examined multiple stakeholders’ values and preferences regarding protection of participants’ privacy and wide sharing of participant data by RPGEH. We conducted 45 semi-structured interviews in person or via phone and two focus groups with seven stakeholder groups, including RPGEH participants and decliners who are KPNC members, KPNC research scientists, external scientists, leadership, Human Subjects Research Protection Program staff, and RPGEH Community Advisory Panel members. Three major themes emerged related to: (1) perceived individual and social harms associated with data sharing; (2) concerns to address when governing access to RPGEH data; and (3) impact of a blurred boundary between research and clinical care in the context of biobanking. The study results were considered in the development of RPGEH data governance and motivated the inclusion of KPNC Community Advisory Panel members and ELSI experts on committees that evaluate data access proposals. Our findings can help inform other biobanks going through similar processes developing data sharing and access policies.
Authors: Tai CG; Harris-Wai J; Schaefer C; Liljestrand P; Somkin CP
Public Health Genomics. 2019 Jun 05:1-10.
Telomere length and socioeconomic status at neighborhood and individual levels among 80,000 adults in the Genetic Epidemiology Research on Adult Health and Aging cohort
Telomere length (TL) may serve as a biologic marker of aging. We examined neighborhood and individual-level socioeconomic status (SES) in relation to TL. The study included 84,996 non-Hispanic white subjects from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort, part of the Research Program on Genes, Environment and Health. Relative TL (T/S) was log2 transformed to improve normality and standardized to have mean 0 and variance 1. Neighborhood SES was measured using the Neighborhood Deprivation Index (NDI), and individual SES was measured by self-reported education level. We fit linear regression models of TL on age, sex, smoking, body mass index, comorbidities, NDI, and education level. We tested for differences in the associations by sex and nonlinearity in the association of NDI with TL. Each SD increase in NDI was associated with a decrease of 0.0192 in standardized TL, 95% confidence interval (CI) = -0.0306, -0.0078. There was no evidence of nonlinearity in the association of NDI with TL. We further found that less than high school education was associated with a decrease of 0.1371 in standardized TL, 95% CI = -0.1919, -0.0823 as compared to a college education. There were no differences in the associations by sex. We found evidence that both lower neighborhood SES and lower individual-level SES are associated with shorter TL among non-Hispanic whites. Our findings suggest that socioeconomic factors may influence aging by contributing to shorter TL.
Authors: Alexeeff, Stacey E; Schaefer, Catherine A; Risch, Neil; Sakoda, Lori C; Quesenberry, Charles P; Van Den Eeden, Stephen K; et al.
Environ Epidemiol. 2019 Jun;3(3):e049. Epub 2019-05-01.
miRNA contributions to pediatric-onset multiple sclerosis inferred from GWAS
Onset of multiple sclerosis (MS) occurs in childhood for approximately 5% of cases (pediatric MS, or ped-MS). Epigenetic influences are strongly implicated in MS pathogenesis in adults, including the contribution from microRNAs (miRNAs), small noncoding RNAs that affect gene expression by binding target gene mRNAs. Few studies have specifically examined miRNAs in ped-MS, but individuals developing MS at an early age may carry a relatively high burden of genetic risk factors, and miRNA dysregulation may therefore play a larger role in the development of ped-MS than in adult-onset MS. This study aimed to look for evidence of miRNA involvement in ped-MS pathogenesis. GWAS results from 486 ped-MS cases and 1362 controls from the U.S. Pediatric MS Network and Kaiser Permanente Northern California membership were investigated for miRNA-specific signals. First, enrichment of miRNA-target gene network signals was evaluated using MIGWAS software. Second, SNPs in miRNA genes and in target gene binding sites (miR-SNPs) were tested for association with ped-MS, and pathway analysis was performed on associated target genes. MIGWAS analysis showed that miRNA-target gene signals were enriched in GWAS (P = 0.038) and identified 39 candidate biomarker miRNA-target gene pairs, including immune and neuronal signaling genes. The miR-SNP analysis implicated dysregulation of miRNA binding to target genes in five pathways, mainly involved in immune signaling. Evidence from GWAS suggests that miRNAs play a role in ped-MS pathogenesis by affecting immune signaling and other pathways. Candidate biomarker miRNA-target gene pairs should be further studied for diagnostic, prognostic, and/or therapeutic utility.
Authors: Rhead B; Schaefer C; Barcellos LF; US Network of Pediatric MS Centers; et al.
Ann Clin Transl Neurol. 2019 Jun;6(6):1053-1061. Epub 2019-05-15.
Patterns of Alcohol Use Among Patients Living With HIV in Urban, Large Rural, and Small Rural Areas
For people living with HIV (PLWH), alcohol use is harmful and may be influenced by unique challenges faced by PLWH living in rural areas. We describe patterns of alcohol use across rurality among PLWH. Veterans Aging Cohort Study electronic health record data were used to identify patients with HIV (ICD-9 codes for HIV or AIDS) who completed AUDIT-C alcohol screening between February 1, 2008, and September 30, 2014. Regression models estimated and compared 4 alcohol use outcomes (any use [AUDIT-C > 0] and alcohol use disorder [AUD; ICD-9 codes for abuse or dependence] diagnoses among all PLWH, and AUDIT-C risk categories: lower- [1-3 men/1-2 women], moderate- [4-5 men/3-5 women], higher- 6-7]), and severe-risk [8-12], and heavy episodic drinking (HED; ?1 past-year occasion) among PLWH reporting use) across rurality (urban, large rural, small rural) and census-defined region. Among 32,699 PLWH (29,540 urban, 1,301 large rural, and 1,828 small rural), both any alcohol use and AUD were highest in urban areas, although this varied across region. Predicted prevalence of any alcohol use was 54.1% (53.5%-54.7%) in urban, 49.6% (46.9%-52.3%) in large rural, and 50.6% (48.3%-52.9%) in small rural areas (P < .01). Predicted prevalence of AUD was 14.4% (14.0%-14.8%) in urban, 11.8% (10.0%-13.5%) in large rural, and 12.3% (10.8%-13.8%) in small rural areas (P < .01). Approximately 12% and 25% had higher- or severe-risk drinking and HED, respectively, but neither differed across rurality. Though some variation across rurality and region was observed, alcohol-related interventions are needed for PLWH across all geographic locations.
Authors: Bensley KM; Justice AC; Williams EC; et al.
J Sex Med. 2019 05;16(5):621-623. Epub 2019-04-05.
Diabetes-Related Emotional Distress Over Time
Many adolescents with type 1 diabetes experience diabetes-related distress (DRD; the negative emotional reactions specific to managing diabetes), but most research on DRD among adolescents relies on cross-sectional data. We assess adolescents’ longitudinal DRD patterns and predictors of chronic DRD. This secondary analysis of data from a depression prevention clinical trial included 264 adolescents with type 1 diabetes randomly assigned to a resilience or education intervention (mean age: 15.7 ± 1.1 years; 59.8% female). Youth reported their DRD at 5 assessments over 16 months. Using latent class growth analysis, we classified adolescents into trajectory groups according to baseline starting point (intercept) and rate of change (slope) of DRD. We examined bivariate associations between trajectory group membership and demographic and clinical factors. Baseline predictors of chronic DRD were assessed via multiple logistic regression. Participants were classified into 4 groups: stable high DRD (7.2%; high intercept, flat slope), stable moderate DRD (28.0%; above-average intercept, flat slope), improving DRD (33.7%; average intercept, downward slope), and low DRD (31.1%; below-average intercept, downward slope). Lower hemoglobin A1c, greater adherence, fewer socioemotional difficulties, and more adaptive coping distinguished the improving and low DRD trajectories. Chronic DRD patterns were associated with female sex and higher depressive symptoms and hemoglobin A1c. In this study of adolescents’ DRD trajectories during and after a psychoeducational intervention, one-third of youth were classified as having chronic, elevated DRD. Links with multiple clinical factors support efforts for routine DRD screening and comprehensive interventions for distressed youth.
Authors: Iturralde E; Rausch JR; Weissberg-Benchell J; Hood KK
Pediatrics. 2019 06;143(6). Epub 2019-05-01.
Disparities in knowledge and use of tobacco treatment among smokers in California following healthcare reform
The Affordable Care Act (ACA) promised to narrow smoking disparities by expanding access to healthcare and mandating comprehensive coverage for tobacco treatment starting in 2014. We examined whether two years after ACA implementation disparities in receiving clinician advice to quit and smokers’ knowledge and use of treatment resources remained. We conducted telephone interviews in 2016 with a stratified random sample of self-reported smokers newly enrolled in the Kaiser Permanente Northern California’s (KPNC) integrated healthcare delivery system in 2014 (N = 491; 50% female; 53% non-white; 6% Spanish language). We used Poisson regression with robust standard errors to test whether sociodemographics, insurance type, comorbidities, smoking status in 2016 (former, light/nondaily [<5 cigarettes per day], daily), and preferred language (English or Spanish) were associated with receiving clinician advice to quit and knowledge and use of tobacco treatment. We included an interaction between smoking status and language to test whether the relation between smoking status and key outcomes varied with preferred language. Overall, 80% of respondents received clinician advice to quit, 84% knew that KPNC offers cessation counseling, 54% knew that cessation pharmacotherapy is free, 54% used pharmacotherapy, and 6% used counseling. In multivariate models, Spanish-speaking light/nondaily smokers had significantly lower rates of all outcomes, while there was no association with other demographic and clinical characteristics. Following ACA implementation, most smokers newly enrolled in KPNC received clinician advice to quit and over half used pharmacotherapy, yet counseling utilization was low. Spanish-language outreach efforts and treatment services are recommended, particularly for adults who are light/nondaily smokers.
Authors: Young-Wolff KC; Adams SR; Tan ASL; Adams AS; Klebaner D; Campbell CI; Satre DD; Salloum RG; Carter-Harris L; Prochaska JJ
Prev Med Rep. 2019 Jun;14:100847. Epub 2019-03-15.
Perceived and objective characteristics of the neighborhood environment are associated with accelerometer-measured sedentary time and physical activity, the CARDIA Study
We investigated cross-sectional and longitudinal associations of neighborhood environment characteristics with accelerometer-measured sedentary time (SED), light-intensity physical activity (LPA), and moderate-to-vigorous intensity physical activity (MVPA). Participants were 2120 men and women in the year 20 (2005-2006) and year 30 CARDIA exams (2015-2016). Year 20 neighborhood characteristics included neighborhood cohesion, resources for physical activity, poverty, and racial residential segregation. Physical activity was measured by accelerometer at years 20 and 30. Multivariable linear regression models examined associations of standardized neighborhood measures at year 20 with SED, LPA, and MVPA assessed that year, and with 10-year changes in SED, LPA, and MVPA. Cross-sectionally, a one standard deviation (SD) increase in cohesion was associated with 4.06 less SED min/day (95% CI: -7.98, -0.15), and 4.46 more LPA min/day (95% CI: 0.88, 8.03). Each one SD increase in resources was associated with 1.19 more MVPA min/day (95% CI: 0.06, 2.31). A one SD increase in poverty was associated with 11.18 less SED min/day (95% CI: -21.16, -1.18) and 10.60 more LPA min/day (95% CI: 1.79, 19.41) among black men. No neighborhood characteristic was associated with 10-year changes in physical activity in the full sample; however, a one SD increase in cohesion was associated with a 10-year decrease of 25.44 SED min/day (95% CI: -46.73, -4.14) and an increase of 19.0 LPA min/day (95% CI, 1.89, 36.10) in black men. Characteristics of the neighborhood environment are associated with accelerometer-measured physical activity. Differences were observed by race and sex, with more robust findings observed in black men.
Authors: Whitaker KM; Xiao Q; Pettee Gabriel K; Gordon Larsen P; Jacobs DR; Sidney S; Reis JP; Barone Gibbs B; Sternfeld B; Kershaw K
Prev Med. 2019 06;123:242-249. Epub 2019-03-30.
Capsule Commentary on Anthenelli et al., Predictors of Neuropsychiatric Adverse Events with Smoking Cessation Medications in the Randomized Controlled EAGLES Trial
Authors: Satre DD; Young-Wolff KC
J Gen Intern Med. 2019 06;34(6):999.
Impact of a health information technology tool addressing information needs of caregivers of adult and pediatric hematopoietic stem cell transplantation patients.
PURPOSE: We developed BMT Roadmap, a health information technology (HIT) application on a tablet, to address caregivers’ unmet needs with patient-specific information from the electronic health record. We conducted a preliminary feasibility study of BMT Roadmap in caregivers of adult and pediatric HSCT patients. The study was registered on ClinicalTrials.gov (NCT03161665; NCT02409121). n METHODS: BMT Roadmap was delivered to 39 caregivers of adult and pediatric patients undergoing first-time HSCT at a single study site. We assessed person-reported outcome measures (PROMs) at baseline (hospital admission), discharge, and day 100: usefulness of BMT Roadmap (Perceived Usefulness); activation (Patient Activation Measure-Caregiver version [PAM-C]); mental health ([POMS-2®]: depression, distress, vigor, and fatigue); anxiety (State-Trait Anxiety Inventory); and quality of life (Caregiver Quality of Life Index-Cancer [CQOLC]). To identify determinants of caregiver activation and quality of life, we used linear mixed models. n RESULTS: BMT Roadmap was perceived useful and activation increased from baseline to discharge (p = 0.001). Further, burden decreased through discharge (p = 0.007). Overall, a pattern of increasing vigor and decreasing depression, distress, fatigue, and anxiety was apparent from baseline to discharge. However, overall quality of life lowered at discharge after accounting for BMT Roadmap use, depression, anxiety, and fatigue (p = 0.04). n CONCLUSIONS: BMT Roadmap was a feasible HIT intervention to implement in HSCT caregivers. BMT Roadmap was associated with increased activation and decreased burden, but quality of life lowered across hospitalization. Findings support the need to further develop caregiver-specific self-directed resources and provide them both inpatient and outpatient across the HSCT trajectory.
Authors: Fauer, Alex J;Brookshire, Kristina;Choi, Sung Won;et al.
Support Care Cancer. 2019 Jun;27(6):2103-2112. doi: 10.1007/s00520-018-4450-4. Epub 2018 Sep 20.
Conducting a pilot randomized controlled trial of community-based mindfulness-based stress reduction versus usual care for moderate-to-severe migraine: protocol for the Mindfulness and Migraine Study (M&M)
Migraine is one of the most common neurological disorders in clinical practice and is a substantial cause of disability worldwide. Current approaches to therapy are primarily based on medication but are often limited by inadequate effectiveness and common side effects. Newer, more effective medications are expensive. Mindfulness-based stress reduction (MBSR), an 8-week classroom-based meditation intervention, is inexpensive, has no known side effects, and has demonstrated clinically meaningful effectiveness for several chronic-pain syndromes. In addition, MBSR has shown promising results for migraine therapy in a few small case studies and pilot studies. We present here the protocol for a two-arm randomized controlled pilot trial of MBSR for moderate-to-severe episodic migraine, which, if successful, will form the basis for a fully powered clinical trial. This study, set in Northern California, is a two-arm parallel-comparison single-blinded randomized controlled pilot trial with the goal of recruiting approximately 60 participants with moderate-to-severe episodic migraine. The feasibility outcomes include ability and time required to recruit, adherence to the MBSR treatment, and ability to measure outcomes using 31-day headache diaries and patient-reported questionnaire data. The active treatment arm consists of an 8-week community-based MBSR class plus usual care, and the wait-list control group is usual care. Recruitment is underway and expected to be complete by the end of 2018. To our knowledge, this is the first pragmatic trial in the U.S. of MBSR for migraine using community-based classes, and if it proves viable, we plan to conduct a fully powered trial to determine the effectiveness of the intervention for reducing headache days for moderate-to-severe episodic migraineurs. Clinicaltrials.gov, NCT02824250 . Registered on 6 July 2016.
Authors: Pressman A; Law H; Stahl R; Scott A; Jacobson A; Dean L; Sudat S; Obillo A; Avins A
Trials. 2019 May 06;20(1):257. Epub 2019-05-06.
Cocaine Use and Pre-Exposure Prophylaxis: Adherence, Care Engagement, and Kidney Function
Concomitant use of cocaine and HIV pre-exposure prophylaxis (PrEP) raises important clinical questions around adherence, retention in care, and renal toxicity. We assessed the associations of confirmed cocaine use with PrEP adherence (both ascertained through objective measures), care engagement, and renal function in the iPrEx open-label extension. Cocaine use was measured in scalp hair samples and categorized as light (500-3000 pg/mg) and moderate to heavy (>3000 pg/mg). PrEP adherence in the first 3 months was measured through plasma tenofovir concentrations. Disengagement from PrEP care was defined as a gap in follow-up greater than 4 months. Serum creatinine was assessed at baseline and quarterly visits. Of the 400 participants included in this analysis, 90% were men who have sex with men, 10% transgender women, 74% Hispanic/Latino; 21% tested positive for cocaine use in the last 3 months. In adjusted analysis, light cocaine use [adjusted odds ratio 2.10 (95% confidence interval: 1.07 to 4.14)] and moderate to heavy use [adjusted odds ratio 2.32 (1.08 to 5.00)] were associated with greater odds of having plasma tenofovir concentrations below the level of quantitation. Participants with moderate to heavy use had a nearly 3-fold higher rate of disengagement from PrEP care compared with nonusers (adjusted hazard ratio 2.90 [1.48 to 5.66]). We found no statistically or clinically significant differences in creatinine clearance and serum creatinine between participants who tested positive for cocaine and those who did not. Cocaine use decreases PrEP adherence and care engagement. Comprehensive approaches are needed to reduce cocaine use and enhance engagement along the PrEP care continuum.
Authors: Hojilla JC; Satre DD; Glidden DV; McMahan VM; Gandhi M; Defechereux P; Guanira JV; Mehrotra M; Grant RM; Carrico AW
J Acquir Immune Defic Syndr. 2019 05 01;81(1):78-82.
Lumbar Spinal Stenosis Severity by CT or MRI Does Not Predict Response to Epidural Corticosteroid versus Lidocaine Injections
Epidural steroid injections may offer little-to-no short-term benefit in the overall population of patients with symptomatic spinal stenosis compared with lidocaine alone. We investigated whether imaging could identify subgroups of patients who might benefit most. A secondary analysis of the Lumbar Epidural Steroid Injections for Spinal Stenosis prospective, double-blind trial was performed, and patients were randomized to receive an epidural injection of lidocaine with or without corticosteroids. Patients (n = 350) were evaluated for qualitative and quantitative MR imaging or CT measures of lumbar spinal stenosis. The primary clinical end points were the Roland-Morris Disability Questionnaire and the leg pain numeric rating scale at 3 weeks following injection. ANCOVA was used to assess the significance of interaction terms between imaging measures of spinal stenosis and injectate type on clinical improvement. There was no difference in the improvement of disability or leg pain scores at 3 weeks between patients injected with epidural lidocaine alone compared with corticosteroid and lidocaine when accounting for the primary imaging measures of qualitative spinal stenosis assessment (interaction coefficients for disability score, -0.1; 95% CI, -1.3 to 1.2; P = .90; and for the leg pain score, 0.1; 95% CI, -0.6 to 0.8; P = .81) or the quantitative minimum thecal sac cross-sectional area (interaction coefficients for disability score, 0.01; 95% CI, -0.01 to 0.03; P = .40; and for the leg pain score, 0.01; 95% CI, -0.01 to 0.03; P = .33). Imaging measures of spinal stenosis are not associated with differential clinical responses following epidural corticosteroid injection.
Authors: Perez FA; Avins AL; Friedly JL; et al.
AJNR Am J Neuroradiol. 2019 05;40(5):908-915. Epub 2019-05-02.
Health Care Use Over 3 Years After Adolescent SBIRT
Most studies on adolescent screening, brief intervention, and referral to treatment (SBIRT) have examined substance use outcomes. However, it may also impact service use and comorbidity-an understudied topic. We address this gap by examining effects of SBIRT on health care use and comorbidities. In a randomized trial sample, we assessed 3 SBIRT care modalities: (1) pediatrician-delivered, (2) behavioral clinician-delivered, and (3) usual. Medical comorbidity and health care use were compared between a brief-intervention group with access to SBIRT for behavioral health (combined pediatrician and behavioral clinician arms) and a group without (usual care) over 1 and 3 years. Among a sample of eligible adolescents (n = 1871), the SBIRT group had fewer psychiatry visits at 1 year (incidence rate ratio [iRR] = 0.76; P = .05) and 3 years (iRR = 0.65; P < .05). Total outpatient visits did not differ in year 1. The SBIRT group was less likely to have mental health diagnoses (odds ratio [OR] = 0.69; 95% confidence interval [CI] = 0.48-1.01) or chronic conditions (OR = 0.66; 95% CI = 0.45-0.98) at 1 year compared with those in usual care. At 3 years, the SBIRT group had fewer total outpatient visits (iRR = 0.85; P < .05) and was less likely to have substance use diagnoses (OR = 0.64; 95% CI = 0.45-0.91) and more likely to have substance use treatment visits (iRR = 2.04; P < .01). Providing SBIRT in pediatric primary care may improve health care use and health, mental health, and substance use outcomes. We recommend further exploring the effects of SBIRT on these outcomes.
Authors: Sterling S; Kline-Simon AH; Jones A; Hartman L; Saba K; Weisner C; Parthasarathy S
Pediatrics. 2019 05;143(5).
Alcohol and Women: A Brief Overview
Authors: McCaul ME; Roach D; Hasin DS; Weisner C; Chang G; Sinha R
Alcohol Clin Exp Res. 2019 05;43(5):774-779. Epub 2019-03-13.
Evaluation of a Pilot Perioperative Smoking Cessation Program: A Pre-Post Study
Surgical clinic and perioperative settings are critical touchpoints for treating smoking, yet health care systems have not typically prioritized smoking cessation among surgical patients. We evaluated the implementation of a pilot smoking cessation intervention integrated into standard perioperative care. English-speaking adult smokers undergoing elective surgery in Kaiser Permanente San Francisco before (2015) and after (2016-2017) the implementation of a smoking cessation intervention were included. Provider outcomes included counseling referrals, cessation medication orders (between surgery scheduling and surgery), and preoperative carbon monoxide testing. Patient outcomes included counseling and medication use, smoking status at surgery and 30 d after discharge, and surgical complications. Multivariable logistic regression analyses examined pre-to-post intervention changes in outcomes using electronic health record data and 30-d postdischarge telephone surveys. The sample included 276 patients (70% male; 59% non-Hispanic white; mean age = 50 y). There were significant pre-to-post increases in tobacco cessation counseling referrals (3% to 28%, adjusted odds ratio [AOR] = 11.12, 95% confidence interval [CI] = 3.78-32.71) and preoperative carbon monoxide testing (38% to 50%, AOR = 1.83, 95% CI = 1.10-3.06). At ∼30 d after discharge, patients in the postintervention period were more likely to report smoking abstinence in the previous 7 d (24% pre, 44% post; AOR = 2.39, 95% CI = 1.11-5.13) and since hospital discharge (18% pre, 39% post; AOR = 3.20, 95% CI = 1.42-7.23). Cessation medication orders and patient use of counseling and medications increased, whereas surgical complications decreased, but pre-to-post differences were not significant. A perioperative smoking cessation program integrated into standard care demonstrated positive smoking-related outcomes; however, larger studies are needed to evaluate the effectiveness of these programs.
Authors: Young-Wolff KC; Adams SR; Fogelberg R; Goldstein AA; Preston PG
J Surg Res. 2019 05;237:30-40. Epub 2019-01-18.
Reproductive period and risk of dementia in a diverse cohort of health care members
Women have >50% greater lifetime risk of dementia than men but the role of female-specific endocrine milieu is not well-understood. This study evaluates associations between indicators of estrogen exposure from women’s reproductive period and dementia risk in a large diverse population. We evaluated 15,754 female members (29.9% nonwhite) of Kaiser Permanente with clinical examinations and health survey data from 1964 to 1973 and were members as of January 1, 1996. In midlife (mean age 51.1 years), women reported age at menarche and menopause and hysterectomy status. Reproductive span was calculated as menopause age minus menarche age. Dementia diagnoses were abstracted from January 1, 1996 to September 30, 2017 medical records (mean age at start of dementia follow-up 76.5 years). Cox proportional hazard models evaluated associations between aspects of reproductive span and dementia risk adjusting for demographics and life course health indicators. Forty-two percent of women developed dementia. Compared to menarche at age 13.0 (mean menarche age), menarche at ?16 was associated with 23% greater dementia risk (adjusted hazard ratio [HR] 1.23; 95% confidence interval [CI] 1.01-1.50) adjusting for demographics and life course health indicators. Natural menopause at age <47.4 (mean menopause age) was associated with 19% elevated dementia risk (HR 1.19; 95% CI 1.07-1.31). Reproductive spans <34.4 years (mean duration) were associated with 20% elevated dementia risk (HR 1.20; 95% CI 1.08-1.32). Hysterectomies were associated with 8% elevated dementia risk (HR 1.08; 95% CI 1.01-1.16). In this large prospective cohort study, endocrine events signaling less estradiol exposure (i.e., later age at menarche, younger age at menopause, shorter reproductive span, and hysterectomies) were associated with elevated risk of dementia.
Authors: Gilsanz P; Lee C; Corrada MM; Kawas CH; Quesenberry CP; Whitmer RA
Neurology. 2019 04 23;92(17):e2005-e2014. Epub 2019-03-28.
Challenges of Population-based Measurement of Suicide Prevention Activities Across Multiple Health Systems
Suicide is a preventable public health problem. Zero Suicide (ZS) is a suicide prevention framework currently being evaluated by Mental Health Research Network investigators embedded in six Health Care Systems Research Network (HCSRN) member health systems implementing ZS. This paper describes ongoing collaboration to develop population-based process improvement metrics for use in, and comparison across, these and other health systems. Robust process improvement metrics are sorely needed by the hundreds of health systems across the country preparing to implement their own best practices in suicide care. Here we articulate three examples of challenges in using health system data to assess suicide prevention activities, each in ascending order of complexity: 1) Mapping and reconciling different versions of suicide risk assessment instruments across health systems; 2) Deciding what should count as adequate suicide prevention follow-up care and how to count it in different health systems with different care processes; and 3) Trying to determine whether a safety planning discussion took place between a clinician and a patient, and if so, what actually happened. To develop broadly applicable metrics, we have advocated for standardization of care processes and their documentation, encouraged standardized screening tools and urged they be recorded as discrete electronic health record (EHR) variables, and engaged with our clinical partners and health system data architects to identify all relevant care processes and the ways they are recorded in the EHR so we are not systematically missing important data. Serving as embedded research partners in our local ZS implementation teams has facilitated this work.
Authors: Yarborough BJH; Ahmedani BK; Boggs JM; Beck A; Coleman KJ; Sterling S; Schoenbaum M; Goldstein-Grumet J; Simon GE
EGEMS (Wash DC). 2019 Apr 12;7(1):13. Epub 2019-04-12.
Implementing a Multifaceted Perioperative Smoking Cessation Intervention in a Large Healthcare System
Authors: Young-Wolff KC; Fogelberg R; Preston PG
Nicotine Tob Res. 2019 Apr 04.
Development of a social media-based intervention targeting tobacco use and heavy episodic drinking in young adults
Tobacco use and heavy episodic drinking (HED) commonly co-occur in young adults. We developed and tested usability of the Smoking Tobacco and Drinking (STAND) intervention for young adults delivered on Facebook. To inform the intervention, focus groups were held with 25 young adults age 18 to 25 (12% female; Mean age = 20.4) who smoked cigarettes and reported at least one HED episode in the past month. Facebook intervention posts (N = 180) were tailored to readiness to quit smoking, and tested in two private Facebook behavioral change groups (Ready, Not Ready) with N = 29 young adults (10% female; Mean age = 20.8). Participants flagged posts in need of change, and we assessed engagement (comment frequency). Focus groups revealed preference for changing one substance at a time and greater receptivity to quitting smoking than reducing drinking. Mean comments per post were 5.3 (SD = 1.1) in Ready groups and 11.7 (SD = 5.1) in Not Ready groups; 94/180 (52.2%) posts were flagged for change. The level of engagement and the flagging of posts for change did not differ by group or by whether the post targeted tobacco, alcohol, or both substances combined (all p > .10). Overall, STAND was rated as easy to understand, providing sound advice, worthy of recommendation, and helpful (all agreement 100% among Ready; 50-70% among Not Ready). The current findings informed development of a social media-based intervention targeting tobacco and alcohol use in young adults. Although there was greater interest in making changes in smoking than drinking behavior, receptivity and acceptability of the Facebook post messages in the STAND intervention was high overall. The intervention is being further refined for evaluation in a larger trial. Trial registration Name of the registry Smoking Tobacco and Drinking Study (STAND); Trial registration number NCT03163303; Date of registration 5/23/17; URL of trial registry record https://clinicaltrials.gov/ct2/show/NCT03163303 .
Authors: Ramo DE; Meacham MC; Kaur M; Corpuz ES; Prochaska JJ; Satre DD
Addict Sci Clin Pract. 2019 04 01;14(1):14. Epub 2019-04-01.
Implementation of alcohol and drug screening, brief intervention, and referral to treatment: Nurse practitioner learner perspectives on a mobile app
Screening, brief Intervention, and referral to treatment (SBIRT) is a widely trained evidence-based strategy to identify and address alcohol and drug use problems. The purpose of this qualitative study was to explore the experience of family nurse practitioner (FNP) learners in the implementation of SBIRT and the perceived clinical utility of an SBIRT mobile app. Twenty-two FNP learners completed didactic SBIRT training and orientation to an SBIRT mobile app. At the conclusion of the study, participant focus groups explored overall SBIRT delivery (N = 19) and SBIRT mobile app utilization (N = 14). Focus group data were analyzed within a Theory of Planned Behavior framework. Participants indicated that the mobile app was useful in the ongoing development of SBIRT knowledge, skill confidence, and motivation. Learners identified the clinical context as a major factor in facilitating the delivery of SBIRT overall. Participants who did not deliver SBIRT indicated that the most significant barriers to SBIRT implementation were lack of support from clinical preceptors and health systems. Findings suggest that a mobile app is an acceptable and feasible tool to improve the delivery of SBIRT. However, collaboration with preceptors and clinical training organizations is essential to optimize clinical translation.
Authors: Curtis AC; Satre DD; Ly K; Wamsley M; Satterfield J
J Am Board Fam Med. 2019 May-Jun;32(3):353-361.
Incidence of dementia after age 90 in a multiracial cohort
Little is known about dementia incidence in diverse populations of oldest-old, the age group with highest dementia incidence. Incident dementia diagnoses from 1/1/2010 to 9/30/2015 were abstracted from medical records for 2350 members of an integrated health care system in California (n = 1702 whites, n = 375 blacks, n = 105 Latinos, n = 168 Asians) aged ≥90 in 2010. We estimated race/ethnicity-specific age-adjusted dementia incidence rates and implemented Cox proportional hazards models and Fine and Gray competing risk of death models adjusted for demographics and comorbidities in midlife and late-life. Dementia incidence rates (n = 771 cases) were lowest among Asians (89.9/1000 person-years), followed by whites (96.9/1000 person-years), Latinos (105.8/1000 person-years), and blacks (121.5/1000 person-years). Cox regression and competing risk models estimated 28% and 36% higher dementia risk for blacks versus whites adjusting for demographics and comorbidities. Patterns of racial/ethnic disparities in dementia seen in younger older adults continue after the age of 90 years, though smaller in magnitude.
Authors: Gilsanz P; Corrada MM; Kawas CH; Mayeda ER; Glymour MM; Quesenberry CP; Lee C; Whitmer RA
Alzheimers Dement. 2019 04;15(4):497-505. Epub 2019-02-20.
Adverse Childhood Experiences and Mental and Behavioral Health Conditions During Pregnancy: The Role of Resilience
Little is known about how exposure to adverse childhood experiences (ACEs) and protective factors, such as resilience, influence prenatal mental and behavioral health. This study examined associations between exposure to ACEs and mental and behavioral health during pregnancy overall and among women with high versus low levels of resilience. Women in two Kaiser Permanente Northern California medical centers were screened for ACEs and resilience during prenatal care (∼14-23 weeks of gestation; N = 355). Multivariable logistic regression analyses examined associations between ACEs and prenatal mental and behavioral health conditions overall and for women with low (≤32) versus high (>32) resilience on the 10-item Connor-Davidson Resilience Scale. Overall, 54% of women reported 0 ACEs, 28% 1-2 ACEs, and 18% 3+ ACEs. Relative to women with 0 ACEs, those with 1-2 ACEs had higher odds of an anxiety or depressive disorder and intimate partner violence (IPV) (odds ratios [ORs] 2.42-3.12, p < 0.05), and those with 3+ ACEs had higher odds of an anxiety or depressive disorder, depression symptoms, and IPV (ORs 3.08-4.71, p < 0.05). In stratified analyses by high (56%) and low (44%) resilience, having one or more ACEs (vs. 0 ACEs) was only associated with worse mental and behavioral health in women with low resilience. ACEs predicted mental and behavioral health conditions among pregnant women, and associations were the strongest among women with low levels of current resilience. Longitudinal research is needed to understand the causal mechanisms underlying these associations.
Authors: Young-Wolff KC; Alabaster A; McCaw B; Stoller N; Watson C; Sterling S; Ridout KK; Flanagan T
J Womens Health (Larchmt). 2019 04;28(4):452-461. Epub 2018-09-05.
Genome-wide Association and Functional Studies Reveal Novel Pharmacological Mechanisms for Allopurinol
Allopurinol, which lowers uric acid (UA) concentration, is increasingly being recognized for its benefits in cardiovascular and renal disease. However, response to allopurinol is variable. We gathered samples from 4,446 multiethnic subjects for a genome-wide association study of allopurinol response. Consistent with previous studies, we observed that the Q141K variant in ABCG2 (rs2231142), which encodes the efflux pump BCRP, associated with worse response to allopurinol. However, for the first time this association reached genome-wide level significance (p=8.06 x 10-11 ). Additionally, we identified a novel association with a variant in GREM2 (rs1934341, p=3.2 x 10-6 ). In vitro studies identified oxypurinol, the active metabolite of allopurinol, as an inhibitor of the UA transporter GLUT9, suggesting that oxypurinol may modulate UA reabsorption. These results provide strong evidence for a role of BCRP Q141K in allopurinol response, and suggest that allopurinol may have additional hypouricemic effects beyond xanthine oxidase inhibition. This article is protected by copyright. All rights reserved.
Authors: Brackman DJ; Ranatunga D; Jorgenson E; Giacomini KM; et al.
Clin Pharmacol Ther. 2019 Mar 28.
Adverse childhood experiences, mental health, substance use, and HIV-related outcomes among persons with HIV
While persons with HIV (PWH) have benefited from significant advances in treatment and resulting longevity, mental health problems remain elevated in this population. Adverse childhood experiences (ACEs) are common among PWH and may negatively affect mental health and HIV-related outcomes. We examined the association between ACEs, depression and anxiety symptoms, substance use, antiretroviral therapy (ART) adherence, and HIV-clinical indicators in a sample of 584 PWH at risk for unhealthy alcohol use enrolled in a primary care-based alcohol intervention study. The sample was 96.9% male, 63.0% non-Hispanic white, with an average age of 49.0 years. ACEs were highly prevalent: 82.5% reported ≥1 ACE, including 34.2% reporting 1-2 ACEs, 25.0% reporting 3-4 ACEs, and 23.3% reporting ≥5 ACEs. Adjusting for demographics, having 1-2, 3-4 or ≥5 ACEs was significantly associated with anxiety (ORs (95%CI): 3.41 (1.13-10.33), 4.36 (1.42-3.36), and 3.96 (1.28-12.19), respectively) and poorer mental health quality of life (Betas (SE): -3.21 (1.40), -6.23 (1.51), and -7.09 (1.54), respectively), but not with other outcomes. Trauma-informed interventions to reduce anxiety and improve mental health quality of life in PWH may reduce the negative health sequelae of ACEs.
Authors: Young-Wolff KC; Sarovar V; Sterling SA; Leibowitz A; McCaw B; Hare CB; Silverberg MJ; Satre DD
AIDS Care. 2019 Mar 19:1-9.
Changes in body composition and weight during the menopause transition
The relation between the menopause transition (MT) and changes in body composition or weight remains uncertain. We hypothesized that, independent of chronological aging, the MT would have a detrimental influence on body composition. Participants were from the longitudinal Study of Women’s Health Across the Nation (SWAN) cohort. We assessed body composition by dual energy x-ray absorptiometry. Multivariable mixed effects regressions fitted piece-wise linear models to repeated measures of outcomes as a function of time before or after the final menstrual period (FMP). Covariates were age at FMP, race, study site, and hormone therapy. Fat and lean mass increased prior to the MT. At the start of the MT, rate of fat gain doubled, and lean mass declined; gains and losses continued until 2 years after the FMP. After that, the trajectories of fat and lean mass decelerated to zero slope. Weight climbed linearly during premenopause without acceleration at the MT. Its trajectory became flat after the MT. Accelerated gains in fat mass and losses of lean mass are MT-related phenomena. The rate of increase in the sum of fat mass and lean mass does not differ between premenopause and the MT; thus, there is no discernable change in rate of weight gain at the start of the MT. NIH, Department of Health and Human Services (DHHS), through the National Institute on Aging, National Institute of Nursing Research, and NIH Office of Research on Women’s Health (U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, and U01AG012495).
Authors: Greendale GA; Sternfeld B; Huang M; Han W; Karvonen-Gutierrez C; Ruppert K; Cauley JA; Finkelstein JS; Jiang SF; Karlamangla AS
JCI Insight. 2019 03 07;4(5). Epub 2019-03-07.
Trends in marijuana use among pregnant women with and without nausea and vomiting in pregnancy, 2009-2016
Cross-sectional studies indicate an elevated prevalence of prenatal marijuana use in women with nausea and vomiting in pregnancy (NVP). However, it is unknown whether differences in marijuana use by NVP status have persisted over time as marijuana becomes more acceptable and accessible and prenatal use increases overall. We compared trends in prenatal marijuana use by NVP status in the first trimester of pregnancy using data from Kaiser Permanente Northern California’s (KPNC) large healthcare system. The sample comprised KPNC pregnant women aged ≥12 who completed a self-administered questionnaire on marijuana use and a urine toxicology test for cannabis during standard prenatal care from 2009 to 2016. The annual prevalence of marijuana use via self-report or toxicology by NVP status was estimated using Poisson regression with a log link function, adjusting for sociodemographics and parity. We tested for linear trends and differences in trends by NVP. Of 220,510 pregnancies, 38,831 (17.6%) had an NVP diagnosis. Prenatal marijuana use was elevated each year among women with NVP. The adjusted prevalence of use increased significantly from 2009 to 2016 at an annual rate of 1.086 (95%CI = 1.069-1.104) among women with NVP, from 6.5% (95%CI = 5.7%-7.2%) to 11.1% (95%CI = 0.2%-12.0%), and 1.069 (95%CI = 1.059-1.080) among women without NVP, from 3.4% (95%CI = 3.2%-3.7%) to 5.8% (95%CI = 5.5%-6.1%). Trends did not vary by NVP status. The prevalence of prenatal marijuana use has remained elevated over time among women with NVP. Clinicians should ask pregnant patients about their reasons for marijuana use and treat NVP with evidence-based interventions.
Authors: Young-Wolff KC; Sarovar V; Tucker LY; Avalos LA; Alexeeff S; Conway A; Armstrong MA; Weisner C; Campbell CI; Goler N
Drug Alcohol Depend. 2019 03 01;196:66-70. Epub 2019-01-18.
A Quality Framework for Emergency Department Treatment of Opioid Use Disorder
Emergency clinicians are on the front lines of responding to the opioid epidemic and are leading innovations to reduce opioid overdose deaths through safer prescribing, harm reduction, and improved linkage to outpatient treatment. Currently, there are no nationally recognized quality measures or best practices to guide emergency department quality improvement efforts, implementation science researchers, or policymakers seeking to reduce opioid-associated morbidity and mortality. To address this gap, in May 2017, the National Institute on Drug Abuse’s Center for the Clinical Trials Network convened experts in quality measurement from the American College of Emergency Physicians’ (ACEP’s) Clinical Emergency Data Registry, researchers in emergency and addiction medicine, and representatives from federal agencies, including the National Institute on Drug Abuse and the Centers for Medicare & Medicaid Services. Drawing from discussions at this meeting and with experts in opioid use disorder treatment and quality measure development, we developed a multistakeholder quality improvement framework with specific structural, process, and outcome measures to guide an emergency medicine agenda for opioid use disorder policy, research, and clinical quality improvement.
Authors: Samuels EA; D'Onofrio G; Huntley K; Levin S; Schuur JD; Bart G; Hawk K; Tai B; Campbell CI; Venkatesh AK
Ann Emerg Med. 2019 03;73(3):237-247. Epub 2018-10-11.
Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use
Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures.
Authors: Liu M; Choquet H; Weisner C; Vrieze S; et al.
Nat Genet. 2019 02;51(2):237-244. Epub 2019-01-14.
Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity
Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
Authors: Kilpeläinen TO; Sternfeld B; Loos RJF; et al.
Nat Commun. 2019 01 22;10(1):376. Epub 2019-01-22.
Associations of Accelerometer-Measured Sedentary Time and Physical Activity With Prospectively Assessed Cardiometabolic Risk Factors: The CARDIA Study
Background Isotemporal substitution examines the effect on health outcomes of replacing sedentary time with light-intensity physical activity or moderate-to-vigorous intensity physical activity; however, existing studies are limited by cross-sectional study designs. Methods and Results Participants were 1922 adults from the CARDIA (Coronary Artery Risk Development in Young Adults) study. Linear regression examined the associations of sedentary, light-intensity physical activity, and moderate-to-vigorous intensity physical activity at year 20 (2005-2006) with waist circumference, blood pressure, glucose, insulin, triglycerides, high-density lipoprotein cholesterol, and a composite risk score at year 30 (2015-2016). Models then examined change in activity with change in cardiometabolic risk over the same 10-year period. Replacing 30 min/day of sedentary time with 30 min/day of light-intensity physical activity at year 20 was associated with a lower composite risk score (-0.01 SD [95% CI, -0.02, -0.00]) at year 30, characterized by lower waist circumference (0.15 cm [95% CI, -0.27, 0.02]), insulin (0.20 ?U/mL [95% CI, -0.35, -0.04]), and higher high-density lipoprotein cholesterol (0.20 mg/dL [95% CI, 0.00, 0.40]; all P<0.05). An increase of 30 min/day in MVPA from year 20 to year 30, when replacing an equivalent increase in sedentary time, was associated with a decrease in the composite risk score (-0.08 [95% CI, -0.13, -0.04]) over the same 10 years, characterized by a decrease in waist circumference (1.52 cm [95% CI, -2.21, -0.84]), insulin (-1.13 ?U/mL [95% CI, -1.95, -0.31]), triglycerides (-6.92 mg/dL [95% CI, -11.69, -2.15]), and an increase in high-density lipoprotein cholesterol (1.59 mg/dL [95% CI, 0.45, 2.73]; all P<0.05). Conclusions Replacement of sedentary time with light-intensity physical activity or moderate-to-vigorous intensity physical activity is associated with improved cardiometabolic health 10 years later.
Authors: Whitaker KM; Pettee Gabriel K; Buman MP; Pereira MA; Jacobs DR; Reis JP; Gibbs BB; Carnethon MR; Staudenmayer J; Sidney S; Sternfeld B
J Am Heart Assoc. 2019 02 19;8(4):e010586.
Level of Alcohol Use Associated with HIV Care Continuum Targets in a National U.S. Sample of Persons Living with HIV Receiving Healthcare
We evaluated associations between levels of alcohol use and HIV care continuum components using national Veterans Aging Cohort Study data for all patients with HIV and AUDIT-C screening (2/1/2008-9/30/2014). Poisson regression models evaluated associations between alcohol use levels (non-drinking, low-, medium-, high-, and very high-level drinking) and: (1) engagement with care (documented CD4 cells/µl or viral load copies/ml labs), (2) ART treatment (≥ 1 prescription), and (3) viral suppression (HIV RNA < 500 copies/ml) within one year. Among 33,224 patients, alcohol use level was inversely associated with all care continuum outcomes (all p < 0.001). Adjusted prevalence of care engagement ranged from 77.8% (95% CI 77.1-78.4%) for non-drinking to 69.1% (66.6-71.6%) for high-level drinking. The corresponding range for ART treatment was 74.0% (73.3-74.7%) to 60.1% (57.3-62.9%) and for viral suppression was 57.3% (56.5-58.1%) to 38.3% (35.6-41.1%). Greater alcohol use is associated with suboptimal HIV treatment across the HIV care continuum.
Authors: Williams EC; Satre DD; Bradley KA; et al.
AIDS Behav. 2019 Jan;23(1):140-151.
A Randomized Controlled Trial of mHealth Mindfulness Intervention for Cancer Patients and Informal Cancer Caregivers: A Feasibility Study Within an Integrated Health Care Delivery System
To assess feasibility and preliminary efficacy of a mobile/online-based (mHealth) mindfulness intervention for cancer patients and their caregivers to reduce distress and improve quality of life (QoL). Two-arm randomized controlled trial within Kaiser Permanente Northern California targeting cancer patients who received chemotherapy and their informal caregivers. The intervention group received a commercially available mindfulness program for 8 weeks. The wait-list control group received usual care. We assessed feasibility using retention and adherence rates and obtained participant-reported data on distress, QoL, sleep, mindfulness, and posttraumatic growth before and immediately after the intervention. Ninety-seven patients (median age 59 years; female 69%; 65% whites) and 31 caregivers (median age 63 years; female 58%; 77% whites) were randomized. Among randomized participants, 74% of the patients and 84% of the caregivers completed the study. Among those in the intervention arm who initiated the mindfulness program, 65% practiced at least 50% of the days during the intervention period. We observed significantly greater improvement in QoL among patients in the intervention arm compared with controls. Caregivers in the intervention group experienced increased mindfulness compared with controls. Participants appreciated the convenience of the intervention and the mindfulness skills they obtained from the program. We demonstrated the feasibility of conducting a randomized trial of an mHealth mindfulness intervention for cancer patients and their informal caregivers. Results from fully powered efficacy trials would inform the potential for clinicians to use this scalable intervention to help improve QoL of those affected by cancer and their caregivers.
Authors: Kubo A; Kurtovich E; McGinnis M; Aghaee S; Altschuler A; Quesenberry C; Kolevska T; Avins AL
Integr Cancer Ther. 2019 Jan-Dec;18:1534735419850634.
Healthcare Effectiveness Data and Information Set (HEDIS) measures of alcohol and drug treatment initiation and engagement among people living with the human immunodeficiency virus (HIV) and patients without an HIV diagnosis
Background: Problematic use of alcohol and other drugs (AOD) is highly prevalent among people living with the human immunodeficiency virus (PLWH), and untreated AOD use disorders have particularly detrimental effects on human immunodeficiency virus (HIV) outcomes. The Healthcare Effectiveness Data and Information Set (HEDIS) measures of treatment initiation and engagement are important benchmarks for access to AOD use disorder treatment. To inform improved patient care, we compared HEDIS measures of AOD use disorder treatment initiation and engagement and health care utilization among PLWH and patients without an HIV diagnosis. Methods: Patients with a new AOD use disorder diagnosis documented between October 1, 2014, and August 15, 2015, were identified using electronic health records (EHR) and insurance claims data from 7 health care systems in the United States. Demographic characteristics, clinical diagnoses, and health care utilization data were also obtained. AOD use disorder treatment initiation and engagement rates were calculated using HEDIS measure criteria. Factors associated with treatment initiation and engagement were examined using multivariable logistic regression models. Results: There were 469 PLWH (93% male) and 86,096 patients without an HIV diagnosis (60% male) in the study cohort. AOD use disorder treatment initiation was similar in PLWH and patients without an HIV diagnosis (10% vs. 11%, respectively). Among those who initiated treatment, few engaged in treatment in both groups (9% PLWH vs. 12% patients without an HIV diagnosis). In multivariable analysis, HIV status was not significantly associated with either AOD use disorder treatment initiation or engagement. Conclusions: AOD use disorder treatment initiation and engagement rates were low in both PLWH and patients without an HIV diagnosis. Future studies need to focus on developing strategies to efficiently integrate AOD use disorder treatment with medical care for HIV.
Authors: Hechter RC; Weisner C; Campbell CI; Satre DD; et al.
Subst Abus. 2019;40(3):302-310. Epub 2019-03-25.
Posttraumatic stress disorder symptoms and television viewing patterns in the Nurses’ Health Study II: A longitudinal analysis
The relation between TV viewing and posttraumatic stress disorder (PTSD) is controversial; prior work focused exclusively on whether TV viewing of disaster events constitutes a traumatic stressor that causes PTSD. This study evaluates a possible bidirectional relation between PTSD and TV viewing in community-dwelling women. Data are from the PTSD subsample of the Nurses’ Health II study, an ongoing prospective study of women aged 24-42 years at enrollment and who have been followed biennially (N = 50,020). Trauma exposure and PTSD symptoms (including date of onset) were assessed via the Brief Trauma Questionnaire and the Short Screening Scale for DSM-IV PTSD. Average TV viewing was reported at 5 times over 18 years of follow-up. Linear mixed models assessed differences in TV viewing patterns by trauma/PTSD status. Among women with trauma/PTSD onset during follow-up (N = 14,374), linear spline mixed models assessed differences in TV viewing patterns before and after PTSD onset. Women with high PTSD symptoms reported more TV viewing (hours/wk) compared to trauma-unexposed women at all follow-up assessments (? = 0.14, SE = 0.01, p < .001). Among the women who experienced trauma during follow-up, significant increases in TV viewing (hours/day) prior to onset of high PTSD symptom levels were evident (? = 0.15, SE = 0.02, p < .001). TV viewing following trauma exposure may be a marker of vulnerability for developing PTSD and also a consequence of having PTSD. High TV viewing levels may be linked with ineffective coping strategies or social isolation, which increase risk of developing PTSD.
Authors: Jung SJ; Winning A; Roberts AL; Nishimi K; Chen Q; Gilsanz P; Sumner JA; Fernandez CA; Rimm EB; Kubzansky LD; Koenen KC
PLoS One. 2019;14(3):e0213441. Epub 2019-03-21.
Patient characteristics associated with treatment initiation and engagement among individuals diagnosed with alcohol and other drug use disorders in emergency department and primary care settings
Background: Treatment initiation and engagement rates for alcohol and other drug (AOD) use disorders differ depending on where the AOD use disorder was identified. Emergency department (ED) and primary care (PC) are 2 common settings where patients are identified; however, it is unknown whether characteristics of patients who initiate and engage in treatment differ between these settings. Methods: Patients identified with an AOD disorder in ED or PC settings were drawn from a larger study that examined Healthcare Effectiveness Data and Information Set (HEDIS) AOD treatment initiation and engagement measures across 7 health systems using electronic health record data (n = 54,321). Multivariable generalized linear models, with a logit link, clustered on health system, were used to model patient factors associated with initiation and engagement in treatment, between and within each setting. Results: Patients identified in the ED had higher odds of initiating treatment than those identified in PC (adjusted odds ratio [aOR] = 1.89, 95% confidence interval [CI] = 1.73-2.07), with no difference in engagement between the settings. Among those identified in the ED, compared with patients aged 18-29, older patients had higher odds of treatment initiation (age 30-49: aOR = 1.25, 95% CI = 1.12-1.40; age 50-64: aOR = 1.42, 95% CI = 1.26-1.60; age 65+: aOR = 1.27, 95% CI = 1.08-1.49). However, among those identified in PC, compared with patients aged 18-29, older patients were less likely to initiate (age 30-49: aOR = 0.81, 95% CI = 0.71-0.94; age 50-64: aOR = 0.68, 95% CI = 0.58-0.78; age 65+: aOR = 0.47, 95% CI = 0.40-0.56). Women identified in ED had lower odds of initiating treatment (aOR = 0.80, 95% CI = 0.72-0.88), whereas sex was not associated with treatment initiation in PC. In both settings, patients aged 65+ had lower odds of engaging compared with patients aged 18-29 (ED: aOR = 0.61, 95% CI = 0.38-0.98; PC: aOR = 0.42, 95% CI = 0.26-0.68). Conclusion: Initiation and engagement in treatment differed by sex and age depending on identification setting. This information could inform tailoring of future AOD interventions.
Authors: Kline-Simon AH; Campbell CI; Weisner C; Sterling SA; Yarborough BJH; et al.
Subst Abus. 2019;40(3):278-284. Epub 2019-01-31.
The association between medical comorbidity and Healthcare Effectiveness Data and Information Set (HEDIS) measures of treatment initiation and engagement for alcohol and other drug use disorders
Background: Medical comorbidity may influence treatment initiation and engagement for alcohol and other drug (AOD) use disorders. We examined the association between medical comorbidity and Healthcare Effectiveness Data and Information Set (HEDIS) treatment initiation and engagement measures.Methods: We used electronic health record and insurance claims data from 7 US health care systems to identify patients with AOD use disorders between October 1, 2014, and August 15, 2015 (N = 86,565). Among patients identified with AOD use disorders in outpatient and emergency department (ED) settings, we examined how Charlson/Deyo comorbidity index scores and medical complications of AOD use were associated with treatment initiation. Among those who initiated treatment in inpatient and outpatient/ED settings, we also examined how comorbidity and AOD use-related medical complications were associated with treatment engagement. Analyses were conducted using generalized estimating equation logistic regression modeling.Results: Among patients identified as having an AOD diagnosis in outpatient and ED settings (n = 69,965), Charlson/Deyo comorbidity index scores of 2 or more were independently associated with reduced likelihood of initiation (risk ratio [RR] = 0.80, 95% confidence interval [CI] = 0.74, 0.86; reference score = 0), whereas prior-year diagnoses of cirrhosis (RR = 1.25, 95% CI = 1.12, 1.35) and pancreatic disease (RR = 1.34, 95% CI = 1.15, 1.56) were associated with greater likelihood of initiation. Among those who were identified in outpatient/ED settings and initiated, higher comorbidity scores were associated with lower likelihood of engagement (score 1: RR = 0.85, 95% CI = 0.76, 0.94; score 2+: RR = 0.61, 95% CI = 0.53, 0.71).Conclusion: Medical comorbidity was associated with lower likelihood of initiating or engaging in AOD treatment, but cirrhosis and pancreatic disease were associated with greater likelihood of initiation. Interventions to improve AOD treatment initiation and engagement for patients with comorbidities are needed, such as integrating medical and AOD treatment.
Authors: Binswanger IA; Campbell CI; Satre DD; Weisner C; Lapham GT; et al.
Subst Abus. 2019;40(3):292-301. Epub 2019-01-24.
Factors associated with Healthcare Effectiveness Data and Information Set (HEDIS) alcohol and other drug measure performance in 2014-2015
Background: Only 10% of patients with alcohol and other drug (AOD) disorders receive treatment. The AOD Initiation and Engagement in Treatment (AOD-IET) measure was added to the national Healthcare Effectiveness Data and Information Set (HEDIS) to improve access to care. This study identifies factors related to improving AOD-IET rates. Methods: We include data from 7 health systems with differing geographic, patient demographic, and organizational characteristics; all used a common Virtual Data Warehouse containing electronic health records and insurance claims data. Multilevel logistic regression models examined AOD-IET among adults (18+). Results: A total of 86,565 patients had an AOD diagnosis qualifying for the HEDIS denominator. Initiation rates varied from 26% to 46%; engagement rates varied from 14% to 29%. Women versus men (odds ratio [OR] = 0.81, 95% confidence interval [CI] = 0.76-0.86); Hispanics (OR = 0.85, 95% CI = 0.79-0.91), black/African Americans (OR = 0.82, 95% CI = 0.75-0.90), and Asian Americans (OR = 0.83, 95% CI = 0.72-0.95) versus whites; and patients aged 65+ versus 18-29 (OR = 0.82, 95% CI = 0.74-0.90) had lower odds of initiation. Patients aged 30-49 versus 18-29 (OR = 1.11, 95% CI = 1.04-1.19) and those with prior psychiatric (OR = 1.26, 95% CI = 1.18-1.35) and medical (OR = 1.18, 95% CI = 1.10-1.26) conditions had higher odds of engagement. Identification in primary care versus other departments was related to lower odds of initiation (emergency department [ED]: OR = 1.55, 95% CI = 1.45-1.66; psychiatry/AOD treatment: OR = 3.58, 95% CI = 3.33-3.84; other outpatient: OR = 1.19, 95% CI = 1.06-1.32). Patients aged 30-49 versus 18-29 had higher odds of engagement (OR = 1.26, 95% CI = 1.10-1.43). Patients aged 65+ versus 18-29 (OR = 0.51, 95% CI = 0.43-0.62) and black/African Americans versus whites (OR = 0.64, 95% CI = 0.53-0.77) had lower odds. Those initiating treatment in psychiatry/AOD treatment versus primary care (OR = 7.02, 95% CI = 5.93-8.31) had higher odds of engagement; those in inpatient (OR = 0.40, 95% CI = 0.32-0.50) or other outpatient (OR = 0.73, 95% CI = 0.59-0.91) settings had lower odds. Discussion: Rates of initiation and engagement varied but were low. Findings identified age, race/ethnicity, co-occurring conditions, and department of identification as key factors associated with AOD-IET. Focusing on these could help programs develop interventions that facilitate AOD-IET for those less likely to receive care.
Authors: Weisner C; Campbell CI; Sterling SA; Satre DD; Kline-Simon AH; et al.
Subst Abus. 2019;40(3):318-327. Epub 2019-01-24.
The prevalence of Healthcare Effectiveness Data and Information Set (HEDIS) initiation and engagement in treatment among patients with cannabis use disorders in 7 US health systems
Background: Cannabis use disorders (CUDs) have increased with more individuals using cannabis, yet few receive treatment. Health systems have adopted the Healthcare Effectiveness Data and Information Set (HEDIS) quality measures of initiation and engagement in alcohol and other drug (AOD) dependence treatment, but little is known about the performance of these among patients with CUDs. Methods: This cohort study utilized electronic health records and claims data from 7 health care systems to identify patients with documentation of a new index CUD diagnosis (no AOD diagnosis ≤60 days prior) from International Classification of Diseases, Ninth revision, codes (October 1, 2014, to August 31, 2015). The adjusted prevalence of each outcome (initiation, engagement, and a composite of both) was estimated from generalized linear regression models, across index identification settings (inpatient, emergency department, primary care, addiction treatment, and mental health/psychiatry), AOD comorbidity (patients with CUD only and CUD plus other AOD diagnoses), and patient characteristics. Results: Among 15,202 patients with an index CUD diagnosis, 30.0% (95% confidence interval [CI]: 29.2-30.7%) initiated, 6.9% (95% CI: 6.2-7.7%) engaged among initiated, and 2.1% (95% CI: 1.9-2.3%) overall both initiated and engaged in treatment. The adjusted prevalence of outcomes varied across index identification settings and was highest among patients diagnosed in addiction treatment, with 25.0% (95% CI: 22.5-27.6%) initiated, 40.9% (95% CI: 34.8-47.0%) engaged, and 12.5% (95% CI: 10.0-15.1%) initiated and engaged. The adjusted prevalence of each outcome was generally highest among patients with CUD plus other AOD diagnosis at index diagnosis compared with those with CUD only, overall and across index identification settings, and was lowest among uninsured and older patients. Conclusion: Among patients with a new CUD diagnosis, the proportion meeting HEDIS criteria for initiation and/or engagement in AOD treatment was low and demonstrated variation across index diagnosis settings, AOD comorbidity, and patient characteristics, pointing to opportunities for improvement.
Authors: Lapham GT; Campbell CI; Yarborough BJH; Hechter RC; Ahmedani BK; Haller IV; Kline-Simon AH; Satre DD; Loree AM; Weisner C; Binswanger IA
Subst Abus. 2019;40(3):268-277. Epub 2019-01-18.
Psychiatric comorbidity and Healthcare Effectiveness Data and Information Set (HEDIS) measures of alcohol and other drug treatment initiation and engagement across 7 health care systems
Background: Psychiatric comorbidity is common among patients with alcohol and other drug (AOD) use disorders. To better understand how psychiatric comorbidity influences AOD treatment access in health care systems, the present study examined treatment initiation and engagement among a large, diverse sample of patients with comorbid psychiatric and AOD use disorders. Methods: This study utilized data from a multisite observational study examining Healthcare Effectiveness Data and Information Set (HEDIS) measures of initiation and engagement in treatment (IET) among patients with AOD use disorders from 7 health care systems. Participants were aged 18 or older with at least 1 AOD index diagnosis between October 1, 2014, and August 15, 2015. Data elements extracted from electronic health records and insurance claims data included patient demographic characteristics, ICD-9 (International Classification of Diseases, Ninth Revision) diagnostic codes, and procedure codes. Descriptive analyses and multivariate logistic regression models were used to examine the relationship between patient-level factors and IET measures. Results: Across health care systems, out of a total of 86,565 patients who had at least 1 AOD index diagnosis during the study period, 66.2% (n = 57,335) patients also had a comorbid psychiatric disorder. Among patients with a comorbid psychiatric disorder, 34.9% (n = 19,998) initiated AOD treatment, and of those, 10.3% (n = 2,060) engaged in treatment. After adjusting for age, sex, and race/ethnicity, patients with comorbid psychiatric disorders were more likely to initiate (odds ratio [OR] = 3.20, 95% confidence interval [CI] = 3.08, 3.32) but no more likely to engage (OR = 0.56, 95% CI = 0.51, 0.61) in AOD treatment, compared with those without a comorbid psychiatric disorder. Conclusions: Findings suggest that identification of comorbid psychiatric disorders may increase initiation in AOD treatment. However, innovative efforts are needed to enhance treatment engagement both generally and especially for individuals without diagnosed psychiatric conditions.
Authors: Loree AM; Satre DD; Campbell CI; Weisner C; Ahmedani BK; et al.
Subst Abus. 2019;40(3):311-317. Epub 2019-01-25.
Predictors of Healthcare Effectiveness Data and Information Set (HEDIS) treatment initiation and engagement among patients with opioid use disorder across 7 health systems
Background: The prevalence of opioid use disorder (OUD) has increased rapidly in the United States and improving treatment access is critical. Among patients with OUD, we examined factors associated with the Healthcare Effectiveness Data and Information Set (HEDIS) performance measures of alcohol and other drug (AOD) treatment initiation and engagement. Methods: Electronic health record and claims data between October 1, 2014, and August 15, 2015, from 7 health systems were used to identify patients (n = 11,490) with a new index OUD diagnosis (no AOD diagnosis prior <60 days) based on International Classification of Diseases (ICD)-9 codes. Multivariable generalized linear models with a logit link clustered on health system were used to examine the associations of patient demographic and clinical characteristics, and department of index diagnosis, with HEDIS measures of treatment initiation and engagement. Results: The prevalence of OUD among all AOD diagnoses varied across health systems, as did rates of AOD initiation (5.7%-21.6%) and engagement (7.6%-24.6%). Those diagnosed in the emergency department (adjusted odds ratio [aOR] = 1.58, 95% confidence interval [CI] = 1.27,1.97) or psychiatry/AOD treatment (aOR = 2.92, 95% CI = 2.47,3.46) were more likely to initiate treatment compared with primary care. Older patients were less likely to initiate (age 50-64 vs. age 18-29: aOR = 0.42, 95% CI = 0.35, 0.51; age 65+ vs. age 18-29: aOR = 0.34, 95% CI = 0.26, 0.43), as were women (aOR = 0.72, 95% CI = 0.62, 0.85). Patients diagnosed in psychiatry/AOD treatment (aOR = 2.67, 95% CI = 1.98, 3.60) compared with primary care were more likely to engage in treatment. Those identified in an inpatient setting (aOR = 0.19, 95% CI = 0.14, 0.27 vs. primary care), those with medical comorbidity (aOR = 0.70, 95% CI = 0.52, 0.95), and older patients (age 50-64 vs. 18-29: aOR = 0.64, 95% CI = 0.46, 0.88; age 65+ vs. 18-29: aOR = 0.36, 95% CI = 0.22, 0.57) were less likely to engage in treatment. Conclusions: Rates of initiation and engagement for OUD patients vary widely with noticeable room for improvement, particularly in this critical time of the opioid crisis. Targeting patient and system factors may improve health system performance, which is key to improving patient outcomes.
Authors: Campbell CI; Weisner C; Binswanger IA; Lapham GT; Ahmedani BK; Yarborough BJH; Haller IV; Altschuler A; Hechter RC; Loree AM; Kline-Simon AH
Subst Abus. 2019;40(3):328-334. Epub 2019-01-24.
Links between age at menarche, antral follicle count, and body mass index in African American and European American women
To examine the relationships between age at menarche, antral follicle count (AFC), and body mass index (BMI) in a multi-ethnic population of women. Community-based, cross-sectional study. Academic setting. A total of 245 African American women and 273 European American women, aged 25-45 years, with regular menstrual cycles and no reproductive disorders. The ethnicity of these women was self-reported and genetically validated. The AFCs were measured by transvaginal ultrasound during the early follicular phase. Anthropometric measurements were taken, and age at menarche was gathered by questionnaire. Determination of the associations between age of menarche and adult AFC and BMI. Earlier age of menarche was associated with both higher BMIs and higher AFCs in adulthood, with control for female age. The antral follicle difference between early (<12 years) vs. late (?15 years) initiation of menarche in both white and black women was +3.81 and +3.34 follicles, respectively, which is equivalent to an approximately 20% difference in AFC. This study provides the first evidence that timing of menarche may influence AFC. Because of limited studies on African American women, this work provides additional needed data and may enhance our ability to prospectively screen and better treat various diseases associated with the female reproductive lifespan.
Authors: Schuh SM; Kadie J; Rosen MP; Sternfeld B; Reijo Pera RA; Cedars MI
Fertil Steril. 2019 04;111(4):629-640.
Discovery of common and rare genetic risk variants for colorectal cancer
To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P?
Authors: Huyghe JR; Caan BJ; Sakoda LC; Peters U; et al.
Nat Genet. 2019 01;51(1):76-87. Epub 2018-12-03.
Diet-related inflammation and risk of prostate cancer in the California Men’s Health Study
The purpose of the study was to examine the relationship between proinflammatory diet and prostate cancer risk. Energy-adjusted Dietary Inflammatory Index (E-DII) scores were computed among 40,161 participants in the California Men’s Health Study. Over 9.7 ± 3.8 years of follow-up, 2707 incident prostate cancer cases were diagnosed and categorized as low-, intermediate-, or high-risk, based on disease grade and stage. Accelerated failure-time models assessed time to diagnosis of prostate cancer. Cox proportional hazard models estimated hazard ratios (HR) and 95% confidence intervals (95% CI). Nonlinear effects of E-DII were modeled as third-order polynomials. Time to prostate cancer diagnosis did not differ by E-DII quartile. The HR for high-risk prostate cancer increased in the third E-DII quartile (HRQ3 vs. Q1 = 1.36; 95% CI: 1.04-1.76), but not in the fourth (HRQ4 vs. Q1 = 0.99; 95% CI: 0.74-1.32, Ptrend = .74), suggesting a nonlinear dose-response. HR curves for prostate cancer increased exponentially above an E-DII threshold of ?+3.0. HR curves for high-risk prostate cancer had a much steeper incline above an E-DII threshold of ?+2.5. Curves were higher among Blacks and Whites relative to other races and among overweight or obese men. No relationship was observed between E-DII scores and intermediate- or low-risk disease. Relationships between proinflammatory diet and prostate cancer risk may be nonlinear, with an increased risk above an E-DII threshold of ?+2.5.
Authors: McMahon DM; Burch JB; Hébert JR; Hardin JW; Zhang J; Wirth MD; Youngstedt SD; Shivappa N; Jacobsen SJ; Caan B; Van Den Eeden SK
Ann Epidemiol. 2019 01;29:30-38. Epub 2018-11-02.
Birth in High Infant Mortality States and Dementia Risk in a Cohort of Elderly African American and White Health Care Members
Birth in areas with high infant mortality rates (IMRs) has been linked to worse long-term health outcomes, yet it is completely unknown if it impacts dementia risk. In total 6268 health care members were followed for dementia diagnosis from 1996 to 2015. Birth state IMRs from 1928 were ranked into quartile (worst IMRs quartile range, whites: 69 to 129 deaths/1000 live births, Non-whites: 129 to 277 deaths/1000 live births). Cox proportional hazard models estimated the dementia risk associated with birth state IMR quartile adjusting for demographics and lifecourse health indicators. Compared with whites born outside of states in the worst IMR quartile, African Americans born in states in the worst IMR quartile had 92% increased dementia risk (HR=1.92; 95% CI: 1.42, 2.59), and African Americans born outside those states had 36% increased risk (HR=1.36; 95% CI: 1.20, 1.53). There was no association between birth state IMR and dementia risk among whites. Birth in states with the highest rates of infant mortality was associated with elevated dementia risk among African Americans but not whites. The large absolute difference in IMRs likely reflects harsher early childhood conditions experienced by African Americans. These findings suggest that childhood conditions may play a role in racial disparities in dementia rates.
Authors: Gilsanz P; Mayeda ER; Glymour MM; Quesenberry CP; Mungas D; DeCarli CS; Whitmer RA
Alzheimer Dis Assoc Disord. 2019 Jan-Mar;33(1):1-6.
How competent are people who use opioids at responding to overdoses? Qualitative analyses of actions and decisions taken during overdose emergencies.
BACKGROUND AND AIMS: Providing take-home naloxone (THN) to people who use opioids is an increasingly common strategy for reversing opioid overdose. However, implementation is hindered by doubts regarding the ability of people who use opioids to administer naloxone and respond appropriately to overdoses. We aimed to increase understanding of the competencies required and demonstrated by opioid users who had recently participated in a THN programme and were subsequently confronted with an overdose emergency.DESIGN: Qualitative study designed to supplement findings from a randomized controlled trial of overdose education and naloxone distribution. Interviews were audio-recorded, transcribed, systematically coded and analysed via Iterative Categorization.SETTING: New York City, USA.PARTICIPANTS: Thirty-nine people who used opioids (32 men, 7 women; aged 22-58 years).INTERVENTION: Trial participants received brief or extended overdose training and injectable or nasal naloxone.MEASUREMENTS: The systematic coding frame comprised deductive codes based on the topic guide and more inductive codes emerging from the data.FINDINGS: In 38 of 39 cases the victim was successfully resuscitated; the outcome of one overdose intervention was unknown. Analyses revealed five core overdose response ‘tasks’: (1) overdose identification; (2) mobilizing support; (3) following basic first aid instructions; (4) naloxone administration; and (5) post-resuscitation management. These tasks comprised actions and decisions that were themselves affected by diverse cognitive, emotional, experiential, interpersonal and social factors over which lay responders often had little control. Despite this, participants demonstrated high levels of competency. They had acquired new skills and knowledge through training and brought critical ‘insider’ understanding to overdose events and the resuscitation actions which they applied.CONCLUSIONS: People who use opioids can be trained to respond appropriately to opioid overdoses and thus to save their peers’ lives. Overdose response requires both practical competency (e.g. skills and knowledge in administering basic first aid and naloxone) and social competency (e.g. willingness to help others, having the confidence to be authoritative and make decisions, communicating effectively and demonstrating compassion and care to victims post-resuscitation).
Authors: Neale, Joanne J; Brown, Caral C; Campbell, Aimee N C ANC; Jones, Jermaine D JD; Metz, Verena E VE; Strang, John J; Comer, Sandra D SD
Addiction (Abingdon, England). 2019 04 ;114(4):708-718. Epub 2018-12-28.
Healthy Lifestyle During the Midlife Is Prospectively Associated With Less Subclinical Carotid Atherosclerosis: The Study of Women’s Health Across the Nation
Background Measures of subclinical atherosclerosis are predictors of future cardiovascular outcomes as well as of physical and cognitive functioning. The menopausal transition is associated with accelerated progression of atherosclerosis in women. The prospective association between a healthy lifestyle during the midlife and subclinical atherosclerosis is unclear. Methods and Results Self-reported data on smoking, diet, and physical activity from 1143 women in the Study of Women’s Health Across the Nation were used to construct a 10-year average Healthy Lifestyle Score ( HLS ) during the midlife. Markers of subclinical atherosclerosis were measured 14 years after baseline and included common carotid artery intima-media thickness ( CCA – IMT ), adventitial diameter ( CCA – AD ), and carotid plaque. The associations of average HLS with CCA – IMT and CCA – AD were estimated using linear models; the association of average HLS with carotid plaque was estimated using cumulative logit models. Average HLS was associated with smaller CCA – IMT and CCA – AD in the fully adjusted models ( P=0.0031 and <0.001, respectively). Compared with participants in the lowest HLS level, those in the highest level had 0.024 mm smaller CCA - IMT (95% confidence interval: -0.048, 0.000), which equals 17% of the SD of CCA - IMT , and 0.16 mm smaller CCA - AD (95% confidence interval: -0.27, -0.04), which equals 24% of the SD of CCA - AD . Among the 3 components of the HLS , abstinence from smoking had the strongest association with subclinical atherosclerosis. Conclusions Healthy lifestyle during the menopausal transition is associated with less subclinical atherosclerosis, highlighting the growing recognition that the midlife is a critical window for cardiovascular prevention in women.
Authors: Wang D; Sternfeld B; Baylin A; et al.
J Am Heart Assoc. 2018 12 04;7(23):e010405.
Genetic risk factors for pediatric-onset multiple sclerosis
Strong evidence supports the role of both genetic and environmental factors in pediatric-onset multiple sclerosis (POMS) etiology. We comprehensively investigated the association between established major histocompatibility complex (MHC) and non-MHC adult multiple sclerosis (MS)-associated variants and susceptibility to POMS. Cases with onset <18 years (n = 569) and controls (n = 16,251) were included from the United States and Sweden. Adjusted logistic regression and meta-analyses were performed for individual risk variants and a weighted genetic risk score (wGRS) for non-MHC variants. Results were compared to adult MS cases (n = 7588). HLA-DRB1*15:01 was strongly associated with POMS (odds ratio (OR)meta = 2.95, p < 2.0 × 10-16). Furthermore, 28 of 104 non-MHC variants studied (23%) were associated (p < 0.05); POMS cases carried, on average, a higher burden of these 28 variants compared to adults (ORavg = 1.24 vs 1.13, respectively), though the difference was not significant. The wGRS was strongly associated with POMS (ORmeta = 2.77, 95% confidence interval: 2.33, 3.32, p < 2.0 × 10-16) and higher, on average, when compared to adult cases. Additional class III risk variants in the MHC region associated with POMS were revealed after accounting for HLA-DRB1*15:01 and HLA-A*02. Pediatric and adult MS share many genetic variants suggesting similar biological processes are present. MHC variants beyond HLA-DRB1*15:01 and HLA-A*02 are also associated with POMS.
Authors: Gianfrancesco MA; Schaefer C; Barcellos LF; Network of Pediatric Multiple Sclerosis Centers; et al.
Mult Scler. 2018 12;24(14):1825-1834. Epub 2017-10-05.
Psychiatric Disorders and Comorbid Cannabis Use: When Should We Be Concerned and What Can We Do About It?
Authors: Satre DD; Borsari B; Tompkins DA; Ramo D
J Clin Psychiatry. 2018 09 11;79(6). Epub 2018-09-11.
Feasibility of expanded emergency department screening for behavioral health problems
Behavioral health conditions and social problems are common yet underrecognized among emergency department (ED) patients. Traditionally, ED-based behavioral health screening is limited. We evaluated the feasibility of expanded behavioral health screening by a trained nonclinician. Prospective observational study of a convenience sample of ED patients. A research assistant (RA) approached a convenience sample of adult ED patients within an integrated healthcare delivery system. Patients completed a paper screening instrument (domains: mood, anxiety, alcohol use, drug use, sleep, intimate partner violence, and chronic pain) and reviewed responses with the RA, who shared positive screening results with the treating ED physician. We abstracted behavioral health and medical diagnoses from the electronic health record (EHR), comparing the screened cohort with the eligible population. We used ?2 tests to assess differences in demographics and comorbidities between screened patients and the eligible group and differences between self-reported symptoms and EHR diagnoses among screened patients. Among 598 screened patients, the prevalence of self-reported symptoms was higher than that of associated EHR diagnoses in the year prior to the ED visit (anxiety, 45% vs 19% [P <.001]; depression, 40% vs 22% [P <.001]; drug use, 7% vs 4% [P = .011]; risky alcohol use, 12% vs 5% [P <.001]; chronic pain, 47% vs 30% [P <.001]; and sleep problems, 47% vs 4% [P <.001]). A dedicated RA was able to integrate screening into patient idle times in the ED visit. The prevalence of behavioral health problems was higher than indicated in the EHR.
Authors: Kene M; Miller Rosales C; Wood S; Rauchwerger AS; Vinson DR; Sterling SA
Am J Med. 2020 05;133(5):567-572. Epub 2020-02-04.
Reduction in the Creatine Kinase Forward Reaction Rate as a Potential Trait Biomarker of Bipolar Disorder: Implications for Mitochondrial and Energy Metabolism Models
Authors: Ridout KK
Biol Psychiatry. 2018 12 01;84(11):e77-e79.
A Prediction Tool to Facilitate Risk-Stratified Screening for Squamous Cell Skin Cancer
Cutaneous squamous cell cancers (cSCCs) present an under-recognized health issue among non-Hispanic whites, one that is likely to increase as populations age. cSCC risks vary considerably among non-Hispanic whites, and this heterogeneity indicates the need for risk-stratified screening strategies that are guided by patients’ personal characteristics and clinical histories. Here we describe cSCCscore, a prediction tool that uses patients’ covariates and clinical histories to assign them personal probabilities of developing cSCCs within 3 years after risk assessment. cSCCscore uses a statistical model for the occurrence and timing of a patient’s cSCCs, whose parameters we estimated using cohort data from 66,995 patients in the Kaiser Permanente Northern California healthcare system. We found that patients’ covariates and histories explained approximately 75% of their interpersonal cSCC risk variation. Using cross-validated performance measures, we also found cSCCscore’s predictions to be moderately well calibrated to the patients’ observed cSCC incidence. Moreover, cSCCscore discriminated well between patients who subsequently did and did not develop a new primary cSCC within 3 years after risk assignment, with area under the receiver operating characteristic curve of approximately 85%. Thus, cSCCscore can facilitate more informed management of non-Hispanic white patients at cSCC risk. cSCCscore’s predictions are available at https://researchapps.github.io/cSCCscore/.
Authors: Wang W; Jorgenson E; Ioannidis NM; Asgari MM; Whittemore AS
J Invest Dermatol. 2018 12;138(12):2589-2594. Epub 2018-07-02.
Characteristics of patients with substance use disorder before and after the Affordable Care Act
The Affordable Care Act (ACA) offered an unprecedented opportunity to expand insurance coverage to patients with substance use disorders (SUDs). We explored the expectations of key stakeholders for the ACA’s impact on SUD care, and examined how clinical characteristics of newly enrolled patients with SUD in a large healthcare delivery system differed pre- and post- ACA implementation. In this mixed-methods study, qualitative interviews were conducted with health system leaders to identify themes regarding how the health system prepared for the ACA. Electronic health record data were used to examine demographics, as well as specific SUD, psychiatric, and medical diagnoses in cohorts of pre-ACA (2012, n = 6066) vs. post-ACA (2014, n = 7099) newly enrolled patients with SUD. Descriptive statistics and logistic regression models were employed to compare pre-ACA and post-ACA measures. Interviewees felt much uncertainty, but anticipated having to care for more SUD patients, who might have greater severity. Quantitative findings affirmed these expectations, with post-ACA SUD patients having higher rates of cannabis and amphetamine use disorders, and more psychiatric and medical conditions, compared to their pre-ACA counterparts. The post-ACA SUD cohort also had more Medicaid patients and greater enrollment in high-deductible plans. Post-ACA, SUD patients had more comorbidities as well as and more financial barriers to care. As federal healthcare policy continues to evolve, with potentially more restrictive coverage criteria, it is essential to continue examining how health systems adapt to changing health policy and its impact on SUD care.
Authors: Campbell CI; Parthasarathy S; Altschuler A; Young-Wolff KC; Satre DD
Drug Alcohol Depend. 2018 12 01;193:124-130. Epub 2018-10-06.
Medical and non-medical marijuana use in depression: Longitudinal associations with suicidal ideation, everyday functioning, and psychiatry service utilization
Marijuana use is clinically problematic in depression, and non-medical and medical use may both contribute to barriers to care in this population. Among outpatients with depression, we examined the differential impact of medical or non-medical marijuana use, relative to no-use, on psychopathology and service use over time. Participants were 307 psychiatry outpatients participating in a trial of drug/alcohol use treatment for depression. Measures of past 30-day marijuana use, depression/anxiety symptoms, psychiatry visits, and functional data related to health status were collected at baseline, 3, 6, and 12 months. Regressions (baseline and 1 year) and growth models (over time) predicted clinical and psychiatry visit outcomes, from medical or non-medical marijuana use (no-use = reference). At baseline, 40.0% of the sample used marijuana and more reported non-medical (71.7%) than medical (28.2%) use. Relative to non-users at baseline, patients using medically had worse mental/physical health functioning (p’s < 0.05), and non-medical use was associated with higher suicidal ideation (B = 1.08, p = .002), worse mental health functioning (B = -3.79, p = .015), and fewer psychiatry visits (B = -0.69, p = .009). Patients using non-medically over time improved less in depression symptoms (B = 1.49, p = .026) and suicidal ideation (B = 1.08, p = .003) than non-users. Participants were psychiatry outpatients, limiting generalizability. Marijuana use, especially non-medical use, among patients with depression may impede depression symptom improvement while lessening the likelihood of psychiatry visits. Marijuana use and associated barriers to care should receive consideration by depression treatment providers.
Authors: Bahorik AL; Sterling SA; Campbell CI; Weisner C; Ramo D; Satre DD
J Affect Disord. 2018 12 01;241:8-14. Epub 2018-07-17.
From Wary Wearers to d-Embracers: Personas of Readiness to Use Diabetes Devices
Diabetes devices such as insulin pumps and continuous glucose monitoring (CGM) are associated with improved health and quality of life in adults with type 1 diabetes (T1D). However, uptake remains low. The aim of this study was to develop different “personas” of adults with T1D in relation to readiness to adopt new diabetes technology. Participants were 1498 T1D Exchange participants who completed surveys on barriers to uptake, technology attitudes, and other psychosocial variables. HbA1c data was available from the T1D Exchange for 30% of the sample. K-means cluster analyses grouped the sample by device barriers and attitudes. The authors assigned descriptive labels based on cluster characteristics. ANOVAs and chi-square tests assessed group differences by demographic and psychosocial variables (eg, diabetes duration, diabetes distress). Analyses yielded five distinct personas. The d-Embracers (54% of participants) endorsed few barriers to device use and had the highest rates of device use, lowest HbA1c, and were the least distressed. The Free Rangers (23%) had the most negative technology attitudes. The Data Minimalists (10%) used pumps but had lower CGM use and did not want more diabetes information. The Wary Wearers (11%) had lower overall device use, were younger, more distressed, endorsed many barriers, and had higher HbA1c. The High Distress (3%) group members were the youngest, had the shortest diabetes duration, reported the most barriers, and were the most distressed. These clinically meaningful personas of device readiness can inform tailored interventions targeting barriers and psychosocial needs to increase device uptake.
Authors: Tanenbaum ML; Adams RN; Iturralde E; Hanes SJ; Barley RC; Naranjo D; Hood KK
J Diabetes Sci Technol. 2018 11;12(6):1101-1107. Epub 2018-08-22.
The Utility and Cross-Validation of a Composite Physical Activity Score in Relation to Cardiovascular Health Indicators: Coronary Artery Risk Development in Young Adults
Single-method assessment of physical activity (PA) has limitations. The utility and cross-validation of a composite PA score that includes reported and accelerometer-derived PA data has not been evaluated. Participants attending the Year 20 exam were randomly assigned to the derivation (two-thirds) or validation (one-third) data set. Principal components analysis was used to create a composite score reflecting Year 20 combined reported and accelerometer PA data. Generalized linear regression models were constructed to estimate the variability explained (R2) by each PA assessment strategy (self-report only, accelerometer only, composite score, or self-report plus accelerometer) with cardiovascular health indicators. This process was repeated in the validation set to determine cross-validation. At Year 20, 3549 participants (45.2 [3.6] y, 56.7% female, and 53.5% black) attended the clinic exam and 2540 agreed to wear the accelerometer. Higher R2 values were obtained when combined assessment strategies were used; however, the approach yielding the highest R2 value varied by cardiovascular health outcome. Findings from the cross-validation also supported internal study validity. Findings support continued refinement of methodological approaches to combine data from multiple sources to create a more robust estimate that reflects the complexities of PA behavior.
Authors: Pettee Gabriel K; Pérez A; Jacobs DR; Lee J; Kohl HW; Sternfeld B
J Phys Act Health. 2018 11 01;15(11):847-856. Epub 2018-10-19.
Evaluating the Impact of Eliminating Copayments for Tobacco Cessation Pharmacotherapy
We examined the impact of the Affordable Care Act-mandated elimination of tobacco cessation pharmacotherapy (TCP) copayments on patient use of TCP, overall and by income. Electronic health record data captured any and combination (eg, nicotine gum plus patch) TCP use among adult smokers newly enrolled in Kaiser Permanente Northern California (KPNC). KPNC eliminated TCP copayments in 2015. We included current smokers newly enrolled in the first 6 months of 2014 (before copayment elimination, N=16,199) or 2015 (after elimination, N=16,469). Multivariable models estimated 1-year changes in rates of any TCP fill, and of combination TCP fill, and tested for differences by income (<$50k, $50?75k, ?$75k). Through telephone surveys in 2016 with a subset of smokers newly enrolled in 2014 (n=306), we assessed barriers to TCP use, with results stratified by income. Smokers enrolled in KPNC in 2015 versus 2014 were more likely to have a TCP fill (9.1% vs. 8.2%; relative risk, 1.19; 95% confidence interval, 1.11-1.27), and combination TCP fill, among those with any fill (42.3% vs. 37.9%; relative risk, 1.12; 95% confidence interval, 1.02-1.23); findings were stronger for low-income smokers. Low-income patients (<$50k) were less likely to report that clinicians discussed smoking treatments with them (58%) compared with higher income smokers ($50?75k, 67%; ?$75k, 83%), and were less aware that TCP was free (40% vs. 53% and 69%, respectively, P-values<0.05). The Affordable Care Act's copayment elimination was associated with a modest increase in TCP use and a greater effect among low-income smokers. Uptake may have been enhanced if promoted to patients directly and via providers.
Authors: Young-Wolff KC; Adams SR; Klebaner D; Adams AS; Campbell CI; Satre DD; Prochaska JJ
Med Care. 2018 11;56(11):912-918.
A functional splicing variant associated with decreased asthma risk abolishes the ability of gasdermin B (GSMDB) to induce epithelial cell pyroptosis
Genetic variants in the chromosomal region 17q21 are consistently associated with asthma. However, mechanistic studies have not yet linked any of the associated variants to a function that could influence asthma, and as a result, the identity of the asthma gene(s) remains elusive. We sought to identify and characterize functional variants in the 17q21 locus. We used the Exome Aggregation Consortium browser to identify coding (amino acid-changing) variants in the 17q21 locus. We obtained asthma association measures for these variants in both the Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort (16,274 cases and 38,269 matched controls) and the EVE Consortium study (5,303 asthma cases and 12,560 individuals). Gene expression and protein localization were determined by quantitative RT-PCR and fluorescence immunostaining, respectively. Molecular and cellular studies were performed to determine the functional effects of coding variants. Two coding variants (rs2305480 and rs11078928) of the gasdermin B (GSDMB) gene in the 17q21 locus were associated with lower asthma risk in both GERA (odds ratio, 0.92; P = 1.01 × 10-6) and EVE (odds ratio, 0.85; joint PEVE = 1.31 × 10-13). In GERA, rs11078928 had a minor allele frequency (MAF) of 0.45 in unaffected (nonasthmatic) controls and 0.43 in asthma cases. For European Americans in EVE, the MAF of rs2305480 was 0.45 for controls and 0.39 for cases; for all EVE subjects, the MAF was 0.32 for controls and 0.27 for cases. GSDMB is highly expressed in differentiated airway epithelial cells, including the ciliated cells. We found that, when the GSDMB protein is cleaved by inflammatory caspase-1 to release its N-terminal fragment, potent pyroptotic cell death is induced. The splice variant rs11078928 deletes the entire exon 6, which encodes 13 amino acids in the critical N-terminus, and abolishes the pyroptotic activity of the GSDMB protein. Our study identified a functional asthma variant in the GSDMB gene of the 17q21 locus and implicates GSDMB-mediated epithelial cell pyroptosis in pathogenesis.
Authors: Panganiban RA; Iribarren C; Lu Q; et al.
J Allergy Clin Immunol. 2018 11;142(5):1469-1478.e2. Epub 2018-01-09.
Gene expression imputation identifies candidate genes and susceptibility loci associated with cutaneous squamous cell carcinoma.
Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer with genetic susceptibility loci identified in recent genome-wide association studies (GWAS). Transcriptome-wide association studies (TWAS) using imputed gene expression levels can identify additional gene-level associations. Here we impute gene expression levels in 6891 cSCC cases and 54,566 controls in the Kaiser Permanente Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort and 25,558 self-reported cSCC cases and 673,788 controls from 23andMe. In a discovery-validation study, we identify 19 loci containing 33 genes whose imputed expression levels are associated with cSCC at false discovery rate
Authors: Ioannidis, Nilah M NM; Wang, Wei W; Furlotte, Nicholas A NA; Hinds, David A DA; ; Bustamante, Carlos D CD; Jorgenson, Eric E; Asgari, Maryam M MM; Whittemore, Alice S AS
Nature communications. 2018 Oct 15;9(1):4264. Epub 2018-10-15.
Genetic variation in the SIM1 locus is associated with erectile dysfunction
Erectile dysfunction affects millions of men worldwide. Twin studies support the role of genetic risk factors underlying erectile dysfunction, but no specific genetic variants have been identified. We conducted a large-scale genome-wide association study of erectile dysfunction in 36,649 men in the multiethnic Kaiser Permanente Northern California Genetic Epidemiology Research in Adult Health and Aging cohort. We also undertook replication analyses in 222,358 men from the UK Biobank. In the discovery cohort, we identified a single locus (rs17185536-T) on chromosome 6 near the single-minded family basic helix-loop-helix transcription factor 1 (SIM1) gene that was significantly associated with the risk of erectile dysfunction (odds ratio = 1.26, P = 3.4 × 10-25). The association replicated in the UK Biobank sample (odds ratio = 1.25, P = 6.8 × 10-14), and the effect is independent of known erectile dysfunction risk factors, including body mass index (BMI). The risk locus resides on the same topologically associating domain as SIM1 and interacts with the SIM1 promoter, and the rs17185536-T risk allele showed differential enhancer activity. SIM1 is part of the leptin-melanocortin system, which has an established role in body weight homeostasis and sexual function. Because the variants associated with erectile dysfunction are not associated with differences in BMI, our findings suggest a mechanism that is specific to sexual function.
Authors: Jorgenson E; Yin J; Shan J; Hoffmann TJ; Thai KK; Van Den Eeden SK; et al.
Proc Natl Acad Sci USA. 2018 Oct 23;115(43):11018-11023. Epub 2018-10-08.
Data Are Needed on the Potential Adverse Effects of Marijuana Use in Pregnancy
Authors: Goler N; Conway A; Young-Wolff KC
Ann Intern Med. 2018 10 02;169(7):492-493. Epub 2018-08-21.
A Large Multi-ethnic Genome-Wide Association Study of Adult Body Mass Index Identifies Novel Loci
Body mass index (BMI), a proxy measure for obesity, is determined by both environmental (including ethnicity, age, and sex) and genetic factors, with > 400 BMI-associated loci identified to date. However, the impact, interplay, and underlying biological mechanisms among BMI, environment, genetics, and ancestry are not completely understood. To further examine these relationships, we utilized 427,509 calendar year-averaged BMI measurements from 100,418 adults from the single large multiethnic Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. We observed substantial independent ancestry and nationality differences, including ancestry principal component interactions and nonlinear effects. To increase the list of BMI-associated variants before assessing other differences, we conducted a genome-wide association study (GWAS) in GERA, with replication in the Genetic Investigation of Anthropomorphic Traits (GIANT) consortium combined with the UK Biobank (UKB), followed by GWAS in GERA combined with GIANT, with replication in the UKB. We discovered 30 novel independent BMI loci (P < 5.0 × 10-8) that replicated. We then assessed the proportion of BMI variance explained by sex in the UKB using previously identified loci compared to previously and newly identified loci and found slight increases: from 3.0 to 3.3% for males and from 2.7 to 3.0% for females. Further, the variance explained by previously and newly identified variants decreased with increasing age in the GERA and UKB cohorts, echoed in the variance explained by the entire genome, which also showed gene-age interaction effects. Finally, we conducted a tissue expression QTL enrichment analysis, which revealed that GWAS BMI-associated variants were enriched in the cerebellum, consistent with prior work in humans and mice.
Authors: Hoffmann TJ; Choquet H; Yin J; Banda Y; Kvale MN; Glymour M; Schaefer C; Risch N; Jorgenson E
Genetics. 2018 10;210(2):499-515. Epub 2018-08-14.
Early Midlife Pulmonary Function and Dementia Risk
Poor pulmonary function (PPF) is associated with increased risk of dementia, yet it is unclear if PPF in early adulthood to midlife increases risk, independent of smoking and subsequent vascular disease. This study evaluated the association between multiple markers of PPF in early adulthood to midlife and long-term risk of dementia. We evaluated 27,387 members of an integrated health care system with forced expiratory volume in 1, 2 seconds, and vital capacity collected from 1964 to 1973 (mean age=41.8±4.2 y). Associations of PPF with dementia diagnoses from January 1, 1996 to September 30, 2015 were evaluated with Cox proportional hazards models adjusted for demographics, height, body mass index, hypertension, smoking status, diabetes, stroke, and heart failure. In total, 7519 individuals (27%) were diagnosed with dementia. In fully adjusted Cox proportional hazards models, for all PPF measures each liter decrease was associated with a 13% to 14% higher risk of dementia. Compared with the highest quintile, the first quintile of PPF measures were associated with a 24% to 28% increased risk of dementia; second to fourth quintiles showed strong dose-dependent associations. Results were similar when stratified by smoking status. In this large, diverse cohort, multiple measures of PPF in early adulthood to midlife were associated with dementia risk independent of smoking and vascular comorbidities.
Authors: Gilsanz P; Mayeda ER; Flatt J; Glymour MM; Quesenberry CP; Whitmer RA
Alzheimer Dis Assoc Disord. 2018 Oct-Dec;32(4):270-275.
Traumatic brain injury associated with dementia risk among people with type 1 diabetes
To examine the association between traumatic brain injury (TBI) and dementia risk among a cohort of middle-aged and elderly individuals with type 1 diabetes (T1D). We evaluated 4,049 members of an integrated health care system with T1D ≥50 years old between January 1, 1996, and September 30, 2015. Dementia and TBI diagnoses throughout the study period were abstracted from medical records. Cox proportional hazards models estimated associations between time-dependent TBI and dementia adjusting for demographics, HbA1c, nephropathy, neuropathy, stroke, peripheral artery disease, depression, and dysglycemic events. Fine and Gray regression models evaluated the association between baseline TBI and dementia risk accounting for competing risk of death. A total of 178 individuals (4.4%) experienced a TBI and 212 (5.2%) developed dementia. In fully adjusted models, TBI was associated with 3.6 times the dementia risk (hazard ratio [HR] 3.64; 95% confidence interval [CI] 2.34, 5.68). When accounting for the competing risk of death, TBI was associated with almost 3 times the risk of dementia (HR 2.91; 95% CI 1.29, 5.68). This study demonstrates a marked increase in risk of dementia associated with TBI among middle-aged and elderly people with T1D. Given the complexity of self-care for individuals with T1D, and the comorbidities that predispose them to trauma and falls, future work is needed on interventions protecting brain health in this vulnerable population, which is now living to old age.
Authors: Gilsanz P; Albers K; Beeri MS; Karter AJ; Quesenberry CP; Whitmer RA
Neurology. 2018 Sep 26.
Gender and alcohol use: influences on HIV care continuum in a national cohort of patients with HIV
To investigate whether gender is associated with three recommended stages of the HIV care continuum and whether gender modifies known associations between level of alcohol use and HIV care among US veterans. Retrospective cohort. Veterans Aging Cohort Study data were used to identify Veterans Health Administration (VA) patients with HIV and AUDIT-C alcohol screening from 1 February 2008 to 30 September 2014. Modified Poisson regression models estimated the relative risk and predicted prevalences of engagement in HIV care (documented CD4 cells/μl or viral load copies/ml lab values), ART treatment (at least one prescription), and viral suppression (HIV RNA <500 copies/ml) in the year following AUDIT-C (1) for women compared to men, and (2) for each level of alcohol use compared to nondrinking among women and among men. A multiplicative interaction between gender and alcohol use was tested. Among 33 224 patients, women (n = 971) were less likely than men (n = 32 253) to receive HIV care (P values <0.001). Respective predicted prevalences for women and men were 71.9% (95% CI 69.1-74.7%) and 77.9% (77.5-78.4%) for engagement, 60.0% (57.0-73.14%) and 73.8% (73.4-74.3%) for ART treatment, and 46.4% (43.3-49.6%) and 55.8% (55.3-56.3%) for viral suppression. Although the interaction between gender and alcohol use was not statistically significant, stratified analyses suggested worse outcomes for women than men at higher levels of alcohol use. In this large national cohort, women were less likely than men to be engaged in HIV medical care, prescribed ART, and virally suppressed. Interventions to improve HIV care for women are needed at all levels of alcohol use.
Authors: Matson TE; Satre DD; Williams EC; et al.
AIDS. 2018 09 24;32(15):2247-2253.
The PPARγ Agonist Pioglitazone Fails to Alter the Abuse Potential of Heroin, But Does Reduce Heroin Craving and Anxiety.
Possibly through its effects on glia, the peroxisome proliferator-activated gamma receptor (PPARγ) agonist pioglitazone (PIO) has been shown to alter the effects of heroin in preclinical models. Until now, these results have not been assessed in humans. Heroin-dependent participants were randomized to either active (45 mg, n = 14) or placebo (0 mg, n = 16) PIO maintenance for the duration of the three-week study. After stabilization on buprenorphine (8 mg), participants began a two-week testing period. On the first to fourth test days, participants could self-administer drug or money by making verbal choices for either option. On the fifth day, active heroin and money were administered and participants could work to receive heroin or money using a progressive ratio choice procedure. Test days 6-10 were identical to test days 1-5 with the exception that, during one of the test weeks, placebo was available on the first four days, and during the other week heroin was available. PIO failed to alter the reinforcing or positive subjective effects of heroin, but it did reduce heroin craving and overall anxiety. Although we were unable to replicate the robust effects found in preclinical models, these data provide an indication of drug effects that deserves further exploration.
Authors: Jones, Jermaine D JD; Bisaga, Adam A; Metz, Verena E VE; Manubay, Jeanne M JM; Mogali, Shanthi S; Ciccocioppo, Roberto R; Madera, Gabriela G; Doernberg, Molly M; Comer, Sandra D SD
Journal of psychoactive drugs. 2019 04 ;50(5):390-401. Epub 2018-09-11.
Long-term Glycemic Control and Dementia Risk in Type 1 Diabetes
Individuals with type 1 diabetes have experienced an increase in life expectancy; yet, it is unknown what level of glycemic control is ideal for maintaining late-life brain health. We investigated the association of long-term glycemic control with dementia in older individuals with type 1 diabetes. We followed 3,433 members of a health care system with type 1 diabetes, ages ≥50 years, from 1996 to 2015. Repeated measurements of hemoglobin A1c (HbA1c), dementia diagnoses, and comorbidities were ascertained from health records. Cox proportional hazards models were fit to evaluate the association of time-varying glycemic exposure with dementia, with adjustment for age, sex, race/ethnicity, baseline health conditions, and frequency of HbA1c measurement. Over a mean follow-up of 6.3 years, 155 individuals (4.5%) were diagnosed with dementia. Patients with ≥50% of HbA1c measurements at 8-8.9% (64-74 mmol/mol) and ≥9% (≥75 mmol/mol) had 65% and 79% higher risk of dementia, respectively, compared with those with
Authors: Lacy ME; Gilsanz P; Karter AJ; Quesenberry CP; Pletcher MJ; Whitmer RA
Diabetes Care. 2018 Sep 04.
Characterization of Statin Low-Density Lipoprotein Cholesterol Dose-Response Using Electronic Health Records in a Large Population-Based Cohort
Low-density lipoprotein cholesterol (LDL-C) response to statin therapy has not been fully elucidated in real-world populations. The primary objective of this study was to characterize statin LDL-C dose-response and its heritability in a large, multiethnic population of statin users. We determined the effect of statin dosing on lipid measures utilizing electronic health records in 33 139 statin users from the Kaiser Permanente GERA cohort (Genetic Epidemiology Research on Adult Health and Aging). The relationship between statin defined daily dose and lipid parameter response (percent change) was determined. Defined daily dose and LDL-C response was associated in a log-linear relationship (β, -6.17; SE, 0.09; P
Authors: Oni-Orisan A; Hoffmann TJ; Ranatunga D; Medina MW; Jorgenson E; Schaefer C; Krauss RM; Iribarren C; Risch N
Circ Genom Precis Med. 2018 Sep;11(9):e002043.
Adverse Childhood Experiences Run Deep: Toxic Early Life Stress, Telomeres, and Mitochondrial DNA Copy Number, the Biological Markers of Cumulative Stress
This manuscript reviews recent evidence supporting the utility of telomeres and mitochondrial DNA copy number (mtDNAcn) in detecting the biological impacts of adverse childhood experiences (ACEs) and outlines mechanisms that may mediate the connection between early stress and poor physical and mental health. Critical to interrupting the health sequelae of ACEs such as abuse, neglect, and neighborhood disorder, is the discovery of biomarkers of risk and resilience. The molecular markers of chronic stress exposure, telomere length and mtDNAcn, represent critical biological links between ACEs and poor health outcomes. We examine how telomeres and mtDNAcn may exacerbate health disparities and contribute to the intergenerational transmission of trauma. Finally, we explore how these molecular markers of early stress exposure may help define the role of resilience and develop effective interventions to moderate ACE health risk impact.
Authors: Ridout KK; Khan M; Ridout SJ
Bioessays. 2018 09;40(9):e1800077. Epub 2018-08-01.
Depression Screening Rates and Symptom Severity by Alcohol Use Among Primary Care Adult Patients
Hazardous alcohol use with depression may exacerbate health conditions and complicate medical care. We examined the rate of depression screening by alcohol use severity among primary care patients screened for hazardous alcohol use and, among those screened, examined patterns of significant depressive symptoms. Using cross-sectional data from primary care patients (n = 2,894,906), we examined past-90-day alcohol use (number of typical drinking days/week and typical number of drinks consumed daily); depression screening rates (using the Patient Health Questionnaire 9 [PHQ-9]); and symptom severity, demographics, and prevalence of selected psychiatric diagnoses. Within 30 days of routine, in-clinic alcohol use screening by medical assistants, 2.4% (n = 68,686) of patients also completed a PHQ-9; these patients were more likely to be female, younger, white, Medicaid insured, and to have a nondepressive psychiatric diagnosis and a lower Charlson comorbidity score. Abstainers and moderate drinkers (1 to 7 drinks/week or 1 to 4 drinks/week for women and individuals >65 years or for men ≤65 years, respectively) were less likely than hazardous drinkers (exceeding weekly limits) to complete the PHQ-9 or to have significant depressive symptoms (PHQ-9 score ≥10). Nonwhite patients with higher Charlson comorbidity scores were more likely to endorse significant depressive symptoms. Only a small fraction of patients in this cohort were screened for depression. Nonwhite patients and those with higher comorbidity burden were more likely to report depression but less likely to be screened. These discrepancies between depression-screening rates and significant depressive symptoms suggest that screening for depression should be enhanced in these at-risk groups.
Authors: Hirschtritt ME; Kline-Simon AH; Kroenke K; Sterling SA
J Am Board Fam Med. 2018 Sep-Oct;31(5):724-732.
Association of behavioral health factors and social determinants of health with high and persistently high healthcare costs
A high proportion of U.S. health care costs are attributable to a relatively small proportion of patients. Understanding behavioral and social factors that predict initial and persistent high costs for these “high utilizers” is critical for health policy-makers. This prospective observational study was conducted at Kaiser Permanente Northern California (KPNC), an integrated healthcare delivery system with 4.1 million members. A stratified random sample of high-cost vs. non-high-cost adult KPNC members matched by age, gender, race/ethnicity, type of health insurance, and medical severity (N = 378) was interviewed between 3/14/2013 and 3/20/2014. Data on health care costs and clinical diagnoses between 1/1/2008 and 12/31/2012 were derived from the electronic health record (EHR). Social-economic status, depression symptoms, adverse childhood experiences (ACEs), interpersonal violence, financial stressors, neighborhood environment, transportation access, and patient activation and engagement were obtained through telephone interviews. Initial and subsequent high-cost status were defined as being classified in top 20% cost levels over 1/1/2009-12/31/2011 and 1/1/2012-12/31/2012, respectively. Psychiatric diagnosis (OR 2.55, 95% CI 1.52-4.29, p < 0.001), financial stressors (OR 1.97, 95% CI 1.19-3.26, p = 0.009), and ACEs (OR 1.10, 95% CI 1.00-1.20, p = 0.051) predicted initial high-cost status. ACEs alone predicted persistent high-cost status in the subsequent year (OR 1.12, 95% CI 1.00-1.25, p = 0.050). Non-medical factors such as psychiatric problems, financial stressors and adverse childhood experiences contribute significantly to the likelihood of high medical utilization and cost. Efforts to predict and reduce high utilization must include measuring and potentially addressing these factors.
Authors: Sterling S; Chi F; Weisner C; Grant R; Pruzansky A; Bui S; Madvig P; Pearl R
Prev Med Rep. 2018 Sep;11:154-159. Epub 2018-06-27.
Stratified probabilistic bias analysis for BMI-related exposure misclassification in postmenopausal women
There is widespread concern about the use of body mass index (BMI) to define obesity status in postmenopausal women because it may not accurately represent an individual’s true obesity status. The objective of the present study is to examine and adjust for exposure misclassification bias from using an indirect measure of obesity (BMI) compared with a direct measure of obesity (percent body fat). We used data from postmenopausal non-Hispanic black and non-Hispanic white women in the Women’s Health Initiative (n=126,459). Within the Women’s Health Initiative, a sample of 11,018 women were invited to participate in a sub-study involving dual-energy x-ray absorptiometry scans. We examined indices of validity comparing BMI-defined obesity (≥30 kg/m), with obesity defined by percent body fat. We then used probabilistic bias analysis models stratified by age and race to explore the effect of exposure misclassification on the obesity-mortality relationship. Validation analyses highlight that using a BMI cutpoint of 30 kg/m to define obesity in postmenopausal women is associated with poor validity. There were notable differences in sensitivity by age and race. Results from the stratified bias analysis demonstrated that failing to adjust for exposure misclassification bias results in attenuated estimates of the obesity-mortality relationship. For example, in non-Hispanic white women 50-59 years of age, the conventional risk difference was 0.017 (95% confidence interval = 0.01, 0.023) and the bias-adjusted risk difference was 0.035 (95% simulation interval = 0.028, 0.043). These results demonstrate the importance of using quantitative bias analysis techniques to account for nondifferential exposure misclassification of BMI-defined obesity. See video abstract at, https://links.lww.com/EDE/B385.
Authors: Banack HR; Cespedes Feliciano EM; Caan BJ; Kroenke CH; Wactawski-Wende J; et al.
Epidemiology. 2018 09;29(5):604-613.
Factors associated with hazardous alcohol use and motivation to reduce drinking among HIV primary care patients: Baseline findings from the Health & Motivation study
Limited primary care-based research has examined hazardous drinking risk factors and motivation to reduce use in persons with HIV (PWH). We computed prevalence ratios (PR) for factors associated with recent (<30 days) hazardous alcohol use (i.e., 4+/5+ drinks in a single day for women/men), elevated Alcohol Use Disorders Identification Test (AUDIT) scores, and importance and confidence (1-10 Likert scales) to reduce drinking among PWH in primary care. Of 614 participants, 48% reported recent hazardous drinking and 12% reported high alcohol use severity (i.e., AUDIT zone 3 or higher). Factors associated with greater alcohol severity included moderate/severe anxiety (PR: 2.07; 95% CI: 1.18, 3.63), tobacco use (PR: 1.79; 1.11, 2.88), and other substance use (PR: 1.72; 1.04, 2.83). Factors associated with lower alcohol severity included age 50-59 years (PR: 0.46; 0.22, 2.00) compared with age 20-39 years, and having some college/college degree (PR: 0.61; 0.38, 0.97) compared with ≤high school. Factors associated with greater importance to reduce drinking (scores >5) included: moderate/severe depression (PR: 1.43; 1.03, 2.00) and other substance use (PR: 1.49; 1.11, 2.01). Lower importance was associated with incomes above $50,000 (PR: 0.65; 0.46, 0.91) and marijuana use (PR: 0.65; 0.49, 0.87). HIV-specific factors (e.g., CD4 and HIV RNA levels) were not associated with alcohol outcomes. This study identified modifiable participant characteristics associated with alcohol outcomes in PWH, including anxiety and depression severity, tobacco use, and other substance use.
Authors: Silverberg MJ; Leyden WA; Leibowitz A; Hare CB; Jang HJ; Sterling S; Catz SL; Parthasarathy S; Horberg MA; Satre DD
Addict Behav. 2018 09;84:110-117. Epub 2018-03-31.
Long-term outcomes of a large, prospective observational cohort of older adults with back pain
Although back pain is common among older adults, there is relatively little research on the course of back pain in this age group. Our primary goals were to report 2-year outcomes of older adults initiating primary care for back pain and to examine the relative importance of patient factors versus medical interventions in predicting 2-year disability and pain. This study used a predictive model using data from a prospective, observational cohort from a primary care setting. The study included patients aged ≥65 years at the time of new primary care visits for back pain. Self-reported 2-year disability (Roland-Morris Disability Questionnaire [RDQ]) and back pain (0-10 numerical rating scale [NRS]). We developed our models using a machine learning least absolute shrinkage and selection operator approach. We evaluated the predictive value of baseline characteristics and the incremental value of interventions that occurred between 0 and 90 days, and the change in patient disability and pain from 0 to 90 days. Limitations included confounding by indication and unmeasured confounding. Of 4,665 patients (89%) with follow-up, both RDQ (from mean 9.6 [95% confidence interval {CI} 9.4-9.7] to mean 8.3 [95% CI 8.0-8.5]) and back pain NRS (from mean 5.0 [95% CI 4.9-5.1] to mean 3.5 [95% CI 3.4-3.6]) scores improved slightly. Only 16% (15%-18%) reported no back pain-related disability or back pain at 2 years after initial visits. Regression model parameters explained 40% of the variation (R2) in 2-year RDQ scores, and the addition of 0- to 3-month change in RDQ score and pain improved prediction (R2=51%). The most consistent predictors of 2-year RDQ scores and back pain NRS scores were 0- to 90-day change in each respective outcome and patient confidence in improvement. Patients experienced 50% and 43% improvement in back pain and disability, respectively, 2 years after their initial visit. However, fewer than 20% of patients had complete resolution of their back pain and disability at that time. Baseline patient factors were more important than early interventions in explaining disability and pain after 2 years.
Authors: Jarvik JG; Avins AL; Heagerty PJ; et al.
Spine J. 2018 09;18(9):1540-1551. Epub 2018-01-31.
Cross-sex Hormones and Acute Cardiovascular Events in Transgender Persons: A Cohort Study
Venous thromboembolism (VTE), ischemic stroke, and myocardial infarction in transgender persons may be related to hormone use. To examine the incidence of these events in a cohort of transgender persons. Electronic medical record-based cohort study of transgender members of integrated health care systems who had an index date (first evidence of transgender status) from 2006 through 2014. Ten male and 10 female cisgender enrollees were matched to each transgender participant by year of birth, race/ethnicity, study site, and index date enrollment. Kaiser Permanente in Georgia and northern and southern California. 2842 transfeminine and 2118 transmasculine members with a mean follow-up of 4.0 and 3.6 years, respectively, matched to 48 686 cisgender men and 48 775 cisgender women. VTE, ischemic stroke, and myocardial infarction events ascertained from diagnostic codes through the end of 2016 in transgender and reference cohorts. Transfeminine participants had a higher incidence of VTE, with 2- and 8-year risk differences of 4.1 (95% CI, 1.6 to 6.7) and 16.7 (CI, 6.4 to 27.5) per 1000 persons relative to cisgender men and 3.4 (CI, 1.1 to 5.6) and 13.7 (CI, 4.1 to 22.7) relative to cisgender women. The overall analyses for ischemic stroke and myocardial infarction demonstrated similar incidence across groups. More pronounced differences for VTE and ischemic stroke were observed among transfeminine participants who initiated hormone therapy during follow-up. The evidence was insufficient to allow conclusions regarding risk among transmasculine participants. Inability to determine which transgender members received hormones elsewhere. The patterns of increases in VTE and ischemic stroke rates among transfeminine persons are not consistent with those observed in cisgender women. These results may indicate the need for long-term vigilance in identifying vascular side effects of cross-sex estrogen. Patient-Centered Outcomes Research Institute and Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Authors: Getahun D; Hunkeler E; Silverberg MJ; Goodman M; et al.
Ann Intern Med. 2018 08 21;169(4):205-213. Epub 2018-07-10.
Association of Nausea and Vomiting in Pregnancy With Prenatal Marijuana Use
Use of marijuana, an antiemetic, is increasing among pregnant women,1,2 and data from 2 small surveys3,4 indicate that women self-report using marijuana to alleviate nausea and vomiting in pregnancy (NVP). To date, only 1 epidemiologic study5 has examined whether women with NVP are at elevated risk of using marijuana. The study of 4735 pregnant women in Hawaii5 from 2009 through 2011 found that self-reported prenatal marijuana use was more prevalent among those with (3.7%) vs without (2.3%) self-reported severe nausea during pregnancy. We used data from a large California health care system with standard universal screening for prenatal marijuana use via self-report and urine toxicologic tests from January 1, 2009, through December 31, 2016, to test whether prenatal marijuana use is elevated among females with a diagnosis of NVP. Methods:Kaiser Permanente Northern California (KPNC) is a multispecialty health care system serving more than 4 million members representative of the Northern California area. The sample consisted of pregnant females 12 years or older in KPNC who completed a self-reported substance use questionnaire and urine toxicologic test in the first trimester (at approximately?8 weeks gestation) during standard prenatal care. All positive toxicologic test findings were confirmed with a laboratory test result. The institutional review board of KPNC approved this study and waived the need for informed consent. Nausea and vomiting during the first trimester of pregnancy (90 days from last menstrual period) was based on International Classification of Disease, Ninth Revision, Clinical Modification, and Tenth Revision, Clinical Modification, diagnostic codes in the electronic health record and categorized as severe (hyperemesis gravidarum [codes 643.00, 643.03, 643.10, 643.13, O21.0, and O21.1]), mild (other NVP diagnoses [codes 536.2, 643.80, 643.90, 643.93, 787.01, 787.02, 787.03, G43.A0, O21.9, R11.0, R11.10, R11.11, and R11.2]), or none. We estimated the adjusted odds of prenatal marijuana use among females with NVP using multilevel logistic regression, controlling for age, race/ethnicity, median neighborhood household income, year, and self-reported marijuana use in the year before pregnancy from the universal screening questionnaire for prenatal substance use. We used in the PROC GLIMMIX procedure in SAS software (version 9.3; SAS Institute, Inc) for all analyses, and 2-sided P?
Authors: Young-Wolff KC; Sarovar V; Tucker LY; Avalos LA; Conway A; Armstrong MA; Goler N
JAMA Intern Med. 2018 Aug 20.
Incorporating machine learning approaches to assess putative environmental risk factors for multiple sclerosis
Multiple sclerosis (MS) incidence has increased recently, particularly in women, suggesting a possible role of one or more environmental exposures in MS risk. The study objective was to determine if animal, dietary, recreational, or occupational exposures are associated with MS risk. Least absolute shrinkage and selection operator (LASSO) regression was used to identify a subset of exposures with potential relevance to disease in a large population-based (Kaiser Permanente Northern California [KPNC]) case-control study. Variables with non-zero coefficients were analyzed in matched conditional logistic regression analyses, adjusted for established environmental risk factors and socioeconomic status (if relevant in univariate screening),± genetic risk factors, in the KPNC cohort and, for purposes of replication, separately in the Swedish Epidemiological Investigation of MS cohort. These variables were also assessed in models stratified by HLA-DRB1*15:01 status since interactions between risk factors and that haplotype have been described. There was a suggestive association of pesticide exposure with having MS among men, but only in those who were positive for HLA-DRB1*15:01 (OR pooled = 3.11, 95% CI 0.87, 11.16, p = 0.08). While this finding requires confirmation, it is interesting given the association between pesticide exposure and other neurological diseases. The study also demonstrates the application of LASSO to identify environmental exposures with reduced multiple statistical testing penalty. Machine learning approaches may be useful for future investigations of concomitant MS risk or prognostic factors.
Authors: Mowry EM; Hedström AK; Gianfrancesco MA; Shao X; Schaefer CA; Shen L; Bellesis KH; Briggs FBS; Olsson T; Alfredsson L; Barcellos LF
Mult Scler Relat Disord. 2018 Aug;24:135-141. Epub 2018-06-23.
Changes in alcohol use associated with changes in HIV disease severity over time: A national longitudinal study in the Veterans Aging Cohort
Among groups of persons living with HIV (PLWH), high-risk drinking trajectories are associated with HIV severity. Whether changes in individuals’ alcohol use are associated with changes in HIV severity over the same period is unknown. Veterans Aging Cohort Study (VACS) data from VA’s EHR (2/1/2008-9/30/2016) identified AUDIT-C screens for all PLWH. Pairs of AUDIT-C screens within 9-15 months were included if CD4 and/or viral load (VL) was measured within 9 months after baseline and follow-up AUDIT-Cs. Linear regression assessed change in HIV severity (CD4 and logVL) associated with AUDIT-C change adjusted for confounders. Mean changes in HIV severity were estimated for each AUDIT-C change value. For all measures of change, positive values indicate improvements (lower drinking and improved HIV severity). Among PLWH, 21,999 and 22,143 were eligible for CD4 and VL analyses, respectively. Most had non- or low-level drinking and stable consumption over time (mean AUDIT-C change = .08, SD = 1.91). HIV severity improved over time [mean CD4 change = 20.5 (SD 180.8); mean logVL change = 0.12 (SD 0.71)]. AUDIT-C changes were associated non-linearly with changes in CD4 (p = 0.03) and logVL (p < 0.001). Improvement in HIV severity was greatest among those with stable AUDIT-C scores over time; those with greater AUDIT-C increases fared worse than those with smaller increases in or stable AUDIT-Cs. Improvement in HIV severity was greatest among PLWH with relatively stable drinking, most of whom initially did not drink or drank at low levels. Those with large changes (especially increases) in drinking appear at greatest risk for poor HIV control.
Authors: Williams EC; Satre DD; Bradley KA; et al.
Drug Alcohol Depend. 2018 08 01;189:21-29. Epub 2018-05-24.
Changes in Psychiatric and Medical Conditions and Health Care Utilization Following a Diagnosis of Sexual Assault: A Retrospective Cohort Study
Sexual assault (SA) is alarmingly common and is associated with higher prevalence of psychiatric and medical conditions. However, many prior studies are limited to cross-sectional designs. Health care systems with electronic health records provide unique longitudinal data to examine whether SA is associated with changes in health and health care utilization. The sample included 1350 Kaiser Permanente Northern California adult female patients with a SA diagnosis from 2009 to 2015 and 4050 adult female patients without a SA diagnosis, matched on age, medical facility, and continuous enrollment during the study period. Using a retrospective cohort design, we tested whether a SA diagnosis was associated with 12-month changes in psychiatric and medical comorbidities and health care utilization using difference-in-difference models. Analyses were conducted in 2017. Patients with a SA diagnosis had a higher prevalence of psychiatric and medical comorbidities and greater health care utilization than matched patients without SA in the 12 months before the SA diagnosis, and greater increases in the prevalence of psychiatric disorders and stress-related somatic conditions, and psychiatry and obstetrics/gynecology utilization (all P<0.001), 12 months after the SA diagnosis, relative to matched non-SA patients during this time. SA is associated with increases in psychiatric disorders and stress-related somatic conditions as well as increases in utilization of psychiatry and obstetrics/gynecology. Clinicians should be trained in how to inquire about, respond to, and refer women who have experienced SA.
Authors: Young-Wolff KC; Sarovar V; Klebaner D; Chi F; McCaw B
Med Care. 2018 08;56(8):649-657.
Common mitochondrial haplogroups and cutaneous squamous cell carcinoma risk
Background: Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in United States, and its incidence is substantially higher in men than women, but the reasons for the difference are unknown. We explored whether common mitochondrial DNA (mtDNA) haplogroups, which have been associated with cancer risk, and in particular squamous cell carcinoma risk arising in other organs, could explain this biological sex difference in cSCC susceptibility.Methods: We performed a retrospective cohort study using data from the Genetic Epidemiology Research in Adult Health and Aging cohort composed of 67,868 non-Hispanic white subjects (7,701 cSCC cases and 60,167 controls). Genotype information on >665,000 SNPs was generated using Affymetrix Axiom arrays designed to maximize genome-wide coverage, and 102 high-quality mtDNA SNPs were used to determine mtDNA haplogroups. Associations between each mtDNA haplogroup and cSCC risk were evaluated by logistic regression analysis adjusting for age, sex, and population stratification using ancestry principal components.Results: cSCC was more common in men (15.4% vs. 8.4% for women). Nine common mtDNA haplogroups (frequency ≥1%) were identified in addition to the most common haplogroup, H, used as the reference group. No association with cSCC risk was detected for any of the mtDNA haplogroups or overall or sex-stratified analyses.Conclusions: Common mitochondrial variation is not associated with cSCC risk.Impact: This well-powered study refutes the hypothesis that common mitochondrial haplogroups play a role in the differential sex predilection of cSCCs. Cancer Epidemiol Biomarkers Prev; 27(7); 838-41. ©2018 AACR.
Authors: Jorgenson E; Choquet H; Yin J; Asgari MM
Cancer Epidemiol Biomarkers Prev. 2018 07;27(7):838-841. Epub 2018-04-25.
Alcohol and Drug Screening, Brief Intervention, and Referral to Treatment (SBIRT) Training and Implementation: Perspectives from 4 Health Professions
Screening, Brief Intervention, and Referral to Treatment (SBIRT) can effectively identify and address substance misuse and substance use disorders (SUDs), and can be delivered by a range of trained health professionals. Yet, barriers remain to effective training and implementation of SBIRT in health and social service settings, and models of interprofessional collaboration in SBIRT delivery are underdeveloped. We reviewed current literature regarding SBIRT effectiveness, training, and implementation by physicians, nurses, psychologists, and social workers. An SBIRT expert and representative from each health profession synthesized literature and training experiences to inform the development of interprofessional training and collaborative implementation strategies. Each of the health professions involved in SBIRT training and implementation have strengths and weaknesses that influence how SBIRT is taught, learned, and delivered. Some of these are specific to the components of SBIRT, for example, screening versus brief intervention, whereas others depend on profession-driven competencies, for example, motivational interviewing. Professional organizations have encouraged a range of tailored SBIRT training initiatives, but true interprofessional training and the implementation of collaborative, team-based care are largely unrealized. SBIRT can be a valuable approach to screening and treatment for SUDs when delivered by a range of healthcare professionals. A more nuanced understanding of the assumptions and characteristics of each profession, informed by the emerging field of implementation science, may shape more effective training curricula and highlight interprofessional models of SBIRT delivery that maximize the strengths of each profession.
Authors: Wamsley M; Satterfield JM; Curtis A; Lundgren L; Satre DD
J Addict Med. 2018 Jul/Aug;12(4):262-272.
Manuscript title: Can survival bias explain the age attenuation of racial inequalities in stroke incidence? A simulation study
In middle age, stroke incidence is higher among black than white Americans. For unknown reasons, this inequality decreases and reverses with age. We conducted simulations to evaluate whether selective survival could account for observed age patterning of black-white stroke inequalities. We simulated birth cohorts of 20,000 blacks and 20,000 whites with survival distributions based on US life tables for the 1919-1921 birth cohort. We generated stroke incidence rates for ages 45-94 years using Reasons for Geographic and Racial Disparities in Stroke (REGARDS) study rates for whites and setting the effect of black race on stroke to incidence rate difference (IRD) = 20/10,000 person-years at all ages, the inequality observed at younger ages in REGARDS. We compared observed age-specific stroke incidence across scenarios, varying effects of U, representing unobserved factors influencing mortality and stroke risk. Despite a constant adverse effect of black race on stroke risk, the observed black-white inequality in stroke incidence attenuated at older age. When the hazard ratio for U on stroke was 1.5 for both blacks and whites, but U only directly influenced mortality for blacks (hazard ratio for U on mortality =1.5 for blacks; 1.0 for whites), stroke incidence rates in late life were lower among blacks (average observed IRD = -43/10,000 person-years at ages 85-94 years versus causal IRD = 20/10,000 person-years) and mirrored patterns observed in REGARDS. A relatively moderate unmeasured common cause of stroke and survival could fully account for observed age attenuation of racial inequalities in stroke.
Authors: Mayeda ER; Banack HR; Bibbins-Domingo K; Zeki Al Hazzouri A; Marden JR; Whitmer RA; Glymour MM
Epidemiology. 2018 07;29(4):525-532.
Patient and System Characteristics Associated with Performance on the HEDIS Measures of Alcohol and Other Drug Treatment Initiation and Engagement
Understand patient and system characteristics associated with performance on the Healthcare Effectiveness Data and Information Set (HEDIS) Alcohol and Other Drug (AOD) Initiation and Engagement of Treatment (IET) measures. This mixed-methods study linked patient and health system data from four Kaiser Permanente regions to HEDIS performance measure data for 44,320 commercially or Medicare-insured adults with HEDIS-eligible AOD diagnoses in 2012. Characteristics associated with IET were examined using multilevel logistic regression models. Key informant interviews (n = 18) focused on opportunities to improve initiation and engagement. Non-white race/ethnicity, alcohol abuse, or nonopioid drug abuse diagnoses were associated with lower odds of treatment initiation among commercially insured. For both insurance groups, those diagnosed in healthcare departments other than specialty AOD treatment were less likely to initiate or engage in treatment. Being diagnosed in facilities with co-located AOD/primary care clinics, and those with medications for addiction treatment available, was each associated with higher odds of initiation and engagement for both commercially and Medicare-insured. Having behavioral medicine specialists or clinical health educators in primary care increased initiation and engagement odds among commercially insured. Key informants recommended were as follows: patient-centered care; increased treatment choices; cross-departmental patient identification, engagement, and coordination; provider education; and use of informatics/technology. Tailoring treatment, enhancing treatment motivation among individuals with lower severity diagnoses, offering medication treatment of addiction, clinician education, care coordination, co-located AOD and primary care departments, and behavioral medicine specialists in primary care may improve rates of initiation and engagement in AOD treatment.
Authors: Yarborough BJH; Chi FW; Green CA; Hinman A; Mertens J; Beck A; Horberg M; Weisner C; Campbell CI
J Addict Med. 2018 Jul/Aug;12(4):278-286.
Psychiatric Disorders and Comorbid Cannabis Use: How Common Is It and What Is the Clinical Impact?
Authors: Satre DD; Bahorik A; Zaman T; Ramo D
J Clin Psychiatry. 2018 06 26;79(5). Epub 2018-06-26.
Design considerations for family-centered health management: preliminary findings with pediatric BMT patients
Blood and marrow transplantation (BMT) is an intensive therapy for patients with life-threatening hematologic cancer as well as non-cancer diagnoses. Children, adolescents and young adults undergoing BMT (“pediatric patients”) experience intensive medical procedures during their treatment and post-treatment recovery phases. We conducted a field study to identify common barriers that interfere with pediatric patient engagement in the management of their health and challenges that caregivers confront. Our study revealed four main factors. By exploring emerging themes, we suggest design opportunities for health technology to support patients and their caregivers over the course of long-term outpatient management.
Authors: Shin, J. Y;Chaar, Dima L;Choi, S. W;et al.
IDC '18: Proceedings of the 17th ACM Conference on Interaction Design and Children. 2018 Jun 19;593–598. doi: 10.1145/3202185.3210781
A multiethnic genome-wide association study of primary open-angle glaucoma identifies novel risk loci
Primary open-angle glaucoma (POAG) is a leading cause of irreversible vision loss, yet much of the genetic risk remains unaccounted for, especially in African-Americans who have a higher risk for developing POAG. We conduct a multiethnic genome-wide association study (GWAS) of POAG in the GERA cohort, with replication in the UK Biobank (UKB), and vice versa, GWAS in UKB with replication in GERA. We identify 24 loci (P < 5.0 × 10-8), including 14 novel, of which 9 replicate (near FMNL2, PDE7B, TMTC2, IKZF2, CADM2, DGKG, ANKH, EXOC2, and LMX1B). Functional studies support intraocular pressure-related influences of FMNL2 and LMX1B, with certain Lmx1b mutations causing high IOP and glaucoma resembling POAG in mice. The newly identified loci increase the proportion of variance explained in each GERA race/ethnicity group, with the largest gain in African-Americans (0.5-3.1%). A meta-analysis combining GERA and UKB identifies 24 additional loci. Our study provides important insights into glaucoma pathogenesis.
Authors: Choquet H; Schaefer C; Risch N; Jorgenson E; et al.
Nat Commun. 2018 06 11;9(1):2278. Epub 2018-06-11.
10-year changes in accelerometer-based physical activity and sedentary time during midlife: CARDIA Study
To describe 10-year changes in accelerometer-determined physical activity (PA) and sedentary time in a midlife cohort, within and by race/sex groups. Coronary Artery Risk Development in Young Adults participants (n = 962) who wore the accelerometer with valid wear (≥4 of 7 days, ≥10 hours per day) at baseline (2005-06; ages 38-50; ActiGraph 7164) and 10-year follow-up (2015-16; ages 48-60; ActiGraph wGT3X-BT). Data were calibrated to account for accelerometer model differences. Participants (aged 45.0 ± 3.5 years at baseline) experienced reductions in accelerometer counts overall [-65.5 (10.2) ct·min·d-1], and within race/sex groups (all p
Authors: Gabriel KP; Sidney S; Sternfeld B; et al.
Am J Epidemiol. 2018 Jun 11.
Comparison of Two Generations of ActiGraph Accelerometers: The CARDIA Study
This study aimed to examine the comparability of the ActiGraph 7164 and wGT3X-BT wear time, count-based estimates, and average time per day in physical activity of different intensities. We studied 87 Coronary Artery Risk Development in Young Adults (CARDIA) participants 48-60 yr of age who simultaneously wore the 7164 and wGT3X-BT accelerometers at the waist in 2015-2016, with wear time of ≥4 of 7 d, ≥10 h·d for both monitors. Freedson cutpoints (counts per minute) were used to define sedentary (<100), light (100-1951), moderate (1952-5724), and vigorous activity (≥5725). Agreement was evaluated using paired-difference tests, intraclass correlation coefficients, and Bland-Altman plots. Given systematic differences in count-based estimates between monitors, a calibration formula applied to the wGT3X-BT values was obtained by linear regression. Total detected wear time minutes per day was nearly identical between the 7164 and the wGT3X-BT (881.5 ± 70.9 vs 880.3 ± 78.1, P = 0.72). The wGT3X-BT values were calibrated to the 7164 values by dividing counts by 1.088. After calibration, no differences were observed between the 7164 and the wGT3X-BT in total counts per day (310,184 ± 129,189 vs 307,085 ± 135,362, P = 0.48), average counts per min per day (349.5 ± 139.5 vs 346.5 ± 147.2, P = 0.54), sedentary (513.2 ± 93.6 vs 509.6 ± 98.6, P = 0.23), light (335.3 ± 81.5 vs 338.7 ± 81.1, P = 0.22), moderate (31.0 ± 21.9 vs 30.3 ± 23.4, P = 0.31), or moderate-to-vigorous minutes per day (33.1 ± 24.6 vs 32.0 ± 26.0, P = 0.13). A significant difference was observed for vigorous minutes per day (0.2 ± 1.0 vs 0.0 ± 0.3, P < 0.01); however, the absolute difference was marginal. Intraclass correlation coefficients showed excellent agreement for all measures (0.95-0.99). After applying a calibration formula, the 7164 and wGT3X-BT were comparable for total wear time, count-based estimates, and average minutes per day in sedentary, light, moderate, and moderate-to-vigorous activity. Findings illustrate a novel methodological approach to facilitate accelerometer data harmonization.
Authors: Whitaker KM; Pettee Gabriel K; Jacobs DR; Sidney S; Sternfeld B
Med Sci Sports Exerc. 2018 06;50(6):1333-1340.
Genetic variants in the HLA class II region associated with risk of cutaneous squamous cell carcinoma
The immune system has been implicated in the pathophysiology of cutaneous squamous cell carcinoma (cSCC) as evidenced by the substantially increased risk of cSCC in immunosuppressed individuals. Associations between cSCC risk and single nucleotide polymorphisms (SNPs) in the HLA region have been identified by genome-wide association studies (GWAS). The translation of the associated HLA SNPs to structural amino acids changes in HLA molecules has not been previously elucidated. Using data from a GWAS that included 7238 cSCC cases and 56,961 controls of non-Hispanic white ancestry, we imputed classical alleles and corresponding amino acid changes in HLA genes. Logistic regression models were used to examine associations between cSCC risk and genotyped or imputed SNPs, classical HLA alleles, and amino acid changes. Among the genotyped SNPs, cSCC risk was associated with rs28535317 (OR = 1.20, p = 9.88 × 10- 11) corresponding to an amino-acid change from phenylalanine to leucine at codon 26 of HLA-DRB1 (OR = 1.17, p = 2.48 × 10- 10). An additional independent association was observed for a threonine to isoleucine change at codon 107 of HLA-DQA1 (OR = 1.14, p = 2.34 × 10- 9). Among the classical HLA alleles, cSCC was associated with DRB1*01 (OR = 1.18, p = 5.86 × 10- 10). Conditional analyses revealed additional independent cSCC associations with DQA1*05:01 and DQA1*05:05. Extended haplotype analysis was used to complement the imputed haplotypes, which identified three extended haplotypes in the HLA-DR and HLA-DQ regions. Associations with specific HLA-DR and -DQ alleles are likely to explain previously observed GWAS signals in the HLA region associated with cSCC risk.
Authors: Wang W; Ollila HM; Whittemore AS; Demehri S; Ioannidis NM; Jorgenson E; Mignot E; Asgari MM
Cancer Immunol Immunother. 2018 May 12.
Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression
Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.
Authors: Wray NR; Schaefer C; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; et al.
Nat Genet. 2018 05;50(5):668-681. Epub 2018-04-26.
Systemic effects of epidural steroid injections for spinal stenosis
This analysis of the lumbar epidural steroid injections for spinal stenosis multicenter randomized controlled trial data identifies the degree of and risk factors for cortisol suppression after epidural steroid injections in older adults with spinal stenosis. Four hundred patients aged 50 years and older with back or leg pain and central lumbar spinal stenosis completed baseline demographic and psychosocial measures. Morning serum cortisol levels were measured at baseline and 3 weeks after initial injection. Patients were randomized to receive epidural injections of either local anesthetic with corticosteroid (n = 200) or local anesthetic only (n = 200). The specific corticosteroid was chosen at the treating physician’s discretion (methylprednisolone, betamethasone, triamcinolone, or dexamethasone). Thirty-two patients (20.3%) treated with corticosteroid experienced cortisol reduction at 3 weeks of >50% compared with 10 patients (6.7%) treated with lidocaine only (adjusted treatment effect = 3.5, 95% confidence interval: 1.6-7.9, P = 0.002). The effect on 3-week cortisol changes did not differ by demographic or patient-level characteristics. Those treated with methylprednisolone or triamcinolone had an average 3-week cortisol reduction of 41.0% (P = 0.005) and 41.6% (P < 0.001) from baseline, respectively, whereas patients treated with betamethasone or dexamethasone were not significantly different than comparable patients in the lidocaine arm. The higher rates of cortisol suppression at 3 weeks in those receiving epidural corticosteroid injections, particularly with longer-acting insoluble corticosteroid formulations, are consistent with sustained systemic absorption of corticosteroid.
Authors: Friedly JL; Avins AL; Jarvik JG; et al.
Pain. 2018 May;159(5):876-883.
Use of a prescription opioid registry to examine opioid misuse and overdose in an integrated health system
Strategies are needed to identify at-risk patients for adverse events associated with prescription opioids. This study identified prescription opioid misuse in an integrated health system using electronic health record (EHR) data, and examined predictors of misuse and overdose. The sample included patients from an EHR-based registry of adults who used prescription opioids in 2011 in Kaiser Permanente Northern California, a large integrated health care system. We characterized time-at-risk for opioid misuse and overdose, and used Cox proportional hazard models to model predictors of these events from 2011 to 2014. Among 396,452 patients, 2.7% were identified with opioid misuse and 1044 had an overdose event. Older patients were less likely to meet misuse criteria or have an overdose. Whites were more likely to be identified with misuse, but not to have an overdose. Alcohol and drug disorders were related to higher risk of misuse and overdose, with the exception that marijuana disorder was not related to opioid misuse. Higher daily opioid dosages and benzodiazepine use increased the risk of both opioid misuse and overdose. We characterized several risk factors associated with misuse and overdose using EHR-based data, which can be leveraged relatively quickly to inform preventive strategies to address the opioid crisis.
Authors: Campbell CI; Bahorik AL; VanVeldhuisen P; Weisner C; Rubinstein AL; Ray GT
Prev Med. 2018 05;110:31-37. Epub 2018-02-02.
Eleven loci with new reproducible genetic associations with allergic disease risk
A recent genome-wide association study (GWAS) identified 99 loci that contain genetic risk variants shared between asthma, hay fever and eczema. Many more risk loci shared between these common allergic diseases remain to be discovered, which could point to new therapeutic opportunities. To identify novel risk loci shared between asthma, hay fever and eczema by applying a gene-based test of association to results from a published GWAS that included data from 360,838 individuals. We used approximate conditional analysis to adjust the results from the published GWAS for the effects of the top risk variants identified in that study. We then analysed the adjusted GWAS results with the EUGENE gene-based approach, which combines evidence for association with disease risk across regulatory variants identified in different tissues. Novel gene-based associations were followed up in an independent sample of 233,898 individuals from the UK Biobank study. Of the 19,432 genes tested, 30 had a significant gene-based association at a Bonferroni-corrected P-value of 2.5×10-6. Of these, 20 were also significantly associated (P
Authors: Ferreira MA; Lu Y; 23andMe Research Team; collaborators of the SHARE study; Jorgenson E; Paternoster L; et al.
J Allergy Clin Immunol. 2018 Apr 18.
Alcohol and Drug Use Among Older Adults: Associations with Widowhood, Relationship Quality, and Physical Health
Authors: Satre DD; Bahorik AL; Mackin RS
J Gerontol B Psychol Sci Soc Sci. 2018 04 16;73(4):633-635.
Depression in type 1 diabetes and risk of dementia
Depression afflicts 14% of individuals with type 1 diabetes (T1D). Depression is a robust risk factor for dementia but it is unknown if this holds true for individuals with T1D, who recently started living to an age conferring dementia risk. We examined if depression is a dementia risk factor among elderly individuals with T1D. 3,742 individuals with T1D age ≥50 were followed for dementia from 1/1/96-9/30/2015. Depression, dementia, and comorbidities were abstracted from electronic medical records. Cox proportional hazard models estimated the association between depression and dementia adjusting for demographics, glycosylated hemoglobin, severe dysglycemic epidsodes, stroke, heart disease, nephropathy, and end stage renal disease. The cumulative incidence of dementia by depression was estimated conditional on survival dementia-free to age 55. Five percent (N = 182) were diagnosed with dementia and 20% had baseline depression. Depression was associated with a 72% increase in dementia (fully adjusted HR = 1.72; 95% CI:1.12-2.65). The 25-year cumulative incidence of dementia was more than double for those with versus without depression (27% vs. 12%). For people with T1D, depression significantly increases dementia risk. Given the pervasiveness of depression in T1D, this has major implications for successful aging in this population recently living to old age.
Authors: Gilsanz P; Schnaider Beeri M; Karter AJ; Quesenberry CP; Adams AS; Whitmer RA
Aging Ment Health. 2018 Apr 10:1-7.
Two Genetic Variants Associated with Plantar Fascial Disorders
Plantar fascial disorder is comprised of plantar fasciitis and plantar fibromatosis. Plantar fasciitis is the most common cause of heel pain, especially for athletes involved in running and jumping sports. Plantar fibromatosis is a rare fibrous hyperproliferation of the deep connective tissue of the foot. To identify genetic loci associated with plantar fascial disorders, a genome-wide association screen was performed using publically available data from the Research Program in Genes, Environment and Health including 21,624 cases of plantar fascial disorders and 80,879 controls. One indel (chr5:118704153:D) and one SNP (rs62051384) showed an association with plantar fascial disorders at genome-wide significance (p<5×10-8) with small effects (odds ratios=0.93 and 1.07 per allele, respectively). The indel chr5:118704153:D is located within TNFAIP8 (encodes a protein induced by TNF alpha) and rs62051384 is located within WWP2 (which is involved in proteasomal degradation). These DNA variants may be informative in explaining why some individuals are at higher risk for plantar fascial disorders than others.
Authors: Kim SK; Ioannidis JPA; Ahmed MA; Avins AL; Kleimeyer JP; Fredericson M; Dragoo JL
Int J Sports Med. 2018 Apr;39(4):314-321. Epub 2018-03-13.
Pediatrician and Behavioral Clinician-Delivered Screening, Brief Intervention and Referral to Treatment: Substance Use and Depression Outcomes
Early intervention for adolescent substance use and mental health problems may mitigate potential harm. We examined patient outcomes from a pragmatic trial of two modalities of delivering screening, brief intervention, and referral to treatment (SBIRT) and usual care (UC) in pediatric primary care. All clinic pediatricians (n = 52) were randomized to three arms: (1) pediatrician-only, in which pediatricians were trained to deliver SBIRT; (2) embedded behavioral clinician (BC), in which pediatricians were trained to refer eligible adolescents to a BC who administered SBIRT; and (3) UC. Using electronic health record data, changes in past year substance use and depression symptoms between the index visit and next screening visit were examined across treatment arms. Among patients who endorsed substance use and/or depression symptoms or were eligible for further assessments, brief interventions, and referrals based on clinician assessment at the index visit, 648 patients (mean age = 15.2 [standard deviation = 1.2]) were rescreened at a follow-up visit between 6 months and 2 years later. Among all patients, self-reported substance use rates did not differ over time or across arms, and depression symptoms increased over time. The embedded BC arm had lower odds of having depression symptoms at follow-up than the physician-only arm, and lower odds than the UC arm although not significant; we found no differences between the pediatrician-only and UC arms. The increase in depression symptoms over time highlights this population’s vulnerability and the importance of developing appropriate interventions. An embedded BC in pediatric primary care trained in SBIRT may benefit patients with depression symptoms.
Authors: Sterling S; Kline-Simon AH; Weisner C; Jones A; Satre DD
J Adolesc Health. 2018 04;62(4):390-396. Epub 2018-02-01.
Diabetic Retinopathy and Dementia in Type 1 Diabetes
Retinopathy impacts over one-third of those with diabetes mellitus and is associated with impaired cognitive performance and cerebrovascular lesions in middle-aged adults with type 1 diabetes. However, the association between diabetic retinopathy (DR) and risk of dementia in type 1 diabetes is unknown. We investigated the association between DR and incident dementia in a large, elderly population with type 1 diabetes. A cohort of 3742 patients with type 1 diabetes aged 50 years and above was followed from January 1, 1996 to September 30, 2015 for incident dementia. DR diagnoses were identified from electronic medical records. Age as timescale Cox proportional hazard models evaluated associations between time-updated DR and dementia risk. Models were adjusted for demographics, severe glycemic events, glycosylated hemoglobin, and vascular comorbidities. Among 3742 patients with type 1 diabetes (47% female, 21% nonwhite), 182 (5%) were diagnosed with dementia during a mean follow-up of 6.2 years. No significant association was found between DR and incident dementia in the main analyses [adjusted Hazard Ratio=1.12; 95% confidence interval, 0.82-1.54), nor among subgroup restricted to those aged 60 years and above or 70 years and above. DR was not associated with risk of dementia, suggesting that pathophysiological processes underlying dementia may be different in type 1 versus type 2 diabetes.
Authors: Rodill LG; Exalto LG; Gilsanz P; Biessels GJ; Quesenberry CP; Whitmer RA
Alzheimer Dis Assoc Disord. 2018 Apr-Jun;32(2):125-130.
The relationship between non-steroidal anti-inflammatory drug use and age-related macular degeneration
To describe the relationship between the incidence of age-related macular degeneration (AMD) and nonsteroidal anti-inflammatory drug (NSAIDs) use. Prospective cohort study. This study consisted of participants in the California Men’s Health Study. Those who completed surveys in 2002-2003 and 2006 were included. Men who self-reported use of aspirin, ibuprofen, naproxen, valdecoxib, celecoxib, and/or rofecoxib at least 3 days per week were considered NSAID users. Patients were categorized as non-users, former users, new users, or longer-term users based on survey responses. NSAID use was also categorized by type: any NSAIDs, aspirin, and/or non-aspirin NSAIDs. Age, race/ethnicity, smoking status, education, income, alcohol use, and Charlson comorbidity index score were included in the multivariate analysis as risk factors for AMD. A total of 51 371 men were included. Average follow-up time was 7.4 years. There were 292 (0.6%) and 1536 (3%) cases of exudative and nonexudative AMD, respectively. Longer-term use of any NSAID was associated with lower risk of exudative AMD (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.50-0.96, P = .029). New users of any NSAIDs (HR = 0.79, 95% CI 0.68-0.93, P = .0039) and aspirin (HR = 0.82, 95% CI 0.70-0.97, P = .018) had a lower risk of nonexudative AMD, although this trend did not persist in longer-term users. The relationship between exudative or nonexudative AMD and the remaining categories of NSAID use were not significant. The overall impact of NSAIDs on AMD incidence is small; however, the lower risk of exudative AMD in longer-term NSAID users may point to a protective effect and deserves further study as a possible mechanism to modulate disease risk.
Authors: Modjtahedi BS; Fong DS; Jorgenson E; Van Den Eeden SK; Quinn V; Slezak JM
Am J Ophthalmol. 2018 04;188:111-122. Epub 2018-01-31.
Documentation of e-cigarette use and associations with smoking from 2012 to 2015 in an integrated healthcare delivery system
It is unclear whether use of electronic nicotine delivery systems (ENDS) precedes cigarette smoking initiation, relapse, and/or quitting. Healthcare systems with electronic health records (EHRs) provide unique data to examine ENDS use and changes in smoking. We examined the incidence of ENDS use (2012-2015) based on clinician documentation and tested whether EHR documented ENDS use is associated with twelve-month changes in patient smoking status using a matched retrospective cohort design. The sample was Kaiser Permanente Northern California (KPNC) patients aged ≥12 with documented ENDS use (N = 7926); 57% were current smokers, 35% former smokers, and 8% never-smokers. ENDS documentation incidence peaked in 2014 for current and former smokers and in 2015 for never-smokers. We matched patients with documented ENDS use to KPNC patients without documented ENDS use (N = 7926) on age, sex, race/ethnicity, and smoking status. Documented ENDS use predicted the likelihood of smoking in the following year. Among current smokers, ENDS use was associated with greater odds of quitting smoking (OR = 1.17, 95%CI = 1.05-1.31). Among former smokers, ENDS use was associated with greater odds of smoking relapse (OR = 1.53, 95%CI = 1.22-1.92). Among never-smokers, ENDS use was associated with greater odds of initiating smoking (OR = 7.41, 95%CI = 3.14-17.5). The overall number of current smokers at 12 months was slightly higher among patients with (N = 3931) versus without (N = 3850) documented ENDS use. Results support both potential harm reduction of ENDS use (quitting combustibles among current smokers) and potential for harm (relapse to combustibles among former smokers, initiation for never-smokers).
Authors: Young-Wolff KC; Klebaner D; Folck B; Tan ASL; Fogelberg R; Sarovar V; Prochaska JJ
Prev Med. 2018 04;109:113-118. Epub 2018-01-31.
Associations of Early Opioid Use with Patient-Reported Outcomes and Healthcare Utilization Among Older Adults with Low Back Pain
The objective of this study was to compare outcomes and health care utilization of older patients who did versus did not fill opioid prescriptions within 90 days of initiating care for low back pain. For patients ≥65 years with new back pain visits, we used propensity scores to match those who filled no opioid prescriptions to those who filled ≥2 opioid prescriptions within 90 days (and the first opioid prescription within 30 d) of the index visit. Over 24 months, we examined patient-reported outcomes, health care utilization, and subsequent opioid prescription fills. Among 1954 patients eligible for matching, 238 (12%) filled ≥2 opioid prescriptions within 90 days; 200 of these were matched to controls. Patients with versus without early opioid prescriptions had similar patient-reported outcomes but were more likely to have filled ≥1 opioid prescription 18 to 24 months after the index visit (odds ratio [95% confidence interval]=2.4 [1.5-3.9]) and to have had ≥1 visit to the emergency department in the subsequent 24 months (OR, 1.6; 95% confidence interval, 1.0-2.5). Among older patients with new back pain visits, filling ≥2 opioid prescriptions within 90 days of the visit was associated with similar back pain-related outcomes but increased likelihood of filling opioid prescriptions 18 to 24 months later compared with matched patients who did not fill early opioid prescriptions.
Authors: Gold LS; Hansen RN; Avins AL; Bauer Z; Comstock BA; Deyo RA; Heagerty PJ; Rundell SD; Suri P; Turner JA; Jarvik JG
Clin J Pain. 2018 04;34(4):297-305.
A Pilot Mobile-based Mindfulness Intervention for Cancer Patients and their Informal Caregivers
Authors: Kubo A; Altschuler A; Kurtovich E; Hendlish S; Laurent CA; Kolevska T; Li Y; Avins A
Mindfulness (N Y). 2018 Dec;9(6):1885-1894. Epub 2018-03-24.
A large electronic-health-record-based genome-wide study of serum lipids
A genome-wide association study (GWAS) of 94,674 ancestrally diverse Kaiser Permanente members using 478,866 longitudinal electronic health record (EHR)-derived measurements for untreated serum lipid levels empowered multiple new findings: 121 new SNP associations (46 primary, 15 conditional, and 60 in meta-analysis with Global Lipids Genetic Consortium data); an increase of 33-42% in variance explained with multiple measurements; sex differences in genetic impact (greater impact in females for LDL, HDL, and total cholesterol and the opposite for triglycerides); differences in variance explained among non-Hispanic whites, Latinos, African Americans, and East Asians; genetic dominance and epistatic interaction, with strong evidence for both at the ABO and FUT2 genes for LDL; and tissue-specific enrichment of GWAS-associated SNPs among liver, adipose, and pancreas eQTLs. Using EHR pharmacy data, both LDL and triglyceride genetic risk scores (477 SNPs) were strongly predictive of age at initiation of lipid-lowering treatment. These findings highlight the value of longitudinal EHRs for identifying new genetic features of cholesterol and lipoprotein metabolism with implications for lipid treatment and risk of coronary heart disease.
Authors: Hoffmann TJ; Schaefer C; Iribarren C; Risch N; et al.
Nat Genet. 2018 03;50(3):401-413. Epub 2018-03-05.
Remote assessment of verbal memory in MS patients using the California Verbal Learning Test
We used the California Verbal Learning Test, Second Edition (CVLT-II), one component of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), to determine feasibility of a remote assessment protocol. We compared telephone-administered CVLT-II data from MS patients to data acquired in person from an independent sample of patients and healthy controls. Mixed factor analyses of variance (ANOVAs) showed no significant differences between patient groups, but between-group effects comparing patients and healthy controls were significant. In this study, CVLT-II assessment by conventional in-person and remote telephone assessment yielded indistinguishable results. The findings indicate that telephone-administered CVLT-II is feasible. Further validation studies are underway.
Authors: Barcellos LF; Bellesis KH; Shen L; Shao X; Chinn T; Frndak S; Drake A; Bakshi N; Marcus J; Schaefer C; Benedict RH
Mult Scler. 2018 03;24(3):354-357. Epub 2017-02-01.
Susceptibility loci associated cutaneous squamous cell carcinoma invasiveness
Genome-wide association studies have identified genetic loci associated with cutaneous squamous cell carcinoma (cSCC) risk, but single-nucleotide polymorphism associations with cSCC invasiveness have not been investigated. We examined associations between cSCC invasiveness and 23 reported single-nucleotide polymorphisms among 67,833 non-Hispanic white subjects. Additionally, we performed a genome-wide scan and identified one SNP with significantly different frequencies in 5,724 subjects with at least one invasive tumor and 1,943 subjects with in situ tumors only. We then compared genotype frequencies among the invasive and in situ groups with those of 60,166 control subjects. The genome-wide scan identified that the T allele in single-nucleotide polymorphism rs41269979 in the class II human leukocyte antigen region was more frequent in the invasive than the in situ group (P = 4.93 × 10-8). Single-nucleotide polymorphisms in five of the 23 previously associated loci showed odds ratio heterogeneity between the in situ and invasive groups: rs447510 in HLA-DQA1 (Phet = 2.93 × 10-3), rs12203592 in IRF4 (Phet = 3.94 × 10-4), rs1805007 in MC1R (Phet = 7.71 × 10-3), and two SNPs in DEF8 (rs4268748, Phet = 1.09 × 10-4 and rs8063761, Phet = 1.40 × 10-4). These findings may provide new insight into the genetic basis of cSCC invasiveness and may help identify individuals at higher risk for developing clinically aggressive cSCC.
Authors: Wang W; Jorgenson E; Whittemore AS; Asgari MM
J Invest Dermatol. 2018 03;138(3):557-561. Epub 2017-10-17.
The Role of Family Caregiving in Adult and Pediatric Allogeneic Hematopoietic Cell Transplantation: Using Health Information Technology to Advance Patient-Centered Care.
Background: Data from our ongoing research program suggests that family caregivers of adult and pediatric patients receiving first-time allogeneic hematopoietic cell transplantation (HCT) desire numerous informational and psychosocial needs. Little research exists examining caregiving with health information technology (HIT)-mediated interventions in HCT. Addressing these challenges with HIT has the potential to increase care delivery and coordination, and ensure positive outcomes. The purpose of this study was to examine the use of a user-centered HIT app “BMT Roadmap” in a sample of adult and pediatric HCT patient-caregiver dyads.
Methods: We used a mixed methods approach to collect quantitative and qualitative person-reported outcome measures (PROs) longitudinally upon admission, discharge, and day 100 post-HCT. Adult and pediatric patient caregivers (n = 39) completed encrypted psychometric surveys and in-person semi-structured interviews. Qualitative data were derived from multiple-reviewer thematic analysis.
Results: Adult caregivers logged on fewer days than pediatric caregivers ( M = 10.09 + 10.67 versus M = 18.26 + 14.35 respectively; t = -1.82, p = .07), reflecting differences in lengths of stay and thus access to the app. After statistical correction for differing access, we found caregivers used the app mostly for viewing patient laboratory values, and adult caregivers devoted more time to the medication and phases of care modules ( t = 2.52, p = .02; t = 1.87, p = .07 respectively). Most adult and pediatric caregivers identified separate educational, organizational, and psychosocial needs during the phase of the transplant. However, both found BMT Roadmap informative and valuable for the caregiving experience.
Conclusion: Caregivers of adult and pediatric patients receiving first-time allogeneic HCT report different caregiving experiences. Thus, they desire different interventions to learn best practices of caregiving. Clearly delineating differences in caregiving for adult and pediatric patients helps with customizable HIT design and may improve long-term patient outcomes.
Authors: Fauer, A;Chaar, Dima L;Choi, S. W;et al.
Biol Blood Marrow Transplant. 2018 Mar 01;24(3):S484–S485. doi: 10.1016/j.bbmt.2017.12.498
Using Natural Language Processing of Free-Text Radiology Reports to Identify Type 1 Modic Endplate Changes
Electronic medical record (EMR) systems provide easy access to radiology reports and offer great potential to support quality improvement efforts and clinical research. Harnessing the full potential of the EMR requires scalable approaches such as natural language processing (NLP) to convert text into variables used for evaluation or analysis. Our goal was to determine the feasibility of using NLP to identify patients with Type 1 Modic endplate changes using clinical reports of magnetic resonance (MR) imaging examinations of the spine. Identifying patients with Type 1 Modic change who may be eligible for clinical trials is important as these findings may be important targets for intervention. Four annotators identified all reports that contained Type 1 Modic change, using N = 458 randomly selected lumbar spine MR reports. We then implemented a rule-based NLP algorithm in Java using regular expressions. The prevalence of Type 1 Modic change in the annotated dataset was 10%. Results were recall (sensitivity) 35/50 = 0.70 (95% confidence interval (C.I.) 0.52-0.82), specificity 404/408 = 0.99 (0.97-1.0), precision (positive predictive value) 35/39 = 0.90 (0.75-0.97), negative predictive value 404/419 = 0.96 (0.94-0.98), and F1-score 0.79 (0.43-1.0). Our evaluation shows the efficacy of rule-based NLP approach for identifying patients with Type 1 Modic change if the emphasis is on identifying only relevant cases with low concern regarding false negatives. As expected, our results show that specificity is higher than recall. This is due to the inherent difficulty of eliciting all possible keywords given the enormous variability of lumbar spine reporting, which decreases recall, while availability of good negation algorithms improves specificity.
Authors: Huhdanpaa HT; Avins AL; Jarvik JG; et al.
J Digit Imaging. 2018 02;31(1):84-90.
Feasibility and Acceptability of Screening for Adverse Childhood Experiences in Prenatal Care
Adverse childhood experiences (ACEs) are common among pregnant women and contribute to increased risk for negative perinatal outcomes, yet few clinicians screen prenatal patients for ACEs. The purpose of this study was to evaluate the feasibility and acceptability of screening for ACEs in standard prenatal care. We evaluated a 4-month pilot (March 2016-June 2016) to screen pregnant women (at ∼14-23 weeks of gestation) for ACEs and resiliency in two Kaiser Permanente Northern California medical centers (N = 480). We examined the acceptability of the screening to patients through telephone surveys (N = 210) and to clinicians through surveys and focus groups (N = 26). Most eligible patients (78%) were screened. Patients who received the screening were significantly more likely to be non-Hispanic White, Asian, or of "Other" or "Unknown" race/ethnicity than African American or Hispanic race/ethnicity (p = 0.02). Among those screened, 88% completed the questionnaires; 54% reported 0 ACEs, 28% reported 1-2 ACEs, and 18% reported ≥3 ACEs. Most patients were somewhat or very comfortable completing the questionnaires (91%) and discussing ACEs with their clinician (93%), and strongly or somewhat strongly agreed that clinicians should ask their prenatal patients about ACEs (85%). Clinicians reported significant pre- to postpilot increases in comfort discussing ACEs, providing education, and offering resources (ps
Authors: Flanagan T; Alabaster A; McCaw B; Stoller N; Watson C; Young-Wolff KC
J Womens Health (Larchmt). 2018 Jan 19.
Statin use and risk of Alzheimer disease: A new view on an old relationship
Authors: Yasar S; Whitmer R
Neurology. 2018 01 16;90(3):103-104. Epub 2017-12-15.
Canadian genome-wide association study and meta-analysis confirm HLA as a risk factor for peanut allergy independent of asthma
Authors: Asai Y; Jorgensen E; Daley D; et al
J Allergy Clin Immunol. 2018 Jan 08.
Alcohol, Marijuana, and Opioid Use Disorders: 5-Year Patterns and Characteristics of Emergency Department Encounters
Changes in substance use patterns stemming from opioid misuse, ongoing drinking problems, and marijuana legalization may result in new populations of patients with substance use disorders (SUDs) using emergency department (ED) resources. This study examined ED admission trends in a large sample of patients with alcohol, marijuana, and opioid use disorders in an integrated health system. In a retrospective design, electronic health record (EHR) data identified patients with ≥1 of 3 common SUDs in 2010 (n = 17,574; alcohol, marijuana, or opioid use disorder) and patients without SUD (n = 17,574). Logistic regressions determined odds of ED use between patients with SUD versus controls (2010-2014); mixed-effect models examined 5-year differences in utilization; moderator models identified subsamples for which patients with SUD may have a greater impact on ED resources. Odds of ED use were higher at each time point (2010-2014) for patients with alcohol (odds ratio [OR] range: 5.31-2.13, Ps < .001), marijuana (OR range: 5.45-1.97, Ps < .001), and opioid (OR range: 7.63-4.19, Ps < .001) use disorders compared with controls; odds decreased over time (Ps < .001). Patients with opioid use disorder were at risk of high ED utilization; patients were 7.63 times more likely to have an ED visit in 2010 compared with controls and remained 5.00 (average) times more likely to use ED services. ED use increased at greater rates for patients with alcohol and opioid use disorders with medical comorbidities relative to controls (Ps < .045). ED use is frequent in patients with SUDs who have access to private insurance coverage and integrated medical services. ED settings provide important opportunities in health systems to identify patients with SUDs, particularly patients with opioid use disorder, to initiate treatment and facilitate ongoing care, which may be effective for reducing excess medical emergencies and ED encounters.
Authors: Bahorik AL; Satre DD; Kline-Simon AH; Weisner CM; Young-Wolff KC; Campbell CI
Subst Abus. 2018 01 02;39(1):59-68. Epub 2017-09-06.
A Sequential Implementation Model for Workforce Development: A Case Study of Medical Residency Training for Substance Use Concerns
In graduate medical education, residency programs are often educationally isolated from each other, with varying needs and patient populations, so strategies are needed when attempting to implement training in evidence-based practices across multiple residencies. Using implementation science as a guide, we adapted a community development model to sequentially implement an evidence-based intervention, Screening, Brief Intervention, and Referral to Treatment (SBIRT) for alcohol and drug use problems, across internal medicine, pediatrics, emergency medicine, psychiatry, and obstetrics and gynecology residency programs. A grant-funded “executive” team coordinated the implementation, enrolled a new residency program annually, and served as the consultative team to span the programs. The team was attentive to aligning implementation with the needs of each program. To assist in planning, the team included a program champion 1 year prior to SBIRT implementation to provide the opportunity to develop resources and work with peers. We evaluated this model through an implementation science lens using a case study approach that included interviews and quantitative tabulation of products and resident perceptions. We successfully instituted SBIRT training in all 5 residency programs through the use of a supported local champion model. Teams developed 90 curricular products and had 57 presentations and publications. Residents reported satisfaction with the SBIRT activities. Champions reported that SBIRT was a useful approach and that they gained valuable knowledge and relationships from working with the executive team when designing learning materials appropriate for their residency. Champions successfully incorporated SBIRT into routine clinical practice. Having a strong team to support subsequent SBIRT champions was essential for implementation. The champions needed financial support to have the necessary time to implement training. The strategy of building a peer network across programs was critical for sustaining the implementation. Collecting and sharing resources aided the champions in developing their materials.
Authors: O'Sullivan PS; Yuan P; Satre DD; Wamsley M; Satterfield J
Teach Learn Med. 2018 Jan-Mar;30(1):84-94. Epub 2017-05-12.
Novel Telestroke Program Improves Thrombolysis for Acute Stroke Across 21 Hospitals of an Integrated Healthcare System
Faster treatment with intravenous alteplase in acute ischemic stroke is associated with better outcomes. Starting in 2015, Kaiser Permanente Northern California redesigned its acute stroke workflow across all 21 Kaiser Permanente Northern California stroke centers to (1) follow a single standardized version of a modified Helsinki model and (2) have all emergency stroke cases managed by a dedicated telestroke neurologist. We examined the effect of Kaiser Permanente Northern California’s Stroke EXpediting the PRrocess of Evaluating and Stopping Stroke program on door-to-needle (DTN) time, alteplase use, and symptomatic intracranial hemorrhage rates. The program was introduced in a staggered fashion from September 2015 to January 2016. We compared DTN times for a seasonally adjusted 9-month period at each center before implementation to the corresponding 9-month calendar period from the start of implementation. The primary outcome was the DTN time for alteplase administration. Secondary outcomes included rate of alteplase administrations per month, symptomatic intracranial hemorrhage, and disposition at time of discharge. This study included 310 patients treated with alteplase in the pre-EXpediting the PRrocess of Evaluating and Stopping Stroke period and 557 patients treated with alteplase in the EXpediting the PRrocess of Evaluating and Stopping Stroke period. After implementation, alteplase administrations increased to 62/mo from 34/mo at baseline (P<0.001). Median DTN time decreased to 34 minutes after implementation from 53.5 minutes prior (P<0.001), and DTN time of <60 minutes was achieved in 87.1% versus 61.0% (P<0.001) of patients. DTN times <30 minutes were much more common in the Stroke EXpediting the PRrocess of Evaluating and Stopping Stroke period (40.8% versus 4.2% before implementation). There was no significant difference in symptomatic intracranial hemorrhage rates in the 2 periods (3.8% versus 2.2% before implementation; P=0.29). Introduction of a standardized modified Helsinki protocol across 21 hospitals using telestroke management was associated with increased alteplase administrations, significantly shorter DTN times, and no increase in adverse outcomes.
Authors: Nguyen-Huynh MN; Klingman JG; Avins AL; Rao VA; Eaton A; Bhopale S; Kim AC; Morehouse JW; Flint AC; KPNC Stroke FORCE Team
Stroke. 2018 Jan;49(1):133-139. Epub 2017-12-15.
Alcohol and Drug Use, Pain and Psychiatric Symptoms among Adults Seeking Outpatient Psychiatric Treatment: Latent Class Patterns and Relationship to Health Status
Substance use, psychiatric problems, and pain frequently co-occur, yet clinical profiles of treatment-seeking patients are poorly understood. To inform service and treatment planning, substance use and symptom patterns were examined in an outpatient psychiatry clinic, along with the relationship of these patterns to demographic characteristics and physical health. Patients (N = 405; age M = 38; 69% White; 60% female) presenting for intake in a psychiatry outpatient clinic completed a computerized assessment of psychiatric problems, drinking, and drug use. Substance use and psychiatric symptom patterns among the sample were identified using latent class analysis. A 4-class model fit the data best: Class (1) Moderate symptoms/wide-range users (22.0%) had moderate depression and panic; tobacco, cocaine, hallucinogen, and ecstasy use; and high cannabis use. Class (2) Moderate depression/panic (37.8%) had moderate depression and panic. Class (3) Depression/anxiety, tobacco, and cannabis users (28.0%) had high depression, obsessions, and panic, and moderate pain severity, social phobia, compulsions, trauma, tobacco, and cannabis use. Class (4) Severe/wide range symptoms/users (12.0%) had high panic, depression, social phobia, obsessions, drug use, and moderate pain. Gender, ethnicity, and health status varied by class. Findings highlight the preponderance of substance use (particularly cannabis) and its relationship to psychiatric symptom severity, pain, and health status among those presenting for mental health treatment.
Authors: Ramo DE; Bahorik AL; Delucchi KL; Campbell CI; Satre DD
J Psychoactive Drugs. 2018 Jan-Mar;50(1):43-53. Epub 2017-12-04.
Adverse impact of marijuana use on clinical outcomes among psychiatry patients with depression and alcohol use disorder
This study examined whether marijuana use was associated with clinically problematic outcomes for patients with depression and alcohol use disorder (AUD). The sample consisted of 307 psychiatry outpatients with mild to severe depression and past 30-day hazardous drinking/drug use, who participated in a trial of substance use treatment. Participants were assessed for AUD based on DSM-IV criteria. Measures of marijuana use, depression symptoms, and functional status related to mental health were collected at baseline, 3, and 6 months. Differences in these outcomes were analyzed among patients with and without AUD using growth models, adjusting for treatment effects. Marijuana was examined as both an outcome (patterns of use) and a predictor (impact on depression and functioning). Forty percent used marijuana and about half the sample met AUD criteria. Fewer patients with AUD used marijuana than those without AUD at baseline. Over 6 months, the proportion of patients with AUD using marijuana increased compared to those without AUD. Patients with AUD using marijuana had greater depressive symptoms and worse functioning than those without AUD. These findings indicate that marijuana use is clinically problematic for psychiatry outpatients with depression and AUD. Addressing marijuana in the context of psychiatry treatment may help improve outcomes.
Authors: Bahorik AL; Campbell CI; Sterling SA; Leibowitz A; Travis A; Weisner CM; Satre DD
Psychiatry Res. 2018 01;259:316-322. Epub 2017-10-19.
Clinical importance of non-participation in a maximal graded exercise test on risk of non-fatal and fatal cardiovascular events and all-cause mortality: CARDIA study
While poor performance during a maximal graded exercise test (GXT) predicts cardiovascular events and premature mortality, the potential clinical importance of non-participation in a GXT, either for medical or non-medical reasons, is currently unknown. Data are from 4086 and 3547 Coronary Artery Risk Development in Young Adults (CARDIA) participants who attended the Year 7 (ages 25-37years) and/or 20 exams (ages 38-50years), respectively, which included a GXT. Cox proportional hazard models were used to examine the effect of GXT disposition (at Year 7 and 20, separately) on risk of non-fatal and fatal cardiovascular events and all-cause mortality obtained through 28years of follow-up. A GXT was not conducted or completed according to protocol in 12.9% and 19.1% of participants attending the Year 7 and 20 exams, respectively. After adjustment, participants who missed the Year 20 GXT for medical reasons had a higher risk of cardiovascular events [HR: 4.06 (95% CI: 1.43, 11.5)] and all-cause mortality [HR: 3.07 (95% CI: 1.11, 12.3)] compared to GXT completers; participants who missed at Year 20 for non-medical reasons also had higher risk of all-cause mortality [HR: 2.53 (95% CI: 1.61, 3.99)]. Findings suggest that non-participation in a GXT, regardless of medical or non-medical reason, to be an important predictor of excess risk of adverse health outcomes and premature mortality. Additional patient follow-up, including identification of potential targets for intervention (e.g., weight management and smoking cessation programs), should be conducted at the point of a missed GXT.
Authors: Pettee Gabriel K; Whitaker KM; Duprez D; Sternfeld B; Lewis CE; Sidney S; Knell G; Jacobs DR
Prev Med. 2018 01;106:137-144. Epub 2017-11-02.
Post-traumatic stress disorder and risk of dementia among members of a health care delivery system
Post-traumatic stress disorder (PTSD) is associated with an increased risk of dementia in male veterans, but little is known in females and civilians. PTSD and comorbidities were abstracted from medical records from 1/1/1996 to 12/31/2001. Dementia incidence from 1/1/2002 to 12/31/2014 in 499,844 health care members aged 60+ years over an average of 8.2 years. Cox proportional hazard models were adjusted for age, demographics, and comorbidities. PTSD was associated with increased risk of dementia over an average of 8 years of follow-up (females: hazard ratio [HR] = 1.59, 95% confidence interval [CI] = 1.30-1.95; males: HR = 1.96, 95% CI = 1.51-2.55). There was a two-fold risk of dementia in those with both PTSD and depression (females: HR = 2.08; 95% CI = 1.66-2.59; males: HR = 2.06; 95% CI = 1.47-2.91) versus those without. PTSD was a risk factor for dementia in both sexes, with a heightened risk in those with comorbid depression.
Authors: Flatt JD; Gilsanz P; Quesenberry CP; Albers KB; Whitmer RA
Alzheimers Dement. 2018 01;14(1):28-34. Epub 2017-06-13.
Prioritizing research topics: a comparison of crowdsourcing and patient registry
A cornerstone of patient-centered outcome research is direct patient involvement throughout the research process. Identifying and prioritizing research topics is a critical but often overlooked point for involvement, as it guides what research questions are asked. We assess the feasibility of involving individuals with low back pain in identifying and prioritizing research topics using two approaches: an existing patient registry and an online crowdsourcing platform. We compare and contrast the diversity of participants recruited, their responses, and resources involved. Eligible participants completed a survey ranking their five highest priority topics from an existing list and supplying additional topics not previously identified. We analyzed their responses using descriptive statistics and content analysis. The patient registry yielded older (mean age 72.4), mostly White (70%), and well-educated (95% high school diploma or higher) participants; crowdsourcing yielded younger (mean age 36.6 years), mostly White (82%), and well-educated (98% high school diploma or higher) participants. The two approaches resulted in similar research priorities by frequency. Both provided open-ended responses that were useful, in that they illuminate additional and nuanced research topics. Overall, both approaches suggest a preference towards topics related to diagnosis and treatment over other topics. Using a patient registry and crowdsourcing are both feasible recruitment approaches for engagement. Researchers should consider their approach, community, and resources when choosing their recruitment approach, as each approach has its own strengths and weaknesses. These approaches are likely most appropriate to supplement or to complement in-person and ongoing engagement strategies.
Authors: Truitt AR; Monsell SE; Avins AL; Nerenz DR; Lawrence SO; Bauer Z; Comstock BA; Edwards TC; Patrick DL; Jarvik JG; Lavallee DC
Qual Life Res. 2018 Jan;27(1):41-50. Epub 2017-04-05.
Characteristics of drug use among pregnant women in the United States: Opioid and non-opioid illegal drug use.
BACKGROUND: The opioid epidemic in the US is affecting pregnant women and their offspring, with rising numbers of maternal and neonatal treatment episodes. The aim of this study was to characterize pregnant drug users in order to inform intervention strategies based on sociodemographic, mental health, and substance use characteristics.METHODS: Data on pregnant women aged 18-44 reporting past-year, nonmedical opioid use or use of non-opioid illegal drugs (other than marijuana) were analyzed from the National Survey on Drug Use and Health (2005-2014). Women (N = 818) were categorized into 3 groups: 1) use of opioids only (n = 281), 2) opioid-polydrug users (n = 241), and 3) other (non-opioid) illegal drug users (n = 296). Characteristics between the 3 groups of women were compared using bivariable analyses.RESULTS: Most women were non-Hispanic White (67.6%), had a high school diploma or less education (61.0%), a household income CONCLUSIONS: Pregnant drug-using women were often of low socioeconomic status, with mental health and substance use patterns suggesting the need for targeted mental health/substance use screening and interventions before and during pregnancy, particularly for opioid-polydrug users.
Authors: Metz, Verena E VE; Brown, Qiana L QL; Martins, Silvia S SS; Palamar, Joseph J JJ
Drug and alcohol dependence. 2018 02 01;183(5):261-266. Epub 2017-12-27.
Trends in Self-reported and Biochemically Tested Marijuana Use Among Pregnant Females in California From 2009-2016
Authors: Young-Wolff KC; Tucker LY; Alexeeff S; Armstrong MA; Conway A; Weisner C; Goler N
JAMA. 2017 12 26;318(24):2490-2491.
The Bidirectional Association Between Depression and Severe Hypoglycemic and Hyperglycemic Events in Type 1 Diabetes
Severe hyperglycemia and hypoglycemia (“severe dysglycemia”) are serious complications of type 1 diabetes (T1D). Depression has been associated with severe dysglycemia in type 2 diabetes but has not been thoroughly examined specifically in T1D. We evaluated bidirectional associations between depression and severe dysglycemia among older people with T1D. We abstracted depression and severe dysglycemia requiring emergency room visit or hospitalization from medical health records in 3,742 patients with T1D during the study period (1996-2015). Cox proportional hazards models estimated the associations between depression and severe dysglycemia in both directions, adjusting for demographics, micro- and macrovascular complications, and HbA1c. During the study period, 41% had depression and 376 (11%) and 641 (20%) had hyperglycemia and hypoglycemia, respectively. Depression was strongly associated with a 2.5-fold increased risk of severe hyperglycemic events (hazard ratio [HR] 2.47 [95% CI 2.00, 3.05]) and 89% increased risk of severe hypoglycemic events (HR 1.89 [95% CI 1.61, 2.22]). The association was strongest within the first 6 months (HRhyperglycemia 7.14 [95% CI 5.29, 9.63]; HRhypoglycemia 5.58 [95% CI 4.46, 6.99]) to 1 year (HRhyperglycemia 5.16 [95% CI 3.88, 6.88]; HRhypoglycemia 4.05 [95% CI 3.26, 5.04]) after depression diagnosis. In models specifying severe dysglycemia as the exposure, hyperglycemic and hypoglycemic events were associated with 143% (HR 2.43 [95% CI 2.03, 2.91]) and 74% (HR 1.75 [95% CI 1.49, 2.05]) increased risk of depression, respectively. Depression and severe dysglycemia are associated bidirectionally among patients with T1D. Depression greatly increases the risk of severe hypoglycemic and hyperglycemic events, particularly in the first 6 months to 1 year after diagnosis, and depression risk increases after severe dysglycemia episodes.
Authors: Gilsanz P; Karter AJ; Beeri MS; Quesenberry CP; Whitmer RA
Diabetes Care. 2017 Dec 18.
A large multi-ethnic genome-wide association study identifies novel genetic loci for intraocular pressure
Elevated intraocular pressure (IOP) is a major risk factor for glaucoma, a leading cause of blindness. IOP heritability has been estimated to up to 67%, and to date only 11 IOP loci have been reported, accounting for 1.5% of IOP variability. Here, we conduct a genome-wide association study of IOP in 69,756 untreated individuals of European, Latino, Asian, and African ancestry. Multiple longitudinal IOP measurements were collected through electronic health records and, in total, 356,987 measurements were included. We identify 47 genome-wide significant IOP-associated loci (P < 5 × 10-8); of the 40 novel loci, 14 replicate at Bonferroni significance in an external genome-wide association study analysis of 37,930 individuals of European and Asian descent. We further examine their effect on the risk of glaucoma within our discovery sample. Using longitudinal IOP measurements from electronic health records improves our power to identify new variants, which together explain 3.7% of IOP variation.
Authors: Choquet H; Thai KK; Yin J; Hoffmann TJ; Kvale MN; Banda Y; Schaefer C; Risch N; Nair KS; Melles R; Jorgenson E
Nat Commun. 2017 Dec 13;8(1):2108. Epub 2017-12-13.
Genome-wide association study identifies a locus associated with rotator cuff injury
Rotator cuff tears are common, especially in the fifth and sixth decades of life, but can also occur in the competitive athlete. Genetic differences may contribute to overall injury risk. Identifying genetic loci associated with rotator cuff injury could shed light on the etiology of this injury. We performed a genome-wide association screen using publically available data from the Research Program in Genes, Environment and Health including 8,357 cases of rotator cuff injury and 94,622 controls. We found rs71404070 to show a genome-wide significant association with rotator cuff injury with p = 2.31×10-8 and an odds ratio of 1.25 per allele. This SNP is located next to cadherin8, which encodes a protein involved in cell adhesion. We also attempted to validate previous gene association studies that had reported a total of 18 SNPs showing a significant association with rotator cuff injury. However, none of the 18 SNPs were validated in our dataset. rs71404070 may be informative in explaining why some individuals are more susceptible to rotator cuff injury than others.
Authors: Roos TR; Roos AK; Avins AL; Ahmed MA; Kleimeyer JP; Fredericson M; Ioannidis JPA; Dragoo JL; Kim SK
PLoS ONE. 2017;12(12):e0189317. Epub 2017-12-11.
CREATE Wellness: A multi-component behavioral intervention for patients not responding to traditional Cardiovascular disease management
Cardiovascular disease (CVD) is the leading cause of death in the US. Many patients do not benefit from traditional disease management approaches to CVD risk reduction. Here we describe the rationale, development, and implementation of a multi-component behavioral intervention targeting patients who have persistently not met goals of CVD risk factor control. Informed by published evidence, relevant theoretical frameworks, stakeholder advice, and patient input, we developed a group-based intervention (Changing Results: Engage and Activate to Enhance Wellness; “CREATE Wellness”) to address the complex needs of patients with elevated or unmeasured CVD-related risk factors. We are testing this intervention in a randomized trial among patients with persistent (i.e > 2 years) sub-optimal risk factor control despite being enrolled in an advanced and highly successful CVD disease management program. The CREATE Wellness intervention is designed as a 3 session, group-based intervention combining proven elements of patient activation, health system engagement skills training, shared decision making, care planning, and identification of lifestyle change barriers. Our key learnings in designing the intervention included the value of multi-level stakeholder input and the importance of pragmatic skills training to address barriers to care. The CREATE Wellness intervention represents an evidence-based, patient-centered approach for patients not responding to traditional disease management. The trial is currently underway at three medical facilities within Kaiser Permanente Northern California and next steps include an evaluation of efficacy, adaptation for non-English speaking patient populations, and modification of the curriculum for web- or phone-based versions. NCT02302612.
Authors: Miller-Rosales C; Sterling SA; Grant RW; et al.
Contemp Clin Trials Commun. 2017 Dec;8:140-146. Epub 2017-10-04.
Physical activity trajectories during midlife and subsequent risk of physical functioning decline in late mid-life: The Study of Women’s Health Across the Nation (SWAN)
The purpose of this study was to examine the importance of midlife physical activity on physical functioning in later life. Data are from 1771 Study of Women’s Health Across the Nation (SWAN) participants, aged 42-52 (46.4±2.7) years at baseline (1996-97). Latent class growth analysis was used to identify physical activity trajectory groups using reported sports and exercise index data collected at seven time-points from baseline to Visit 13 (2011-13); objective measures of physical functioning performance were collected at Visit 13. The sports and exercise index (henceforth: physical activity) is a measure of moderate to vigorous intensity physical activity during discretionary periods of the day. Multivariable linear regression analyses were used to model each continuous physical performance measure as a function of the physical activity trajectory class. Across midlife, five physical activity trajectory classes emerged, including: lowest (26.2% of participants), increasing (13.4%), decreasing (22.4%), middle (23.9%), and highest (14.1%) physical activity. After full adjustment, women included in the middle and highest physical activity groups demonstrated ≥5% better physical functioning performance than those who maintained low physical activity levels (all comparisons; p<0.05). Statistically significant differences were also noted when physical activity trajectory groups were compared to the increasing physical activity group. Results from the current study support health promotion efforts targeting increased (or maintenance of) habitual physical activity in women during midlife to reduce future risk of functional limitations and disability. These findings have important public health and clinical relevance as future generations continue to transition into older adulthood.
Authors: Pettee Gabriel K; Sternfeld B; Colvin A; Stewart A; Strotmeyer ES; Cauley JA; Dugan S; Karvonen-Gutierrez C
Prev Med. 2017 Dec;105:287-294. Epub 2017-10-05.
Sedentary Time, Physical Activity, and Adiposity: Cross-sectional and Longitudinal Associations in CARDIA
Higher sedentary time (ST) and lower moderate- to vigorous-intensity physical activity (MVPA) have each been associated with greater adiposity, but most studies are cross-sectional and measure ST and MVPA by self-report. This study evaluated associations between objective ST and MVPA with current and 5-year changes in BMI and waist circumference. The Coronary Artery and Risk Development in Young Adults longitudinal cohort study recruited black or white young adults from four U.S. cities. This analysis (conducted in 2016) used data from 2005 to 2006 as baseline and 2010 to 2011 as 5-year follow-up. Accelerometers measured baseline ST (total and prolonged in bouts of ≥10 minutes) and MVPA (bouts of ≥10 minutes). BMI and waist circumference were assessed at baseline and repeated 5 years later. Regression models included sedentary time and MVPA simultaneously with adjustment for demographics and lifestyle factors. Participants (n=1,826) were 57% female; 40% black; aged 38-50 years; and had a BMI of 28.7 (SD=6.3). At baseline, total and prolonged ST were directly associated with BMI and waist circumference, whereas MVPA was inversely related (all p<0.05). Longitudinally, only prolonged ST (per hour/day) was associated with greater increases in BMI (0.077, p=0.033) and waist circumference (0.198 cm, p=0.028). Associations between ST and adiposity were more apparent in less active participants. Risk of ≥5% increase in BMI across assessments increased by 8%-10% (p<0.05) per hour/day of ST. Time spent sedentary was associated with increases in adiposity over time. Reducing sedentary time may be a novel strategy for weight control.
Authors: Barone Gibbs B; Pettee Gabriel K; Carnethon MR; Gary-Webb T; Jakicic JM; Rana JS; Reis JP; Siddique J; Sternfeld B; Lewis CE
Am J Prev Med. 2017 Dec;53(6):764-771. Epub 2017-10-09.
Do you vape? Leveraging electronic health records to assess clinician documentation of electronic nicotine delivery system use among adolescents and adults
Use of electronic nicotine delivery systems (ENDS) has increased substantially over the past decade. However, unlike smoking, which is systematically captured by clinicians through routine screening and discrete documentation fields in the electronic health record (EHR), unknown is the extent to which clinicians are documenting patients’ use of ENDS. Data were gathered from medical visits with patients aged 12 and older (N=9,119; 55% male) treated in a large, integrated healthcare system. We used natural language processing to assess the incidence rates of clinician documentation of patients’ ENDS use in unstructured tobacco comments in the EHR, and the words most frequently documented in relation to ENDS, from 2006-2015. ENDS documentation in the EHR increased dramatically over time (from 0.01 to 9.5 per 10,000 patients, p<0.0001), particularly among adults aged 18-24 and 25-44. Most prevalent were "e-cig," "electronic cigarettes", and "vape," with much variation in spelling and phrasing of these words. Records of adolescent and young adult patients were more likely to contain the word "vape", and less likely to have "e-cig" and "electronic cigarette" than records of adults (ps<0.0001). The relatively low observed number of patients with ENDS terms in the EHR suggested vast under documentation. While healthcare providers are increasingly documenting patients' use of ENDS in the EHR, overall documentation rates remain low. Discrete EHR fields for standard screening and documentation of ENDS that reflect the language used by patients would provide more complete longitudinal population-level surveillance of ENDS use and its association with short- and long-term health outcomes.
Authors: Young-Wolff KC; Klebaner D; Folck B; Carter-Harris L; Salloum RG; Prochaska JJ; Fogelberg R; Tan ASL
Prev Med. 2017 Dec;105:32-36. Epub 2017-08-16.
Posttraumatic stress disorder onset and inflammatory and endothelial function biomarkers in women
BACKGROUND: Research has linked posttraumatic stress disorder (PTSD) with higher circulating levels of inflammatory and endothelial function (EF) biomarkers, and effects may be bidirectional. We conducted the first investigation of new-onset PTSD and changes in inflammatory and EF biomarkers.METHODS: Data were from women in the Nurses’ Health Study II. Biomarkers obtained at two blood draws, 10-16 years apart, included C-reactive protein (CRP), tumor necrosis factor-alpha receptor-II (TNFRII), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). PTSD was assessed via interview. Analyses compared biomarker levels in women with PTSD that onset between draws (n = 175) to women with no history of trauma (n = 175) and to women with history of trauma at draw 1 and no PTSD at either draw (n = 175). We examined if PTSD onset was associated with biomarker change over time and if pre-PTSD-onset biomarker levels indicated risk of subsequent PTSD using linear mixed models and linear regression, respectively. Biomarkers were log-transformed.RESULTS: Compared to women without trauma, women in the PTSD onset group had larger increases in VCAM-1 over time (b = 0.003, p = .068). They also had higher TNFRII (b = 0.05, p = .049) and ICAM-1 (b = 0.04, p = .060) levels at draw 1 (prior to trauma and PTSD onset). However, pre-PTSD-onset biomarker levels did not predict onset of more severe PTSD.CONCLUSIONS: PTSD onset (vs. no trauma) was associated with increases in one inflammation-related biomarker. Effects may be small and cumulative; longer follow-up periods with larger samples are needed. We did not observe strong support that pre-PTSD-onset biomarkers predicted risk of subsequent PTSD.
Authors: Sumner, Jennifer A JA; Chen, Qixuan Q; Roberts, Andrea L AL; Winning, Ashley A; Rimm, Eric B EB; Gilsanz, Paola P; Glymour, M Maria MM; Tworoger, Shelley S SS; Koenen, Karestan C KC; Kubzansky, Laura D LD
Brain, behavior, and immunity. 2018 Mar ;69():203-209. Epub 2017-11-20.
Associations of Race and Ethnicity with Patient-Reported Outcomes and Health Care Utilization among Older Adults Initiating a New Episode of Care for Back Pain
Secondary analysis of the Back Pain Outcomes using Longitudinal Data (BOLD) cohort study. To characterize associations of self-reported race/ethnicity with back pain (BP) patient-reported outcomes (PROs) and health care utilization among older adults with a new episode of care for BP. No prior longitudinal studies have characterized associations between multiple race/ethnicity groups, and BP-related PROs and health care utilization in the United States. This study included 5117 participants ≥65 years from three US health care systems. The primary BP-related PROs were BP intensity and back-related functional limitations over 24 months. Health care utilization measures included common diagnostic tests and treatments related to BP (spine imaging, spine-related relative value units [RVUs], and total RVUs) over 24 months. Analyses were adjusted for multiple potential confounders including sociodemographics, clinical characteristics, and study site. Baseline BP ratings were significantly higher for blacks vs. whites (5.8 vs. 5.0; P < 0.001). Participants in all race/ethnicity groups showed statistically significant, but modest improvements in BP over 24 months. Blacks and Hispanics did not have statistically significant improvement in BP-related functional limitations over time, unlike whites, Asians, and non-Hispanics; however, the magnitude of differences in improvement between groups was small. Blacks had less spine-related health care utilization over 24 months than whites (spine-related RVU ratio of means 0.66, 95% confidence interval [CI] 0.51-0.86). Hispanics had less spine-related health care utilization than non-Hispanics (spine-related RVU ratio of means 0.60; 95% CI 0.40-0.90). Blacks and Hispanics had slightly less improvement in BP-related functional limitations over time, and less spine-related health care utilization, as compared to whites and non-Hispanics, respectively. Residual confounding may explain some of the association between race/ethnicity and health outcomes. Further studies are needed to understand the factors underlying these differences and which differences reflect disparities. 3.
Authors: Milani CJ; Avins A; Suri P; et al.
Spine. 2017 Nov 20.
A Genetic Marker Associated with De Quervain’s Tenosynovitis
De Quervain’s tenosynovitis is a repetitive strain injury involving synovial inflammation of the tendons of the first extensor compartment of the wrist. It is relatively common in the general population, and is the most common radial-sided tendinopathy seen in athletes. Identifying a genetic marker associated with de Quervain’s tenosynovitis could provide a useful tool to help identify those individuals with an increased risk for injury. A genome-wide association screen was performed using publically available data from the Research Program in Genes, Environment and Health (RPGEH) including 4,129 cases and 98,374 controls. rs35360670 on chromosome 8 showed an association with de Quervain’s tenosynovitis at genome-wide significance (p=1.9×10-8; OR=1.46; 95% CI=1.38-1.59). This study is the first genome-wide screen for de Quervain’s tenosynovitis and provides insights regarding its genetic etiology as well as a DNA marker with the potential to inform athletes and other high-risk individuals about their relative risk for injury.
Authors: Kim SK; Ahmed MA; Avins AL; Ioannidis JPA
Int J Sports Med. 2017 Nov;38(12):942-948. Epub 2017-10-06.
Specialty addiction and psychiatry treatment initiation and engagement: Results from an SBIRT randomized trial in pediatrics
Many adolescents needing specialty addiction or psychiatry treatment never access care. We examined initiation and engagement with addiction and/or psychiatry treatment among adolescents referred to treatment from a trial comparing two different modalities of delivering Screening, Brief Intervention and Referral to Treatment (SBIRT) to Usual Care in pediatric primary care. We hypothesized that both intervention arms would have higher initiation and engagement rates than usual care. We randomized all pediatricians (n=52) in a pediatric primary care clinic to three arms: 1) pediatrician-only arm, in which pediatricians were trained to deliver SBIRT for substance use and/or mental health problems; 2) embedded-behavioral health clinician (embedded-BHC arm), in which pediatricians referred adolescents who endorsed substance use and/or mental health problems to a BHC; and 3) Usual Care (UC). We used electronic health record (EHR) data to examine specialty addiction and psychiatry treatment initiation and engagement rates after referral. Among patients who screened positive for substance use and/or mental health problems and were referred to specialty addiction and/or psychiatry (n=333), those in the embedded-BHC arm had almost four times higher odds of initiating treatment than those in the pediatrician-only arm, OR=3.99, 95% CI=[1.99-8.00]. Compared to UC, those in the pediatrician-only arm had lower odds of treatment initiation (OR=0.53, 95% CI=[0.28-0.99]), while patients in the embedded-BHC arm had marginally higher odds (OR=1.83, 95% CI=[0.99-3.38]). Black patients and those with other/unknown race/ethnicity had lower odds of treatment initiation compared with white adolescents; there were no gender or age differences. We found no differences in treatment engagement across the three arms. Embedded BHCs can have a significant positive impact on facilitating treatment initiation for pediatric primary care adolescents referred to addiction and/or psychiatry services. ClinicalTrials.gov #NCT02408952.
Authors: Sterling S; Kline-Simon AH; Jones A; Satre DD; Parthasarathy S; Weisner C
J Subst Abuse Treat. 2017 Nov;82:48-54. Epub 2017-09-10.
Female sex, early-onset hypertension, and risk of dementia
To evaluate the association of early-adulthood and mid-adulthood hypertension with dementia in men and women. We evaluated 5,646 members of a diverse integrated health care delivery system who had clinical examinations and health survey data from 1964 to 1973 (mean age 32.7 years; early adulthood) and 1978-1985 (mean age 44.3 years; mid-adulthood) and were members as of January 1, 1996 (mean age 59.8 years). Hypertension categories based on measurements of blood pressure (BP) and change in hypertension categories between the 2 examinations (e.g., onset hypertension) were used to predict dementia incidence from January 1, 1996, to September 30, 2015. Cox proportional hazard models were adjusted for demographics, vascular comorbidities, and hypertension treatment; inverse probability weighting accounted for differential attrition between first BP measurement and start of follow-up. A total of 532 individuals (9.4%) were diagnosed with dementia. Early adulthood hypertension was not associated with dementia, though effect estimates were elevated among women. Mid-adulthood hypertension was associated with 65% (95% confidence interval [CI] 1.25-2.18) increased dementia risk among women but not men. Onset of hypertension in mid-adulthood predicted 73% higher dementia risk in women (95% CI 1.24-2.40) compared to stable normotensive. There was no evidence that hypertension or changes in hypertension increased dementia risk among men. Though midlife hypertension was more common in men, it was only associated with dementia risk in women. Sex differences in the timing of dementia risk factors have important implications for brain health and hypertension management.
Authors: Gilsanz P; Mayeda ER; Glymour MM; Quesenberry CP; Mungas DM; DeCarli C; Dean A; Whitmer RA
Neurology. 2017 Oct 31;89(18):1886-1893. Epub 2017-10-04.
Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology
Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals, partly because of a shared genetic origin. To identify shared risk variants, we performed a genome-wide association study (GWAS; n = 360,838) of a broad allergic disease phenotype that considers the presence of any one of these three diseases. We identified 136 independent risk variants (P < 3 × 10(-8)), including 73 not previously reported, which implicate 132 nearby genes in allergic disease pathophysiology. Disease-specific effects were detected for only six variants, confirming that most represent shared risk factors. Tissue-specific heritability and biological process enrichment analyses suggest that shared risk variants influence lymphocyte-mediated immunity. Six target genes provide an opportunity for drug repositioning, while for 36 genes CpG methylation was found to influence transcription independently of genetic effects. Asthma, hay fever and eczema partly coexist because they share many genetic risk variants that dysregulate the expression of immune-related genes.
Authors: Ferreira MA; Vonk JM; Baurecht H; Marenholz I; Tian C; Hoffman JD; Helmer Q; Tillander A; Ullemar V; van Dongen J; Lu Y; Rüschendorf F; Esparza-Gordillo J; Medway CW; Mountjoy E; Burrows K; Hummel O; Grosche S; Brumpton BM; Witte JS; Hottenga JJ; Willemsen G; Zheng J; Rodríguez E; Hotze M; Franke A; Revez JA; Beesley J; Matheson MC; Dharmage SC; Bain LM; Fritsche LG; Gabrielsen ME; Balliu B; 23andMe Research Team; AAGC collaborators; BIOS consortium; LifeLines Cohort Study; Nielsen JB; Zhou W; Hveem K; Langhammer A; Holmen OL; Løset M; Abecasis GR; Willer CJ; Arnold A; Homuth G; Schmidt CO; Thompson PJ; Martin NG; Duffy DL; Novak N; Schulz H; Karrasch S; Gieger C; Strauch K; Melles RB; Hinds DA; Hübner N; Weidinger S; Magnusson PKE; Jansen R; Jorgenson E; Lee YA; Boomsma DI; Almqvist C; Karlsson R; Koppelman GH; Paternoster L
Nat Genet. 2017 Oct 30.
Genome-wide association study and meta-analysis in multiple populations identifies new loci for peanut allergy and establishes c11orf30/EMSY as a genetic risk factor for food allergy
Peanut allergy (PA) is a complex disease with both environmental and genetic risk factors. Previously PA loci were identified in FLG and HLA in candidate gene studies, and loci in HLA in a genome-wide association study and meta-analysis. To investigate genetic susceptibility to PA. Eight hundred and fifty cases and 926 hyper-controls and >7.8 million genotyped and imputed single nucleotide polymorphisms (SNPs) were analyzed in a genome-wide association study to identify susceptibility variants for PA in the Canadian population. Meta-analysis of two phenotypes (PA and food allergy) was conducted using 7 studies from the Canadian, American (2), Australian, German and Dutch (2) populations. A SNP near ITGA6 reached genome-wide significance with PA (p=1.80×10(-8)), while SNPs associated with SKAP1, MMP12/MMP13, CTNNA3, ARHGAP24, ANGPT4, c11orf30 (EMSY), and EXOC4 reached a threshold suggestive of association (p≤1.49×10(-6)). In the meta-analysis of PA, loci in or near ITGA6, ANGPT4, MMP12/MMP13, c11orf30 and EXOC4 were significant (p≤1.49×10(-6)). When a phenotype of any food allergy was used for meta-analysis, the c11orf30 locus reached genome-wide significance (p=7.50×10(-11)), while SNPs associated with ITGA6, ANGPT4, MMP12/MMP13, EXOC4 and additional c11orf30 SNPs were suggestive (p≤1.49×10(-6)). Functional annotation indicated SKAP1 regulates expression of CBX1, which co-localizes with the EMSY protein coded by c11orf30. This study identifies multiple novel loci as risk factors for PA and food allergy and establishes c11orf30 as a risk locus for both peanut and food allergy. Multiple genes (c11orf30/EMSY, SKAP1 and CTNNA3) identified by this study are involved in epigenetic regulation of gene expression.
Authors: Asai Y; Eslami A; van Ginkel CD; Akhabir L; Wan M; Ellis G; Ben-Shoshan M; Martino D; Ferreira MA; Allen K; Mazer B; de Groot H; de Jong NW; Gerth van Wijk RN; Dubois AEJ; Chin R; Cheuk S; Hoffman J; Jorgensen E; Witte JS; Melles RB; Hong X; Wang X; Hui J; Musk AWB; Hunter M; James AL; Koppelman GH; Sandford AJ; Clarke AE; Daley D
J Allergy Clin Immunol. 2017 Oct 10.
Pioglitazone, a PPARγ agonist, reduces nicotine craving in humans, with marginal effects on abuse potential.
Possibly through their actions upon glia, peroxisome proliferator-activated receptor agonists (PPAR) have been shown to alter the abuse potential of addictive drugs in several preclinical models. The current study extends this research into the human laboratory as the first clinical study into the effects of the PPAR gamma agonist, pioglitazone, on the abuse potential of nicotine. Heavy smokers were recruited for this 3-week study. Upon admission, participants were randomized to either active (45mg, n=14) or placebo (0mg, n=13) PIO maintenance conditions for the duration of the study. After 5-7days of stabilization on a 7mg nicotine patch, participants began laboratory testing. On the 1st-4th test days, participants could self-administer cigarettes or receive money by making verbal choices for either option. On the 5th day, participants were administered 10 puffs of their usual brand of cigarette in the morning and later chose between smoking and money by making finger presses on a computer mouse in a progressive ratio self-administration task. Later on the 5th day participants also underwent a smoking cue exposure session. The 8th-11th test days were identical to the 1st-4th test days with the exception that during one of the test weeks de-nicotinized cigarettes were available, and during the other nicotinized cigarettes were available. Nicotinized cigarettes were always administered on the 5th and 12th days. On some measures PIO increased indicators of abuse potential, though this effect was typically not statistically significant. However, PIO did significantly reduce measures of craving.
Authors: Jones, Jermaine D JD; Comer, Sandra D SD; Metz, Verena E VE; Manubay, Jeanne M JM; Mogali, Shanthi S; Ciccocioppo, Roberto R; Martinez, Suky S; Mumtaz, Mudassir M; Bisaga, Adam A
Pharmacology, biochemistry, and behavior. 2017 Dec 01;163(5):90-100. Epub 2017-10-08.
The interaction between smoking and HLA genes in multiple sclerosis: replication and refinement
Interactions between environment and genetics may contribute to multiple sclerosis (MS) development. We investigated whether the previously observed interaction between smoking and HLA genotype in the Swedish population could be replicated, refined and extended to include other populations. We used six independent case-control studies from five different countries (Sweden, Denmark, Norway, Serbia, United States). A pooled analysis was performed for replication of previous observations (7190 cases, 8876 controls). Refined detailed analyses were carried out by combining the genetically similar populations from the Nordic studies (6265 cases, 8401 controls). In both the pooled analyses and in the combined Nordic material, interactions were observed between HLA-DRB*15 and absence of HLA-A*02 and between smoking and each of the genetic risk factors. Two way interactions were observed between each combination of the three variables, invariant over categories of the third. Further, there was also a three way interaction between the risk factors. The difference in MS risk between the extremes was considerable; smokers carrying HLA-DRB1*15 and lacking HLA-A*02 had a 13-fold increased risk compared with never smokers without these genetic risk factors (OR 12.7, 95% CI 10.8-14.9). The risk of MS associated with HLA genotypes is strongly influenced by smoking status and vice versa. Since the function of HLA molecules is to present peptide antigens to T cells, the demonstrated interactions strongly suggest that smoking alters MS risk through actions on adaptive immunity.
Authors: Hedström AK; Schaefer CA; Alfredsson L; et al.
Eur J Epidemiol. 2017 Oct;32(10):909-919. Epub 2017-06-08.
Two genetic loci associated with ankle injury
Ankle injuries, including sprains, strains and other joint derangements and instability, are common, especially for athletes involved in indoor court or jumping sports. Identifying genetic loci associated with these ankle injuries could shed light on their etiologies. A genome-wide association screen was performed using publicly available data from the Research Program in Genes, Environment and Health (RPGEH) including 1,694 cases of ankle injury and 97,646 controls. An indel (chr21:47156779:D) that lies close to a collagen gene, COL18A1, showed an association with ankle injury at genome-wide significance (p = 3.8×10-8; OR = 1.99; 95% CI = 1.75-2.23). A second DNA variant (rs13286037 on chromosome 9) that lies within an intron of the transcription factor gene NFIB showed an association that was nearly genome-wide significant (p = 5.1×10-8; OR = 1.63; 95% CI = 1.46-1.80). The ACTN3 R577X mutation was previously reported to show an association with acute ankle sprains, but did not show an association in this cohort. This study is the first genome-wide screen for ankle injury that yields insights regarding the genetic etiology of ankle injuries and provides DNA markers with the potential to inform athletes about their genetic risk for ankle injury.
Authors: Kim SK; Kleimeyer JP; Ahmed MA; Avins AL; Fredericson M; Dragoo JL; Ioannidis JPA
PLoS ONE. 2017;12(9):e0185355. Epub 2017-09-28.
Intimate Partner Violence, Smoking, and Pregnancy: What Can We Do to Help?
Authors: Young-Wolff KC; McCaw B; Avalos LA
J Womens Health (Larchmt). 2017 Sep 22.
Study of Methods for Assessing Research Topic Elicitation and pRioritization (SMARTER): Study Protocol to Compare Qualitative Research Methods and Advance Patient Engagement in Research
Involving patients as partners in research is a defining characteristic of patient-centered outcomes research (PCOR). While patients’ experiential knowledge of a health condition or treatment may yield research priorities not reflected by researchers and policy makers, the methods for identifying and effectively collaborating with patients are still evolving. Patient registries and crowdsourcing may offer ease of access and convenience to both researchers and patients. Surveys and focus groups, including online modalities, have been described for prioritizing research topics. However, little is known about how these different methods compare in producing consistent priorities and similar perceptions of engagement quality among participants. The aims of this study are (1) to compare how different engagement methods used to elicit patient priorities for research perform as measured by rankings for priorities generated and participant satisfaction; and (2) to determine characteristics of individuals choosing to participate in research prioritization activities. Participants in the Back pain Outcomes using Longitudinal Data (BOLD) patient registry, established to evaluate the natural history of back pain among individuals 65 years and older, and participants on the Amazon Mechanical Turk (MTurk) crowdsourcing platform, to provide input on priorities for research via a questionnaire, are invited. For BOLD participants, we subsequently randomize interested respondents to 1 of 3 interactive prioritization activities to further develop priorities: a Delphi panel, an online crowd voting activity, or an in-person facilitated prioritization activity using nominal group technique (NGT). Participants involved in each activity complete a survey to evaluate the quality of the experience and a subset of these participants discuss their experience further in an interview. Descriptive statistics are used to characterize the rankings produced by each method and compare the top 5 rated topics resulting from each prioritization activity. We use rank-ordered logistic regression models to identify associations of the ranked priority topics with baseline patient characteristics. We analyze responses to the evaluation using a mixed-methods approach wherein we tabulate responses to Likert-scale questions and use content analysis to enumerate themes emerging from interviews for the 3 activities. In Phase I, we invite approximately 3000 BOLD participants and 500 Amazon MTurk workers to complete a research topic prioritization survey. Based on these results, we include additional topics into a subsequent prioritization survey. In Phase II, we invite BOLD participants to join 1 of 3 activities: 90 participants for Delphi panel, 100 participants for crowd voting, and 60 participants for focus groups. Of the Phase II participants, 30 will be interviewed to evaluate the activities. This study informs decisions about how to conduct outreach to patient registry participants for providing input on research priorities, how individuals 65 years and older wish to participate in engagement activities, and how different research prioritization methods compare in terms of rankings generated and participant satisfaction.
Authors: Lavallee DC; Comstock B; Scott MR; Avins AL; Nerenz DR; Edwards TC; Patrick DL; Lawrence SO; Bauer Z; Truitt AR; Jarvik JG
JMIR Res Protoc. 2017 Sep 07;6(9):e168. Epub 2017-09-07.
Genetic contributors to variation in alcohol consumption vary by race/ethnicity in a large multi-ethnic genome-wide association study
Alcohol consumption is a complex trait determined by both genetic and environmental factors, and is correlated with the risk of alcohol use disorders. Although a small number of genetic loci have been reported to be associated with variation in alcohol consumption, genetic factors are estimated to explain about half of the variance in alcohol consumption, suggesting that additional loci remain to be discovered. We conducted a genome-wide association study (GWAS) of alcohol consumption in the large Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort, in four race/ethnicity groups: non-Hispanic whites, Hispanic/Latinos, East Asians and African Americans. We examined two statistically independent phenotypes reflecting subjects’ alcohol consumption during the past year, based on self-reported information: any alcohol intake (drinker/non-drinker status) and the regular quantity of drinks consumed per week (drinks/week) among drinkers. We assessed these two alcohol consumption phenotypes in each race/ethnicity group, and in a combined trans-ethnic meta-analysis comprising a total of 86 627 individuals. We observed the strongest association between the previously reported single nucleotide polymorphism (SNP) rs671 in ALDH2 and alcohol drinker status (odd ratio (OR)=0.40, P=2.28 × 10-72) in East Asians, and also an effect on drinks/week (beta=-0.17, P=5.42 × 10-4) in the same group. We also observed a genome-wide significant association in non-Hispanic whites between the previously reported SNP rs1229984 in ADH1B and both alcohol consumption phenotypes (OR=0.79, P=2.47 × 10-20for drinker status and beta=-0.19, P=1.91 × 10-35for drinks/week), which replicated in Hispanic/Latinos (OR=0.72, P=4.35 × 10-7and beta=-0.21, P=2.58 × 10-6, respectively). Although prior studies reported effects of ADH1B and ALDH2 on lifetime measures, such as risk of alcohol dependence, our study adds further evidence of the effect of the same genes on a cross-sectional measure of average drinking. Our trans-ethnic meta-analysis confirmed recent findings implicating the KLB and GCKR loci in alcohol consumption, with strongest associations observed for rs7686419 (beta=-0.04, P=3.41 × 10-10for drinks/week and OR=0.96, P=4.08 × 10-5for drinker status), and rs4665985 (beta=0.04, P=2.26 × 10-8for drinks/week and OR=1.04, P=5 × 10-4for drinker status), respectively. Finally, we also obtained confirmatory results extending previous findings implicating AUTS2, SGOL1 and SERPINC1 genes in alcohol consumption traits in non-Hispanic whites.
Authors: Jorgenson E; Thai KK; Hoffmann TJ; Sakoda LC; Kvale MN; Banda Y; Schaefer C; Risch N; Mertens J; Weisner C; Choquet H
Mol Psychiatry. 2017 Sep;22(9):1359-1367. Epub 2017-05-09.
Association Between Birth in a High Stroke Mortality State, Race, and Risk of Dementia
Birth in a group of predominantly southern US states is robustly linked to increased stroke risk. Given the role of cerebrovascular disease in dementia risk, geographic patterning may also occur for dementia incidence. To determine whether birth in 9 high stroke mortality states (HSMSs) is associated with dementia in a diverse cohort of individuals living in Northern California. An observational cohort study included 7423 members of Kaiser Permanente Northern California (KPNC), an integrated health care delivery system, with health survey and clinical examination data available. Data were collected between 1964 and 1973 when the individuals were middle-aged and 1996 and 2015 when participants were in later life. Self-reported state of birth in an HSMS (top quintile of states for stroke mortality). Dementia diagnoses obtained from electronic health records from January 1, 1996, to October 15, 2015. Place of birth, race, educational level, and midlife vascular risk factors data were collected between 1964 and 1973. Of the 7423 persons included in the analysis, 4049 (54.5%) were women; 1354 (18.2%) were black. The mean (SD) age of study participants at their first visit between 1963 and 1974 was 42.94 (1.73) years and mean (SD) age at the beginning of follow-up for dementia in 1996 was 71.14 (2.72) years. Dementia was diagnosed in 2254 (30.4%) of the participants and was more common among those born in an HSMS than those born outside of one (455 [39.0%] vs 1799 [28.8%]). Birth in an HSMS was 9.6 times more common for black participants (795 [58.7%]) than nonblack participants (371 [6.1%]). Overall, birth in an HSMS was associated with a 28% higher risk of dementia (adjusted hazard ratio [aHR], 1.28; 95% CI, 1.13-1.46) adjusted for age, sex, and race. Compared with nonblack persons born outside of an HSMS, black individuals born in an HSMS had the highest dementia risk (aHR, 1.67; 95% CI, 1.48-1.88), followed by black individuals not born in an HSMS (aHR, 1.48; 95% CI, 1.28-1.72), and nonblack persons born in an HSMS had a 46% increased risk (aHR, 1.46; 95% CI, 1.23-1.74). Cumulative 20-year dementia risks at age 65 years were 30.13% (95% CI, 26.87%-32.93%) and 21.80% (95% CI, 20.51%-22.91%) for individuals born in and outside an HSMS, respectively. To our knowledge, this is the first study to date of place of birth and incident dementia and shows increased risk for individuals born in an HSMS, even though all participants subsequently resided in California. Birth in an HSMS was common among black participants. Place of birth has enduring consequences for dementia risk and may be a major contributor to racial disparities in dementia.
Authors: Gilsanz P; Mayeda ER; Glymour MM; Quesenberry CP; Whitmer RA
JAMA Neurol. 2017 Sep 01;74(9):1056-1062.
Serious mental illness and medical comorbidities: Findings from an integrated health care system
To examine the odds associated with having medical comorbidities among patients with serious mental illness (SMI) in a large integrated health system. In a secondary analysis of electronic health record data, this study identified 25,090 patients with an ICD-9 SMI diagnosis of bipolar disorder (n=20,308) or schizophrenia (n=4782) and 25,090 controls who did not have a SMI, matched on age, gender, and medical home facility. Conditional logistic regressions compared the odds associated with having nine medical comorbidity categories and fifteen chronic or serious conditions among patients with SMI versus controls. Results showed having a SMI was associated with significantly higher odds of each medical comorbidity examined (p’s<0.001), except no evidence of a significant association was found between having schizophrenia and musculoskeletal diseases. A similar pattern was found regarding the chronic or severe conditions, where having schizophrenia or bipolar was associated with >1.5 times the odds of each condition (p’s<0.001). In an integrated health system where patients may have fewer barriers to care, SMI patients are likely to present for treatment with a range of medical comorbidities, including chronic and severe conditions. SMI patients may need outreach strategies focused on disease prevention, screening and early diagnosis, and treatment to address medical comorbidities and associated poor health outcomes.
Authors: Bahorik AL; Satre DD; Kline-Simon AH; Weisner CM; Campbell CI
J Psychosom Res. 2017 Sep;100:35-45. Epub 2017-07-08.
The role of marijuana use disorder in predicting emergency department and inpatient encounters: A retrospective cohort study
Marijuana use disorder (MUD) is the most common illegal drug use disorder and its prevalence is increasing. It is associated with psychiatric and medical problems, but little is known about its impact on emergency department (ED) and inpatient utilization rates. In a retrospective cohort design, we used electronic health record (EHR) data to identify patients with MUD (n=2752) and demographically matched patients without MUD (n=2752) in 2010. Logistic regressions determined risk of ED and inpatient visits each year from 2010 to 2014 for MUD patients versus controls; mixed-effect growth models examined differences in utilization rates over 5-years. Patient characteristics predicting increased risk of utilization were examined among the MUD sample only. Rates of ED (OR=0.87, p<0.001) and inpatient (OR=0.76, p<0.001) services use significantly declined over 5 years for all patients. Patients with MUD exhibited a significantly greater decline in ED (OR=0.81, p<0.001) and inpatient (OR=0.64, p<0.001) use relative to controls. However, MUD patients had significantly greater risk of having ED and inpatient visits at each time point (p's<0.001). MUD patients with co-occurring other substance use, medical, and/or psychiatric disorders had a greater risk of having ED or inpatient encounters over 5 years (p's<0.001). MUD patients remain at high risk for ED and inpatient visits despite decreasing utilization rates over 5 years. Addressing MUD patients' comorbid conditions in outpatient settings may help reduce inappropriate service use.
Authors: Campbell CI; Bahorik AL; Kline-Simon AH; Satre DD
Drug Alcohol Depend. 2017 09 01;178:170-175. Epub 2017-06-10.
Trajectories of remission and mortality over 13 years after intake to substance use treatment
Little is known about the relationships between long-term patterns of substance use and mortality risk among substance use disorder (SUD) patients. To determine distinct patterns of remission and relapse of SUD over time and examine their relationship with mortality. The study site was Kaiser Permanente of Northern California. Data for 997 adults who entered substance use treatment between 1994 and 1996 and 4,241 non-SUD patients with similar demographic distributions (35% women in both groups) were analyzed. Latent class growth analysis identified distinct remission trajectory groups over 13 years among SUD patients, and survival analyses were conducted to examine the risk of death between remission trajectory groups, and SUD and non-SUD patients within each remission trajectory group. Three distinct remission trajectory groups were identified among SUD patients: 1) early relapse-low remission probabilities; 2) declining remission-decreasing remission probabilities; and 3) stable remission-stable remission probabilities across all time points. Among the SUD patients, the early relapse group had a higher risk of death than those stably remitted; stable and declining remission groups did not differ. Comparisons within each remission trajectory group showed that SUD patients in the early relapse and stable remission groups had higher risks of death compared with non-SUD patients; there were no differences within the declining group. SUD patients in the stable remission group had lower survival rates compared with non-SUD patients. These findings underline the importance of continuously addressing healthcare needs of individuals with SUD, even in the presence of long-term remission.
Authors: Kline-Simon AH; Chi FW; Mertens JR; Weisner C
Am J Drug Alcohol Abuse. 2017 Sep;43(5):583-590. Epub 2017-02-16.
Alcohol and Drug Use and Aberrant Drug-Related Behavior Among Patients on Chronic Opioid Therapy
To better identify individuals on chronic opioid therapy (COT) at high risk for aberrant-drug related behavior (ADRB). We examine whether patients with low level alcohol and drug use have similar characteristics to those with alcohol and drug disorders. We then examined the relationship of alcohol and drug use to ADRBs among COT patients. The sample was 972 randomly selected COT patients (age 21-80 years old) from a large health system in Northern California, USA, and interviewed in 2009. Logistic regression models were used to model the dependent variables of: alcohol use, illicit drug use, alcohol disorders, illicit drug disorders, and ADRBs. The odds of daily/weekly alcohol use were lower for those with a high daily opioid dose (120+ mg/day vs. <20 mg/day) (OR = 0.32, p < 0.010). Illicit drug disorders were associated with depression (OR = 2.31, p < .001) and being on a high daily opioid dose (OR = 5.51, p < .01). Participants with illicit drug use had higher odds of giving (OR = 2.57, p < 0.01) and receiving opioids from friends or family (OR = 3.25, p < 0.001), but disorder diagnoses were not associated with ADRBs. Findings reinforce that illicit drug use should be of high concern to clinicians prescribing opioids, and suggest it should be considered separately from alcohol use and alcohol disorders in the evaluation of ADRBs. Frequent alcohol use is low, but not uncommon, and suggests a need to discuss specific issues regarding safe use of opioids among persons who use alcohol that may differ from their risk of drug use.
Authors: Campbell CI; Kline-Simon AH; Von Korff M; Saunders KW; Weisner C
Subst Use Misuse. 2017 08 24;52(10):1283-1291. Epub 2017-03-27.
Alzheimer’s disease genetic risk variants beyondAPOEε4 predict mortality
INTRODUCTION: We hypothesized that, like apolipoprotein E (APOE), other late-onset Alzheimer’s disease (LOAD) genetic susceptibility loci predict mortality.METHODS: We used a weighted genetic risk score (GRS) from 21 non-APOELOAD risk variants to predict survival in the Adult Changes in Thought and the Health and Retirement Studies. We meta-analyzed hazard ratios and examined models adjusted for cognitive performance or limited to participants with dementia. For replication, we assessed the GRS-longevity association in the Cohorts for Heart and Aging Research in Genomic Epidemiology, comparing cases surviving to age ≥90 years with controls who died between ages 55 and 80 years.RESULTS: Higher GRS predicted mortality (hazard ratio = 1.05; 95% confidence interval: 1.00-1.10,P = .04). After adjusting for cognitive performance or restricting to participants with dementia, the relationship was attenuated and no longer significant. In case-control analysis, the GRS was associated with reduced longevity (odds ratio = 0.64; 95% confidence interval: 0.41-1.00,P = .05).DISCUSSION: Non-APOELOAD susceptibility loci confer risk for mortality, likely through effects on dementia incidence.
Authors: Mez, Jesse J; Marden, Jessica R JR; Mukherjee, Shubhabrata S; Walter, Stefan S; Gibbons, Laura E LE; Gross, Alden L AL; Zahodne, Laura B LB; Gilsanz, Paola P; Brewster, Paul P; Nho, Kwangsik K; Crane, Paul K PK; Larson, Eric B EB; Glymour, M Maria MM
Alzheimer's & dementia (Amsterdam, Netherlands). 2017 Mar ;8():188-195. Epub 2017-08-14.
Long term effects of repeated injections of local anesthetic with or without corticosteroid for lumbar spinal stenosis: a randomized trial
To determine the overall long-term effectiveness of treatment with epidural corticosteroid injections for lumbar central spinal stenosis and the effect of repeat injections, including crossover injections, on outcomes through 12 months. Multicenter, double-blind, randomized controlled trial comparing epidural injections of corticosteroid plus lidocaine versus lidocaine alone. Sixteen clinical sites. Participants with imaging-confirmed lumbar central spinal stenosis (N=400). Participants were randomized to receive either epidural injections with corticosteroid plus lidocaine or lidocaine alone with the option of blinded crossover after 6 weeks to receive the alternate treatment. Participants could receive 1 to 2 injections from 0 to 6 weeks and up to 2 injections from 6 to 12 weeks. After 12 weeks, participants received usual care. Primary outcomes were the Roland-Morris Disability Questionnaire (RDQ) (range, 0-24, where higher scores indicate greater disability) and leg pain intensity (range, 0 [no pain] to 10 [pain as bad as you can imagine]). Secondary outcomes included opioid use, spine surgery, and crossover rates. At 12 months, both treatment groups maintained initial observed improvements, with no significant differences between groups on the RDQ (adjusted mean difference, -0.4; 95% confidence interval [CI], -1.6 to 0.9; P=.55), leg pain (adjusted mean difference, 0.1; 95% CI, -0.5 to 0.7; P=.75), opioid use (corticosteroid plus lidocaine: 41.4% vs lidocaine alone: 36.3%; P=.41), or spine surgery (corticosteroid plus lidocaine: 16.8% vs lidocaine alone: 11.8%; P=.22). Fewer participants randomized to corticosteroid plus lidocaine (30%, n=60) versus lidocaine alone (45%, n=90) crossed over after 6 weeks (P=.003). Among participants who crossed over at 6 weeks, the 6- to 12-week RDQ change did not differ between the 2 randomized treatment groups (adjusted mean difference, -1.0; 95% CI, -2.6 to 0.7; P=.24). In both groups, participants crossing over at 6 weeks had worse 12-month trajectories compared with participants who did not choose to crossover. For lumbar spinal stenosis symptoms, epidural injections of corticosteroid plus lidocaine offered no benefits from 6 weeks to 12 months beyond that of injections of lidocaine alone in terms of self-reported pain and function or reduction in use of opioids and spine surgery. In patients with improved pain and function 6 weeks after initial injection, these outcomes were maintained at 12 months. However, the trajectories of pain and function outcomes after 3 weeks did not differ by injectate type. Repeated injections of either type offered no additional long-term benefit if injections in the first 6 weeks did not improve pain.
Authors: Friedly JL; Avins AL; Jarvik JG; et al.
Arch Phys Med Rehabil. 2017 Aug;98(8):1499-1507.e2. Epub 2017-04-08.
Smoking Status and Opioid Related Problems and Concerns among Men and Women on Chronic Opioid Therapy
Smokers on chronic opioid therapy (COT) for noncancer pain use prescription opioids at higher dosages and are at increased risk for opioid misuse and dependence relative to nonsmokers. The current study aims to assess whether smoking is associated with problems and concerns with COT from the perspective of the patient. In a large sample (N=972) of adult patients prescribed opioids for chronic noncancer pain, we examined sex-specific associations between smoking status and patient perceptions of problems and concerns with COT using regression analyses, adjusting for covariates. The sample self-identified as 27% current smokers, 44% former smokers, and 29% never smokers. Current smoking (vs. never smoking) was associated with increased odds of an opioid use disorder among males and females, and higher daily opioid dose among males only. Current and former smokers reported significantly fewer problems with opioids relative to never smokers, and this was driven primarily by lower endorsement of problems that are affected by the stimulant properties of nicotine (eg, difficulties thinking clearly, felt less alert or sleepy). This study contributes to an understanding of perceived problems and concerns with COT among current, former, and never smokers with chronic noncancer pain. Results suggest that current and former smokers may be a difficult population to target to decrease COT, given that they perceive fewer problems with prescription opioid use, despite higher odds of having an opioid use disorder (males and females) and greater opioid doses (males only).
Authors: Young-Wolff KC; Klebaner D; Weisner C; Von Korff M; Campbell CI
Clin J Pain. 2017 Aug;33(8):730-737.
Abuse liability of intravenous buprenorphine vs. buprenorphine/naloxone: Importance of absolute naloxone amount.
BACKGROUND: This study sought to determine the relative importance of a range of Bup/Nx doses compared to Bup alone in producing subjective and reinforcing effects.METHODS: Heroin-using volunteers (n=13) were transitioned onto daily oral hydromorphone (40mg). Laboratory sessions assessed the reinforcing and subjective effects of intravenous (IV) doses of Bup (1.51, 2.16, 6.15, and 8.64mg) and Bup/Nx (1.51/0.44, 2.16/0.61, 6.15/1.71, and 8.64/2.44mg). Placebo (Pbo), heroin (25mg) and Nx (0.3mg) were tested as neutral, positive, and negative controls, respectively.RESULTS: IV Bup alone was self-administered substantially less than IV heroin, though the two largest doses of Bup produced positive subjective effects, drug "Liking" (0-100mm), which were comparable to heroin (mean difference: Heroin vs Bup 6.15mg: -3.4mm, Heroin vs Bup 8.64mg: -11.3mm). All indicators of abuse potential seen with IV Bup alone were substantially decreased with the addition of Nx. All Bup/Nx combinations produced ratings of aversive effects, "Bad", which were comparable to, or greater than IV, Nx. On three of the four measures of aversive effects, the largest difference is seen with the 8.64 vs 8.64/2.44 condition.CONCLUSIONS: This study further demonstrates the ability of the Bup/Nx combination to deter IV use. Although none of the Bup/Nx combinations showed indications of abuse potential, formulations with larger absolute Nx, may be less abusable as they precipitate a greater degree of withdrawal.
Authors: Jones, Jermaine D JD; Manubay, Jeanne M JM; Mogali, Shanthi S; Metz, Verena E VE; Madera, Gabriela G; Martinez, Suky S; Mumtaz, Mudassir M; Comer, Sandra D SD
Drug and alcohol dependence. 2017 10 01;179(5):362-369. Epub 2017-07-26.
Two Genetic Loci associated with Medial Collateral Ligament Injury
Medial collateral ligament (MCL) injuries are a common knee injury, especially in competitive athletes. Identifying genetic loci associated with MCL injury could shed light on its etiology. A genome-wide association screen was performed using data from the Research Program in Genes, Environment and Health (RPGEH) including 1 572 cases of MCL injury and 100 931 controls. 2 SNPs (rs80351309 and rs6083471) showed an association with MCL injury at genome-wide significance (p<5×10-8) with moderate effects (odds ratios=2.12 and 1.57, respectively). For rs80351309, the genotypes were imputed with only moderate accuracy, so this SNP should be viewed with caution until its association with MCL injury can be validated. The SNPs rs80351309 and rs6083471 show a statistically significant association with MCL injury. It will be important to replicate this finding in future studies.
Authors: Roos AK; Avins AL; Ahmed MA; Kleimeyer JP; Roos TR; Fredericson M; Ioannidis JPA; Dragoo JL; Kim S
Int J Sports Med. 2017 Jul;38(7):501-507. Epub 2017-05-08.
A Genetic Marker Associated with Shoulder Dislocation
Shoulder dislocations are common shoulder injuries associated with athletic activity in contact sports, such as football, rugby, wrestling, and hockey. Identifying genetic loci associated with shoulder dislocation could shed light on underlying mechanisms for injury and identify predictive genetic markers. To identify DNA polymorphisms associated with shoulder dislocation, a genome-wide association screen was performed using publically available data from the Research Program in Genes, Environment and Health including 662 cases of shoulder dislocation and 82 602 controls from the European ancestry group. rs12913965 showed an association with shoulder dislocation at genome-wide significance (p=9.7×10-9; odds ratio=1.6) from the European ancestry group. Individuals carrying one copy of the risk allele (T) at rs12913965 showed a 69% increased risk for shoulder dislocation in our cohort. rs12913965 is located within an intron of the TICRR gene, which encodes TOPBP1 interacting checkpoint and replication regulator involved in the cell cycle. rs12913965 is also associated with changes in expression of the ISG20 gene, which encodes an antiviral nuclease induced by interferons. This genetic marker may one day be used to identify athletes with a higher genetic risk for shoulder dislocation. It will be important to replicate this finding in future studies.
Authors: Kim S; Kleimeyer JP; Ahmed MA; Avins AL; Fredericson M; Dragoo JL; Ioannidis JPA
Int J Sports Med. 2017 Jul;38(7):508-514. Epub 2017-05-18.
Maternal serum cytokine levels and risk of bipolar disorder
Prenatal exposure to influenza has previously been associated with increased risk of bipolar disorder (BD), an association that may be mediated by maternal cytokines. The objective of this study was to determine the association between maternal levels of cytokines measured during each trimester of pregnancy and the risk of BD in offspring. We conducted a case-control study nested in the Child Health and Development Study, a birth cohort that enrolled pregnant women in 1959-1966. Potential cases with DSM-IV-TR bipolar I disorder, bipolar II disorder, BD not otherwise specified, and BD with psychotic features were ascertained through electronic medical records, a public agency database, and a mailing to the cohort. Diagnoses were confirmed by clinical interview. Nine cytokines (IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-γ, TNF-α and GM-CSF) were measured simultaneously by Luminex assays in archived prenatal maternal serum samples from 85 cases and 170 matched controls. Data were analyzed using conditional logistic regression. In the overall study sample, there were no significant associations between prenatal maternal cytokine levels and BD after adjustment for confounders. The risk of BD without psychotic features was decreased among subjects with higher maternal levels of first trimester log-transformed IL-4 (OR (95% CI)=0.76 (0.58, 0.98); p=0.04) and third trimester log-transformed IL-6 (OR (95% CI)=0.64 (0.42, 0.98); p=0.04). In conclusion, higher levels of prenatal maternal cytokines were not associated with increased risk for BD. Further studies with larger samples are necessary to confirm the finding.
Authors: Cheslack-Postava K; Cremers S; Bao Y; Shen L; Schaefer CA; Brown AS
Brain Behav Immun. 2017 Jul;63:108-114. Epub 2016-07-29.
Heterogeneity in 14-year Dementia Incidence Between Asian American Subgroups
Asian Americans are a rapidly growing and diverse population. Prior research on dementia among Asian Americans focused on Japanese Americans or Asian Americans overall, although marked differences in cardiometabolic conditions between subgroups have been documented. We compared dementia incidence among 4 Asian American subgroups (n=8384 Chinese; n=4478 Japanese; n=6210 Filipino; n=197 South Asian) and whites (n=206,490) who were Kaiser Permanente Northern California members aged 64 years and above with no dementia diagnoses as of January 1, 2000. Dementia diagnoses were collected from medical records January 1, 2000 to December 31, 2013. Baseline medical utilization and comorbidities (diabetes, depression, hypertension, stroke, cardiovascular disease) were abstracted from medical records January 1, 1996 to December 31, 1999. We calculated age-standardized dementia incidence rates and Cox models adjusted for age, sex, medical utilization, and comorbidities. Mean baseline age was 71.7 years; mean follow-up was 9.6 years. Age-standardized dementia incidence rates were higher among whites than “All Asian-Americans” or any subgroup. Compared with Chinese (13.7/1000 person-years), dementia incidence was slightly higher among Japanese [14.8/1000 person-years; covariate-adjusted hazard ratio (adjusted-HR)=1.08; 95% confidence interval (CI), 0.99-1.18] and Filipinos (17.3/1000 person-years; adjusted-HR=1.20; 95% CI, 1.11-1.31), and lower among South Asians (12.1/1000 person-years; adjusted-HR=0.81; 95% CI, 0.53-1.25). Future studies are needed to understand how immigration history, social, environmental, and genetic factors contribute to dementia risk in the growing and diverse Asian American population.
Authors: Mayeda ER; Glymour MM; Quesenberry CP; Whitmer RA
Alzheimer Dis Assoc Disord. 2017 Jul-Sep;31(3):181-186.
Cross-Sectional and Longitudinal Associations of Chronic Posttraumatic Stress Disorder With Inflammatory and Endothelial Function Markers in Women
BACKGROUND: Posttraumatic stress disorder (PTSD) may contribute to heightened cardiovascular disease risk by promoting a proinflammatory state and impaired endothelial function. Previous research has demonstrated associations of PTSD with inflammatory and endothelial function biomarkers, but most work has been cross-sectional and does not separate the effects of trauma exposure from those of PTSD.METHODS: We investigated associations of trauma exposure and chronic PTSD with biomarkers of inflammation (C-reactive protein and tumor necrosis factor alpha receptor II) and endothelial function (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) in 524 middle-aged women in the Nurses’ Health Study II. Using linear mixed models, we examined associations of trauma/PTSD status with biomarkers measured twice, 10 to 16 years apart, in cardiovascular disease-free women, considering either average levels over time (cross-sectional) or change in levels over time (longitudinal). Biomarker levels were log-transformed. Trauma/PTSD status (based on structured diagnostic interviews) was defined as no trauma at either blood draw (n = 175), trauma at blood draw 1 but no PTSD at either draw (n = 175), and PTSD that persisted beyond blood draw 1 (chronic PTSD; n = 174). The reference group was women without trauma.RESULTS: In models adjusted for known potential confounders, women with chronic PTSD had higher average C-reactive protein (B = 0.27, p < .05), tumor necrosis factor alpha receptor II (B = 0.07, p < .01), and intercellular adhesion molecule-1 (B = 0.04, p < .05) levels. Women with trauma but without PTSD had higher average tumor necrosis factor alpha receptor II levels (B = 0.05, p < .05). In addition, women with chronic PTSD had a greater increase in vascular cell adhesion molecule-1 over time (B = 0.003, p < .05).CONCLUSIONS: Increased inflammation and impaired endothelial function may be pathways by which chronic PTSD increases cardiovascular disease risk.
Authors: Sumner, Jennifer A JA; Chen, Qixuan Q; Roberts, Andrea L AL; Winning, Ashley A; Rimm, Eric B EB; Gilsanz, Paola P; Glymour, M Maria MM; Tworoger, Shelley S SS; Koenen, Karestan C KC; Kubzansky, Laura D LD
Biological psychiatry. 2017 Dec 15;82(12):875-884. Epub 2017-06-27.
Predictors of Persistent Disability and Back Pain in Older Adults with a New Episode of Care for Back Pain
To identify predictors of persistent disability and back pain in older adults. Prospective cohort study. Back pain outcomes using longitudinal data registry. Five thousand two hundred twenty adults age 65 years and older with a new primary care visit for back pain. Baseline measurements included: demographics, health, and back pain characteristics. We abstracted imaging findings from 348 radiology reports. The primary outcomes were the Roland-Morris Disability Questionnaire (RMDQ) and back pain intensity. We defined persistent disability as RMDQ of 4/24 or higher at both six and 12 months and persistent back pain as pain 3/10 or higher at both six and 12 months. There were 2,498 of 4,143 (60.3%) participants with persistent disability, and 2,099 of 4,144 (50.7%) had persistent back pain. Adjusted analyses showed the following characteristics most strongly predictive of persistent disability and persistent back pain: sex, race, worse baseline clinical characteristics of back pain, leg pain, back-related disability and duration of symptoms, smoking, anxiety symptoms, depressive symptoms, a history of falls, greater number of comorbidities, knee osteoarthritis, wide-spread pain syndromes, and an index diagnosis of lumbar spinal stenosis. Within the imaging data subset, central spinal stenosis was not associated with disability or pain. We found that many predictors in older adults were similar to those for younger populations.
Authors: Rundell SD; Sherman KJ; Heagerty PJ; Mock CN; Dettori NJ; Comstock BA; Avins AL; Nedeljkovic SS; Nerenz DR; Jarvik JG
Pain Med. 2017 Jun 01;18(6):1049-1062.
Alcohol brief intervention in primary care: Blood pressure outcomes in hypertensive patients
In clinical trials alcohol brief intervention (BI) in adult primary care has been efficacious in reducing alcohol consumption, but we know little about its impact on health outcomes. Hypertension is a prevalent and costly chronic condition in the U.S. and worldwide, and alcohol use is a modifiable hypertension risk factor. To evaluate the effect of receiving BI for unhealthy drinking on blood pressure (BP) control among adult hypertensive patients by analyzing secondary data from a clustered, randomized controlled trial on alcohol screening, brief intervention and referral to treatment (SBIRT) implementation by primary care physicians (PCP intervention arm) and non-physician providers and medical assistants (NPP&MA intervention arm) in a large, integrated health care delivery system. Observational, prospective cohort study. 3811 adult hypertensive primary care patients screening positive for past-year heavy drinking at baseline, of which 1422 (37%) had an electronic health record BP measure at baseline and 18-month follow-up. Change in BP and controlled BP (systolic/diastolic BP <140/90mmHg). Overall no significant associations were found between alcohol BI and BP change at 18-month follow-up when analyzing the combined sample of subjects in both intervention arms. However, moderation analyses found that receiving BI for positive past-year unhealthy drinking was positively associated with better BP control at 18months in the PCP intervention arm, and for those with lower heavy drinking frequency and poor BP control at the index screening. Our findings suggest that hypertensive patients may benefit from receiving physician brief intervention for unhealthy alcohol use in primary care. Findings also highlight potential population-level benefits of alcohol BI if widely applied, suggesting a need for the development of innovative strategies to facilitate SBIRT delivery in primary care settings.
Authors: Chi FW; Weisner CM; Mertens JR; Ross TB; Sterling SA
J Subst Abuse Treat. 2017 Jun;77:45-51. Epub 2017-03-22.
Prescription opioid registry protocol in an integrated health system
To establish a prescription opioid registry protocol in a large health system and to describe algorithms to characterize individuals using prescription opioids, opioid use episodes, and concurrent use of sedative/hypnotics. Protocol development and retrospective cohort study. Using Kaiser Permanente Northern California (KPNC) electronic health record data, we selected patients using prescription opioids in 2011. Opioid and sedative/hypnotic fills, and physical and psychiatric comorbidity diagnoses, were extracted for years 2008 to 2014. Algorithms were developed to identify each patient’s daily opioid and sedative/hypnotic use, and morphine daily-dose equivalent. Opioid episodes were classified as long-term, episodic, or acute. Logistic regression was used to predict characteristics associated with becoming a long-term opioid user. In 2011, 18% of KPNC adult members filled at least 1 opioid prescription. Among those patients, 25% used opioids long term and their average duration of use was more than 4 years. Sedative/hypnotics were used by 76% of long-term users. Being older, white, living in a more deprived neighborhood, having a chronic pain diagnosis, and use of sedative/hypnotics were predictors of initiating long-term opioid use. This study established a population-based opioid registry that is flexible and can be used to address important questions of prescription opioid use. It will be used in future studies to answer a broad range of other critical public health issues relating to prescription opioid use.
Authors: Ray GT; Bahorik AL; VanVeldhuisen PC; Weisner CM; Rubinstein AL; Campbell CI
Am J Manag Care. 2017 May 01;23(5):e146-e155. Epub 2017-05-01.
The high price of depression: Family members’ health conditions and health care costs
To compare the health conditions and health care costs of family members of patients diagnosed with a Major Depressive Disorder (MDD) to family members of patients without an MDD diagnosis. Using electronic health record data, we identified family members (n=201,914) of adult index patients (n=92,399) diagnosed with MDD between 2009 and 2014 and family members (n=187,011) of matched patients without MDD. Diagnoses, health care utilization and costs were extracted for each family member. Logistic regression and multivariate models were used to compare diagnosed health conditions, health services cost, and utilization of MDD and non-MDD family members. Analyses covered the 5years before and after the index patient’s MDD diagnosis. MDD family members were more likely than non-MDD family members to be diagnosed with mood disorders, anxiety, substance use disorder, and numerous other conditions. MDD family members had higher health care costs than non-MDD family members in every period analyzed, with the highest difference being in the year before the index patient’s MDD diagnosis. Family members of patients with MDD are more likely to have a number of health conditions compared to non-MDD family members, and to have higher health care cost and utilization.
Authors: Ray GT; Weisner CM; Taillac CJ; Campbell CI
Gen Hosp Psychiatry. 2017 05;46:79-87. Epub 2017-04-08.
Association of the Affordable Care Act With Smoking and Tobacco Treatment Utilization Among Adults Newly Enrolled in Health Care
To examine rates of smoking and tobacco treatment utilization by insurance coverage status (Medicaid, commercial, exchange) among newly enrolled patients in the post Affordable Care Act (ACA) era. We examined new members who enrolled in Kaiser Permanente Northern California through Medicaid, the California exchange, or nonexchange commercial plans (N=122,298) in the first 6 months of 2014 following ACA implementation. We compared these groups on smoking prevalence and tested whether smokers in each group differed on sociodemographic characteristics and in their utilization of tobacco treatment (pharmacotherapy and counseling) in 2014. Smoking prevalence was higher among Medicaid (22%) than exchange (13%) or commercial (12%) patients (P<0.0001). Controlling for key sociodemographic and clinical characteristics, Medicaid (odds ratio, 1.49; 95% confidence interval, 1.29-1.73) smokers had greater odds of tobacco treatment use than commercial smokers. Other groups at risk for underuse included men, younger patients, Asians, and Latinos. In this cohort of newly enrolled patients after ACA implementation, Medicaid patients were more likely to be smokers compared with exchange and commercial patients, but they were also more likely to use tobacco treatment. Low tobacco treatment use among exchange and commercial plan smokers, as well as younger men, Asians and Latinos poses a significant obstacle to improving public health and additional targeted outreach strategies may be needed to engage these patients with available health services.
Authors: Young-Wolff KC; Klebaner D; Campbell CI; Weisner C; Satre DD; Adams AS
Med Care. 2017 May;55(5):535-541.
Assessing the accuracy of opioid overdose and poisoning codes in diagnostic information from electronic health records, claims data, and death records
The purpose of this study is to assess positive predictive value (PPV), relative to medical chart review, of International Classification of Diseases (ICD)-9/10 diagnostic codes for identifying opioid overdoses and poisonings. Data were obtained from Kaiser Permanente Northwest and Northern California. Diagnostic data from electronic health records, submitted claims, and state death records from Oregon, Washington, and California were linked. Individual opioid-related poisoning codes (e.g., 965.xx and X42), and adverse effects of opioids codes (e.g., E935.xx) combined with diagnoses possibly indicative of overdoses (e.g., respiratory depression), were evaluated by comparison with chart audits. Opioid adverse effects codes had low PPV to detect overdoses (13.4%) as assessed in 127 charts and were not pursued. Instead, opioid poisoning codes were assessed in 2100 individuals who had those codes present in electronic health records in the period between the years 2008 and 2012. Of these, 10/2100 had no available information and 241/2100 were excluded potentially as anesthesia-related. Among the 1849 remaining individuals with opioid poisoning codes, 1495 events were accurately identified as opioid overdoses; 69 were miscodes or misidentified, and 285 were opioid adverse effects, not overdoses. Thus, PPV was 81%. Opioid adverse effects or overdoses were accurately identified in 1780 of 1849 events (96.3%). Opioid poisoning codes have a predictive value of 81% to identify opioid overdoses, suggesting ICD opioid poisoning codes can be used to monitor overdose rates and evaluate interventions to reduce overdose. Further research to assess sensitivity, specificity, and negative predictive value are ongoing. Copyright © 2017 John Wiley & Sons, Ltd.
Authors: Green CA; Perrin NA; Janoff SL; Campbell CI; Chilcoat HD; Coplan PM
Pharmacoepidemiol Drug Saf. 2017 May;26(5):509-517. Epub 2017-01-10.
Socioeconomic differences in adolescent substance abuse treatment participation and long-term outcomes
Socioeconomic status (SES) has been consistently linked to poorer access, utilization and outcomes of health care services, but this relationship has been understudied in adolescent substance abuse treatment research. This study examined SES differences in adolescent’s treatment participation and long-term outcomes of abstinence and 12-step attendance over five years after treatment. Data are from 358 adolescents (ages 13-18) who were recruited at intake to substance abuse treatment between 2000 and 2002 at four Kaiser Permanente Northern California outpatient treatment programs. Follow-up interviews of adolescents and their parents were conducted at 1, 3, and 5years, with over 80% response rates across time points. Using parent SES as a proxy for adolescent SES, no socioeconomic differences were found in treatment initiation, treatment retention, or long-term abstinence from alcohol or drugs. Parent education, but not parent income, was significantly associated with 12-step attendance post-treatment such that adolescents with higher parent education were more likely to attend than those with lower parent education. Findings suggest a lack of socioeconomic disparities in substance abuse treatment participation in adolescence, but potential disparities in post-treatment 12-step attendance during the transition from adolescence to young adulthood.
Authors: Lui CK; Sterling SA; Chi FW; Lu Y; Campbell CI
Addict Behav. 2017 May;68:45-51. Epub 2017-01-06.
Evidence for a causal relationship between low vitamin D, high BMI, and pediatric-onset MS
To utilize Mendelian randomization to estimate the causal association between low serum vitamin D concentrations, increased body mass index (BMI), and pediatric-onset multiple sclerosis (MS) using genetic risk scores (GRS). We constructed an instrumental variable for vitamin D (vitD GRS) by computing a GRS for 3 genetic variants associated with levels of 25(OH)D in serum using the estimated effect of each risk variant. A BMI GRS was also created that incorporates the cumulative effect of 97 variants associated with BMI. Participants included non-Hispanic white individuals recruited from over 15 sites across the United States (n = 394 cases, 10,875 controls) and Sweden (n = 175 cases, 5,376 controls; total n = 16,820). Meta-analysis findings demonstrated that a vitD GRS associated with increasing levels of 25(OH)D in serum decreased the odds of pediatric-onset MS (odds ratio [OR] 0.72, 95% confidence interval [CI] 0.55, 0.94; p = 0.02) after controlling for sex, genetic ancestry, HLA-DRB1*15:01, and over 100 non-human leukocyte antigen MS risk variants. A significant association between BMI GRS and pediatric disease onset was also demonstrated (OR 1.17, 95% CI 1.05, 1.30; p = 0.01) after adjusting for covariates. Estimates for each GRS were unchanged when considered together in a multivariable model. We provide evidence supporting independent and causal effects of decreased vitamin D levels and increased BMI on susceptibility to pediatric-onset MS.
Authors: Gianfrancesco MA; Barcellos LF; Waubant E; Network of Pediatric Multiple Sclerosis Centers; et al.
Neurology. 2017 Apr 25;88(17):1623-1629. Epub 2017-03-29.
A Digital Tool to Promote Alcohol and Drug Use Screening, Brief Intervention, and Referral to Treatment Skill Translation: A Mobile App Development and Randomized Controlled Trial Protocol
Translation of knowledge and skills from classroom settings to clinical practice is a major challenge in healthcare training, especially for behavioral interventions. For example, screening, brief intervention, and referral to treatment (SBIRT) is a highly-promoted approach to identifying and treating individuals at risk for alcohol or drug problems, yet effective, routine use of SBIRT has lagged. The objective of this paper is to describe the development, pilot testing, and trial protocol of a mobile app based on the theory of planned behavior (TPB) to promote SBIRT skill translation and application. Intended for use after classroom training occurs, the mobile app has three primary functions designed to increase behavioral intent to deliver SBIRT: (1) review skills (ie, address knowledge and beliefs about SBIRT), (2) apply skills with patients (ie, build confidence and perceived behavioral control), and (3) report performance data (ie, increase accountability and social norms and/or influence). The app includes depression and anxiety screening tools due to high comorbidity with substance use. A randomized controlled trial (RCT) is in progress among health and social service learners (N=200) recruited from 3 universities and 6 different training programs in nursing, social work, internal medicine, psychiatry, and psychology. Participants are randomized to SBIRT classroom instruction alone or classroom instruction plus app access prior to beginning their field placement rotations. TPB-based data are collected via Qualtrics or via the mobile app pre-post and SBIRT utilization, weekly for 10 weeks. Key outcomes include the frequency of and self-reported confidence in delivery of SBIRT. Beta testing with advanced practice nursing students (N=22) indicated that the app and its associated assessment tools were acceptable and useful. The system usability scale (SUS) mean was 65.8 (n=19), which indicated that the SBIRT app was acceptable but could benefit from improvement. Indeed, modifications were implemented prior to starting the trial. Enrollment of trial participants began in September 2016. Results are expected by December 2017. This report describes the process of TPB-based app development and testing, and the protocol for a RCT to determine the effectiveness of the app in enhancing skill translation. If effective, this approach could improve SBIRT implementation, fidelity, and clinical outcomes.
Authors: Satre DD; Ly K; Wamsley M; Curtis A; Satterfield J
JMIR Res Protoc. 2017 Apr 18;6(4):e55. Epub 2017-04-18.
Patterns of marijuana use among psychiatry patients with depression and its impact on recovery
Depression is associated with substance-related problems that worsen depression-related disability. Marijuana is frequently used by those with depression, yet whether its use contributes to significant barriers to recovery in this population has been understudied. Participants were 307 psychiatry outpatients with depression; assessed at baseline, 3-, and 6-months on symptom (PHQ-9 and GAD-7), functioning (SF-12) and past-month marijuana use for a substance use intervention trial. Longitudinal growth models examined patterns and predictors of marijuana use and its impact on symptom and functional outcomes. A considerable number of (40.7%; n=125) patients used marijuana within 30-days of baseline. Over 6-months, marijuana use decreased (B=-1.20, p<.001), but patterns varied by demographic and clinical characteristics. Depression (B=0.03, p<.001) symptoms contributed to increased marijuana use over the follow-up, and those aged 50+(B=0.44, p<.001) increased their marijuana use compared to the youngest age group. Marijuana use worsened depression (B=1.24, p<.001) and anxiety (B=0.80, p=.025) symptoms; marijuana use led to poorer mental health (B=-2.03, p=.010) functioning. Medical marijuana (26.8%; n=33) was associated with poorer physical health (B=-3.35, p=.044) functioning. Participants were psychiatry outpatients, limiting generalizability. Marijuana use is common and associated with poor recovery among psychiatry outpatients with depression. Assessing for marijuana use and considering its use in light of its impact on depression recovery may help improve outcomes.
Authors: Bahorik AL; Leibowitz A; Sterling SA; Travis A; Weisner C; Satre DD
J Affect Disord. 2017 Apr 15;213:168-171. Epub 2017-02-14.
Smoke-Free Laws and Hazardous Drinking: A Cross-Sectional Study among U.S. Adults
Tobacco and alcohol use are strongly associated. This cross-sectional study examined the relationship of smoke-free law coverage and smoke-free bar law coverage with hazardous drinking behaviors among a representative sample of U.S. adult drinkers (n= 17,057). We merged 2009 National Health Interview Survey data, American Nonsmokers’ Rights Foundation U.S. Tobacco Control Laws Database, and Census Population Estimates. Hazardous drinking outcomes included heavy drinking (>14 drinks/week for men; >7 drinks/week for women) and binge drinking (≥5 drinks on one or more days during past year). Chi-square tests compared hazardous drinking by sociodemographic factors. Multivariable logistic regression models were used to examine if smoke-free law and bar law coverages were associated with hazardous drinking, controlling for sociodemographics and smoking status. Subset analyses were conducted among drinkers who also smoked (n= 4074) to assess the association between law coverages and hazardous drinking. Among all drinkers, smoke-free law coverage was not associated with heavy drinking (adjusted odds ratio (AOR) = 1.22, 95% confidence interval (CI) = 0.99-1.50) or binge drinking (AOR = 1.09, 95% CI = 0.93-1.26). Smoke-free bar law coverage was also found to be unrelated to hazardous drinking. Similar results were found among those drinkers who smoked. Findings suggest that smoke-free laws and bar laws are not associated with elevated risk for alcohol-related health issues.
Authors: Jiang N; Gonzalez M; Ling PM; Young-Wolff KC; Glantz SA
Int J Environ Res Public Health. 2017 04 13;14(4). Epub 2017-04-13.
Effects of Ibudilast on the Subjective, Reinforcing, and Analgesic Effects of Oxycodone in Recently Detoxified Adults with Opioid Dependence.
Ibudilast, a nonselective phosphodiesterase inhibitor, is used clinically in Asia for the treatment of asthma and poststroke dizziness. Recent preclinical studies have suggested that it also inhibits glial cell activation in rodents, and may alter opioid-mediated effects, including analgesia and withdrawal symptoms. The effects of ibudilast on the abuse potential of opioids in humans are largely unknown. The present study was designed to examine the influence of ibudilast on subjective (including drug craving), reinforcing, and analgesic effects of oxycodone in human volunteers diagnosed with opioid dependence (equivalent to moderate-severe opioid use disorder). Non-treatment-seeking opioid-dependent male volunteers (n=11) underwent an in-patient detoxification with morphine, followed by maintenance on placebo (0 mg b.i.d.) and active ibudilast (50 mg b.i.d.). Under each maintenance dose, six experimental sample and choice sessions were completed involving oral oxycodone administration (0, 15, and 30 mg/70 kg, p.o.). Subjective effects of oxycodone and drug craving were measured with visual analog scales (VAS) and a Drug Effects Questionnaire. The cold pressor test was used to produce pain, and a modified progressive-ratio choice procedure was used to measure the reinforcing effects of oxycodone. Under the active ibudilast condition compared with the placebo condition, ratings of drug liking following 15 mg of oxycodone were decreased significantly. The mean drug breakpoint value was also significantly lower in the active vs the placebo ibudilast condition under the 15 mg oxycodone condition, but not significantly lower under the 30 mg oxycodone condition. Heroin craving was significantly reduced under active ibudilast vs placebo, and similar effects were observed for tobacco and cocaine craving. Furthermore, mean subjective ratings of pain were lower in the active ibudilast condition. Our data suggest that ibudilast may be useful for treating opioid use disorders and it may enhance the analgesic effects of oxycodone.
Authors: Metz, Verena E VE; Jones, Jermaine D JD; Manubay, Jeanne J; Sullivan, Maria A MA; Mogali, Shanthi S; Segoshi, Andrew A; Madera, Gabriela G; Johnson, Kirk W KW; Comer, Sandra D SD
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2017 Aug 01;42(9):1825-1832. Epub 2017-04-10.
Posttraumatic stress disorder and accelerated aging: PTSD and leukocyte telomere length in a sample of civilian women
BACKGROUND: Studies in male combat veterans have suggested posttraumatic stress disorder (PTSD) is associated with shorter telomere length (TL). We examined the cross-sectional association of PTSD with TL in women exposed to traumas common in civilian life.METHODS: Data are from a substudy of the Nurses’ Health Study II (N = 116). PTSD and subclinical PTSD were assessed in trauma-exposed women using diagnostic interviews. An array of health behaviors and conditions were assessed. DNA was extracted from peripheral blood leukocytes (collected 1996-1999). Telomere repeat copy number to single gene copy number (T/S) was determined by quantitative real-time PCR telomere assay. We used linear regression models to assess associations and examine whether a range of important health behaviors (e.g., cigarette smoking) and medical conditions (e.g., hypertension) previously associated with TL might explain a PTSD-TL association. We further examined whether type of trauma exposure (e.g., interpersonal violence) was associated with TL and whether trauma type might explain a PTSD-TL association.RESULTS: Relative to not having PTSD, women with a PTSD diagnosis had shorter log-transformed TL (β = -.112, 95% confidence interval (CI) = -0.196, -0.028). Adjustment for health behaviors and medical conditions did not attenuate this association. Trauma type was not associated with TL and did not account for the association of PTSD with TL.CONCLUSIONS: Our results add to growing evidence that PTSD may be associated with more rapid cellular aging as measured by telomere erosion. Moreover, the association could not be explained by health behaviors and medical conditions assessed in this study, nor by type of trauma exposure.
Authors: Roberts, Andrea L AL; Koenen, Karestan C KC; Chen, Qixuan Q; Gilsanz, Paola P; Mason, Susan M SM; Prescott, Jennifer J; Ratanatharathorn, Andrew A; Rimm, Eric B EB; Sumner, Jennifer A JA; Winning, Ashley A; De Vivo, Immaculata I; Kubzansky, Laura D LD
Depression and anxiety. 2017 05 ;34(5):391-400. Epub 2017-04-05.
Motivation deficits and use of alcohol and illicit drugs among individuals with schizophrenia
This study examined the impact of substance use on intrinsic motivation and evaluated the association between intrinsic motivation and substance use recovery among individuals with schizophrenia. Alcohol and illicit drug use and intrinsic motivation were evaluated at baseline and 6-months for 1434 individuals with schizophrenia from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) using self-rated substance use assessments and a derived motivation measure from the Heinrichs-Carpenter Quality of Life Scale. Results revealed patients had moderate motivation deficits overall and a considerable number were using alcohol or illicit drugs at baseline (n=576; 40.2%). Regression models at baseline showed patients with low levels of motivation had higher odds of substance use and those who were using substances had greater motivation deficits. At 6-months, substance using patients continued to demonstrate greater motivation deficits; however, those with high levels of motivation exhibited a greater reduction in their use of substances. Findings remained significant after adjusting for clinical confounds and were consistent across any substance, alcohol, and cannabis use. Our results emphasize concerns about substance use compounding motivation deficits in schizophrenia, and suggest that disentangling the motivation-substance use relationship in schizophrenia may facilitate efforts aimed at ameliorating these challenges and improving outcomes.
Authors: Bahorik AL; Greeno CG; Cochran G; Cornelius JR; Eack SM
Psychiatry Res. 2017 Apr 05;253:391-397. Epub 2017-04-05.
Buprenorphine Treatment and Patient Use of Health Services after the Affordable Care Act in an Integrated Health Care System
The Affordable Care Act (ACA) was expected to benefit patients with substance use disorders, including opioid use disorders (OUDs). This study examined buprenorphine use and health services utilization by patients with OUDs pre- and post-ACA in a large health care system. Using electronic health record data, we examined demographic and clinical characteristics (substance use, psychiatric and medical conditions) of two patient cohorts using buprenorphine: those newly enrolled in 2012 (“pre-ACA,” N = 204) and in 2014 (“post-ACA,” N = 258). Logistic and negative binomial regressions were used to model persistent buprenorphine use, and to examine whether persistent use was related to health services utilization. Buprenorphine patients were largely similar pre- and post-ACA, although more post-ACA patients had a marijuana use disorder (p < .01). Post-ACA patients were more likely to have high-deductible benefit plans (p < .01). Use of psychiatry services was lower post-ACA (IRR: 0.56, p < .01), and high-deductible plans were also related to lower use of psychiatry services (IRR: 0.30, p < .01). The relationship between marijuana use disorder and prescription opioid use is complex, and deserves further study, particularly with increasingly widespread marijuana legalization. Access to psychiatry services may be more challenging for buprenorphine patients post-ACA, especially for patients with deductible plans.
Authors: Campbell CI; Parthasarathy S; Young-Wolff KC; Satre DD
J Psychoactive Drugs. 2017 Apr-Jun;49(2):160-168. Epub 2017-04-20.
Expectations and Attitudes of Individuals With Type 1 Diabetes After Using a Hybrid Closed Loop System.
Purpose The first hybrid closed loop (HCL) system, which automates insulin delivery but requires user inputs, was approved for treatment of type 1 diabetes (T1D) by the US Food and Drug Administration in September 2016. The purpose of this study was to explore the benefits, expectations, and attitudes of individuals with T1D following a clinical trial of an HCL system. Methods Thirty-two individuals with T1D (17 adults, 15 adolescents) participated in focus groups after 4 to 5 days of system use. Content analysis generated themes regarding perceived benefits, hassles, and limitations. Results Some participants felt misled by terms such as "closed loop" and "artificial pancreas," which seemed to imply a more "hands-off" experience. Perceived benefits were improved glycemic control, anticipated reduction of long-term complications, better quality of life, and reduced mental burden of diabetes. Hassles and limitations included unexpected tasks for the user, difficulties wearing the system, concerns about controlling highs, and being reminded of diabetes. Conclusion Users are willing to accept some hassles and limitations if they also perceive health and quality-of-life benefits beyond current self-management. It is important for clinicians to provide a balanced view of positives and negatives to help manage expectations.
Authors: Iturralde E; Tanenbaum ML; Hanes SJ; Suttiratana SC; Ambrosino JM; Ly TT; Maahs DM; Naranjo D; Walders-Abramson N; Weinzimer SA; Buckingham BA; Hood KK;
Diabetes Educ. 2017 Apr;43(2):223-232. doi: 10.1177/0145721717697244.
Smoking, Mental Illness, and Public Health
Tobacco use remains the leading preventable cause of death worldwide. In particular, people with mental illness are disproportionately affected with high smoking prevalence; they account for more than 200,000 of the 520,000 tobacco-attributable deaths in the United States annually and die on average 25 years prematurely. Our review aims to provide an update on smoking in the mentally ill. We review the determinants of tobacco use among smokers with mental illness, presented with regard to the public health HAVE framework of “the host” (e.g., tobacco user characteristics), the “agent” (e.g., nicotine product characteristics), the “vector” (e.g., tobacco industry), and the “environment” (e.g., smoking policies). Furthermore, we identify the significant health harms incurred and opportunities for prevention and intervention within a health care systems and larger health policy perspective. A comprehensive effort is warranted to achieve equity toward the 2025 Healthy People goal of reducing US adult tobacco use to 12%, with attention to all subgroups, including smokers with mental illness.
Authors: Prochaska JJ; Das S; Young-Wolff KC
Annu Rev Public Health. 2017 Mar 20;38:165-185. Epub 2016-12-16.
Post-traumatic Stress Disorder and 20-Year Physical Activity Trends Among Women
INTRODUCTION: Post-traumatic stress disorder (PTSD) may be associated with physical inactivity, a modifiable lifestyle factor that contributes to risk of cardiovascular and other chronic diseases; however, no study has evaluated the association between PTSD onset and subsequent physical activity (PA) changes.METHOD: Analyses were conducted between October 2014 and April 2016, using data from the ongoing Nurses’ Health Study II (N=50,327). Trauma exposure and PTSD symptoms were assessed using two previously validated measures, the Brief Trauma Questionnaire and Short Screening Scale for DSM-IV PTSD. Average PA (hours/week) was assessed using self-report measures at six time points across 20 years (1989-2009). Linear mixed models with time-updated PTSD assessed differences in PA trajectories by trauma/PTSD status. Among a subsample of women whose trauma/PTSD onset during follow-up, group differences in PA patterns before and after onset were assessed using linear spline models.RESULTS: PA decreased more steeply over time among trauma-exposed women reporting four or five (β= -2.5E-3, SE=1.0E-3, p=0.007) or six or seven PTSD symptoms (β= -6.7E-3, SE=1.1E-3, pCONCLUSIONS: Decreases in PA associated with PTSD symptoms may be a pathway through which PTSD influences cardiovascular and other chronic diseases.
Authors: Winning, Ashley A; Gilsanz, Paola P; Koenen, Karestan C KC; Roberts, Andrea L AL; Chen, Qixuan Q; Sumner, Jennifer A JA; Rimm, Eric B EB; Maria Glymour, M M; Kubzansky, Laura D LD
American journal of preventive medicine. 2017 Jun ;52(6):753-760. Epub 2017-03-18.
No evidence of compensatory drug use risk behavior among heroin users after receiving take-home naloxone.
INTRODUCTION: Some fear that distribution of naloxone to persons at risk of experiencing an opioid overdose may reduce the perceived negative consequences of drug use, leading to riskier patterns of use. This study assessed whether participation in naloxone/overdose training altered drug use frequency, quantity or severity among heroin users in and out of treatment.METHODS: Clinical interviews were performed assessing patterns of heroin and other drug use prior to, and at multiple timepoints after overdose education and naloxone training. This study compared baseline drug use to that at 1 and 3months post training.RESULTS: Both current heroin users (n=61) and former users in agonist maintenance (n=69) typically showed decreases in heroin and polydrug use at both 1 and 3months after training. The Addiction Severity Index drug composite score also decreased at follow up.CONCLUSIONS: This analysis found no evidence of compensatory drug use following naloxone/overdose training among two groups of heroin users. These findings support the acceptance and expansion of naloxone distribution to at-risk populations and may assist in allaying concerns about the potential for unintended negative consequences on drug use.
Authors: Jones, Jermaine D JD; Campbell, Aimee A; Metz, Verena E VE; Comer, Sandra D SD
Addictive behaviors. 2017 08 01;71(9):104-106. Epub 2017-03-09.
Cumulative receipt of an anti-poverty tax credit for families did not impact tobacco smoking among parents
The effect of anti-poverty tax credit interventions on tobacco consumption is unclear. Previous studies have estimated short-term effects, did not isolate the effects of cumulative dose of tax credits, produced conflicting results, and used methods with limited control for some time-varying confounders (e.g., those affected by prior treatment) and treatment regimen (i.e., study participants’ tax credit receipt pattern over time). We estimated the longer-term, cumulative effect of New Zealand’s Family Tax Credit (FTC) on tobacco consumption, using a natural experiment (administrative errors leading to exogenous variation in FTC receipt) and methods specifically for controlling confounding, reverse causation, and treatment regimen. We extracted seven waves (2002-2009) of the nationally representative Survey of Family, Income and Employment including 4404 working-age (18-65 years) parents in families. The exposure was the total numbers of years of receiving FTC. The outcomes were regular smoking and the average daily number of cigarettes usually smoked at wave 7. We estimated average treatment effects using inverse probability of treatment weighting and marginal structural modelling. Each additional year of receiving FTC affected neither the odds of regular tobacco smoking among all parents (odds ratio 1.02, 95% confidence interval 0.94-1.11), nor the number of cigarettes smoked among parents who smoked regularly (rate ratio 1.01, 95% confidence interval 0.99-1.03). We found no evidence for an association between the cumulative number of years of receiving an anti-poverty tax credit and tobacco smoking or consumption among parents. The assumptions of marginal structural modelling are quite demanding, and we therefore cannot rule out residual confounding. Nonetheless, our results suggest that tax credit programme participation will not increase tobacco consumption among poor parents, at least in this high-income country.
Authors: Pega, Frank F; Gilsanz, Paola P; Kawachi, Ichiro I; Wilson, Nick N; Blakely, Tony T
Social science & medicine (1982). 2017 04 ;179(5):160-165. Epub 2017-03-02.
Quantifying Worry in the Face of Uncertainty: Radiation Exposure from Medical Imaging
Background The degree to which people worry about radiation exposure from medical imaging has not been quantified. Such concern is important for clinical decision making and policy generation. Objective The aim of this study was to quantify the degree of worry as a consequence of radiation exposure. Design A time trade-off methodology was used to estimate health state utilities associated with radiation exposure from computed tomography scans in an inclusive sample of physicians. Health state utilities were elicited from in-person interviews using a software-guided, hypothetical scenario in which the subject is exposed to two separate computed tomography scans. Results One hundred and eighteen interviews were conducted. The overall mean and median utility values for the health state of concern due to radiation exposure were 0.95 (95% confidence interval: 0.94–0.96) and 0.98 (interquartile range: 0.91–1.00), respectively. The utility score distribution was highly skewed toward higher values. Five respondents (4.3%) recorded a utility score of ≤0.8 and 17 respondents (14.5%) were willing to sacrifice at least 5 or more years of life to live free of the radiation-exposure worry. Conclusions and relevance The physician respondents generally demonstrated low levels of disutility; however, a subset of physicians expressed much greater disutility for the future risk of malignancy. Given the potential for physicians to influence health care decisions and policies, further study of radiation-related concerns seems warranted. Physicians, patients, and the general public should be aware of the potential impact such differing views held by physicians may have on their clinical recommendations. Résumé Contexte Le degré d’inquiétude de la population face à l’exposition au rayonnement par imagerie médicale n’a pas été quantifié. Ces inquiétudes sont importantes pour la prise de décisions cliniques et l’élaboration des politiques. Objectif La présente étude vise à quantifier le degré d’inquiétude face à l’exposition au rayonnement. Conception Une méthodologie d’arbitrage temporel a été utilisée pour estimer les valeurs d’usage de l’état de santé associées à l’exposition aux examens de TDM dans un échantillon inclusif de médecins. Les valeurs d’usage de l’état de santé ont été obtenue à partir d’entrevues en personne à l’aide d’un scénario hypothétique guidé par logiciel dans lequel e sujet est exposé à deux examens de TDM distincts. Résultats Cent dix-huit entrevues ont été réalisées. Les valeurs d’usage moyennes et médianes pour l’état d’inquiétude face à la santé en raison de l’exposition au rayonnement ont été respectivement de 0,95 (IC 95%: 0,94 à 0,96) et de 0,98 (plage interquartile: 0,91 à 1,00). La distribution des valeurs d’usage était fortement asymétrique vers les valeurs plus élevées. Cinq répondants (4,3%) ont enregistré un score de 0,8 ou moins et 17 répondants (14,5%) étaient près à sacrifier au moins 5 années de vie ou plus pour vivre sans inquiétude liée à l’exposition au rayonnement. Conclusions et pertinence Les médecins répondants ont généralement démontré un faible niveau de désutilité; cependant, un sous-ensemble de médecins a exprimé une désutilité beaucoup plus grande face au risque de tumeur maligne future. Compte tenu du potentiel d’influencer les décisions et les politiques en matière de santé des médecins, d’autres études sur les préoccupations liées au rayonnement semblent indiquées. Les médecins, les patients et le grand public devraient être conscients des effets potentiels que de telles opinions discordantes par les médecins peuvent avoir sur leurs recommandations cliniques.
Authors: Coppolino M; Avins AL; Callen A; Sumner W
J Med Imaging Radiat Sci. 2017 Mar;48(1):16-21. Epub 2017-02-07.
Post-treatment Low-risk Drinking as a Predictor of Future Drinking and Problem Outcomes among Individuals with Alcohol Use Disorders: A 9-year Follow-up
Treatment for alcohol use disorders (AUDs) has traditionally been abstinence oriented, but new research and regulatory guidelines suggest that low-risk drinking may also be an acceptable treatment outcome. However, little is known about long-term outcomes for patients who become low-risk drinkers posttreatment. This study explores a posttreatment low-risk drinking outcome as a predictor of future drinking and psychosocial outcomes over 9 years. Study participants were adults with AUDs at treatment entry who received follow-up interviews 6 months posttreatment intake (N = 1,061) in 2 large randomized studies conducted at Kaiser Permanente Northern California, a large private, nonprofit, integrated health system. Six-month drinking status was defined as abstinent, low-risk (nonabstinent, no 5+ drinking days), or heavy drinking (1 or more days of 5+ drinks). Using logistic regression models, we explored the relationship between past 30-day drinking status at 6 months and odds of being abstinent or a low-risk drinker (compared to heavy drinking), and positive Addiction Severity Index psychosocial outcomes over 9 years (9-year follow-up rate of 73%). Abstainers and low-risk drinkers at 6 months had higher odds of recent abstinence/low-risk drinking over 9 years than heavy drinkers; abstainers had better drinking outcomes than low-risk drinkers. Additionally, among those with interview data, 95% of abstainers and 94% of low-risk drinkers at 6 months were abstinent/low-risk drinkers at 9 years; surprisingly, 89% of heavy drinkers at 6 months were also abstinent/low-risk drinkers although still significantly fewer than the other groups. Abstainers and low-risk drinkers at 6 months had better psychiatric outcomes, and abstainers had better family/social outcomes than heavy drinkers; medical outcomes did not differ. Low-risk drinkers and abstainers showed no reliable differences across psychosocial measures. The findings suggest that a low-risk drinking outcome may be reasonable over the long-term for some alcohol-dependent individuals receiving addiction treatment.
Authors: Kline-Simon AH; Litten RZ; Weisner CM; Falk DE
Alcohol Clin Exp Res. 2017 Mar;41(3):653-658. Epub 2017-02-07.
Neighborhood Differences in Post-Stroke Mortality
BACKGROUND: Post-stroke mortality is higher among residents of disadvantaged neighborhoods, but it is not known whether neighborhood inequalities are specific to stroke survival or similar to mortality patterns in the general population. We hypothesized that neighborhood disadvantage would predict higher poststroke mortality, and neighborhood effects would be relatively larger for stroke patients than for individuals with no history of stroke.METHODS AND RESULTS: Health and Retirement Study participants aged ≥50 years without stroke at baseline (n=15 560) were followed ≤12 years for incident stroke (1715 events over 159 286 person-years) and mortality (5325 deaths). Baseline neighborhood characteristics included objective measures based on census tracts (family income, poverty, deprivation, residential stability, and percent white, black, or foreign-born) and self-reported neighborhood social ties. Using Cox proportional hazard models, we compared neighborhood mortality effects for people with versus people without a history of stroke. Most neighborhood variables predicted mortality for both stroke patients and the general population in demographic-adjusted models. Neighborhood percent white predicted lower mortality for stroke survivors (hazard ratio, 0.75 for neighborhoods in highest 25th percentile versus below, 95% confidence interval, 0.62-0.91) more strongly than for stroke-free adults (hazard ratio, 0.92; 95% confidence interval, 0.83-1.02;P=0.04 for stroke-by-neighborhood interaction). No other neighborhood characteristic had different effects for people with versus without stroke. Neighborhood-mortality associations emerged within 3 months after stroke, when associations were often stronger than among stroke-free individuals.CONCLUSIONS: Neighborhood characteristics predict mortality, but most effects are similar for individuals without stroke. Eliminating disparities in stroke survival may require addressing pathways that are not specific to traditional poststroke care.
Authors: Osypuk, Theresa L TL; Ehntholt, Amy A; Moon, J Robin JR; Gilsanz, Paola P; Glymour, M Maria MM
Circulation. Cardiovascular quality and outcomes. 2017 Feb ;10(2):120-128. Epub 2017-02-22.
Causal Effect of Genetic Variants Associated With Body Mass Index on Multiple Sclerosis Susceptibility
Multiple sclerosis (MS) is an autoimmune disease with both genetic and environmental risk factors. Recent studies indicate that childhood and adolescent obesity double the risk of MS, but this association may reflect unmeasured confounders rather than causal effects of obesity. We used separate-sample Mendelian randomization to estimate the causal effect of body mass index (BMI) on susceptibility to MS. Using data from non-Hispanic white members of the Kaiser Permanente Medical Care Plan of Northern California (KPNC) (2006-2014; 1,104 cases of MS and 10,536 controls) and a replication data set from Sweden (the Epidemiological Investigation of MS (EIMS) and the Genes and Environment in MS (GEMS) studies, 2005-2013; 5,133 MS cases and 4,718 controls), we constructed a weighted genetic risk score using 97 variants previously established to predict BMI. Results were adjusted for birth year, sex, education, smoking status, ancestry, and genetic predictors of MS. Estimates in KPNC and Swedish data sets suggested that higher genetically induced BMI predicted greater susceptibility to MS (odds ratio = 1.13, 95% confidence interval: 1.04, 1.22 for the KPNC sample; odds ratio = 1.09, 95% confidence interval: 1.03, 1.15 for the Swedish sample). Although the mechanism remains unclear, to our knowledge, these findings support a causal effect of increased BMI on susceptibility to MS for the first time, and they suggest a role for inflammatory pathways that characterize both obesity and the MS disease process.
Authors: Gianfrancesco MA; Schaefer C; Barcellos LF; et al.
Am J Epidemiol. 2017 02 01;185(3):162-171.
Bidirectional associations of accelerometer-determined sedentary behavior and physical activity with reported time in bed: Women’s Health Study
To examine the day-to-day, bidirectional associations of accelerometer-derived sedentary behavior and physical activity (PA) with reported time in bed in a large cohort of older women. Data are from 10086 Women’s Health Study participants (aged 71.6 years; SD, 5.7) who agreed to wear an accelerometer and complete a diary for 7 consecutive days. Generalized linear (multilevel) models with repeated measures were used to examine the adjusted associations of the following: (1) reported time in bed with next-day accelerometer-determined counts and time spent sedentary and in light- and moderate-to-vigorous-intensity PA (MVPA) and (2) accelerometer estimates with reported time in bed that night, expressed as short (<7 hours), optimal (7-9 hours), and long (>9 hours) sleep. Across days, short sleep was associated with an average of 5500 (SE, 1352) higher accelerometer counts the following day but was also related to higher average sedentary (46.5 [SE, 1.5] minutes) and light-intensity PA (11.9 [SE, 1.2] minutes) than optimal sleep (all P<.001). Long sleep was associated with lower accelerometer counts, time spent sedentary and in light-intensity PA, and a reduced likelihood of engaging in ≥20 minutes of MVPA (all P<.001) than optimal sleep. Higher PA during the day (higher accelerometer counts and ≥20 minutes of accumulated MVPA) was associated with a reduced likelihood of reporting short or long sleep that night (all P<.001). Findings support the bidirectional associations of accelerometer-determined sedentary behavior and PA with reported time in bed in older women. Future studies are needed to confirm findings with sleep actigraphy in older women.
Authors: Pettee Gabriel K; Sternfeld B; Shiroma EJ; Pérez A; Cheung J; Lee IM
Sleep Health. 2017 02;3(1):49-55. Epub 2016-11-04.
Patient-reported pathways to opioid use disorders and pain-related barriers to treatment engagement
Risk factors associated with developing opioid use disorders (OUD) are documented, but less is known about different pathways to initiation of opioids or opioid dependence, or how such pathways affect treatment engagement. We recruited 283 adults with electronic medical record (EMR) evidence of opioid dependence diagnoses. Open-ended and structured interview items focused on prior opioid treatment experiences, barriers to and knowledge of treatment options. Interviews were audio-recorded, transcribed, and coded. In exploratory analyses, we used a modified grounded theory approach to organize emergent, patient-reported themes describing participants’ perceived pathways to opioid dependence. 121 participants described one or more pathways to OUD. Qualitative analyses revealed five pathway themes. Three pathways were related to pain control: inadequately controlled chronic pain, exposure to opioids during acute pain episodes, and chronic pain among individuals with prior substance use disorders. A fourth pathway included individuals for whom opioids provided relief from emotional distress; the fifth related to recreational or non-medically supervised opioid use. We identified pain-related barriers to reducing/stopping opioids and treatment engagement barriers among individuals who perceived themselves solely as pain patients. Patients’ perceptions of inadequately controlled pain, patients’ previous substance use disorders, and the relief from emotional distress that some patients feel while using opioids are relevant when making clinical decisions about whether to initiate or sustain opioid therapy, and for how to monitor certain individuals. Among individuals with pain and OUD, treatment barriers include fear of uncontrolled pain, and stigmatization of being treated alongside people with non-medical opioid use.
Authors: Stumbo SP; Yarborough BJ; McCarty D; Weisner C; Green CA
J Subst Abuse Treat. 2017 Feb;73:47-54. Epub 2016-11-15.
Post-traumatic stress disorder symptom duration and remission in relation to cardiovascular disease risk among a large cohort of women
BACKGROUND: Prior studies suggest that post-traumatic stress disorder (PTSD) is associated with elevated cardiovascular disease (CVD) risk, but effects of duration and remission of PTSD symptoms have rarely been evaluated.METHOD: We examined the association of time-updated PTSD symptom severity, remission and duration with incident CVD risk (552 confirmed myocardial infarctions or strokes) over 20 years in 49 859 women in the Nurses’ Health Study II. Among women who reported trauma on the Brief Trauma Questionnaire, PTSD symptoms, assessed by a screener, were classified by symptom severity and chronicity: (a) no symptoms, (b) 1-3 ongoing, (c) 4-5 ongoing, (d) 6-7 ongoing, (e) 1-3 remitted, (f) 4-7 remitted symptoms. Inverse probability weighting was used to estimate marginal structural logistic regression models, adjusting for time-varying and time-invariant confounders.RESULTS: Compared with women with no trauma exposure, women with trauma/no PTSD [odds ratio (OR) 1.30, 95% confidence interval (CI) 1.03-1.65] and women with trauma/6-7 symptoms (OR 1.69, 95% CI 1.08-2.63) had elevated risk of CVD; women with remitted symptoms did not have elevated CVD risk. Among women exposed to trauma, every 5 additional years of PTSD symptomology was associated with 9% higher CVD incidence compared with women with trauma/no PTSD.CONCLUSIONS: The findings suggest that alleviating PTSD symptoms shortly after onset may attenuate CVD risk.
Authors: Gilsanz, P P; Winning, A A; Koenen, K C KC; Roberts, A L AL; Sumner, J A JA; Chen, Q Q; Glymour, M M MM; Rimm, E B EB; Kubzansky, L D LD
Psychological medicine. 2017 Jun ;47(8):1370-1378. Epub 2017-01-05.
Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men
Sex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin. Statistical analyses of individual participant data from 12,330 male controls aged 25-85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates. Older age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones. Circulating sex hormones in men are strongly associated with age and body mass index, and to a lesser extent with smoking status and alcohol consumption.
Authors: Watts EL; Habel LA; Schaefer CA; Travis RC; et al.
PLoS ONE. 2017;12(12):e0187741. Epub 2017-12-27.
Genome-wide association screens for Achilles tendon and ACL tears and tendinopathy
Achilles tendinopathy or rupture and anterior cruciate ligament (ACL) rupture are substantial injuries affecting athletes, associated with delayed recovery or inability to return to competition. To identify genetic markers that might be used to predict risk for these injuries, we performed genome-wide association screens for these injuries using data from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort consisting of 102,979 individuals. We did not find any single nucleotide polymorphisms (SNPs) associated with either of these injuries with a p-value that was genome-wide significant (p<5x10-8). We found, however, four and three polymorphisms with p-values that were borderline significant (p<10-6) for Achilles tendon injury and ACL rupture, respectively. We then tested SNPs previously reported to be associated with either Achilles tendon injury or ACL rupture. None showed an association in our cohort with a false discovery rate of less than 5%. We obtained, however, moderate to weak evidence for replication in one case; specifically, rs4919510 in MIR608 had a p-value of 5.1x10-3 for association with Achilles tendon injury, corresponding to a 7% chance of false replication. Finally, we tested 2855 SNPs in 90 candidate genes for musculoskeletal injury, but did not find any that showed a significant association below a false discovery rate of 5%. We provide data containing summary statistics for the entire genome, which will be useful for future genetic studies on these injuries.
Authors: Kim SK; Roos TR; Roos AK; Kleimeyer JP; Ahmed MA; Goodlin GT; Fredericson M; Ioannidis JP; Avins AL; Dragoo JL
PLoS ONE. 2017;12(3):e0170422. Epub 2017-03-30.
Genome-wide association analyses using electronic health records identify new loci influencing blood pressure variation
Longitudinal electronic health records on 99,785 Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort individuals provided 1,342,814 systolic and diastolic blood pressure measurements for a genome-wide association study on long-term average systolic, diastolic, and pulse pressure. We identified 39 new loci among 75 genome-wide significant loci (P ≤ 5 × 10(-8)), with most replicating in the combined International Consortium for Blood Pressure (ICBP; n = 69,396) and UK Biobank (UKB; n = 152,081) studies. Combining GERA with ICBP yielded 36 additional new loci, with most replicating in UKB. Combining all three studies (n = 321,262) yielded 241 additional genome-wide significant loci, although no replication sample was available for these. All associated loci explained 2.9%, 2.5%, and 3.1% of variation in systolic, diastolic, and pulse pressure, respectively, in GERA non-Hispanic whites. Using multiple blood pressure measurements in GERA doubled the variance explained. A normalized risk score was associated with time to onset of hypertension (hazards ratio = 1.18, P = 8.2 × 10(-45)). Expression quantitative trait locus analysis of blood pressure loci showed enrichment in aorta and tibial artery.
Authors: Hoffmann TJ; Ehret GB; Nandakumar P; Ranatunga D; Schaefer C; Kwok PY; Iribarren C; Chakravarti A; Risch N
Nat Genet. 2017 Jan;49(1):54-64. Epub 2016-11-14.
Faculty Development Efforts to Promote Screening, Brief Intervention and Referral to Treatment (SBIRT) in an Internal Medicine Faculty-Resident Practice
Screening, brief intervention, and referral to treatment (SBIRT) is a practical means to address substance misuse in primary care. Important barriers to implementing SBIRT include adequacy of training and provider confidence as well as logistical hurdles and time constraints. A faculty development initiative aimed at increasing SBIRT knowledge and treatment of substance use disorders (SUDs) should lead to increased use of SBIRT by faculty and the residents they teach. This study examined how a faculty development program to promote SBIRT influenced faculty practice and resident teaching. This was a cross-sectional study of faculty exposed to multiple SBIRT educational interventions over a 5-year period in an academic faculty-resident general medicine practice. Participants completed a brief online survey followed by a semistructured interview. Quantitative responses were examined descriptively. Qualitative questions were reviewed to identify key themes. Fifteen of 29 faculty (52%) completed the survey and 13 (45%) completed the interviews regarding faculty development interventions. Faculty thought that SBIRT was an important skill and had confidence in screening for substance use disorders, although confidence in making treatment referrals and prescribing pharmacotherapy were rated lower. Many faculty reported screening more frequently for SUDs after attending faculty development sessions. However, several reported that the training did not improve their SBIRT teaching to residents during clinic precepting sessions. To improve uptake of SBIRT, a majority of faculty recommended electronic health record (EHR) alerts. SBIRT is a highly valued set of skills, and training may enhance rates of screening for substance misuse. However, participants did not report a substantial change in SBIRT teaching as a result of faculty development. In the future, small, targeted faculty development sessions, potentially involving strategies for using the electronic health record (EHR), may be an effective way to enhance primary care SBIRT skills.
Authors: Stone A; Wamsley M; O'Sullivan P; Satterfield J; Satre DD; Julian K
Subst Abus. 2017 Jan-Mar;38(1):31-34. Epub 2016-11-29.
Validation of a theoretically motivated approach to measuring childhood socioeconomic circumstances in the Health and Retirement Study
Childhood socioeconomic status (cSES) is a powerful predictor of adult health, but its operationalization and measurement varies across studies. Using Health and Retirement Study data (HRS, which is nationally representative of community-residing United States adults aged 50+ years), we specified theoretically-motivated cSES measures, evaluated their reliability and validity, and compared their performance to other cSES indices. HRS respondent data (N = 31,169, interviewed 1992-2010) were used to construct a cSES index reflecting childhood social capital (cSC), childhood financial capital (cFC), and childhood human capital (cHC), using retrospective reports from when the respondent was <16 years (at least 34 years prior). We assessed internal consistency reliability (Cronbach's alpha) for the scales (cSC and cFC), and construct validity, and predictive validity for all measures. Validity was assessed with hypothesized correlates of cSES (educational attainment, measured adult height, self-reported childhood health, childhood learning problems, childhood drug and alcohol problems). We then compared the performance of our validated measures with other indices used in HRS in predicting self-rated health and number of depressive symptoms, measured in 2010. Internal consistency reliability was acceptable (cSC = 0.63, cFC = 0.61). Most measures were associated with hypothesized correlates (for example, the association between educational attainment and cSC was 0.01, p < 0.0001), with the exception that measured height was not associated with cFC (p = 0.19) and childhood drug and alcohol problems (p = 0.41), and childhood learning problems (p = 0.12) were not associated with cHC. Our measures explained slightly more variability in self-rated health (adjusted R2 = 0.07 vs. <0.06) and number of depressive symptoms (adjusted R2 > 0.05 vs. < 0.04) than alternative indices. Our cSES measures use latent variable models to handle item-missingness, thereby increasing the sample size available for analysis compared to complete case approaches (N = 15,345 vs. 8,248). Adopting this type of theoretically motivated operationalization of cSES may strengthen the quality of research on the effects of cSES on health outcomes.
Authors: Vable AM; Gilsanz P; Nguyen TT; Kawachi I; Glymour MM
PLoS ONE. 2017;12(10):e0185898. Epub 2017-10-13.
Changes in Medication Use After Dementia Diagnosis in an Observational Cohort of Individuals with Diabetes Mellitus
To assess changes in medication use after a diagnosis of dementia in individuals with type 2 diabetes mellitus. Difference-in-differences analysis of changes in the number of dispensed chronic medications between individuals with and without newly diagnosed dementia. Integrated healthcare delivery system, Kaiser Permanente Northern California. Individuals aged 50 and older without prevalent dementia with type 2 diabetes mellitus enrolled in a baseline survey. During 5 years of follow-up, 193 individuals with a new diagnosis of dementia were identified, and risk-set sampling was used to randomly select five reference subjects per case matched on 5-year age categories and sex (965 matched participants), resulting in an analytical sample of 1,158. The exposure was new diagnosis of dementia. The primary outcome was change in number of current chronic medications (total, cardiovascular (blood pressure and lipid control), diabetes mellitus) at three times: 1 year before index date (preindex date), date of diagnosis of dementia or matched reference date (index date), and up to 1 year after index date or end of follow-up if censored before 1 year (postindex date). After adjustment, the number of chronic medications and the subset of cardiovascular medications declined after a dementia diagnosis in the overall cohort and in age-, sex-, and time-matched reference individuals, but the decline was significantly greater in the group with dementia (0.71 medications fewer than the reference group, P = .02). The number of diabetes mellitus medications declined in both groups, but the declines were not statistically different (0.18 medications fewer than the reference group, P = .008). Use of cardiometabolic medications fell after a diagnosis of dementia, as recommended in national guidelines.
Authors: Sarkar U; Lyles C; Steinman M; Huang ES; Moffet HH; Whitmer RA; Warton EM; Karter AJ
J Am Geriatr Soc. 2017 Jan;65(1):77-82. Epub 2016-09-19.
The impact of comorbid knee and hip osteoarthritis on longitudinal clinical and health care use outcomes in older adults with new visits for back pain
To examine if a comorbid diagnosis of knee or hip osteoarthritis (OA) in older adults with new back pain visits is associated with long-term patient-reported outcomes and back-related health care use. Prospective cohort study. Three integrated health systems forming the Back pain Outcomes using Longitudinal Data cohort. Participants (N=5155) were older adults (≥65y) with a new visit for back pain and a complete electronic health record data. Not applicable; we obtained OA diagnoses using diagnostic codes in the electronic health record 12 months prior to the new back pain visit. The Roland-Morris Disability Questionnaire (RDQ) and the EuroQol-5D (EQ-5D) were key patient-reported outcomes. Health care use, measured by relative-value units (RVUs), was summed for the 12 months after the initial visit. We used linear mixed-effects models to model patient-reported outcomes. We also used generalized linear models to test the association between comorbid knee or hip OA and total back-related RVUs. Of the 5155 participants, 368 (7.1%) had a comorbid knee OA diagnosis, and 94 (1.8%) had a hip OA diagnosis. Of the participants, 4711 (91.4%) had neither knee nor hip OA. In adjusted models, the 12-month RDQ score was 1.23 points higher (95% confidence interval [CI], 0.72-1.74) for patients with knee OA and 1.26 points higher (95% CI, 0.24-2.27) for those with hip OA than those without knee or hip OA, respectively. A lower EQ-5D score was found among participants with knee OA (.02 lower; 95% CI, -.04 to -.01) and hip OA diagnoses (.03 lower; 95% CI, -.05 to -.01) compared with those without knee or hip OA, respectively. Comorbid knee or hip OA was not significantly associated with total 12-month back-related resource use. Comorbid knee or hip OA in older adults with a new back pain visit was associated with modestly worse long-term disability and health-related quality of life.
Authors: Rundell SD; Avins AL; Jarvik JG; et al.
Arch Phys Med Rehabil. 2017 Jan;98(1):43-50. Epub 2016-08-09.
Efficacy of Prophylactic Antibiotics in Simple Knee Arthroscopy
To determine the association between the use of preoperative antibiotics and the risk of postoperative infection after simple knee arthroscopy. The electronic medical records of a large integrated health care organization were used to identify patients who underwent simple knee arthroscopy between 2007 and 2012. Patient demographics, potential infection risk factors, and antibiotic administration data were extracted. Simple knee arthroscopy included debridement, meniscectomy, meniscus repair, synovectomy, microfracture, and lateral release. Complex knee arthroscopy, septic knees, and cases involving fractures were excluded. Deep infection was defined as a positive synovial fluid culture or signs and symptoms of infection and gross pus in the knee. Superficial infection was defined as clinical signs of infection localized to a portal site and treatment with an antibiotic. Of 40,810 simple knee arthroscopies, 32,836 (80.5%) received preoperative antibiotics and 7,974 (19.5%) did not. There were 25 deep infections in the antibiotic group (0.08%) and 11 in the no-antibiotics group (0.14%) (risk ratio = 0.55, 95% confidence interval: 0.27 to 1.12, P = .10). There were 134 superficial infections in the antibiotic group (0.41%) and 32 in the no-antibiotics group (0.40%) (risk ratio = 1.01, 95% confidence interval: 0.29 to 1.49, P = .93). In our large sample of patients who underwent simple knee arthroscopy, there was no association between preoperative antibiotic use and postoperative deep or superficial infection rates at the 95% confidence level (P = .05). There was an association between preoperative antibiotic use and a decreased deep infection rate at the P = .10 level. Level IV, case series.
Authors: Wyatt RWB; Maletis GB; Lyon LL; Schwalbe J; Avins AL
Arthroscopy. 2017 Jan;33(1):157-162. Epub 2016-06-30.
Affordable Care Act Implementation in a California Health Care System Leads to Growth in HIV-Positive Patient Enrollment and Changes in Patient Characteristics
This study examined implementation of the Affordable Care Act (ACA) in relation to HIV-positive patient enrollment in an integrated health care system; as well as changes in new enrollee characteristics, benefit structure, and health care utilization after key ACA provisions went into effect in 2014. This mixed-methods study was set in Kaiser Permanente Northern California (KPNC). Qualitative interviews with 29 KPNC leaders explored planning for ACA implementation. Quantitative analyses compared newly enrolled HIV-positive patients in KPNC between January and December 2012 (“pre-ACA,” N = 661) with newly enrolled HIV-positive patients between January and December 2014 (“post-ACA,” N = 880) on demographics; medical, psychiatric, and substance use disorder diagnoses; HIV clinical indicators; and type of health care utilization. Interviews found that ACA preparation focused on enrollment growth, staffing, competition among health plans, concern about cost sharing, and HIV pre-exposure prophylaxis (PrEP) services. Quantitative analyses found that post-ACA HIV-positive patient enrollment grew. New enrollees in 2014 were more likely than 2012 enrollees to be enrolled in high-deductible plans (P < 0.01) or through Medicaid (P < 0.01), and marginally more likely to have better HIV viral control (P < 0.10). They also were more likely to be diagnosed with asthma (P < 0.01) or substance use disorders (P < 0.05) and to have used primary care health services in the 6 months postenrollment (P < 0.05) than the pre-ACA cohort. As anticipated by KPNC interviewees, ACA implementation was followed by HIV-positive patient enrollment growth and changing benefit structures and patient characteristics. Although HIV viral control improved, comorbid diagnosis findings reinforced the importance of coordinated health care.
Authors: Satre DD; Altschuler A; Parthasarathy S; Silverberg MJ; Volberding P; Campbell CI
J Acquir Immune Defic Syndr. 2016 Dec 15;73(5):e76-e82.
Changes in Depressive Symptoms and Subsequent Risk of Stroke in the Cardiovascular Health Study
BACKGROUND AND PURPOSE: Depression is associated with stroke, but the effects of changes in depressive symptoms on stroke risk are not well understood. This study examined whether depressive symptom changes across 2 successive annual assessments were associated with incident stroke the following year.METHODS: We used visit data from 4319 participants of the Cardiovascular Health Study who were stroke free at baseline to examine whether changes in depressive symptoms classified across 2 consecutive annual assessments predicted incident first stroke during the subsequent year. Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression scale (high versus low at ≥10). Survival models were inverse probability weighted to adjust for demographics, health behaviors, medical conditions, past depressive symptoms, censoring, and survival.RESULTS: During follow-up, 334 strokes occurred. Relative to stable low scores of depressive symptoms, improved depression symptoms were associated with almost no excess risk of stroke (adjusted hazards ratio, 1.02; 95% confidence interval, 0.66-1.58). New-onset symptoms were nonsignificantly associated with elevated stroke risk (adjusted hazards ratio, 1.44; 95% confidence interval, 0.97-2.14), whereas persistently high depressive symptoms were associated with elevated adjusted hazard of all-cause stroke (adjusted hazards ratio, 1.65; 95% confidence interval, 1.06-2.56). No evidence for effect modification by race, age, or sex was found.CONCLUSIONS: Persistently high symptoms of depression predicted elevated hazard of stroke. Participants with improved depressive symptoms had no elevation in stroke risk. Such findings suggest that strategies to reduce depressive symptoms may ameliorate stroke risk.
Authors: Gilsanz, Paola P; Kubzansky, Laura D LD; Tchetgen Tchetgen, Eric J EJ; Wang, Qianyi Q; Kawachi, Ichiro I; Patton, Kristen K KK; Fitzpatrick, Annette L AL; Kop, Willem J WJ; Longstreth, W T WT; Glymour, M Maria MM
Stroke. 2017 01 ;48(1):43-48. Epub 2016-12-06.
Racial Differences in HIV and HCV Risk Behaviors, Transmission, and Prevention Knowledge among Non-Treatment-Seeking Individuals with Opioid Use Disorder.
In light of New York’s recently reinforced strategy to end the AIDS epidemic by expanding testing, treatment, and access to pre-exposure prophylaxis (PrEP), we assessed drug use and sexual risk behaviors, along with HIV/Hepatitis C virus (HCV) transmission and prevention knowledge among non-treatment-seeking adults with opioid use disorder (OUD) in New York City. Over the course of 18 months, volunteers screening for research studies in the Opioid Laboratory at the New York State Psychiatric Institute completed a locally developed self-assessment questionnaire. A total of 138 adults with OUD (24 female, 114 male) with a mean age of 46.5 years (SD = 9.5 yrs) were assessed. Significant differences among the four racial/ethnic subgroups (n = 65 African-Americans, n = 34 Hispanics, n = 31 Caucasians or Whites, n = 8 Multiracial) were found. Whites were the youngest (p = 0.001), most frequently injecting drugs (p
Authors: Metz, Verena E VE; Sullivan, Maria A MA; Jones, Jermaine D JD; Evans, Elizabeth E; Luba, Rachel R; Vogelman, Jonathan J; Comer, Sandra D SD
Journal of psychoactive drugs. 2017 08 01;49(1):59-68. Epub 2016-12-05.
The role of hazardous drinking reductions in predicting depression and anxiety symptom improvement among psychiatry patients: A longitudinal study
Co-occurrence of depression, anxiety, and hazardous drinking is high in clinical samples. Hazardous drinking can worsen depression and anxiety symptoms (and vice versa), yet less is known about whether reductions in hazardous drinking improve symptom outcomes. Three hundred and seven psychiatry outpatients were interviewed (baseline, 3-, 6-months) for hazardous drinking (drinking over recommended daily limits), depression (PHQ-9), and anxiety (GAD-7) as part of a hazardous drinking intervention trial. Longitudinal growth models tested associations between hazardous drinking and symptoms (and reciprocal effects between symptoms and hazardous drinking), adjusting for treatment effects. At baseline, participants had moderate anxiety (M=10.81; SD=10.82) and depressive symptoms (M=13.91; SD=5.58); 60.0% consumed alcohol at hazardous drinking levels. Over 6-months, participants’ anxiety (B=-3.03, p<.001) and depressive symptoms (B=-5.39, p<.001) improved. Continued hazardous drinking led to slower anxiety (B=0.09, p=.005) and depressive symptom (B=0.10, p=.004) improvement; reductions in hazardous drinking led to faster anxiety (B=-0.09, p=.010) and depressive (B=-0.10, p=.015) symptom improvement. Neither anxiety (B=0.07, p=.066) nor depressive (B=0.05, p=.071) symptoms were associated with hazardous drinking outcomes. Participants were psychiatry outpatients, limiting generalizability. Reducing hazardous drinking can improve depression and anxiety symptoms but continued hazardous use slows recovery for psychiatry patients. Hazardous drinking-focused interventions may be helpful in promoting symptom improvement in clinical populations.
Authors: Bahorik AL; Leibowitz A; Sterling SA; Travis A; Weisner C; Satre DD
J Affect Disord. 2016 Dec;206:169-173. Epub 2016-07-19.
The Kaiser Permanente Northern California research program on genes, environment, and health (RPGEH) pregnancy cohort: study design, methodology and baseline characteristics
Exposures during the prenatal period may have lasting effects on maternal and child health outcomes. To better understand the effects of the in utero environment on children’s short- and long-term health, large representative pregnancy cohorts with comprehensive information on a broad range of environmental influences (including biological and behavioral) and the ability to link to prenatal, child and maternal health outcomes are needed. The Research Program on Genes, Environment and Health (RPGEH) pregnancy cohort at Kaiser Permanente Northern California (KPNC) was established to create a resource for conducting research to better understand factors influencing women’s and children’s health. Recruitment is integrated into routine clinical prenatal care at KPNC, an integrated health care delivery system. We detail the study design, data collection, and methodologies for establishing this cohort. We also describe the baseline characteristics and the cohort’s representativeness of the underlying pregnant population in KPNC. While recruitment is ongoing, as of October 2014, the RPGEH pregnancy cohort included 16,977 pregnancies (53 % from racial and ethnic minorities). RPGEH pregnancy cohort participants consented to have blood samples obtained in the first trimester (mean gestational age 9.1 weeks ± 4.2 SD) and second trimester (mean gestational age 18.1 weeks ± 5.5 SD) to be stored for future use. Women were invited to complete a questionnaire on health history and lifestyle. Information on women’s clinical and health assessments before, during and after pregnancy and women and children’s health outcomes are available in the health system’s electronic health records, which also allows long-term follow-up. This large, racially- and ethnically-diverse cohort of pregnancies with prenatal biospecimens and clinical data is a valuable resource for future studies on in utero environmental exposures and maternal and child perinatal and long term health outcomes. The baseline characteristics of RPGEH Pregnancy Cohort demonstrate that it is highly representative of the underlying population living in the broader community in Northern California.
Authors: Hedderson MM; Ferrara A; Avalos LA; Van den Eeden SK; Gunderson EP; Li DK; Schaefer C; Croen LA; et al.
BMC Pregnancy Childbirth. 2016 Nov 29;16(1):381. Epub 2016-11-29.
Avoidant coping and diabetes-related distress: Pathways to adolescents’ Type 1 diabetes outcomes.
OBJECTIVE:
Adolescents with Type 1 diabetes (T1D) are vulnerable to diabetes-related distress and often struggle to complete self-management tasks needed to maintain blood glucose values in target range. One way that youth with T1D handle problems is through avoidant coping. The current study examined cross-time associations between avoidant coping style and diabetes outcomes and tested the possible mediating role of diabetes-related distress.
METHOD:
Adolescents with T1D (N = 264) were assessed 4 times over 1 year to measure avoidant coping style, diabetes-related distress, adherence (on the basis of glucometer data and self-report), and glycemic control (hemoglobin A1c). Mediation and direct effects were tested across time using time-lagged autoregressive path models, making use of the repeated measurement of all constructs.
RESULTS:
The hypothesized mediation effect was found for all 3 diabetes outcomes. Higher levels of avoidant coping style were associated with greater diabetes-related distress at the subsequent time point, which was related in turn to fewer blood glucose checks, less frequent self-care behaviors, and poorer glycemic control (higher A1c) at the next assessment.
CONCLUSIONS:
In the context of diabetes, an avoidant coping style may contribute to greater diabetes-specific distress followed by deterioration in self-management and glycemic control over time. Maladaptive coping styles are modifiable factors that offer an entry point into intervention before further difficulties can take hold. (PsycINFO Database Record(c) 2017 APA, all rights reserved).
Authors: Iturralde E; Weissberg-Benchell J; Hood KK;
Health Psychol. 2017 Mar;36(3):236-244. doi: 10.1037/hea0000445. Epub 2016 Nov 3.
Response to Dr Fiscella: Transparency and Debate are Essential to Improve Guidelines and Measures
Authors: Harris AH; Chen C; Weisner CM; Chalk M; Capoccia V; Thomas CP
J Addict Med. 2016 Nov/Dec;10(6):453-454.
Marijuana use and service utilization among adolescents 7 years post substance use treatment
In an environment of increasingly liberal attitudes towards marijuana use and legalization, little is known about long-term trajectories of marijuana use among clinical samples of adolescents, and how these trajectories relate to health services utilization over time. Latent growth curve analysis was used to identify distinct trajectories of marijuana use in a clinical sample of adolescents (N=391) over 7 years post substance use treatment in an integrated health system. We examined psychiatric problems and polysubstance use associated with the identified trajectory groups using general linear models. Nonlinear mixed-effects logistic regressions were used to examine associations between health services use and the trajectory groups. We identified three marijuana use trajectory groups: (1) Abstinent (n=117); (2) Low/Stable use (n=174); and (3) Increasing use (n=100). Average externalizing and anxiety/depression scores were significantly lower over time for the Abstinent group compared to the Increasing and Low/Stable groups. The Low Stable and the Increasing group had fewer psychiatric visits over time (p<0.05) and the Low/Stable group used more substance use treatment services over time compared with the Abstinent group (p<0.001). Treated adolescents showed distinct marijuana use patterns, one of which indicated a group of adolescents at risk of increased use over time. These individuals have greater psychiatric and polysubstance use over time, but may not be accessing needed services.
Authors: Campbell CI; Sterling S; Chi FW; Kline-Simon AH
Drug Alcohol Depend. 2016 Nov 01;168:1-7. Epub 2016-08-23.
Use of Electronic Cigarettes Among Cancer Survivors in the U.S
The population-level patterns of electronic cigarette (e-cigarette) use among cancer survivors in the U.S. are unknown. The objective of this study was to examine the prevalence and correlates of e-cigarette use among cancer survivors in a nationally representative sample. A cross-sectional analysis was conducted of the 2014 National Health Interview Survey of the U.S. non-institutionalized civilian population. The main study outcomes were the prevalence and correlates of ever and current e-cigarette use among adults with self-reported history of cancer, excluding non-melanoma skin cancer (N=2,695). Multivariable logistic regression analyses examined whether e-cigarette use differed by cigarette smoking status and demographic subgroups. The analyses were performed in 2015. The prevalence of e-cigarette use among adult cancer survivors was lower than the general population: 2.8% of cancer survivors reported currently using e-cigarettes and an additional 6.3% had previously used e-cigarettes but were not currently using them. Use of e-cigarettes was most common among cancer survivors who currently smoked cigarettes: 34.3% of current smokers were ever e-cigarette users and 15.6% were current e-cigarette users, compared with former smokers (2.7% ever and 1.4% current e-cigarette users) and never smokers (small sample/estimates unavailable). E-cigarettes are not part of current evidence-based smoking-cessation strategies. However, the finding that cancer survivors who currently smoke cigarettes are more likely to use e-cigarettes highlights the importance of addressing e-cigarette use in patient-provider communications around tobacco cessation.
Authors: Salloum RG; Getz KR; Tan ASL; Carter-Harris L; Young-Wolff KC; George TJ; Shenkman EA
Am J Prev Med. 2016 Nov;51(5):762-766. Epub 2016-05-27.
Patient-provider discussions about lung cancer screening pre- and post-guidelines: Health Information National Trends Survey (HINTS)
In 2013, the USPSTF issued a Grade B recommendation that long-term current and former smokers receive lung cancer screening. Shared decision-making is important for individuals considering screening, and patient-provider discussions an essential component of the process. We examined prevalence and predictors of lung cancer screening discussions pre- and post-USPSTF guidelines. Data were obtained from two cycles of the Health Information National Trends Survey (2012; 2014). The analyzed sample comprised screening-eligible current and former smokers with no personal history of lung cancer (n=746 in 2012; n=795 in 2014). Descriptive and multiple logistic regression analyses were conducted; patient-reported discussion about lung cancer screening with provider was the outcome of interest. Contrary to expectations, patient-provider discussions about lung cancer screening were more prevalent pre-guideline, but overall patient-provider discussions were low in both years (17% in 2012; 10% in 2014). Current smokers were more likely to have had a discussion than former smokers. Significant predictors of patient-provider discussions included family history of cancer and having healthcare coverage. The prevalence of patient-provider discussions about lung cancer screening is suboptimal. There is a critical need for patient and provider education about shared decision-making and its importance in cancer screening decisions.
Authors: Carter-Harris L; Tan AS; Salloum RG; Young-Wolff KC
Patient Educ Couns. 2016 Nov;99(11):1772-1777. Epub 2016-05-17.
Comparing Variability, Severity, and Persistence of Depressive Symptoms as Predictors of Future Stroke Risk
OBJECTIVE: Numerous studies show that depressive symptoms measured at a single assessment predict greater future stroke risk. Longer-term symptom patterns, such as variability across repeated measures or worst symptom level, might better reflect adverse aspects of depression than a single measurement. This prospective study compared five approaches to operationalizing depressive symptoms at annual assessments as predictors of stroke incidence.DESIGN: Cohort followed for incident stroke over an average of 6.4 years.SETTING: The Adult Changes in Thought cohort follows initially cognitively intact, community- dwelling older adults from a population base defined by membership in Group Health, a Seattle-based nonprofit healthcare organization.PARTICIPANTS: 3,524 individuals aged 65 years and older.MEASUREMENTS: We identified 665 incident strokes using ICD codes. We considered both baseline Center for Epidemiologic Studies-Depression scale (CES-D) score and, using a moving window of three most recent annual CES-D measurements, we compared most recent, maximum, average, and intra-individual variability of CES-D scores as predictors of subsequent stroke using Cox proportional hazards models.RESULTS: Greater maximum (hazard ratio [HR]: 1.18; 95% CI: 1.07-1.30), average (HR: 1.20; 95% CI: 1.05-1.36) and intra-individual variability (HR: 1.15; 95% CI: 1.06-1.24) in CES-D were each associated with elevated stroke risk, independent of sociodemographics, cardiovascular risks, cognition, and daily functioning. Neither baseline nor most recent CES-D was associated with stroke. In a combined model, intra-individual variability in CES-D predicted stroke, but average CES-D did not.CONCLUSIONS: Capturing the dynamic nature of depression is relevant in assessing stroke risk. Fluctuating depressive symptoms may reflect a prodrome of reduced cerebrovascular integrity.
Authors: Zahodne, Laura B LB; Gilsanz, Paola P; Glymour, M Maria MM; Gibbons, Laura E LE; Brewster, Paul P; Hamilton, Jamie J; Mez, Jesse J; Marden, Jessica R JR; Nho, Kwangsik K; Larson, Eric B EB; Crane, Paul K PK; Gross, Alden L AL
The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. 2017 Feb ;25(2):120-128. Epub 2016-10-24.
A Large Genome-Wide Association Study of Age-Related Hearing Impairment Using Electronic Health Records
Age-related hearing impairment (ARHI), one of the most common sensory disorders, can be mitigated, but not cured or eliminated. To identify genetic influences underlying ARHI, we conducted a genome-wide association study of ARHI in 6,527 cases and 45,882 controls among the non-Hispanic whites from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. We identified two novel genome-wide significant SNPs: rs4932196 (odds ratio = 1.185, p = 4.0×10-11), 52Kb 3′ of ISG20, which replicated in a meta-analysis of the other GERA race/ethnicity groups (1,025 cases, 12,388 controls, p = 0.00094) and in a UK Biobank case-control analysis (30,802 self-reported cases, 78,586 controls, p = 0.015); and rs58389158 (odds ratio = 1.132, p = 1.8×10-9), which replicated in the UK Biobank (p = 0.00021). The latter SNP lies just outside exon 8 and is highly correlated (r2 = 0.96) with the missense SNP rs5756795 in exon 7 of TRIOBP, a gene previously associated with prelingual nonsyndromic hearing loss. We further tested these SNPs in phenotypes from audiologist notes available on a subset of GERA (4,903 individuals), stratified by case/control status, to construct an independent replication test, and found a significant effect of rs58389158 on speech reception threshold (SRT; overall GERA meta-analysis p = 1.9×10-6). We also tested variants within exons of 132 other previously-identified hearing loss genes, and identified two common additional significant SNPs: rs2877561 (synonymous change in ILDR1, p = 6.2×10-5), which replicated in the UK Biobank (p = 0.00057), and had a significant GERA SRT (p = 0.00019) and speech discrimination score (SDS; p = 0.0019); and rs9493627 (missense change in EYA4, p = 0.00011) which replicated in the UK Biobank (p = 0.0095), other GERA groups (p = 0.0080), and had a consistent significant result for SRT (p = 0.041) and suggestive result for SDS (p = 0.081). Large cohorts with GWAS data and electronic health records may be a useful method to characterize the genetic architecture of ARHI.
Authors: Hoffmann TJ; Keats BJ; Yoshikawa N; Schaefer C; Risch N; Lustig LR
PLoS Genet. 2016 Oct;12(10):e1006371. Epub 2016-10-20.
Mendelian randomization shows a causal effect of low vitamin D on multiple sclerosis risk
We sought to estimate the causal effect of low serum 25(OH)D on multiple sclerosis (MS) susceptibility that is not confounded by environmental or lifestyle factors or subject to reverse causality. We conducted mendelian randomization (MR) analyses using an instrumental variable (IV) comprising 3 single nucleotide polymorphisms found to be associated with serum 25(OH)D levels at genome-wide significance. We analyzed the effect of the IV on MS risk and both age at onset and disease severity in 2 separate populations using logistic regression models that controlled for sex, year of birth, smoking, education, genetic ancestry, body mass index at age 18-20 years or in 20s, a weighted genetic risk score for 110 known MS-associated variants, and the presence of one or more HLA-DRB1*15:01 alleles. Findings from MR analyses using the IV showed increasing levels of 25(OH)D are associated with a decreased risk of MS in both populations. In white, non-Hispanic members of Kaiser Permanente Northern California (1,056 MS cases and 9,015 controls), the odds ratio (OR) was 0.79 (p = 0.04, 95% confidence interval (CI): 0.64-0.99). In members of a Swedish population from the Epidemiological Investigation of Multiple Sclerosis and Genes and Environment in Multiple Sclerosis MS case-control studies (6,335 cases and 5,762 controls), the OR was 0.86 (p = 0.03, 95% CI: 0.76-0.98). A meta-analysis of the 2 populations gave a combined OR of 0.85 (p = 0.003, 95% CI: 0.76-0.94). No association was observed for age at onset or disease severity. These results provide strong evidence that low serum 25(OH)D concentration is a cause of MS, independent of established risk factors.
Authors: Rhead B; Schaefer C; Barcellos LF; et al.
Neurol Genet. 2016 Oct;2(5):e97. Epub 2016-09-13.
High-Deductible Health Plans: Implications for Substance Use Treatment
To examine whether high-deductible health plans are related to patient complexity, health services use, and medical care costs among substance use treatment patients. Electronic health record data from Kaiser Permanente Northern California; 2007-2011. Retrospective analysis of electronic health record data of substance use treatment patients (N = 31,001). We examined relationship of patient demographics, health comorbidities, and services use and cost to deductible level: none, low ($1-$999), and high (?$1,000). Demographic, membership, diagnostic, and utilization data were merged with cost data. Utilization and costs were summarized into 6-month intervals. Generalized estimation methods for repeated measures with logistic, Poisson, and linear regression were used. Substance use patients with deductible plans were younger and had less comorbidity than those without deductibles. Patients with high deductibles had lower emergency room and hospital use 12- to 6-month pretreatment, but rates became similar to other groups in the 6 months immediately prior to treatment; treatment costs were similar. Immediately prior to entering treatment, substance use patients with and without high deductibles have similar patterns of health services utilization. We discuss implications for health policy and treatment, particularly in an era of health reform.
Authors: Parthasarathy S; Campbell CI
Health Serv Res. 2016 Oct;51(5):1939-59. Epub 2016-02-03.
Maternal T. gondii, offspring bipolar disorder and neurocognition
Prenatal exposure to maternal Toxoplasma gondii (T. gondii) IgG antibody titer has been associated previously with an increased risk of offspring schizophrenia (SZ) and cognitive impairment. We examined maternal T. gondii, offspring bipolar disorder (BP) and childhood cognition using a population-based birth cohort. Maternal sera, drawn in the third trimester, were analyzed for T. gondii IgG antibody titer, and offspring cognition at ages 5 and 9-11 was measured with the Peabody Picture Vocabulary Test (PPVT) and the Raven Matrices (Raven). Raw scores were standardized and the ages combined. Potential cases with BP from the cohort were identified by database linkages. This protocol identified 85 cases who were matched 1:2 to controls. Maternal T. gondii IgG was not associated with the risk of BP in offspring. Neither moderate [HR=1.43 (CI: 0.49, 4.17)] nor high IgG titer [HR=1.6 [CI: 0.74, 3.48)] were associated with offspring BP. Associations were not observed between maternal T. gondii and BP with psychotic features or BP type 1. In addition, maternal T. gondii was not associated with childhood cognition. Our study suggests that T. gondii may be specific to SZ among major psychotic disorders, though further studies with larger sample sizes are required.
Authors: Freedman D; Bao Y; Shen L; Schaefer CA; Brown AS
Psychiatry Res. 2016 Sep 30;243:382-9. Epub 2016-07-07.
Alcohol, Cannabis, and Opioid Use Disorders, and Disease Burden in an Integrated Health Care System
We examined prevalence of major medical conditions and extent of disease burden among patients with and without substance use disorders (SUDs) in an integrated health care system serving 3.8 million members. Medical conditions and SUDs were extracted from electronic health records in 2010. Patients with SUDs (n = 45,461; alcohol, amphetamine, barbiturate, cocaine, hallucinogen, and opioid) and demographically matched patients without SUDs (n = 45,461) were compared on the prevalence of 19 major medical conditions. Disease burden was measured as a function of 10-year mortality risk using the Charlson Comorbidity Index. P-values were adjusted using Hochberg’s correction for multiple-inference testing within each medical condition category. The most frequently diagnosed SUDs in 2010 were alcohol (57.6%), cannabis (14.9%), and opioid (12.9%). Patients with these SUDs had higher prevalence of major medical conditions than non-SUD patients (alcohol use disorders, 85.3% vs 55.3%; cannabis use disorders, 41.9% vs 23.0%; and opioid use disorders, 44.9% vs 26.1%; all P < 0.001). Patients with these SUDs also had higher disease burden than non-SUD patients; patients with opioid use disorders (M = 0.48; SE = 1.46) had particularly high disease burden (M = 0.23; SE = 0.09; P < 0.001). Common SUDs, particularly opioid use disorders, are associated with substantial disease burden for privately insured individuals without significant impediments to care. This signals the need to explore the full impact SUDs have on the course and outcome of prevalent conditions and initiate enhanced service engagement strategies to improve disease burden.
Authors: Bahorik AL; Satre DD; Kline-Simon AH; Weisner CM; Campbell CI
J Addict Med. 2017 Jan/Feb;11(1):3-9.
Smoking Trends Among Adults With Behavioral Health Conditions in Integrated Health Care: A Retrospective Cohort Study
Individuals with behavioral health conditions (BHCs) smoke at high rates and have limited success with quitting, despite impressive gains in recent decades in reducing the overall prevalence of smoking in the United States. This study examined smoking disparities among individuals with BHCs within an integrated health care delivery system with convenient access to tobacco treatments. The sample consisted of patients in an integrated health care delivery system in 2010-a group (N=155,733) with one or more of the five most prevalent BHCs (depressive disorders, anxiety disorders, substance use disorders, bipolar and related disorders, and attention-deficit hyperactivity disorder) and a group (N=155,733) without BHCs who were matched on age, sex, and medical home facility. The odds of smoking among patients with BHCs versus without BHCs were examined over four years using logistic regression generalized estimating equation models. Tobacco cessation medication utilization among a subset of smokers in 2010 was also examined. Although smoking prevalence decreased from 2010 to 2013 overall, the likelihood of smoking decreased significantly more slowly among patients with BHCs compared with patients without BHCs (p<.001), most notably among patients with substance use and bipolar and related disorders. Tobacco cessation medication use was low, and smokers with BHCs were more likely than smokers without BHCs to utilize these products (6.2% versus 3.6%, p<.001). Smoking decreased more slowly among individuals with BHCs compared with individuals without BHCs, even within an integrated health care system, highlighting the need to prioritize smoking cessation within specialty behavioral health treatment.
Authors: Young-Wolff KC; Kline-Simon AH; Das S; Mordecai DJ; Miller-Rosales C; Weisner C
Psychiatr Serv. 2016 Sep 01;67(9):996-1003. Epub 2016-04-15.
A call for comparative effectiveness research to learn whether routine clinical care decisions can protect from dementia and cognitive decline
Common diseases like diabetes, hypertension, and atrial fibrillation are probable risk factors for dementia, suggesting that their treatments may influence the risk and rate of cognitive and functional decline. Moreover, specific therapies and medications may affect long-term brain health through mechanisms that are independent of their primary indication. While surgery, benzodiazepines, and anti-cholinergic drugs may accelerate decline or even raise the risk of dementia, other medications act directly on the brain to potentially slow the pathology that underlies Alzheimer’s and other dementia. In other words, the functional and cognitive decline in vulnerable patients may be influenced by the choice of treatments for other medical conditions. Despite the importance of these questions, very little research is available. The Alzheimer’s Drug Discovery Foundation convened an advisory panel to discuss the existing evidence and to recommend strategies to accelerate the development of comparative effectiveness research on how choices in the clinical care of common chronic diseases may protect from cognitive decline and dementia.
Authors: Dacks PA; Whitmer RA; Fillit HM; et al.
Alzheimers Res Ther. 2016 Aug 20;8:33. Epub 2016-08-20.
Hazardous drinking among young adults seeking outpatient mental health services
Alcohol use can have a significant negative impact on young adults in mental health treatment. This cross-sectional study examined prevalence and factors associated with hazardous drinking among young adults seeking outpatient mental health services, rate of alcohol use disorders (AUDs), and the relationship between hazardous drinking and other types of substance use. Participants were 487 young adults ages 18-25 who completed self-administered computerized screening questions for alcohol and drug use. Alcohol use patterns were assessed and predictors of hazardous drinking (≥5 drinks on one or more occasions in the past year) were identified using logistic regression. Of the 487 participants, 79.8 % endorsed prior-year alcohol use, 52.3 % reported one or more episodes of hazardous drinking in the prior year and 8.2 % were diagnosed with an AUD. Rates of recent and lifetime alcohol, tobacco and marijuana use were significantly greater in those with prior-year hazardous drinking. In logistic regression, prior-year hazardous drinking was associated with lifetime marijuana use (OR 3.30, p < 0.001; 95 % CI 2.05, 5.28), lifetime tobacco use (OR 1.88, p = 0.004; 95 % CI 1.22, 2.90) and older age (OR 1.18 per year, p < 0.001; 95 % CI 1.08, 1.29). In an outpatient mental health setting, high rates of hazardous drinking were identified, and drinking was associated with history of other substance use. Results highlight patient characteristics associated with hazardous drinking that mental health providers should be aware of in treating young adults, especially older age and greater use of tobacco and marijuana.
Authors: Ordóñez AE; Ranney R; Schwartz M; Mathews CA; Satre DD
Addict Sci Clin Pract. 2016 08 09;11(1):12. Epub 2016-08-09.
The Association of Refractive Error with Glaucoma in a Multiethnic Population
To evaluate the association between refractive error and the prevalence of glaucoma by race or ethnicity. Cross-sectional study. Kaiser Permanente Northern California Health Plan members with refractive error measured at 35 years of age or older between 2008 and 2014 and with no history of cataract surgery, refractive surgery, or a corneal disorder. We identified 34 040 members with glaucoma or ocular hypertension (OHTN; cases) and 403 398 members without glaucoma (controls). Glaucoma cases were classified as primary angle-closure glaucoma (PACG); 1 of the 4 forms of open-angle glaucoma: primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), pigmentary glaucoma (PIGM), and pseudoexfoliation glaucoma (PEX); or OHTN. Refractive error, expressed as spherical equivalent (SE), was coded as a continuous trait and also as categories. Logistic regression analyses were used to estimate the association between refractive error and the prevalence of glaucoma overall and in specific racial or ethnic groups. The association between refractive error and glaucoma subtypes evaluated as odds ratios (ORs) with 95% confidence intervals (CIs). In controls, the mean SE was -0.59 diopters (D) (standard deviation, 2.62 D). Each 1-D reduction in SE was associated with a 22% decrease in the odds of PACG (OR, 0.78; 95% CI, 0.77-0.80) and with increases in the odds of open-angle glaucoma ranging from 1.23 (95% CI, 1.20-1.26) for PIGM, to 1.07 (95% CI, 1.03-1.11) for PEX, and to 1.05 (95% CI, 1.04-1.06) for OHTN. In addition, we observed a stronger association between myopia and POAG among non-Hispanic whites (OR, 1.12; 95% CI, 1.11-1.13) and NTG among Asians (OR, 1.17; 95% CI, 1.15-1.20) and non-Hispanic whites (OR, 1.19; 95% CI, 1.15-1.22). Myopia was associated with an increased prevalence of all forms of open-angle glaucoma and OHTN, whereas hyperopia was associated with a substantially increased prevalence of PACG. Although high myopia is a strong risk factor for glaucoma subtypes, low and moderate myopia also have a significant effect on glaucoma risk. Additionally, there were moderate racial differences in the association of myopia with the risk of POAG and NTG.
Authors: Shen L; Melles RB; Metlapally R; Barcellos L; Schaefer C; Risch N; Herrinton LJ; Wildsoet C; Jorgenson E
Ophthalmology. 2015 Aug 7.
Multiple sclerosis risk loci and disease severity in 7,125 individuals from 10 studies
We investigated the association between 52 risk variants identified through genome-wide association studies and disease severity in multiple sclerosis (MS). Ten unique MS case data sets were analyzed. The Multiple Sclerosis Severity Score (MSSS) was calculated using the Expanded Disability Status Scale at study entry and disease duration. MSSS was considered as a continuous variable and as 2 dichotomous variables (median and extreme ends; MSSS of ?5 vs >5 and MSSS of <2.5 vs ?7.5, respectively). Single nucleotide polymorphisms (SNPs) were examined individually and as both combined weighted genetic risk score (wGRS) and unweighted genetic risk score (GRS) for association with disease severity. Random-effects meta-analyses were conducted and adjusted for cohort, sex, age at onset, and HLA-DRB1*15:01. A total of 7,125 MS cases were analyzed. The wGRS and GRS were not strongly associated with disease severity after accounting for cohort, sex, age at onset, and HLA-DRB1*15:01. After restricting analyses to cases with disease duration ?10 years, associations were null (p value ?0.05). No SNP was associated with disease severity after adjusting for multiple testing. The largest meta-analysis of established MS genetic risk variants and disease severity, to date, was performed. Results suggest that the investigated MS genetic risk variants are not associated with MSSS, even after controlling for potential confounders. Further research in large cohorts is needed to identify genetic determinants of disease severity using sensitive clinical and MRI measures, which are critical to understanding disease mechanisms and guiding development of effective treatments.
Authors: George MF; Schaefer C; Barcellos LF; et al.
Neurol Genet. 2016 Aug;2(4):e87. Epub 2016-08-04.
Examination of the Effects of an Intervention Aiming to Link Patients Receiving Addiction Treatment With Health Care: The LINKAGE Clinical Trial
Research has shown that higher activation and engagement with health care is associated with better self-management. To our knowledge, the linkage intervention (LINKAGE) is the first to engage patients receiving addiction treatment with health care using the electronic health record and a patient activation approach. To examine the effects of an intervention aiming to link patients receiving addiction treatment with health care. A nonrandomized clinical trial evaluating the LINKAGE intervention vs usual care by applying an alternating 3-month off-and-on design over 30 months. Participants were recruited from an outpatient addiction treatment clinic in a large health system between April 7, 2011, and October 2, 2013. Six group-based, manual-guided sessions on patient engagement in health care and the use of health information technology resources in the electronic health record, as well as facilitated communication with physicians, vs usual care. Primary outcomes, measured at 6 months after enrollment, were patient activation (by interview using the Patient Activation Measure), patient engagement in health care (by interview and electronic health record), and alcohol, drug, and depression outcomes (by interview using the Addiction Severity Index for alcohol and drug outcomes and Patient Health Questionnaire (PHQ) for depression). A total of 503 patients were recruited and assigned to the LINKAGE (n?=?252) or usual care (n?=?251) conditions, with no differences in baseline characteristics between conditions. The mean (SD) age of the patients was 42.5 (11.8) years, 31.0% (n?=?156) were female, and 455 (90.5%) completed the 6-month interview. Compared with usual care participants, LINKAGE participants showed an increase in the mean number of log-in days (incidence rate ratio, 1.53; 95% CI, 1.19-1.97; P?=?.001). Similar results were found across types of patient portal use (communicating by email, viewing laboratory test results and information, and obtaining medical advice). LINKAGE participants were more likely to talk with their physicians about addiction problems (odds ratio, 2.30; 95% CI, 1.52-3.49; P?
Authors: Weisner CM; Chi FW; Lu Y; Ross TB; Wood SB; Hinman A; Pating D; Satre D; Sterling SA
JAMA Psychiatry. 2016 Aug 01;73(8):804-14.
Depression, Compulsive Sexual Behavior, and Sexual Risk-Taking Among Urban Young Gay and Bisexual Men: The P18 Cohort Study
Young gay, bisexual, and other men who have sex with men (YMSM) are at increased likelihood of experiencing depression and engaging in condomless sexual behaviors. The goal of the current investigation was to examine the relationship between negative mood and compulsive sexual behavior (CSB) and to assess for their individual and combined influence on sexual risk-taking behavior among a diverse sample of YMSM in New York City (the P18 Cohort Study). We first analyzed sociodemographic, depressive symptoms, CSB, and sexual risk-taking from the cross-sectional data of 509, 18- or 19-year-old YMSM recruited using non-probability sampling. We found a significant positive correlation between CSB and depression and between CSB and frequency of condomless anal sex acts reported over the last 30 days. Multivariate results found that the presence of both depression and CSB contributed to elevated sexual risk-taking among these urban YMSM. Clinical implications include the importance of assessing for CSB when depression is present and vice versa in order to improve HIV prevention. Informed by minority stress theory and syndemic theory, our results suggest that interventions focused on the health of YMSM recognize that mental health and social context all interact to increase physical health vulnerability vis-a-vis sexual behaviors, depression, and CSB. Thus, HIV prevention and intervention programs need to incorporate mental health components and services that address these needs.
Authors: Storholm ED; Satre DD; Kapadia F; Halkitis PN
Arch Sex Behav. 2016 Aug;45(6):1431-41. Epub 2015-08-27.
Common coding variants in the HLA-DQB1 region confer susceptibility to age-related macular degeneration
Age-related macular degeneration (AMD) risk variants in the complement system point to the important role of immune response and inflammation in the pathogenesis of AMD. Although the human leukocyte antigen (HLA) region has a central role in regulating immune response, previous studies of genetic variation in HLA genes and AMD have been limited by sample size or incomplete coverage of the HLA region by first-generation genotyping arrays and imputation panels. Here, we conducted a large-scale HLA fine-mapping study with 4841 AMD cases and 23 790 controls of non-Hispanic white ancestry from the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging cohort. Genotyping was conducted using custom Affymetrix Axiom arrays, with dense coverage of the HLA region. Classic HLA polymorphisms were imputed using SNP2HLA, which utilizes a large reference panel to provide improved imputation accuracy of variants in this region. We examined a total of 6937 SNPs and 172 classical HLA alleles, conditioning on established AMD risk variants, which revealed novel associations with two non-synonymous SNPs in perfect linkage disequilibrium, rs9274390 and rs41563814 (odds ratio (OR)=1.21; P=1.4 × 10(-11)) corresponding to amino-acid changes at position 66 and 67 in HLA-DQB1, respectively, and the DQB1*02 classical HLA allele (OR=1.22; P=3.9 × 10(-10)) with the risk of AMD. We confirmed these association signals, again conditioning on established risk variants, in the MMAP data set of subjects with advanced AMD (rs9274390/rs41563814: OR=1.28; P=1.30 × 10(-3), DQB1*02: OR=1.32; P=9.00 × 10(-4)). These findings support a role of HLA class II alleles in the risk of AMD.
Authors: Jorgenson E; Melles RB; Hoffmann TJ; Jia X; Sakoda LC; Kvale MN; Banda Y; Schaefer C; Risch N; Shen L
Eur J Hum Genet. 2016 Jul;24(7):1049-55. Epub 2016-01-06.
Demographic, Insurance, and Health Characteristics of Newly Enrolled HIV-Positive Patients After Implementation of the Affordable Care Act in California
To examine changes in HIV-positive patient enrollment in a large health care delivery system before and after key Affordable Care Act (ACA) provisions went into effect in 2014. Analyses compared HIV-positive patients newly enrolled in Kaiser Permanente Northern California between January and June 2012 (n?=?339) to those newly enrolled between January and June 2014 through the California insurance exchange or via other mechanisms (n?=?549). After the ACA, the HIV-positive patient enrollment increased. These new enrollees were more likely to be male (93.6% vs 89.1%; P?=?.01), to be enrolled in high-deductible benefit plans (??$1000; 18.8% vs 5.5%; P?=?.01), and to have better HIV viral control (HIV RNA levels below limits of quantification 79.5% vs 73.6%; P?=?.05) compared with pre-ACA new enrollees. Among post-ACA new enrollees, there were more patients in the lowest and highest age groups. Post-ACA exchange enrollees (22%) were more likely to be male and to have high-deductible plans than those enrolled through other mechanisms. More men, higher deductibles, and better HIV viral control characterize newly enrolled HIV-positive patients after the ACA in California. Evolving characteristics of HIV-positive enrollees may affect HIV policy, patient care needs, and service utilization.
Authors: Satre DD; Parthasarathy S; Altschuler A; Silverberg MJ; Storholm E; Campbell CI
Am J Public Health. 2016 Jul;106(7):1211-3. Epub 2016-04-14.
A key challenge for motivational interviewing: training in clinical practice
Authors: Weisner C; Satre DD
Addiction. 2016 07;111(7):1154-6. Epub 2016-02-29.
A Randomized Clinical Trial of Motivational Interviewing to Reduce Alcohol and Drug Use Among Patients With Depression
This study examined the efficacy of Motivational Interviewing (MI) to reduce hazardous drinking and drug use among adults in treatment for depression. Randomized controlled trial based in a large outpatient psychiatry program in an integrated health care system in Northern California. The sample consisted of 307 participants ages 18 and over who reported hazardous drinking, drug use (primarily cannabis) or misuse of prescription drugs in the prior 30 days, and who scored ≥5 on the Patient Health Questionnaire (PHQ-9). Participants were randomized to receive either 3 sessions of MI (1 in person and 2 by phone) or printed literature about alcohol and drug use risks (control), as an adjunct to usual outpatient depression care. Measures included alcohol and drug use in the prior 30 days and PHQ-9 depression symptoms. Participants completed baseline in-person interviews and telephone follow-up interviews at 3 and 6 months (96 and 98% of the baseline sample, respectively). Electronic health records were used to measure usual care. At 6 months, MI was more effective than control in reducing rate of cannabis use (p = .037); and hazardous drinking (≥4 drinks in a day for women, ≥5 drinks in a day for men; p = .060). In logistic regression, assignment to MI predicted lower cannabis use at 6 months (p = .016) after controlling for covariates. Depression improved in both conditions. MI can be an effective intervention for cannabis use and hazardous drinking among patients with depression. (PsycINFO Database Record
Authors: Satre DD; Leibowitz A; Sterling SA; Lu Y; Travis A; Weisner C
J Consult Clin Psychol. 2016 Jul;84(7):571-9. Epub 2016-03-17.
Diabetes Technology: Uptake, Outcomes, Barriers, and the Intersection With Distress.
Patients managing type 1 diabetes have access to new technologies to assist in management. This manuscript has two aims: 1) to briefly review the literature on diabetes technology use and how this relates to psychological factors and 2) to present an example of human factors research using our data to examine psychological factors associated with technology use. Device/technology uptake and use has increased over the years and at present day is a common clinical practice. There are mixed results in terms of health and psychosocial outcomes, with specific subgroups doing better than others with technology. Our data demonstrated that patients have moderately elevated diabetes distress across differing types of technology used, from low-tech to high-tech options, possibly meaning that technology does not add or take away distress. In addition, users on multiple daily injections compared to all other technology groups have less positive attitudes about technology. Finally, we discuss implications for clinical practice and future research.
Authors: Naranjo D; Tanenbaum ML; Iturralde E; Hood KK;
J Diabetes Sci Technol. 2016 Jun 28;10(4):852-8. doi: 10.1177/1932296816650900. Print 2016 Jul.
Transforming the Health Care Response to Intimate Partner Violence: Addressing “Wicked Problems”
Authors: Young-Wolff KC; Kotz K; McCaw B
JAMA. 2016 Jun 21;315(23):2517-8.
A randomized clinical trial aimed at preventing poor psychosocial and glycemic outcomes in teens with type 1 diabetes (T1D).
Adolescents with type 1 diabetes have an increased risk for a variety of emotional and behavioral challenges as well as negative diabetes outcomes. This study was designed to compare the effectiveness of a depression-prevention, resilience promotion program with an advanced diabetes education program. Each program consisted of 9 group-based sessions. There were 264 adolescents enrolled in this multi-site randomized clinical trial. The primary outcomes were depressive symptoms and glycemic control; secondary outcomes included resilience skills, diabetes management and adherence, and diabetes-specific distress. The goal of the present paper is to describe the study design, the intervention, and the baseline characteristics of the sample. Preliminary data suggests that enrollment, randomization and retention were successful. Longitudinal follow-up and examination of mechanisms of action as they relate to psychosocial and glycemic outcomes will be explored in the future.
Authors: Weissberg-Benchell J; Rausch J; Iturralde E; Jedraszko A; Hood K;
Contemp Clin Trials. 2016 Jul;49:78-84. doi: 10.1016/j.cct.2016.05.006. Epub 2016 Jun 4.
Protocol: changes in rates of opioid overdose and poisoning events in an integrated health system following the introduction of a formulation of OxyContin® with abuse-deterrent properties
Addiction, overdoses and deaths resulting from prescription opioids have increased dramatically over the last decade. In response, several manufacturers have developed formulations of opioids with abuse-deterrent properties. For many of these products, the Food and Drug Administration (FDA) recognized the formulation with labeling claims and mandated post-marketing studies to assess the abuse-deterrent effects. In response, we assess differences in rates of opioid-related overdoses and poisonings prior to and following the introduction of a formulation of OxyContin® with abuse-deterrent properties. To assess effects of this formulation, electronic medical record (EMR) data from Kaiser Permanente Northwest (KPNW) and Kaiser Permanente Northern California (KPNC) are linked to state death data and compared to chart audits. Overdose and poisoning events will be categorized by intentionality and number of agents involved, including illicit drugs and alcohol. Using 6-month intervals over a 10-year period, trends will be compared in rates of opioid-related overdoses and poisoning events associated with OxyContin® to rates of events associated with other oxycodone and opioid formulations. Qualitative interviews with patients and relatives of deceased patients will be conducted to capture circumstances surrounding events. This study assesses and tracks changes in opioid-related overdoses and poisoning events prior to and following the introduction of OxyContin® with abuse-deterrent properties. Public health significance is high because these medications are designed to reduce abuse-related behaviors that lead to important adverse outcomes, including overdoses and deaths.
Authors: Janoff SL; Perrin NA; Coplan PM; Chilcoat HD; Campbell CI; Green CA
BMC Pharmacol Toxicol. 2016 May 14;17(1):21. Epub 2016-05-14.
High consumption of coffee is associated with decreased multiple sclerosis risk; results from two independent studies
Previous studies on consumption of caffeine and risk of multiple sclerosis (MS) have yielded inconclusive results. We aimed to investigate whether consumption of coffee is associated with risk of MS. Using two population-representative case-control studies (a Swedish study comprising 1620 cases and 2788 controls, and a US study comprising 1159 cases and 1172 controls), participants with different habits of coffee consumption based on retrospective data collection were compared regarding risk of MS, by calculating ORs with 95% CIs. Logistic regression models were adjusted for a broad range of potential confounding factors. Compared with those who reported no coffee consumption, the risk of MS was substantially reduced among those who reported a high consumption of coffee exceeding 900 mL daily (OR 0.70 (95% CI 0.49 to 0.99) in the Swedish study, and OR 0.69 (95% CI 0.50 to 0.96) in the US study). Lower odds of MS with increasing consumption of coffee were observed, regardless of whether coffee consumption at disease onset or 5 or 10 years prior to disease onset was considered. In accordance with studies in animal models of MS, high consumption of coffee may decrease the risk of developing MS. Caffeine, one component of coffee, has neuroprotective properties, and has been shown to suppress the production of proinflammatory cytokines, which may be mechanisms underlying the observed association. However, further investigations are needed to determine whether exposure to caffeine underlies the observed association and, if so, to evaluate its mechanisms of action.
Authors: Hedström AK; Mowry EM; Gianfrancesco MA; Shao X; Schaefer CA; Shen L; Olsson T; Barcellos LF; Alfredsson L
J Neurol Neurosurg Psychiatr. 2016 May;87(5):454-60. Epub 2016-03-03.
Identification of Susceptibility Loci for Cutaneous Squamous Cell Carcinoma
We report a genome-wide association study of cutaneous squamous cell carcinoma conducted among non-Hispanic white members of the Kaiser Permanente Northern California health care system. The study includes a genome-wide screen of 61,457 members (6,891 cases and 54,566 controls) genotyped on the Affymetrix Axiom European array and a replication phase involving an independent set of 6,410 additional members (810 cases and 5,600 controls). Combined analysis of screening and replication phases identified 10 loci containing single-nucleotide polymorphisms (SNPs) with P-values < 5 × 10(-8). Six loci contain genes in the pigmentation pathway; SNPs at these loci appear to modulate squamous cell carcinoma risk independently of the pigmentation phenotypes. Another locus contains HLA class II genes studied in relation to elevated squamous cell carcinoma risk following immunosuppression. SNPs at the remaining three loci include an intronic SNP in FOXP1 at locus 3p13, an intergenic SNP at 3q28 near TP63, and an intergenic SNP at 9p22 near BNC2. These findings provide insights into the genetic factors accounting for inherited squamous cell carcinoma susceptibility.
Authors: Asgari MM; Wang W; Ioannidis NM; Itnyre J; Hoffmann T; Jorgenson E; Whittemore AS
J Invest Dermatol. 2016 May;136(5):930-7. Epub 2016-01-29.
Specifying and Pilot Testing Quality Measures for the American Society of Addiction Medicine’s Standards of Care
In 2013, the American Society of Addiction Medicine (ASAM) approved its Standards of Care for the Addiction Specialist Physician. Subsequently, an ASAM Performance Measures Panel identified and prioritized the standards to be operationalized into performance measures. The goal of this study is to describe the process of operationalizing 3 of these standards into quality measures, and to present the initial measure specifications and results of pilot testing these measures in a large health care system. By presenting the process rather than just the end results, we hope to shed light on the measure development process to educate, and also to stimulate debate about the decisions that were made. Each measure was decomposed into major concepts. Then each concept was operationalized using commonly available administrative data sources. Alternative specifications examined and sensitivity analyses were conducted to inform decisions that balanced accuracy, clinical nuance, and simplicity. Using data from the US Veterans Health Administration (VHA), overall performance and variation in performance across 119 VHA facilities were calculated. Three measures were operationalized and pilot tested: pharmacotherapy for alcohol use disorder, pharmacotherapy for opioid use disorder, and timely follow-up after medically managed withdrawal (aka detoxification). Each measure was calculable with available data, and showed ample room for improvement (no ceiling effects) and wide facility-level variability. Next steps include conducting feasibility and pilot testing in other health care systems and other contexts such as standalone addiction treatment programs, and also to study the specification and predictive validity of these measures.
Authors: Harris AH; Weisner CM; Chalk M; Capoccia V; Chen C; Thomas CP
J Addict Med. 2016 May-Jun;10(3):148-55.
Point Prevalence of Co-Occurring Behavioral Health Conditions and Associated Chronic Disease Burden AmongAdolescents
To examine the point prevalence of behavioral health conditions (BHCs) and co-occurring chronic medical conditions among adolescents in an integrated health system. The sample consisted of adolescents in an integrated health care system diagnosed with at least 1 of the 5 most prevalent BHCs in 2014 (n = 30,643), and patients without a BHC matched on age, sex, and medical home facility (n = 30,643). Electronic health record data was used to identify all adolescents aged 11 to 18 years with at least 1 BHC diagnosis on their diagnosis list, which included current and pre-existing diagnoses from an outpatient (including psychiatry and chemical dependency specialty treatment), inpatient, or emergency department visit at a Kaiser Permanente Northern California (KPNC) facility between January 1, 2014, and December 31, 2014. The odds of having general medical conditions and specific chronic diseases were compared between adolescents with and without BHCs. Among adolescents with at least 1 BHC in 2014, the 5 most common BHCs were: depressive disorders (42%), anxiety disorders (40%), attention-deficit/hyperactivity disorders (ADHDs; 37%), substance use disorders (SUDs; 10%), and bipolar spectrum disorders (8%). Overall, patients with a BHC did not have higher odds of any medical comorbidity compared with non-BHC patients. However, compared to individuals without BHCs, adolescents with depression (odds ratio [OR] = 1.16, 95% CI = 1.08-1.26), anxiety (OR = 1.30, 95% CI = 1.20-1.41), and substance use (OR = 1.25, 95% CI = 1.05-1.49) disorders had significantly higher odds of any medical comorbidities; individuals with ADHD and bipolar disorder did not differ from patients without BHCs. BHCs were common and were associated with a disproportionately higher burden of chronic medical disease among adolescents in a large, private health care delivery system. As comorbidity can lead to elevated symptom burden, functional impairment, and treatment complexity, the study findings call for implementation of effective collaborative models of care for these patients.
Authors: Kline-Simon AH; Weisner C; Sterling S
J Am Acad Child Adolesc Psychiatry. 2016 May;55(5):408-14. Epub 2016-03-02.
Potential Unintended Consequences of Electronic Cigarette Use in Drinking Venues
Authors: Young-Wolff KC; McKee SA
Alcohol Clin Exp Res. 2016 05;40(5):939-41. Epub 2016-04-07.
A meta-analysis of individual participant data reveals an association between circulating levels of IGF-I and prostate cancer risk
The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ? 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. After mutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development. Cancer Res; 76(8); 2288-300. ©2016 AACR.
Authors: Travis RC; Hamdy FC; Schenk JM; Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group; et al.
Cancer Res. 2016 04 15;76(8):2288-300. Epub 2016-02-26.
Prevalence of migraine in a diverse community-electronic methods for migraine ascertainment in a large integrated health plan
The growing availability of electronic health data provides an opportunity to ascertain diagnosis-specific cases via systematic methods for sample recruitment for clinical research and health services evaluation. We developed and implemented a migraine probability algorithm (MPA) to identify migraine from electronic health records (EHR) in an integrated health plan. We identified all migraine outpatient diagnoses and all migraine-specific prescriptions for a five-year period (April 2008-March 2013) from the Kaiser Permanente, Northern California (KPNC) EHR. We developed and evaluated the MPA in two independent samples, and derived prevalence estimates of medically-ascertained migraine in KPNC by age, sex, and race. The period prevalence of medically-ascertained migraine among KPNC adults during April 2008-March 2013 was 10.3% (women: 15.5%, men: 4.5%). Estimates peaked with age in women but remained flat for men. Prevalence among Asians was half that of whites. We demonstrate the feasibility of an EHR-based algorithm to identify cases of diagnosed migraine and determine that prevalence patterns by our methods yield results comparable to aggregate estimates of treated migraine based on direct interviews in population-based samples. This inexpensive, easily applied EHR-based algorithm provides a new opportunity for monitoring changes in migraine prevalence and identifying potential participants for research studies.
Authors: Pressman A; Jacobson A; Eguilos R; Gelfand A; Huynh C; Hamilton L; Avins A; Bakshi N; Merikangas K
Cephalalgia. 2016 Apr;36(4):325-34. Epub 2015-06-11.
Methadone, buprenorphine and preferences for opioid agonist treatment: A qualitative analysis
Patients and clinicians have begun to recognize the advantages and disadvantages of buprenorphine relative to methadone, but factors that influence choices between these two medications remain unclear. For example, we know little about how patients’ preferences and previous experiences influence treatment decisions. Understanding these issues may enhance treatment engagement and retention. Adults with opioid dependence (n=283) were recruited from two integrated health systems to participate in interviews focused on prior experiences with treatment for opioid dependence, knowledge of medication options, preferences for treatment, and experiences with treatment for chronic pain in the context of problems with opioids. Interviews were audio-recorded, transcribed verbatim, and coded using Atlas.ti. Our analysis revealed seven areas of consideration for opioid agonist treatment decision-making: (1) awareness of treatment options; (2) expectations and goals for duration of treatment and abstinence; (3) prior experience with buprenorphine or methadone; (4) need for accountability and structured support; (5) preference to avoid methadone clinics or associated stigma; (6) fear of continued addiction and perceived difficulty of withdrawal; and (7) pain control. The availability of medication options increases the need for clear communication between clinicians and patients, for additional patient education about these medications, and for collaboration and patient influence over choices in treatment decision-making. Our results suggest that access to both methadone and buprenorphine will increase treatment options and patient choice and may enhance treatment adherence and outcomes.
Authors: Yarborough BJ; Stumbo SP; McCarty D; Mertens J; Weisner C; Green CA
Drug Alcohol Depend. 2016 Mar 1;160:112-8. Epub 2016-Jan-06.
Association Between Lifetime Marijuana Use and Cognitive Function in Middle Age: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Marijuana use is increasingly common in the United States. It is unclear whether it has long-term effects on memory and other domains of cognitive function. To study the association between cumulative lifetime exposure to marijuana use and cognitive performance in middle age. We used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a cohort of 5115 black and white men and women aged 18 to 30 years at baseline from March 25, 1985, to June 7, 1986 (year 0), and followed up over 25 years from June 7, 1986, to August 31, 2011, to estimate cumulative years of exposure to marijuana (1 year = 365 days of marijuana use) using repeated measures and to assess associations with cognitive function at year 25. Linear regression was used to adjust for demographic factors, cardiovascular risk factors, tobacco smoking, use of alcohol and illicit drugs, physical activity, depression, and results of the mirror star tracing test (a measure of cognitive function) at year 2. Data analysis was conducted from June 7, 1986, to August 31, 2011. Three domains of cognitive function were assessed at year 25 using the Rey Auditory Verbal Learning Test (verbal memory), the Digit Symbol Substitution Test (processing speed), and the Stroop Interference Test (executive function). Among 3385 participants with cognitive function measurements at the year 25 visit, 2852 (84.3%) reported past marijuana use, but only 392 (11.6%) continued to use marijuana into middle age. Current use of marijuana was associated with worse verbal memory and processing speed; cumulative lifetime exposure was associated with worse performance in all 3 domains of cognitive function. After excluding current users and adjusting for potential confounders, cumulative lifetime exposure to marijuana remained significantly associated with worse verbal memory. For each 5 years of past exposure, verbal memory was 0.13 standardized units lower (95% CI, -0.24 to -0.02; P = .02), corresponding to a mean of 1 of 2 participants remembering 1 word fewer from a list of 15 words for every 5 years of use. After adjustment, we found no associations with lower executive function (-0.03 [95% CI, -0.12 to 0.07]; P = .56) or processing speed (-0.04 [95% CI, -0.16 to 0.08]; P = .51). Past exposure to marijuana is associated with worse verbal memory but does not appear to affect other domains of cognitive function.
Authors: Auer R; Whitmer RA; Pletcher MJ; et al.
JAMA Intern Med. 2016 Mar;176(3):352-61.
A novel method for estimating transgender status using electronic medical records
We describe a novel algorithm for identifying transgender people and determining their male-to-female (MTF) or female-to-male (FTM) identity in electronic medical records of an integrated health system. A computer program scanned Kaiser Permanente Georgia electronic medical records from January 2006 through December 2014 for relevant diagnostic codes, and presence of specific keywords (e.g., “transgender” or “transsexual”) in clinical notes. Eligibility was verified by review of de-identified text strings containing targeted keywords, and if needed, by an additional in-depth review of records. Once transgender status was confirmed, FTM or MTF identity was assessed using a second program and another round of text string reviews. Of 813,737 members, 271 were identified as possibly transgender: 137 through keywords only, 25 through diagnostic codes only, and 109 through both codes and keywords. Of these individuals, 185 (68%, 95% confidence interval [CI]: 62%-74%) were confirmed as definitely transgender. The proportions (95% CIs) of definite transgender status among persons identified via keywords, diagnostic codes, and both were 45% (37%-54%), 56% (35%-75%), and 100% (96%-100%). Of the 185 definitely transgender people, 99 (54%, 95% CI: 46%-61%) were MTF, 84 (45%, 95% CI: 38%-53%) were FTM. For two persons, gender identity remained unknown. Prevalence of transgender people (per 100,000 members) was 4.4 (95% CI: 2.6-7.4) in 2006 and 38.7 (95% CI: 32.4-46.2) in 2014. The proposed method of identifying candidates for transgender health studies is low cost and relatively efficient. It can be applied in other similar health care systems.
Authors: Roblin D; Hunkeler E; Goodman M; et al.
Ann Epidemiol. 2016 Mar;26(3):198-203. Epub 2016-02-04.
Inequalities in dementia incidence between six racial and ethnic groups over 14years
Reducing racial/ethnic disparities is a primary objective of the National Alzheimer’s Plan (NAPA), yet direct comparisons within large samples representing diversity of the United States are lacking. Dementia incidence from January 1, 2000 to December 31, 2013 and a 25-year cumulative risk in 274,283 health care members aged 64+ (n = 18,778 African-American, n = 4543 American Indian/Alaska Native [AIAN], n = 21,000 Latino, n = 440 Pacific Islander, n = 206,490 white, n = 23,032 Asian-Americans). Cox proportional hazard models were adjusted for age, sex, medical utilization, and comorbidities. Dementia incidence (n = 59,555) was highest for African-Americans (26.6/1000 person-years) and AIANs (22.2/1000 person-years); intermediate for Latinos (19.6/1000 person-years), Pacific Islanders (19.6/1000 person-years), and whites (19.3/1000 person-years) and lowest among Asian-Americans (15.2/1000 person-years). Risk was 65% greater for African-Americans (hazard ratio = 1.65; 95% confidence interval = 1.58-1.72) versus Asian-Americans. Cumulative 25-year risk at age 65 was as follows: 38% African-Americans, 35% AIANs, 32% Latino, 25% Pacific Islanders, 30% white, and 28% Asian-Americans. Dementia rates varied over 60% between groups, providing a comprehensive benchmark for the NAPA goal of reducing disparities.
Authors: Mayeda ER; Glymour MM; Quesenberry CP; Whitmer RA
Alzheimers Dement. 2016 Mar;12(3):216-24. Epub 2016-02-11.
Fetal exposure to maternal stress and risk for schizophrenia spectrum disorders among offspring: Differential influences of fetal sex
Exposure to adverse life events during pregnancy has been linked to increased risk of schizophrenia spectrum disorders (SSD) in offspring. Nevertheless, much of the previous work inferred maternal stress from severe life events rather than directly assessing maternal reports of stress. The present study aimed to examine maternal reports of stress during pregnancy and risk for offspring SSD. Participants were 95 SSD cases and 206 controls who were offspring from a large birth cohort study that followed pregnant women from 1959 to 1966. During pregnancy interviews, women were asked if anything worrisome had occurred recently. Interviews were qualitatively coded for stress-related themes, including reports of daily life stress, by two independent raters. None of the maternal psychosocial stress themes were significantly associated with increased odds of offspring SSD in analyses of the full sample. However, results indicated a significant daily life stress by infant sex interaction. Maternal daily life stress during pregnancy was associated with significantly increased odds of SSD among male offspring. Findings suggest sex-specific fetal sensitivity to maternal reported daily life stress during pregnancy on risk for SSD, with males appearing to be more vulnerable to the influences of maternal stress during pregnancy.
Authors: Fineberg AM; Ellman LM; Schaefer CA; Maxwell SD; Shen L; H Chaudhury N; Cook AL; Bresnahan MA; Susser ES; Brown AS
Psychiatry Res. 2016 Feb 28;236:91-7. Epub 2015-12-18.
First translational ‘Think Tank’ on cerebrovascular disease, cognitive impairment and dementia
As the human population continues to age, an increasing number of people will exhibit significant deficits in cognitive function and dementia. It is now recognized that cerebrovascular, metabolic and neurodegenerative diseases all play major roles in the evolution of cognitive impairment and dementia. Thus with our more recent recognition of these relationships and our need to understand and more positively impact on this world health problem, “The Leo and Anne Albert Charitable Trust” (Gene Pranzo, Trustee with significant support from Susan Brogan, Meeting Planner) provided generous support for this inaugural international workshop that was held from April 13-16, 2015 at the beautiful Ritz Carlton Golf Resort in North Naples, Florida. Researchers from SUNY Downstate Medical Center, Brooklyn, NY organized the event by selecting the present group of translationally inclined preclinical, clinical and population scientists focused on cerebrovascular disease (CVD) risk and its progression to vascular cognitive impairment (VCI) and dementia. Participants at the workshop addressed important issues related to aging, cognition and dementia by: (1) sharing new data, information and perspectives that intersect vascular, metabolic and neurodegenerative diseases, (2) discussing gaps in translating population risk, clinical and preclinical information to the progression of cognitive loss, and (3) debating new approaches and methods to fill these gaps that can translate into future therapeutic interventions. Participants agreed on topics for group discussion prior to the meeting and focused on specific translational goals that included promoting better understanding of dementia mechanisms, the identification of potential therapeutic targets for intervention, and discussed/debated the potential utility of diagnostic/prognostic markers. Below summarizes the new data-presentations, concepts, novel directions and specific discussion topics addressed by this international translational team at our “First Leo and Anne Albert Charitable Trust ‘Think Tank’ VCI workshop”.
Authors: Barone FC; Whitmer R; Zhang ZG; et al.
J Transl Med. 2016 Feb 13;14:50. Epub 2016-Feb-13.
Feasibility study for remote assessment of cognitive function in multiple sclerosis
Cognitive impairment is common in multiple sclerosis (MS), and affects employment and quality of life. Large studies are needed to identify risk factors for cognitive decline. Currently, a MS-validated remote assessment for cognitive function does not exist. Studies to determine feasibility of large remote cognitive function investigations in MS have not been published. To determine whether MS patients would participate in remote cognitive studies. We utilized the Modified Telephone Interview for Cognitive Status (TICS-M), a previously validated phone assessment for cognitive function in healthy elderly populations to detect mild cognitive impairment. We identified factors that influenced participation rates. We investigated the relationship between MS risk factors and TICS-M score in cases, and score differences between cases and control individuals. The TICS-M was administered to MS cases and controls. Linear and logistic regression models were utilized. 11.5% of eligible study participants did not participate in cognitive testing. MS cases, females and individuals with lower educational status were more likely to refuse (p<0.001). Cases who did complete testing did not differ in terms of perceived cognitive deficit compared to cases that did participate. More severe disease, smoking, and being male were associated with a lower TICS-M score among cases (p<0.001). The TICS-M score was significantly lower in cases compared to controls (p=0.007). Our results demonstrate convincingly that a remotely administered cognitive assessment is quite feasible for conducting large epidemiologic studies in MS, and lay the much needed foundation for future work that will utilize MS-validated cognitive measures.
Authors: George MF; Holingue CB; Briggs FB; Shao X; Bellesis KH; Whitmer RA; Schaefer C; Benedict RH; Barcellos LF
J Neurol Neuromedicine. 2016;1(8):10-18.
Assessing the Value of High-Quality Care for Work-Associated Carpal Tunnel Syndrome in a Large Integrated Health Care System: Study Design
Little is known about quality of care for occupational health disorders, although it may affect worker health and workers’ compensation costs. Carpal tunnel syndrome (CTS) is a common work-associated condition that causes substantial disability. To describe the design of a study that is assessing quality of care for work-associated CTS and associations with clinical outcomes and costs. Prospective observational study of 477 individuals with new workers’ compensation claims for CTS without acute trauma who were treated at 30 occupational health clinics from 2011 to 2013 and followed for 18 months. Timing of key clinical events, adherence to 45 quality measures, changes in scores on the Boston Carpal Tunnel Questionnaire and 12-item Short Form Health Survey Version 2 (SF-12v2), and costs associated with medical care and disability. Two hundred sixty-seven subjects (56%) received a diagnosis of CTS and had claims filed around the first visit to occupational health, 104 (22%) received a diagnosis before that visit and claim, and 98 (21%) received a diagnosis or had claims filed after that visit. One hundred seventy-eight (37%) subjects had time off work, which started around the time of surgery in 147 (83%) cases and lasted a median of 41 days (interquartile range = 42 days). The timing of diagnosis varied, but time off work was generally short and related to surgery. If associations of quality of care with key medical, economic, and quality-of-life outcomes are identified for work-associated CTS, systematic efforts to evaluate and improve quality of medical care for this condition are warranted.
Authors: Conlon C; Asch S; Hanson M; Avins A; Levitan B; Roth C; Robbins M; Dworsky M; Seabury S; Nuckols T
Perm J. 2016 Fall;20(4):87-95. Epub 2016-10-03.
The introduction of generic risperidone in Medicare Part D
The introduction of generic second-generation antipsychotics (SGAs), starting with risperidone in July 2008, could reduce antipsychotic spending and cost-related use barriers. This study examines associations between generic risperidone use and spending and adherence after introduction among Medicare Advantage (MA) beneficiaries. Historic cohort study. The study included MA beneficiaries receiving SGA treatment prior to July 2008. We examined antipsychotic spending using linear models, adherence (proportion of days covered ? 80%) using logistic models, and nonpersistence (time to first gap in antipsychotic use > 30 days) in 2009 using Cox proportional hazard models, comparing beneficiaries with versus without generic use, adjusting for individual and plan characteristics. Between July 2008 and December 2009, 22.8% of beneficiaries had ? 1 fill of generic risperidone: 73% of those previously using branded risperidone and 6.7% of those previously using other SGAs. Beneficiaries in private fee-for-service (FFS) versus health maintenance organization (HMO) plans had lower rates of generic use (hazard ratio [HR], 0.73 [95% CI, 0.56-0.96]); however, cost-sharing levels were not associated with generic use. Compared with beneficiaries who continued using other SGAs, those who switched from other SGAs to generic risperidone in 2008 had lower out-of-pocket spending (-$214; 95% CI, -$314 to -$115), higher adherence (odds ratio, 2.34; 95% CI, 1.62-3.40) and lower rates of nonpersistence (HR, 0.56; 95% CI, 0.46-0.69) in 2009. Generic use was concentrated among patients previously using branded risperidone. HMO plans appeared to be more effective at encouraging generic use than unmanaged private FFS plans; however, patient financial incentives had limited influence on switching. Additional opportunity remains to encourage greater generic SGA use, reduce spending, and potentially improve treatment adherence and outcomes.
Authors: Fung V; Price M; Busch AB; Landrum MB; Fireman B; Nierenberg AA; Newhouse JP; Hsu J
Am J Manag Care. 2016 Jan;22(1):41-8.
Measures of outcome for stimulant trials: ACTTION recommendations and research agenda
The development and approval of an efficacious pharmacotherapy for stimulant use disorders has been limited by the lack of a meaningful indicator of treatment success, other than sustained abstinence. In March, 2015, a meeting sponsored by Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) was convened to discuss the current state of the evidence regarding meaningful outcome measures in clinical trials for stimulant use disorders. Attendees included members of academia, funding and regulatory agencies, pharmaceutical companies, and healthcare organizations. The goal was to establish a research agenda for the development of a meaningful outcome measure that may be used as an endpoint in clinical trials for stimulant use disorders. Based on guidelines for the selection of clinical trial endpoints, the lessons learned from prior addiction clinical trials, and the process that led to identification of a meaningful indicator of treatment success for alcohol use disorders, several recommendations for future research were generated. These include a focus on the validation of patient reported outcome measures of functioning, the exploration of patterns of stimulant abstinence that may be associated with physical and/or psychosocial benefits, the role of urine testing for validating self-reported measures of stimulant abstinence, and the operational definitions for reduction-based measures in terms of frequency rather than quantity of stimulant use. These recommendations may be useful for secondary analyses of clinical trial data, and in the design of future clinical trials that may help establish a meaningful indicator of treatment success.
Authors: Kiluk BD; Woody G; Strain EC; et al.
Drug Alcohol Depend. 2016 Jan 1;158:1-7. Epub 2015-11-21.
Effect of Early Adult Patterns of Physical Activity and Television Viewing on Midlife Cognitive Function
Sedentary behaviors and physical inactivity are not only increasing worldwide but also are critical risk factors for adverse health outcomes. Yet, few studies have examined the effects of sedentary behavior on cognition or the long-term role of either behavior in early to middle adulthood. To investigate the association between 25-year patterns of television viewing and physical activity and midlife cognition. Prospective study of 3247 adults (black and white races; aged 18-30 years) enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) Study (March 25, 1985, to August 31, 2011). Data analysis was performed June 1, 2014, through April 15, 2015. We assessed television viewing and physical activity at repeated visits (?3 assessments) over 25 years using a validated questionnaire. A 25-year pattern of high television viewing was defined as watching TV above the upper baseline quartile (>3 hours/d) for more than two-thirds of the visits, and a 25-year pattern of low physical activity was defined as activity levels below the lower, sex-specific baseline quartile for more than two-thirds of the of the visits. We evaluated cognitive function at year 25 using the Digit Symbol Substitution Test (DSST), Stroop test, and Rey Auditory Verbal Learning Test. At baseline, the mean (SD) age of the 3247 study participants was 25.1 (3.6) years, 1836 (56.5%) were female, 1771 (54.5%) were white, and 3015 (92.9%) had completed at least high school. Compared with participants with low television viewing, those with high television viewing during 25 years (353 of 3247 [10.9%]) were more likely to have poor cognitive performance (<1 SD below the race-specific mean) on the DSST and Stroop test, with findings reported as adjusted odds ratio (95% CI): DSST, 1.64 (1.21-2.23) and Stroop test, 1.56 (1.13-2.14), but not the Rey Auditory Verbal Learning Test, adjusted for age, race, sex, educational level, smoking, alcohol use, body mass index, and hypertension. Low physical activity during 25 years in 528 of 3247 participants (16.3%) was significantly associated with poor performance on the DSST, 1.47 (1.14-1.90). Compared with participants with low television viewing and high physical activity, the odds of poor performance were almost 2 times higher for adults with both high television viewing and low physical activity in 107 of 3247 (3.3%) (DSST, 1.95 [1.19-3.22], and Stroop test, 2.20 [1.36-3.56]). High television viewing and low physical activity in early adulthood were associated with worse midlife executive function and processing speed. This is one of the first studies to demonstrate that these risk behaviors may be critical targets for prevention of cognitive aging even before middle age.
Authors: Hoang TD; Reis J; Zhu N; Jacobs DR; Launer LJ; Whitmer RA; Sidney S; Yaffe K
JAMA Psychiatry. 2016 Jan;73(1):73-9.
Diabetes Pathology and Risk of Primary Open-Angle Glaucoma: Evaluating Causal Mechanisms by Using Genetic Information
Although type 2 diabetes (T2D) predicts glaucoma, the potential for unmeasured confounding has hampered causal conclusions. We performed separate sample genetic instrumental variable analyses using the Genetic Epidemiology Research Study on Adult Health and Aging cohort (n = 69,685; 1995-2013) to estimate effects of T2D on primary open-angle glaucoma (POAG; 3,554 cases). Genetic instrumental variables for overall and mechanism-specific (i.e., linked to T2D via influences on adiposity, ?-cell function, insulin regulation, or other metabolic processes) T2D risk were constructed by using 39 genetic polymorphisms established to predict T2D in other samples. Instrumental variable estimates indicated that T2D increased POAG risk (odds ratio = 2.53, 95% confidence interval: 1.04, 6.11). The instrumental variable for ?-cell dysregulation also significantly predicted POAG (odds ratio?-cell = 5.26, 95% confidence interval: 1.75, 15.85), even among individuals without diagnosed T2D, suggesting that metabolic dysregulation may increase POAG risk prior to T2D diagnosis. The T2D risk variant in the melatonin receptor 1B gene (MTNR1B) predicted risk of POAG independently of T2D status, indicating possible pleiotropic physiological functions of melatonin, but instrumental variable effect estimates were significant even excluding MTNR1B variants. To our knowledge, this is the first genetic instrumental variable study of T2D and glaucoma, providing a novel approach to evaluating this hypothesized relationship. Our findings substantially bolster observational evidence that T2D increases POAG risk.
Authors: Shen L; Walter S; Melles RB; Glymour MM; Jorgenson E
Am J Epidemiol. 2015 Nov 25.
Lumbar Imaging With Reporting Of Epidemiology (LIRE)-Protocol for a pragmatic cluster randomized trial
Diagnostic imaging is often the first step in evaluating patients with back pain and likely functions as a “gateway” to a subsequent cascade of interventions. However, lumbar spine imaging frequently reveals incidental findings among normal, pain-free individuals suggesting that treatment of these “abnormalities” may not be warranted. Our prior work suggested that inserting the prevalence of imaging findings in patients without back pain into spine imaging reports may reduce subsequent interventions. We are now conducting a pragmatic cluster randomized clinical trial to test the hypothesis that inserting this prevalence data into lumbar spine imaging reports for studies ordered by primary care providers will reduce subsequent spine-related interventions. We are using a stepped wedge design that sequentially randomizes 100 primary care clinics at four health systems to receive either standard lumbar spine imaging reports, or reports containing prevalence data for common imaging findings in patients without back pain. We capture all outcomes passively through the electronic medical record. Our primary outcome is spine-related intervention intensity based on Relative Value Units (RVUs) during the following year. Secondary outcomes include subsequent prescriptions for opioid analgesics and cross-sectional lumbar spine re-imaging. If our study shows that adding prevalence data to spine imaging reports decreases subsequent back-related RVUs, this intervention could be easily generalized and applied to other kinds of testing, as well as other conditions where incidental findings may be common. Our study also serves as a model for cluster randomized trials that are minimal risk and highly pragmatic.
Authors: Jarvik JG; Avins AL; Heagerty PJ; et al.
Contemp Clin Trials. 2015 Nov;45(Pt B):157-63. Epub 2015-10-19.
Implementation of Screening, Brief Intervention, and Referral to Treatment for Adolescents in Pediatric Primary Care: A Cluster Randomized Trial
Early intervention for substance use is critical to improving adolescent outcomes. Studies have found promising results for Screening, Brief Intervention, and Referral to Treatment (SBIRT), but little research has examined implementation. To compare SBIRT implementation in pediatric primary care among trained pediatricians, pediatricians working in coordination with embedded behavioral health care practitioners (BHCPs), and usual care (UC). The study is a 2-year (November 1, 2011, through October 31, 2013), nonblinded, cluster randomized, hybrid implementation and effectiveness trial examining SBIRT implementation outcomes across 2 modalities of implementation and UC. Fifty-two pediatricians from a large general pediatrics clinic in an integrated health care system were randomized to 1 of 3 SBIRT implementation arms; patients aged 12 to 18 years were eligible. Two modes of SBIRT implementation, (1) pediatrician only (pediatricians trained to provide SBIRT) and (2) embedded BHCP (BHCP trained to provide SBIRT), and (3) UC. Implementation of SBIRT (primary outcome), which included assessments, brief interventions, and referrals to specialty substance use and mental health treatment. The final sample included 1871 eligible patients among 47 pediatricians; health care professional characteristics did not differ across study arms. Patients in the pediatrician-only (adjusted odds ratio [AOR],?10.37; 95% CI,?5.45-19.74; P < .001) and the embedded BHCP (AOR,?18.09; 95% CI, 9.69-33.77; P < .001) arms had higher odds of receiving brief interventions compared with patients in the UC arm. Patients in the embedded BHCP arm were more likely to receive brief interventions compared with those in the pediatrician-only arm (AOR,?1.74; 95% CI,?1.31-2.31; P < .001). The embedded BHCP arm had lower odds of receiving a referral compared with the pediatrician-only (AOR,?0.58; 95% CI,?0.43-0.78; P < .001) and UC (AOR,?0.65; 95% CI,?0.48-0.89; P = .006) arms; odds of referrals did not differ between the pediatrician-only and UC arms. The intervention arms had better screening, assessment, and brief intervention rates than the UC arm. Patients in the pediatrician-only and UC arms had higher odds of being referred to specialty treatment than those in the embedded BHCP arm, suggesting lingering barriers to having pediatricians fully address substance use in primary care. Findings also highlight age and ethnic groups less likely to receive these important services. Clinicaltrials.gov Identifier: NCT02408952.
Authors: Sterling S; Kline-Simon AH; Satre DD; Jones A; Mertens J; Wong A; Weisner C
JAMA Pediatr. 2015 Nov;169(11):e153145. Epub 2015-11-02.
The effects of pioglitazone, a PPARγ receptor agonist, on the abuse liability of oxycodone among nondependent opioid users.
AIMS: Activation of PPARγ by pioglitazone (PIO) has shown some efficacy in attenuating addictive-like responses in laboratory animals. The ability of PIO to alter the effects of opioids in humans has not been characterized in a controlled laboratory setting. The proposed investigation sought to examine the effects of PIO on the subjective, analgesic, physiological and cognitive effects of oxycodone (OXY).METHODS: During this investigation, nondependent prescription opioid abusers (N=17 completers) were maintained for 2-3weeks on ascending daily doses of PIO (0mg, 15mg, 45mg) prior to completing a laboratory session assessing the aforementioned effects of OXY [using a within-session cumulative dosing procedure (0, 10, and 20mg, cumulative dose=30mg)].RESULTS: OXY produced typical mu opioid agonist effects: miosis, decreased pain perception, and decreased respiratory rate. OXY also produced dose-dependent increases in positive subjective responses. Yet, ratings such as: drug "liking," "high," and "good drug effect," were not significantly altered as a function of PIO maintenance dose.DISCUSSION: These data suggest that PIO may not be useful for reducing the abuse liability of OXY. These data were obtained with a sample of nondependent opioid users and therefore may not be applicable to dependent populations or to other opioids. Although PIO failed to alter the abuse liability of OXY, the interaction between glia and opioid receptors is not well understood so the possibility remains that medications that interact with glia in other ways may show more promise.
Authors: Jones, Jermaine D JD; Sullivan, Maria A MA; Manubay, Jeanne M JM; Mogali, Shanthi S; Metz, Verena E VE; Ciccocioppo, Roberto R; Comer, Sandra D SD
Physiology & behavior. 2016 May 15;159(1):33-9. Epub 2015-10-09.
Cultural Adaptation of Screening, Brief Intervention and Referral to Treatment Using Motivational Interviewing
This clinical case presentation and discussion illustrates a culturally adapted alcohol and drug use intervention using the Screening, Brief Intervention, and Referral to Treatment (SBIRT) approach, incorporating motivational interviewing skills. This case conference serves to complement the accompanying review article on SBIRT with diverse cultural groups, placing information from the review in the context of a typical clinical setting. In this example, SBIRT is provided in a primary care clinic to a Latino patient who reports hazardous drinking, depression, chronic pain and use of prescription opioids.
Authors: Satre DD; Manuel JK; Larios S; Steiger S; Satterfield J
J Addict Med. 2015 Sep-Oct;9(5):352-7.
Adapting Screening, Brief Intervention, and Referral to Treatment for Alcohol and Drugs to Culturally Diverse Clinical Populations
To review the literature on the screening, brief intervention, and referral to treatment (SBIRT) approach to alcohol and drug use with racial and ethnic subgroups in the United States and to develop recommendations for culturally competent SBIRT practice. Articles reporting on the use of SBIRT components (screening, brief intervention, referral to treatment) for alcohol and drug use were identified through a comprehensive literature search of PubMed from 1995 to 2015. A synthesis of the published literature on racial and ethnic considerations regarding SBIRT components (including motivational interviewing techniques) was created using evidence-based findings. Recommendations on culturally competent use of SBIRT with specific ethnic groups are also described. On the basis of the literature reviewed, SBIRT offers a useful set of tools to help reduce risky or problematic substance use. Special attention to validated screeners, appropriate use of language/literacy, trust building, and incorporation of patient and community health care preferences may enhance SBIRT acceptability and effectiveness. Providers should consider the implications of previous research when adapting SBIRT for diverse populations, and use validated screening and brief intervention methods. The accompanying case illustration provides additional information relevant to clinical practice.
Authors: Manuel JK; Satre DD; Tsoh J; Moreno-John G; Ramos JS; McCance-Katz EF; Satterfield JM
J Addict Med. 2015 Sep-Oct;9(5):343-51.
Trajectories of Symptoms and Function in Older Adults with Low Back Disorders
Prospective cohort study. To determine whether there are distinct trajectories of back pain and function among older adults and to identify characteristics that distinguish among patients with substantially different prognoses. Although the differential diagnosis and course of low back pain among older adults may differ from middle-aged adults, there is little evidence. Better understanding variability in recovery among older adults may help target patients for more intensive clinical interventions, plan resource use, and design clinical studies of more homogeneous patient groups. Patients aged 65 years or older with a new episode of care for back pain were recruited at 3 geographically diverse sites. Patients completed pain intensity and Roland-Morris Disability measures at baseline and 3, 6, and 12 months later. We used latent class analysis to identify distinct trajectories of pain and function and then logistic regression to identify predictors of membership in the improving trajectories. There were 3929 participants who completed outcome measures at every follow-up interval. Latent class analysis identified subgroups with low, intermediate, or high pain or disability scores who remained relatively stable over time. However, small subgroups showed dramatic improvement from baseline to 1 year (17% with major improvement in Roland score, pain intensity, or both). Shorter pain duration, higher patient confidence in improvement, and fewer comorbid conditions at baseline were each associated independently with favorable prognosis. Although most patients remained relatively stable over a year, latent class analysis identified small groups with major improvement in pain, function, or both. This technique may, therefore, be useful for studying back pain prognosis. Our results should help assemble more prognostically homogeneous groups for research, and the technique may help identify subgroups of patients with uniquely successful responses to investigational interventions. 3.
Authors: Deyo RA; Bryan M; Comstock BA; Turner JA; Heagerty P; Friedly J; Avins AL; Nedeljkovic SS; Nerenz DR; Jarvik JG
Spine. 2015 Sep 1;40(17):1352-62.
Characterizing Race/Ethnicity and Genetic Ancestry for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort
Using genome-wide genotypes, we characterized the genetic structure of 103,006 participants in the Kaiser Permanente Northern California multi-ethnic Genetic Epidemiology Research on Adult Health and Aging Cohort and analyzed the relationship to self-reported race/ethnicity. Participants endorsed any of 23 race/ethnicity/nationality categories, which were collapsed into seven major race/ethnicity groups. By self-report the cohort is 80.8% white and 19.2% minority; 93.8% endorsed a single race/ethnicity group, while 6.2% endorsed two or more. Principal component (PC) and admixture analyses were generally consistent with prior studies. Approximately 17% of subjects had genetic ancestry from more than one continent, and 12% were genetically admixed, considering only nonadjacent geographical origins. Self-reported whites were spread on a continuum along the first two PCs, indicating extensive mixing among European nationalities. Self-identified East Asian nationalities correlated with genetic clustering, consistent with extensive endogamy. Individuals of mixed East Asian-European genetic ancestry were easily identified; we also observed a modest amount of European genetic ancestry in individuals self-identified as Filipinos. Self-reported African Americans and Latinos showed extensive European and African genetic ancestry, and Native American genetic ancestry for the latter. Among 3741 genetically identified parent-child pairs, 93% were concordant for self-reported race/ethnicity; among 2018 genetically identified full-sib pairs, 96% were concordant; the lower rate for parent-child pairs was largely due to intermarriage. The parent-child pairs revealed a trend toward increasing exogamy over time; the presence in the cohort of individuals endorsing multiple race/ethnicity categories creates interesting challenges and future opportunities for genetic epidemiologic studies.
Authors: Banda Y; Croen LA; Iribarren C; Kushi LH; Quesenberry CP; Sakoda LC; Van Den Eeden SK; Whitmer RA; Schaefer C; Risch N; et al.
Genetics. 2015 Aug;200(4):1285-95. Epub 2015-06-19.
Automated Assay of Telomere Length Measurement and Informatics for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort
The Kaiser Permanente Research Program on Genes, Environment, and Health (RPGEH) Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort includes DNA specimens extracted from saliva samples of 110,266 individuals. Because of its relationship to aging, telomere length measurement was considered an important biomarker to develop on these subjects. To assay relative telomere length (TL) on this large cohort over a short time period, we created a novel high throughput robotic system for TL analysis and informatics. Samples were run in triplicate, along with control samples, in a randomized design. As part of quality control, we determined the within-sample variability and employed thresholds for the elimination of outlying measurements. Of 106,902 samples assayed, 105,539 (98.7%) passed all quality control (QC) measures. As expected, TL in general showed a decline with age and a sex difference. While telomeres showed a negative correlation with age up to 75 years, in those older than 75 years, age positively correlated with longer telomeres, indicative of an association of longer telomeres with more years of survival in those older than 75. Furthermore, while females in general had longer telomeres than males, this difference was significant only for those older than age 50. An additional novel finding was that the variance of TL between individuals increased with age. This study establishes reliable assay and analysis methodologies for measurement of TL in large, population-based human studies. The GERA cohort represents the largest currently available such resource, linked to comprehensive electronic health and genotype data for analysis.
Authors: Lapham K; Croen LA; Iribarren C; Kushi LH; Quesenberry CP; Sakoda LC; Van Den Eeden SK; Whitmer RA; Risch N; Schaefer C; Blackburn EH; et al.
Genetics. 2015 Aug;200(4):1061-72. Epub 2015-06-19.
Genotyping Informatics and Quality Control for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort
The Kaiser Permanente (KP) Research Program on Genes, Environment and Health (RPGEH), in collaboration with the University of California-San Francisco, undertook genome-wide genotyping of >100,000 subjects that constitute the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. The project, which generated >70 billion genotypes, represents the first large-scale use of the Affymetrix Axiom Genotyping Solution. Because genotyping took place over a short 14-month period, creating a near-real-time analysis pipeline for experimental assay quality control and final optimized analyses was critical. Because of the multi-ethnic nature of the cohort, four different ethnic-specific arrays were employed to enhance genome-wide coverage. All assays were performed on DNA extracted from saliva samples. To improve sample call rates and significantly increase genotype concordance, we partitioned the cohort into disjoint packages of plates with similar assay contexts. Using strict QC criteria, the overall genotyping success rate was 103,067 of 109,837 samples assayed (93.8%), with a range of 92.1-95.4% for the four different arrays. Similarly, the SNP genotyping success rate ranged from 98.1 to 99.4% across the four arrays, the variation depending mostly on how many SNPs were included as single copy vs. double copy on a particular array. The high quality and large scale of genotype data created on this cohort, in conjunction with comprehensive longitudinal data from the KP electronic health records of participants, will enable a broad range of highly powered genome-wide association studies on a diversity of traits and conditions.
Authors: Kvale MN; Croen LA; Iribarren C; Kushi LH; Quesenberry CP; Sakoda LC; Van Den Eeden SK; Whitmer RA; Schaefer C; Risch N; et al.
Genetics. 2015 Aug;200(4):1051-60. Epub 2015-06-19.
Sex and Age Differences in Global Pain Status Among Patients Using Opioids Long Term for Chronic Noncancer Pain
The use of chronic opioid therapy (COT) has risen dramatically in recent years, especially among women. However, little is known about factors influencing overall pain and function (global pain status) among COT users. Characterizing the typical experiences of COT patients by age-sex group could help clinicians and patients better weigh the risks and benefits of COT. Thus, we sought to characterize global pain status among COT users in community practice by age and sex. Telephone survey of 2,163 health plan members aged 21-80 years using COT. We assessed average/usual pain (0-10 scale); pain-related interference (0-10); activity limitation days, last 3 months; and pain impact, last 2 weeks (0-11). Status on each indicator was classified as low (better pain/function), moderate, or high (worse pain/function). Global pain status was categorized as favorable if 2-4 indicators were low and 0-1 was high and unfavorable if 2-4 indicators were high and 0-1 was low. Among female COT patients, 15% (vs. 26% of males) had favorable global pain status and 59% (vs. 42% of males) had unfavorable status. Under age 65 years, women fared more poorly than men on every indicator. Among 65- to 80-year-olds, women and men had similar global pain status. Although pain and function among COT users vary considerably, only one in five reported low pain levels and high levels of function. Young and middle-aged women seem to be at particularly high risk for unfavorable global pain status. More research is needed about how to best manage pain in this group.
Authors: LeResche L; Saunders K; Dublin S; Thielke S; Merrill JO; Shortreed SM; Campbell C; Von Korff MR
J Womens Health (Larchmt). 2015 Aug;24(8):629-35. Epub 2015-07-08.
Ethnic Differences in Geriatric Conditions and Diabetes Complications Among Older, Insured Adults With Diabetes: The Diabetes and Aging Study
The aim of this study was to evaluate ethnic differences in burden of prevalent geriatric conditions and diabetic complications among older, insured adults with diabetes. An observational study was conducted among 115,538 diabetes patients, aged ³60, in an integrated health care system with uniform access to care. Compared with Whites, Asians and Filipinos were more likely to be underweight but had substantively lower prevalence of falls, urinary incontinence, polypharmacy, depression, and chronic pain, and were least likely of all groups to have at least one geriatric condition. African Americans had significantly lower prevalence of incontinence and falls, but higher prevalence of dementia; Latinos had a lower prevalence of falls. Except for end-stage renal disease (ESRD), Whites tended to have the highest rates of prevalent diabetic complications. Among these insured older adults, ethnic health patterns varied substantially; differences were frequently small and rates were often better among select minority groups, suggesting progress toward the Healthy People 2020 objective to reduce health disparities.
Authors: Karter AJ; Adams AS; Whitmer RA; Huang ES; et al.
J Aging Health. 2015 Aug;27(5):894-918. Epub 2015-02-05.
Differences in the Genetic Susceptibility to Age-Related Macular Degeneration Clinical Subtypes
We compared across age-related macular degeneration (AMD) subtypes the effect of AMD risk variants, their predictive power, and heritability. The prevalence of AMD was estimated among active non-Hispanic white Kaiser Permanente Northern California members who were at least 65 years of age as of June 2013. The genetic analysis included 5,170 overall AMD cases ascertained from electronic health records (EHR), including 1,239 choroidal neovascularization (CNV) cases and 1,060 nonexudative AMD cases without CNV, and 23,130 controls of non-Hispanic white ancestry from the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. Imputation was based on the 1000 Genomes Project reference panel. The narrow-sense heritability due to common autosomal single nucleotide polymorphisms (SNPs) was 0.37 for overall AMD, 0.19 for AMD unspecified, 0.20 for nonexudative AMD, and 0.60 for CNV. For the 19 previously reported AMD risk loci, the area under the receiver operating characteristic (ROC) curve was 0.675 for overall AMD, 0.640 for AMD unspecified, 0.678 for nonexudative AMD, and 0.766 for CNV. The individual effects on the risk of AMD for 18 of the 19 SNPs were in a consistent direction with those previously reported, including a protective effect of the APOE ?4 allele. Conversely, the risk of AMD was significantly increased in carriers of the ?2 allele. These findings provide an independent confirmation of many of the previously identified AMD risk loci, and support a potentially greater role of genetic factors in the development of CNV. The replication of established associations validates the use of EHR in genetic studies of ophthalmologic traits.
Authors: Shen L; Hoffmann TJ; Melles RB; Sakoda LC; Kvale MN; Banda Y; Schaefer C; Risch N; Jorgenson E
Invest Ophthalmol Vis Sci. 2015 Jul;56(8):4290-9.
Clinical decision rule for primary care patient with acute low back pain at risk of developing chronic pain
Primary care clinicians need to identify candidates for early interventions to prevent patients with acute pain from developing chronic pain. We conducted a 2-year prospective cohort study of risk factors for the progression to chronic pain and developed and internally validated a clinical decision rule (CDR) that stratifies patients into low-, medium-, and high-risk groups for chronic pain. This is a prospective cohort study in primary care. Patients with acute low back pain (LBP, ?30 days duration) were included. Outcome measures were self-reported perceived nonrecovery and chronic pain. Patients were surveyed at baseline, 6 months, and 2 years. We conducted bivariate and multivariate regression analyses of demographic, clinical, and psychosocial variables for chronic pain outcomes, developed a CDR, and assessed its performance by calculating the bootstrapped areas under the receiver-operating characteristic curve (AUC) and likelihood ratios. Six hundred five patients enrolled: 13% had chronic pain at 6 months and 19% at 2 years. An eight-item CDR was most parsimonious for classifying patients into three risk levels. Bootstrapped AUC was 0.76 (0.70-0.82) for the 6-month CDR. Each 10-point score increase (60-point range) was associated with an odds ratio of 11.1 (10.8-11.4) for developing chronic pain. Using a less than 5% probability of chronic pain as the cutoff for low risk and a greater than 40% probability for high risk, likelihood ratios were 0.26 (0.14-0.48) and 4.4 (3.0-6.3) for these groups, respectively. A CDR was developed that may help primary care clinicians classify patients with strictly defined acute LBP into low-, moderate-, and high-risk groups for developing chronic pain and performed acceptably in 1,000 bootstrapped replications. Validation in a separate sample is needed.
Authors: Mehling WE; Ebell MH; Avins AL; Hecht FM
Spine J. 2015 Jul 1;15(7):1577-86. Epub 2015-03-13.
Cardiorespiratory fitness and brain volume and white matter integrity: The CARDIA Study
We hypothesized that greater cardiorespiratory fitness is associated with lower odds of having unfavorable brain MRI findings. We studied 565 healthy, middle-aged, black and white men and women in the CARDIA (Coronary Artery Risk Development in Young Adults) Study. The fitness measure was symptom-limited maximal treadmill test duration (Maxdur); brain MRI was measured 5 years later. Brain MRI measures were analyzed as means and as proportions below the 15th percentile (above the 85th percentile for white matter abnormal tissue volume). Per 1-minute-higher Maxdur, the odds ratio for having less whole brain volume was 0.85 (p = 0.04) and for having low white matter integrity was 0.80 (p = 0.02), adjusted for age, race, sex, clinic, body mass index, smoking, alcohol, diet, physical activity, education, blood pressure, diabetes, total cholesterol, and lung function (plus intracranial volume for white matter integrity). No significant associations were observed between Maxdur and abnormal tissue volume or blood flow in white matter. Findings were similar for associations with continuous brain MRI measures. Greater physical fitness was associated with more brain volume and greater white matter integrity measured 5 years later in middle-aged adults.
Authors: Zhu N; Whitmer RA; Bryan RN; et al.
Neurology. 2015 Jun 9;84(23):2347-53. Epub 2015-05-08.
A Preliminary Study: Efficacy of Mindfulness-Based Cognitive Therapy versus Sertraline as First-line Treatments for Major Depressive Disorder
Major depressive disorder (MDD) is the leading cause of disability in the developed world, yet broadly effective treatments remain elusive. The primary aim of this pilot study was to investigate the efficacy of Mindfulness-Based Cognitive Therapy (MBCT) monotherapy, compared to sertraline monotherapy, for patients with acute MDD. This open-label, nonrandomized controlled trial examined a MBCT cohort (N=23) recruited to match the gender, age, and depression severity of a depressed control group (N=20) that completed 8 weeks of monotherapy with the antidepressant sertraline. The 17-item clinician-rated Hamilton Depression Severity Rating Scale (HAMD-17) was the primary outcome measure of depression to assess overall change after 8 weeks and rates of response and remission. The 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16) was the secondary outcome measure to further assess depression severity. Both cohorts were demographically similar and showed significant improvement in depression ratings. No difference was found in the degree of change in HAMD-17 scores (t(34) = 1.42, p = .165) between groups. Secondary analysis showed statistically significant differences in mean scores of the QIDS-SR16 (t (32) = 4.39, p < 0.0001), with the MCBT group showing greater mean improvement. This study was limited by the small sample size and non-randomized, non-blinded design. Preliminary findings suggest that an 8-week course of MBCT monotherapy may be effective in treating MDD and a viable alternative to antidepressant medication. Greater changes in the self-rated QIDS-SR16 for the MBCT cohort raise the possibility that patients derive additional subjective benefit from enhanced self-efficacy skills.
Authors: Eisendrath SJ; Gillung E; Delucchi K; Mathalon DH; Yang TT; Satre DD; Rosser R; Sipe WE; Wolkowitz OM
Mindfulness (N Y). 2015 Jun 01;6(3):475-482.
Need and utility of a polyethylene glycol marker to ensure against urine falsification among heroin users.
BACKGROUND: Deceptive methods of falsifying urine samples are of concern for anyone who relies on accurate urine toxicology results. A novel method to combat these efforts utilizes polyethylene glycol (PEG) markers administered orally prior to providing a urine sample. By using various PEG combinations to create a tracer capsule of unique composition, each urine sample can be matched to that individual. The goal of this study was to determine the effectiveness of using the PEG marker system among active heroin users screening for research studies.METHODS: Upon each screening visit, participants (N=55) were randomized to provide an unobserved urine sample, or the PEG tracer procedure was used. LCMS analysis was used to distinguish the PEG combinations, and allowed us to provide a unique qualitative analysis of patterns of drug use (N=168, total urine specimens).RESULTS: The unique composition of the tracer capsules was accurately detected in 83.5% of the urine specimens. Analyses of inconsistencies implicated a number of possible attempts at fraudulence (11.4%) and investigator/lab error (5.1%). Among this sample, the concurrent use of multiple classes of psychoactive drugs was more common than not, though concomitant drug use was often underreported.CONCLUSION: Urine drug testing should be the minimum standard for obtaining information about drug use as self-report was unreliable even in a situation where there were no perceived adverse consequences for full disclosure. In cases where there are significant pressures for individuals to falsify these data, more protective collection methods such as the PEG marker system should be considered.
Authors: Jones, Jermaine D JD; Atchison, Jared J JJ; Madera, Gabriela G; Metz, Verena E VE; Comer, Sandra D SD
Drug and alcohol dependence. 2015 Aug 01;153(1):201-6. Epub 2015-05-27.
Oral steroids for acute radiculopathy due to a herniated lumbar disk: a randomized clinical trial
Oral steroids are commonly used to treat acute sciatica due to a herniated disk but have not been evaluated in an appropriately powered clinical trial. To determine if oral prednisone is more effective than placebo in improving function and pain among patients with acute sciatica. Randomized, double-blind, placebo-controlled clinical trial conducted from 2008 to 2013 in a large integrated health care delivery system in Northern California. Adults (n=269) with radicular pain for 3 months or less, an Oswestry Disability Index (ODI) score of 30 or higher (range, 0-100; higher scores indicate greater dysfunction), and a herniated disk confirmed by magnetic resonance imaging were eligible. Participants were randomly assigned in a 2:1 ratio to receive a tapering 15-day course of oral prednisone (5 days each of 60 mg, 40 mg, and 20 mg; total cumulative dose?=?600 mg; n?=?181) or matching placebo (n?=?88). The primary outcome was ODI change at 3 weeks; secondary outcomes were ODI change at 1 year, change in lower extremity pain (measured on a 0-10 scale; higher scores indicate more pain), spine surgery, and Short Form 36 Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) scores (0-100 scale; higher scores better). Observed baseline and 3-week mean ODI scores were 51.2 and 32.2 for the prednisone group and 51.1 and 37.5 for the placebo group, respectively. The prednisone-treated group showed an adjusted mean 6.4-point (95% CI, 1.9-10.9; P?=?.006) greater improvement in ODI scores at 3 weeks than the placebo group and a mean 7.4-point (95% CI, 2.2-12.5; P?=?.005) greater improvement at 52 weeks. Compared with the placebo group, the prednisone group showed an adjusted mean 0.3-point (95% CI, -0.4 to 1.0; P?=?.34) greater reduction in pain at 3 weeks and a mean 0.6-point (95% CI, -0.2 to 1.3; P?=?.15) greater reduction at 52 weeks. The prednisone group showed an adjusted mean 3.3-point (95% CI, 1.3-5.2; P?=?.001) greater improvement in the SF-36 PCS score at 3 weeks, no difference in the SF-36 PCS score at 52 weeks (mean, 2.5; 95% CI, -0.3 to 5.4; P?=?.08), no change in the SF-36 MCS score at 3 weeks (mean, 2.2; 95% CI, -0.4 to 4.8; P?=?.10), and an adjusted 3.6-point (95% CI, 0.6-6.7; P?=?.02) greater improvement in the SF-36 MCS score at 52 weeks. There were no differences in surgery rates at 52-week follow-up. Having 1 or more adverse events at 3-week follow-up was more common in the prednisone group than in the placebo group (49.2% vs 23.9%; P?
Authors: Goldberg H; Avins AL; et al.
JAMA. 2015 May 19;313(19):1915-23.
Genome-wide association study identifies ABCG2 (BCRP) as an allopurinol transporter and a determinant of drug response
The first-line treatment of hyperuricemia, which causes gout, is allopurinol. The allopurinol response is highly variable, with many users failing to achieve target serum uric acid (SUA) levels. No genome-wide association study (GWAS) has examined the genetic factors affecting allopurinol effectiveness. Using 2,027 subjects in Kaiser Permanente’s Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort, we conducted a GWAS of allopurinol-related SUA reduction, first in the largest ethnic group, non-Hispanic white (NHW) subjects, and then in a stratified transethnic meta-analysis. ABCG2, encoding the efflux pump BCRP, was associated with SUA reduction in NHW subjects (P = 2 × 10(-8) ), and a missense allele (rs2231142) was associated with a reduced response (P = 3 × 10(-7) ) in the meta-analysis. Isotopic uptake studies in cells demonstrated that BCRP transports allopurinol and genetic variants in ABCG2 affect this transport. Collectively, this first GWAS of allopurinol response demonstrates that ABCG2 is a key determinant of response to the drug.
Authors: Wen CC; Yee SW; Liang X; Hoffmann TJ; Kvale MN; Banda Y; Jorgenson E; Schaefer C; Risch N; Giacomini KM
Clin Pharmacol Ther. 2015 May;97(5):518-25. Epub 2015-04-06.
Screening and Brief Intervention for Substance Misuse: Does It Reduce Aggression and HIV-Related Risk Behaviours?
To explore whether reducing substance misuse through a brief motivational intervention also reduces aggression and HIV risk behaviours. Participants were enrolled in a randomized controlled trial in primary care if they screened positive for substance misuse. Substance misuse was assessed using the Alcohol, Smoking and Substance Involvement Screening Test; aggression, using a modified version of the Explicit Aggression Scale; and HIV risk, through a count of common risk behaviours. The intervention was received on the day of the baseline interview, with a 3-month follow-up. Participants who received the intervention were significantly more likely to reduce their alcohol use than those who did not; no effect was identified for other substances. In addition, participants who reduced substance misuse (whether as an effect of the intervention or not) also reduced aggression but not HIV risk behaviours. Reducing substance misuse through any means reduces aggression; other interventions are needed for HIV risk reduction.
Authors: Ward CL; Mertens JR; Bresick GF; Little F; Weisner CM
Alcohol Alcohol. 2015 May;50(3):302-9. Epub 2015-03-01.
Racial/Ethnic differences in health care visits made before suicide attempt across the United States
Suicide is a public health concern, but little is known about the patterns of health care visits made before a suicide attempt, and whether those patterns differ by race/ethnicity. To examine racial/ethnic variation in the types of health care visits made before a suicide attempt, when those visits occur, and whether mental health or substance use diagnoses were documented. Retrospective, longitudinal study, 2009-2011. 22,387 individuals who attempted suicide and were enrolled in the health plan across 10 health systems in the Mental Health Research Network. Cumulative percentage of different types of health care visits made in the 52 weeks before a suicide attempt, by self-reported racial/ethnicity and diagnosis. Data were from the Virtual Data Warehouse at each site. Over 38% of the individuals made any health care visit within the week before their suicide attempt and ?95% within the preceding year; these percentages varied across racial/ethnic groups (P<0.001). White individuals had the highest percentage of visits (>41%) within 1 week of suicide attempt. Asian Americans were the least likely to make visits within 52 weeks. Hawaiian/Pacific Islanders had proportionally the most inpatient and emergency visits before an attempt, but were least likely to have a recorded mental health or substance use diagnosis. Overall, visits were most common in primary care and outpatient general medical settings. This study provides temporal evidence of racial/ethnic differences in health care visits made before suicide attempt. Health care systems can use this information to help focus the design and implementation of their suicide prevention initiatives.
Authors: Ahmedani BK; Hunkeler EM; Williams K; et al.
Med Care. 2015 May;53(5):430-5.
Symptom severity and readiness to quit among hospitalized smokers with mental illness
Authors: Anzai N; Young-Wolff KC; Prochaska JJ
Psychiatr Serv. 2015 Apr 1;66(4):443-4.
Drinking experience uncovers genetic influences on alcohol expectancies across adolescence
To test whether drinking onset moderates genetic and environmental contributions to individual differences in the etiology of alcohol expectancies across adolescence. Longitudinal twin design. Community sample from Los Angeles, CA, USA. A total of 1292 male and female twins, aged 11–18years, were assessed at 1 (n = 440), 2 (n = 587) or 3 (n = 265) occasions as part of the risk factors for the Antisocial Behavior Twin Study. Social behavioral (SB) alcohol expectancies were measured using an abbreviated version of the Social Behavioral subscale from the Alcohol Expectancy Questionnaire for adolescents (AEQ-A). Drinking onset was defined as >1 full drink of alcohol. Alcohol expectancies increased over age and the increase became more rapid following onset of drinking. The importance of genetic and environmental influences on SB scores varied with age and drinking status, such that variation prior to drinking onset was attributed solely to environmental influences, whereas all post-onset variation was attributed to genetic influences. Results did not differ significantly by sex. Only environmental factors explain beliefs about the social and behavioral consequences of alcohol use prior to drinking onset,whereas genetic factors explain an increasing proportion of the variance in these beliefs after drinking onset.
Authors: Young-Wolff KC; Wang P; Tuvblad C; Baker LA; Raine A; Prescott CA
Addiction. 2015 Apr;110(4):610-8.
Systematic Literature Review of Imaging Features of Spinal Degeneration in Asymptomatic Populations
Degenerative changes are commonly found in spine imaging but often occur in pain-free individuals as well as those with back pain. We sought to estimate the prevalence, by age, of common degenerative spine conditions by performing a systematic review studying the prevalence of spine degeneration on imaging in asymptomatic individuals. We performed a systematic review of articles reporting the prevalence of imaging findings (CT or MR imaging) in asymptomatic individuals from published English literature through April 2014. Two reviewers evaluated each manuscript. We selected age groupings by decade (20, 30, 40, 50, 60, 70, 80 years), determining age-specific prevalence estimates. For each imaging finding, we fit a generalized linear mixed-effects model for the age-specific prevalence estimate clustering in the study, adjusting for the midpoint of the reported age interval. Thirty-three articles reporting imaging findings for 3110 asymptomatic individuals met our study inclusion criteria. The prevalence of disk degeneration in asymptomatic individuals increased from 37% of 20-year-old individuals to 96% of 80-year-old individuals. Disk bulge prevalence increased from 30% of those 20 years of age to 84% of those 80 years of age. Disk protrusion prevalence increased from 29% of those 20 years of age to 43% of those 80 years of age. The prevalence of annular fissure increased from 19% of those 20 years of age to 29% of those 80 years of age. Imaging findings of spine degeneration are present in high proportions of asymptomatic individuals, increasing with age. Many imaging-based degenerative features are likely part of normal aging and unassociated with pain. These imaging findings must be interpreted in the context of the patient’s clinical condition.
Authors: Brinjikji W; Avins AL; Jarvik JG; et al.
AJNR Am J Neuroradiol. 2015 Apr;36(4):811-6. Epub 2014-11-27.
Implications of an Alcohol Addiction RDoC for Delivery Science Research and Clinical Care
Authors: Weisner C
Alcohol Clin Exp Res. 2015 Apr;39(4):593.
Association of early imaging for back pain with clinical outcomes in older adults
In contrast to the recommendations for younger adults, many guidelines allow for older adults with back pain to undergo imaging without waiting 4 to 6 weeks. However, early imaging may precipitate interventions that do not improve outcomes. To compare function and pain at the 12-month follow-up visit among older adults who received early imaging with those who did not receive early imaging after a new primary care visit for back pain without radiculopathy. Prospective cohort of 5239 patients 65 years or older with a new primary care visit for back pain (2011-2013) in 3 US health care systems. We matched controls 1:1 using propensity score matching of demographic and clinical characteristics, including diagnosis, pain severity, pain duration, functional status, and prior resource use. Diagnostic imaging (plain films, computed tomography [CT], magnetic resonance imaging [MRI]) of the lumbar or thoracic spine within 6 weeks of the index visit. back or leg pain-related disability measured by the modified Roland-Morris Disability Questionnaire (score range, 0-24; higher scores indicate greater disability) 12 months after enrollment. Among the 5239 patients, 1174 had early radiographs and 349 had early MRI/CT. At 12 months, neither the early radiograph group nor the early MRI/CT group differed significantly from controls on the disability questionnaire. The mean score for patients who underwent early radiography was 8.54 vs 8.74 among the control group (difference, -0.10 [95% CI, -0.71 to 0.50]; mixed model, P?=?.36). The mean score for the early MRI/CT group was 9.81 vs 10.50 for the control group (difference,-0.51 [-1.62 to 0.60]; mixed model, P?=?.18). Among older adults with a new primary care visit for back pain, early imaging was not associated with better 1-year outcomes. The value of early diagnostic imaging in older adults for back pain without radiculopathy is uncertain.
Authors: Jarvik JG; Avins AL; Deyo RA; et al.
JAMA. 2015 Mar 17;313(11):1143-53.
Perinatal oxytocin increases the risk of offspring bipolar disorder and childhood cognitive impairment
We tested the hypothesis that perinatal oxytocin, given to pregnant women to induce labor, is related to offspring bipolar disorder (BP) and worse childhood cognitive performance among offspring. We also tested the association between childhood cognition and later BP. A population-based birth cohort derived from the Child Health and Development Study (CHDS) which included nearly all pregnant women receiving obstetric care from the Kaiser Permanente Medical Care Plan, Northern California Region (KPNC) between 1959 and 1966. Prospectively obtained medical and offspring cognitive performance were used. Potential cases with BP from the cohort were identified by database linkages. This protocol identified 94 cases who were matched 1:8 to controls. Perinatal oxytocin was associated with a 2.4 times increased odds of later BP. Oxytocin was also associated with decreased performance on the Raven Matrices, but not on the Peabody Picture Vocabulary Test (PPVT). Childhood cognition was not associated with later BP. Loss to follow-up must be considered in all birth cohort studies. In addition, the childhood cognitive battery did not include tests related to multiple domains of cognition which have been associated with later BP. A third limitation is the modest sample size of those exposed to oxytocin. This study provides evidence for a potentially important perinatal risk factor for BP and cognitive impairment in childhood. While the association between perinatal oxytocin and offspring BP must be viewed cautiously until further studies can attempt to replicate the result, it lends support to the broader view that neurodevelopmental factors contribute to BP.
Authors: Freedman D; Brown AS; Shen L; Schaefer CA
J Affect Disord. 2015 Mar 1;173:65-72. Epub 2014-11-08.
Prevalence of behavioral health disorders and associated chronic disease burden in a commercially insured health system: findings of a case-control study
The objective was to examine prevalence of behavioral health disorders (BHDs) and co-occurring chronic medical conditions in a 3.4 million-member integrated health system. Clinical databases identified 255,993 patients diagnosed with the most prevalent BHDs (cases): depression, anxiety, substance use, bipolar spectrum and attention deficit and hyperactivity (ADHD); non-BHD matched controls were created for all unique cases. Cases and controls were compared for prevalence of general medical conditions and specific chronic diseases and the Charlson Comorbidity Index (CMI). The five most common BHDs were depression (58%), anxiety (42%), substance use (16%), bipolar spectrum (6%) and ADHD (4%). Compared to controls, patients with depression (80.1% vs. 66.3%), anxiety (78.0% vs. 63.0%), substance use (74.0% vs. 59.9%), bipolar (75.3% vs. 60.7%) and ADHD (60.6% vs. 53.1%; all P<.001) had significantly higher prevalence of any medical comorbidities. Excluding ADHD, BHD cases had higher prevalence of selected chronic diseases and average CMI. BHDs in a largely commercially insured, employment-based health system are common and associated with a disproportionately higher burden of chronic medical disease and associated 10-year mortality risk rate. Given that co-occurrence of behavioral and medical conditions leads to elevated symptom burden, functional impairment, and healthcare costs, these findings highlight the importance of developing effective collaborative models of care in (nonpublic) employment-based health systems.
Authors: Young JQ; Kline-Simon AH; Mordecai DJ; Weisner C
Gen Hosp Psychiatry. 2015 Mar-Apr;37(2):101-8. Epub 2014-12-20.
Diabetes and Cognition
Dementia is a major cause of disability and death among older adults. Those with type 2 diabetes (T2D) are 50-100% more likely to develop dementia than those without T2D, but it is unknown whether this association reflects a causal relationship. Proposed mechanisms through which T2D could cause dementia include the effects of insulin dysregulation and chronic hyperglycemia on features of Alzheimer’s disease and macrovascular and microvascular disorders in the brain. More research is needed to elucidate the link between T2D and dementia and identify strategies to maintain cognitive function among people with T2D.
Authors: Mayeda ER; Whitmer RA; Yaffe K
Clin Geriatr Med. 2015 Feb;31(1):101-15, ix. Epub 2014-11-15.
Prevalence and correlates of electronic-cigarette use in young adults: Findings from three studies over five years
We aimed to examine prevalence and correlates of past-month electronic cigarette (“e-cigarette”) use and use of e-cigarettes to aid a cessation attempt in three samples of young adult smokers recruited online in 2009-2010 (Study 1), 2010-2011 (Study 2), and 2013 (Study 3). Participants were young adults aged 18 to 25 who smoked at least one cigarette in the previous month (Study 1, N=1987 and Study 2, N=570) or smoked 3 or more days each week and used Facebook 4 or more days per week (Study 3, N=79). We examined both past-month e-cigarette use and ever use of e-cigarettes to quit conventional cigarettes. Prevalence of past-month use of e-cigarettes was higher in each subsequent study: Study 1 (6%), Study 2 (19%), and Study 3 (41%). In multivariate analyses, significant correlates of past-month e-cigarette use were identified for Study 1 (male sex OR=2.1, p=.03; past-year quit attempt OR=1.6, p=.03) and Study 2 (male sex, OR=1.7, p=.03; younger age OR=0.88, p=.05), but not Study 3. In multivariate analyses, significant correlates of ever use of e-cigarette to quit conventional cigarettes were identified for Study 1 (education, OR=1.2, p=.02; smoking within 30min of waking, OR=2.8, p=.02; past year quit attempt OR=4.1, p=.02), and Study 3 (desire to quit smoking, OR=1.3, p=.02), but not Study 2. E-cigarette use is increasingly common among young adults, particularly men. E-cigarette use for quitting conventional cigarettes appears more common among those more nicotine dependent and interested in quitting.
Authors: Ramo DE; Young-Wolff KC; Prochaska JJ
Addict Behav. 2015 Feb;41:142-7. Epub 2014-10-23.
Electronic Cigarettes in Jails: A Panacea or Public Health Problem?
Authors: Young-Wolff KC; Karan LD; Prochaska JJ
JAMA Psychiatry. 2015 Feb;72(2):103-4.
A genome-wide association study identifies four novel susceptibility loci underlying inguinal hernia
Inguinal hernia repair is one of the most commonly performed operations in the world, yet little is known about the genetic mechanisms that predispose individuals to develop inguinal hernias. We perform a genome-wide association analysis of surgically confirmed inguinal hernias in 72,805 subjects (5,295 cases and 67,510 controls) and confirm top associations in an independent cohort of 92,444 subjects with self-reported hernia repair surgeries (9,701 cases and 82,743 controls). We identify four novel inguinal hernia susceptibility loci in the regions of EFEMP1, WT1, EBF2 and ADAMTS6. Moreover, we observe expression of all four genes in mouse connective tissue and network analyses show an important role for two of these genes (EFEMP1 and WT1) in connective tissue maintenance/homoeostasis. Our findings provide insight into the aetiology of hernia development and highlight genetic pathways for studies of hernia development and its treatment.
Authors: Jorgenson E; Makki N; Shen L; Chen DC; Tian C; Eckalbar WL; Hinds D; Ahituv N; Avins A
Nat Commun. 2015;6:10130. Epub 2015-12-21.
Imputation of the Rare HOXB13 G84E Mutation and Cancer Risk in a Large Population-Based Cohort
An efficient approach to characterizing the disease burden of rare genetic variants is to impute them into large well-phenotyped cohorts with existing genome-wide genotype data using large sequenced referenced panels. The success of this approach hinges on the accuracy of rare variant imputation, which remains controversial. For example, a recent study suggested that one cannot adequately impute the HOXB13 G84E mutation associated with prostate cancer risk (carrier frequency of 0.0034 in European ancestry participants in the 1000 Genomes Project). We show here that-by utilizing the 1000 Genomes Project data plus an enriched reference panel of mutation carriers-we were able to accurately impute the G84E mutation into a large cohort of 83,285 non-Hispanic White participants from the Kaiser Permanente Research Program on Genes, Environment and Health Genetic Epidemiology Research on Adult Health and Aging cohort. Imputation authenticity was confirmed via a novel classification and regression tree method, and then empirically validated analyzing a subset of these subjects plus an additional 1,789 men from the California Men’s Health Study specifically genotyped for the G84E mutation (r2 = 0.57, 95% CI = 0.37-0.77). We then show the value of this approach by using the imputed data to investigate the impact of the G84E mutation on age-specific prostate cancer risk and on risk of fourteen other cancers in the cohort. The age-specific risk of prostate cancer among G84E mutation carriers was higher than among non-carriers, and this difference increased with age. Risk estimates from Kaplan-Meier curves were 36.7% versus 13.6% by age 72, and 64.2% versus 24.2% by age 80, for G84E mutation carriers and non-carriers, respectively (p = 3.4×10-12). The G84E mutation was also suggestively associated with an increase in risk for the following cancer sites by approximately 50% in a pleiotropic manner: breast, non-Hodgkin’s lymphoma, kidney, bladder, melanoma, endometrium, and pancreas (p = 0.042).
Authors: Hoffmann TJ; Sakoda LC; Habel LA; Asgari MM; Corley D; Kushi LH; Quesenberry CP; Schaefer C; Van Den Eeden SK; Risch N; Witte JS; et al.
PLoS Genet. 2015 Jan;11(1):e1004930. Epub 2015-01-28.
Recent evidence exploring the associations between physical activity and menopausal symptoms in midlife women: perceived risks and possible health benefits
Although the health benefits of physical activity are well established, the prevalence of midlife women accumulating sufficient physical activity to meet current physical activity guidelines is strikingly low, as shown in United States (U.S.) based surveillance systems that utilize either (or both) participant-reported and device-based (i.e., accelerometers) measures of activity. For midlife women, these low prevalence estimates may be due, in part, to a general lack of time given more pressing work commitments and family obligations. Further, the benefits or “reward” of allocating limited time to physical activity may be perceived, by some, as too distant for immediate action or attention. However, shifting the health promotion message from the long term benefits of physical activity to the more short-term, acute benefits may encourage midlife women to engage in more regular physical activity. In this article, we review the latest evidence (i.e., past 5 years) regarding the impact of physical activity on menopausal symptoms. Recent studies provide strong support for the absence of an effect of physical activity on vasomotor symptoms; evidence is still inconclusive regarding the role of physical activity on urogenital symptoms (vaginal dryness, urinary incontinence) and sleep, but consistently suggestive of a positive impact on mood and weight control. To further advance this field, we also propose additional considerations and future research directions.
Authors: Pettee Gabriel K; Mason JM; Sternfeld B
Womens Midlife Health. 2015;1:1. Epub 2015-08-11.
Physician versus non-physician delivery of alcohol screening, brief intervention and referral to treatment in adult primary care: the ADVISe cluster randomized controlled implementation trial
Unhealthy alcohol use is a major contributor to the global burden of disease and injury. The US Preventive Services Task Force has recommended alcohol screening and intervention in general medical settings since 2004. Yet less than one in six US adults report health care professionals discussing alcohol with them. Little is known about methods for increasing implementation; different staffing models may be related to implementation effectiveness. This implementation trial compared delivery of alcohol screening, brief intervention and referral to specialty treatment (SBIRT) by physicians versus non-physician providers receiving training, technical assistance, and feedback reports. The study was a cluster randomized implementation trial (ADVISe [Alcohol Drinking as a Vital Sign]). Within a private, integrated health care system, 54 adult primary care clinics were stratified by medical center and randomly assigned in blocked groups of three to SBIRT by physicians (PCP arm) versus non-physician providers and medical assistants (NPP and MA arm), versus usual care (Control arm). NIH-recommended screening questions were added to the electronic health record (EHR) to facilitate SBIRT. We examined screening and brief intervention and referral rates by arm. We also examined patient-, physician-, and system-level factors affecting screening rates and, among those who screened positive, rates of brief intervention and referral to treatment. Screening rates were highest in the NPP and MA arm (51 %); followed by the PCP arm (9 %) and the Control arm (3.5 %). Screening increased over the 12 months after training in the NPP and MA arm but remained stable in the PCP arm. The PCP arm had higher brief intervention and referral rates (44 %) among patients screening positive than either the NPP and MA arm (3.4 %) or the Control arm (2.7 %). Higher ratio of MAs to physicians was related to higher screening rates in the NPP and MA arm and longer appointment times to screening and intervention rates in the PCP arm. Findings suggest that time frames longer than 12 months may be required for full SBIRT implementation. Screening by MAs with intervention and referral by physicians as needed can be a feasible model for increasing the implementation of this critical and under-utilized preventive health service within currently predominant primary care models. Clinical Trials NCT01135654.
Authors: Mertens JR; Chi FW; Weisner CM; Satre DD; Ross TB; Allen S; Pating D; Campbell CI; Lu YW; Sterling SA
Addict Sci Clin Pract. 2015;10:26. Epub 2015-11-19.
Interaction between passive smoking and two HLA genes with regard to multiple sclerosis risk
The recently described interaction between smoking, human leukocyte antigen (HLA) DRB1*15 and absence of HLA-A*02 with regard to multiple sclerosis (MS) risk shows that the risk conveyed by smoking differs depending on genetic background. We aimed to investigate whether a similar interaction exists between passive smoking and HLA genotype. We used one case-control study with incident cases of MS (736 cases, 1195 controls) and one with prevalent cases (575 cases, 373 controls). Never-smokers with different genotypes and passive smoking status were compared with regard to occurrence of MS, by calculating odds ratios (ORs) with 95% confidence intervals (CIs). The potential interaction between different genotypes and passive smoking was evaluated by calculating the attributable proportion (AP) due to interaction. An interaction was observed between passive smoking and carriage of HLA-DRB1*15 (AP 0.3, 95% CI 0.02-0.5 in the incident study, and AP 0.4, 95% CI 0.1-0.7 in the prevalent study), as well as between passive smoking and absence of HLA-A*02. Compared with non-smokers without any of these two genetic risk factors, non-exposed subjects with the two risk genotypes displayed an OR of 4.5 (95% CI 3.3-6.1) whereas the same genotype for subjects exposed to passive smoking rendered an OR of 7.7 (95% CI 5.5-10.8). The risk of developing MS associated with different HLA genotypes may be influenced by exposure to passive smoking. The finding supports our hypothesis that priming of the immune response in the lungs may subsequently lead to MS in people with a genetic susceptibility to the disease.
Authors: Hedström AK; Bomfim IL; Barcellos LF; Briggs F; Schaefer C; Kockum I; Olsson T; Alfredsson L
Int J Epidemiol. 2014 Dec;43(6):1791-8. Epub 2014-10-15.
Association of Age at Depression Onset with Cognitive Functioning in Individuals with Late-Life Depression and Executive Dysfunction
To compare patterns of cognitive performance in older adults with late-onset depression (LOD; ?65 years of age) with that of older adults with early-onset depression (EOD; <65 years). Participants were 171 adults aged 60 years or older with major depression and executive dysfunction who were participating in a randomized psychotherapy trial. Participants included 72 LOD and 99 EOD individuals. Cognitive performance on measures of verbal learning, memory, and executive functioning were evaluated. Demographic and clinical characteristics, severity of cerebrovascular risk factors, and disability ratings were also compared between groups. The LOD group was older and had fewer previous episodes of depression and lower severity of depression compared with EOD participants. The LOD group demonstrated poorer performance on measures of verbal learning (F(1,161) = 4.28, p = 0.04) and memory (F(1,160) = 4.65, p = 0.03) than the EOD group. Linear regression analysis demonstrated that LOD and fewer years of education were significant predictors of poorer verbal learning (F(7,114) = 6.25, p <0.001) and memory (F(7,113)=7.24, p <0.001). Performance on measures of executive functioning, severity of vascular risk factors, and disability ratings did not differ between the two groups. In older adults with depression and executive dysfunction, LOD was associated with poorer performance on measures of verbal learning and memory. Aging-related brain changes associated with LOD may play a more important role, leading to dysfunction in these cognitive domains than a history of recurrent depressive episodes in older adults with a dysexecutive syndrome.
Authors: Mackin RS; Nelson JC; Delucchi KL; Raue PJ; Satre DD; Kiosses DN; Alexopoulos GS; Arean PA
Am J Geriatr Psychiatry. 2014 Dec;22(12):1633-41. Epub 2014-02-26.
Cognitive Outcomes after Psychotherapeutic Interventions for Major Depression in Older Adults with Executive Dysfunction
The purpose of this study was to determine the impact of psychotherapy on cognitive functioning in older adults with late-life depression (LLD) and executive dysfunction. Two hundred twenty-one adults aged 60 years and older participated in a randomized clinical trial comparing the efficacy of Problem Solving Therapy (PST) and Supportive Therapy (ST) for LLD. Cognitive performance on seven tests of executive functioning, verbal learning, and memory was evaluated at baseline, after 12 weeks of treatment, and at 24 weeks after the completion of treatment. Performance on a measure of executive functioning with a significant information processing speed component (Stroop Color and Word Test) improved after treatment, F (1, 312) = 8.50, p = 0.002, and improved performance was associated with a reduction in depressive symptoms but not treatment type. Performance on other measures of executive functioning, verbal learning, and memory did not change significantly after 12 weeks of psychotherapy treatment. Our results suggest that improvements in cognitive functioning after psychotherapy treatment for depression in older adults with executive dysfunction are likely focal and not distributed across all cognitive domains. Although previous analyses reported that PST was superior to ST in the treatment of depression, this analysis indicated no difference between the two treatments with regard to improvements in cognitive functioning.
Authors: Mackin RS; Nelson JC; Delucchi K; Raue P; Byers A; Barnes D; Satre DD; Yaffe K; Alexopoulos GS; Arean PA
Am J Geriatr Psychiatry. 2014 Dec;22(12):1496-503. Epub 2013-11-16.
Seroprevalence of Aquaporin-4-IgG in a Northern California Population Representative Cohort of Multiple Sclerosis
Using an aquaporin-4 (AQP4) M1-isoform-specific enzyme-linked immunosorbent assay (ELISA) and a fixed transfected cell-based assay (CBA), we tested AQP4-IgG in a northern California population representative cohort of 3293 potential cases with multiple sclerosis (MS). Seropositive cases were tested additionally by fluorescence-activated cell sorting, a live transfected cell-based assay. Sera samples were available in 1040 cases; 7 yielded positive results, 4 by ELISA alone and 3 by both ELISA and CBA. Clinical data (episodes of optic neuritis and longitudinally extensive transverse myelitis [reported on at least 1 magnetic resonance imaging spine]) supported the alternative diagnosis of neuromyelitis optica for 2 patients as seropositive by both ELISA and CBA. These 2 patients alone tested positive by a fluorescence-activated cell-sorting assay. The diagnosis of MS was considered correct in the other 5 patients. Thus, 5 ELISA results and 1 fixed CBA result were false positive. Sensitive serological evaluation for AQP4-IgG in this large population-representative cohort of predominantly white non-Hispanic patients with MS reveals that neuromyelitis optica spectrum disorder is rarely misdiagnosed as MS in contemporary US neurological practice (0.2%). The frequency of a false-positive result for ELISA and CBA in this MS cohort were 0.5% and 0.1%, respectively. This finding reflects the superior specificity of CBA and justifies caution in interpreting AQP4-IgG results obtained by ELISA.
Authors: Pittock SJ; Lennon VA; Bakshi N; Shen L; McKeon A; Quach H; Briggs FB; Bernstein AL; Schaefer CA; Barcellos LF
JAMA Neurol. 2014 Nov;71(11):1433-6.
Estimating genotype error rates from high-coverage next-generation sequence data
Exome and whole-genome sequencing studies are becoming increasingly common, but little is known about the accuracy of the genotype calls made by the commonly used platforms. Here we use replicate high-coverage sequencing of blood and saliva DNA samples from four European-American individuals to estimate lower bounds on the error rates of Complete Genomics and Illumina HiSeq whole-genome and whole-exome sequencing. Error rates for nonreference genotype calls range from 0.1% to 0.6%, depending on the platform and the depth of coverage. Additionally, we found (1) no difference in the error profiles or rates between blood and saliva samples; (2) Complete Genomics sequences had substantially higher error rates than Illumina sequences had; (3) error rates were higher (up to 6%) for rare or unique variants; (4) error rates generally declined with genotype quality (GQ) score, but in a nonlinear fashion for the Illumina data, likely due to loss of specificity of GQ scores greater than 60; and (5) error rates increased with increasing depth of coverage for the Illumina data. These findings, especially (3)-(5), suggest that caution should be taken in interpreting the results of next-generation sequencing-based association studies, and even more so in clinical application of this technology in the absence of validation by other more robust sequencing or genotyping methods.
Authors: Wall JD; Tang LF; Zerbe B; Kvale MN; Kwok PY; Schaefer C; Risch N
Genome Res. 2014 Nov;24(11):1734-9. Epub 2014-10-10.
Advising depression patients to reduce alcohol and drug use: Factors associated with provider intervention in outpatient psychiatry
Mental health clinicians have an important opportunity to help depression patients reduce co-occurring alcohol and drug use. This study examined demographic and clinical patient characteristics and service factors associated with receiving a recommendation to reduce alcohol and drug use from providers in a university-based outpatient psychiatry clinic. The sample consisted of 97 participants ages 18 and older who reported hazardous drinking (?3?drinks/occasion), illegal drug use (primarily cannabis) or misuse of prescription drugs, and who scored ?15 on the Beck Depression Inventory-II (BDI-II). Participants were interviewed at intake and 6 months. At 6-month telephone interview, 30% of participants reported that a clinic provider had recommended that they reduce alcohol or drug use. In logistic regression, factors associated with receiving advice to reduce use included greater number of drinks consumed in the 30 days prior to intake (p?=?.035); and greater depression severity on the BDI-II (p?=?.096) and hazardous drinking at 6 months (p?=?.05). While participants with greater alcohol intake and depression symptom severity were more likely to receive advice to reduce use, the low overall rate of recommendation to reduce use highlights the need to improve alcohol and drug use intervention among depression patients, and potentially to address alcohol and drug training and treatment implementation issues among mental health providers.
Authors: Satre DD; Leibowitz AS; Mertens JR; Weisner C
Am J Addict. 2014 Nov-Dec;23(6):570-5. Epub 2014-08-27.
Significant Life Events and their Impact on Alcohol and Drug Use: A Qualitative Study
This study used a life-course perspective to identify and understand life events related to long-term alcohol and other drug (AOD) use trajectories across the life span. Using a purposive sample, we conducted semi-structured telephone interviews with 48 participants (n = 30 abstinent and 18 non-abstinent) from a longitudinal study of AOD outcomes 15 years following outpatient AOD treatment. A content analysis was conducted using ATLAS.ti software to identify events and salient themes. Caregiving for an ill or dependent family member was related to better AOD outcomes by reinforcing abstinence and reduced drinking, and contributing to alcohol cessation in most individuals who cited caregiving as a pivotal event. Grandparenting and parenting an adult child were motivational for sustaining abstinence and reduced drinking. Findings were mixed on death of a loved one, which was related to abstinence in some and relapse in others. Redemption and mutual fulfillment as caregivers, reconciliations with adult children, and legacy-building as grandparents were themes associated with maintaining abstinence and reduced drinking. AOD treatment has the opportunity to employ motivational interventions for relapse prevention that address the meaning and lifelong reach of intimate relationships for individuals and their AOD use across the life span.
Authors: Jessup MA; Ross TB; Jones AL; Satre DD; Weisner CM; Chi FW; Mertens JR
J Psychoactive Drugs. 2014 Nov-Dec;46(5):450-9.
Predictors of Abstinence from Heavy Drinking During Treatment in COMBINE and External Validation in PREDICT
The goal of the current study was to use tree-based methods (Zhang and Singer, 2010, Recursive Partitioning and Applications, 2nd ed. Springer, New York) to identify predictors of abstinence from heavy drinking in COMBINE (Anton et al. JAMA 2006; 295:2003), the largest study of pharmacotherapy for alcoholism in the United States to date, and to validate these results in PREDICT (Mann et al. Addict Biol 2012; 18:937), a parallel study conducted in Germany. We compared a classification tree constructed according to purely statistical criteria to a tree constructed according to a combination of statistical criteria and clinical considerations for prediction of no heavy drinking during treatment in COMBINE. We considered over 100 baseline predictors. The tree approach was compared to logistic regression. The trees and a deterministic forest identified the most important predictors of no heavy drinking for direct testing in PREDICT. The tree built using both clinical and statistical considerations consisted of 4 splits based on consecutive days of abstinence (CDA) prior to randomization, age, family history of alcoholism, and confidence to resist drinking in response to withdrawal and urges. The tree based on statistical considerations with 4 splits also split on CDA and age but also on gamma-glutamyl transferase level and drinking goal. Deterministic forest identified CDA, age, and drinking goal as the most important predictors. Backward elimination logistic regression among the top 18 predictors identified in the deterministic forest analyses identified only age and CDA as significant main effects. Longer CDA and goal of complete abstinence were associated with better outcomes in both data sets. The most reliable predictors of abstinence from heavy drinking were CDA and drinking goal. Trees provide binary decision rules and straightforward graphical representations for identification of subgroups based on response and may be easier to implement in clinical settings.
Authors: Gueorguieva R; Wu R; O'Connor PG; Weisner C; Fucito LM; Hoffmann S; Mann K; O'Malley SS
Alcohol Clin Exp Res. 2014 Oct;38(10):2647-56.
Obesity during childhood and adolescence increases susceptibility to multiple sclerosis after accounting for established genetic and environmental risk factors
To investigate the association between obesity and multiple sclerosis (MS) while accounting for established genetic and environmental risk factors. Participants included members of Kaiser Permanente Medical Care Plan, Northern California Region (KPNC) (1235 MS cases and 697 controls). Logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI). Body mass index (BMI) or body size was the primary predictor of each model. Both incident and prevalent MS cases were studied. In analyses stratified by gender, being overweight at ages 10 and 20 were associated with MS in females (p<0.01). Estimates trended in the same direction for males, but were not significant. BMI in 20s demonstrated a linear relationship with MS (p-trend=9.60×10(-4)), and a twofold risk of MS for females with a BMI?30kg/m(2) was observed (OR=2.15, 95% CI 1.18, 3.92). Significant associations between BMI in 20s and MS in males were not observed. Multivariate modelling demonstrated that significant associations between BMI or body size with MS in females persisted after adjusting for history of infectious mononucleosis and genetic risk factors, including HLA-DRB1*15:01 and established non-HLA risk alleles. Results show that childhood and adolescence obesity confer increased risk of MS in females beyond established heritable and environmental risk factors. Strong evidence for a dose-effect of BMI in 20s and MS was observed. The magnitude of BMI association with MS is as large as other known MS risk factors.
Authors: Gianfrancesco MA; Schaefer C; Barcellos LF; et al.
Obes Res Clin Pract. 2014 Sep-Oct;8(5):e435-47. Epub 2014-03-06.
Midlife risk score for the prediction of dementia four decades later
The objective of this study was to obtain external validation of the only available midlife dementia risk score cardiovascular risk factors , aging and dementia study (CAIDE) constituting age, education, hypertension, obesity, and hyperlipidemia in a larger, more diverse population. Our second aim was to improve the CAIDE risk score by additional midlife risk factors. This retrospective cohort study was conducted in an integrated health care delivery system. A total of 9480 Kaiser Permanente members who participated in a health survey study (age range, 40-55 years) from 1964 to 1973 were included in this study. Dementia diagnoses from primary care and medical specialist visits were collected from January 1, 1994 to January 16, 2006, using International Classification of Diseases 9 codes 290.0, 290.1 for “possible dementia,” and 331.0 and 290.4 for “specialist confirmed dementia.” Risk model prediction and validation were examined with the C statistic, net reclassification improvement, and integrated discrimination improvement. Dementia risk per sum score was calculated with Kaplan-Meier estimates. A total of 2767 participants (25%) were diagnosed with any type of dementia, of which 1011 diagnoses (10.7%) were specialist-confirmed diagnoses. Average time between midlife examination and end of follow-up was 36.1 years. The CAIDE risk score replicated well with a C statistic of 0.75, quite similar to the original CAIDE C statistic of 0.78. The CAIDE score also predicted well within different race strata. Other midlife risk factors (central obesity, depressed mood, diabetes mellitus, head trauma, lung function, and smoking) did not improve predictability. The risk score allowed stratification of participants into those with 40-year low (9%) and high (29%) dementia risk. A combination of modifiable vascular risk factors in midlife is highly predictive of the likelihood of dementia decades later. Possible dementia prevention strategies should point to a life course perspective on maintaining vascular health.
Authors: Exalto LG; Quesenberry CP; Barnes D; Kivipelto M; Biessels GJ; Whitmer RA
Alzheimers Dement. 2014 Sep;10(5):562-70. Epub 2013-09-10.
Abuse potential of intranasal buprenorphine versus buprenorphine/naloxone in buprenorphine-maintained heroin users.
In spite of the clinical utility of buprenorphine, parenteral abuse of this medication has been reported in several laboratory investigations and in the real world. Studies have demonstrated lower abuse liability of the buprenorphine/naloxone combination relative to buprenorphine alone. However, clinical research has not yet examined the utility of the combined formulation to deter intranasal use in a buprenorphine-maintained population. Heroin-using volunteers (n = 12) lived in the hospital for 8-9 weeks and were maintained on each of three sublingual buprenorphine doses (2, 8, 24 mg). Under each maintenance dose, participants completed laboratory sessions during which the reinforcing and subjective effects of intranasal doses of buprenorphine (8, 16 mg), buprenorphine/naloxone (8/2, 8/8, 8/16, 16/4 mg) and controls (placebo, heroin 100 mg, naloxone 4 mg) were assessed. Intranasal buprenorphine alone typically produced increases in positive subjective effects and the 8 mg dose was self-administered above the level of placebo. The addition of naloxone dose dependently reduced positive subjective effects and increased aversive effects. No buprenorphine/naloxone combination dose was self-administered significantly more than placebo. These data suggest that within a buprenorphine-dependent population, intranasal buprenorphine/naloxone has reduced abuse potential in comparison to buprenorphine alone. These data strongly argue in favor of buprenorphine/naloxone rather than buprenorphine alone as the more reasonable option for managing the risk of buprenorphine misuse.
Authors: Jones, Jermaine D JD; Sullivan, Maria A MA; Vosburg, Suzanne K SK; Manubay, Jeanne M JM; Mogali, Shanthi S; Metz, Verena V; Comer, Sandra D SD
Addiction biology. 2015 Jul 01;20(4):784-98. Epub 2014-07-25.
Should pregnant women with substance use disorders be managed differently?
Pregnant women with substance use disorders have multiple special needs, which might be best managed within a multiprofessional treatment setting involving medical, psychological and social care. Adequate treatment provision remains a challenge for healthcare professionals, who should undergo special training and education when working with this patient population. Careful assessment and screening is necessary to tailor interventions individually to the woman’s needs in order to achieve beneficial clinical outcomes for mothers and newborns, whereas the choice of treatment options highly depends on the type of substance of abuse and evidence-based treatment interventions available. Economic considerations have shown that early multiprofessional treatment might yield better clinical outcomes and save healthcare costs over the lifespan.
Authors: Metz, Verena V; Köchl, Birgit B; Fischer, Gabriele G
Neuropsychiatry. 2012 Jan 25;2(1):29-41. Epub 2014-07-15.
Comparison of a drug versus money and drug versus drug self-administration choice procedure with oxycodone and morphine in opioid addicts.
This double-blind, placebo-controlled study investigated the effects of oral morphine (0, 45, 135 mg/70 kg) and oral oxycodone (0, 15, 45 mg/70 kg) on buprenorphine-maintained opioid addicts. As a 3: 1 morphine : oxycodone oral dose ratio yielded equivalent subjective and physiological effects in nondependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures – that is, a drug versus money and a drug versus drug procedure – were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater than those of high-dose morphine. The study demonstrated that a 3: 1 oral dose ratio of morphine : oxycodone was not equipotent in buprenorphine-dependent individuals. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest.
Authors: Comer, Sandra D SD; Metz, Verena E VE; Cooper, Ziva D ZD; Kowalczyk, William J WJ; Jones, Jermaine D JD; Sullivan, Maria A MA; Manubay, Jeanne M JM; Vosburg, Suzanne K SK; Smith, Mary E ME; Peyser, Deena D; Saccone, Phillip A PA
Behavioural pharmacology. 2013 Sep 01;24(5-6):504-16. Epub 2014-07-15.
Substance abuse/dependence treatment: a European perspective.
During the past decade, substantial progress has been made in the field of addiction medicine in Europe, particularly regarding the development of new treatment interventions, resulting in a wide range of therapeutic options for patients with substance use disorders. However, not all interventions are evidence based. Patients with cannabis and cocaine/amphetamine use disorders and special patient populations especially lack evidence-based treatment recommendations. Many patients undergo treatment that has not been scientifically evaluated for quality and efficacy. Moreover, there are large disparities regarding availability and treatment access across Europe, with the new member states of the European Union (EU) reporting long waiting lists and low treatment coverage. Even in Austria, which ranks among the countries with relatively high treatment coverage and good diversification of treatment in opioid maintenance therapy due to the availability of methadone, buprenorphine, and slow-release oral morphine (SROM), a considerable population of untreated or inadequately treated patients exists. Treatment for substance use disorders in Europe still has scope for improvement in terms of treatment availability and access, which is ideally provided by further development and implementation of evidence-based interventions.
Authors: Metz, Verena E VE; Brandt, Laura L; Unger, Annemarie A; Fischer, Gabriele G
Substance abuse. 2014 Dec 01;35(3):309-20. Epub 2014-07-15.
Characteristics and quality of life of opioid-dependent pregnant women in Austria.
This study investigated pregnant opioid-dependent women undergoing maintenance therapy, applying a multidisciplinary, case-management approach at the Addiction Clinic of the Medical University of Vienna, Austria. It aimed at characterizing the patients’ basic demographic and clinical parameters and evaluating their overall quality of life (QoL) prepartum and postpartum. Three hundred ninety women were treated between 1994 and 2009 with buprenorphine (n = 77), methadone (n = 184), or slow-release oral morphine (SROM) (n = 129) on an outpatient basis throughout their pregnancy and postpartum period. All patients were subject to standardized prepartum and postpartum medical and psychiatric assessments, including QoL assessments using a German adaptation of the Lancashire QoL Profile (Berliner Lebensqualitaetsprofil), and regular supervised urine toxicologies. No medication group differences were revealed regarding basic demographic or clinical data. Mean maintenance doses (SD) at time of delivery were as follows: 64 mg (36 mg) methadone, 10 mg (6 mg) buprenorphine, 455 mg (207 mg) SROM. However, buprenorphine-medicated women showed significantly less concomitant benzodiazepine consumption than methadone- or SROM-maintained women (p = 0.005), and significantly less concomitant opioid consumption than methadone-maintained women (p = 0.033) during the last trimester. Overall QoL was good prepartum and postpartum in all measured domains except "finances" and "prospect of staying in the same housing situation," and no differences were observed in QoL among the three medication groups (p = 0.177). QoL improved significantly after delivery in most of the domains (p < 0.001). Although opioid-dependent pregnant women face high-risk pregnancies and show variability in addiction severity, they report good QoL independent of the medication administered. These results show that individually tailored treatment interventions are effective for this patient population and suggest a QoL improvement after delivery.
Authors: Metz, Verena E VE; Comer, Sandra D SD; Wuerzl, Johanna J; Pribasnig, Anna A; Fischer, Gabriele G
Archives of women's mental health. 2014 Dec 01;17(6):529-39. Epub 2014-07-15.
Association between alcohol and cardiovascular disease; Mendelian randomisation analysis based on individual participant data
To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. Mendelian randomisation meta-analysis of 56 epidemiological studies. 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)). Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.
Authors: Holmes MV; Dale CE; Zuccolo L; Silverwood RJ; Guo Y; Ye Z; Prieto-Merino D; Dehghan A; Trompet S; Wong A; Cavadino A; Drogan D; Padmanabhan S; Li S; Yesupriya A; Leusink M; Sundstrom J; Hubacek JA; Pikhart H; Swerdlow DI; Panayiotou AG; Borinskaya SA; Finan C; Shah S; Kuchenbaecker KB; Shah T; Engmann J; Folkersen L; Eriksson P; Ricceri F; Melander O; Sacerdote C; Gamble DM; Rayaprolu S; Ross OA; McLachlan S; Vikhireva O; Sluijs I; Scott RA; Adamkova V; Flicker L; Bockxmeer FM; Power C; Marques-Vidal P; Meade T; Marmot MG; Ferro JM; Paulos-Pinheiro S; Humphries SE; Talmud PJ; Mateo Leach I; Verweij N; Linneberg A; Skaaby T; Doevendans PA; Cramer MJ; van der Harst P; Klungel OH; Dowling NF; Dominiczak AF; Kumari M; Nicolaides AN; Weikert C; Boeing H; Ebrahim S; Gaunt TR; Price JF; Lannfelt L; Peasey A; Kubinova R; Pajak A; Malyutina S; Voevoda MI; Tamosiunas A; Maitland-van der Zee AH; Norman PE; Hankey GJ; Bergmann MM; Hofman A; Franco OH; Cooper J; Palmen J; Spiering W; de Jong PA; Kuh D; Hardy R; Uitterlinden AG; Ikram MA; Ford I; Hyppönen E; Almeida OP; Wareham NJ; Khaw KT; Hamsten A; Husemoen LL; Tjønneland A; Tolstrup JS; Rimm E; Beulens JW; Verschuren WM; Onland-Moret NC; Hofker MH; Wannamethee SG; Whincup PH; Morris R; Vicente AM; Watkins H; Farrall M; Jukema JW; Meschia J; Cupples LA; Sharp SJ; Fornage M; Kooperberg C; LaCroix AZ; Dai JY; Lanktree MB; Siscovick DS; Jorgenson E; Spring B; Coresh J; Li YR; Buxbaum SG; Schreiner PJ; Ellison RC; Tsai MY; Patel SR; Redline S; Johnson AD; Hoogeveen RC; Hakonarson H; Rotter JI; Boerwinkle E; de Bakker PI; Kivimaki M; Asselbergs FW; Sattar N; Lawlor DA; Whittaker J; Davey Smith G; Mukamal K; Psaty BM; Wilson JG; Lange LA; Hamidovic A; Hingorani AD; Nordestgaard BG; Bobak M; Leon DA; Langenberg C; Palmer TM; Reiner AP; Keating BJ; Dudbridge F; Casas JP; InterAct Consortium
BMJ. 2014;349:g4164. Epub 2014-07-10.
A randomized trial of epidural glucocorticoid injections for spinal stenosis
Epidural glucocorticoid injections are widely used to treat symptoms of lumbar spinal stenosis, a common cause of pain and disability in older adults. However, rigorous data are lacking regarding the effectiveness and safety of these injections. In a double-blind, multisite trial, we randomly assigned 400 patients who had lumbar central spinal stenosis and moderate-to-severe leg pain and disability to receive epidural injections of glucocorticoids plus lidocaine or lidocaine alone. The patients received one or two injections before the primary outcome evaluation, performed 6 weeks after randomization and the first injection. The primary outcomes were the score on the Roland-Morris Disability Questionnaire (RMDQ, in which scores range from 0 to 24, with higher scores indicating greater physical disability) and the rating of the intensity of leg pain (on a scale from 0 to 10, with 0 indicating no pain and 10 indicating “pain as bad as you can imagine”). At 6 weeks, there were no significant between-group differences in the RMDQ score (adjusted difference in the average treatment effect between the glucocorticoid-lidocaine group and the lidocaine-alone group, -1.0 points; 95% confidence interval [CI], -2.1 to 0.1; P=0.07) or the intensity of leg pain (adjusted difference in the average treatment effect, -0.2 points; 95% CI, -0.8 to 0.4; P=0.48). A prespecified secondary subgroup analysis with stratification according to type of injection (interlaminar vs. transforaminal) likewise showed no significant differences at 6 weeks. In the treatment of lumbar spinal stenosis, epidural injection of glucocorticoids plus lidocaine offered minimal or no short-term benefit as compared with epidural injection of lidocaine alone. (Funded by the Agency for Healthcare Research and Quality; ClinicalTrials.gov number, NCT01238536.).
Authors: Friedly JL; Avins AL; Jarvik JG; et al.
N Engl J Med. 2014 Jul 3;371(1):11-21.
Smoking and Risk of Multiple Sclerosis: Evidence of Modification by NAT1 Variants
Tobacco smoke is an established risk factor for multiple sclerosis (MS). We hypothesized that variation in genes involved in metabolism of tobacco smoke constituents may modify MS risk in smokers. A three-stage gene-environment investigation was conducted for NAT1, NAT2, and GSTP1 variants. The discovery analysis was conducted among 1588 white MS cases and controls from the Kaiser Permanente Northern California Region HealthPlan (Kaiser). The replication analysis was carried out in 988 white MS cases and controls from Sweden. Tobacco smoke exposure at the age of 20 years was associated with greater MS risk in both data sets (in Kaiser, odds ratio [OR] = 1.51 [95% confidence interval (CI) = 1.17-1.93]; in Sweden, OR = 1.35 [1.04-1.74]). A total of 42 NAT1 variants showed evidence for interaction with tobacco smoke exposure (P(corrected) < 0.05). Genotypes for 41 NAT1 single nucleotide polymorphisms (SNPs) were studied in the replication data set. A variant (rs7388368C>A) within a dense transcription factor-binding region showed evidence for interaction (Kaiser, OR for interaction = 1.75 [95% CI = 1.19-2.56]; Sweden, OR = 1.62 [1.05-2.49]). Tobacco smoke exposure was associated with MS risk among rs7388368A carriers only; homozygote individuals had the highest risk (A/A, OR = 5.17 [95% CI = 2.17-12.33]). We conducted a three-stage analysis using two population-based case-control datasets that consisted of a discovery population, a replication population, and a pooled analysis. NAT1 emerged as a genetic effect modifier of tobacco smoke exposure in MS susceptibility.
Authors: Briggs FB; Schaefer C; Barcellos LF; et al.
Epidemiology. 2014 Jul;25(4):605-14.
Adverse socioeconomic position during the life course is associated with multiple sclerosis
Adverse socioeconomic position (SEP) in childhood and adulthood is associated with a proinflammatory phenotype, and therefore an important exposure to consider for multiple sclerosis (MS), a complex neuroinflammatory autoimmune disease. The objective was to determine whether SEP over the life course confers increased susceptibility to MS. 1643 white, non-Hispanic MS case and control members recruited from the Kaiser Permanente Medical Care Plan, Northern California Region, for which comprehensive genetic, clinical and environmental exposure data have been collected were studied. Logistic regression models investigated measures of childhood and adulthood SEP, and accounted for effects due to established MS risk factors, including HLA-DRB1*15:01 allele carrier status, smoking history, history of infectious mononucleosis, family history of MS and body size. Multiple measures of childhood and adulthood SEP were significantly associated with risk of MS, including parents renting versus owning a home at age 10: OR=1.48, 95% CI 1.09 to 2.02, p=0.013; less than a college education versus at least a college education based on parental household: OR=1.28, 95% CI 1.01 to 1.63, p=0.041; low versus high life course SEP: OR=1.50, 95% CI 1.09 to 2.05, p=0.012; and low versus high social mobility: OR=1.74, 95% CI 1.27 to 2.39, p=5.7×10(-4). Results derived from a population-representative case-control study provide support for the role of adverse SEP in MS susceptibility and add to the growing evidence linking lower SEP to poorer health outcomes. Both genetic and environmental contributions to chronic conditions are important and must be characterised to fully understand MS aetiology.
Authors: Briggs FB; Acuña BS; Shen L; Bellesis KH; Ramsay PP; Quach H; Bernstein A; Schaefer C; Barcellos LF
J Epidemiol Community Health. 2014 Jul;68(7):622-9. Epub 2014-02-27.
National Prevalence of Receipt of Antidepressant Prescriptions by Persons Without a Psychiatric Diagnosis
The study addressed recent concerns regarding increasing prescription of antidepressant drugs to patients with no recorded psychiatric diagnosis. Records from ten large integrated health systems in the Mental Health Research Network were used to examine diagnoses received by 1,011,946 health plan members who filled at least one antidepressant prescription in 2010. Among individuals filling antidepressant prescriptions, psychiatric diagnoses recorded during the year were depressive disorders (48%), anxiety disorders (27%), bipolar disorders (3%), and attention deficit disorders (3%). The proportion of those filling prescriptions who had no psychiatric diagnosis was 39%, which fell to 27% after the analysis excluded prescriptions for antidepressants often prescribed for nonpsychiatric indications (tricyclic antidepressants, trazodone, and bupropion). Prescription of antidepressants to patients without an appropriate diagnosis appears to be less common than previously reported.
Authors: Simon GE; Stewart C; Beck A; Ahmedani BK; Coleman KJ; Whitebird RR; Lynch F; Owen-Smith AA; Waitzfelder BE; Soumerai SB; Hunkeler EM
Psychiatr Serv. 2014 Jul;65(7):944-6.
Effectiveness of nurse-practitioner-delivered brief motivational intervention for young adult alcohol and drug use in primary care in South Africa: a randomized clinical trial
To assess the effectiveness of brief motivational intervention for alcohol and drug use in young adult primary care patients in a low-income population and country. A randomized controlled trial in a public-sector clinic in Delft, a township in the Western Cape, South Africa recruited 403 patients who were randomized to either single-session, nurse practitioner-delivered Brief Motivational Intervention plus referral list or usual care plus referral list, and followed up at 3 months. Although rates of at-risk alcohol use and drug use did not differ by treatment arm at follow-up, patients assigned to the Brief Motivational Intervention had significantly reduced scores on ASSIST (Alcohol, Smoking and Substance Involvement Screening Test) for alcohol-the most prevalent substance. Brief Motivational Intervention may be effective at reducing at-risk alcohol use in the short term among low-income young adult primary care patients; additional research is needed to examine long-term outcomes.
Authors: Mertens JR; Ward CL; Bresick GF; Broder T; Weisner CM
Alcohol Alcohol. 2014 Jul-Aug;49(4):430-8. Epub 2014-06-04.
Cognitive impairment in ORIGIN: timing is everything
Authors: Whitmer RA
Lancet Diabetes Endocrinol. 2014 Jul;2(7):531-2. Epub 2014-06-02.
Health Care Contacts in the Year Before Suicide Death
Suicide prevention is a public health priority, but no data on the health care individuals receive prior to death are available from large representative United States population samples. To investigate variation in the types and timing of health services received in the year prior to suicide, and determine whether a mental health condition was diagnosed. Longitudinal study from 2000 to 2010 within eight Mental Health Research Network health care systems serving eight states. In all, 5,894 individuals who died by suicide, and were health plan members in the year before death. Health system contacts in the year before death. Medical record, insurance claim, and mortality records were linked via the Virtual Data Warehouse, a federated data system at each site. Nearly all individuals received health care in the year prior to death (83 %), but half did not have a mental health diagnosis. Only 24 % had a mental health diagnosis in the 4-week period prior to death. Medical specialty and primary care visits without a mental health diagnosis were the most common visit types. The individuals more likely to make a visit in the year prior to death (p?
Authors: Ahmedani BK; Hunkeler EM; Solberg LI; et al.
J Gen Intern Med. 2014 Jun;29(6):870-7. Epub 2014-02-25.
Serological Documentation of Maternal Influenza Exposure and Bipolar Disorder in Adult Offspring
The authors examined whether serologically confirmed maternal exposure to influenza was associated with an increased risk of bipolar disorder in the offspring and with subtypes of bipolar disorder, with and without psychotic features. The study used a nested case-control design in the Child Health and Development Study birth cohort. In all, 85 individuals with bipolar disorder were identified following extensive ascertainment and diagnostic assessment and matched to 170 comparison subjects in the analysis. Serological documentation of maternal exposure to influenza was determined using the hemagglutination inhibition assay. No association was observed between serologically documented maternal exposure to influenza and bipolar disorder in offspring. However, maternal serological influenza exposure was related to a significant fivefold greater risk of bipolar disorder with psychotic features. The results suggest that maternal influenza exposure may increase the risk for offspring to develop bipolar disorder with psychotic features. Taken together with earlier associations between prenatal influenza exposure and schizophrenia, these results may suggest that prenatal influenza is a risk factor for psychosis rather than for a specific psychotic disorder diagnosis.
Authors: Canetta SE; Bao Y; Co MD; Ennis FA; Cruz J; Terajima M; Shen L; Kellendonk C; Schaefer CA; Brown AS
Am J Psychiatry. 2014 May 1;171(5):557-63.
Comparison of health care needs of child family members of adults with alcohol or drug dependence versus adults with asthma or diabetes
To compare the health problems, preventive care utilization, and medical costs of child family members (CFMs) of adults diagnosed with alcohol or drug dependence (AODD) to CFMs of adults diagnosed with diabetes or asthma. Child family members of adults diagnosed with AODD between 2002 and 2005 and CFMs of matched adults diagnosed with diabetes or asthma were followed up to 7 years after diagnosis of the index adult. Logistic regression was used to determine whether the CFMs of AODD adults were more likely to be diagnosed with medical conditions, or get preventive care, than the CFMs of adults with asthma or diabetes. Children’s health services use was compared using multivariate models. In Year 5 after index date, CFMs of adults with AODD were more likely to be diagnosed with depression and AODD than CFMs of adults with asthma or diabetes and were less likely to be diagnosed with asthma, otitis media, and pneumonia than CFMs of adults with asthma. CFMs of AODD adults were less likely than CFMs of adult asthmatic patients to have annual well-child visits. CFMs of AODD adults had similar mean annual total health care costs to CFMs of adults with asthma but higher total costs ($159/yr higher, confidence interval, $56-$253) than CFMs of adult diabetic patients. CFMs of adults with AODD had higher emergency department, higher outpatient alcohol and drug program, higher outpatient psychiatry, and lower primary care costs than CFMs of either adult asthmatic patients or diabetic patients. Children in families with an alcohol- or drug-dependent adult have unique patterns of health conditions, and differences in the types of health services used, compared to children in families with an adult asthmatic or diabetic family member. However, overall cost and utilization for health care services is similar or only somewhat higher. This is the first study of its kind, and the results have implications for the reduction of parental alcohol or drug dependence stigma by health care providers, clearly an important issue in this era of health reform.
Authors: Ray GT; Mertens JR; Weisner C
J Dev Behav Pediatr. 2014 May;35(4):282-91.
Early adult to midlife cardiovascular risk factors and cognitive function
Studies have linked midlife and late-life cardiovascular risk factors (CVRFs) to cognitive function, yet little is known about CVRF exposure in early adulthood and subsequent cognitive function. In addition, most studies rely on single assessments of CVRFs, which may not accurately reflect long-term exposure. We sought to determine the association between cumulative exposure to CVRFs from early to middle adulthood and cognitive function at midlife. In a prospective study of 3381 adults (age, 18-30 years at baseline) with 25 years of follow-up, we assessed cognitive function at year 25 (2010-2011) with the Digit Symbol Substitution Test, Stroop Test, and Rey Auditory Verbal Learning Test analyzed with standardized z scores. The primary predictor was 25-year cumulative exposure estimated by areas under the curve for resting systolic and diastolic blood pressures, fasting blood glucose, and total cholesterol. Higher cumulative systolic and diastolic blood pressures and fasting blood glucose were consistently associated with worse cognition on all 3 tests. These associations were significant primarily for exposures above recommended guidelines; cognitive test z scores were between 0.06 and 0.30 points less, on average, for each 1-SD increase in risk factor area under the curve after adjustment for age, race, sex, and education (P<0.05 for all). Fewer significant associations were observed for cholesterol. Cumulative exposure to CVRFs from early to middle adulthood, especially above recommended guidelines, was associated with worse cognition in midlife. The meaning of this association and whether it warrants more aggressive treatment of CVRFs earlier in life require further investigation.
Authors: Yaffe K; Vittinghoff E; Pletcher MJ; Hoang TD; Launer LJ; Whitmer R; Coker LH; Sidney S
Circulation. 2014 Apr 15;129(15):1560-7. Epub 2014-03-31.
Cardiorespiratory fitness and cognitive function in middle age: The CARDIA Study
To investigate whether greater cardiorespiratory fitness (CRF) is associated with better cognitive function 25 years later. We studied 2,747 participants in the community-based Coronary Artery Risk Development in Young Adults Study of black and white men and women aged 18 to 30 years at recruitment in 1985-1986 (baseline year 0). Symptom-limited maximal treadmill test durations at years 0 and 20 provided measures of CRF. Cognitive tests at year 25 measured verbal memory (Rey Auditory Verbal Learning Test [RAVLT]), psychomotor speed (Digit Symbol Substitution Test [DSST]), and executive function (Stroop Test). Per minute of baseline CRF, the RAVLT was 0.12 words recalled higher (standard error [SE] = 0.03, p < 0.0001), the DSST was 0.92 digits higher (SE = 0.13, p < 0.0001), and the Stroop Test score was 0.52 lower (better performance, SE = 0.11, p < 0.0001), after accounting for race, sex, age, education, and clinical center. Compared with the lowest quartile of CRF, each cognitive test was 21% to 34% of an SD better in the highest CRF quartile. Further adjustment for lifestyle and clinical measures attenuated coefficients for RAVLT and DSST slightly, while the coefficient predicting the Stroop Test lost more than half its value (p = 0.07). Analysis in the subset of 1,957 participants who also completed the year-20 treadmill test showed that 20-year change in CRF was positively associated only with DSST (p < 0.001). Better verbal memory and faster psychomotor speed at ages 43 to 55 years were clearly associated with better CRF 25 years earlier.
Authors: Zhu N; Whitmer RA; Sternfeld B; et al.
Neurology. 2014 Apr 15;82(15):1339-46. Epub 2014-04-02.
Racial/ethnic differences in dementia risk among older type 2 diabetes patients: The Diabetes and Aging Study
OBJECTIVE Although patients with type 2 diabetes have double the risk of dementia, potential racial/ethnic differences in dementia risk have not been explored in this population. We evaluated racial/ethnic differences in dementia and potential explanatory factors among older diabetic patients. RESEARCH DESIGN AND METHODS We identified 22,171 diabetic patients without preexisting dementia aged ?60 years (14,546 non-Hispanic whites, 2,484 African Americans, 2,363 Latinos, 2,262 Asians, 516 Native Americans) from the Kaiser Permanente Northern California Diabetes Registry. We abstracted prevalent medical history (1 January 1996 to 31 December 1997) and dementia incidence (1 January 1998 to 31 December 2007) from medical records and calculated age-adjusted incidence densities. We fit Cox proportional hazards models adjusted for age, sex, education, diabetes duration, and markers of clinical control. RESULTS Dementia was diagnosed in 3,796 (17.1%) patients. Age-adjusted dementia incidence densities were highest among Native Americans (34/1,000 person-years) and African Americans (27/1,000 person-years) and lowest among Asians (19/1,000 person-years). In the fully adjusted model, hazard ratios (95% CIs) (relative to Asians) were 1.64 (1.30-2.06) for Native Americans, 1.44 (1.24-1.67) for African Americans, 1.30 (1.15-1.47) for non-Hispanic whites, and 1.19 (1.02-1.40) for Latinos. Adjustment for diabetes-related complications and neighborhood deprivation index did not change the results. CONCLUSIONS Among type 2 diabetic patients followed for 10 years, African Americans and Native Americans had a 40-60% greater risk of dementia compared with Asians, and risk was intermediate for non-Hispanic whites and Latinos. Adjustment for sociodemographics, diabetes-related complications, and markers of clinical control did not explain observed differences. Future studies should investigate why these differences exist and ways to reduce them.
Authors: Mayeda ER; Karter AJ; Huang ES; Moffet HH; Haan MN; Whitmer RA
Diabetes Care. 2014 Apr;37(4):1009-15. Epub 2013-11-22.
Alcohol and drug treatment involvement, 12-step attendance and abstinence: 9-year cross-lagged analysis of adults in an integrated health plan
This study explored causal relationships between post-treatment 12-step attendance and abstinence at multiple data waves and examined indirect paths leading from treatment initiation to abstinence 9-years later. Adults (N = 1945) seeking help for alcohol or drug use disorders from integrated healthcare organization outpatient treatment programs were followed at 1-, 5-, 7- and 9-years. Path modeling with cross-lagged partial regression coefficients was used to test causal relationships. Cross-lagged paths indicated greater 12-step attendance during years 1 and 5 and were casually related to past-30-day abstinence at years 5 and 7 respectfully, suggesting 12-step attendance leads to abstinence (but not vice versa) well into the post-treatment period. Some gender differences were found in these relationships. Three significant time-lagged, indirect paths emerged linking treatment duration to year-9 abstinence. Conclusions are discussed in the context of other studies using longitudinal designs. For outpatient clients, results reinforce the value of lengthier treatment duration and 12-step attendance in year 1.
Authors: Witbrodt J; Ye Y; Bond J; Chi F; Weisner C; Mertens J
J Subst Abuse Treat. 2014 Apr;46(4):412-9. Epub 2013-11-12.
Does age at first treatment episode make a difference in outcomes over 11 years?
This study examines the associations between age at first substance use treatment entry and trajectory of outcomes over 11 years. We found significant differences in individual and treatment characteristics between adult intakes first treated during young adulthood (25 years or younger) and those first treated at an older age. Compared to their first treated older age counterparts matched on demographics and dependence type, those who entered first treatment during young adulthood had on average an earlier onset for substance use but a shorter duration between first substance use and first treatment entry; they also had worse alcohol and other drug outcomes 11 years post treatment entry. While subsequent substance use treatment and 12-step meeting attendance are important for both age groups in maintaining positive outcomes, relationships varied by age group. Findings underline the importance of different continuing care management strategies for those entering first treatment at different developmental stages.
Authors: Chi FW; Weisner C; Grella CE; Hser YI; Moore C; Mertens J
J Subst Abuse Treat. 2014 Apr;46(4):482-90. Epub 2013-12-23.
Interaction between adolescent obesity and HLA risk genes in the etiology of multiple sclerosis
We investigated potential interactions between human leukocyte antigen (HLA) genotype and body mass index (BMI) status in relation to the risk of developing multiple sclerosis (MS). We used 2 case-control studies, one with incident cases (1,510 cases, 2,017 controls) and one with prevalent cases (937 cases, 609 controls). Subjects with different genotypes and BMI were compared with regard to incidence of MS by calculating odds ratios (ORs) with 95% confidence intervals (CIs) employing logistic regression. Potential interactions between genotypes and BMI were evaluated by calculating the attributable proportion due to interaction. In both cohorts, a significant interaction was observed between HLA-DRB1*15 and obesity, regardless of HLA-A*02 status. Similarly, there was a significant interaction between absence of A*02 and obesity, regardless of DRB1*15 status. In the incident cohort, obese subjects with the most susceptible genotype (carriage of DRB1*15 and absence of A*02) had an OR of 16.2 (95% CI 7.5-35.2) compared to nonobese subjects without the genetic risk factors. The corresponding OR in the prevalent study was 13.8 (95% CI 4.1-46.8). We observed striking interactions between BMI status and HLA genotype with regard to MS risk. Hypothetically, a low-grade inflammatory response inherent to obesity synergizes with the adaptive, HLA molecule-restricted arm of the immune system, causing MS. Prevention of adolescent obesity may thus lower the risk of developing MS, predominantly among people with a genetic susceptibility to the disease.
Authors: Hedström AK; Lima Bomfim I; Barcellos L; Gianfrancesco M; Schaefer C; Kockum I; Olsson T; Alfredsson L
Neurology. 2014 Mar 11;82(10):865-72. Epub 2014-02-05.
Dementia and cognitive decline in type 2 diabetes and prediabetic stages: towards targeted interventions
Type 2 diabetes is associated with dementia, and also with more slight cognitive decrements. In this Review we discuss trajectories from normal cognition to dementia in people with type 2 diabetes, and explore opportunities for treatment. Slight diabetes-associated cognitive decrements and dementia affect different age groups and show a different evolution. These cognitive entities should therefore not be regarded as a continuum, although their effects might be additive. Vascular damage is a key underlying process in both entities. Glucose-mediated processes and other metabolic disturbances might also have a role. No treatment has been established, but management of vascular risk factors and optimisation of glycaemic control could have therapeutic benefit. We identify possible opportunities for intervention to improve cognitive outcomes in people with type 2 diabetes, and suggest how treatment can be tailored to individual risk profiles and comorbidities.
Authors: Biessels GJ; Strachan MW; Visseren FL; Kappelle LJ; Whitmer RA
Lancet Diabetes Endocrinol. 2014 Mar;2(3):246-55. Epub 2013-10-18.
‘The chief of the service is very enthusiastic about it’: A qualitative study of the adoption of buprenorphine for opioid addiction treatment
Qualified physicians may prescribe buprenorphine to treat opioid dependence, but medication use remains controversial. We examined adoption of buprenorphine in two not-for-profit integrated health plans, over time, completing 101 semi-structured interviews with clinicians and clinician-administrators from primary and specialty care. Transcripts were reviewed, coded, and analyzed. A strong leader championing the new treatment was critical for adoption in both health plans. Once clinicians began using buprenorphine, patients’ and other clinicians’ experiences affected decisions more than did the champion. With experience, protocols developed to manage unsuccessful patients and changed to support maintenance rather than detoxification. Diffusion outside addiction and mental health settings was nonexistent; primary care clinicians cited scope-of-practice issues and referred patients to specialty care. With greater diffusion came questions about long-term use and safety. Recognizing how implementation processes develop may suggest where, when, and how to best expend resources to increase adoption of such treatments.
Authors: Green CA; McCarty D; Mertens J; Lynch FL; Hilde A; Firemark A; Weisner CM; Pating D; Anderson BM
J Subst Abuse Treat. 2014 Mar;46(3):390-401. Epub 2013-10-23.
How complete are E-codes in commercial plan claims databases?
Authors: Lu CY; Hunkeler EM; Soumerai SB; et al.
Pharmacoepidemiol Drug Saf. 2014 Feb;23(2):218-20.
Do Patient-perceived Pros and Cons of Opioids Predict Sustained Higher-Dose Use?
Chronic opioid therapy (COT) is associated with various adverse outcomes, especially at higher doses, yet little is known about predictors of sustained higher-dose COT. This study aimed to ascertain, among higher-dose COT patients, the association of patient-perceived pros and cons of opioids with continued higher-dose use 1 year later. Patients (N=1229) in 2 large health plans prescribed ?50 mg morphine-equivalent dose (MED) per day for chronic noncancer pain completed a survey assessing opioid benefits and harms. The Prescribed Opioid Difficulties Scale questionnaire assessed psychosocial problems, concerns, benefits, and side effects related to opioid use. Logistic regression models estimated the associations of the reported benefits and problems with higher-dose continuation (?50 mg MED/d) versus dose reduction (<50 mg MED/d) 1 year later. Over 80% of participants continued higher-dose opioid use at 1 year, regardless of reported problems, concerns, side effects, pain reduction, or perceived helpfulness. Higher scores on the Prescribed Opioid Difficulties Scale Problems subscale (odds ratio=0.79, 95% confidence interval, 0.68-0.92) and Concerns subscale (odds ratio=0.76, 95% confidence interval, 0.65-0.90) were negatively associated with higher-dose use 1 year later. Other baseline measures (opioid helpfulness, reduction in pain, number of side effects, and side effect bothersomeness) were not significantly associated with continued higher-dose use. The large majority of patients continued using higher-dose opioids regardless of baseline characteristics. These findings suggest the difficulty of reducing opioid dose among chronic higher-dose opioid users.
Authors: Thielke SM; Turner JA; Shortreed SM; Saunders K; Leresche L; Campbell CI; Weisner CC; Korff MV
Clin J Pain. 2014 Feb;30(2):93-101.
Five-Year Healthcare Utilization and Costs Among Lower-Risk Drinkers Following Alcohol Treatment
Lower-risk drinking is increasingly being examined as a treatment outcome for some patients following addiction treatment. However, few studies have examined the relationship between drinking status (lower-risk drinking in particular) and healthcare utilization and cost, which has important policy implications. Participants were adults with alcohol dependence and/or abuse diagnoses who received outpatient alcohol and other drug treatment in a private, nonprofit integrated healthcare delivery system and had a follow-up interview 6 months after treatment entry (N = 995). Associations between past 30-day drinking status at 6 months (abstinence, lower-risk drinking defined as nonabstinence and no days of 5+ drinking, and heavy drinking defined as 1 or more days of 5+ drinking) and repeated measures of at least 1 emergency department (ED), inpatient or primary care visit, and their costs over 5 years were examined using mixed-effects models. We modeled an interaction between time and drinking status to examine trends in utilization and costs over time by drinking group. Heavy drinkers and lower-risk drinkers were not significantly different from the abstainers in their cost or utilization at time 0 (i.e., 6 months postintake). Heavy drinkers had increasing odds of inpatient (p < 0.01) and ED (p < 0.05) utilization over 5 years compared with abstainers. Lower-risk drinkers and abstainers did not significantly differ in their service use in any category over time. No differences were found in changes in primary care use among the 3 groups over time. The cost analyses paralleled the utilization results. Heavy drinkers had increasing ED (p < 0.05) and inpatient (p < 0.001) costs compared with the abstainers; primary care costs did not significantly differ. Lower-risk drinkers did not have significantly different medical costs compared with those who were abstinent over 5 years. However, post hoc analyses found lower-risk drinkers and heavy drinkers to not significantly differ in their ED use or costs over time. Performance measures for treatment settings that consider treatment outcomes may need to take into account both abstinence and reduction to nonheavy drinking. Future research should examine whether results are replicated in harm reduction treatment, or whether such outcomes are found only in abstinence-based treatment.
Authors: Kline-Simon AH; Weisner CM; Parthasarathy S; Falk DE; Litten RZ; Mertens JR
Alcohol Clin Exp Res. 2014 Feb;38(2):579-86. Epub 2013-10-07.
Back pain in seniors: the back pain outcomes using longitudinal data (BOLD) cohort baseline data
Back pain represents a substantial burden globally, ranking first in a recent assessment among causes of years lived with disability. Though back pain is widely studied among working age adults, there are gaps with respect to basic descriptive epidemiology among seniors, especially in the United States. Our goal was to describe how pain, function and health-related quality of life vary by demographic and geographic factors among seniors presenting to primary care providers with new episodes of care for back pain. We examined baseline data from the Back pain Outcomes using Longitudinal Data (BOLD) registry, the largest inception cohort to date of seniors presenting to a primary care provider for back pain. The sample included 5,239 patients ? 65 years old with a new primary care visit for back pain at three integrated health systems (Northern California Kaiser-Permanente, Henry Ford Health System [Detroit], and Harvard Vanguard Medical Associates [Boston]). We examined differences in patient characteristics across healthcare sites and associations of patient sociodemographic and clinical characteristics with baseline patient-reported measures of pain, function, and health-related quality of life. Patients differed across sites in demographic and other characteristics. The Detroit site had more African-American patients (50%) compared with the other sites (7-8%). The Boston site had more college graduates (68%) compared with Detroit (20%). Female sex, lower educational status, African-American race, and older age were associated with worse functional disability as measured by the Roland-Morris Disability Questionnaire. Except for age, these factors were also associated with worse pain. Baseline pain and functional impairment varied substantially with a number of factors in the BOLD cohort. Healthcare site was an important factor. After controlling for healthcare site, lower education, female sex, African-American race, and older age were associated with worse physical disability and all of these factors except age were associated with worse pain. Clinical Trials.gov NCT01776242; Registration date: June 13, 2012.
Authors: Jarvik JG; Avins AL; Deyo RA; et al.
BMC Musculoskelet Disord. 2014;15:134. Epub 2014-04-23.
Severe Diabetic Retinal Disease and Dementia Risk in Type 2 Diabetes
Persons with type 2 diabetes are at an increased risk of dementia compared to those without, but the etiology of this increased risk is unclear. Cerebral microvascular disease may mediate the link between diabetes and dementia. Given the anatomical and physiological similarities between cerebral and retinal microvessels, we examined the longitudinal association between diabetic retinal disease and dementia in patients with type 2 diabetes. Longitudinal cohort study of 29,961 patients with type 2 diabetes aged ?60 years. Electronic medical records were used to collect diagnoses and treatment of severe diabetic retinal disease (i.e., diabetic proliferative retinopathy and macular edema) between 1996-1998 and dementia diagnoses for the next ten years (1998-2008). The association between diabetic retinal disease and dementia was evaluated by Cox proportional hazard models adjusted for sociodemographics, as well as diabetes-specific (e.g., diabetes duration, pharmacotherapy, HbA1c, hypoglycemia, hyperglycemia) and vascular (e.g., vascular disease, smoking, body mass index) factors. 2,008 (6.8%) patients had severe diabetic retinal disease at baseline and 5,173 (17.3%) participants were diagnosed with dementia during follow-up. Those with diabetic retinal disease had a 42% increased risk of incident dementia (demographics adjusted Hazards Ratio (HR) = 1.42, 95% Confidence Interval (CI) 1.27, 1.58); further adjustment for diabetes-specific (HR 1.29; 95% CI 1.14, 1.45) and vascular-related disease conditions (HR 1.35; 95% CI 1.21, 1.52) attenuated the relation slightly. Diabetic patients with severe diabetic retinal disease have an increased risk of dementia. This may reflect a causal link between microvascular disease and dementia.
Authors: Exalto LG; Biessels GJ; Karter AJ; Huang ES; Quesenberry CP; Whitmer RA
J Alzheimers Dis. 2014;42 Suppl 3:S109-17.
Effectiveness of a pharmacist-based gout care management programme in a large integrated health plan: results from a pilot study
The study objective was to determine the feasibility of using a pharmacist-staffed, protocol-based structured approach to improving the management of chronic, recurrent gout. The study was carried out in the outpatient clinic of a single Kaiser Permanente medical centre. This is a community-based clinic. We report on 100 consecutive patients between the ages of 21 and 94 (75% men) with chronic or recurrent gout, referred by their primary physicians for the purpose of management of urate-lowering therapy. Patients with stage 5 chronic kidney disease or end-stage kidney disease were excluded. The programme consisted of a trained clinical pharmacist and a rheumatologist. The pharmacist contacted each patient by phone, provided educational and dietary materials, and used a protocol that employs standard gout medications to achieve and maintain a serum uric acid (sUA) level of 6 mg/dL or less. Incident gout flares or adverse reactions to medications were managed in consultation with the rheumatologist. The primary outcome measure was the achievement and maintenance of an sUA of 6 or less for a period of at least 3 months. In 95 evaluable patients enrolled in our pilot programme, an sUA of 6 mg/dL or less was achieved and maintained in 78 patients with 4 still in the programme to date. Five patients declined to participate after referral, and another 13 patients did not complete the programme. (The majority of these were due to non-adherence.) A structured pharmacist-staffed programme can effectively and safely lower and maintain uric acid levels in a high percentage of patients with recurrent gout in a primary care setting. This care model is simple to implement, efficient and warrants further validation in a clinical trial.
Authors: Goldfien RD; Ng MS; Yip G; Hwe A; Jacobson A; Pressman A; Avins AL
BMJ Open. 2014;4(1):e003627. Epub 2014-01-10.
Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi-experimental study
To investigate if the widely publicized warnings in 2003 from the US Food and Drug Administration about a possible increased risk of suicidality with antidepressant use in young people were associated with changes in antidepressant use, suicide attempts, and completed suicides among young people. Quasi-experimental study assessing changes in outcomes after the warnings, controlling for pre-existing trends. Automated healthcare claims data (2000-10) derived from the virtual data warehouse of 11 health plans in the US Mental Health Research Network. Study cohorts included adolescents (around 1.1 million), young adults (around 1.4 million), and adults (around 5 million). Rates of antidepressant dispensings, psychotropic drug poisonings (a validated proxy for suicide attempts), and completed suicides. Trends in antidepressant use and poisonings changed abruptly after the warnings. In the second year after the warnings, relative changes in antidepressant use were -31.0% (95% confidence interval -33.0% to -29.0%) among adolescents, -24.3% (-25.4% to -23.2%) among young adults, and -14.5% (-16.0% to -12.9%) among adults. These reflected absolute reductions of 696, 1216, and 1621 dispensings per 100,000 people among adolescents, young adults, and adults, respectively. Simultaneously, there were significant, relative increases in psychotropic drug poisonings in adolescents (21.7%, 95% confidence interval 4.9% to 38.5%) and young adults (33.7%, 26.9% to 40.4%) but not among adults (5.2%, -6.5% to 16.9%). These reflected absolute increases of 2 and 4 poisonings per 100,000 people among adolescents and young adults, respectively (approximately 77 additional poisonings in our cohort of 2.5 million young people). Completed suicides did not change for any age group. Safety warnings about antidepressants and widespread media coverage decreased antidepressant use, and there were simultaneous increases in suicide attempts among young people. It is essential to monitor and reduce possible unintended consequences of FDA warnings and media reporting.
Authors: Lu CY; Hunkeler EM; Soumerai SB; et al.
BMJ. 2014;348:g3596. Epub 2014-06-18.
Positive and Negative Interactions Observed Between Siblings: Moderating Effects for Children Exposed to Parents’ Conflict.
This study investigated links between interparental conflict appraisals (specifically threat and self-blame), sibling relationship quality (positive and negative dimensions), and anxiety in sibling pairs comprised of an adolescent and a younger sibling close in age. Sibling relationship quality was measured through behavioral observation. Links between self-blame and anxiety were moderated by sibling relationship quality. In older siblings, positive behavior with a sibling was associated with an attenuated relation between self-blame and anxiety. A paradoxical moderating effect was found for negative interactions; for both younger and older siblings, a relation between self-blame and anxiety was weakened in the presence of sibling negativity. Results offered support for theorized benefits of sibling relationship quality in helping early adolescents adjust to conflict between parents.
Authors: Iturralde E; Margolin G; Spies Shapiro LA
J Res Adolesc. 2013 Dec 1;23(4). doi: 10.1111/jora.12020.
Use of antipsychotic medications in pediatric populations: what do the data say?
Recent reports of antipsychotic medication use in pediatric populations describe large increases in rates of use. Much interest in the increasing use has focused on potentially inappropriate prescribing for non-Food and Drug Administration-approved uses and use amongst youth with no mental health diagnosis. Different studies of antipsychotic use have used different time periods, geographic and insurance populations of youth, and aggregations of diagnoses. We review recent estimates of use and comment on the similarities and dissimilarities in rates of use. We also report new data obtained on 11 health maintenance organizations that are members of the Mental Health Research Network in order to update and extend the knowledge base on use by diagnostic indication. Results indicate that most use in pediatric populations is for disruptive behaviors and not psychotic disorders. Differences in estimates are likely a function of differences in methodology; however, there is remarkable consistency in estimates of use by diagnosis.
Authors: Penfold RB; Hunkeler EM; Simon GE; et al.
Curr Psychiatry Rep. 2013 Dec;15(12):426.
The effect of bariatric surgery on psychiatric course among patients with bipolar disorder
Bariatric surgery is the most effective therapy for severe obesity. People with bipolar disorder have increased risk of obesity, yet are sometimes considered ineligible for bariatric surgery due to their bipolar disorder diagnosis. This study aimed to determine if bariatric surgery alters psychiatric course among stable patients with bipolar disorder. A matched cohort study (2006-2009) with mean follow-up of 2.17 years was conducted within Kaiser Permanente Northern California, a group practice integrated health services delivery organization that provides medical and psychiatric care to 3.3 million people. Participants were 144 severely obese patients with bipolar disorder who underwent bariatric surgery, and 1,440 control patients with bipolar disorder, matched for gender, medical center, and contemporaneous health plan membership. Controls met referral criteria for bariatric surgery. Hazard ratio for psychiatric hospitalization, and change in rate of outpatient psychiatric utilization from baseline to Years 1 and 2, were compared between groups. A total of 13 bariatric surgery patients (9.0%) and 153 unexposed to surgery (10.6%) had psychiatric hospitalization during follow-up. In multivariate Cox models adjusting for potential confounding factors, the hazard ratio of psychiatric hospitalization associated with bariatric surgery was 1.03 [95% confidence interval (CI): 0.83-1.23]. In fully saturated multivariate general linear models, change in outpatient psychiatric utilization was not significantly different for surgery patients versus controls, from baseline to Year 1 (-0.4 visits/year, 95% CI: -0.5 to 0.4) or baseline to Year 2 (0.4 visits/year, 95% CI: -0.1 to 1.0). Bariatric surgery did not affect psychiatric course among stable patients with bipolar disorder. The results of this study suggest that patients with bipolar disorder who have been evaluated as stable can be considered for bariatric surgery.
Authors: Ahmed AT; Warton EM; Schaefer CA; Shen L; McIntyre RS
Bipolar Disord. 2013 Nov;15(7):753-63. Epub 2013-08-05.
Fine-Mapping the Genetic Association of the Major Histocompatibility Complex in Multiple Sclerosis: HLA and Non-HLA Effects
The major histocompatibility complex (MHC) region is strongly associated with multiple sclerosis (MS) susceptibility. HLA-DRB1*15:01 has the strongest effect, and several other alleles have been reported at different levels of validation. Using SNP data from genome-wide studies, we imputed and tested classical alleles and amino acid polymorphisms in 8 classical human leukocyte antigen (HLA) genes in 5,091 cases and 9,595 controls. We identified 11 statistically independent effects overall: 6 HLA-DRB1 and one DPB1 alleles in class II, one HLA-A and two B alleles in class I, and one signal in a region spanning from MICB to LST1. This genomic segment does not contain any HLA class I or II genes and provides robust evidence for the involvement of a non-HLA risk allele within the MHC. Interestingly, this region contains the TNF gene, the cognate ligand of the well-validated TNFRSF1A MS susceptibility gene. The classical HLA effects can be explained to some extent by polymorphic amino acid positions in the peptide-binding grooves. This study dissects the independent effects in the MHC, a critical region for MS susceptibility that harbors multiple risk alleles.
Authors: Patsopoulos NA; Barcellos LF; Schaefer C; de Bakker PI; et al.
PLoS Genet. 2013 Nov;9(11):e1003926. Epub 2013-11-21.
Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis
Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
Authors: International Multiple Sclerosis Genetics Consortium (IMSGC); Barcellos LF; Schaefer C; McCauley JL; et al.
Nat Genet. 2013 Nov;45(11):1353-60. Epub 2013-09-29.
Risk score for prediction of 10 year dementia risk in individuals with type 2 diabetes: a cohort study
Although patients with type 2 diabetes are twice as likely to develop dementia as those without this disease, prediction of who has the highest future risk is difficult. We therefore created and validated a practical summary risk score that can be used to provide an estimate of the 10 year dementia risk for individuals with type 2 diabetes. Using data from two longitudinal cohorts of patients with type 2 diabetes (aged ?60 years) with 10 years of follow-up, we created (n=29,961) and validated (n=2413) the risk score. We built our prediction model by evaluating 45 candidate predictors using Cox proportional hazard models and developed a point system for the risk score based on the size of the predictor’s ? coefficient. Model prediction was tested by discrimination and calibration methods. Dementia risk per sum score was calculated with Kaplan-Meier estimates. Microvascular disease, diabetic foot, cerebrovascular disease, cardiovascular disease, acute metabolic events, depression, age, and education were most strongly predictive of dementia and constituted the risk score (C statistic 0·736 for creation cohort and 0·746 for validation cohort). The dementia risk was 5·3% (95% CI 4·2-6·3) for the lowest score (-1) and 73·3% (64·8-81·8) for the highest (12-19) sum scores. To the best of our knowledge, this is the first risk score for the prediction of 10 year dementia risk in patients with type 2 diabetes mellitus. The risk score can be used to increase vigilance for cognitive deterioration and for selection of high-risk patients for participation in clinical trials. Kaiser Permanente Community Benefit, National Institute of Health, Utrecht University, ZonMw, and Fulbright.
Authors: Exalto LG; Biessels GJ; Karter AJ; Huang ES; Katon WJ; Minkoff JR; Whitmer RA
Lancet Diabetes Endocrinol. 2013 Nov;1(3):183-90. Epub 2013-08-20.
Maternal smoking during pregnancy and bipolar disorder in offspring
OBJECTIVE: Maternal smoking during pregnancy is associated with a number of adverse externalizing outcomes for offspring from childhood to adulthood. The relationship between maternal smoking and bipolar disorder in offspring, which includes externalizing symptoms among its many manifestations, has not been investigated in depth. The authors examined whether offspring exposed to maternal smoking in utero would be at increased lifetime risk for bipolar disorder after accounting for other factors related to maternal smoking. METHOD: Individuals with bipolar disorder (N=79) were ascertained from the birth cohort of the Child Health and Development Study. Case subjects were identified by a combination of clinical, database, and direct mailing sources; all case subjects were directly interviewed and diagnosed using DSM-IV criteria. Comparison subjects (N=654) were matched to case subjects on date of birth (+/-30 days), sex, membership in the cohort at the time of illness onset, and availability of maternal archived sera. RESULTS: After adjusting for potential confounders, offspring exposed to in utero maternal smoking exhibited a twofold greater risk for bipolar disorder (odds ratio=2.014, 95% confidence interval=1.48-2.53, p=0.01). The associations were noted primarily among bipolar offspring without psychotic features. CONCLUSIONS: Prenatal tobacco exposure may be one suspected cause of bipolar disorder. However, it will be necessary to account for other unmeasured familial factors before causal teratogenic effects can be suggested.
Authors: Talati A; Bao Y; Kaufman J; Shen L; Schaefer CA; Brown AS
Am J Psychiatry. 2013 Oct 1;170(10):1178-85.
Parental age and risk of bipolar disorder in offspring
We investigated prospectively documented parental age and bipolar disorder (BD) in a multi-ethnic birth cohort. The study was based on a nested case-control design from the Child Health and Development Study (CHDS) birth cohort from 1959 to 1966. Potential cases with BD were ascertained by database linkages between CHDS, Kaiser Permanente Medical Care Plan (KPNC), and Alameda County Behavioral Health Care Services, and mailed questionnaires. Consensus diagnoses with the SCID for DSM-IV-TR were made. The total number of BD cases was 94. Controls (N=746) were selected from the birth cohort and matched on date of birth, sex, and KPNC membership or residence in Alameda County. For every 10-year increment of paternal age, there was no significant association with BD, adjusting for maternal age. There was also no significant association between maternal age, modeled in 10-year increments, and risk of BD after adjustment for paternal age and maternal race, although there was a suggestion for a protective relationship between increasing maternal age and BD with psychotic features. These findings suggest that if advanced paternal age is a risk factor for BD, the strength of the relationship is small.
Authors: Brown A; Bao Y; McKeague I; Shen L; Schaefer C
Psychiatry Res. 2013 Aug 15;208(3):225-31. Epub 2013-06-19.
Examination of rare missense variants in the CHRNA5-A3-B4 gene cluster to level of response to alcohol in the San Diego Sibling Pair study
BACKGROUND:Common variants in the CHRNA5-A3-B4 gene cluster have been shown to be associated with nicotine dependence and alcohol use disorders (AUDs) and related traits, including the level of response (LR) to alcohol. Recently, rare variants (MAF < 0.05) in CHRNB4 have been reported to be associated with a decreased risk of developing nicotine dependence. However, the role of rare variants in the CHRNA5-A3-B4 gene cluster to the LR to alcohol has not yet been established.METHODS:To determine whether rare variants in the CHRNA5-A3-B4 gene cluster contribute to the LR to alcohol, the coding regions of these 3 genes were sequenced in 538 subjects from the San Diego Sibling Pair study.RESULTS:The analyses identified 16 rare missense variants, 9 of which were predicted to be damaging using in silico analysis tools. Carriers of these variants were compared to noncarriers using a family-based design for each gene and for the gene cluster as a whole. In these analyses, a CHRNA5 carrier status was significantly associated with the phenotype related to the feeling of intoxication experienced during the alcohol challenge (p = 0.039).CONCLUSIONS:These results indicate that rare genetic variation in the CHRNA5-A3-B4 gene cluster contributes modestly to the LR to alcohol in the San Diego Sibling Pair study and may protect against AUDs. However, replication studies are needed to confirm our findings.
Authors: Choquet H; Joslyn G; Lee A; Kasberger J; Robertson M; Brush G; Schuckit MA; White R; Jorgenson E
Alcohol Clin Exp Res. 2013 Aug;37(8):1311-6. doi: 10.1111/acer.12099. Epub 2013 Mar 4.
Factors Associated With Treatment Initiation for Psychiatric and Substance Use Disorders Among Persons With HIV
Prior studies of individuals with HIV infection have found that accessing psychiatric and substance abuse treatment when needed can improve health and prolong life, yet little is known about factors associated with treatment initiation. In a retrospective cohort design including individuals with HIV infection (?14 years old) in an integrated health care system in Northern California, this study included 822 patients with a major psychiatric diagnosis and 1,624 with a substance use disorder diagnosis. Data were extracted from a regional HIV registry and computerized databases. Twenty-four percent (N=198) of study patients with psychiatric diagnoses and 15% (N=245) with substance abuse or dependence received one or more specialty care visits within 12 months of diagnosis. Among patients with a psychiatric diagnosis, significant predictors of visiting a psychiatry clinic included not having an AIDS diagnosis at baseline or before the study (p=.049), having a diagnosis of major depression (p=.013), having a diagnosis of bipolar disorder (p<.001), and receiving a psychiatric diagnosis in 1996 versus later years of the study (p<.01). Among patients with a substance use disorder, significant predictors of initiating substance abuse treatment included age <30 (p=.015) and being in the HIV transmission risk group of injection drug use (p<.001). Clinical, diagnostic, and demographic factors were associated with specialty care treatment initiation in this sample of individuals with HIV infection and substance use or psychiatric disorders. Developing strategies to enhance treatment initiation has the potential to improve outcomes for individuals with HIV infection.
Authors: Satre DD; DeLorenze GN; Quesenberry CP; Tsai A; Weisner C
Psychiatr Serv. 2013 Aug 1;64(8):745-53.
Patients’ attitudes about the use of placebo treatments: telephone survey
OBJECTIVE: To examine the attitudes of US patients about the use of placebo treatments in medical care. DESIGN: One time telephone surveys. SETTING: Northern California. PARTICIPANTS: 853 members of Kaiser Permanente Northern California, aged 18-75, who had been seen by a primary care provider for a chronic health problem at least once in the prior six months. RESULTS: The response rate was 53.4% (853/1598) of all members who were eligible to participate, and 73.2% (853/1165) of all who could be reached by telephone. Most respondents (50-84%) judged it acceptable for doctors to recommend placebo treatments under conditions that varied according to doctors’ level of certainty about the benefits and safety of the treatment, the purpose of the treatment, and the transparency with which the treatment was described to patients. Only 21.9% of respondents judged that it was never acceptable for doctors to recommend placebo treatments. Respondents valued honesty by physicians regarding the use of placebos and believed that non-transparent use could undermine the relationship between patients and physicians. CONCLUSIONS: Most patients in this survey seemed favorable to the idea of placebo treatments and valued honesty and transparency in this context, suggesting that physicians should consider engaging with patients to discuss their values and attitudes about the appropriateness of using treatments aimed at promoting placebo responses in the context of clinical decision making.
Authors: Hull SC; Colloca L; Avins A; Gordon NP; Somkin CP; Kaptchuk TJ; Miller FG
BMJ. 2013 Jul 2;347:f3757.
Gestational Influenza and Bipolar Disorder in Adult Offspring
IMPORTANCE: Gestational influenza has been associated previously with schizophrenia in offspring, but the relationship between this exposure and bipolar disorder (BD) is unclear. The identification of gestational influenza as a risk factor for BD may have potential for preventive approaches. OBJECTIVE: To test the hypothesis that maternal influenza during pregnancy is related to BD among offspring. DESIGN: Nested case-control study of a population-based birth cohort from the Child Health and Development Study (CHDS). From January 1, 1959, through December 31, 1966, the CHDS recruited nearly all pregnant women receiving obstetric care from the Kaiser Permanente Medical Care Plan, Northern California Region (KPNC). Data on treated maternal influenza from the CHDS were used. Potential cases with BD from the cohort were identified by database linkages of identifiers among the CHDS, Kaiser Permanente database, and a large county health care database; by a mailed questionnaire to the CHDS cohort with subsequent interviews; and from an earlier psychiatric follow-up study on this birth cohort. SETTING: The CHDS, Kaiser Permanente, and county health care databases. PARTICIPANTS: Cases of BD (n = 92) confirmed by structured research interviews and consensus diagnosis among the 214 subjects (48% of those ascertained) who participated and control subjects (n = 722) matched on date of birth, sex, and membership in KPNC or residence in Alameda County. EXPOSURES: Influenza. MAIN OUTCOME AND MEASURES: Bipolar I or II disorder, BD not otherwise specified, or BD with psychotic features. RESULTS: We found a significant, nearly 4-fold increase in the risk of BD (odds ratio, 3.82 [95% CI, 1.58-9.24; P = .003]) after exposure to maternal influenza at any time during pregnancy. The findings were not confounded by maternal age, race, educational level, gestational age at birth, and maternal psychiatric disorders. CONCLUSIONS AND RELEVANCE: Maternal influenza may be a risk factor for BD. Although replication is required, the findings suggest that prevention of maternal influenza during pregnancy may reduce the risk of BD.
Authors: Parboosing R; Bao Y; Shen L; Schaefer CA; Brown AS
JAMA Psychiatry. 2013 Jul;70(7):677-85.
Clinical and ethical aspects of placebos in clinical practice-reply
Authors: Avins AL
JAMA Intern Med. 2013 Apr 22;173(8):711-2.
ALDH1A3 loss of function causes bilateral anophthalmia/microphthalmia and hypoplasia of the optic nerve and optic chiasm
The major active retinoid, all-trans retinoic acid, has long been recognized as critical for the development of several organs, including the eye. Mutations in STRA6, the gene encoding the cellular receptor for vitamin A, in patients with Matthew-Wood syndrome and anophthalmia/microphthalmia (A/M), have previously demonstrated the importance of retinol metabolism in human eye disease. We used homozygosity mapping combined with next-generation sequencing to interrogate patients with anophthalmia and microphthalmia for new causative genes. We used whole-exome and whole-genome sequencing to study a family with two affected brothers with bilateral A/M and a simplex case with bilateral anophthalmia and hypoplasia of the optic nerve and optic chiasm. Analysis of novel sequence variants revealed homozygosity for two nonsense mutations in ALDH1A3, c.568A>G, predicting p.Lys190*, in the familial cases, and c.1165A>T, predicting p.Lys389*, in the simplex case. Both mutations predict nonsense-mediated decay and complete loss of function. We performed antisense morpholino (MO) studies in Danio rerio to characterize the developmental effects of loss of Aldh1a3 function. MO-injected larvae showed a significant reduction in eye size, and aberrant axonal projections to the tectum were noted. We conclude that ALDH1A3 loss of function causes anophthalmia and aberrant eye development in humans and in animal model systems.
Authors: Yahyavi M; Abouzeid H; Gawdat G; de Preux AS; Xiao T; Bardakjian T; Schneider A; Choi A; Jorgenson E; Baier H; El Sada M; Schorderet DF; Slavotinek AM
Hum Mol Genet. 2013 Aug 15;22(16):3250-8. Epub 2013-04-15.
Genetic analysis of a population heavy drinking phenotype identifies risk variants in whites
Genetic association studies thus far have used detailed diagnoses of alcoholism to identify loci associated with risk. This proof-of-concept analysis examined whether population data of lifetime heaviest alcohol consumption may be used to identify genetic loci that modulate risk. We conducted a genetic association study in European Americans between variants in approximately 2100 genes and alcohol consumption as part of the Candidate gene Association Resource project. We defined cases as individuals with a history of drinking 5 or more drinks per day almost every day of the week and controls as current light drinkers (1-5 drinks per week). We cross-validated identified single nucleotide polymorphisms in a meta-analysis of 2 cohorts of unrelated individuals–Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health Study (CHS)–and in a separate cohort of related individuals–Framingham Heart Study (FHS). The most significant variant in the meta-analysis of ARIC and CHS was rs6933598 in methylenetetrahydrofolate dehydrogenase (P = 7.46 × 10(-05)) with a P value in FHS of 0.042. The top variants in FHS were rs12249562 in cubulin (P = 3.03 × 10(-05)) and rs9839267 near cholecystokinin (P = 3.05 × 10(-05)) with a P value of 0.019 for rs9839267 in CHS. We have here shown feasibility in evaluating lifetime incidence of heavy alcohol drinking from population-based studies for the purpose of conducting genetic association analyses.
Authors: Hamidovic A; Goodloe RJ; Young TR; Styn MA; Mukamal KJ; Choquet H; Kasberger JL; Buxbaum SG; Papanicolaou GJ; White W; Volcik K; Spring B; Hitsman B; Levy D; Jorgenson E.;
J Clin Psychopharmacol. 2013 Apr;33(2):206-10. doi: 10.1097/JCP.0b013e318287009a.
Safety and Toxicity of Saw palmetto in the Complementary and Alternative Medicine for Urological Symptoms (CAMUS) Trial
PURPOSE: Extracts of the saw palmetto berry are used by many men in the United States as self-treatment for lower urinary tract symptoms due to benign prostatic hyperplasia. While the most recent data from double-blind clinical trials do not support efficacy superior to that of placebo, there are sparse data on saw palmetto toxicity. MATERIALS AND METHODS: A total of 369 patients were randomized in the CAMUS (Complementary and Alternative Medicine for Urological Symptoms) trial, of whom 357 were included in this modified intent to treat analysis. Participants were randomized to 320, 640 and 960 mg daily of an ethanolic saw palmetto extract or to an identical-appearing placebo in an escalating manner at 6-month intervals for a total of 18 months of followup. Adverse event assessments, vital signs, and blood and urine laboratory tests were obtained at regular intervals. RESULTS: There were no statistically significant differences between the groups in the rates of serious or nonserious adverse events, changes in vital signs, digital prostate examination findings or study withdrawal rates. Overall, there were no significant intergroup differences in laboratory test abnormalities, while differences in individual laboratory tests were rare and small in magnitude. No evidence of significant dose-response phenomena was identified. CONCLUSIONS: The saw palmetto extract used in the CAMUS trial showed no evidence of toxicity at doses up to 3 times the usual clinical dose during an 18-month period.
Authors: Avins AL; Lee JY; Meyers CM; Barry MJ; CAMUS Study Group
J Urol. 2013 Apr;189(4):1415-20. Epub 2012 Oct 9.
Motivational interviewing to reduce hazardous drinking and drug use among depression patients
This randomized study examined the efficacy of motivational interviewing (MI) to reduce substance use among adults with depression in outpatient psychiatry. The sample consisted of 104 participants ages 18 and over who reported hazardous drinking (three drinks or more per occasion), illegal drug use or misuse of prescription drugs in the prior 30 days, and who scored >/= 15 on the Beck Depression Inventory-II (BDI-II). Participants were randomized to receive either three sessions of MI or printed literature about alcohol and drug use risks, as an adjunct to usual outpatient depression care, and completed telephone follow-up interviews at 3 and 6 months (93 and 99% of the baseline sample, respectively). Among participants reporting any hazardous drinking at baseline (n=73), MI-treated participants were less likely than controls to report hazardous drinking at 3 months (60.0 vs. 81.8%, p=.043). MI is a promising intervention to reduce hazardous drinking among depression patients.
Authors: Satre DD; Delucchi K; Lichtmacher J; Sterling SA; Weisner C
J Subst Abuse Treat. 2013 Mar;44(3):323-9. Epub 2012 Sep 19.
Contribution of common PCSK1 genetic variants to obesity in 8,359 subjects from multi-ethnic American population
Common PCSK1 variants (notably rs6232 and rs6235) have been shown to be associated with obesity in European, Asian and Mexican populations. To determine whether common PCSK1 variants contribute to obesity in American population, we conducted association analyses in 8,359 subjects using two multi-ethnic American studies: the Coronary Artery Risk Development in Young Adults (CARDIA) study and the Multi-Ethnic Study of Atherosclerosis (MESA). By evaluating the contribution of rs6232 and rs6235 in each ethnic group, we found that in European-American subjects from CARDIA, only rs6232 was associated with BMI (P = 0.006) and obesity (P = 0.018) but also increased the obesity incidence during the 20 years of follow-up (HR = 1.53 [1.07-2.19], P = 0.019). Alternatively, in African-American subjects from CARDIA, rs6235 was associated with BMI (P = 0.028) and obesity (P = 0.018). Further, by combining the two case-control ethnic groups from the CARDIA study in a meta-analysis, association between rs6235 and obesity risk remained significant (OR = 1.23 [1.05-1.45], P = 9.5×10(-3)). However, neither rs6232 nor rs6235 was associated with BMI or obesity in the MESA study. Interestingly, rs6232 was associated with BMI (P = 4.2×10(-3)) and obesity (P = 3.4×10(-3)) in the younger European-American group combining samples from the both studies [less than median age (53 years)], but not among the older age group (P = 0.756 and P = 0.935 for BMI and obesity, respectively). By combining all the case-control ethnic groups from CARDIA and MESA in a meta-analysis, we found no significant association for the both variants and obesity risk. Finally, by exploring the full PCSK1 locus, we observed that no variant remained significant after correction for multiple testing. These results indicate that common PCSK1 variants (notably rs6232 and rs6235) contribute modestly to obesity in multi-ethnic American population. Further, these results suggest that the association of rs6232 with obesity may be age-dependent in European-Americans. However, multiple replication studies in multi-ethnic American population are needed to confirm our findings.
Authors: Choquet H; Kasberger J; Hamidovic A; Jorgenson E
PLoS One. 2013;8(2):e57857. doi: 10.1371/journal.pone.0057857. Epub 2013 Feb 25.
Posttreatment Low-Risk Drinking as a Predictor of Future Drinking and Problem Outcomes Among Individuals with Alcohol Use Disorders
BACKGROUND: Treatment for alcohol disorders has traditionally been abstinence-oriented, but evaluating the merits of a low-risk drinking outcome as part of a primary treatment endpoint is a timely issue given new pertinent regulatory guidelines. This study explores a posttreatment low-risk drinking outcome as a predictor of future drinking and problem severity outcomes among individuals with alcohol use disorders in a large private, not for profit, integrated care health plan. METHODS: Study participants include adults with alcohol use disorders at 6 months (N = 995) from 2 large randomized studies. Logistic regression models were used to explore the relationship between past 30-day drinker status at 6 months posttreatment (abstinent [66%], low-risk drinking [14%] defined as nonabstinence and no days of 5+ drinking, and heavy drinking [20%] defined as 1 or more days of 5+ drinking) and 12-month outcomes, including drinking status and Addiction Severity Index measures of medical, psychiatric, family/social, and employment severity, controlling for baseline covariates. RESULTS: Compared to heavy drinkers, abstinent individuals and low-risk drinkers at 6 months were more likely to be abstinent or low-risk drinkers at 12 months (adj. ORs = 16.7 and 3.4, respectively; p < 0.0001); though, the benefit of abstinence was much greater than that of low-risk drinking. Compared to heavy drinkers, abstinent and low-risk drinkers were similarly associated with lower 12-month psychiatric severity (adj. ORs = 1.8 and 2.2, respectively, p < 0.01) and family/social problem severity (adj. OR = 2.2; p < 0.01). While abstinent individuals had lower 12-month employment severity than heavy drinkers (adj. OR = 1.9; p < 0.01), low-risk drinkers did not differ from heavy drinkers. The drinking groups did not differ on 12-month medical problem severity. CONCLUSIONS: Compared to heavy drinkers, low-risk drinkers did as well as abstinent individuals for many of the outcomes important to health and addiction policy. Thus, an endpoint that allows low-risk drinking may be tenable for individuals undergoing alcohol specialty treatment.
Authors: Kline-Simon AH; Falk DE; Litten RZ; Mertens JR; Fertig J; Ryan M; Weisner CM
Alcohol Clin Exp Res. 2013 Jan;37 Suppl 1:E373-80. Epub 2012 Jul 24.
12-step participation and outcomes over 7 years among adolescent substance use patients with and without psychiatric comorbidity
This study examines the associations between 12-step participation and outcomes over 7 years among 419 adolescent substance use patients with and without psychiatric comorbidities. Although level of participation decreased over time for both groups, comorbid adolescents participated in 12-step groups at comparable or higher levels across time points. Results from mixed-effects logistic regression models indicated that for both groups, 12-step participation was associated with both alcohol and drug abstinence at follow-ups, increasing the likelihood of either by at least 3 times. Findings highlight the potential benefits of 12-step participation in maintaining long-term recovery for adolescents with and without psychiatric disorders.
Authors: Chi FW; Sterling S; Campbell CI; Weisner C
Subst Abus. 2013;34(1):33-42.
Team-based learning exercise efficiently teaches brief intervention skills to medicine residents
Evaluations of substance use screening and brief intervention (SBI) curricula typically focus on learner attitudes and knowledge, although effects on clinical skills are of greater interest and utility. Moreover, these curricula often require large amounts of training time and teaching resources. This study examined whether a 3-hour SBI curriculum for internal medicine residents utilizing a team-based learning (TBL) format is effective for SBI skills as measured by a standardized patient (SP) assessment. A waitlist-controlled design was employed. Twenty-four postgraduate year 2 (PGY-2) and PGY-3 residents participated in a SP assessment prior to the TBL session (waitlist control group) and 32 participated in a SP assessment after the TBL session (intervention group). The intervention residents demonstrated better brief intervention skills than waitlist control residents, but there were no differences between the groups in screening and assessment skills. Residents receiving the TBL curriculum prior to the SP assessment reported increased confidence in all SBI skills. Findings indicate that a brief educational intervention can improve brief intervention skills. However, more intensive education may be needed to improve substance use screening and assessment.
Authors: Wamsley MA; Julian KA; O'Sullivan P; McCance-Katz EF; Batki SL; Satre DD; Satterfield J
Subst Abus. 2013;34(4):344-9.
Symptom Burden of Adults with Type 2 Diabetes Across the Disease Course: Diabetes & Aging Study
BACKGROUND: Reducing symptom burden is paramount at the end-of-life, but typically considered secondary to risk factor control in chronic disease, such as diabetes. Little is known about the symptom burden experienced by adults with type 2 diabetes and the need for symptom palliation. OBJECTIVE: To examine pain and non-pain symptoms of adults with type 2 diabetes over the disease course – at varying time points before death and by age. DESIGN: Survey follow-up study. PARTICIPANTS: 13,171 adults with type 2 diabetes, aged 30-75 years, from Kaiser Permanente, Northern California, who answered a baseline symptom survey in 2005-2006. MAIN MEASURES: Pain and non-pain symptoms were identified by self-report and medical record data. Survival status from baseline was categorized into 6-24, or alive >24 months. KEY RESULTS: Mean age was 60 years; 48 % were women, and 43 % were non-white. Acute pain was prevalent (41.8 %) and 39.7 % reported chronic pain, 24.6 % fatigue, 23.7 % neuropathy, 23.5 % depression, 24.2 % insomnia, and 15.6 % physical/emotional disability. Symptom burden was prevalent in all survival status categories, but was more prevalent among those with shorter survival, p< .001. Adults >/= 60 years who were alive >24 months reported more physical symptoms such as acute pain and dyspnea, whereas participants <60 years reported more psychosocial symptoms, such as depressed mood and insomnia. Adjustment for duration of diabetes and comorbidity reduced the association between age and pain, but did not otherwise change our results. CONCLUSIONS: In a diverse cohort of adults with type 2 diabetes, pain and non-pain symptoms were common among all patients, not only among those near the end of life. However, symptoms were more prevalent among patients with shorter survival. Older adults reported more physical symptoms, whereas younger adults reported more psychosocial symptoms. Diabetes care management should include not only good cardiometabolic control, but also symptom palliation across the disease course.
Authors: Sudore RL; Karter AJ; Adams A; Whitmer RA; Schillinger D; et al.
J Gen Intern Med. 2012 Dec;27(12):1674-81. Epub 2012 Aug 2.
Prescribed opioid difficulties, depression and opioid dose among chronic opioid therapy patients
BACKGROUND: Chronic opioid therapy has increased dramatically, as have complications related to prescription opioids. Little is known about the problems and concerns attributed to opioids by patients receiving different opioid doses. METHODS: We surveyed 1883 patients who were receiving chronic opioid therapy for chronic noncancer pain. Opioid regimen characteristics were ascertained from electronic pharmacy records. Patient-reported opioid-related problems and concerns were measured using the Prescription Opioid Difficulties Scale. Depression was assessed with the Patient Health Questionnaire. RESULTS: Patients prescribed higher opioid doses reported modestly higher pain intensity and pain impact. After adjustment, patients on higher doses attributed higher levels of psychosocial problems and control concerns to prescribed opioids (P<.0001). They also had higher levels of depression and were more likely to meet criteria for clinical depression. Over 60% of patients receiving 120+ mg daily (morphine equivalent) were clinically depressed, a 2.6-fold higher risk (95% confidence interval: 1.5-4.4) than patients on low-dose regimens (<20 mg daily). CONCLUSIONS: Higher opioid doses were associated with somewhat higher pain severity and higher levels of patient-reported opioid-related psychosocial problems, control concerns and depression. These findings may result from patient selection for high-dose therapy or problems caused by higher-dose opioids.
Authors: Merrill JO; Von Korff M; Banta-Green CJ; Sullivan MD; Saunders KW; Campbell CI; Weisner C
Gen Hosp Psychiatry. 2012 Nov-Dec;34(6):581-7. Epub 2012 Sep 5.
12-Step participation reduces medical use costs among adolescents with a history of alcohol and other drug treatment
BACKGROUND: Adolescents who attend 12-step groups following alcohol and other drug (AOD) treatment are more likely to remain abstinent and to avoid relapse post-treatment. We examined whether 12-step attendance is also associated with a corresponding reduction in health care use and costs. METHODS: We used difference-in-difference analysis to compare changes in seven-year follow-up health care use and costs by changes in 12-step participation. Four Kaiser Permanente Northern California AOD treatment programs enrolled 403 adolescents, 13-18-years old, into a longitudinal cohort study upon AOD treatment entry. Participants self-reported 12-step meeting attendance at six-month, one-year, three-year, and five-year follow-up. Outcomes included counts of hospital inpatient days, emergency room (ER) visits, primary care visits, psychiatric visits, AOD treatment costs and total medical care costs. RESULTS: Each additional 12-step meeting attended was associated with an incremental medical cost reduction of 4.7% during seven-year follow-up. The medical cost offset was largely due to reductions in hospital inpatient days, psychiatric visits, and AOD treatment costs. We estimate total medical use cost savings at $145 per year (in 2010 U.S. dollars) per additional 12-step meeting attended. CONCLUSIONS: The findings suggest that 12-step participation conveys medical cost offsets for youth who undergo AOD treatment. Reduced costs may be related to improved AOD outcomes due to 12-step participation, improved general health due to changes in social network following 12-step participation, or better compliance to both AOD treatment and 12-step meetings.
Authors: Mundt MP; Parthasarathy S; Chi FW; Sterling S; Campbell CI
Drug Alcohol Depend. 2012 Nov 1;126(1-2):124-30. Epub 2012 May 26.
A Web-Delivered Care Management and Patient Self-Management Program for Recurrent Depression: A Randomized Trial
OBJECTIVE This study assessed the impact of an Internet-delivered care management and patient self-management program, eCare for Moods, on patients treated for recurrent or chronic depression. METHODS Patients with recurrent or chronic depression were randomly assigned to eCare (N=51) or usual specialty mental health care (N=52). The 12-month eCare program integrates with ongoing depression care, links to patients’ electronic medical records, and provides clinicians with panel management and decision support. Participants were interviewed at baseline and six, 12, 18, and 24 months after enrollment. Telephone interviewers blind to treatment used a timeline follow-back method to estimate depression severity on a 6-point scale for each of the 105 study weeks (including the baseline). Differences between groups in weekly severity over two years were examined by generalized estimating equations. RESULTS Participants in eCare experienced more reduction in depressive symptoms (estimate=-.74 on the 6-point scale over two years; 95% confidence interval [CI]=-1.38 to -.09, p=.025) and were less often depressed (-.24 over two years; CI=-.46 to -.03, p=.026). At 24 months, 43% of eCare and 30% of usual-care participants were depression free; the number needed to treat to attain one additional depression-free participant was 8. eCare participants had other favorable outcomes: improved general mental health (p=.002), greater satisfaction with specialty care (p=.003) and with learning new coping skills (p<.001), and more confidence in managing depression (p=.006). CONCLUSIONS Internet-delivered care management can help improve outcomes of patients treated for recurrent or chronic depression.
Authors: Hunkeler EM; Fireman B; Taylor CB; et al.
Psychiatr Serv. 2012 Nov;63(11):1063-71.
An update on type 2 diabetes, vascular dementia and Alzheimer’s disease
The risk of dementia is increased in people with type 2 diabetes mellitus (T2DM). This review gives an update on the relation between T2DM and specific dementia subtypes – i.e. Alzheimer’s disease and vascular dementia – and underlying pathologies. We will show that while epidemiological studies link T2DM to Alzheimer’s disease as well as vascular dementia, neuropathological studies attribute the increased dementia risk in T2DM patients primarily to vascular lesions in the brain. Risk factors for dementia among patients with T2DM are also addressed. Currently, there is evidence that microvascular complications, atherosclerosis and severe hypoglycemic events increase dementia risk. However, for a more complete understanding of risk factors for dementia in T2DM a life time perspective is needed. This should identify which individuals are at increased risk, what are vulnerable periods in life, and what are windows of opportunity for treatment. Currently, there are no DM specific treatments for dementia, but we will review observations from clinical trials that tried to prevent cognitive decline through intensified glycemic control and address other clinical implications of the association between T2DM and dementia.
Authors: Exalto LG; Whitmer RA; Kappele LJ; Biessels GJ
Exp Gerontol. 2012 Nov;47(11):858-64. Epub 2012 Aug 3.
Hormone therapy and Alzheimer disease dementia: New findings from the Cache County Study
OBJECTIVES: Observational studies suggest reduced risk of Alzheimer disease (AD) in users of hormone therapy (HT), but trials show higher risk. We examined whether the association of HT with AD varies with timing or type of HT use. METHODS: Between 1995 and 2006, the population-based Cache County Study followed 1,768 women who had provided a detailed history on age at menopause and use of HT. During this interval, 176 women developed incident AD. Cox proportional hazard models evaluated the association of HT use with AD, overall and in relation to timing, duration of use, and type (opposed vs unopposed) of HT. RESULTS: Women who used any type of HT within 5 years of menopause had 30% less risk of AD (95% confidence interval 0.49-0.99), especially if use was for 10 or more years. By contrast, AD risk was not reduced among those who had initiated HT 5 or more years after menopause. Instead, rates were increased among those who began ‘opposed’ estrogen-progestin compounds within the 3 years preceding the Cache County Study baseline (adjusted hazard ratio 1.93; 95% confidence interval 0.94-3.96). This last hazard ratio was similar to the ratio of 2.05 reported in randomized trial participants assigned to opposed HT. CONCLUSIONS: Association of HT use and risk of AD may depend on timing of use. Although possibly beneficial if taken during a critical window near menopause, HT (especially opposed compounds) initiated in later life may be associated with increased risk. The relation of AD risk to timing and type of HT deserves further study.
Authors: Shao H; Whitmer RA; Cache County Investigators; et al.
Neurology. 2012 Oct 30;79(18):1846-52. Epub 2012 Oct 24.
Needling the Status Quo: Comment on ‘Acupuncture for Chronic Pain’
Authors: Avins AL
Arch Intern Med. 2012 Oct 22;172(19):1454-5.
Integrating Substance Use Treatment Into Adolescent Health Care
Substance use (SU) problems are common among adolescents, a serious health risk for them and a major public health problem, but are inadequately addressed in most pediatric health care settings. Primary care offers an excellent context for SU assessment and treatment for adolescents and their families, offering better access and a less stigmatized environment for receiving treatment than specialty programs. This paper examines the literature on the integration of substance use treatment with adolescent health care, focusing on 2 areas: Screening, Brief Intervention, and Referral to Treatment (SBIRT) in Emergency Departments and Primary Care, and School- and College-Based Health Centers.
Authors: Sterling S; Valkanoff T; Hinman A; Weisner C
Curr Psychiatry Rep. 2012 Oct;14(5):453-61.
Performance measures for substance use disorders — what research is needed?
In 2010, the Washington Circle convened a meeting, supported by the National Institute on Drug Abuse (NIDA) and the Substance Abuse and Mental Health Services Administration (SAMHSA), for a multidisciplinary group of experts to focus on the research gaps in performance measures for substance use disorders. This article presents recommendations in three areas: development of new performance measures; methodological and other considerations in using performance measures; and implementation research focused on using performance measures for accountability and quality improvement.
Authors: Garnick DW; Horgan CM; Acevedo A; McCorry F; Weisner C
Addict Sci Clin Pract. 2012 Sep 11;7(1):18.
Ten-year stability of remission in private alcohol and drug outpatient treatment: Non-problem users versus abstainers
BACKGROUND: This study examined stability of remission in patients who were abstainers and non-problem users at 1-year after entering private, outpatient alcohol and drug treatment. We examined: (a) How does risk of relapse change over time? (b) What was the risk of relapse for non-problem users versus abstainers? (c) What individual, treatment, and extra-treatment characteristics predicted time to relapse, and did these differ by non-problem use versus abstinence? METHODS: The sample consisted of 684 adults in remission (i.e., abstainers or non-problem users) 1 year following treatment intake. Participants were interviewed at intake, and 1, 5, 7, 9, and 11 years after intake. We used discrete-time survival analysis to examine when relapse is most likely to occur and predictors of relapse. RESULTS: Relapse was most likely at 5-year, and least likely at 11-year follow-up. Non-problem users had twice the odds of relapse compared to abstainers. Younger individuals and those with fewer 12-step meetings and shorter index treatment had higher odds of relapse than others. We found no significant interactions between non-problem use and the other covariates suggesting that significant predictors of outcome did not differ for non-problem users. CONCLUSIONS: Non-problem use is not an optimal 1-year outcome for those in an abstinence-oriented, heterogeneous substance use treatment program. Future research should examine whether these results are found in harm reduction treatment and self-help models, or in those with less severe problems. Results suggest treatment retention and 12-step participation are prognostic markers of long-term positive outcomes for those achieving remission at 1 year.
Authors: Mertens JR; Kline-Simon AH; Delucchi KL; Moore C; Weisner CM
Drug Alcohol Depend. 2012 Sep 1;125(1-2):67-74. Epub 2012 Apr 26.
Depression and Ambivalence Toward Chronic Opioid Therapy for Chronic Noncancer Pain
OBJECTIVES:: Chronic opioid therapy (COT) for chronic noncancer pain (CNCP) is characterized by both high rates of patient-initiated discontinuation and by perceived helpfulness among those who sustain opioid use. This study examines predictors of the desire to cut down or stop opioid therapy among patients receiving COT who report that opioids are helpful for relieving pain. METHODS:: We conducted a cross-sectional survey of 1737 selected patients receiving COT for CNCP who perceived opioids to be helpful in relieving their pain. Ambivalence about opioid use was assessed by agreement/disagreement with a statement indicating that they would like to stop or cut down the use of prescribed opioid medications. Depression was measured with the 8-item Patient Health Questionnaire. RESULTS:: A high percentage (43.3%) of survey respondents who found opioids helpful also reported the desire to stop or cut down opioids. Half of these patients reporting the desire to stop or cut down were clinically depressed, compared with a third of those not wanting to stop or cut down, a highly significant difference after controlling for covariates (P<0.0001). The group wanting to stop or cut down opioid use also reported significantly higher levels of opioid-related psychosocial problems and opioid control concerns. DISCUSSION:: There are high rates of ambivalence about opioid use among COT recipients who consider opioids helpful for pain relief. Depressed patients are more likely to be ambivalent about use of prescribed opioids. Eliciting patient ambivalence may be helpful in patients who are not benefiting from long-term opioid use as an initial step toward consideration of discontinuation.
Authors: Howe CQ; Sullivan MD; Saunders KW; Merrill JO; Banta-Green CJ; Weisner C; Campbell CI; Von Korff M
Clin J Pain. 2012 Sep;28(7):561-6.
Placebo adherence and mortality in the heart and estrogen/progestin replacement study
BACKGROUND: Analyses from double-blind randomized trials have reported lower mortality among participants who were more adherent to placebo compared with those who were less adherent. We explored this phenomenon by analyzing data from the placebo arm of the Heart and Estrogen/Progestin Replacement Study (HERS), a randomized, double-blind, placebo-controlled trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Our primary aim was to measure and explain the association between adherence to placebo and total mortality among the placebo-allocated participants in the HERS. Secondary aims included assessment of the association between placebo adherence and cause-specific morbidity and mortality. METHODS: Participants with ‘higher placebo adherence’ were defined as having taken at least 75% of their placebo study medication during each individual’s participation in the study, whereas those with ‘lower placebo adherence’ took less than 75%. The primary outcome was in-study all-cause mortality. RESULTS: More adherent participants had significantly lower total mortality compared with less adherent participants (hazard ratio, 0.52; 95% confidence interval, 0.29-0.93). Adjusting for available confounders did not change the magnitude or significance of the estimates. Analyses revealed that the association of higher adherence and mortality might be explained, in part, by time-dependent confounding. CONCLUSIONS: Analyses of the HERS data support a strong association between adherence to placebo study medication and mortality. Although probably not due to simple confounding by healthy lifestyle factors, the underlying mechanism for the association remains unclear. Further analyses of this association are necessary to explain this observation.
Authors: Padula AM; Pressman AR; Vittinghoff E; Grady D; Neuhaus J; Ackerson L; Rudd P; Avins AL
Am J Med. 2012 Aug;125(8):804-10.
Remission from alcohol and other drug problem use in public and private treatment samples over seven years
BACKGROUND: The treatment of alcohol and other drugs is now more commonly framed in terms of a chronic condition which requires ongoing monitoring. A model which includes continuing access to health care may optimize outcomes. Most studies of chronic care models have not included health care and have only examined short term effects. METHODS: The sample (n=783) included consecutive admissions in ten public and private alcohol and other drug (AOD) treatment programs followed over seven years. The outcome was remission which was defined as alcohol and drug abstinence or non-problem use. RESULTS: In the private sample, receiving health care services predicted remission across the seven years; however this did not occur in the public sample. More patients in the public treatment sample received AOD treatment readmissions each year, while more of those in the private sector received psychiatric and general health visits. Except for drug problem severity, there were no other clinical differences between the samples. There were no differences in the proportions of patients in the two sectors who received the full spectrum of chronic care services. In the final models, 12-step participation was markedly significant for both samples. CONCLUSIONS: Models of chronic care for substance use need to consider differences between private and public treatment and should take into account that individuals may not always have access, or avail themselves of services that may optimize long-term outcomes.
Authors: Delucchi KL; Weisner C; Kline Simon AH
Drug Alcohol Depend. 2012 Jul 1;124(1-2):57-62. Epub 2011 Dec 29.
Do 12-step meeting attendance trajectories over 9 years predict abstinence?
This study grouped treatment-seeking individuals (n = 1825) by common patterns of 12-step attendance using 5 waves of data (75% interviewed Year 9) to isolate unique characteristics and use-related outcomes distinguishing each class profile. The ‘high’ class reported the highest attendance and abstention. The ‘descending’ class reported high baseline alcohol severity, long treatment episodes, and high initial attendance and abstinence, but by Year 5, their attendance and abstinence dropped. The ‘early-drop’ class, which started with high attendance and abstinence but with low problem severity, reported no attendance after Year 1. The ‘rising’ class, with fairly high alcohol and psychiatric severity throughout, reported initially low attendance, followed by increasing attendance paralleling their abstention. Last, the ‘low’ and ‘no’ classes, which reported low problem severity and very low/no attendance, had the lowest abstention. Female gender and high alcohol severity predicted attendance all years. Consistent with a sustained benefit for 12-step exposure, abstinence patterns aligned much like attendance profiles.
Authors: Witbrodt J; Mertens J; Kaskutas LA; Bond J; Chi F; Weisner C
J Subst Abuse Treat. 2012 Jul;43(1):30-43. Epub 2011 Dec 27.
Depression and prescription opioid misuse among chronic opioid therapy recipients with no history of substance abuse
PURPOSE Opioid misuse in the context of chronic opioid therapy (COT) is a growing concern. Depression may be a risk factor for opioid misuse, but it has been difficult to tease out the contribution of co-occurring substance abuse. This study aims to examine whether there is an association between depression and opioid misuse in patients receiving COT who have no history of substance abuse. METHODS A telephone survey was conducted at Group Health Cooperative and Kaiser Permanente of Northern California. We interviewed 1,334 patients on COT for noncancer pain who had no history of substance abuse. Patients were asked about 3 forms of opioid misuse: (1) self-medicating for symptoms other than pain, (2) self-increasing doses, and (3) giving to or getting opioids from others. Depression was evaluated by the 8-item Patient Health Questionnaire (PHQ-8). RESULTS Compared with patients who were not depressed (PHQ-8 score 0 to 4), patients with moderate depression (PHQ-8 score 10 to 14) and severe depression (PHQ-8 score 15 or higher) were 1.8 and 2.4 times more likely, respectively, to misuse their opioid medications for non-pain symptoms. Patients with mild (PHQ-8 score 5 to 9), moderate, and severe depression were 1.9, 2.9, and 3.1 times more likely, respectively, to misuse their opioid medications by self-increasing their dose. There was no statistically significant association between depression and giving opioids to or getting them from others. CONCLUSION In patients with no substance abuse history, depressive symptoms are associated with increased rates of some forms of self-reported opioid misuse. Clinicians should be alert to the risk of patients with depressive symptoms using opioids to relieve these symptoms and thereby using more opioids than prescribed.
Authors: Grattan A; Sullivan MD; Saunders KW; Campbell CI; Von Korff MR
Ann Fam Med. 2012 Jul-Aug;10(4):304-11.
Audio recordings of mindfulness-based stress reduction training to improve cancer patients’ mood and quality of life-a pilot feasibility study
PURPOSE: Mindfulness-based stress reduction (MBSR), typically taught in eight weekly classes, helps patients cope with illness, including cancer. Current research is almost exclusively based on post-treatment class attendance. Research suggests that short courses and alternative delivery techniques may also be beneficial. This pilot study assessed whether it would be feasible for cancer patients receiving chemotherapy to listen to MBSR audio recordings individually during treatment and at home and evaluate whether the intervention shows preliminary evidence of efficacy to improve patients’ mood and quality of life (QoL). METHODS: Patients were recruited from two oncology clinics. Inclusion criteria included a score >/=8 on the Hospital Anxiety and Depression Scale (HADS). Participants were asked to listen to study CDs containing MBSR instructions at least 5 days/week for 3 months and to maintain study diaries of their meditation practices. RESULTS: Twenty-three patients enrolled in the study, and 20 (87%; 95% confidence interval (CI), 66% to 97%) completed the study protocol. Analysis showed that participants listened to study CDs an average of 39 times during the study; mean HADS scores declined from 18.3 to 12.2 (change = -6.1 points; 95% CI, -2.9 to -9.4). Participants reported subjectively that participation improved their mood and QoL. CONCLUSIONS: This pilot study demonstrates the feasibility of investigating an individual audio MBSR intervention for patients with cancer and provides preliminary evidence that MBSR may benefit chemotherapy patients’ mood and QoL. Fully powered comparative clinical trials to asses this MBSR modality to help improve mood and QoL for patients receiving chemotherapy are feasible and needed.
Authors: Altschuler A; Rosenbaum E; Gordon P; Canales S; Avins AL
Support Care Cancer. 2012 Jun;20(6):1291-7. Epub 2011 Jun 19.
The Role of Continuing Care in 9-year Cost Trajectories of Patients With Intakes Into an Outpatient Alcohol and Drug Treatment Program
BACKGROUND: The importance of a continuing care approach for substance use disorders (SUDs) is increasingly being recognized. Our prior research found that a Continuing Care model for SUDs that incorporates 3 components (regular primary care, and specialty SUD and psychiatric treatment as needed) is beneficial to long-term remission. The study builds on this work to examine the cost implications of this model. OBJECTIVES: To examine associations between receiving Continuing Care and subsequent health care costs over 9 years among adults entering outpatient SUD treatment in a private nonprofit, integrated managed care health plan. We also compare the results to a similar analysis of a demographically matched control group without SUDs. STUDY DESIGN: Longitudinal observational study. MEASURES: Measures collected over 9 years include demographic characteristics, self-reported alcohol and drug use and Addiction Severity Index, and health care utilization and cost data from health plan databases. RESULTS: Within the treatment sample, SUD patients receiving all components of Continuing Care had lower costs than those receiving fewer components. Compared with the demographically matched non-SUD controls, those not receiving Continuing Care had significantly higher inpatient costs (excess cost = $65.79/member-month; P < 0.01) over 9 years, whereas no difference was found between those receiving Continuing Care and controls. CONCLUSIONS: Although a causal link cannot be established between receiving Continuing Care and reduced long-term costs in this observational study, the findings reinforce the importance of access to health care and development of interventions that optimize patients receiving those services and that may reduce costs to health systems.
Authors: Parthasarathy S; Chi FW; Mertens JR; Weisner C
Med Care. 2012 Jun;50(6):540-6.
Low maternal retinol as a risk factor for schizophrenia in adult offspring
BACKGROUND: Prenatal micronutrient deficiency has been linked to later development of schizophrenia among offspring; however, no study has specifically investigated the association between vitamin A and this disorder. Vitamin A is an essential nutrient which is required by the early embryo and fetus for gene expression and regulation, cell differentiation, proliferation and migration. Previous work suggests that vitamin A deficiency in the second trimester may be particularly relevant to the etiopathogenesis of neurobehavioral phenotypes some of which are observed in schizophrenia. METHODS: We examined whether low maternal vitamin A levels in the second trimester are associated with the risk of schizophrenia and other schizophrenia spectrum disorders (SSD) in the Prenatal Determinants of Schizophrenia study; third trimester vitamin A levels were also examined in relation to SSD. The cases were derived from a population-based birth cohort; all cohort members belonged to a prepaid health plan. Archived maternal serum samples were assayed for vitamin A in cases (N=55) and up to 2 controls per case (N=106) matched on length of membership in the health plan, date of birth (+/-28days), sex, and gestational timing and availability of archived maternal sera. RESULTS: For the second trimester, low maternal vitamin A, defined as values in the lowest tertile of the distribution among controls, was associated with a greater than threefold increased risk of SSD, adjusting for maternal education and age (OR=3.04, 95% CI=1.06, 8.79, p=.039). No association between third trimester maternal vitamin A and SSD was observed. CONCLUSIONS: Although further investigations are warranted, this is the first birth cohort study to our knowledge to report an association between low maternal vitamin A levels and SSD among offspring.
Authors: Bao Y; Ibram G; Blaner WS; Quesenberry CP; Shen L; McKeague IW; Schaefer CA; Susser ES; Brown AS
Schizophr Res. 2012 May;137(1-3):159-65. Epub 2012 Feb 29.
Midlife vs Late-Life Depressive Symptoms and Risk of Dementia: Differential Effects for Alzheimer Disease and Vascular Dementia
CONTEXT: Depression and dementia are common in older adults and often co-occur, but it is unclear whether depression is an etiologic risk factor for dementia. OBJECTIVE: To clarify the timing and nature of the association between depression and dementia. DESIGN: We examined depressive symptoms assessed in midlife (1964-1973) and late life (1994-2000) and the risks of dementia, Alzheimer disease (AD), and vascular dementia (VaD) (2003-2009) in a retrospective cohort study. Depressive symptoms were categorized as none, midlife only, late life only, or both. Cox proportional hazards models (age as timescale) adjusted for demographics and medical comorbidities were used to examine depressive symptom category and risk of dementia, AD, or VaD. SETTING: Kaiser Permanente Medical Care Program of Northern California. PARTICIPANTS: Thirteen thousand five hundred thirty-five long-term Kaiser Permanente members. Main Outcome Measure Any medical record diagnosis of dementia or neurology clinic diagnosis of AD or VaD. RESULTS: Subjects had a mean (SD) age of 81.1 (4.5) years in 2003, 57.9% were women, and 24.2% were nonwhite. Depressive symptoms were present in 14.1% of subjects in midlife only, 9.2% in late life only, and 4.2% in both. During 6 years of follow-up, 22.5% were diagnosed with dementia (5.5% with AD and 2.3% with VaD). The adjusted hazard of dementia was increased by approximately 20% for midlife depressive symptoms only (hazard ratio, 1.19 [95% CI, 1.07-1.32]), 70% for late-life symptoms only (1.72 [1.54-1.92]), and 80% for both (1.77 [1.52-2.06]). When we examined AD and VaD separately, subjects with late-life depressive symptoms only had a 2-fold increase in AD risk (hazard ratio, 2.06 [95% CI, 1.67-2.55]), whereas subjects with midlife and late-life symptoms had more than a 3-fold increase in VaD risk (3.51 [2.44-5.05]). CONCLUSIONS: Depressive symptoms in midlife or in late life are associated with an increased risk of developing dementia. Depression that begins in late life may be part of the AD prodrome, while recurrent depression may be etiologically associated with increased risk of VaD.
Authors: Barnes DE; Yaffe K; Byers AL; McCormick M; Schaefer C; Whitmer RA
Arch Gen Psychiatry. 2012 May;69(5):493-8.
New Models for Large Prospective Studies: Is There a Better Way?
Large prospective cohort studies are critical for identifying etiologic factors for disease, but they require substantial long-term research investment. Such studies can be conducted as multisite consortia of academic medical centers, combinations of smaller ongoing studies, or a single large site such as a dominant regional health-care provider. Still another strategy relies upon centralized conduct of most or all aspects, recruiting through multiple temporary assessment centers. This is the approach used by a large-scale national resource in the United Kingdom known as the ‘UK Biobank,’ which completed recruitment/examination of 503,000 participants between 2007 and 2010 within budget and ahead of schedule. A key lesson from UK Biobank and similar studies is that large studies are not simply small studies made large but, rather, require fundamentally different approaches in which ‘process’ expertise is as important as scientific rigor. Embedding recruitment in a structure that facilitates outcome determination, utilizing comprehensive and flexible information technology, automating biospecimen processing, ensuring broad consent, and establishing essentially autonomous leadership with appropriate oversight are all critical to success. Whether and how these approaches may be transportable to the United States remain to be explored, but their success in studies such as UK Biobank makes a compelling case for such explorations to begin.
Authors: Manolio TA; Schaefer C; Collins FS; et al.
Am J Epidemiol. 2012 May 1;175(9):859-66. Epub 2012 Mar 12.
Adherence to placebo and mortality in the Beta Blocker Evaluation of Survival Trial (BEST)
BACKGROUND: Randomized controlled trials have reported lower mortality among patients who adhere to placebo compared with those who do not. We explored this phenomenon by reanalyzing data from the placebo arm of the Beta Blocker Evaluation of Survival Trial (BEST), a randomized, double-blind, placebo-controlled trial of bucindolol and mortality. AIMS: Our primary aim was to measure and explain the association between adherence to placebo and total mortality among the placebo-allocated participants in the BEST trial. Secondary aims included assessment of the association between placebo adherence and cause-specific mortality. METHODS: Participants with ‘higher placebo adherence’ were defined as having taken at least 75% of their placebo study medication over the entire course of each individual’s participation in the study, while those with ‘lower placebo adherence’ took <75%. Primary outcome was in-study all-cause mortality. To account for confounding, we adjusted for all available modifiable, non-modifiable and psychosocial variables. RESULTS: Adherent participants had a significantly lower total mortality compared to less-adherent participants (HR=0.61, 95% Confidence Interval: 0.46-0.82). Adjusting for available confounders did not change the magnitude or significance of the estimates. When considering cause-specific mortality, CVD and pump failure showed similar associations. CONCLUSIONS: Analyses of the BEST trial data support a strong association between adherence to placebo study medication and total mortality. While probably not due to publication bias or simple confounding by healthy lifestyle factors, the underlying explanation for the association remains a mystery. Prospective examination of this association is necessary to better understand the underlying mechanism of this observation.
Authors: Pressman A; Avins AL; Neuhaus J; Ackerson L; Rudd P
Contemp Clin Trials. 2012 May;33(3):492-8. Epub 2012 Jan 12.
Twelve-step attendance trajectories over seven years among adolescents entering substance use treatment in an integrated health plan
AIMS: This study examines 12-Step attendance trajectories over 7 years, factors associated with the trajectories, and relationships between the trajectories and long-term substance use outcomes among adolescents entering out-patient substance use treatment in a private, non-profit integrated managed-care health plan. DESIGN: Longitudinal observational study. SETTING: Four Kaiser Permanente Northern California substance use treatment programs. PARTICIPANTS: A total of 391 adolescents entering treatment between 2000 and 2002 who completed at least one follow-up interview in year 1, and at least one during years 3-7, after treatment entry. MEASUREMENTS: Alcohol and drug use, 12-Step meeting attendance and activity involvement and post-treatment medical service utilization. FINDINGS: Semiparametric group-based modeling identified three distinct 12-Step attendance trajectory groups over 7 years: low/no attendance (60%), early but not continued (26%) and continued (14%). There were lower proportions of males and of adolescents with prior substance use treatment experience in the low/no attendance group (P = 0.019 and P = 0.003, respectively). In addition, those in the low/no attendance group had lower perception on circumstances, motivation and readiness for treatment at baseline (P = 0.023). Multivariate logistic generalized estimating equation analyses found that those in the continued group were more likely to be abstinent from both alcohol and drugs during follow-ups than those in the low/no attendance group [odds ratio (OR) = 2.40, P = 0.003 and OR = 1.96, P = 0.026, respectively]. However, no differences in long-term outcomes were found between those in the other two groups. CONCLUSION: Robust connection with 12-Step groups appears to be associated with better long-term outcomes among adolescents with substance use disorders.
Authors: Chi FW; Campbell CI; Sterling S; Weisner C
Addiction. 2012 May;107(5):933-42. Epub 2012 Feb 11.
Effects of age and life transitions on alcohol and drug treatment outcome over nine years
OBJECTIVE: The purpose of this study was to examine the effects of age, common life transitions, treatment, and social support on outcomes 5-9 years after alcohol and other drug (AOD) treatment intake. METHOD: Participants were patients from a large outpatient AOD treatment program in an integrated health plan. There were 1,951 participants interviewed at intake, of whom 1,646 (84%) completed one or more telephone follow-up interviews at 5, 7, and 9 years. Measures included AOD use based on the Addiction Severity Index; treatment; and changes in marital, employment, and health status in the years between each follow-up. We compared participants by age group (18-39, 40-54, and >/=55 years old at intake) and examined factors (time invariant and time varying) associated with outcomes at 5, 7, and 9 years by fitting mixed-effects logistic random intercept models. RESULTS: Changes in marital, employment, and health status varied significantly by age. Factors associated with remission across Years 5-9 included being in the middle-aged versus younger group (p < .001); female gender (p < .001); not losing a partner to separation, divorce, or death (p < .001); not experiencing a decline in health (p = .021); having any close friends supportive of recovery (p < .001); and not having any close friends who encourage AOD use (p < .001). Additional predictors, including employment changes, varied by drug versus alcohol abstinence outcome measures. CONCLUSIONS: Negative life transitions vary by age and are associated with worse outcomes. Older age and social support are associated with long-term AOD remission and abstinence. Findings inform treatment strategies to enhance recovery across the life span.
Authors: Satre DD; Chi FW; Mertens JR; Weisner CM
J Stud Alcohol Drugs. 2012 May;73(3):459-68.
The prognosis of acute low back pain in primary care in the United States: a 2-year prospective cohort study
STUDY DESIGN: Prospective cohort study. OBJECTIVE: To assess the prognosis of patients presenting with acute low back pain (LBP) in a primary care setting in the United States. SUMMARY OF BACKGROUND DATA: Practice guidelines for acute LBP based on return-to-work outcomes underestimate the development of chronic pain in the primary care setting. Because of differences in inclusion criteria, chronic pain definitions, and national health systems, prognostic cohort studies have reported a wide range of results limiting interpretation and generalization. Current data from carefully designed prognostic studies of acute LBP are lacking for the US primary care system. METHODS: Members of a large health service organization were enrolled after seeking medical care for acute LBP, with or without sciatica, of up to 30 days duration, with no episode in the past 12 months and no history of spine surgery. We conducted phone interviews at baseline, 6 months, and 2 years. Based on receiver operating characteristic analyses, a combination of global perceived recovery with pain intensity was used as primary outcome for chronic pain. Recurrence and multiple secondary outcomes were assessed to allow for comparison with other studies. RESULTS: Six hundred five patients had an average pain intensity of 5.6 (numeric rating scale = 0-10) and disability of 15.8 (Roland-Morris scale = 0-24). Eight percent had declared sick leave between pain onset and baseline interview. Thirteen percent of 521 patients (86% follow-up) experienced chronic pain at 6 months and 19% of 443 patients at 2 years. At 6 months, 54% had experienced at least 1 LBP recurrence, and 47% in the subsequent 18 months. CONCLUSION: The prognosis of strictly defined acute LBP, with or without sciatica, is less favorable than commonly stated in practice guidelines based on failure to return to work. Broad initiatives to develop new means for the primary and secondary prevention of recurrent and chronic LBP are urgently needed.
Authors: Mehling WE; Gopisetty V; Bartmess E; Acree M; Pressman A; Goldberg H; Hecht FM; Carey T; Avins AL
Spine (Phila Pa 1976). 2012 Apr 15;37(8):678-84.
Association of Depression With Increased Risk of Dementia in Patients With Type 2 Diabetes: The Diabetes and Aging Study
CONTEXT: Although depression is a risk factor for dementia in the general population, its association with dementia among patients with diabetes mellitus has not been well studied. OBJECTIVE: To determine whether comorbid depression in patients with type 2 diabetes increases the risk of development of dementia. DESIGN: The Diabetes and Aging Study was a cohort investigation that surveyed a racially/ethnically stratified random sample of patients with type 2 diabetes. SETTING: A large, integrated, nonprofit managed care setting in Northern California. PARTICIPANTS: A sample of 19 239 diabetes registry members 30 to 75 years of age. MAIN OUTCOME MEASURES: The Patient Health Questionnaire 8, International Classification of Diseases, Ninth Revision (ICD-9) diagnoses of depression, and/or antidepressant prescriptions in the 12 months prior to baseline were used to identify prevalent cases of depression. Clinically recognized dementia was identified among subjects with no prior ICD-9 Clinical Modification (ICD-9-CM) diagnoses of dementia. To exclude the possibility that depression was a prodrome of dementia, dementia diagnoses were only based on ICD-9-CM diagnoses identified in years 3 to 5 postbaseline. The risk of dementia for patients with depression and diabetes relative to patients with diabetes alone was estimated using Cox proportional hazard regression models that adjusted for sociodemographic, clinical, and health risk factors and health use. RESULTS: During the 3- to 5-year period, 80 of 3766 patients (2.1%) with comorbid depression and diabetes (incidence rate of 5.5 per 1000 person-years) vs 158 of 15 473 patients (1.0%) with diabetes alone (incidence rate of 2.6 per 1000 person-years) had 1 or more ICD-9-CM diagnoses of dementia. Patients with comorbid depression had a 100% increased risk of dementia during the 3 to 5 years postbaseline (adjusted hazard ratio, 2.02; 95% confidence interval, 1.73-2.35). CONCLUSION: Depression in patients with diabetes was associated with a substantively increased risk for development of dementia compared with those with diabetes alone.
Authors: Katon W; Lyles CR; Parker MM; Karter AJ; Huang ES; Whitmer RA
Arch Gen Psychiatry. 2012 Apr;69(4):410-7. Epub 2011 Dec 5.
Gene-centric analysis of serum cotinine levels in African and European American populations
To date, most genetic association studies of tobacco use have been conducted in European American subjects using the phenotype of smoking quantity (cigarettes per day). However, smoking quantity is a very imprecise measure of exposure to tobacco smoke constituents. Analyses of alternate phenotypes and populations may improve our understanding of tobacco addiction genetics. Cotinine is the major metabolite of nicotine, and measuring serum cotinine levels in smokers provides a more objective measure of nicotine dose than smoking quantity. Previous genetic association studies of serum cotinine have focused on individual genes. We conducted a genetic association study of the biomarker in African American (N=365) and European American (N=315) subjects from the Coronary Artery Risk Development in Young Adults study using a chip containing densely-spaced tag SNPs in ∼2100 genes. We found that rs11187065, located in the non-coding region (intron 1) of insulin-degrading enzyme (IDE), was the most strongly associated SNP (p=8.91 × 10(-6)) in the African American cohort, whereas rs11763963, located on chromosome 7 outside of a gene transcript, was the most strongly associated SNP in European Americans (p=1.53 × 10(-6)). We then evaluated how the top variant association in each population performed in the other group. We found that the association of rs11187065 in IDE was also associated with the phenotype in European Americans (p=0.044). Our top SNP association in European Americans, rs11763963 was non-polymorphic in our African American sample. It has been previously shown that psychostimulant self-administration is reduced in animals with lower insulin because of interference with dopamine transmission in the brain reward centers. Our finding provides a platform for further investigation of this, or additional mechanisms, involving the relationship between insulin and self-administered nicotine dose.
Authors: Hamidovic A; Goodloe RJ; Bergen AW; Benowitz NL; Styn MA; Kasberger JL; Choquet H; Young TR; Meng Y; Palmer C; Pletcher M; Kertesz S; Hitsman B; Spring B; Jorgenson E
Neuropsychopharmacology. 2012 Mar;37(4):968-74. doi: 10.1038/npp.2011.280. Epub 2011 Nov 16.
Concurrent Use of Alcohol and Sedatives Among Persons Prescribed Chronic Opioid Therapy: Prevalence and Risk Factors
Taking opioids with other central nervous system (CNS) depressants can increase risk of oversedation and respiratory depression. We used telephone survey and electronic health care data to assess the prevalence of, and risk factors for, concurrent use of alcohol and/or sedatives among 1,848 integrated care plan members who were prescribed chronic opioid therapy (COT) for chronic noncancer pain. Concurrent sedative use was defined by receiving sedatives for 45+ days of the 90 days preceding the interview; concurrent alcohol use was defined by consuming 2+ drinks within 2 hours of taking an opioid in the prior 2 weeks. Some analyses were stratified by substance use disorder (SUD) history (alcohol or drug). Among subjects with no SUD history, 29% concurrently used sedatives versus 39% of those with an SUD history. Rates of concurrent alcohol use were similar (12 to 13%) in the 2 substance use disorder strata. Predictors of concurrent sedative use included SUD history, female gender, depression, and taking opioids at higher doses and for more than 1 pain condition. Male gender was the only predictor of concurrent alcohol use. Concurrent use of CNS depressants was common among this sample of COT users regardless of substance use disorder status. PERSPECTIVE: Risks associated with concurrent use of CNS depressants are not restricted to COT users who abuse those substances. And, the increased risk of concurrently using CNS depressants is not restricted to opioid users with a prior SUD history. COT requires close monitoring, regardless of substance use disorder history.
Authors: Saunders KW; Von Korff M; Campbell CI; Banta-Green CJ; Sullivan MD; Merrill JO; Weisner C
J Pain. 2012 Mar;13(3):266-75. Epub 2012 Jan 29.
Peer Influences on Adolescent Alcohol and Other Drug Use Outcomes
PURPOSE: To examine the role of family environment and peer networks in abstinence outcomes for adolescents 1 year after intake to alcohol and other drug (AOD) treatment. DESIGN: Survey of 419 adolescents 13 to 18 years of age at consecutive intakes to AOD treatment programs at four sites of a large health system, with telephone follow-up survey 1 year after intake. METHODS: Examined association of 1-year abstinence with baseline characteristics. Using logistic regression, we examined characteristics predicting 1-year abstinence and predicting having fewer than four substance-using friends at 1 year. RESULTS: We found that family environment scores related to family conflict, limit setting, and positive family experiences, were not related to abstinence outcomes, but peer networks were related. Adolescents with fewer (less than four) AOD-using friends were more likely to be abstinent than those with four or more AOD-using friends (65% vs. 41%, p= .0002). Having fewer than four AOD-using friends at intake predicted abstinence at 1 year (odds ratio [OR]= 2.904, p= .0002) and also predicted having fewer than four AOD-using friends at 1 year (OR= 2.557, p= 0.0007). CONCLUSIONS: Although family environment is an important factor in the development of AOD problems in adolescents, it did not play a significant role in treatment success. The quality of adolescent peer networks did independently predict positive outcomes. CLINICAL RELEVANCE: For physicians, advanced practice registered nurses, and other primary and behavioral care providers who screen and care for adolescents with AOD and other behavioral problems, our finding suggest the importance of focusing on improving the quality of their peer networks.
Authors: Ramirez R; Hinman A; Sterling S; Weisner C; Campbell C
J Nurs Scholarsh. 2012 Mar;44(1):36-44. Epub 2012 Feb 16.
Influence of site differences between urban and rural American and Central European opioid-dependent pregnant women and neonatal outcome characteristics.
BACKGROUND: Multi-center trials enable the recruitment of larger study samples, although results might be influenced by site-specific factors.METHODS: Site differences of a multi-center prospective double-blind, double-dummy randomized controlled trial (7 centers: Central Europe (Vienna)/USA (3 urban/3 rural centers)) comparing safety and efficacy of methadone and buprenorphine in pregnant opioid-dependent women and their neonates.RESULTS: Urban US women had the highest rate of concomitant opioid (p = 0.050) and cocaine consumption (p = 0.003), the highest dropout rate (p = 0.001), and received the lowest voucher sums (p = 0.001). Viennese neonates had significantly higher Apgar scores 1 min (p = 0.001) and 5 min after birth (p < 0.001) and were more often born by cesarean section (p = 0.024). Rural US newborns had a significantly shorter neonatal abstinence syndrome treatment duration compared to Viennese and urban US sites (p = 0.006), in addition to other site-specific differences, suggesting a more severely affected group of women in the urban US sites.CONCLUSION: This clinical trial represents a role model for pharmacological treatment in this unique sample of pregnant women and demonstrates the clinical importance of considering site-specific factors in research and clinical practice.
Authors: Baewert, Andjela A; Jagsch, Reinhold R; Winklbaur, Bernadette B; Kaiser, Gerda G; Thau, Kenneth K; Unger, Annemarie A; Aschauer, Constantin C; Weninger, Manfred M; Metz, Verena V
European addiction research. 2012 Jan 25;18(3):130-9. Epub 2012-02-21.
Opioid dependent and pregnant: what are the best options for mothers and neonates?
Pregnancy in opioid-dependent women is a major public health issue. Women who are afflicted by opioid addiction are a highly vulnerable group of patients frequently becoming pregnant unplanned and at risk of adverse pregnancy outcomes and peri-natal complications. Opioid agonist maintenance treatment is the best option for the majority of women. Ideally, early and closely monitored treatment in an interdisciplinary team approach including social workers, nurses, psychologists, psychiatrists, gynecologists, anesthesiologists, and pediatricians should be provided. The treatment of comorbid psychiatric conditions, the resolution of financial, legal, and housing issues, and the psychosocial support provided have a significant effect on optimizing pregnancy outcomes. This paper aims to update health professionals in the field of gynecology and obstetrics on the latest optimal treatment approaches for mothers suffering from opioid dependence and their neonates.
Authors: Unger, Annemarie A; Metz, Verena V; Fischer, Gabriele G
Obstetrics and gynecology international. 2012 Jan 25;2012(1):195954. Epub 2012-02-07.
Formal and informal substance use treatment utilization and alcohol abstinence over seven years: Is the relationship different for blacks and whites?
BACKGROUND: This study examines whether the effects of formal substance use treatment utilization and Alcoholics Anonymous (AA) on 30-day abstinence vary for black versus white Americans. METHODS: The current analysis utilizes data from a longitudinal sample of 1013 black and white, dependent and problem drinkers across a 7-year period. Participants were identified through a probability survey in the general population and consecutive intakes in chemical dependency treatment programs in a California County. Generalized Estimating Equations assessing interactions between race and treatment utilization incorporated variables from four post-baseline interviews, controlling for baseline variables. RESULTS: Formal treatment utilization was associated with 30-day abstinence (OR:1.6, 95%CI: 1.3, 2.1), yet this relationship did not differ for blacks and whites. In contrast, there was a significant interaction between AA utilization, race and 30-day abstinence. While both whites and blacks who attended AA were more likely to report 30-day abstinence compared to their non-AA attending counterparts (white OR:4.0, 95%CI: 3.2-5.1 and black OR:2.2, 95%CI: 1.5-3.2), the relationship was stronger for whites. Among those who did not attend AA, blacks were more likely than whites to be abstinent. Post hoc analyses suggest that these latter findings may be related to greater religiosity and ‘drier’ social networks among black Americans. CONCLUSIONS: While utilization of formal treatment may yield similar benefits for blacks and whites, AA utilization may be more important for maintaining abstinence among whites than blacks. Future research should investigate racial differences in social network drinking patterns and religious reinforcement of sobriety, and the role these may play in AA outcomes.
Authors: Avalos LA; Mulia N
Drug Alcohol Depend. 2012 Feb 1;121(1-2):73-80. Epub 2011 Sep 21.
Study Protocol: The Back pain Outcomes using Longitudinal Data (BOLD) Registry
BACKGROUND: Back pain is one of the most important causes of functional limitation, disability, and utilization of health care resources for adults of all ages, but especially among older adults. Despite the high prevalence of back pain in this population, important questions remain unanswered regarding the comparative effectiveness of commonly used diagnostic tests and treatments in the elderly. The overall goal of the Back pain Outcomes using Longitudinal Data (BOLD) project is to establish a rich, sustainable registry to describe the natural history and evaluate prospectively the effectiveness, safety, and cost-effectiveness of interventions for patients 65 and older with back pain. METHODS/DESIGN: BOLD is enrolling 5,000 patients >/= 65 years old who present to a primary care physician with a new episode of back pain. We are recruiting study participants from three integrated health systems (Kaiser-Permanente Northern California, Henry Ford Health System in Detroit and Harvard Vanguard Medical Associates/ Harvard Pilgrim Health Care in Boston). Registry patients complete validated, standardized measures of pain, back pain-related disability, and health-related quality of life at enrollment and 3, 6 and 12 months later. We also have available for analysis the clinical and administrative data in the participating health systems’ electronic medical records. Using registry data, we will conduct an observational cohort study of early imaging compared to no early imaging among patients with new episodes of back pain. The aims are to: 1) identify predictors of early imaging and; 2) compare pain, functional outcomes, diagnostic testing and treatment utilization of patients who receive early imaging versus patients who do not receive early imaging. In terms of predictors, we will examine patient factors as well as physician factors. DISCUSSION: By establishing the BOLD registry, we are creating a resource that contains patient-reported outcome measures as well as electronic medical record data for elderly patients with back pain. The richness of our data will allow better matching for comparative effectiveness studies than is currently possible with existing datasets. BOLD will enrich the existing knowledge base regarding back pain in the elderly to help clinicians and patients make informed, evidence-based decisions regarding their care.
Authors: Jarvik JG; Avins AL; Deyo RA; et al.
BMC Musculoskelet Disord. 2012 May 3;13:64.
Using Standardized Patients to Evaluate Screening, Brief Intervention, and Referral to Treatment (SBIRT) Knowledge and Skill Acquisition for Internal Medicine Residents
Comprehensive clinical competency curricula for hazardous drinking and substance use disorders (SUDs) exists for medical students, residents, and practicing health care providers. Evaluations of these curricula typically focus on learner attitudes and knowledge, although changes in clinical skills are of greater interest and utility. The authors present a pre-post clinical skill evaluation of a 10-hour screening, brief intervention, and referral to treatment (SBIRT) curriculum for hazardous drinking and SUDs for primary care internal medicine residents using standardized patient examinations to better determine the impact of SBIRT training on clinical practice. Residents had large improvements in history taking, substance use screening skills, SUD assessment and diagnostic skills, and in SBIRT knowledge, including documentation, systems, and diversity issues. Residents made moderate improvements in brief intervention skills. Future SBIRT curricular evaluations would ideally include a controlled comparison with larger samples from multiple institutions.
Authors: Satterfield JM; O'Sullivan P; Satre DD; Tsoh JY; Batki SL; Julian K; McCance-Katz EF; Wamsley M
Subst Abus. 2012;33(3):303-7.
Randomised trial comparing hand expression with breast pumping for mothers of term newborns feeding poorly
OBJECTIVE: Breast pumping or hand expression may be recommended when newborns latch or suck poorly. A recent trial found worse outcomes among mothers who used a breast pump in the early postpartum period. The objective of this study was to compare bilateral electric breast pumping to hand expression among mothers of healthy term infants feeding poorly at 12-36 h after birth. DESIGN: Randomised controlled trial. SETTING: Well-baby nursery and postpartum unit. PATIENTS: 68 mothers of newborns 12-36 h old who were latching or sucking poorly were randomly assigned to either 15 min of bilateral electric pumping or 15 min of hand expression. MAIN OUTCOME MEASURES: Milk transfer, maternal pain, breastfeeding confidence and breast milk expression experience (BMEE) immediately after the intervention, and breastfeeding rates at 2 months after birth. RESULTS: The median volume of expressed milk (range) was 0.5 (0-5) ml for hand expressing mothers and 1 (0-40) ml for pumping mothers (p=0.07). Maternal pain, breastfeeding confidence and BMEE did not differ by intervention. At 2 months, mothers assigned to hand expression were more likely to be breastfeeding (96.1%) than mothers assigned to breast pumping (72.7%) (p=0.02). CONCLUSIONS: Hand expression in the early postpartum period appears to improve eventual breastfeeding rates at 2 months after birth compared with breast pumping, but further research is needed to confirm this. However, in circumstances where either pumping or hand expression would be appropriate for healthy term infants 12-36 h old feeding poorly, providers should consider recommending hand expression.
Authors: Flaherman VJ; Gay B; Scott C; Avins A; Lee KA; Newman TB
Arch Dis Child Fetal Neonatal Ed. 2012 Jan;97(1):F18-23. Epub 2011 Jul 11.
Central Obesity, Leptin and Cognitive Decline: The Sacramento Area Latino Study on Aging
BACKGROUND/AIMS: Central obesity is a risk factor for cognitive decline. Leptin is secreted by adipose tissue and has been associated with better cognitive function. Aging Mexican Americans have higher levels of obesity than non-Hispanic Whites, but no investigations examined the relationship between leptin and cognitive decline among them or the role of central obesity in this association. METHODS: We analyzed 1,480 dementia-free older Mexican Americans who were followed over 10 years. Cognitive function was assessed every 12-15 months with the Modified Mini Mental State Exam (3MSE) and the Spanish and English Verbal Learning Test (SEVLT). RESULTS: For females with a small waist circumference (
Authors: Zeki Al Hazzouri A; Haan MN; Whitmer RA; Yaffe K; Neuhaus J
Dement Geriatr Cogn Disord. 2012;33(6):400-9. Epub 2012 Jul 17.
Functional disability among chronic pain patients receiving long-term opioid treatment
This study of 2,163 adult chronic, non-cancer-pain, long-term opioid therapy patients examines the relationship of depression to functional disability by measuring average pain interference, activity limitation days, and employment status. Those with more depression symptoms compared to those with fewer were more likely to have worse disability on all 3 measures (average pain interference score >5, OR = 5.36, p < .0001; activity limitation days >/= 30, OR = 4.05, p < .0001; unemployed due to health reasons, OR = 4.06, p < .0001). Depression might play a crucial role in the lives of these patients; identifying and treating depression symptoms in chronic pain patients should be a priority.
Authors: Valkanoff TA; Kline-Simon AH; Sterling S; Campbell C; Von Korff M
J Soc Work Disabil Rehabil. 2012;11(2):128-42.
Study Protocol- Lumbar Epidural Steroid Injections for Spinal Stenosis (LESS): a double-blind randomized controlled trial of epidural steroid injections for lumbar spinal stenosis among older adults
BACKGROUND: Lumbar spinal stenosis is one of the most common causes of low back pain among older adults and can cause significant disability. Despite its prevalence, treatment of spinal stenosis symptoms remains controversial. Epidural steroid injections are used with increasing frequency as a less invasive, potentially safer, and more cost-effective treatment than surgery. However, there is a lack of data to judge the effectiveness and safety of epidural steroid injections for spinal stenosis. We describe our prospective, double-blind, randomized controlled trial that tests the hypothesis that epidural injections with steroids plus local anesthetic are more effective than epidural injections of local anesthetic alone in improving pain and function among older adults with lumbar spinal stenosis. METHODS: We will recruit up to 400 patients with lumbar central canal spinal stenosis from at least 9 clinical sites over 2 years. Patients with spinal instability who require surgical fusion, a history of prior lumbar surgery, or prior epidural steroid injection within the past 6 months are excluded. Participants are randomly assigned to receive either ESI with local anesthetic or the control intervention (epidural injections with local anesthetic alone). Subjects receive up to 2 injections prior to the primary endpoint at 6 weeks, at which time they may choose to crossover to the other intervention.Participants complete validated, standardized measures of pain, functional disability, and health-related quality of life at baseline and at 3 weeks, 6 weeks, and 3, 6, and 12 months after randomization. The primary outcomes are Roland-Morris Disability Questionnaire and a numerical rating scale measure of pain intensity at 6 weeks. In order to better understand their safety, we also measure cortisol, HbA1c, fasting blood glucose, weight, and blood pressure at baseline, and at 3 and 6 weeks post-injection. We also obtain data on resource utilization and costs to assess cost-effectiveness of epidural steroid injection. DISCUSSION: This study is the first multi-center, double-blind RCT to evaluate the effectiveness of epidural steroid injections in improving pain and function among older adults with lumbar spinal stenosis. The study will also yield data on the safety and cost-effectiveness of this procedure for older adults. TRIAL REGISTRATION: Clinicaltrials.gov NCT01238536.
Authors: Friedly JL Md; Avins AL Md Mph; Jarvik JG Md Mph; et al.
BMC Musculoskelet Disord. 2012 Mar 29;13:48.
Screening for adolescent alcohol and drug use in pediatric health-care settings: predictors and implications for practice and policy
This paper used data from a study of pediatric primary care provider (PCP) screening practices to examine barriers to and facilitators of adolescent alcohol and other drug (AOD) screening in pediatric primary care. A web-based survey (N?=?437) was used to examine the influence of PCP factors (attitudes and knowledge, training, self-efficacy, comfort with alcohol and drug issues); patient characteristics (age, gender, ethnicity, comorbidities and risk factors); and organizational factors (screening barriers, staffing resources, confidentiality issues) on AOD screening practices. Self-reported and electronic medical record (EMR)-recorded screening rates were also assessed. More PCPs felt unprepared to diagnose alcohol abuse (42%) and other drug abuse (56%) than depression (29%) (p?
Authors: Sterling S; Kline-Simon AH; Wibbelsman C; Wong A; Weisner C
Addict Sci Clin Pract. 2012;7(1):13. Epub 2012-08-16.
Using Needs Assessment to Develop Curricula for Screening, Brief Intervention, and Referral to Treatment (SBIRT) in Academic and Community Health Settings
This article describes the use of a brief needs assessment survey in the development of alcohol and drug screening, brief intervention, and referral to treatment (SBIRT) curricula in 2 health care settings in the San Francisco Bay Area. The samples included university medical center faculty (n = 27) and nonphysician community health and social service providers in a nearby suburban county (n = 21). Informed by curriculum development theory and motivational interviewing strategies, questions regarding clinical and educational priorities, perceived importance and confidence with screening and intervention techniques, and referral resource availability were included. Medical center faculty expressed greater concern about limited appointment time (P = .003), adequacy of training (P = .025), and provider confidence (P = .038) as implementation obstacles and had lower confidence in delivering SBIRT (P = .046) and providing treatment referrals (P = .054) than community providers. The authors describe their approach to integrating needs assessment results into subsequent curriculum development. Findings highlight potential differences between physician and nonphysician training needs.
Authors: Satre DD; McCance-Katz EF; Moreno-John G; Julian KA; O'Sullivan PS; Satterfield JM
Subst Abus. 2012;33(3):298-302.
Should we reconsider the routine use of placebo controls in clinical research?
BACKGROUND: Modern clinical-research practice favors placebo controls over usual-care controls whenever a credible placebo exists. An unrecognized consequence of this preference is that clinicians are more limited in their ability to provide the benefits of the non-specific healing effects of placebos in clinical practice. METHODS: We examined the issues in choosing between placebo and usual-care controls. We considered why placebo controls place constraints on clinicians and the trade-offs involved in the choice of control groups. RESULTS: We find that, for certain studies, investigators should consider usual-care controls, even if an adequate placebo is available. Employing usual-care controls would be of greatest value for pragmatic trials evaluating treatments to improve clinical care and for which threats to internal validity can be adequately managed without a placebo-control condition. CONCLUSIONS: Intentionally choosing usual-care controls, even when a satisfactory placebo exists, would allow clinicians to capture the value of non-specific therapeutic benefits that are common to all interventions. The result could be more effective, patient-centered care that makes the best use of both specific and non-specific benefits of medical interventions.
Authors: Avins AL; Cherkin DC; Sherman KJ; Goldberg H; Pressman A
Trials. 2012 Apr 27;13:44.
Design and coverage of high throughput genotyping arrays optimized for individuals of East Asian, African American, and Latino race/ethnicity using imputation and a novel hybrid SNP selection algorithm
Four custom Axiom genotyping arrays were designed for a genome-wide association (GWA) study of 100,000 participants from the Kaiser Permanente Research Program on Genes, Environment and Health. The array optimized for individuals of European race/ethnicity was previously described. Here we detail the development of three additional microarrays optimized for individuals of East Asian, African American, and Latino race/ethnicity. For these arrays, we decreased redundancy of high-performing SNPs to increase SNP capacity. The East Asian array (712,930 SNPs) was designed using greedy pairwise SNP selection. However, removing SNPs from the target set based on imputation coverage is more efficient than pairwise tagging. Therefore, we developed a novel hybrid SNP selection method for the African American and Latino arrays utilizing rounds of greedy pairwise SNP selection, followed by removal from the target set of SNPs covered by imputation. The arrays provide excellent genome-wide coverage and are valuable additions for large-scale GWA studies.
Authors: Hoffmann TJ; Iribarren C; Quesenberry C; Van den Eeden SK; Whitmer RA; Schaefer C; Risch N; et al.
Genomics. 2011 Dec;98(6):422-30. Epub 2011 Aug 28.
Innovative policy strategies need empirical evaluation
Authors: Weisner C
Addiction. 2011 Dec;106(12):2069-70.
Continuing care and long-term substance use outcomes in managed care: early evidence for a primary care-based model
OBJECTIVES: How best to provide ongoing services to patients with substance use disorders to sustain long-term recovery is a significant clinical and policy question that has not been adequately addressed. Analyzing nine years of prospective data for 991 adults who entered substance abuse treatment in a private, nonprofit managed care health plan, this study aimed to examine the components of a continuing care model (primary care, specialty substance abuse treatment, and psychiatric services) and their combined effect on outcomes over nine years after treatment entry. METHODS: In a longitudinal observational study, follow-up measures included self-reported alcohol and drug use, Addiction Severity Index scores, and service utilization data extracted from the health plan databases. Remission, defined as abstinence or nonproblematic use, was the outcome measure. RESULTS: A mixed-effects logistic random intercept model controlling for time and other covariates found that yearly primary care, and specialty care based on need as measured at the prior time point, were positively associated with remission over time. Persons receiving continuing care (defined as having yearly primary care and specialty substance abuse treatment and psychiatric services when needed) had twice the odds of achieving remission at follow-ups (p<.001) as those without. CONCLUSIONS: Continuing care that included both primary care and specialty care management to support ongoing monitoring, self-care, and treatment as needed was important for long-term recovery of patients with substance use disorders.
Authors: Chi FW; Parthasarathy S; Mertens JR; Weisner CM
Psychiatr Serv. 2011 Oct;62(10):1194-200.
Effect of increasing doses of saw palmetto extract on lower urinary tract symptoms: a randomized trial
CONTEXT: Saw palmetto fruit extracts are widely used for treating lower urinary tract symptoms attributed to benign prostatic hyperplasia (BPH); however, recent clinical trials have questioned their efficacy, at least at standard doses (320 mg/d). OBJECTIVE: To determine the effect of saw palmetto extract (Serenoa repens, from saw palmetto berries) at up to 3 times the standard dose on lower urinary tract symptoms attributed to BPH. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, multicenter, placebo-controlled randomized trial at 11 North American clinical sites conducted between June 5, 2008, and October 10, 2010, of 369 men aged 45 years or older, with a peak urinary flow rate of at least 4 mL/s, an American Urological Association Symptom Index (AUASI) score of between 8 and 24 at 2 screening visits, and no exclusions. INTERVENTIONS: One, 2, and then 3 doses (320 mg/d) of saw palmetto extract or placebo, with dose increases at 24 and 48 weeks. MAIN OUTCOME MEASURES: Difference in AUASI score between baseline and 72 weeks. Secondary outcomes included measures of urinary bother, nocturia, peak uroflow, postvoid residual volume, prostate-specific antigen level, participants’ global assessments, and indices of sexual function, continence, sleep quality, and prostatitis symptoms. RESULTS: Between baseline and 72 weeks, mean AUASI scores decreased from 14.42 to 12.22 points (-2.20 points; 95% CI, -3.04 to -0.36) with saw palmetto extract and from 14.69 to 11.70 points (-2.99 points; 95% CI, -3.81 to -2.17) with placebo. The group mean difference in AUASI score change from baseline to 72 weeks between the saw palmetto extract and placebo groups was 0.79 points favoring placebo (upper bound of the 1-sided 95% CI most favorable to saw palmetto extract was 1.77 points, 1-sided P = .91). Saw palmetto extract was no more effective than placebo for any secondary outcome. No clearly attributable adverse effects were identified. CONCLUSION: Increasing doses of a saw palmetto fruit extract did not reduce lower urinary tract symptoms more than placebo. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00603304.
Authors: Barry MJ; Avins AL; Complementary and Alternative Medicine for Urological Symptoms (CAMUS) Study Group; et al.
JAMA. 2011 Sep 28;306(12):1344-51.
Performance of the American Urological Association Symptom Index with and without an additional urge incontinence item
OBJECTIVE: To examine the value of adding an urge incontinence question to the American Urological Association Symptom Index (AUASI) among men in the Complementary and Alternative Medicine for Urological Symptoms (CAMUS) trial. METHODS: The CAMUS study was a randomized trial of Saw palmetto fruit extract versus placebo among men aged >/=45 years with an AUASI score of >/=8 and
Authors: Barry MJ; Avins AL; Meleth S; Complementary and Alternative Medicine for Urological Symptoms Study Group
Urology. 2011 Sep;78(3):550-4. Epub 2011 Jul 8.
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
Authors: International Multiple Sclerosis Genetics Consortium; Barcellos LF; Schaefer CA; Compston A; et al.
Nature. 2011 Aug 10;476(7359):214-9.
First-trimester fetal heart rate in mothers with opioid addiction.
AIM: To investigate the difference in fetal heart rate of opioid-dependent mothers compared to non-dependent mothers in the first trimester of pregnancy.DESIGN: The data of 74 consecutive singleton pregnancies of mothers enrolled in a maintenance programme for opioid-dependent women was matched to 74 non-exposed singleton pregnancies by maternal age, crown-rump length, smoking status, ethnic background and mode of conception.MEASUREMENT: Fetal heart rate measured as part of first-trimester screening by Doppler ultrasound between 11+0 and 13+6 gestational weeks was compared retrospectively.FINDINGS: The mean fetal heart rate in opioid-dependent mothers was 156.0 beats per minute (standard deviation 7.3) compared to 159.6 (6.5) in controls. The difference in fetal heart rate was significant (P = 0.02). There was a significant difference in mean maternal body mass index (P = 0.01) but not in mean nuchal translucency (P = 0.3), gestational age (0.5), fetal gender (P = 0.3) and parity (P = 0.3) between both groups. Fifty-five per cent (41 of 74) of cases were taking methadone, 30% (22 of 74) buprenorphine and 15% (11 of 74) were taking slow-release morphines throughout the pregnancy.CONCLUSIONS: In fetuses of opioid-dependent mothers a decreased fetal heart rate can already be observed between 11+0 and 13+6 gestational weeks. The effect of opioid intake needs to be taken into consideration when interpreting fetal heart rate in opioid-dependent mothers at first-trimester screening.
Authors: Schmid, Maximilian M; Kuessel, Lorenz L; Klein, Katharina K; Metz, Verena V; Fischer, Gabriele G; Krampl-Bettelheim, Elisabeth E
Addiction (Abingdon, England). 2010 Jul 25;105(7):1265-8. Epub 2011-08-08.
Impact of treatment approach on maternal and neonatal outcome in pregnant opioid-maintained women.
OBJECTIVE: The objective of this study is to compare maternal and neonatal outcome of opioid-dependent women maintained on buprenorphine or methadone throughout pregnancy in a randomized double-blind double-dummy clinical trial (CT) with a comparison group undergoing a structured standard protocol (SP) at the Medical University of Vienna, Austria.METHODS: One hundred and fourteen subjects were included in the analysis, with 77 in SP (n = 51 methadone, n = 26 buprenorphine), and 37 in CT (n = 19 methadone, n = 18 buprenorphine), comparing maternal concomitant consumption during third trimester, demographic birth data, duration of treatment for neonatal abstinence syndrome (NAS), morphine dose for NAS treatment and length of hospital stay (LOS).RESULTS: Both study groups yielded healthy neonates with no significant demographic differences and equivalently low rates of positive maternal urine toxicologies. However, NAS parameters were significantly better in CT regarding total medication dose administered to neonates (p = 0.014) and LOS (p = 0.015). Superior results were achieved in buprenorphine compared with methadone-exposed neonates regarding gestational age at birth (p = 0.003), birth weight (p = 0.011), total morphine dose administered (p = 0.008), NAS treatment duration (p = 0.008) and LOS (p = 0.001).CONCLUSIONS: Comparably favorable outcome for mothers and infants and efficacy and safety of opioid medications were shown in both treatment approaches. Neonatal care could benefit from transferring successful CT procedures into clinical practice.
Authors: Metz, Verena V; Jagsch, Reinhold R; Ebner, Nina N; Würzl, Johanna J; Pribasnig, Anna A; Aschauer, Constantin C; Fischer, Gabriele G
Human psychopharmacology. 2011 Aug 25;26(6):412-21. Epub 2011-08-08.
Next generation genome-wide association tool: design and coverage of a high-throughput European-optimized SNP array
The success of genome-wide association studies has paralleled the development of efficient genotyping technologies. We describe the development of a next-generation microarray based on the new highly-efficient Affymetrix Axiom genotyping technology that we are using to genotype individuals of European ancestry from the Kaiser Permanente Research Program on Genes, Environment and Health (RPGEH). The array contains 674,517 SNPs, and provides excellent genome-wide as well as gene-based and candidate-SNP coverage. Coverage was calculated using an approach based on imputation and cross validation. Preliminary results for the first 80,301 saliva-derived DNA samples from the RPGEH demonstrate very high quality genotypes, with sample success rates above 94% and over 98% of successful samples having SNP call rates exceeding 98%. At steady state, we have produced 462 million genotypes per week for each Axiom system. The new array provides a valuable addition to the repertoire of tools for large scale genome-wide association studies.
Authors: Hoffmann TJ; Iribarren C; Quesenberry C; Van den Eeden SK; Whitmer RA; Schaefer C; Risch N; et al.
Genomics. 2011 Aug;98(2):79-89. Epub 2011 Apr 30.
Does gender moderate the relationship between childhood maltreatment and adult depression?
Although considerable evidence demonstrates that adults who report childhood maltreatment are at increased risk of depression in adulthood, little is known about whether gender moderates risk. In a sample of 5,673 adult Health Maintenance Organization (HMO) patients, the authors employed the Patient Health Questionnaire-8 (PHQ-8) to assess major depressive disorder (MDD) and the Childhood Trauma Questionnaire (CTQ) to assess five different types of childhood maltreatment: emotional, physical, and sexual abuse, as well as emotional and physical neglect. Logistic regression models tested the main and interactive effects of gender and childhood maltreatment. Consistent with previous studies, men and women with histories of each type of childhood adversity were significantly more likely to meet criteria for MDD. However, the authors found no evidence that gender moderates the risk of depression. These findings suggest that men and women reporting history of childhood maltreatment are equally likely to suffer major depression in adulthood.
Authors: Arnow BA; Blasey CM; Hunkeler EM; Lee J; Hayward C
Child Maltreat. 2011 Aug;16(3):175-83. Epub 2011 Jul 4.
Patterns of alcohol and drug use among depressed older adults seeking outpatient psychiatric services
OBJECTIVE: Alcohol and drug use and related problems may compromise depression treatment, and older adults may be especially at risk for poor outcomes. However, alcohol and drug use among older adults have not been studied in settings in which depression treatment is provided. This study examined the prevalence and clinical and demographic correlates of alcohol and drug use and misuse of prescription drugs among adults with depression seeking outpatient psychiatric care (excluding chemical dependency treatment). METHODS: The sample included 154 older adults (age 60 years and older who scored >/=10 on the Beck Depression Inventory-II [BDI-II] at intake). Participants also completed alcohol and drug use questions and the Short Michigan Alcohol Screening Test. RESULTS: Recent alcohol and drug use, heavy episodic drinking, and history of alcohol-related problems were common. Alcohol use in the prior 30 days was reported by 53% of men and 50% of women. Cannabis use in the prior 30 days was reported by 12% of men and 4% of women; and misuse of sedatives in the prior 30 days was reported by 16% of men and 9% of women. In exact logistic regression, higher BDI-II score was associated with cannabis use (odds ratio = 15.8, 95% confidence interval = 2.0-734.0, exactp = 0.003). CONCLUSIONS: Older adults with depression are likely to present for treatment with a range of concurrent alcohol and drug use patterns, including cannabis use and misuse of prescription medication. Clinicians should evaluate depressed patients for substance use and related problems and consider appropriate interventions.
Authors: Satre DD; Sterling SA; Mackin RS; Weisner C
Am J Geriatr Psychiatry. 2011 Aug;19(8):695-703.
What do I tell patients about saw palmetto for benign prostatic hyperplasia?
Saw palmetto is widely used to treat lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH). Although there is passionate support for herbal and complementary therapies for LUTS, clinical evidence is mixed. Because there is a well-recognized, profound placebo effect in tests of efficacy for agents treating LUTS, it is imperative that all therapies be tested in placebo-controlled trials. This article reviews evidence of the efficacy and safety of saw palmetto for men with LUTS caused by BPH, with particular emphasis on published randomized clinical trials and the upcoming Complementary and Alternative Medicine for Urologic Symptoms (CAMUS) trial.
Authors: Kane CJ; Raheem OA; Bent S; Avins AL
Urol Clin North Am. 2011 Aug;38(3):261-77.
A comparison of two worlds: How does Bayes hold up to the status quo for the analysis of clinical trials?
BACKGROUND: There is a paucity of literature comparing Bayesian analytic techniques with traditional approaches for analyzing clinical trials using real trial data. METHODS: We compared Bayesian and frequentist group sequential methods using data from two published clinical trials. We chose two widely accepted frequentist rules, O’Brien-Fleming and Lan-DeMets, and conjugate Bayesian priors. Using the nonparametric bootstrap, we estimated a sampling distribution of stopping times for each method. Because current practice dictates the preservation of an experiment-wise false positive rate (Type I error), we approximated these error rates for our Bayesian and frequentist analyses with the posterior probability of detecting an effect in a simulated null sample. Thus for the data-generated distribution represented by these trials, we were able to compare the relative performance of these techniques. RESULTS: No final outcomes differed from those of the original trials. However, the timing of trial termination differed substantially by method and varied by trial. For one trial, group sequential designs of either type dictated early stopping of the study. In the other, stopping times were dependent upon the choice of spending function and prior distribution. CONCLUSIONS: Results indicate that trialists ought to consider Bayesian methods in addition to traditional approaches for analysis of clinical trials. Though findings from this small sample did not demonstrate either method to consistently outperform the other, they did suggest the need to replicate these comparisons using data from varied clinical trials in order to determine the conditions under which the different methods would be most efficient.
Authors: Pressman AR; Avins AL; Hubbard A; Satariano WA
Contemp Clin Trials. 2011 Jul;32(4):561-8. Epub 2011 Mar 29.
Maternal serum docosahexaenoic acid and schizophrenia spectrum disorders in adult offspring
It is believed that during mid-to-late gestation, docosahexaenoic acid (DHA), an n-3 fatty acid, plays an important role in fetal and infant brain development, including neurocognitive and neuromotor functions. Deficits in several such functions have been associated with schizophrenia. Though sufficient levels of DHA appear to be important in neurodevelopment, elevated maternal DHA levels have also been associated with abnormal reproductive outcomes in both animal models and humans. Our objective was to assess whether a disturbance in maternal DHA levels, measured prospectively during pregnancy, was associated with risk of schizophrenia and other schizophrenia spectrum disorders (SSD) in adult offspring. In order to test the hypothesis that abnormal levels of DHA are associated with SSD, a case-control study nested within a large, population-based birth cohort, born from 1959 through 1967 and followed up for SSD from 1981 through 1997, was utilized. Maternal levels of both DHA and arachidonic acid (AA), an n-6 fatty acid, were analyzed in archived maternal sera from 57 cases of SSD and 95 matched controls. There was a greater than twofold increased risk of SSD among subjects exposed to maternal serum DHA in the highest tertile (OR=2.38, 95% CI=1.19, 4.76, p=0.01); no such relationship was found between AA and SSD. These findings suggest that elevated maternal DHA is associated with increased risk for the development of SSD in offspring.
Authors: Harper KN; Hibbeln JR; Deckelbaum R; Quesenberry CP Jr; Schaefer CA; Brown AS
Schizophr Res. 2011 May;128(1-3):30-6. Epub 2011 Feb 15.
Alcohol screening and changes in problem drinking behaviors in medical care settings: a longitudinal perspective
OBJECTIVE: Although the effect of alcohol assessment in medical settings has received attention, the longitudinal study of such efforts has been restricted to studying a single assessment/intervention dose. Such interventions can be recurrent and have effects on subsequent problem drinking. METHOD: A sample of problem drinkers in the general population (n = 672) and with admissions to chemical-dependency programs (n = 926) was interviewed at baseline and 1, 3, 5, and 7 years later. At each wave, respondents were asked about their drinking, their medical visits, and the intensity of the medical contact (whether during the visit they were asked about their drinking and, if so, whether they received or were referred to alcohol treatment). RESULTS: Rates of problem drinking declined over time, from 48% at the 1-year follow up to 38% at the 7-year follow-up. Problem drinkers were more likely at each wave to receive or be referred to treatment. Alcohol and drug severity increased with more intensive medical-contact types over time. Predicting subsequent problem drinking status from prior intensity of medical contact, odds of problem drinking at subsequent waves decreased with time, age, and prior drug severity while increasing with volume and alcohol severity. Odds of problem drinking were lower among prior problem drinkers receiving assessment and treatment/referral, compared with the assessed-only group. Examined separately, this effect was found only for those drinkers with lower volumes (average < 0.5 drinks/day). Conclusions: Alcohol assessment may be effective in reducing problem drinking but may be most effective among the non-heaviest drinkers.
Authors: Bond JC; Weisner CM; Delucchi KL
J Stud Alcohol Drugs. 2011 May;72(3):471-9.
Subdiagnostic alcohol use by depressed men and women seeking outpatient psychiatric services: consumption patterns and motivation to reduce drinking
BACKGROUND: This study examined alcohol use patterns among men and women with depression seeking outpatient psychiatric treatment, including factors associated with recent heavy episodic drinking and motivation to reduce alcohol consumption. METHODS: The sample consisted of 1,183 patients aged 18 and over who completed a self-administered, computerized intake questionnaire and who scored >/= 10 on the Beck Depression Inventory-II (BDI-II). Additional measures included current and past alcohol questions based on the Addiction Severity Index, heavy episodic drinking (>/= 5 drinks on 1 or more occasions in the past year), alcohol-related problems on the Short Michigan Alcoholism Screening Test (SMAST), and motivation to reduce drinking using the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES). RESULTS: Among those who consumed any alcohol in the past year (73.9% of the sample), heavy episodic drinking in the past year was reported by 47.5% of men and 32.5% of women. In logistic regression, prior-year heavy episodic drinking was associated with younger age (p = 0.011), male gender (p = 0.001), and cigarette smoking (p = 0.002). Among patients reporting heavy episodic drinking, motivation to reduce alcohol consumption was associated with older age (p = 0.008), greater usual quantity of alcohol consumed (p < 0.001), and higher SMAST score (p < 0.001). CONCLUSIONS: In contrast to prior clinical studies, we examined subdiagnostic alcohol use and related problems among psychiatric outpatients with depression. Patients reporting greater drinking quantities and alcohol-related problems also express more motivation to reduce drinking, providing intervention opportunities for mental health providers that should not be overlooked.
Authors: Satre DD; Chi FW; Eisendrath S; Weisner C
Alcohol Clin Exp Res. 2011 Apr;35(4):695-702. Epub 2011 Jan 11.
Stopping smoking during first year of substance use treatment predicted 9-year alcohol and drug treatment outcomes
This study examined the association between stopping smoking at 1 year after substance use treatment intake and long-term substance use outcomes. Nine years of prospective data from 1185 adults (39% female) in substance use treatment at a private health care setting were analyzed by multivariate logistic generalized estimating equation models. At 1 year, 14.1% of 716 participants who smoked cigarettes at intake reported stopping smoking, and 10.7% of the 469 non-smokers at intake reported smoking. After adjusting for sociodemographics, substance use severity and diagnosis at intake, length of stay in treatment, and substance use status at 1 year, those who stopped smoking at 1 year were more likely to be past-year abstinent from drugs, or in past-year remission of drugs and alcohol combined, at follow-ups than those who continued to smoke (OR=2.4, 95% CI: 1.2-4.7 and OR=1.6, 95% CI: 1.1-2.4, respectively). Stopping smoking at 1 year also predicted past-year alcohol abstinence through 9 years after intake among those with drug-only dependence (OR=2.4, 95% CI: 1.2-4.5). We found no association between past-year alcohol abstinence and change in smoking status at 1 year for those with alcohol dependence or other substance use diagnoses when controlling for alcohol use status at 1 year. Stopping smoking during the first year after substance use treatment intake predicted better long-term substance use outcomes through 9 years after intake. Findings support promoting smoking cessation among smoking clients in substance use treatment.
Authors: Tsoh JY; Chi FW; Mertens JR; Weisner CM
Drug Alcohol Depend. 2011 Apr 1;114(2-3):110-8. Epub 2010 Nov 2.
Catastrophizing, depression and pain-related disability
OBJECTIVE: The objective of the study was to examine catastrophizing, depression and their interactive effects in predicting disability in patients with chronic pain. METHOD: A battery of questionnaires was mailed to primary care patients in a large integrated health care delivery system. The Patient Health Questionnaire was used to assess major depression, the Coping Strategies Questionnaire assessed catastrophizing and the Graded Chronic Pain Scale was used to assess pain intensity and two measures of disability, including self-report of pain interference and days missed from usual activities. Patient medical records were used to assess severe medical illness. Of the 5808 respondents, 2618 met criteria for chronic pain. Multiple regression analyses, covarying for age, gender, severe medical illness and pain intensity, estimated the main and interactive effects of catastrophic thinking and depression on two measures of pain-related disability. RESULTS: Both catastrophic thinking and depression were statistically significant predictors of both measures of pain-related disability, with larger effect sizes observed for catastrophic thinking. CONCLUSIONS: Routine assessment of both catastrophic thinking and depression is important in the treatment of chronic pain patients, and modification of these factors may reduce disability and increase the ability of chronic pain patients to participate in daily life activity.
Authors: Arnow BA; Blasey CM; Constantino MJ; Robinson R; Hunkeler E; Lee J; Fireman B; Khaylis A; Feiner L; Hayward C
Gen Hosp Psychiatry. 2011 Mar-Apr;33(2):150-6. Epub 2011 Feb 21.
Heavy smoking in midlife and long-term risk of Alzheimer disease and vascular dementia
BACKGROUND: Smoking is a risk factor for several life-threatening diseases, but its long-term association with dementia is controversial and somewhat understudied. Our objective was to investigate the long-term association of amount of smoking in middle age on the risk of dementia, Alzheimer disease (AD), and vascular dementia (VaD) several decades later in a large, diverse population. METHODS: We analyzed prospective data from a multiethnic population-based cohort of 21,123 members of a health care system who participated in a survey between 1978 and 1985. Diagnoses of dementia, AD, and VaD made in internal medicine, neurology, and neuropsychology were collected from January 1, 1994, to July 31, 2008. Multivariate Cox proportional hazards models were used to investigate the association between midlife smoking and risk of dementia, AD, and VaD. RESULTS: A total of 5367 people (25.4%) were diagnosed as having dementia (including 1136 cases of AD and 416 cases of VaD) during a mean follow-up period of 23 years. Results were adjusted for age, sex, education, race, marital status, hypertension, hyperlipidemia, body mass index, diabetes, heart disease, stroke, and alcohol use. Compared with nonsmokers, those smoking more than 2 packs a day had an elevated risk of dementia (adjusted hazard ratio [HR], 2.14; 95% CI, 1.65-2.78), AD (adjusted HR, 2.57; 95% CI, 1.63-4.03), and VaD (adjusted HR, 2.72; 95% CI, 1.20-6.18). CONCLUSIONS: In this large cohort, heavy smoking in midlife was associated with a greater than 100% increase in risk of dementia, AD, and VaD more than 2 decades later. These results suggest that the brain is not immune to long-term consequences of heavy smoking.
Authors: Rusanen M; Kivipelto M; Zhou J; Whitmer RA; Quesenberry CP Jr
Arch Intern Med. 2011 Feb 28;171(4):333-9. Epub 2010 Oct 25.
Time-scheduled vs. pain-contingent opioid dosing in chronic opioid therapy
Some expert guidelines recommend time-scheduled opioid dosing over pain-contingent dosing for patients receiving chronic opioid therapy (COT). The premise is that time-scheduled dosing results in more stable opioid blood levels and better pain relief, fewer adverse effects, less reinforcement of pain behaviors, and lower addiction risk. We report results of a survey of 1781 patients receiving COT for chronic noncancer pain, in which 967 reported time-scheduled opioid dosing only and 325 reported pain-contingent opioid dosing only. Opioid-related problems and concerns were assessed with the Prescribed Opioids Difficulties Scale. We hypothesized that respondents using time-scheduled opioid dosing would report significantly fewer problems and concerns than those using pain-contingent dosing. Patients receiving time-scheduled dosing received substantially higher average daily opioid doses than those using pain-contingent dosing (97.2 vs. 37.2mg average daily dose morphine equivalents, P < .0001). Contrary to expectation, time-scheduled opioid dosing was associated with higher levels of patient opioid control concerns than pain-contingent dosing (6.2 vs. 4.8, P=.008), after adjusting for patient and drug regimen differences. Opioid-related psychosocial problems were somewhat greater among patients using time-scheduled dosing, but this difference was nonsignificant after controlling for patient and drug regimen differences (5.9 vs. 5.0, P=.14). Time-scheduled dosing typically involved higher dosage levels and was associated with higher levels of patient concerns about opioid use. Controlled comparative effectiveness research is needed to assess benefits and risks of time-scheduled opioid dosing relative to pain-contingent opioid dosing among COT patients in ambulatory care. Patients with time-scheduled dosing received higher opioid dosage than patients with pain-contingent dosing. Time-scheduled dosing was associated with greater opioid control concerns than pain-contingent dosing.
Authors: Von Korff M; Merrill JO; Rutter CM; Sullivan M; Campbell CI; Weisner C
Pain. 2011 Jun;152(6):1256-62. Epub 2011 Feb 5.
Excess mortality among HIV-infected patients diagnosed with substance use dependence or abuse receiving care in a fully integrated medical care program
BACKGROUND: We examined the association between substance use (SU) disorder and mortality among HIV-infected patients in a large, private medical care program. METHODS: In a retrospective cohort design, HIV-infected patients (>/=14 years old) from a large health plan (Northern California) were studied to examine mortality associated with diagnosis of SU dependence or abuse over an 11-year period. RESULTS: At study entry or during follow-up, 2,279 (25%) of 9,178 HIV-infected patients had received a diagnosis of SU disorder. Diagnoses were categorized as alcohol dependence/abuse only, illicit drugs only, or both. Cause of death differed by the category of SU diagnosis. Mortality rates ranged from 35.5 deaths per 1,000 person-years in patients with an SU disorder to 17.5 deaths among patients without an SU disorder. Regression results indicated mortality risk was significantly higher in all categories of SU disorder compared to no SU diagnosis (hazard ratios ranging from 1.65 to 1.67) after adjustment for SU treatment and confounders. CONCLUSIONS: A diagnosis of SU dependence/abuse is associated with higher mortality among HIV-infected patients for whom access to medical services is not a significant factor.
Authors: DeLorenze GN; Weisner C; Tsai AL; Satre DD; Quesenberry CP Jr
Alcohol Clin Exp Res. 2011 Feb;35(2):203-10. Epub 2010 Nov 8.
Executive Function in Preschool Children: Test-Retest Reliability
Research suggests that executive function (EF) may distinguish between children who are well- or ill-prepared for kindergarten, however, little is known about the test-retest reliability of measures of EF for children. We aimed to establish a battery of EF measures that are sensitive to both development and individual differences across the preschool period using Conflict and Delay subtests that had a cool (abstract) or hot (extrinsic reward) focus. Results from 151 children in three age groups (2.5, 3.5, and 4.5) suggested acceptable same-day test-retest reliability on all but Delay-Cool subtasks. These findings will inform appropriate measurement selection and development for future studies.
Authors: Beck DM; Schaefer C; Pang K; Carlson SM
J Cogn Dev. 2011 Jan 01;12(2):169-193.
Timing of hormone therapy and dementia: the critical window theory revisited
OBJECTIVE: Although previous research has shown that initiation of postmenopausal estrogen hormone therapy (HT) in late life increases risk of dementia, animal studies and some observational studies have suggested that midlife use of HT may be beneficial; however, this has not been rigorously investigated in large population-based studies. Our objective was to compare HT use in midlife with that in late life on risk of dementia among 5,504 postmenopausal female members of an integrated healthcare delivery system. METHODS: HT use was determined at midlife (mean age, 48.7 years) from a survey in 1964 and in late life (mean age, 76 years) using pharmacy databases from 1994 to 1998. Risk of dementia diagnosis was evaluated with inpatient and outpatient diagnoses made in Neurology, Neuropsychology, and Internal Medicine from 1999 to 2008. Cox proportional hazard models were used to examine effects of HT use at different times on dementia risk with adjustment for age, education, race, body mass index, number of children, and comorbidities. RESULTS: A total of 1,524 women (27%) were diagnosed with dementia during the follow-up period. Compared to women never on HT, those taking HT only at midlife had a 26% decreased risk (multivariate adjusted hazards ratio [aHR], 0.74; 95% confidence interval [CI], 0.58-0.94 ), whereas those taking HT only in late life had a 48% increased risk (aHR, 1.48; 95% CI, 1.10-1.98), and women taking HT at both mid and late life had a similar risk of dementia (aHR, 1.02; 95% CI, 0.78-1.34 ). INTERPRETATION: These findings suggest that use of HT in midlife only may protect against cognitive impairment, whereas HT initiation in late life could have deleterious effects.
Authors: Whitmer RA; Quesenberry CP; Zhou J; Yaffe K
Ann Neurol. 2011 Jan;69(1):163-9. Epub 2010 Nov 12.
Initial Status in Growth Curve Modeling for Randomized Trials
The growth curve modeling (GCM) technique has been widely adopted in longitudinal studies to investigate progression over time. The simplest growth profile involves two growth factors, initial status (intercept) and growth trajectory (slope). Conventionally, all repeated measures of outcome are included as components of the growth profile, and the first measure is used to reflect the initial status. Selection of the initial status, however, can greatly influence study findings, especially for randomized trials. In this article, we propose an alternative GCM approach involving only post-intervention measures in the growth profile and treating the first wave after intervention as the initial status. We discuss and empirically illustrate how choices of initial status may influence study conclusions in addressing research questions in randomized trials using two longitudinal studies. Data from two randomized trials are used to illustrate that the alternative GCM approach proposed in this article offers better model fitting and more meaningful results.
Authors: Chou CP; Chi F; Weisner C; Pentz M; Hser YI
J Drug Issues. 2010 Dec;40(1):155-172.
Placebo adherence and its association with morbidity and mortality in the studies of left ventricular dysfunction
BACKGROUND: A provocative finding from several double-blind clinical trials has been the association between greater adherence to placebo study medication and better health outcomes. We used data from the Studies of Left Ventricular Dysfunction (SOLVD) Treatment Trial (SOLVD-TT) and the SOLVD Prevention Trial (SOLVD-PT) to examine whether such associations could be validated and to examine several sources of bias and potential confounding. METHODS: Survival analytic methods were used to estimate the association between placebo adherence and several health outcomes, employing a number of modeling techniques to test for the existence of alternative explanations for the association. Higher adherence was defined as having taken >/=75% of prescribed study medication. RESULTS: Higher placebo adherence was associated with improved overall survival in both SOLVD-TT and SOLVD-PT [hazard ratio (HR) = 0.52, 95% confidence interval (CI): 0.35 to 0.79 and HR = 0.52, 95%CI: 0.38 to 0.71, respectively]. Associations were similar for fatal or non-fatal cardiovascular or coronary heart disease events. Adjustment for both modifiable and non-modifiable cardiac risk factors (including age, gender, diabetes, blood pressure, smoking, weight, alcohol use, and levels of education) had minimal effect on the strength of the association. Little evidence of bias was found as an explanation for this relationship. CONCLUSIONS: In these two trials, better adherence to placebo was associated with markedly superior health outcomes, including total in-study mortality and incident cardiovascular events. No important confounders were identified. These data suggest there may exist strong but unrecognized determinants of health outcomes for which placebo adherence is a marker.
Authors: Avins AL; Pressman A; Ackerson L; Rudd P; Neuhaus J; Vittinghoff E
J Gen Intern Med. 2010 Dec;25(12):1275-81. Epub 2010 Aug 13.
Epidemiologic study of aripiprazole use and the incidence of suicide events
PURPOSE: Because second generation antipsychotics (SGA) might affect the risk of suicide, systematic assessment of suicide risk associated with SGA in the postmarketing setting is important and of interest to regulatory authorities. To fulfill a postmarketing request, our objective was to determine suicide event (attempted or completed) incidence in patients with schizophrenia or bipolar disorder, prescribed aripiprazole. METHODS: Using administrative data from three US sources, we assessed study endpoints of suicide attempts and death by suicide in patients aged >/=18 enrolled continuously for >/=3 months in their health plans before receiving their first ever antipsychotic (November 2002-December 2005). RESULTS: Among 20 489 antipsychotic users (8985 patient-years), unadjusted suicide event rates (per 1000 patient-years) were: 20.69 (aripiprazole); 23.99 (olanzapine); 32.33 (quetiapine); 19.69 (risperidone); 48.52 (ziprasidone). Compared with current users of other SGA combined, aripiprazole users did not have an increased risk of suicide events (crude hazard ratio (HR) = 0.79, 95%CI: 0.48-1.30; adjusted HR = 0.69, 95%CI: 0.42-1.14-(controlling for study site, age, sex, index prescription year, antipsychotic use history, other pharmacotherapy exposure, comorbidity presence, schizophrenia/bipolar disorder, suicide attempts, number inpatient/outpatient encounters). CONCLUSIONS: In this large, multi-site study, compared with other SGA combined, aripiprazole is not associated with an increased risk of suicide events in an inception cohort of patients with ICD-9/ICD-10 codes indicative of schizophrenia or bipolar disorder.
Authors: Ulcickas YM; Quesenberry CP Jr; et al.
Pharmacoepidemiol Drug Saf. 2010 Nov;19(11):1124-30.
Mortality after diagnosis of psychiatric disorders and co-occurring substance use disorders among HIV-infected patients
We examined the associations between psychiatric diagnoses, substance use disorders, health services, and mortality among 9751 HIV-infected patients (>/=14 years old) in a large, private medical care program, in a retrospective cohort design over a 12-year period. All study data were extracted from computerized clinical and administrative databases. Results showed that 25.4% (n = 2472) of the 9751 study subjects had received a psychiatric diagnosis (81.1% had major depression, 17.1% had panic disorder, 14.2% had bipolar disorder, and 8.1% had anorexia/bulimia); and 25.5% (n = 2489) had been diagnosed with substance use disorder; 1180 (12.1%) patients had received both psychiatric and substance diagnoses. In comparison to patients with neither a psychiatric diagnosis nor a SU diagnosis, the highest risk of death was found among patients with dual psychiatric and substance use diagnoses who had no psychiatric treatment visits and no substance treatment (relative hazards [RH] = 4.17, 95% confidence interval [CI] = 2.35 to 7.40). Among dually diagnosed patients, receiving psychiatric and/or substance use disorder treatment somewhat reduced the risk of death compared to patients with neither diagnosis. The lowest risks of death were observed among patients with a single diagnosis who had received corresponding treatment. Our study findings suggest that screening for psychiatric and substance problems at the initiation and during the course of HIV/AIDS treatment and providing psychiatric and substance use disorder treatment may extend life for these vulnerable patients.
Authors: DeLorenze GN; Satre DD; Tsai AL; Weisner CM; Quesenberry CP Jr
AIDS Patient Care STDS. 2010 Nov;24(11):705-12. Epub 2010 Oct 23.
The time is now: missed opportunities to address patient needs in community clinics in Cape Town, South Africa
SUMMARY OBJECTIVE: To investigate the prevalence and correlates of missed opportunities for addressing reproductive and mental health needs during patients’ visits to primary healthcare facilities. METHODS: We selected a random sample of participants from 14 of the 49 clinics in Cape Town’s public health sector using stratified, cluster random sampling (n = 2618). Participants were screened to identify those at risk for unsafe sexual behaviour and a mental disorder (specifically substance use, depression, anxiety, and suicide). Information pertaining to whether or not respondents were asked about these issues during clinic visits during the previous year was elicited. The rates and correlates of missed opportunities for providing reproductive and mental health interventions were calculated. RESULTS: The criteria of a strict definition of a missed opportunity for reproductive or mental health care information were fulfilled by 25% of the sample, while 46% met criteria for a looser definition. After adjusting for the effects of other variables in the model, men and Coloured respondents were more likely to have satisfied the definition of a missed opportunity for an intervention, while having completed high school and having children increased the likelihood of receiving an intervention. CONCLUSION: Consultations with primary healthcare providers in which these issues are not discussed may represent missed opportunities. Persons presenting for routine care can be counselled, screened and, if required, treated. Interventions are needed at the patient, provider, and community levels to increase the opportunities to provide reproductive and mental health care to patients during routine visits.
Authors: Sorsdahl K; Flisher AJ; Ward C; Mertens J; Bresick G; Sterling S; Weisner C
Trop Med Int Health. 2010 Oct;15(10):1218-26.
Age and gender trends in long-term opioid analgesic use for noncancer pain
OBJECTIVES: We describe age and gender trends in long-term use of prescribed opioids for chronic noncancer pain in 2 large health plans. METHODS: Age- and gender-standardized incident (beginning in each year) and prevalent (ongoing) opioid use episodes were estimated with automated health care data from 1997 to 2005. Profiles of opioid use in 2005 by age and gender were also compared. RESULTS: From 1997 to 2005, age-gender groups exhibited a total percentage increase ranging from 16% to 87% for incident long-term opioid use and from 61% to 135% for prevalent long-term opioid use. Women had higher opioid use than did men. Older women had the highest prevalence of long-term opioid use (8%-9% in 2005). Concurrent use of sedative-hypnotic drugs and opioids was common, particularly among women. CONCLUSIONS: Risks and benefits of long-term opioid use are poorly understood, particularly among older adults. Increased surveillance of the safety of long-term opioid use is needed in community practice settings.
Authors: Campbell CI; Weisner C; Leresche L; Ray GT; Saunders K; Sullivan MD; Banta-Green CJ; Merrill JO; Silverberg MJ; Boudreau D; Satre DD; Von Korff M
Am J Public Health. 2010 Dec;100(12):2541-7. Epub 2010 Aug 19.
Structural brain alterations in schizophrenia following fetal exposure to the inflammatory cytokine interleukin-8
BACKGROUND: Maternal infection during pregnancy has been repeatedly associated with increased risk for schizophrenia. Nevertheless, most viruses do not cross the placenta; therefore, the damaging effects to the fetus appear to be related to maternal antiviral responses to infection (e.g. proinflammatory cytokines). Fetal exposure to the proinflammatory cytokine interleukin-8 (IL-8) has been significantly associated with risk of schizophrenia in offspring. This study sought to determine the association between fetal exposure to IL-8 and structural brain changes among schizophrenia cases and controls. METHODS: Subjects were 17 cases diagnosed with schizophrenia from the Developmental Insult and Brain Anomaly in Schizophrenia (DIBS) study. Psychiatric diagnoses were determined among offspring with semi-structured interviews and medical records review. IL-8 was determined from assays in archived prenatal sera and volumetric analyses of neuroanatomical regions were obtained from T1-weighted magnetic resonance imaging in adulthood. Eight controls were included for exploratory purposes. RESULTS: Among cases, fetal exposure to increases in IL-8 was associated with significant increases in ventricular cerebrospinal fluid, significant decreases in left entorhinal cortex volumes and significant decreases in right posterior cingulate volumes. Decreases that approached significance also were found in volumes of the right caudate, the putamen (bilaterally), and the right superior temporal gyrus. No significant associations were observed among controls. CONCLUSION: Fetal exposure to elevations in maternal IL-8 led to structural neuroanatomic alterations among cases in regions of the brain consistently implicated in schizophrenia research. In utero exposure to elevations in IL-8 may partially account for brain disturbances commonly found in schizophrenia.
Authors: Ellman LM; Deicken RF; Vinogradov S; Kremen WS; Poole JH; Kern DM; Tsai WY; Schaefer CA; Brown AS
Schizophr Res. 2010 Aug;121(1-3):46-54. Epub 2010 Jun 9.
Glucosamine and the ongoing enigma of chronic low back pain
Authors: Avins AL
JAMA. 2010 Jul 7;304(1):93-4.
Is pregnancy after breast cancer safe?
The impact of treatment on subsequent fertility and the safety of childbearing are major complicating factors for young women diagnosed with breast cancer. As national data indicate women are postponing first pregnancy to older ages; therefore, many young patients are seeking clinical guidance regarding the safety of conception and treatment options that may not prevent subsequent pregnancy. Newly developed chemotherapy protocols of brief duration have improved life expectancy enabling some women to consider childbearing. This study was conducted to compare prognosis among breast cancer patients with and without a subsequent pregnancy. Medical record review of female members of a Northern California prepaid health care plan enabled the identification of 107 women with one or more subsequent pregnancies and 344 cases without a pregnancy, who were diagnosed between 1968 and 1995. Sets were matched on age, year and stage at diagnosis, months of survival and recurrence status at conception. Among the matched sets, neither risk of recurrence nor death differed significantly by subsequent pregnancy history during an average 12 years of follow-up (adjusted hazard ratio [HR] recurrence: 1.2 [0.8, 2.0]; adjusted HR death: 1.0 [0.6, 1.9]). Women interested in preserving their fertility and considering pregnancy are a self-selected population; therefore, to reduce potential bias, cases were matched on recurrence status at time of conception. Although the number of cases was limited, subgroup analyzes indicated a small, nonsignificant adverse effect among women who conceived within 12 months of diagnosis. This analysis of carefully matched cases provides reassurance that long-term prognosis was not adversely affected by subsequent pregnancy.
Authors: Kranick JA; Schaefer C; Rowell S; Desai M; Petrek JA; Hiatt RA; Senie RT
Breast J. 2010 Jul-Aug;16(4):404-11. Epub 2010 May 26.
Access to treatment for adolescents with substance use and co-occurring disorders: challenges and opportunities
OBJECTIVE: To review the research on economic and systemic barriers faced by adolescents needing treatment for alcohol and drug problems, particularly those with co-occurring conditions. METHOD: We reviewed the literature on adolescent access to alcohol and drug services, including early intervention, and integrated and specialty mental health treatment for those with co-occurring disorders, examining the role of health care systems, public policy (health reform), treatment financing and reimbursement systems (public and private), implementation of evidence-based practices, confidentiality practices, and treatment costs and cost/benefits. RESULTS: Barriers to treatment, particularly integrated treatment, are largely rooted in our organizationally fragmented health care system, which encompasses public and private, carved-out and integrated systems, and different funding mechanisms (Medicaid versus block grants versus private insurance that include ‘high deductible’ plans and other cost controls.) In both systems, carved-out programs de-link services from other mental health and general health care. Barriers are also rooted in disciplinary differences and weak clinical linkages between psychiatry, primary care and substance use, and in confidentiality policies that inhibit communication and coordination, while protecting patient privacy. CONCLUSION: In this era of health care reform, we have the opportunity to increase access for adolescents and develop new models of integrated services for those with co-occurring conditions. We discuss opportunities for improving treatment access and implementation of evidence-based practices, examine implications of health reform and parity legislation for psychiatric and substance use treatment, and comment on key unanswered questions and future research opportunities.
Authors: Sterling S; Weisner C; Hinman A; Parthasarathy S
J Am Acad Child Adolesc Psychiatry. 2010 Jul;49(7):637-46; quiz 725-6. Epub 2010 May 8.
Predictors of longitudinal substance use and mental health outcomes for patients in two integrated service delivery systems
AIM: Individuals who have both substance use disorders and mental health problems have poorer treatment outcomes. This study examines the relationship of service utilization and 12-step participation to outcomes at 1 and 5 years for patients treated in one of two integrated service delivery systems: the Department of Veterans Affairs (VA) system and a health maintenance organization (HMO). METHODS: Sub-samples from each system were selected using multiple criteria indicating severity of mental health problems at admission to substance use disorder treatment (VA=401; HMO=331). Separate and multiple group structural equation model analyses used baseline characteristics, service use, and 12-step participation as predictors of substance use and mental health outcomes at 1 and 5 years following admission. RESULTS: Substance use and related problems showed stability across time, however, these relationships were stronger among VA patients. More continuing care substance use outpatient visits were associated with reductions in mental health symptoms in both groups, whereas receipt of outpatient mental health services was associated with more severe psychological symptoms. Participation in 12-step groups had a stronger effect on reducing cocaine use among VA patients, whereas it had a stronger effect on reducing alcohol use among HMO patients. More outpatient psychological services had a stronger effect on reducing alcohol use among HMO patients. CONCLUSION: Common findings across these two systems demonstrate the persistence of substance use and related psychological problems, but also show that continuing care services and participation in 12-step groups are associated with better outcomes in both systems.
Authors: Grella CE; Stein JA; Weisner C; Chi F; Moos R
Drug Alcohol Depend. 2010 Jul 1;110(1-2):92-100. Epub 2010 Mar 24.
Individuals receiving addiction treatment: are medical costs of their family members reduced?
AIMS: To examine whether alcohol and other drug (AOD) treatment is related to reduced medical costs of family members. DESIGN: Using the administrative databases of a private, integrated health plan, we matched AOD treatment patients with health plan members without AOD disorders on age, gender and utilization, identifying family members of each group. SETTING: Kaiser Permanente Northern California. PARTICIPANTS: Family members of abstinent and non-abstinent AOD treatment patients and control family members. MEASUREMENTS: We measured abstinence at 1 year post-intake and examined health care costs per member-month of family members of AOD patients and of controls through 5 years. We used generalized estimating equation methods to examine differences in average medical cost per member-month for each year, between family members of abstinent and non-abstinent AOD patients and controls. We used multilevel models to examine 4-year cost trajectories, controlling for pre-intake cost, age, gender and family size. RESULTS: AOD patients’ family members had significantly higher costs and more psychiatric and medical conditions than controls in the pre-treatment year. At 2-5 years, each year family members of AOD patients abstinent at 1 year had similar average per member-month medical costs to controls (e.g. difference at year 5 = $2.63; P > 0.82), whereas costs for family members of non-abstinent patients were higher (e.g. difference at year 5 = $35.59; P = 0.06). Family members of AOD patients not abstinent at 1 year, had a trajectory of increasing medical cost (slope = $10.32; P = 0.03) relative to controls. CONCLUSIONS: Successful AOD treatment is related to medical cost reductions for family members, which may be considered a proxy for their improved health.
Authors: Weisner C; Parthasarathy S; Moore C; Mertens JR
Addiction. 2010 Jul;105(7):1226-34. Epub 2010 May 14.
Treatment expectations and preferences as predictors of outcome of acupuncture for chronic back pain
STUDY DESIGN: Preplanned secondary analysis of data from participants receiving acupuncture in a randomized clinical trial. OBJECTIVE: To determine whether patients’ expectations of and preferences for acupuncture predict short and long-term treatment outcomes for persons with chronic back pain. SUMMARY OF BACKGROUND DATA: Although accumulating evidence suggests that patient expectations and treatment preferences may predict treatment outcomes, few studies have examined this relationship for acupuncture. METHODS: Four hundred seventy-seven acupuncture-naive participants with chronic low back pain who were randomized to 1 of 3 acupuncture or simulated acupuncture treatments were the focus of this analysis. Ten treatments were provided during a 7-week period, and participants were masked to treatment assignment. Before randomization, participants provided expectations regarding treatment success, impressions, and knowledge about acupuncture and treatment preferences. Outcomes of interest were functional status (Roland score) and symptom bothersomeness at 8 and 52 weeks postrandomization, obtained by telephone interviewers masked to treatment assignment. RESULTS: Persons with high pretreatment expectations for the success of acupuncture were more likely to report greater general expectations for improvement, a preference for acupuncture, having heard acupuncture was a very effective treatment and having a very or moderately positive impression of acupuncture. However, none of these variables was a significant predictor of improvement in back-related symptoms or function at 8 or 52 weeks. After 1 treatment, participants’ revised expectations of treatment success were only associated with back-symptoms at the end of treatment. After 5 treatments, revised expectation of success was predictive of both symptoms and function at 8 and 52 weeks. CONCLUSION: Pretreatment expectations and preferences for acupuncture were not found predictive of treatment outcomes for patients with chronic back pain. These results differ from previous studies evaluating acupuncture for chronic back pain. These inconsistent results suggest that the relationship between expectations and outcomes may be more complex than previously believed.
Authors: Sherman KJ; Cherkin DC; Ichikawa L; Avins AL; Delaney K; Barlow WE; Khalsa PS; Deyo RA
Spine (Phila Pa 1976). 2010 Jul 1;35(15):1471-7.
Drinking Patterns, Gender and Health II: Predictors of Preventive Service Use
Chronic diseases and injuries are elevated among people with substance use problems/dependence, yet heavier drinkers use fewer routine and preventive health services than non-drinkers and moderate drinkers, while former drinkers and abstainers use more than moderate drinkers. Researchers hypothesize that drinking clusters with attitudes and practices that produce better health among moderate drinkers and that heavy drinkers avoid doctors until becoming ill, subsequently quitting and using more services. Gender differences in alcohol consumption, health-related attitudes, practices, and prevention-services use may affect these relationships. A stratified random sample of health-plan members (7884; 2995 males, 4889 females) completed a mail survey that was linked to 24 months of health-plan records. Data were used to examine relationships between alcohol use, gender, health-related attitudes/practices, health, and prevention-service use. Controlling for attitudes, practices, and health, female lifelong abstainers and former drinkers were less likely to have mammograms; individuals with alcohol use disorders and positive AUDIT scores were less likely to obtain influenza vaccinations. AUDIT-positive women were less likely to undergo colorectal screening than AUDIT-positive men. Consistent predictors of prevention-services use were: self-report of having a primary care provider (positive); disliking visiting the doctor (negative); smoking cigarettes (negative), and higher BMI (negative). When factors associated with drinking are controlled, patterns of alcohol consumption have limited effects on preventive service use. Individuals with stigmatized behaviors (e.g., hazardous/harmful drinking, smoking, or high BMIs) are less likely to receive care. Making care experiences positive and carefully addressing stigmatized health practices could increase preventive service use.
Authors: Green CA; Polen MR; Leo MC; Perrin NA; Anderson BM; Weisner CM
Addict Res Theory. 2010 Jul;18(2):143-159.
When clinical practice guidelines meet the black box
Authors: Avins AL
Arch Intern Med. 2010 Jun 28;170(12):1013-4.
Cognitive decline in schizophrenia from childhood to midlife: a 33-year longitudinal birth cohort study
BACKGROUND: We examined cognitive deficits before and after onset of schizophrenia in a longitudinal study that: 1) covers a long time interval; 2) minimizes test unreliability by including the identical measure at both childhood and post-onset cognitive assessments; and 3) minimizes bias by utilizing a population-based sample in which participants were selected neither for signs of illness in childhood nor for being at risk for schizophrenia. METHODS: Participants in the present study, Developmental Insult and Brain Anomaly in Schizophrenia (DIBS), were ascertained from an earlier epidemiologic study conducted in Oakland, CA. The original version of the Peabody Picture Vocabulary Test (PPVT), a test of receptive vocabulary, was administered at age 5 or 9 and repeated as part of the DIBS study at an average age of 40. There were 10 DIBS cases with DSM-IV schizophrenia or schizoaffective disorder and 15 demographically similar DIBS controls with both child and adult PPVT scores. RESULTS: Cases scored significantly lower than controls in childhood (d=0.95) and adulthood (d=1.67). Residualized scores indicating the number of SDs above or below one’s predicted adult score revealed a mean case-control difference of -1.51SDs, consistent with significant relative decline over time among the cases (p<0.0013). CONCLUSIONS: In this prospective study, individuals who developed adult schizophrenia manifested impaired receptive vocabulary during childhood and further relative deterioration (or lack of expected improvement) between childhood and midlife. Limitations should also be acknowledged, including the small sample size and the fact that we cannot be certain when the continued deterioration took place.
Authors: Kremen WS; Vinogradov S; Poole JH; Schaefer CA; Deicken RF; Factor-Litvak P; Brown AS
Schizophr Res. 2010 May;118(1-3):1-5. Epub 2010 Feb 12.
Relationship of opioid use and dosage levels to fractures in older chronic pain patients
BACKGROUND: Opioids have been linked to increased risk of fractures, but little is known about how opioid dose affects fracture risk. OBJECTIVE: To assess whether risk of fracture increases with opioid dose among older patients initiating sustained use of opioids for chronic non-cancer pain. DESIGN: A cohort study that uses Cox proportional hazards models to compare fracture risk among current opioid users vs. persons no longer using opioids. PARTICIPANTS: Members of an integrated health care plan (N = 2,341) age 60 years and older who received 3+ opioid prescriptions within a 90-day period for chronic, non-cancer pain between 2000 and 2005. MEASUREMENTS: Time-varying measures of opioid use and average daily dose in morphine equivalents were calculated from automated data. Fractures were identified from automated data and then validated through medical record review. RESULTS: Compared with persons not currently using opioids, opioid use was associated with a trend towards increased fracture risk (1.28 (95% CI (0.99, 1.64 )). Higher dose opioid use (>or=50 mg/day) was associated with a 9.95% annual fracture rate and a twofold increase in fracture risk (2.00 (95% CI (1.24, 3.24)). Of the fractures in the study cohort, 34% were of the hip or pelvis, and 37% were associated with inpatient care. CONCLUSIONS: Higher doses (>or=50 mg/day) of opioids for chronic non-cancer pain were associated with a 2.00 increase in risk of fracture confirmed by medical record review. Clinicians should consider fracture risk when prescribing higher-dose opioid therapy for older adults.
Authors: Saunders KW; Dunn KM; Merrill JO; Sullivan M; Weisner C; Braden JB; Psaty BM; Von Korff M
J Gen Intern Med. 2010 Apr;25(4):310-5. Epub 2010 Jan 5.
Stress, substance use and sexual risk behaviors among primary care patients in Cape Town, South Africa
We assessed the relationship between stress, substance use and sexual risk behaviors in a primary care population in Cape Town, South Africa. A random sample of participants (and over-sampled 18-24-year-olds) from 14 of the 49 clinics in Cape Town’s public health sector using stratified random sampling (n = 2,618), was selected. We evaluated current hazardous drug and alcohol use and three domains of stressors (Personal Threats, Lacking Basic Needs, and Interpersonal Problems). Several personal threat stressors and an interpersonal problem stressor were related to sexual risk behaviors. With stressors included in the model, hazardous alcohol use, but not hazardous drug use, was related to higher rates of sexual risk behaviors. Our findings suggest a positive screening for hazardous alcohol use should alert providers about possible sexual risk behaviors and vice versa. Additionally, it is important to address a broad scope of social problems and incorporate stress and substance use in HIV prevention campaigns.
Authors: Avalos LA; Mertens JR; Ward CL; Flisher AJ; Bresick GF; Weisner CM
AIDS Behav. 2010 Apr;14(2):359-70. Epub 2009 Feb 10.
Drinking Patterns, Gender and Health I: Attitudes and Health Practices
Despite considerable research, relationships among gender, alcohol consumption, and health remain controversial, due to potential confounding by health-related attitudes and practices associated with drinking, measurement challenges, and marked gender differences in drinking. We examined gender/alcohol consumption differences in health-related attitudes and practices, and evaluated how these factors affected relationships among gender, alcohol consumption, and health status. A stratified random sample of adult health-plan members completed a mail survey, yielding 7884 respondents (2995 male/4889 female). Using MANCOVAs and adjusting for health-related attitudes, values, and practices, we examined gender differences in relationships between alcohol consumption and health. More frequent heavy drinking was associated with worse health-related attitudes and values, worse feelings about visiting the doctor, and worse health-related practices. Relationships between health-related practices and alcohol use differed by gender, and daily or almost daily heavy drinking was associated with significantly lower physical and mental health for women compared to men. Drinking status (lifelong abstainers, former drinkers, and level of regular alcohol consumption) was related to health status and vitality, even after adjusting for health-related attitudes, values, and practices. Relationships did not differ by gender. Former drinkers reported lower physical and mental health status than either lifelong abstainers or current drinkers. Drinking status is independently related to physical health, mental health, and vitality, even after controlling for the health-related attitudes, values, and practices expected to confound these relationships. Among current drinkers, women who engage in very frequent heavy drinking have worse physical and mental health than their male counterparts.
Authors: Polen MR; Green CA; Perrin NA; Anderson BM; Weisner CM
Addict Res Theory. 2010 Apr 01;18(2):122-142.
Transitioning into and out of problem drinking across seven years
OBJECTIVE: The extent to which problem drinkers transition into and out of problem drinking was examined using Markov modeling. METHOD: Study participants (N = 1,350) were randomly sampled from one county’s general population and from consecutive admissions to public and private alcohol treatment programs in the same county, and they were assessed at 1-, 3-, 5-, and 7-year follow-ups. At baseline, all met the criteria for problem drinking. Individuals were classified as ‘problem drinkers’ if they reported at least two of three criteria (heavy episodic drinking, social consequences, dependence symptoms according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) during the prior 12 months. RESULTS: Although all possible patterns were observed, a latent Markov model with heterogeneous transitions and five patterns fit the data. The sampling frame and baseline alcohol severity related to pattern. CONCLUSIONS: The data indicate that, although they do change over time, problem drinkers on the whole are more likely either to remain problem drinkers or to cease to be problem drinkers than they are to move into and out of problem-drinking status. Once they transition out of problem drinking, they are more likely to remain nonproblem drinkers.
Authors: Delucchi KL; Weisner C
J Stud Alcohol Drugs. 2010 Mar;71(2):210-8.
Commentary on ‘Developing a national strategy to prevent dementia: Leon Thal Symposium 2009.’ Dementia risk indices: A framework for identifying individuals with a high dementia risk
Authors: Barnes DE; Covinsky KE; Whitmer RA; Kuller LH; Lopez OL; Yaffe K
Alzheimers Dement. 2010 Mar;6(2):138-41.
Psychiatric disorders and cognitive dysfunction among older, postmenopausal women: results from the Women’s Health Initiative Memory Study
OBJECTIVE: To estimate the frequency of depressive symptoms and selected psychiatric disorders in the Women’s Health Initiative Memory Study (WHIMS) cohort and related them to cognitive syndromes. DESIGN: WHIMS was a randomized, double-blinded, placebo-controlled prevention clinical trial examining whether opposed and unopposed hormone therapy reduced the risk of dementia in healthy postmenopausal women. Participants scoring below a designated cutpoint on a cognitive screener received a comprehensive neuropsychiatric workup and adjudicated outcome of no cognitive impairment, mild cognitive impairment, or probable dementia. PARTICIPANTS: Seven thousand four hundred seventy-nine WHIMS participants between age 65 and 79 years and free of dementia at the time of enrollment in WHIMS. Five hundred twenty-one unique participants contributed complete data required for these analyses. MEASURES: Depressive symptoms were measured with the 15-item Geriatric Depression Scale and the presence of selected psychiatric disorders (major depression, generalized anxiety, and panic and alcohol abuse) was made using the PRIME-MD. RESULTS: The 18% of women had at least one psychiatric disorder with depression being the most common (16%) followed by general anxiety or panic (6%) and alcohol abuse (1%). Depression and the presence of a psychiatric disorder were associated with impaired cognitive status. Participants having a psychiatric disorder were more than twice as likely to be diagnosed with cognitive impairment as those with no psychiatric disorder (odds ratio = 2.06, 95% confidence interval = 1.17-3.60). Older age, white race, and diabetes were also associated with cognitive impairment. CONCLUSION: The frequency of a psychiatric disorder is associated with poorer cognitive functioning among older women enrolled in WHIMS. That approximately one in five women had a probable psychiatric disorder, most typically depression, highlights the need for greater detection and treatment efforts in this population.
Authors: Colenda CC; Legault C; Rapp SR; DeBon MW; Hogan P; Wallace R; Hershey L; Ockene J; Whitmer R; Phillips LS; Sarto GE
Am J Geriatr Psychiatry. 2010 Feb;18(2):177-86.
Opioid prescriptions for chronic pain and overdose: a cohort study
BACKGROUND: Long-term opioid therapy for chronic noncancer pain is becoming increasingly common in community practice. Concomitant with this change in practice, rates of fatal opioid overdose have increased. The extent to which overdose risks are elevated among patients receiving medically prescribed long-term opioid therapy is unknown. OBJECTIVE: To estimate rates of opioid overdose and their association with an average prescribed daily opioid dose among patients receiving medically prescribed, long-term opioid therapy. DESIGN: Cox proportional hazards models were used to estimate overdose risk as a function of average daily opioid dose (morphine equivalents) received at the time of overdose. SETTING: HMO. PATIENTS: 9940 persons who received 3 or more opioid prescriptions within 90 days for chronic noncancer pain between 1997 and 2005. MEASUREMENTS: Average daily opioid dose over the previous 90 days from automated pharmacy data. Primary outcomes–nonfatal and fatal overdoses–were identified through diagnostic codes from inpatient and outpatient care and death certificates and were confirmed by medical record review. RESULTS: 51 opioid-related overdoses were identified, including 6 deaths. Compared with patients receiving 1 to 20 mg/d of opioids (0.2% annual overdose rate), patients receiving 50 to 99 mg/d had a 3.7-fold increase in overdose risk (95% CI, 1.5 to 9.5) and a 0.7% annual overdose rate. Patients receiving 100 mg/d or more had an 8.9-fold increase in overdose risk (CI, 4.0 to 19.7) and a 1.8% annual overdose rate. LIMITATIONS: Increased overdose risk among patients receiving higher dose regimens may be due to confounding by patient differences and by use of opioids in ways not intended by prescribing physicians. The small number of overdoses in the study cohort is also a limitation. CONCLUSION: Patients receiving higher doses of prescribed opioids are at increased risk for overdose, which underscores the need for close supervision of these patients. PRIMARY FUNDING SOURCE: National Institute of Drug Abuse.
Authors: Dunn KM; Saunders KW; Rutter CM; Banta-Green CJ; Merrill JO; Sullivan MD; Weisner CM; Silverberg MJ; Campbell CI; Psaty BM; Von Korff M
Ann Intern Med. 2010 Jan 19;152(2):85-92.
Ethnic disparities in accessing treatment for depression and substance use disorders in an integrated health plan
OBJECTIVE: This study examined ethnic differences in accessing treatment for depression and substance use disorders (SUDs) among men and women in a large integrated health plan, and explored factors potentially contributing to health care disparities. METHODS: Participants were 22,543 members ages 20 to 65 who responded to health surveys in 2002 and 2005. Survey questions were linked to provider-assigned diagnoses, electronic medication, psychiatry, and chemical dependency program records. RESULTS: Among women diagnosed with depression, Latinas (p < .01) and Asian-Americans (p < .001) were less likely than Whites to fill an antidepressant prescription. Among men diagnosed with depression, African Americans (p < .01) were less likely than Whites to do so. Among women diagnosed with an SUD, African Americans (p < .05) were less likely than Whites to have one or more chemical dependency program visits. CONCLUSIONS: Results demonstrated ethnic differences in accessing depression and SUD treatment among patients diagnosed with these disorders, which persisted after controlling for education, income, having a regular health care provider and length of health plan enrollment. Findings highlight potential gender differences in ethnic disparities, lower antidepressant utilization among Asian Americans, and the effects of co-occurring disorders in accessing behavioral health care.
Authors: Satre DD; Campbell CI; Gordon NS; Weisner C
Int J Psychiatry Med. 2010;40(1):57-76.
Addiction treatment ultimatums and U.S. health reform: A case study
AIMS: Increased access to health care, including addiction treatment, has long been a goal of health reform in the U.S. An unanswered question is whether reform will change the way people get to addiction treatment; when treatment is easily accessible, do individuals self-refer, or do they still enter treatment via ultimatums, and if so, from which sources? To begin examining this, we used a single case study of a U.S. health plan that provides access similar to that called for in health reform. METHOD: Using a case study method of data from studies conducted in a large, private non-profit, integrated managed care health plan which includes addiction services, we examined the prevalence and source of ultimatums to enter treatment, and the characteristics of those receiving them. The plan is highly representative of changes to U.S. health care and other countries due to health reform. RESULTS: Many individuals entering addiction treatment had received an ultimatum stemming from employment, legal, medical, and family sources. Having more employment problems, an occupation with public safety concerns, being older, male, and ethnicity predicted an employment ultimatum. Higher legal problem severity predicted a legal ultimatum. More men (and younger people) had family ultimatums, and more women (and older people) had medical ultimatums. Being younger, male, married, having higher employment and family problem severity, and being drug or combined drug/alcohol dependent rather than dependent on alcohol-only predicted an ultimatum from one’s family. On the whole, an ultimatum from one source was not related to having one from another source. Those most likely to receive ultimatums from multiple sources were women, those separated/divorced, and those having higher psychiatric and legal problem severity. CONCLUSIONS: Even in an insured population with good access to addiction treatment, individuals often receive ultimatums to enter treatment rather than being self-referred. Understanding the treatment entry process, and how it is affected by health care systems, could benefit from international and other comparative research.
Authors: Weisner C; Hinman A; Lu Y; Chi FW; Mertens J
Nordisk Alkohol Nark. 2010;27(6):685-698.
Drinking patterns, gender and health III: Avoiding versus seeking health care
Inability to predict most health services use and costs using demographics and health status suggests that other factors affect use, including attitudes and practices that influence health and willingness to seek care. Alcohol consumption has generated interest because heavy, chronic consumption causes adverse health consequences, acute consumption increases injury, and moderate drinking is linked to better health while hazardous drinking and alcohol-related problems are stigmatized and may affect willingness to seek care. A stratified random sample of health-plan members completed a mail survey, yielding 7884 respondents (2995 male/4889 female). We linked survey data to 24 months of health-plan records to examine relationships between alcohol use, gender, health-related attitudes, practices, health, and service use. In-depth interviews with a stratified 150-respondent subsample explored individuals’ reasons for seeking or avoiding care. Quantitative results suggest health-related practices and attitudes predict subsequent service use. Consistent predictors of care were having quit drinking, current at-risk consumption, cigarette smoking, higher BMI, disliking visiting doctors, and strong religious/spiritual beliefs. Qualitative analyses suggest embarrassment and shame are strong motivators for avoiding care. Although models included numerous health, functional status, attitudinal and behavioral predictors, variance explained was similar to previous reports, suggesting more complex relationships than expected. Qualitative analyses suggest several potential predictive factors not typically measured in service-use studies: embarrassment and shame, fear, faith that the body will heal, expectations about likelihood of becoming seriously ill, disliking the care process, the need to understand health problems, and the effects of self-assessments of health-related functional limitations.
Authors: Green CA; Polen MR; Leo MC; Janoff SL; Anderson BM; Weisner CM; Perrin NA
Addict Res Theory. 2010 Jan 01;18(2):160-180.
Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis
OBJECTIVE: To investigate whether angiotensin receptor blockers protect against Alzheimer’s disease and dementia or reduce the progression of both diseases. DESIGN: Prospective cohort analysis. SETTING: Administrative database of the US Veteran Affairs, 2002-6. Population 819 491 predominantly male participants (98%) aged 65 or more with cardiovascular disease. MAIN OUTCOME MEASURES: Time to incident Alzheimer’s disease or dementia in three cohorts (angiotensin receptor blockers, lisinopril, and other cardiovascular drugs, the ‘cardiovascular comparator’) over a four year period (fiscal years 2003-6) using Cox proportional hazard models with adjustments for age, diabetes, stroke, and cardiovascular disease. Disease progression was the time to admission to a nursing home or death among participants with pre-existing Alzheimer’s disease or dementia. RESULTS: Hazard rates for incident dementia in the angiotensin receptor blocker group were 0.76 (95% confidence interval 0.69 to 0.84) compared with the cardiovascular comparator and 0.81 (0.73 to 0.90) compared with the lisinopril group. Compared with the cardiovascular comparator, angiotensin receptor blockers in patients with pre-existing Alzheimer’s disease were associated with a significantly lower risk of admission to a nursing home (0.51, 0.36 to 0.72) and death (0.83, 0.71 to 0.97). Angiotensin receptor blockers exhibited a dose-response as well as additive effects in combination with angiotensin converting enzyme inhibitors. This combination compared with angiotensin converting enzyme inhibitors alone was associated with a reduced risk of incident dementia (0.54, 0.51 to 0.57) and admission to a nursing home (0.33, 0.22 to 0.49). Minor differences were shown in mean systolic and diastolic blood pressures between the groups. Similar results were observed for Alzheimer’s disease. CONCLUSIONS: Angiotensin receptor blockers are associated with a significant reduction in the incidence and progression of Alzheimer’s disease and dementia compared with angiotensin converting enzyme inhibitors or other cardiovascular drugs in a predominantly male population.
Authors: Li NC; Lee A; Whitmer RA; Kivipelto M; Lawler E; Kazis LE; Wolozin B
BMJ. 2010 Jan 12;340:b5465.
Trends in long-term opioid therapy for chronic non-cancer pain
OBJECTIVE: To report trends and characteristics of long-term opioid use for non-cancer pain. METHODS: CONSORT (CONsortium to Study Opioid Risks and Trends) includes adult enrollees of two health plans serving over 1 per cent of the US population. Using automated data, we constructed episodes of opioid use between 1997 and 2005. We estimated age-sex standardized rates of opioid use episodes beginning in each year (incident) and on-going in each year (prevalent), and the per cent change in rates annualized (PCA) over the 9-year period. Long-term episodes were defined as > 90 days with 120+ days supply or 10+ opioid prescriptions in a given year. RESULTS: Over the study period, incident long-term use increased from 8.5 to 12.1 per 1000 at Group Health (GH) (6.0% PCA), and 6.3 to 8.6 per 1000 at Kaiser Permanente of Northern California (KPNC) (5.5% PCA). Prevalent long-term use doubled from 23.9 to 46.8 per 1000 at GH (8.5% PCA), and 21.5 to 39.2 per 1000 at KPNC (8.1% PCA). Non-Schedule II opioids were the most commonly used opioid among patients engaged in long-term opioid therapy, particularly at KPNC. Long-term use of Schedule II opioids also increased substantially at both health plans. Among prevalent long-term users in 2005, 28.6% at GH and 30.2% at KPNC were also regular users of sedative hypnotics. CONCLUSION: Long-term opioid therapy for non-cancer pain is increasingly prevalent, but the benefits and risks associated with such therapy are inadequately understood. Concurrent use of opioids and sedative-hypnotics was unexpectedly common and deserves further study.
Authors: Boudreau D; Von Korff M; Rutter CM; Saunders K; Ray GT; Sullivan MD; Campbell CI; Merrill JO; Silverberg MJ; Banta-Green C; Weisner C
Pharmacoepidemiol Drug Saf. 2009 Dec;18(12):1166-75.
Trends in long-term opioid therapy for noncancer pain among persons with a history of depression
OBJECTIVE: We report trends in long-term opioid use among patients with a history of depression from two large health plans. METHODS: Using claims data, age- and gender-adjusted rates for long-term (>90 days) opioid use episodes were calculated for 1997-2005, comparing those with and without a depression diagnosis in the prior 2 years. Opioid use characteristics were calculated for those with a long-term episode in 2005. RESULTS: Incident and prevalent long-term opioid use rates were three times higher in those with a history of depression. Prevalent long-term use per 1000 in patients with a history of depression increased from 69.8 to 125.9 at Group Health and from 84.3 to 117.5 at Kaiser Permanente of Northern California between 1997 and 2005. Those with a history of depression were more likely to receive a higher average daily dose, greater days supply, and Schedule II opioids than nondepressed persons. CONCLUSION: Persons with a history of depression are more likely to receive long-term opioid therapy for noncancer pain than those without a history of depression. Results suggest that long-term opioid therapy for noncancer pain is being prescribed to a different population in clinical practice than the clinical trial populations where opioid efficacy has been established.
Authors: Braden JB; Sullivan MD; Ray GT; Saunders K; Merrill J; Silverberg MJ; Rutter CM; Weisner C; Banta-Green C; Campbell C; Von Korff M
Gen Hosp Psychiatry. 2009 Nov-Dec;31(6):564-70. Epub 2009 Aug 27.
Trends in prescribed opioid therapy for non-cancer pain for individuals with prior substance use disorders
Long-term opioid therapy for non-cancer pain has increased. Caution is advised in prescribing for persons with substance use disorders, but little is known about actual health plan practices. This paper reports trends and characteristics of long-term opioid use in persons with non-cancer pain and a substance abuse history. Using health plan data (1997-2005), the study compared age-sex-standardized rates of incident, incident long-term and prevalent long-term prescription opioid use, and medication use profiles in those with and without substance use disorder histories. The CONsortium to Study Opioid Risks and Trends study included adult enrollees of two health plans, Kaiser Permanente of Northern California (KPNC) and Group Health Cooperative (GH) of Seattle, Washington. At KPNC (1999-2005), prevalence of long-term use increased from 11.6% to 17.0% for those with substance use disorder histories and from 2.6% to 3.9% for those without substance use disorder histories. Respective GH rates (1997-2005), increased from 7.6% to 18.6% and from 2.7% to 4.2%. Among persons with an opioid disorder, KPNC rates increased from 44.1% to 51.1%, and GH rates increased from 15.7% to 52.4%. Long-term opioid users with a prior substance abuse diagnosis received higher dosage levels, were more likely to use Schedule II and long-acting opioids, and were more often frequent users of sedative-hypnotic medications in addition to their opioid use. Since these patients are viewed as higher risk, the increased use of long-term opioid therapy suggests the importance of improved understanding of the benefits and risks of opioid therapy among persons with a history of substance abuse, and the need for more careful screening for substance abuse history than is the usual practice.
Authors: Weisner CM; Campbell CI; Ray GT; Saunders K; Merrill JO; Banta-Green C; Sullivan MD; Silverberg MJ; Mertens JR; Boudreau D; Von Korff M
Pain. 2009 Oct;145(3):287-93. Epub 2009 Jul 5.
Medical Conditions of Hazardous Drinkers and Drug Users in Primary Care Clinics in Cape Town, South Africa
Research has identified a wide range of health conditions related to alcohol and drug use in studies conducted primarily in developed countries and in populations with severe alcohol and drug problems. Little is known about medical conditions in those with less severe alcohol and drug use in developing countries. We used WHO AUDIT and ASSIST screeners to identify hazardous drinking or drug use in public health clinics in Cape Town, South Africa, and included questions about doctor-diagnosed medical conditions. Using logistic regression we examined the relationship of medical conditions to hazardous alcohol, drug and tobacco use. Those with hazardous substance use had higher prevalence of many health conditions including tuberculosis. Hepatitis B, migraine, chronic bronchitis, and liver cirrhosis. Optimal treatment for some medical conditions may include treatment of underlying hazardous substance use, particularly use of drugs other than alcohol. In these populations, access to substance use treatment is limited and even brief interventions or advice may be useful.
Authors: Mertens JR; Flisher AJ; Ward CL; Bresick GF; Sterling SA; Weisner CM
J Drug Issues. 2009 Oct;39(4).
Three-year chemical dependency and mental health treatment outcomes among adolescents: the role of continuing care
BACKGROUND: Few studies have examined the effects of treatment factors, including the types of services [chemical dependency (CD), psychiatric, or both], on long-term outcomes among adolescents following CD treatment, and whether receiving continuing care may contribute to better outcomes. This study examines the effect of the index CD and ongoing CD and psychiatric treatment episodes, 12-step participation, and individual characteristics such as CD and mental health (MH) severity and gender, age, and ethnicity, on 3-year CD and MH outcomes. METHODS: Participants were 296 adolescents aged 13 to 18 seeking treatment at 4 CD programs of a nonprofit, managed care, integrated health system. We surveyed participants at intake, 1 year, and 3 years, and examined survey and administrative data, and CD and psychiatric utilization. RESULTS: At 3 years, 29.7% of the sample reported total abstinence from both alcohol and drugs (excluding tobacco). Compared with girls, boys had only half the odds of being abstinent (OR = 0.46, p = 0.0204). Gender also predicted Externalizing severity at 3 years (coefficients 18.42 vs. 14.77, p < 0.01). CD treatment readmission in the second and third follow-up years was related to abstinence at 3 years (OR = 0.24, p = 0.0066 and OR = 3.33, p = 0.0207, respectively). Abstinence at 1 year predicted abstinence at 3 years (OR = 4.11, p < 0.0001). Those who were abstinent at 1 year also had better MH outcomes (both lower Internalizing and Externalizing scores) than those who were not (11.75 vs. 15.55, p = 0.0012 and 15.13 vs. 18.06, p = 0.0179, respectively). CONCLUSIONS: A CD treatment episode resulting in good 1-year CD outcomes may contribute significantly to both CD and MH outcomes 3 years later. The findings also point to the value of providing a continuing care model of treatment for adolescents.
Authors: Sterling S; Chi F; Campbell C; Weisner C
Alcohol Clin Exp Res. 2009 Aug;33(8):1417-29. Epub 2009 Apr 30.
Predicting risk of dementia in older adults: The late-life dementia risk index
OBJECTIVE: To develop a late-life dementia risk index that can accurately stratify older adults into those with a low, moderate, or high risk of developing dementia within 6 years. METHODS: Subjects were 3,375 participants in the Cardiovascular Health Cognition Study without evidence of dementia at baseline. We used logistic regression to identify those factors most predictive of developing incident dementia within 6 years and developed a point system based on the logistic regression coefficients. RESULTS: Subjects had a mean age of 76 years at baseline; 59% were women and 15% were African American. Fourteen percent (n = 480) developed dementia within 6 years. The final late-life dementia risk index included older age (1-2 points), poor cognitive test performance (2-4 points), body mass index <18.5 (2 points), > or =1 apolipoprotein E epsilon4 alleles (1 point), cerebral MRI findings of white matter disease (1 point) or ventricular enlargement (1 point), internal carotid artery thickening on ultrasound (1 point), history of bypass surgery (1 point), slow physical performance (1 point), and lack of alcohol consumption (1 point) (c statistic, 0.81; 95% confidence interval, 0.79-0.83). Four percent of subjects with low scores developed dementia over 6 years compared with 23% of subjects with moderate scores and 56% of subjects with high scores. CONCLUSIONS: The late-life dementia risk index accurately stratified older adults into those with low, moderate, and high risk of developing dementia. This tool could be used in clinical or research settings to target prevention and intervention strategies toward high-risk individuals.
Authors: Barnes DE; Covinsky KE; Whitmer RA; Kuller LH; Lopez OL; Yaffe K
Neurology. 2009 Jul 21;73(3):173-9. Epub 2009 May 13.
Organizational determinants of outpatient substance abuse treatment duration in women
Longer treatment duration has consistently been related to improved substance use outcomes. This study examined how tailored women’s programming and organizational characteristics were related to duration in outpatient substance abuse treatment in women. Data were from two waves of a national outpatient substance abuse treatment unit survey (n = 571 in 1999/2000, n = 566 in 2005). Analyses were conducted separately for methadone and nonmethadone programs. Negative binomial regressions tested associations between organizational determinants, tailored programming, and women’s treatment duration. Of the tailored programming services, childcare was significantly related to longer duration in the nonmethadone programs, but few other organizational factors were. Tailored programming was not associated to treatment duration in methadone programs, but ownership, affiliation, and accreditation were related to longer duration. Study findings suggest evidence for how external relationships related to resources, treatment constraints, and legitimacy may influence women’s treatment duration. Methadone programs may be more vulnerable to external influences.
Authors: Campbell CI; Alexander JA; Lemak CH
J Subst Abuse Treat. 2009 Jul;37(1):64-72. Epub 2008 Nov 26.
NSAID exposure and risk of Alzheimer disease: is timing everything?
Authors: Bennett DA; Whitmer RA
Neurology. 2009 Jun 2;72(22):1884-5. Epub 2009 Apr 22.
Prenatal exposure to maternal infection and executive dysfunction in adult schizophrenia
OBJECTIVE: Executive dysfunction is one of the most prominent and functionally important cognitive deficits in schizophrenia. Although strong associations have been identified between executive impairments and structural and functional prefrontal cortical deficits, the etiological factors that contribute to disruption of this important cognitive domain remain unclear. Increasing evidence suggests that schizophrenia has a neurodevelopmental etiology, and several prenatal infections have been associated with risk of this disorder. The authors examined whether prenatal infection is associated with executive dysfunction in patients with schizophrenia. METHOD: The authors assessed the relationship between serologically documented prenatal exposure to influenza and toxoplasmosis and performance on the Wisconsin Card Sorting Test and the Trail Making Test, part B (Trails B), as well as other measures of executive function, in 26 patients with schizophrenia from a large and well-characterized birth cohort. RESULTS: Patients who were exposed to infection in utero committed significantly more total errors on the Wisconsin Card Sorting Test and took significantly more time to complete the Trails B than unexposed patients. Exposed patients also exhibited deficits on figural fluency, letter-number sequencing, and backward digit span. CONCLUSIONS: Prenatal infections previously associated with schizophrenia are related to impaired performance on the Wisconsin Card Sorting Test and Trails B. The pattern of results suggests that cognitive set-shifting ability may be particularly vulnerable to this gestational exposure. Further work is needed to elucidate the specificity of prenatal infection to these executive function measures and to examine correlates with neuroanatomic and neurophysiologic anomalies.
Authors: Brown AS; Vinogradov S; Kremen WS; Poole JH; Deicken RF; Penner JD; McKeague IW; Kochetkova A; Kern D; Schaefer CA
Am J Psychiatry. 2009 Jun;166(6):683-90. Epub 2009 Apr 15.
Twelve-Step affiliation and 3-year substance use outcomes among adolescents: social support and religious service attendance as potential mediators
AIMS: Twelve-Step affiliation among adolescents is little understood. We examined 12-Step affiliation and its association with substance use outcomes 3 years post-treatment intake among adolescents seeking chemical dependency (CD) treatment in a private, managed-care health plan. We also examined the effects of social support and religious service attendance on the relationship. DESIGN: We analyzed data for 357 adolescents, aged 13-18, who entered treatment at four Kaiser Permanente Northern California CD programs between March 2000 and May 2002 and completed both baseline and 3-year follow-up interviews. MEASURES: Measures at follow-up included alcohol and drug use, 12-Step affiliation, social support and frequency of religious service attendance. FINDINGS: At 3 years, 68 adolescents (19%) reported attending any 12-Step meetings, and 49 (14%) reported involvement in at least one of seven 12-Step activities, in the previous 6 months. Multivariate logistic regression analyses indicated that after controlling individual and treatment factors, 12-Step attendance at 1 year was marginally significant, while 12-Step attendance at 3 years was associated with both alcohol and drug abstinence at 3 years [odds ratio (OR) 2.58, P < 0.05 and OR 2.53, P < 0.05, respectively]. Similarly, 12-Step activity involvement was associated significantly with 30-day alcohol and drug abstinence. There are possible mediating effects of social support and religious service attendance on the relationship between post-treatment 12-Step affiliation and 3-year outcomes. CONCLUSIONS: The findings suggest the importance of 12-Step affiliation in maintaining long-term recovery, and help to understand the mechanism through which it works among adolescents.
Authors: Chi FW; Kaskutas LA; Sterling S; Campbell CI; Weisner C
Addiction. 2009 Jun;104(6):927-39. Epub 2009 Mar 13.
A randomized trial comparing acupuncture, simulated acupuncture, and usual care for chronic low back pain
BACKGROUND: Acupuncture is a popular complementary and alternative treatment for chronic back pain. Recent European trials suggest similar short-term benefits from real and sham acupuncture needling. This trial addresses the importance of needle placement and skin penetration in eliciting acupuncture effects for patients with chronic low back pain. METHODS: A total of 638 adults with chronic mechanical low back pain were randomized to individualized acupuncture, standardized acupuncture, simulated acupuncture, or usual care. Ten treatments were provided over 7 weeks by experienced acupuncturists. The primary outcomes were back-related dysfunction (Roland-Morris Disability Questionnaire score; range, 0-23) and symptom bothersomeness (0-10 scale). Outcomes were assessed at baseline and after 8, 26, and 52 weeks. RESULTS: At 8 weeks, mean dysfunction scores for the individualized, standardized, and simulated acupuncture groups improved by 4.4, 4.5, and 4.4 points, respectively, compared with 2.1 points for those receiving usual care (P < .001). Participants receiving real or simulated acupuncture were more likely than those receiving usual care to experience clinically meaningful improvements on the dysfunction scale (60% vs 39%; P < .001). Symptoms improved by 1.6 to 1.9 points in the treatment groups compared with 0.7 points in the usual care group (P < .001). After 1 year, participants in the treatment groups were more likely than those receiving usual care to experience clinically meaningful improvements in dysfunction (59% to 65% vs 50%, respectively; P = .02) but not in symptoms (P > .05). CONCLUSIONS: Although acupuncture was found effective for chronic low back pain, tailoring needling sites to each patient and penetration of the skin appear to be unimportant in eliciting therapeutic benefits. These findings raise questions about acupuncture’s purported mechanisms of action. It remains unclear whether acupuncture or our simulated method of acupuncture provide physiologically important stimulation or represent placebo or nonspecific effects.
Authors: Cherkin DC; Avins AL; Deyo RA; et al.
Arch Intern Med. 2009 May 11;169(9):858-66.
Association between prenatal tobacco exposure and outcome of neonates born to opioid-maintained mothers. Implications for treatment.
BACKGROUND: Prenatal nicotine exposure is associated with increased neonatal mortality, low birth weight, and smaller head circumference. Opioid-dependent pregnant women show a particularly high prevalence of tobacco smoking and are at greater risk for additional adverse events. However, little is known about the impact of tobacco smoking on opioid-maintained pregnant women and neonatal outcomes.PATIENTS AND METHODS: This study examined the effect of cigarette smoking on 139 opioid-maintained pregnant women and their neonates. Forty-five percent of the participants were maintained on slow-release oral morphine (SROM), 39% received methadone maintenance, and 16% received buprenorphine. Participants were divided into two groups: (1) women who reported a low cigarette consumption of < or =10 cigarettes/day (56.8%) and (2) those reporting heavy consumption of > or =20 cigarettes/day (43.2%). Neonatal outcome measures were assessed, and a standardized Finnegan score was applied to determine the neonatal abstinence syndrome (NAS).RESULTS: Fifty-two percent of the newborns did not require treatment for NAS (54% of neonates born to methadone-maintained mothers, 30% born to SROM-maintained mothers, and 95% born to buprenorphine-maintained mothers; p < 0.001). Heavy cigarette consumption was associated with significantly lower neonatal birth weight (p < 0.001), smaller birth length (p = 0.017) as well as with the severity of NAS (p = 0.03). With regard to concomitant consumption of opioids (p = 0.54), cocaine (p = 0.25), amphetamines (p = 0.90) or benzodiazepines (p = 0.09), no significant differences between heavy or low nicotine consumption were noted.CONCLUSION: Heavy tobacco smoking in opioid-maintained pregnant women is associated with adverse medical and developmental consequences for the newborn. Future treatment programs for this target group should focus on an individualized approach to opioid maintenance therapy in addition to offering specially tailored counseling for smoking cessation.
Authors: Winklbaur, Bernadette B; Baewert, Andjela A; Jagsch, Reinhold R; Rohrmeister, Klaudia K; Metz, Verena V; Aeschbach Jachmann, Crispa C; Thau, Kenneth K; Fischer, Gabriele G
European addiction research. 2009 Jul 25;15(3):150-6. Epub 2009-05-07.
Substance use, symptom, and employment outcomes of persons with a workplace mandate for chemical dependency treatment
OBJECTIVE: This study examined the role of workplace mandates to chemical dependency treatment in treatment adherence, alcohol and drug abstinence, severity of employment problems, and severity of psychiatric problems. METHODS: The sample included 448 employed members of a private, nonprofit U.S. managed care health plan who entered chemical dependency treatment with a workplace mandate (N=75) or without one (N=373); 405 of these individuals were followed up at one year (N=70 and N=335, respectively), and 362 participated in a five-year follow up (N=60 and N=302, respectively). Propensity scores predicting receipt of a workplace mandate were calculated. Logistic regression and ordinary least-squares regression were used to predict length of stay in chemical dependency treatment, alcohol and drug abstinence, and psychiatric and employment problem severity at one and five years. RESULTS: Overall, participants with a workplace mandate had one- and five-year outcomes similar to those without such a mandate. Having a workplace mandate also predicted longer treatment stays and improvement in employment problems. When other factors related to outcomes were controlled for, having a workplace mandate predicted abstinence at one year, with length of stay as a mediating variable. CONCLUSIONS: Workplace mandates can be an effective mechanism for improving work performance and other outcomes. Study participants who had a workplace mandate were more likely than those who did not have a workplace mandate to be abstinent at follow-up, and they did as well in treatment, both short and long term. Pressure from the workplace likely gets people to treatment earlier and provides incentives for treatment adherence.
Authors: Weisner C; Lu Y; Hinman A; Monahan J; Bonnie RJ; Moore CD; Chi FW; Appelbaum PS
Psychiatr Serv. 2009 May;60(5):646-54.
Prenatal infection and cavum septum pellucidum in adult schizophrenia
Increased length of the cavum septum pellucidum (CSP) and in utero infection are each associated with increased risk of schizophrenia. Hence, we examined whether prenatal infections are related to CSP length in schizophrenia patients. In a well-characterized birth cohort, in utero infection was assessed using serologic biomarkers or physician diagnoses. Magnetic resonance images were acquired, and CSP length was quantified by a standard protocol. In utero infection was associated with increased CSP length in exposed schizophrenia cases compared to unexposed cases, suggesting that prenatal infection plays a role in a neurodevelopmental morphologic anomaly that has been related previously to schizophrenia.
Authors: Brown AS; Deicken RF; Vinogradov S; Kremen WS; Poole JH; Penner JD; Kochetkova A; Kern D; Schaefer CA
Schizophr Res. 2009 Mar;108(1-3):285-7. Epub 2009 Jan 8.
Youth exposed to violence: stability, co-occurrence, and context.
With considerable literature establishing how separate types of violence disrupt the lives of children, there is emerging interest in examining violence across multiple interpersonal domains. This article examines four commonly occurring and frequently researched domains of violence exposure: marital physical aggression, mother-to-youth aggression, father-to-youth aggression, and community violence. A community-based sample of 103 parents and youth provided three waves of data at annual intervals beginning when the youth were aged 9-10. We explored stability of exposure, co-occurrence across different types of violence exposure, and associations with co-occurring risk factors. Approximately 30-45% of youth reported intermittent exposure over the 3 years. In addition to overlap among types of violence exposure within the family, we found overlap between parent-to-youth aggression and community violence, an association that was exacerbated in families where fathers reported high levels of global distress symptoms. Mother-to-youth, father-to-youth, and community violence related to youth behavior problems beyond the contextual risk factors of low income, stressful life events, and parents’ global distress symptoms. These results highlight the importance of examining violence longitudinally, across multiple types, and with attention to contextual factors.
Authors: Margolin G; Vickerman KA; Ramos MC; Serrano SD; Gordis EB; Iturralde E; Oliver PH; Spies LA
Clin Child Fam Psychol Rev. 2009 Mar;12(1):39-54. doi: 10.1007/s10567-009-0040-9.
Relationships among depression, chronic pain, chronic disabling pain, and medical costs
OBJECTIVE: Although evidence suggests that patients with depression use more medical services than those without depression, few studies have examined whether specific subgroups of patients with depression have higher utilization than others. The study compared costs for general medical care with and without psychiatric care for patients with major depression and disabling chronic pain (reference group) with costs for five other groups: those with depression and nondisabling chronic pain, those with major depressive disorder alone, those with no depression who had disabling chronic pain, those with depression who had chronic pain that was not disabling, and those who had neither pain nor depression. Costs for the group with major depressive disorder alone were compared to costs for the three groups without depression. METHODS: A questionnaire assessing major depressive disorder, chronic pain, and pain-related disability was mailed to a random sample of Kaiser Permanente patients who visited a primary care clinic. A total of 5,808 patients responded (54% participation rate). Costs for a two-year period were obtained from Kaiser Permanente’s Cost Management Information System. Analyses were adjusted for presence of any of four major chronic medical illnesses. RESULTS: Total costs for patients in the reference group were significantly higher than costs for the other five subgroups. Regression analyses indicated that continuous measures of severity of pain and severity of depression were associated with increased costs, but no statistically significant interaction of depression and pain on total cost was observed. CONCLUSIONS: Patients with major depressive disorder and comorbid disabling chronic pain had higher medical service costs than other groups of patients with and without depression. However, findings suggest that the increases in cost from having both pain and depression are additive and not multiplicative.
Authors: Arnow BA; Blasey CM; Lee J; Fireman B; Hunkeler EM; Dea R; Robinson R; Hayward C
Psychiatr Serv. 2009 Mar;60(3):344-50.
Self-initiated tobacco cessation and substance use outcomes among adolescents entering substance use treatment in a managed care organization
PURPOSE: Adolescents with substance use (SU) problems have high rates of tobacco use, yet SU treatment has historically ignored treatment for tobacco use. Barriers to such efforts include the belief that tobacco cessation could compromise other SU abstinence. This study examines self-initiated tobacco cessation and 12-month alcohol and drug abstinence in adolescents entering SU treatment in a private, managed care organization. RESULTS: Self-initiated tobacco cessation at 6 months, and at both 6 and 12 months, were related to higher odds of drug abstinence but not alcohol abstinence. CONCLUSION: Self-initiated tobacco cessation was not related to poor SU outcomes, and may be important to maintaining drug abstinence. Implementing tobacco cessation efforts in SU treatment can be challenging, but comprised SU outcomes may not be a barrier. The positive associations for drug abstinence and lack of associations for alcohol abstinence could be due to differences in motivation, medical conditions, or to the illicit nature of drug use. Tobacco use has serious long-term health consequences, and tobacco cessation efforts in adolescent SU treatment programs need further research.
Authors: Campbell CI; Chi F; Sterling S; Kohn C; Weisner C
Addict Behav. 2009 Feb;34(2):171-9. Epub 2008 Oct 10.
Family members of people with alcohol or drug dependence: health problems and medical cost compared to family members of people with diabetes and asthma
AIMS: To compare the medical costs and prevalence of health conditions of family members of people with an alcohol or drug dependence (AODD) diagnosis to family members of people with diabetes and asthma. SETTING: Kaiser Permanente of Northern California (KPNC). PARTICIPANTS: Family members of people diagnosed with AODD between 2002 and 2005, and matched samples of family members of people diagnosed with diabetes and asthma. MEASUREMENTS: Logistic regression was used to determine whether the family members of people with AODD were more likely to be diagnosed with medical conditions than family members of people with diabetes or asthma. Multivariate models were used to compare health services cost and utilization of AODD family members and diabetes and asthma family members. Analyses were for the year before, and 2 years following, initial diagnosis of the index person. FINDINGS: In the year before initial diagnosis of the index person, AODD family members were more likely to be diagnosed with substance use disorders, depression and trauma than diabetes or asthma family members. AODD family members had higher total health-care costs than diabetes family members in the year following, and the second year following, the index date ($217 and $293, respectively). AODD family members had higher total health-care costs than asthma family members in the year before, and second year following, the index date ($104 and $269, respectively). CONCLUSIONS: AODD family members have unique patterns of health conditions compared to the diabetes and asthma family members and have similar, or higher, health-care cost and utilization.
Authors: Ray GT; Mertens JR; Weisner C
Addiction. 2009 Feb;104(2):203-14.
Midlife serum cholesterol and increased risk of Alzheimer’s and vascular dementia three decades later
AIMS: To investigate midlife cholesterol in relation to Alzheimer’s disease (AD) and vascular dementia (VaD) in a large multiethnic cohort of women and men. METHODS: The Kaiser Permanente Northern California Medical Group (healthcare delivery organization) formed the database for this study. The 9,844 participants underwent detailed health evaluations during 1964-1973 at ages 40-45 years; they were still members of the health plan in 1994. AD and VaD were ascertained by medical records between 1 January 1994 and 1 June 2007. Cox proportional hazards models – adjusted for age, education, race/ethnic group, sex, midlife diabetes, hypertension, BMI and late-life stroke – were conducted. RESULTS: In total, 469 participants had AD and 127 had VaD. With desirable cholesterol levels (<200 mg/dl) as a reference, hazard ratios (HR) and 95% CI for AD were 1.23 (0.97-1.55) and 1.57 (1.23-2.01) for borderline (200-239 mg/dl) and high cholesterol (>or=240 mg/dl), respectively. HR and 95% CI for VaD were 1.50 (1.01-2.23) for borderline and 1.26 (0.82-1.96) for high cholesterol. Further analyses for AD (cholesterol quartiles, 1st quartile reference) indicated that cholesterol levels >220 mg/dl were a significant risk factor: HR were 1.31 (1.01-1.71; 3rd quartile, 221-248 mg/dl) and 1.58 (1.22-2.06; 4th quartile, 249-500 mg/dl). CONCLUSION: Midlife serum total cholesterol was associated with an increased risk of AD and VaD. Even moderately elevated cholesterol increased dementia risk. Dementia risk factors need to be addressed as early as midlife, before underlying disease(s) or symptoms appear.
Authors: Solomon A; Kivipelto M; Wolozin B; Zhou J; Whitmer RA
Dement Geriatr Cogn Disord. 2009;28(1):75-80. Epub 2009 Aug 4.
Comparing recruitment strategies in a study of acupuncture for chronic back pain
BACKGROUND: Meeting recruitment goals is challenging for many clinical trials conducted in primary care populations. Little is known about how the use of different recruitment strategies affects the types of individuals choosing to participate or the conclusions of the study. METHODS: A secondary analysis was performed using data from participants recruited to a clinical trial evaluating acupuncture for chronic back pain among primary care patients in a large integrated health care organization. We used two recruitment methods: mailed letters of invitation and an advertisement in the health plan’s magazine. For these two recruitment methods, we compared recruitment success (% randomized, treatment completers, drop outs and losses to follow-up), participant characteristics, and primary clinical outcomes. A linear regression model was used to test for interaction between treatment group and recruitment method. RESULTS: Participants recruited via mailed letters closely resembled those responding to the advertisement in terms of demographic characteristics, most aspects of their back pain history and current episode and beliefs and expectations about acupuncture. No interaction between method of recruitment and treatment group was seen, suggesting that study outcomes were not affected by recruitment strategy. CONCLUSION: In this trial, the two recruitment strategies yielded similar estimates of treatment effectiveness. However, because this finding may not apply to other recruitment strategies or trial circumstances, trials employing multiple recruitment strategies should evaluate the effect of recruitment strategy on outcome. TRIAL REGISTRATION: Clinical Trials.gov NCT00065585.
Authors: Sherman KJ; Hawkes RJ; Ichikawa L; Cherkin DC; Deyo RA; Avins AL; Khalsa PS
BMC Med Res Methodol. 2009 Oct 27;9:69.
Characteristics of patients with chronic back pain who benefit from acupuncture
BACKGROUND: Although many clinicians believe there are clinically important subgroups of persons with ‘non-specific’ low back pain, such subgroups have not yet been clearly identified. As part of a large trial evaluating acupuncture for chronic low back pain, we sought to identify subgroups of participants that were particularly responsive to acupuncture. METHODS: We performed a secondary analysis of data for the 638 participants in our clinical trial comparing different types of acupuncture to usual care to identify baseline characteristics that predicted responses to individualized, standardized, or simulated acupuncture treatments. After identifying factors that predicted improvements in back-related function or symptoms, we determined if these factors were more likely to predict improvement for those receiving the acupuncture treatments than for those receiving usual care. This was accomplished by testing for an interaction between the prognostic factors and treatment group in four models: functional outcomes (measured by the Roland-Morris Disability Scale) at 8 and 52 weeks post-randomization and symptom outcomes (measured with a numerical rating scale) at 8 and 52 weeks. RESULTS: Overall, the strongest predictors of improvement in back function and symptoms were higher baseline levels of these measures, receipt of an acupuncture treatment, and non-use of narcotic analgesics. Benefit from acupuncture compared to usual care was greater with worse pre-treatment levels of back dysfunction (interaction p < 0.004 for the functional outcome, Roland Morris Disability Scale at 8 weeks). No other consistent interactions were observed. CONCLUSION: This secondary analysis found little evidence for the existence of subgroups of patients with chronic back pain that would be especially likely to benefit from acupuncture. However, persons with chronic low back pain who had more severe baseline dysfunction had the most short-term benefit from acupuncture.
Authors: Sherman KJ; Cherkin DC; Ichikawa L; Avins AL; Barlow WE; Khalsa PS; Deyo RA
BMC Musculoskelet Disord. 2009 Sep 21;10:114.
Health Services Research for Drug and Alcohol Treatment and Prevention
Health services research is a multidisciplinary field that examines ways to organize, manage, finance, and deliver high-quality care. This specialty within substance abuse research developed from policy analyses and needs assessments that shaped federal policy and promoted system development in the 1970s. After the authorization of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA), patient information systems supported studies of treatment processes and outcomes. Health services research grew substantially in the 1990s when NIAAA and NIDA moved into the National Institutes of Health and legislation allocated 15% of their research portfolio to services research. The next decade will emphasize research on quality of care, adoption and use of evidence-based practices (including medication), financing reforms and integration of substance abuse treatment with primary care and mental health services.
Authors: McCarty D; Roman PM; Sorensen J; Weisner C
J Drug Issues. 2009 Jan;39(1):197-208.
The role of medical conditions and primary care services in 5-year substance use outcomes among chemical dependency treatment patients
INTRODUCTION: Health problems are prevalent in chemical dependency (CD) treatment populations, and often precede reductions in substance use among untreated populations. Few studies have examined whether medical problems predict better long-term outcomes in treated individuals, or how primary care utilization and CD/primary care service integration affects long-term outcomes among those with health problems. METHOD: In a sample of 598 CD patients in a private health plan, logistic regression models examined whether substance abuse-related medical conditions (SAMCs), integrated medical and CD care, and on-going primary care predicted remission of CD problems at 5 years. RESULTS: Those with SAMCs were no more likely than others to be remitted at 5 years except among young adults and those with medical, but not psychiatric SAMCs. Higher levels of medical problem severity at intake and receiving integrated CD and primary care in the index treatment episode predicted remission in the full sample and among those with SAMCs. Among those with SAMCs, individuals with ongoing medical care – 2-10 primary care visits – in the 5 years following intake were more likely to be remitted at 5 years than those with fewer visits. CONCLUSIONS: This study highlights the potentially important role of medical services in the long-term treatment of CD disorders. CD treatment may benefit from a disease management approach similar to that recommended for other chronic medical problems: specialty care when the condition is severe followed by services in primary care when the condition is stabilized.
Authors: Mertens JR; Flisher AJ; Satre DD; Weisner CM
Drug Alcohol Depend. 2008 Nov 1;98(1-2):45-53. Epub 2008 Jun 20.
Insulin-like growth factors, their binding proteins, and prostate cancer risk: analysis of individual patient data from 12 prospective studies
BACKGROUND: Some, but not all, published results have shown an association between circulating blood levels of some insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) and the subsequent risk for prostate cancer. PURPOSE: To assess the association between levels of IGFs and IGFBPs and the subsequent risk for prostate cancer. DATA SOURCES: Studies identified in PubMed, Web of Science, and CancerLit. STUDY SELECTION: The principal investigators of all studies that published data on circulating concentrations of sex steroids, IGFs, or IGFBPs and prostate cancer risk using prospectively collected blood samples were invited to collaborate. DATA EXTRACTION: Investigators provided individual participant data on circulating concentrations of IGF-I, IGF-II, IGFBP-II, and IGFBP-III and participant characteristics to a central data set in Oxford, United Kingdom. DATA SYNTHESIS: The study included data on 3700 men with prostate cancer and 5200 control participants. On average, case patients were 61.5 years of age at blood collection and received a diagnosis of prostate cancer 5 years after blood collection. The greater the serum IGF-I concentration, the greater the subsequent risk for prostate cancer (odds ratio [OR] in the highest vs. lowest quintile, 1.38 [95% CI, 1.19 to 1.60]; P < 0.001 for trend). Neither IGF-II nor IGFBP-II concentrations were associated with prostate cancer risk, but statistical power was limited. Insulin-like growth factor I and IGFBP-III were correlated (r = 0.58), and although IGFBP-III concentration seemed to be associated with prostate cancer risk, this was secondary to its association with IGF-I levels. Insulin-like growth factor I concentrations seemed to be more positively associated with low-grade than high-grade disease; otherwise, the association between IGFs and IGFBPs and prostate cancer risk had no statistically significant heterogeneity related to stage or grade of disease, time between blood collection and diagnosis, age and year of diagnosis, prostate-specific antigen level at recruitment, body mass index, smoking, or alcohol intake. LIMITATIONS: Insulin-like growth factor concentrations were measured in only 1 sample for each participant, and the laboratory methods to measure IGFs differed in each study. Not all patients had disease stage or grade information, and the diagnosis of prostate cancer may differ among the studies. CONCLUSION: High circulating IGF-I concentrations are associated with a moderately increased risk for prostate cancer.
Authors: Roddam AW; Schaefer C; Quesenberry CP Jr; Galan P; et al.
Ann Intern Med. 2008 Oct 7;149(7):461-71, W83-8.
Maternal iron deficiency and the risk of schizophrenia in offspring
CONTEXT: Iron is essential for brain development and functioning. Emerging evidence suggests that iron deficiency in early life leads to long-lasting neural and behavioral deficits in infants and children. Adopting a life course perspective, we examined the effects of early iron deficiency on the risk of schizophrenia in adulthood. OBJECTIVE: To determine whether maternal iron deficiency, assessed by maternal hemoglobin concentration during pregnancy, increases the susceptibility to schizophrenia spectrum disorders (SSDs) among offspring. DESIGN: Data were drawn from a population-based cohort born from 1959 through 1967 and followed up for development of SSD from 1981 through 1997. PARTICIPANTS: Of 6872 offspring for whom maternal hemoglobin concentration was available, 57 had SSDs (0.8%) and 6815 did not (99.2%). MAIN OUTCOME MEASURE: Prospectively assayed, the mean value of maternal hemoglobin concentration was the primary exposure. Hemoglobin concentration was analyzed as a continuous and a categorical variable. RESULTS: A mean maternal hemoglobin concentration of 10.0 g/dL or less was associated with a nearly 4-fold statistically significant increased rate of SSDs (adjusted rate ratio, 3.73; 95% confidence interval, 1.41-9.81; P = .008) compared with a mean maternal hemoglobin concentration of 12.0 g/dL or higher, adjusting for maternal education and ethnicity. For every 1-g/dL increase in mean maternal hemoglobin concentration, a 27% decrease in the rate of SSDs was observed (95% confidence interval, 0.55-0.96; P = .02). CONCLUSIONS: The findings suggest that maternal iron deficiency may be a risk factor for SSDs among offspring. Given that this hypothesis offers the potential for reducing the risk for SSDs, further investigation in independent samples is warranted.
Authors: Insel BJ; Schaefer CA; McKeague IW; Susser ES; Brown AS
Arch Gen Psychiatry. 2008 Oct;65(10):1136-44.
Central obesity and increased risk of dementia more than three decades later
BACKGROUND: Numerous reports show that a centralized distribution of adiposity is a more dangerous risk factor for cardiovascular disease and diabetes than total body obesity. No studies have evaluated whether the same pattern exists with dementia. The objective was to evaluate the association between midlife central obesity and risk of dementia three decades later. METHODS: A longitudinal analysis was conducted of 6,583 members of Kaiser Permanente of Northern California who had their sagittal abdominal diameter (SAD) measured in 1964 to 1973. Diagnoses of dementia were from medical records an average of 36 years later, January 1, 1994, to June 16, 2006. Cox proportional hazard models adjusted for age, sex, race, education, marital status, diabetes, hypertension, hyperlipidemia, stroke, heart disease, and medical utilization were conducted. RESULTS: A total of 1,049 participants (15.9%) were diagnosed with dementia. Compared with those in the lowest quintile of SAD, those in the highest had nearly a threefold increased risk of dementia (hazard ratio, 2.72; 95% CI, 2.33-3.33), and this was only mildly attenuated after adding body mass index (BMI) to the model (hazard ratio, 1.92; 95% CI, 1.58-2.35). Those with high SAD (>25 cm) and normal BMI had an increased risk (hazard ratio, 1.89; 95% CI, 0.98-3.81) vs those with low SAD (<25 cm) and normal BMI (18.5-24.9 kg/m(2)), whereas those both obese (BMI >30 kg/m(2)) and with high SAD had the highest risk of dementia (HR, 3.60; 95% CI, 2.85-4.55). CONCLUSIONS: Central obesity in midlife increases risk of dementia independent of diabetes and cardiovascular comorbidities. Fifty percent of adults have central obesity; therefore, mechanisms linking central obesity to dementia need to be unveiled.
Authors: Whitmer RA; Gustafson DR; Barrett-Connor E; Haan MN; Gunderson EP; Yaffe K
Neurology. 2008 Sep 30;71(14):1057-64. Epub 2008 Mar 26.
De facto long-term opioid therapy for noncancer pain
OBJECTIVES: This paper describes characteristics of opioid use episodes for noncancer pain and defines thresholds for de facto long-term opioid therapy. METHODS: CONSORT (CONsortium to Study Opioid Risks and Trends) includes adult members of 2 health plans serving over 1% of the US population. Opioid use episodes beginning in the years 1997 to 2005 were classified as acute, episodic, long-term/lower dose, or long-term/higher dose. RESULTS: On the basis of evaluation of the likelihood of opioid use continuing, long-term opioid therapy was defined by episodes lasting longer than 90 days with 10+ opioid prescriptions or 120+ days supply of opioids dispensed. Long-term/higher dose episodes (<1.5% of all opioid use episodes) were characterized by daily or near daily use, a mean duration of about 1000 days, and an average daily dose of about 55 mg. They accounted for more than half the total morphine equivalents dispensed from the years 1997 to 2006. Short-acting, non-Schedule II opioids (eg, hydrocodone with acetaminophen) were, by far, the most commonly prescribed medications for acute, episodic, and long-term episodes. Long-acting (sustained-release) opioids were the predominately prescribed medication in a minority of long-term episodes (6% to 12%). DISCUSSION: Long-term opioid therapy was characterized by the diversity in medications prescribed, dosage levels, and frequency of use. The proposed threshold for long-term opioid therapy provides a checkpoint for physicians to review whether an explicit decision to sustain opioid therapy has been reached, and to ensure that a documented treatment plan and provisions for monitoring medication use and patient outcomes are in place.
Authors: Korff MV; Saunders K; Thomas Ray G; Boudreau D; Campbell C; Merrill J; Sullivan MD; Rutter CM; Silverberg MJ; Banta-Green C; Weisner C
Clin J Pain. 2008 Jul-Aug;24(6):521-7.
A detailed safety assessment of a saw palmetto extract
BACKGROUND: Saw palmetto is commonly used by men for lower-urinary tract symptoms. Despite its widespread use, very little is known about the potential toxicity of this dietary supplement. METHODS: The Saw palmetto for Treatment of Enlarged Prostates (STEP) study was a randomized clinical trial performed among 225 men with moderate-to-severe symptoms of benign prostatic hyperplasia, comparing a standardized extract of the saw palmetto berry (160 mg twice daily) with a placebo over a 1-year period. As part of this study, detailed data were collected on serious and non-serious adverse events, sexual functioning, and laboratory tests of blood and urine. Between-group differences were assessed with mixed-effects regression models. RESULTS: There were no significant differences observed between the saw palmetto and placebo-allocated participants in the risk of suffering at least one serious adverse event (5.4% vs. 9.7%, respectively; p=0.31) or non-serious symptomatic adverse event (34.8% vs. 30.1%, p=0.48). There were few significant between-group differences in sexual functioning or for most laboratory analyses, with only small differences observed in changes over time in total bilirubin (p=0.001), potassium (p=0.03), and the incidence of glycosuria (0% in the saw palmetto group vs. 3.7% in the placebo group, p=0.05). CONCLUSIONS: Despite careful assessment, no evidence for serious toxicity of saw palmetto was observed in this clinical trial. Given the sample size and length of this study, however, these data do not rule out potential rare adverse effects associated with the use of saw palmetto.
Authors: Avins AL; Bent S; Staccone S; Badua E; Padula A; Goldberg H; Neuhaus J; Hudes E; Shinohara K; Kane C
Complement Ther Med. 2008 Jun;16(3):147-54. Epub 2008 Feb 20.
Congenital anomalies and early functional impairments in a prospective birth cohort: risk of schizophrenia-spectrum disorder in adulthood
BACKGROUND: Adversities operating over intrauterine life have been associated with risk of schizophrenia, but the biology of resultant developmental perturbation is poorly understood. AIMS: To examine the relationship of congenital anomalies and related functional impairments in infancy to risk of schizophrenia. METHOD: Using the Congenital Anomalies data-set from the Prenatal Determinants of Schizophrenia birth cohort, congenital anomalies and related functional impairments were categorised and related to subsequent risk of schizophrenia-spectrum disorder. RESULTS: The presence of any hypothesis-based congenital anomaly or related functional impairment was associated with a doubling of risk of schizophrenia-spectrum disorder. In contrast, having any other congenital anomaly or related functional impairment was not associated with risk of schizophrenia-spectrum disorder. CONCLUSIONS: These findings constitute evidence for early events, which may result from both genetic predisposition and environmental insults, in the pathogenesis of schizophrenia.
Authors: Waddington JL; Brown AS; Lane A; Schaefer CA; Goetz RR; Bresnahan M; Susser ES
Br J Psychiatry. 2008 Apr;192(4):264-7.
Computerized screening for alcohol and drug use among adults seeking outpatient psychiatric services
OBJECTIVE: This study examined routine computerized screening for alcohol and drug use of men and women seeking outpatient psychiatric services (excluding chemical dependency treatment) and prevalence based on electronic medical records of consecutive admissions. METHODS: The sample of 422 patients, ages 18-91, completed a self-administered questionnaire. Measures included 30-day, one-year, and lifetime substance use and alcohol-related problems. RESULTS: Seventy-five percent of patients completed electronic intakes during the study period. Prior-month alcohol use was reported by 90 men (70%) and 180 women (62%). Of these patients, heavy drinking (five or more drinks on one occasion) was reported by 37 men (41%) and 41 women (23%). Prior-month cannabis use was reported by 17 men (13%) and 32 women (11%). CONCLUSIONS: Computerized intake systems that include alcohol and drug screening can be integrated into outpatient psychiatric settings. Heavy drinking and use of nonprescribed drugs are commonly reported, which provides an important intervention opportunity.
Authors: Satre D; Wolfe W; Eisendrath S; Weisner C
Psychiatr Serv. 2008 Apr;59(4):441-4.
Tailored treatment in the outpatient substance abuse treatment sector: 1995-2005
Interest in improving the quality of addiction treatment has led to the development of clinical paradigms that emphasize the principle of tailored care-matching treatments to the specific needs of each client or client subgroup. This work analyzes how trends in the provision of tailored treatment practices (TTPs) have changed between 1995 and 2005 across outpatient substance abuse treatment (OSAT) programs in the United States. Categories of interest include measures to capture needs assessment and treatment planning activities, treatment offerings for special populations, and case management activities. Results show that TTPs have diffused in an uneven fashion in the population of OSAT programs between 1995 and 2005. Specifically, needs assessment/treatment planning and case management remain a relatively common practice among OSAT programs, while treatment for special populations (especially same-race therapy) is less widely practiced and, indeed, experienced some decline over the study period. This trend is troublesome given that minority clients constitute a large proportion of those utilizing OSAT programs.
Authors: Alexander JA; Nahra TA; Lemak CH; Pollack H; Campbell CI
J Subst Abuse Treat. 2008 Apr;34(3):282-92. Epub 2007 Jun 28.
The relationship between alcohol consumption and glycemic control among patients with diabetes: the Kaiser Permanente Northern California Diabetes Registry
BACKGROUND: Alcohol consumption is a common behavior. Little is known about the relationship between alcohol consumption and glycemic control among people with diabetes. OBJECTIVE: To evaluate the association between alcohol consumption and glycemic control. DESIGN: Survey follow-up study, 1994-1997, among Kaiser Permanente Northern California members. PATIENTS: 38,564 adult diabetes patients. MEASUREMENTS: Self-reported alcohol consumption, and hemoglobin A1C (A1C), assessed within 1 year of survey date. Linear regression of A1C by alcohol consumption was performed, adjusted for sociodemographic variables, clinical variables, and diabetes disease severity. Least squares means estimates were derived. RESULTS: In multivariate-adjusted models, A1C values were 8.88 (lifetime abstainers), 8.79 (former drinkers), 8.90 (<0.1 drink/day), 8.71 (0.1-0.9 drink/day), 8.51 (1-1.9 drinks/day), 8.39 (2-2.9 drinks/day), and 8.47 (>/=3 drinks/day). Alcohol consumption was linearly (p < 0.001) and inversely (p = 0.001) associated with A1C among diabetes patients. CONCLUSIONS: Alcohol consumption is inversely associated with glycemic control among diabetes patients. This supports current clinical guidelines for moderate levels of alcohol consumption among diabetes patients. As glycemic control affects incidence of complications of diabetes, the lower A1C levels associated with moderate alcohol consumption may translate into lower risk for complications.
Authors: Ahmed AT; Karter AJ; Warton EM; Doan JU; Weisner CM
J Gen Intern Med. 2008 Mar;23(3):275-82. Epub 2008 Jan 8.
Nine-year psychiatric trajectories and substance use outcomes: an application of the group-based modeling approach
This study identifies longitudinal psychiatric trajectories of 934 adult individuals entering chemical dependency treatment in a private, managed care health plan and examines the relationship of these trajectories with substance use (SU) outcomes. The authors apply a group-based modeling approach to identify trajectory groups based on repeated measures of psychiatric severity for 9 years and identify four distinct groups. Results of multivariate logistic generalized estimating equation models find an association between psychiatric trajectories and long-term SU. Older cohorts and life course measures of marital status and employment status as individuals changed over time are related to drug and some alcohol outcomes.
Authors: Chi FW; Weisner CM
Eval Rev. 2008 Feb;32(1):39-58.
Alcohol in emerging adulthood: 7-year study of problem and dependent drinkers
OBJECTIVE: This study examined the level, changes and predictors of alcohol consumption and binge drinking over a 7-year period among young adults (18-25 years) who met the criteria for problem drinking. METHOD: Interviews with 270 18 to 25 years old problem and dependent drinkers from representative public and private substance use treatment programs and the general population were conducted after 1, 3, 5, and 7 years. Measures included demographic characteristics, severity measures, and both formal and informal influences on drinking. RESULTS: Overall alcohol consumption declined over time but leveled off around 24 years of age. Being male, not attending AA over time, as well as more baseline dependence symptoms and greater ASI alcohol and legal severity were associated with greater consumption and binge drinking. In addition, greater levels of binge drinking were associated with less education, earlier age of first use, and a larger social network of heavy drinkers. In conclusion, more attention should be paid to heavy drinking among young adults and to the factors that influence their drinking patterns.
Authors: Delucchi KL; Matzger H; Weisner C
Addict Behav. 2008 Jan;33(1):134-42. Epub 2007 May 3.
Prevalence and correlates of substance use among South African primary care clinic patients
We aimed to assess prevalence and correlates of hazardous use of tobacco, alcohol and other drugs in a primary care population in Cape Town, South Africa. Stratified random sampling was used to select 14 of the 49 clinics in the public health sector in Cape Town, and every ‘nth’ patient, with those ages 18-25 oversampled (N = 2,618). Data were collected from December 2003 through 2004, using the World Health Organization Alcohol, Smoking, and Substance Involvement Screening Test. Hazardous use of tobacco was most common, followed by alcohol and then other drugs. Hazardous tobacco use was associated with the 18-25 years age group, no religious involvement, high school completion, and higher stress. Hazardous alcohol use was associated with male gender, younger men, no religious involvement, employment, some high school education, and higher stress. Hazardous use of other drugs was associated with Colored (mixed) race (particularly among men), no religious involvement, employment, and stress. For all substances, women, particularly Black women, had the lowest rates of hazardous use. Although the study is cross-sectional, it does identify groups that may be at high risk of substance misuse and for whom intervention is urgent. Because prevalence of substance use is high in this population, routine screening should be introduced in primary care clinics.
Authors: Ward CL; Mertens JR; Flisher AJ; Bresick GF; Sterling SA; Little F; Weisner CM
Subst Use Misuse. 2008;43(10):1395-410.
Efficacy of acupuncture for chronic low back pain: protocol for a randomized controlled trial
BACKGROUND: Chronic back pain is a major public health problem and the primary reason patients seek acupuncture treatment. Therefore, an objective assessment of acupuncture efficacy is critical for making informed decisions about its appropriate role for patients with this common condition. This study addresses methodological shortcomings that have plagued previous studies evaluating acupuncture for chronic low back pain. METHODS AND DESIGN: A total of 640 participants (160 in each of four arms) between the ages of 18 and 70 years of age who have low back pain lasting at least 3 months will be recruited from integrated health care delivery systems in Seattle and Oakland. They will be randomized to one of two forms of Traditional Chinese Medical (TCM) acupuncture needling (individualized or standardized), a ‘control’ group (simulated acupuncture), or to continued usual medical care. Ten treatments will be provided over 7 weeks. Study participants and the ‘Diagnostician’ acupuncturists who evaluate participants and propose individualized treatments will be masked to the acupuncture treatment actually assigned each participant. The ‘Therapist’ acupuncturists providing the treatments will not be masked but will have limited verbal interaction with participants. The primary outcomes, standard measures of dysfunction and bothersomeness of low back pain, will be assessed at baseline, and after 8, 26, and 52 weeks by telephone interviewers masked to treatment assignment. General health status, satisfaction with back care, days of back-related disability, and use and costs of healthcare services for back pain will also be measured. The primary analysis comparing outcomes by randomized treatment assignment will be analysis of covariance adjusted for baseline value. For both primary outcome measures, this trial will have 99% power to detect the presence of a minimal clinically significant difference among all four treatment groups and over 80% power for most pairwise comparisons. Secondary analyses will compare the proportions of participants in each group that improve by a clinically meaningful amount. CONCLUSION: Results of this trial will help clarify the value of acupuncture needling as a treatment for chronic low back pain. TRIAL REGISTRATION: Clinical Trials.gov NCT00065585.
Authors: Cherkin DC; Sherman KJ; Hogeboom CJ; Erro JH; Barlow WE; Deyo RA; Avins AL
Trials. 2008 Feb 28;9:10.
Gender differences in the relationship of community services and informal support to seven-year drinking trajectories of alcohol-dependent and problem drinkers
OBJECTIVE: The purpose of this study was to examine how community service contacts and informal support are related to the course of drinking for dependent and problem-drinking persons in a population-based sample of women versus men over 7 years. METHOD: Alcohol-dependent (n = 600) and problem-drinking (n = 992) men and women were identified through probability surveys in the general population and treatment programs throughout a California county. Participants were interviewed at baseline and again 1, 3, 5, and 7 years later. Models predicting the differential impact of community services and informal influences on men and women’s alcohol consumption over time were estimated using a multilevel mixed model, while controlling for demographic characteristics and problem severity. RESULTS: Dependent and problem-drinking men consumed more than women, yet a trend of reduced drinking over time was found for both men and women. Alcoholics Anonymous attendance was related to decreased consumption for men and women regardless of severity; contact with the mental health system was similarly related to decreased consumption for both genders. For problem-drinking women, welfare contacts were related to decreased consumption. A family intervention was the only informal influence that had differential effects on dependent and problem-drinking men and women’s alcohol consumption. CONCLUSIONS: Findings point to the continued benefits of facilitating social support and mental health visits for both dependent and problem-drinking men and women. Developing means to identify and intervene in the range of community service settings, particularly in the mental health and legal system, continues to be important. Innovative interventions for families to encourage engagement in chemical dependency treatment are also warranted.
Authors: Ammon L; Bond J; Matzger H; Weisner C
J Stud Alcohol Drugs. 2008 Jan;69(1):140-50.
Initial experience with a group presentation of study results to research participants
BACKGROUND: Despite ethical imperatives, informing research participants about the results of the studies in which they take part is not often performed. This is due, in part, to the costs and burdens of communicating with each participant after publication of the results. METHODS: Following the closeout and publication of a randomized clinical trial of saw palmetto for treatment of symptoms of benign prostatic hyperplasia, patients were invited back to the research center to participate in a group presentation of the study results. RESULTS: Approximately 10% of participants attended one of two presentation sessions. Reaction to the experience of the group presentation was very positive among the attendees. CONCLUSION: A group presentation to research participants is an efficient method of communicating study results to those who desire to be informed and was highly valued by those who attended. Prospectively planning for such presentations and greater scheduling flexibility may result in higher attendance rates. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov #NCT00037154.
Authors: Avins AL; Bent S; Padula A; Staccone S; Badua E; Goldberg H
Trials. 2008 Mar 21;9:16.
Substance use, education, employment, and criminal activity outcomes of adolescents in outpatient chemical dependency programs
Although the primary outcome of interest in clinical evaluations of addiction treatment programs is usually abstinence, participation in these programs can have a wide range of consequences. This study evaluated the effects of treatment initiation on substance use, school attendance, employment, and involvement in criminal activity at 12 months post-admission for 419 adolescents (aged 12 to 18) enrolled in chemical dependency recovery programs in a large managed care health plan. Instrumental variables estimation methods were used to account for unobserved selection into treatment by jointly modeling the likelihood of participation in treatment and the odds of attaining a certain outcome or level of an outcome. Treatment initiation significantly increased the likelihood of attending school, promoted abstinence, and decreased the probability of adolescent employment, but it did not significantly affect participation in criminal activity at the 12-month follow-up. These findings highlight the need to address selection in a non-experimental study and demonstrate the importance of considering multiple outcomes when assessing the effectiveness of adolescent treatment.
Authors: Balsa AI; Homer JF; French MT; Weisner CM
J Behav Health Serv Res. 2009 Jan;36(1):75-95. Epub 2007 Dec 7.
Collaborative depression care, screening, diagnosis and specificity of depression treatments in the primary care setting
The identification, referral and specific treatment of midlife patients in primary care who are distressed by mood, anxiety, sleep and stress-related symptoms, with or without clinically confirmed menopausal symptoms, are confounded by many structural issues in the delivery of women’s healthcare. Diagnosis, care delivery, affordability of treatment, time commitment for treatment, treatment specificity for a particular patient’s symptoms and patient receptiveness to diagnosis and treatment all play roles in the successful amelioration of symptoms in this patient population. The value of screening for depression in primary care, the limitations of commonly used screening instruments relative to culture and ethnicity, and which clinical care systems make best use of diagnostic screening programs will be discussed in the context of the midlife woman. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) program illustrates the relatively high rate of unremitted patients, regardless of clinical setting, who are receiving antidepressants. Nonmedication treatment approaches, referred to in the literature as ‘nonsomatic treatments’, for depression, anxiety and stress, include different forms of cognitive-behavioral therapy, interpersonal therapy, structured daily activities, mindfulness therapies, relaxation treatment protocols and exercise. The specificity of these treatments, their mechanisms of action, the motivation and time commitment required of patients, and the availability of trained practitioners to deliver them are reviewed. Midlife women with menopausal symptoms and depression/anxiety comorbidity represent a challenging patient population for whom an individualized treatment plan is often necessary. Treatment for depression comorbid with distressing menopausal symptoms would be facilitated by the implementation of a collaborative care program for depression in the primary care setting.
Authors: Alexander JL; Richardson G; Grypma L; Hunkeler EM
Expert Rev Neurother. 2007 Nov;7(11 Suppl):S59-80.
Concurrent and simultaneous drug and alcohol use: results of the 2000 National Alcohol Survey
This study estimates the prevalence, assesses predictors and evaluates factors associated with concurrent and simultaneous use of drugs and alcohol in the United States population. Using data from the 2000 National Alcohol Survey (n=7612), respondents were asked if they used specific drugs in the last 12 months. Current drinkers who reported using each type of drug were asked if they used alcohol and the drug at the same time. Approximately 10% reported using marijuana in the last 12 months (concurrent use); 7% reported drinking alcohol and using marijuana at the same time (simultaneous use). Approximately 5% of current drinkers reported using drugs other than marijuana in the last 12 months; 1.7% reported drinking alcohol and using drugs other than marijuana at the same time. Being younger, having less than a high school education, not having a regular partner and having heavier drinking patterns were associated with using alcohol and marijuana simultaneously. Simultaneous use of marijuana and alcohol as well as other drugs and alcohol were significantly related to social consequences, alcohol dependence, and depression. These results mirror clinical populations in which increasingly younger clients report use of alcohol and drugs and need treatment for both.
Authors: Midanik LT; Tam TW; Weisner C
Drug Alcohol Depend. 2007 Sep 6;90(1):72-80. Epub 2007 Apr 18.
Type 2 diabetes and risk of cognitive impairment and dementia
Diabetes is a major public health burden. Even a modest effect of diabetes on cognitive function has significant public health implications. Several lines of mechanistic evidence implicate a role of insulin and glucose metabolism on risk of developing dementia, including Alzheimer’s disease. Population-based studies have shown that those with type 2 diabetes mellitus have an increased risk of cognitive impairment, dementia, and neurodegeneration. There are many mechanisms through which diabetes could increase risk of dementia, including glycemia, insulin resistance, oxidative stress, advanced glycation endproducts, inflammatory cytokines, and microvascular and macrovascular disease. This paper presents a review of the evidence on diabetes and increased risk of dementia and cognitive impairment, a discussion of different possible mechanisms, and remaining gaps in our knowledge.
Authors: Whitmer RA
Curr Neurol Neurosci Rep. 2007 Sep;7(5):373-80.
Race and risk of schizophrenia in a US birth cohort: another example of health disparity?
BACKGROUND: Immigrant groups in Western Europe have markedly increased rates of schizophrenia. The highest rates are found in ethnic groups that are predominantly black. Separating minority race/ethnicity from immigration in Western Europe is difficult; in the US, these issues can be examined separately. Here we compared rates of schizophrenia between whites and African Americans and evaluated whether the association was mediated by socioeconomic status (SES) of family of origin in a US birth cohort. METHODS: Study subjects were offspring of women enrolled during pregnancy at Alameda County Kaiser Permanente Medical Care Plan clinics (1959-66) in the Child Health and Development Study. For schizophrenia spectrum disorders, 12 094 of the 19 044 live births were followed over 1981-97. The analysis is restricted to cohort members whose mothers identified as African American or white at intake. Stratified proportional hazards regression was the method of analysis; the robustness of findings to missing data bias was assessed using multiple imputation. RESULTS: African Americans were about 3-fold more likely than whites to be diagnosed with schizophrenia [Rate Ratio (RR) = 3.27; 95% confidence interval (CI): 1.71-6.27]. After adjusting for indicators of family SES at birth, the RR was about 2-fold (RR = 1.92; 95% CI: 0.86-4.28). Using multiple imputation in the model including family SES indicators, the RR for race and schizophrenia was strengthened in comparison with the estimate obtained without imputation. CONCLUSION: The data indicate substantially elevated rates of schizophrenia among African Americans in comparison with whites in this birth cohort. The association may have been partly but not wholly mediated by an effect of race on family SES.
Authors: Bresnahan M; Begg MD; Brown A; Schaefer C; Sohler N; Insel B; Vella L; Susser E
Int J Epidemiol. 2007 Aug;36(4):751-8. Epub 2007 Apr 17.
Risk of suicide attempt and suicide death in patients treated for bipolar disorder
OBJECTIVES: To evaluate demographic and clinical predictors of suicide attempt and suicide death in a population-based sample of people treated for bipolar disorder (BD). METHODS: Computerized records were used to identify 32,360 individuals treated for BD at two large prepaid health plans. Suicide attempts were identified using computerized records of outpatient visit diagnoses and hospital discharge diagnoses. Suicide deaths were identified using state death certificate data. RESULTS: Overall event rates were 1.06 per 1,000 person-years for suicide death, 5.6 per 1,000 person-years for suicide attempt leading to hospitalization, and 13.9 per 1,000 person-years for suicide attempt not leading to hospitalization. Men had a significantly lower rate of suicide attempt [hazard ratio (HR) 0.68, 95% confidence interval (CI) 0.56-0.83] but a higher rate of suicide death (HR 2.70, 95% CI 1.69-4.31). Suicide attempts were significantly more frequent among younger patients, but suicide deaths did not vary significantly by age. Substance use comorbidity was significantly related to risk of suicide attempt (HR 2.53, 95% CI 2.07-3.09) but not to risk of suicide death (HR 1.02, 95% CI 0.54-1.93). Comorbid anxiety disorder was associated with significantly higher risk of both suicide attempt (HR 1.40, 95% CI 1.14-1.72) and suicide death (HR 1.81, 95% CI 1.09-2.99). CONCLUSIONS: Among people treated for BD, risk of suicide death is significantly related to male sex and comorbid anxiety disorder. The predictors of suicide death differ markedly from predictors of suicide attempt.
Authors: Simon GE; Hunkeler E; Fireman B; Lee JY; Savarino J
Bipolar Disord. 2007 Aug;9(5):526-30.
Tailoring of outpatient substance abuse treatment to women, 1995-2005
BACKGROUND: Tailoring substance abuse treatment to women often leads to better outcomes. Previous evidence, however, suggests limited availability of such options. OBJECTIVES: This investigation sought to depict recent changes in outpatient substance abuse treatment (OSAT) tailoring to women and to identify unit and contextual factors associated with these practices. RESEARCH DESIGN: Data were from 2 waves of a national OSAT unit survey (N = 618 in 1995, N = 566 in 2005). Comparisons of weighted means between waves indicate which practices changed over time. Multiple logistic regressions with generalized estimating equations test associations between unit and contextual attributes and tailoring to women. MEASURES: Tailoring to women was measured as availability of prenatal care, child care, single sex therapy, and same sex therapists, and the percentage of staff trained to meet female clients’ needs. RESULTS: Two measures of tailoring to women declined significantly between 1995 and 2005: availability of single sex therapy (from 66% to 44% of units) and percent of staff trained to work with women (from 42% to 32% of units). No aspect of tailoring to women became more common. Proportion of female clients, total number of clients, methadone status, and private and government managed care were associated with higher odds of tailoring to women. For-profit facilities, which became more prevalent during the study period, had lower odds than other units of tailoring treatment to women. CONCLUSIONS: Some key aspects of OSAT tailoring to women decreased significantly in the last decade. Managed care contracts may offer 1 mechanism for counteracting these trends.
Authors: Campbell CI; Wells R; Alexander JA; Jiang L; Nahra TA; Lemak CH
Med Care. 2007 Aug;45(8):775-80.
Creating a culture of research
There is widespread concern about the ability of the current model of clinical research to keep pace with the growing need for testing new approaches to disease management and prevention. In response, important innovations are emerging in critical areas of research infrastructure and practice. However, success in fulfilling the promise of clinical research will also require a fundamental shift in the relationship between the clinical-research enterprise and all segments of society. In this article, we outline proposals to help create the necessary recognition and engage participation by patients, clinicians, health-care delivery systems, and the research community to establish the long-lasting growth needed for achieving the full potential of clinical research.
Authors: Avins AL; Goldberg H
Contemp Clin Trials. 2007 Jul;28(4):557-62. Epub 2007 Feb 27.
Do licensing and accreditation matter in outpatient substance abuse treatment programs?
Licensing and accreditation are widely used to improve and convey organizational quality. The objective of this study was to provide substance abuse treatment stakeholders with better evidence about how well licensing and accreditation actually correlate with staffing and treatment practices. Regressions using data from national surveys of outpatient substance abuse treatment facilities indicated that no form of licensing or accreditation was associated with better staff-to-client ratios or with one important aspect of comprehensive treatment — the percentage of clients receiving routine medical care. There were several positive associations between licensing/accreditation and other aspects of treatment comprehensiveness. Three categories of licensure/accreditation were also positively associated with use of after-treatment plans. Post hoc analyses revealed that accreditation was associated with units’ organizational contexts and referral sources as well as the nature of the competitive environment. Licensing/accreditation may reveal as much about units’ institutional environments as about the quality of treatment provided.
Authors: Wells R; Lemak CH; Alexander JA; Nahra TA; Ye Y; Campbell CI
J Subst Abuse Treat. 2007 Jul;33(1):43-50. Epub 2007 Jan 16.
Metabolic syndrome and cognitive decline in elderly Latinos: findings from the Sacramento Area Latino Study of Aging study
OBJECTIVES: To investigate the effect of metabolic syndrome on cognitive function in an elderly Latino population and to determine whether inflammation modifies this association. DESIGN: A longitudinal cohort study. SETTING: Sacramento area and the surrounding California counties from 1998 to 1999. PARTICIPANTS: One thousand six hundred twenty-four Latinos aged 60 and older who participated in the Sacramento Area Latino Study of Aging. MEASUREMENTS: Baseline metabolic syndrome was calculated using the Third Adult Treatment Panel of the National Cholesterol Education Program. Cognitive function was measured using the Modified Mini-Mental State Examination (3MS) and the Delayed Word-List Recall (DelRec), a verbal memory test. The effect of metabolic syndrome on cognitive change scores was examined using random effects models; in addition, the effect of the individual components of the syndrome on cognitive change was examined. RESULTS: Of the 1,624 participants, 718 (44%) had metabolic syndrome at baseline. Those with metabolic syndrome had worse 3-year change scores on 3MS (P=.04) and DelRec (P=.03). Multivariate adjustment attenuated the results for DelRec but not for 3MS. This association was especially pronounced in participants with a high serum level of inflammation, resulting in an average 3MS score 0.64 points lower per year (P=.03) for those with metabolic syndrome. Individual components of metabolic syndrome were not associated with cognitive decline except for elevated glucose on the DelRec (P=.02) and high blood pressure on 3MS (P=.05). CONCLUSION: Metabolic syndrome and inflammation may both contribute to cognitive decline in older people of diverse backgrounds. The results also suggest that, in elderly Latinos, the composite measure of metabolic syndrome is a greater risk for cognitive decline than its individual components.
Authors: Yaffe K; Haan M; Blackwell T; Cherkasova E; Whitmer RA; West N
J Am Geriatr Soc. 2007 May;55(5):758-62.
Gender differences in seven-year alcohol and drug treatment outcomes among older adults
This study examined participants at seven-year follow-up to assess long-term outcomes of older women (n = 25) and men (n = 59) ages 55 and over in an outpatient addiction program. It measured demographic characteristics, alcohol and drug use, psychiatric symptoms, Addiction Severity Index, treatment length, and outcomes. At seven years, 76.0% of women reported abstinence in the prior 30 days versus 54.2% of men, p = .05. Logistic regression analysis found that longer treatment stay predicted abstinence. Findings indicate that older women have better long-term addiction outcome than older men, but treatment length is more significant than gender in predicting outcome.
Authors: Satre DD; Blow FC; Chi FW; Weisner C
Am J Addict. 2007 May-Jun;16(3):216-21.
Tamoxifen treatment and new-onset depression in breast cancer patients
The authors conducted a retrospective cohort study of female patients diagnosed with breast cancer (BRCA), evaluating the risk of new-onset depression associated with tamoxifen treatment among those with estrogen receptor-positive (ER+) tumors, versus estrogen receptor-negative (ER-) tumors, who were not receiving tamoxifen. A total cohort of 2,943 patients was identified. The hazard-ratio for new-onset depression in the tamoxifen group was nonsignificant. A post-hoc analysis revealed that chemotherapy and ER+ status were significantly and independently associated with an increased risk for developing depression.
Authors: Lee KC; Ray GT; Hunkeler EM; Finley PR
Psychosomatics. 2007 May-Jun;48(3):205-10.
Alcohol consumption, medical conditions, and health behavior in older adults
OBJECTIVES: To examine associations between drinking patterns, medical conditions, and behavioral health risks among older adults. METHODS: Analyses compared survey participants (health plan members ages 65 to 90, N = 6662) who drank moderately to those who drank over recommended limits or did not drink. RESULTS: Overlimit drinking was associated with smoking; not trying to eat low-fat foods (in men), and lower BMI (in women). Predictors of not drinking during the prior 12 months included ethnicity, lower education, worse self-reported health, diabetes and heart problems. CONCLUSIONS: Significant relationships exist between health and alcohol consumption patterns, which vary by gender.
Authors: Satre DD; Gordon NP; Weisner C
Am J Health Behav. 2007 May-Jun;31(3):238-48.
Body mass index in midlife and risk of Alzheimer disease and vascular dementia
Prior work has suggested that obesity and overweight as measured by body mass index (BMI) increases risk of dementia. It is unknown if there is a difference in the risk of developing Alzheimer disease (AD) versus vascular dementia (VaD) associated with high body weight. The goal of this study was to examine the association between midlife BMI and risk of both AD and VaD an average of 36 years later in a large (N= 10,136) and diverse cohort of members of a health care delivery system. Participants aged 40-45 participated in health exams between 1964 and 1968. AD and VaD diagnoses were obtained from Neurology visits between January 1, 1994 and June 15, 2006. Those with diagnoses of general dementia from primary care providers were excluded from the study. BMI was analyzed in WHO categories of underweight, overweight and obese, as well as in subdivisions of WHO categories. All models were fully adjusted for age, education, race, sex, marital status, smoking, hyperlipidemia, hypertension, diabetes, ischemic heart disease and stroke. Cox proportional hazard models showed that compared to those with a normal BMI (18.5-24.9), those obese (BMI > or = 30) at midlife had a 3.10 fold increase in risk of AD (fully adjusted model, Hazard Ratio=3.10, 95% CI 2.19-4.38), and a five fold increase in risk of VaD (fully adjusted model, HR=5.01, 95% CI 2.98-8.43) while those overweight ( BMI > or = 25 and <30) had a two fold increase in risk of AD and VaD (fully adjusted model, HR=2.09, 95% CI 1.69-2.60 for AD and HR=1.95, 95% CI 1.29-2.96 for VaD). These data suggest that midlife BMI is strongly predictive of both AD and VaD, independent of stroke, cardiovascular and diabetes co morbidities. Future studies need to unveil the mechanisms between adiposity and excess risk of AD and VaD.
Authors: Whitmer RA; Gunderson EP; Quesenberry CP Jr; Zhou J; Yaffe K
Curr Alzheimer Res. 2007 Apr;4(2):103-9.
The epidemiology of adiposity and dementia
Adipose tissue is the largest endocrine gland in the body, yet only recently has its role in neurodegenerative disease been considered. Prospective population level evidence has emerged to show that both obesity and overweight, is associated with an increased risk of all cause dementia, Alzheimer’s disease (AD), and underlying neurodegenerative changes. Weight loss in late life however is associated with dementia, and those categorized as underweight are also at a greater risk of dementia. Given the current epidemic of obesity, and the expected age-related increase in dementia incidence, even a small association between these two diseases has far reaching public health implications. However, due to the effects of both AD-associated weight loss and age-related changes in body composition, there are methodological challenges in appropriately evaluating obesity as a risk factor for developing dementia. There is a need to take a ‘life course approach’ and to consider the role of risk factors prior to the onset of old age. Our work has shown that both obesity and overweight, as measured by body mass index and skinfold thickness, in middle-age are strongly associated with an increased risk of all cause dementia, Alzheimer disease & Vascular dementia, independent of the development of diabetes and cardiovascular-related morbidities. There is also value in assessing regional body shape distributions of adiposity, particular the role of abdominal obesity. Mechanistic pathways such as adipocyte secreted proteins and hormones, and inflammatory cytokines could explain the association between obesity and increased risk of dementia.
Authors: Whitmer RA
Curr Alzheimer Res. 2007 Apr;4(2):117-22.
The pharmacogenetics research network: from SNP discovery to clinical drug response
The NIH Pharmacogenetics Research Network (PGRN) is a collaborative group of investigators with a wide range of research interests, but all attempting to correlate drug response with genetic variation. Several research groups concentrate on drugs used to treat specific medical disorders (asthma, depression, cardiovascular disease, addiction of nicotine, and cancer), whereas others are focused on specific groups of proteins that interact with drugs (membrane transporters and phase II drug-metabolizing enzymes). The diverse scientific information is stored and annotated in a publicly accessible knowledge base, the Pharmacogenetics and Pharmacogenomics Knowledge base (PharmGKB). This report highlights selected achievements and scientific approaches as well as hypotheses about future directions of each of the groups within the PGRN. Seven major topics are included: informatics (PharmGKB), cardiovascular, pulmonary, addiction, cancer, transport, and metabolism.
Authors: Giacomini KM; Schaefer CA; Pharmacogenetics Research Network; et al.
Clin Pharmacol Ther. 2007 Mar;81(3):328-45.
Medical conditions of adolescents in alcohol and drug treatment: comparison with matched controls
PURPOSE: Alcohol and drug problems are associated with medical problems among adults. Research on the relationship of adolescent alcohol and drug use disorders to specific medical problems is less developed and focused on acute consequences. This study addresses gaps in the literature regarding medical comorbidities in adolescents with alcohol and drug use disorders. METHODS: This study compares the prevalence of medical conditions among 417 adolescent alcohol and drug treatment patients with 2082 demographically matched controls from the same managed care health plan and examines whether comparisons vary among substance-type subgroups. RESULTS: Approximately one-fourth of the comorbid conditions examined were more common among adolescent alcohol and drug patients than among matched controls, and several were highly costly conditions (e.g., asthma, injury). We also found that pain-related diagnoses, including headache and abdominal pain, were more prevalent among alcohol and drug patients. CONCLUSIONS: Our findings point to the importance of examining comorbid medical and chemical dependency in both adolescent primary care and specialty care. Moreover, optimal treatment of many common medical disorders may require identification, intervention, and treatment of a substance use problem.
Authors: Mertens JR; Flisher AJ; Fleming MF; Weisner CM
J Adolesc Health. 2007 Feb;40(2):173-9. Epub 2006 Nov 29.
Homocysteine, B vitamins, and the incidence of dementia and cognitive impairment: results from the Sacramento Area Latino Study on Aging
BACKGROUND: High concentrations of homocysteine have been linked to a greater risk of Alzheimer disease, dementia, and cognitive decline. OBJECTIVE: We evaluated the association between homocysteine and 4.5-y combined incidences of dementia and cognitive impairment without dementia (CIND) in a cohort of 1779 Mexican Americans aged 60-101 y. DESIGN: Homocysteine, red blood cell (RBC) folate, and plasma vitamin B-12 were measured at baseline. New cases of dementia or CIND were ascertained by neuropsychological and clinical examinations and expert adjudication. We used proportional hazards models to estimate the risk of homocysteine-associated dementia or CIND and the influence of RBC folate and plasma vitamin B-12 on that association. RESULTS: High homocysteine concentrations were associated with a greater risk of dementia or CIND: hazard ratio (HR): 2.39; 95% CI: 1.11, 5.16. Plasma vitamin B-12 modified the association between homocysteine and the outcome. The rates of dementia or CIND associated with homocysteine for those in the lowest and highest tertiles of vitamin B-12, respectively, were significantly higher (HR: 1.61, P = 0.04) and lower (HR: 0.94, P = 0.015) than the risk for those in the middle tertile. CONCLUSIONS: Homocysteine is an independent risk factor for both dementia and CIND. Higher plasma vitamin B-12 may reduce the risk of homocysteine-associated dementia or CIND.
Authors: Haan MN; Miller JW; Aiello AE; Whitmer RA; Jagust WJ; Mungas DM; Allen LH; Green R
Am J Clin Nutr. 2007 Feb;85(2):511-7.
The excess medical cost and health problems of family members of persons diagnosed with alcohol or drug problems
BACKGROUND: Having a family member with substance use problems affects family functioning, which may lead to increased medical problems and increased health care utilization and costs in the other family members. AIM: We sought to estimate the excess medical costs and prevalence of diagnosed health conditions of family members of persons with an alcohol or drug diagnosis (AOD) compared with the family members of similar persons without an AOD. METHODS: Using a large health plan’s administrative databases, we identified persons who received an AOD between 2001 and 2004 and a similar group of persons with no AOD during that time. Using a hierarchical linear mixed model, we compared the cost and utilization of the family members of the AOD and non-AOD patients in the 2 years prior to the AOD patient’s first AOD. Using logistic regression, we determined whether the family members of patients with AODs were more likely than comparison family members to be diagnosed with medical conditions. RESULTS: Family members of patients with AODs had greater health care costs than comparison family members in the second year before the index date (490 dollars) and in the year before the index date (433 dollars). This was the case for both adult and child family members. They also were more likely to be diagnosed with many medical conditions, especially substance abuse and depression. CONCLUSIONS: Family members of patients with AODs have greater health care costs and are more likely to be diagnosed with a number of medical conditions than family members of similar persons without an AOD.
Authors: Ray GT; Mertens JR; Weisner C
Med Care. 2007 Feb;45(2):116-22.
Nonmedical use of prescription drugs among a longitudinal sample of dependent and problem drinkers
BACKGROUND: Increasing trends in the nonmedical use of prescription drugs (NMPD) have been documented, yet little is known about the demographic, severity, and social network influences related to NMPD among treated and untreated problem and dependent drinkers. METHODS: To determine NMPD over four post-baseline interviews, the current study uses a 7-year longitudinal sample of 1598 dependent and problem drinkers, many also using illegal drugs, who were identified through a probability survey in the general population and consecutive intakes in public and private chemical dependency treatment programs in a California county. A panel model incorporating variables from the four post-baseline interviews was used, with baseline variables added for control. RESULTS: The use of illegal drugs (OR=2.18, CI 1.28-3.70), including marijuana (OR=2.66, CI 1.74-4.08), and the nonmedical use of prescription drugs prior to the baseline interview (OR=2.53, CI 1.48-4.33) were related to NMPD over the study period. Larger heavy alcohol and drug using social networks were also related to NMPD (OR=1.03, CI 1.01-1.05). CONCLUSIONS: When examining a sample of dependent and problem drinkers, many of the results obtained were similar to results in the literature predicting drug, and even alcohol, use more generally. In this sample, illegal drug use, and marijuana use were important predictors of NMPD. Thus, the nonmedical use of prescription drugs may not be the first problem noticed by health and psychiatric providers.
Authors: Matzger H; Weisner C
Drug Alcohol Depend. 2007 Jan 12;86(2-3):222-9. Epub 2006 Aug 22.
Elevated prenatal homocysteine levels as a risk factor for schizophrenia
CONTEXT: Elevated prenatal homocysteine level is a plausible risk factor for schizophrenia because of its partial antagonism of N-methyl-D-aspartate receptors under physiologic glycine concentrations and its association with abnormal placental function and pregnancy complications. OBJECTIVE: We examined whether elevated maternal levels of homocysteine during the third trimester were associated with adult schizophrenia risk. DESIGN: Nested case-control study of a large birth cohort, born from 1959 through 1967 and followed up for schizophrenia from 1981 through 1997. SETTING: Population-based birth cohort and health plan. PARTICIPANTS: Cases (n = 63) were diagnosed with schizophrenia and other spectrum disorders (mostly schizophrenia and schizoaffective disorder). Controls (n = 122) belonged to the birth cohort; had not been diagnosed with a schizophrenia spectrum or major affective disorder; and were matched to cases on date of birth, sex, length of time in the cohort, and availability of maternal serum samples. MAIN MEASURES: Archived maternal serum samples were assayed for homocysteine levels during pregnancies of cases and matched controls. RESULTS: In a model that tested for a threshold effect of third-trimester homocysteine levels, an elevated homocysteine level was associated with a greater than 2-fold statistically significant increase in schizophrenia risk (odds ratio, 2.39; 95% confidence interval, 1.18-4.81; P = .02). CONCLUSIONS: These findings indicate that elevated third-trimester homocysteine levels may be a risk factor for schizophrenia. Elevated third-trimester homocysteine levels may elevate schizophrenia risk through developmental effects on brain structure and function and/or through subtle damage to the placental vasculature that compromises oxygen delivery to the fetus. If future studies both replicate this association and support a causal link, then the use of folic acid supplementation would merit evaluation as a strategy for prevention of schizophrenia in offspring.
Authors: Brown AS; Bottiglieri T; Schaefer CA; Quesenberry CP Jr; Liu L; Bresnahan M; Susser ES
Arch Gen Psychiatry. 2007 Jan;64(1):31-9.
Cigarette smoking and long-term alcohol and drug treatment outcomes: a telephone follow-up at five years
This prospective study examined the relationship between cigarette smoking and five-year substance abuse treatment outcomes. Of 749 individuals who began private outpatient treatment, 598 (80%) were re-interviewed by telephone at five years. At five-year follow-up, 53% reported smoking cigarettes in the prior 30 days. Smokers were less likely to be abstinent from alcohol and drugs in the prior 30 days (48.3% vs. 64.0%), and had higher Addiction Severity Index (ASI) scores in employment, alcohol, drug, psychiatric, and family/social problems; worse self-reported health; and greater self-reported depression. Findings inform understanding of long-term substance abuse treatment outcomes and potential service needs of smokers.
Authors: Satre DD; Kohn CS; Weisner C
Am J Addict. 2007 Jan-Feb;16(1):32-7.
Physical activity and dementia: The need for prevention trials
Dementia is a common and debilitating disease that will increase dramatically for the next 50 years unless a prevention or treatment is identified. This review summarizes the evidence that physical activity is associated with a reduced risk of dementia in older adults and recommends that prevention trials be performed to determine whether this association is causal.
Authors: Barnes DE; Whitmer RA; Yaffe K
Exerc Sport Sci Rev. 2007 Jan;35(1):24-9.
Reducing suicidal ideation in depressed older primary care patients
OBJECTIVES: To determine the effect of a primary care-based collaborative care program for depression on suicidal ideation in older adults. DESIGN: Randomized, controlled trial. SETTING: Eighteen diverse primary care clinics. PARTICIPANTS: One thousand eight hundred one adults aged 60 and older with major depression or dysthymia. INTERVENTION: Participants randomized to collaborative care had access to a depression care manager who supported antidepressant medication management prescribed by their primary care physician and offered a course of Problem Solving Treatment in Primary Care for 12 months. Participants in the control arm received care as usual. MEASUREMENTS: Participants had independent assessments of depression and suicidal ideation at baseline and 3, 6, 12, 18, and 24 months. Depression was assessed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (SCID). Suicidal ideation was determined using the SCID and the Hopkins Symptoms Checklist. RESULTS: At baseline, 139 (15.3%) intervention subjects and 119 (13.3%) controls reported thoughts of suicide. Intervention subjects had significantly lower rates of suicidal ideation than controls at 6 months (7.5% vs 12.1%) and 12 months (9.8% vs 15.5%) and even after intervention resources were no longer available at 18 months (8.0% vs 13.3%) and 24 months (10.1% vs 13.9%). There were no completed suicides in either group. Information on suicide attempts or hospitalization for suicidal ideation was not available. CONCLUSION: Primary care-based collaborative care programs for depression represent one strategy to reduce suicidal ideation and potentially the risk of suicide in older primary care patients.
Authors: Unutzer J; Hunkeler E; for the IMPACT Investigators; et al.
J Am Geriatr Soc. 2006 Oct;54(10):1550-6.
Midlife obesity and long-term risk of nursing home admission
OBJECTIVE: Obesity is a growing problem among middle-aged individuals. We investigated whether obesity in middle-aged individuals influences the need for future nursing home care and whether the risk of nursing home admission associated with obesity is greater in whites than in blacks. RESEARCH METHODS AND PROCEDURES: The study population (N = 8804) consisted of long-term members of the Kaiser Permanente Medical Care Plan ages 75 to 85 years in 1995 who had completed a standardized, multiphasic health checkup while in their 50s. The multiphasic health checkup examinations were performed as part of routine medical care between the years 1964 and 1973 and included standardized measurements of BMI. We used health plan records to assess incident nursing home admissions from 1995 to 2002. The risk of nursing home admission associated with standard categories of midlife BMI was estimated using Cox proportional hazard analysis. RESULTS: During an average follow-up of 5.1 years, the nursing home admission rate was 6.8 per 100 person-years of observation. After adjustment for comorbidities, midlife obesity predicted incident nursing home admission approximately 25 years later [hazard ratio (HR), 1.30; 95% confidence interval (CI), 1.15 to 1.46; p < 0.001]. Overweight BMI at midlife was not associated with future nursing home admission (HR, 1.05; 95% CI, 0.97 to 1.14; p = 0.23). The risk of nursing home admission associated with midlife obesity was higher in whites (HR, 1.34; 95% CI, 1.17 to 1.54; p < 0.001) than in blacks (HR 1.15; 95% CI, 0.87 to 1.52; p = 0.32), but the difference between races was not significant (p for interaction = 0.65). DISCUSSION: Obesity among middle-aged individuals is associated with an increased risk of nursing home admission in late life and may be an important target for reducing the future societal burden of nursing home care.
Authors: Elkins JS; Whitmer RA; Sidney S; Sorel M; Yaffe K; Johnston SC
Obesity (Silver Spring). 2006 Aug;14(8):1472-8.
Saw palmetto and lower urinary tract symptoms: what is the latest evidence?
The use of dietary supplements for treating a wide range of health conditions has grown rapidly in the United States. In the field of men’s health, the most common dietary supplement used is an extract of the berry of the saw palmetto plant, with which men commonly self-medicate in order to treat lower urinary tract symptoms. Throughout the past two decades, substantial literature has emerged examining the biologic and clinical effects of saw palmetto extracts. Several lines of evidence suggest that saw palmetto may exert physiologic effects consistent with a beneficial clinical effect on the mechanisms of benign prostatic hyperplasia. Although most clinical studies tend to suggest a modest efficacy benefit of saw palmetto, more recent studies are less consistent and the precise clinical value of saw palmetto for treating lower urinary tract symptoms remains undefined. Overall, there appear to be few safety concerns with short-term use of this herbal medicine, although large-scale and longer-term safety studies have not been performed. Higher-quality studies are currently underway to better define the potential benefits and risks of plant-based extracts for treating symptoms related to benign prostatic hyperplasia.
Authors: Avins AL; Bent S
Curr Urol Rep. 2006 Jul;7(4):260-5.
Course of recovery from alcoholism
This article represents the proceedings of a symposium at the 2005 Research Society on Alcoholism meeting in Santa Barbara, California, organized and chaired by Kamilla L. Venner. This symposium integrated current empirical research on the course of recovery from alcoholism from multiple perspectives, an aim that is consistent with NIAAA’s new focus on the process of recovery. The presentations and presenters were as follows: (1) The Role of Community Services and Informal Support on 7-Year Drinking Outcomes in Treated and Untreated Drinkers, by Helen Matzger; (2) The Sequence of Recovery Events in a Native American Sample, by Kamilla L. Venner; (3) Transformational Change in Recovery, by Alyssa A. Forcehimes; (4) Social Settings and Substance Use: Contextual Factors in Recovery, by Rudolf H. Moos; and (5) A Broader View of Change in Drinking Behavior, by discussant Mark L. Willenbring. A theme connecting the presentations was that treatment is but one discrete aspect to recovery and that sustained recovery is often influenced by an individual interaction with others within a social context. Collectively, presentations underscored the need to think more broadly about factors contributing to the remission of alcohol dependence.
Authors: Venner KL; Matzger H; Forcehimes AA; Moos RH; Feldstein SW; Willenbring ML; Weisner C
Alcohol Clin Exp Res. 2006 Jun;30(6):1079-90.
Chemical dependency patients with cooccurring psychiatric diagnoses: service patterns and 1-year outcomes
BACKGROUND: Improving services and treatment outcomes for individuals with cooccurring alcohol and drug use disorders and psychiatric conditions has been a critical challenge to clinicians and policy makers. This study examined 1-year outcomes for individuals entering chemical dependency (CD) treatment with and without cooccurring psychiatric diagnoses targeted by California parity legislation. Among those with cooccurring conditions (i.e., dual-diagnosis patients), we examined a model including individual characteristics, treatment services, and extratreatment characteristics to understand CD outcome predictors in this population. We hypothesized that longer CD treatment duration and receiving psychiatric services would predict higher abstinence levels. In particular,patterns of psychiatric services (amount of services, receiving a critical dose, or receiving services concurrently with CD treatment) were assessed in relation to outcome. METHODS: We examined abstinence rates 1 year after intake for 747 adults with and without cooccurring conditions. Among dual-diagnosis patients, logistic regression was used to examine predictors of abstinence. RESULTS: At baseline, dual-diagnosis patients (N=104) had higher levels of medical, family, and employment problems than others. They had similar CD retention and received more psychiatric services during the year after intake and had comparable CD outcomes at 1 year. Length of stay in CD treatment, hours of psychiatric services, number of months with concurrent CD and psychiatric services, and number of 12-step meetings attended were independent predictors of abstinence for dual diagnosis patients. CONCLUSIONS: Chemical dependency outcomes in patients with cooccurring psychiatric conditions were positively associated with the number and patterning of services. Receiving psychiatric services concurrently with CD treatment may be beneficial for dual-diagnosis patients. Future studies should examine how best to integrate services to optimize treatment outcomes.
Authors: Chi FW; Satre DD; Weisner C
Alcohol Clin Exp Res. 2006 May;30(5):851-9.
Adolescents entering chemical dependency treatment in private managed care: ethnic differences in treatment initiation and retention
PURPOSE: There has been little research on adolescents of different ethnicities in chemical dependency (CD) treatment, despite a focus on ethnic disparities in health care in recent years. In particular, little is known about ethnic differences in utilization of adolescent CD services. METHODS: We examined treatment initiation and treatment retention in a sample of African American, Native American, Latino, Asian American, and Caucasian adolescents entering CD treatment in a private, managed care health plan (n = 419). Our conceptual framework included ethnicity as the main factor as well as measures of external pressure and internal motivation/readiness for treatment, family environment, psychiatric co-morbidities, and severity of alcohol and drug problems. Logistic and Poisson regression were used to examine differences. RESULTS: The study found ethnic differences in treatment initiation and treatment retention. Native American adolescents had lower odds of returning after intake to initiate treatment compared with Caucasians (odds ratio [OR] .35, p = .009), and African American youth spent less time in treatment than Caucasians (RR: .49, p < .001). CONCLUSIONS: Study findings indicate differences in treatment initiation for Native Americans and in treatment retention for African Americans. Intake and orientation sessions offer an opportunity to intervene with Native American youth. Given their high psychiatric co-morbidity, they may also benefit from the availability of psychiatric services. Even after adjusting for severity, we found shorter treatment retention for African American adolescents and suggest that organizational factors, such as cultural competency, may play an important role.
Authors: Campbell CI; Weisner C; Sterling S
J Adolesc Health. 2006 Apr;38(4):343-50.
Comorbid depression, chronic pain, and disability in primary care
OBJECTIVES: The objectives of this study were to provide estimates of the prevalence and strength of association between major depression and chronic pain in a primary care population and to examine the clinical burden associated with the two conditions, singly and together. METHODS: A random sample of Kaiser Permanente patients who visited a primary care clinic was mailed a questionnaire assessing major depressive disorder (MDD), chronic pain, pain-related disability, somatic symptom severity, panic disorder, other anxiety, probable alcohol abuse, and health-related quality of life (HRQL). Instruments included the Patient Health Questionnaire, SF-8, and Graded Chronic Pain Questionnaire. A total of 5808 patients responded (54% of those eligible to participate). RESULTS: Among those with MDD, a significantly higher proportion reported chronic (i.e., nondisabling or disabling) pain than those without MDD (66% versus 43%, respectively). Disabling chronic pain was present in 41% of those with MDD versus 10% of those without MDD. Respondents with comorbid depression and disabling chronic pain had significantly poorer HRQL, greater somatic symptom severity, and higher prevalence of panic disorder than other respondents. The prevalence of probable alcohol abuse/dependence was significantly higher among persons with MDD compared with individuals without MDD regardless of pain or disability level. Compared with participants without MDD, the prevalence of other anxiety among those with MDD was more than sixfold greater regardless of pain or disability level. CONCLUSIONS: Chronic pain is common among those with MDD. Comorbid MDD and disabling chronic pain are associated with greater clinical burden than MDD alone.
Authors: Arnow BA; Hunkeler EM; Blasey CM; Lee J; Constantino MJ; Fireman B; Kraemer HC; Dea R; Robinson R; Hayward C
Psychosom Med. 2006 Mar-Apr;68(2):262-8.
Saw palmetto for benign prostatic hyperplasia
BACKGROUND: Saw palmetto is used by over 2 million men in the United States for the treatment of benign prostatic hyperplasia and is commonly recommended as an alternative to drugs approved by the Food and Drug Administration. METHODS: In this double-blind trial, we randomly assigned 225 men over the age of 49 years who had moderate-to-severe symptoms of benign prostatic hyperplasia to one year of treatment with saw palmetto extract (160 mg twice a day) or placebo. The primary outcome measures were changes in the scores on the American Urological Association Symptom Index (AUASI) and the maximal urinary flow rate. Secondary outcome measures included changes in prostate size, residual urinary volume after voiding, quality of life, laboratory values, and the rate of reported adverse effects. RESULTS: There was no significant difference between the saw palmetto and placebo groups in the change in AUASI scores (mean difference, 0.04 point; 95 percent confidence interval, -0.93 to 1.01), maximal urinary flow rate (mean difference, 0.43 ml per minute; 95 percent confidence interval, -0.52 to 1.38), prostate size, residual volume after voiding, quality of life, or serum prostate-specific antigen levels during the one-year study. The incidence of side effects was similar in the two groups. CONCLUSIONS: In this study, saw palmetto did not improve symptoms or objective measures of benign prostatic hyperplasia. (ClinicalTrials.gov number, NCT00037154.).
Authors: Bent S; Kane C; Shinohara K; Neuhaus J; Hudes ES; Goldberg H; Avins AL
N Engl J Med. 2006 Feb 9;354(6):557-66.
Long term outcomes from the IMPACT randomised trial for depressed elderly patients in primary care
OBJECTIVE: To determine the long term effectiveness of collaborative care management for depression in late life. DESIGN: Two arm, randomised, clinical trial; intervention one year and follow-up two years. SETTING: 18 primary care clinics in eight US healthcare organisations. Patients 1801 primary care patients aged 60 and older with major depression, dysthymia, or both. INTERVENTION: Patients were randomly assigned to a 12 month collaborative care intervention (IMPACT) or usual care for depression. Teams including a depression care manager, primary care doctor, and psychiatrist offered education, behavioural activation, antidepressants, a brief, behaviour based psychotherapy (problem solving treatment), and relapse prevention geared to each patient’s needs and preferences. MAIN OUTCOME MEASURES: Interviewers, blinded to treatment assignment, conducted interviews in person at baseline and by telephone at each subsequent follow up. They measured depression (SCL-20), overall functional impairment and quality of life (SF-12), physical functioning (PCS-12), depression treatment, and satisfaction with care. RESULTS: IMPACT patients fared significantly (P < 0.05) better than controls regarding continuation of antidepressant treatment, depressive symptoms, remission of depression, physical functioning, quality of life, self efficacy, and satisfaction with care at 18 and 24 months. One year after IMPACT resources were withdrawn, a significant difference in SCL-20 scores (0.23, P < 0.0001) favouring IMPACT patients remained. CONCLUSIONS: Tailored collaborative care actively engages older adults in treatment for depression and delivers substantial and persistent long term benefits. Benefits include less depression, better physical functioning, and an enhanced quality of life. The IMPACT model may show the way to less depression and healthier lives for older adults.
Authors: Hunkeler EM; Unutzer J; et al.
BMJ. 2006 Feb 4;332(7536):259-63. Epub 2006 Jan 20.
Depression treatment preferences in older primary care patients
PURPOSE: For depressed older primary care patients, this study aimed to examine (a) characteristics associated with depression treatment preferences; (b) predictors of receiving preferred treatment; and (c) whether receiving preferred treatment predicted satisfaction and depression outcomes. DESIGN AND METHODS: Data are from 1,602 depressed older primary care patients who participated in a multisite, randomized clinical trial comparing usual care to collaborative care, which offered medication and counseling for up to 12 months. Baseline assessment included demographics, depression, health information, prior depression treatment, potential barriers, and treatment preferences (medication, counseling). At 12 months, services received, satisfaction, and depression outcomes were assessed. RESULTS: More patients preferred counseling (57%) than medication (43%). Previous experience with a treatment type was the strongest predictor of preference. In addition, medication preference was predicted by male gender and diagnosis of major depression (vs dysthymia). The collaborative care model greatly improved access to preferred treatment, especially for counseling (74% vs 33% in usual care). Receipt of preferred treatment did not predict satisfaction or depression outcomes; these outcomes were most strongly impacted by treatment condition. IMPLICATIONS: Many depressed older primary care patients desire counseling, which is infrequently available in usual primary care. Discussion of treatment preferences should include an assessment of prior treatment experiences. A collaborative care model that increases collaboration between primary care and mental health professionals can increase access to preferred treatment. If preferred treatment is not available, collaborative care still results in good satisfaction and depression outcomes.
Authors: Gum AM; Arean PA; Hunkeler E; Tang L; Katon W; Hitchcock P; Steffens DC; Dickens J; Unutzer J
Gerontologist. 2006 Feb;46(1):14-22.
Cost-effectiveness and net benefit of enhanced treatment of depression for older adults with diabetes and depression
OBJECTIVE: To determine the incremental cost-effectiveness and net benefit of a depression collaborative care program compared with usual care for patients with diabetes and depression. RESEARCH DESIGN AND METHODS: This article describes a preplanned subgroup analysis of patients with diabetes from the Improving Mood-Promoting Access to Collaborative (IMPACT) randomized controlled trial. The setting for the study included 18 primary care clinics from eight health care organizations in five states. A total of 418 of 1,801 patients randomized to the IMPACT intervention (n = 204) versus usual care (n = 214) had coexisting diabetes. A depression care manager offered education, behavioral activation, and a choice of problem-solving treatment or support of antidepressant management by the primary care physician. The main outcomes were incremental cost-effectiveness and net benefit of the program compared with usual care. RESULTS: Relative to usual care, intervention patients experienced 115 (95% CI 72-159) more depression-free days over 24 months. Total outpatient costs were 25 dollars (95% CI -1,638 to 1,689) higher during this same period. The incremental cost per depression-free day was 25 cents (-14 dollars to 15 dollars) and the incremental cost per quality-adjusted life year ranged from 198 dollars (144-316) to 397 dollars (287-641). An incremental net benefit of 1,129 dollars (692-1,572) was found. CONCLUSIONS: The IMPACT intervention is a high-value investment for older adults with diabetes; it is associated with high clinical benefits at no greater cost than usual care.
Authors: Katon W; Unutzer J; Fan MY; Williams JW Jr; Schoenbaum M; Lin EH; Hunkeler EM
Diabetes Care. 2006 Feb;29(2):265-70.
Dissecting racial and ethnic differences
Authors: Risch N
N Engl J Med. 2006 Jan 26;354(4):408-11.
Addiction treatment history, medical services utilization, and cost: a longitudinal analysis of problem drinkers
Few studies have examined the long-term patterns of health services utilization and cost for alcohol use disorders. This paper used data from baseline, 3-year, and 5-year follow-up interviews to compare utilization and cost of medical care services for problem drinkers who received chemical dependence treatment and those who did not. The analysis examined overnight hospital stays, emergency room visits, and medical office visits. The unadjusted analysis indicates that in the year immediately preceding each follow-up period, a significantly higher percentage of the chemical dependency treatment group stayed overnight at a hospital or used ER services. In terms of medical office visits, a significantly lower percentage of the treatment sample had office visits at the 5-year follow-up, but otherwise no significant differences existed. Most of the significant differences between the two groups vanished when we controlled for covariates. Researchers, policy makers, and clinicians could benefit from such information to develop alternative delivery models, formulate research initiatives, and determine areas for potential intervention and improvement.
Authors: Alexandre PK; French MT; Matzger H; Weisner C
J Addict Dis. 2006;25(1):105-20.
Availability of services for women in outpatient substance abuse treatment: 1995-2000
Women entering substance abuse treatment have more severe substance abuse problems and more medical and psychiatric comorbidities than men. Research shows that specialized women’s services are associated with better retention and outcomes but relatively little is known about their availability nationwide. This study examined the adoption and implementation of reproductive and female-sensitive social services in a national sample of outpatient substance abuse treatment (OSAT) organizations in 1995 (N = 617) and 2000 (N = 571) by several organizational factors. Overall, reproductive and social services for women have not been widely adopted, although some services did increase over the study period, particularly social services. There was no evidence of large-scale decreases in service availability over the study period, although child care did decline. Nonprofit and public ownership (relative to for-profit) were associated with greater service provision. Managed care units had greater service adoption compared to nonmanaged care units, and this increased over time. Public units and hospital-affiliated units had greater service implementation than other units. However, OSAT units did not always implement the services they adopted, suggesting access to some services may be restricted.
Authors: Campbell CI; Alexander JA
J Behav Health Serv Res. 2006 Jan;33(1):1-19.
Adolescents with co-occurring substance use and mental conditions in a private managed care health plan: prevalence, patient characteristics, and treatment initiation and engagement
This study examined the prevalence, patient characteristics, and treatment initiation and engagement of adolescents with co-occurring substance use (SU) and serious mental health (MH) diagnoses in a private, managed care health plan. We identified 2,005 adolescents aged 12-17, who received both SU and MH diagnoses within a 1-year window between 1/1/2000 and 12/31/2002; 57% were girls. Gender variations were found in diagnoses received and point of identification. Being dually diagnosed in specialty departments (rather than Primary Care and Emergency) and receiving both diagnoses within a shorter time period were associated with treatment initiation and engagement.
Authors: Chi FW; Sterling S; Weisner C
Am J Addict. 2006;15 Suppl 1:67-79.
Translating research findings into practice: example of treatment services for adolescents in managed care
An important question in the alcoholism treatment field is how research findings can be translated into real-world clinical practice. Researchers have developed a new research-practice integration (RPI) model that can both drive the formulation of studies and new research questions and promote improvements in treatment quality. The hallmark of this model is a collaborative relationship between the key stakeholders in both alcohol and other drug (AOD) treatment and research, including health plan administrators and clinicians, treatment program administrators, psychiatry and primary care departments, patients and their families, purchasers, and researchers. The issue of technology transfer is especially relevant in the realm of adolescent AOD treatment. The implementation and feasibility of the RPI model are illustrated by a case study of a managed health care plan’s treatment services for adolescents with AOD dependence. In this setting, key research findings are being used to shape the plan’s adolescent health services.
Authors: Sterling S; Weisner C
Alcohol Res Health. 2006;29(1):11-8.
Health care services use by adolescents with intakes into an outpatient alcohol and drug treatment program
We examined utilization and cost in the 1 year pre- and post-intake among a sample of adolescents (N=419) entering chemical dependency (CD) treatment. Multivariate analyses showed that these youth used significantly more medical services than a demographically matched sample of members without substance use (SU) problems. Their utilization and costs were higher than matched members, and they did not show the same reductions in post-treatment costs that adults do. This is of concern since it would appear that the medical and mental health problems of adolescents entering CD treatment may be so severe that there are no short-term reductions in post-treatment cost, including ER and hospitalizations.
Authors: Parthasarathy S; Weisner C
Am J Addict. 2006;15 Suppl 1:113-21.
Maternal-fetal blood incompatibility and the risk of schizophrenia in offspring
OBJECTIVE: Predicated on a maternal immune response to paternally inherited foreign fetal blood antigens, we hypothesized that maternal-fetal blood incompatibility increases susceptibility to schizophrenia in the offspring. The relation between schizophrenia and maternal-fetal blood incompatibility, arising from the D antigen of the Rhesus (Rh) and the ABO blood group antigens, was examined in a cohort of live-births. METHOD: The data were drawn from the Prenatal Determinants of Schizophrenia Study, a cohort of births occurring between 1959 and 1967 to women enrolled in a Kaiser Permanente Plan-Northern California Region (KP). Adult offspring belonging to the KP from 1981 to 1997 were followed for the incidence of schizophrenia spectrum disorder (SSD). Cox proportional hazards regression was the primary analytic technique. RESULTS: Among second and later born offspring, the adjusted incidence rate ratio (RR(adj)) of SSD was 1.80 (95% CI=0.71-4.58) for the Rh incompatible offspring compared with the Rh compatible offspring; with the males exhibiting higher rate ratio (RR(adj)=2.37; 95% CI=0.82-6.86) than the females (RR(adj)=0.93 95% CI=0.12-7.01). Among all offspring, the RR(adj) for ABO incompatibility was lower and the elevated rate ratio was similarly limited to the males (RR(adj)=1.68; 95% CI=0.76-3.70). For Rh and/or ABO incompatibility, the RR(adj) was 1.57 (95% CI=0.87-2.82). A statistically significant result was detected only for the male offspring (RR(adj)=2.22; 95% CI=1.10-4.47). CONCLUSION: Although the results should be interpreted with caution given the few events of SSD, the findings extend the line of evidence that maternal-fetal blood incompatibility is a risk factor for schizophrenia spectrum disorder; with the strongest evidence to date implicating that the susceptibility pertains only to male offspring.
Authors: Insel BJ; Brown AS; Bresnahan MA; Schaefer CA; Susser ES
Schizophr Res. 2005 Dec 15;80(2-3):331-42. Epub 2005 Jul 11.
Response to Zhang et al. (2005): loss-of-function mutation in tryptophan hydroxylase-2 identified in unipolar major depression. Neuron 45, 11-16
Authors: Glatt CE; Carlson E; Taylor TR; Risch N; Reus VI; Schaefer CA
Neuron. 2005 Dec 8;48(5):704-5; author reply 705-6.
Alcoholics anonymous careers: patterns of AA involvement five years after treatment entry
BACKGROUND: Most formal treatment programs recommend Alcoholics Anonymous (AA) attendance during treatment and as a form of aftercare, but we know very little about treatment seekers’ patterns of AA involvement over time and how these relate to abstinence. METHOD: This paper applies latent class growth curve modeling to longitudinal data from 349 dependent drinkers recruited when they were entering treatment and were re-interviewed at one or more follow-up interviews one, three and five years later, and who reported having attended AA at least once. RESULTS: Four classes of AA ‘careers’ of meeting attendance emerged: The low AA group mainly just attended AA during the 12 months following treatment entry. The medium and high AA groups were characterized by stable attendance at the second and third follow-ups-at about 60 meetings a year for the medium group and over 200 meetings per year for the high group, followed by slight increases for the medium group and slight decreases for the high group by year five. The declining AA group doubled its meeting attendance postbaseline, to almost 200 meetings during the year following treatment entry, but by year five they were only attending about six meetings on average. Decreases in AA meetings did not necessarily signal disengagement from AA; at the five-year follow-up, a third of the low AA group and over half of the declining AA group said they felt like a member of AA. Activities other than meeting attendance, such as having a sponsor, otherwise paralleled the meeting careers, but social networks were similar by year five. Rates of abstinence by year five (for the past 30 days) were 43% for the low AA group, 73% for the medium group, 79% for the high group and 61% for the declining group. Rates of dependence symptoms and social consequences of drinking did not differ between the groups at year five. CONCLUSIONS: The prototypical AA careers derived empirically are consistent with anecdotal data about AA meetings: some never connect; some connect but briefly; and others maintain stable (and sometimes quite high) rates of AA attendance. However, contrary to AA lore, many who connect only for a while do well afterwards.
Authors: Kaskutas LA; Ammon L; Delucchi K; Room R; Bond J; Weisner C
Alcohol Clin Exp Res. 2005 Nov;29(11):1983-90.
Readmission among chemical dependency patients in private, outpatient treatment: patterns, correlates and role in long-term outcome
OBJECTIVE: Similar to other chronic conditions, chemical dependency is a chronic, relapsing condition. Yet predominant treatment models do not provide ongoing, long-term treatment services; readmission is the available long-term care for alcohol and drug patients. We examine readmission patterns and the role of readmission in 5-year outcome in chemical dependency patients in a private, integrated health plan. METHOD: We used health plan utilization databases and self-report at 5-year follow-up to measure readmission and routine primary care services in 647 chemical dependency outpatients from a private health plan. Logistic regression was used to examine whether readmission and primary medical care predicted abstinence at 5 years. RESULTS: Controlling for demographic characteristics and dependence type, higher odds for past-year alcohol and drug abstinence at 5 years following treatment was predicted by having been readmitted in the first 4 years after index episode (odds ratio =1.59, p = .006). Receiving routine medical care predicted past 30-day (but not past-year) abstinence at 5-year follow-up. CONCLUSIONS: The relationship of readmissions to better outcome at 5 years suggests that long-term continuing care may benefit patients’ long-term outcomes. More research is needed on the relationship of primary medical care to long-term outcome in chemical dependency patients.
Authors: Mertens JR; Weisner CM; Ray GT
J Stud Alcohol. 2005 Nov;66(6):842-7.
Five-year trajectories of health care utilization and cost in a drug and alcohol treatment sample
BACKGROUND: The study examined the effect of individual characteristics on longitudinal patterns of health care utilization and cost among individuals entering chemical dependency (CD) treatment. METHOD: Structured interviews and computerized administrative databases were linked to obtain severity, utilization and cost data. Total medical costs and their components were examined for the 6 months prior to intake through 5 years post-intake. Statistical analyses were conducted using the hierarchical linear modeling framework. RESULTS: Age was positively correlated with total medical costs. Women had higher inpatient utilization and higher inpatient, primary care and total cost at baseline (p<.05). However, they had steeper decline in primary care costs. While age was not related to inpatient and ER use at baseline (after controlling for psychiatric and medical severity), older individuals had smaller declines in hospital days and inpatient cost over time. Individuals with high medical and psychiatric severity had higher utilization and costs (p<.01). Those who were abstinent had higher costs. CONCLUSIONS: There are important differences in patient characteristics and treatment outcomes that influence utilization and cost trajectories. The relationship between medical severity at intake and primary care cost pre-intake among patients with drug and alcohol problems suggests an opportunity to identify and treat drug and alcohol problems in primary care settings. It also suggests that medical evaluations and treatment should not be overlooked during CD treatment. The positive association between abstinence and trajectories of primary care and total medical costs suggests that maintaining abstinence over a long term requires some kind of continuing care either in primary care settings or via additional contacts with specialty CD departments.
Authors: Parthasarathy S; Weisner CM
Drug Alcohol Depend. 2005 Nov 1;80(2):231-40.
Reasons for drinking less and their relationship to sustained remission from problem drinking
AIMS: To compare representative general population and treated samples on their reasons for drinking less and whether particular reasons were related to sustained remission from problem drinking for either group. PARTICIPANTS AND DESIGN: A total of 659 problem drinking adults in a Northern California county identified through a probability survey in the general population (n = 239) and a survey of consecutive admissions to public and private alcohol and drug programs (n = 420), who reported drinking less at the one-year follow-up and provided reasons for reducing their drinking, were assessed 1-, 3-, and 5-years post-baseline regarding their problem drinking status. MEASUREMENTS: Logistic regression models were used to predict sustained remission from problem drinking. RESULTS: While the treated sample endorsed a majority of reasons in significantly higher proportions than the general population sample, the same three reasons were significant for both groups in predicting sustained remission from problem drinking: hitting rock bottom, experiencing a traumatic event and undergoing a spiritual awakening. Interventions by medical personnel and family members were either non-significant predictors or significantly negatively related to sustained improvement for both general population and treated problem drinkers. CONCLUSIONS: General population and treatment samples have similar reasons for cutting down as they relate to sustained remission from problem drinking.
Authors: Matzger H; Kaskutas LA; Weisner C
Addiction. 2005 Nov;100(11):1637-46.
Community providers’ views of alcohol and drug problems
This study contrasts community health and social service providers’ views on alcohol vs. other drug abuse. A probability sample of 457 social work and other providers from a county’s public and private medical and mental health clinics, welfare and criminal justice systems, and substance abuse programs, as well as clergy, private therapists, and physicians were interviewed. For both alcohol and drug problems, providers thought only of severe dysfunctions, which suggest that less severe forms of these problems may evade detection. In addition, drug problems were viewed as more harmful than alcohol problems, which may result in providers minimizing alcohol problems.
Authors: Gassman RA; Weisner C
J Soc Work Pract Addict. 2005 Oct;5(4):101-15. Epub 2008 Oct 13.
Alcohol consumption, risk of injury, and high-cost medical care
This study examined the effect of alcohol use on the probabilities of injury, inpatient hospital stay, and emergency department visit. Data were obtained from a sample of adults (N = 1219) recruited from a Northern California county. Alcohol use measures included number of drinks, heavy drinking days, and an indicator variable for problem drinking. Models were estimated for men and women separately while controlling for confounders. Results indicate that most alcohol use measures were not significantly related to injury probability or medical care utilization. Among the exceptions, problem drinking was a significant positive predictor of any emergency department visit for both sexes. When drinkers during the past year were divided into light, moderate, and heavy drinking groups and compared to lifetime abstainers, all male drinkers had a higher probability of injury, and light and moderate female drinkers had a lower probability of an emergency department visit.
Authors: Salome HJ; French MT; Matzger H; Weisner C
J Behav Health Serv Res. 2005 Oct-Dec;32(4):368-80.
Adolescents in private chemical dependency programs: who are most at risk for HIV?
Consecutive intakes (N = 419) between ages 13 and 18 years to chemical dependency (CD) programs in a large private health plan were interviewed. The prevalence of six HIV risk behaviors was measured and categorized into zero, one, and multiple risk groups. The relationships between both demographic characteristics and substance use with HIV risk behaviors were examined. Approximately half the sample reported at least one risk behavior, with 17% reporting multiple risk behaviors. Those most likely to report multiple risk behaviors were heavy drinking boys, as well as girls who reported using narcotic analgesics. Implications of these findings for pediatricians and CD clinicians are discussed.
Authors: Ammon L; Sterling S; Mertens J; Weisner C
J Subst Abuse Treat. 2005 Jul;29(1):39-45.
Spontaneous bleeding associated with ginkgo biloba: a case report and systematic review of the literature: a case report and systematic review of the literature
BACKGROUND: Ginkgo biloba (ginkgo) is a herbal remedy used by over 2% of the adult population in the United States. Several review articles have suggested that ginkgo may increase the risk of bleeding. OBJECTIVE: To report a case of bleeding associated with using ginkgo, to systematically review the literature for similar case reports, and to evaluate whether using ginkgo is causally related to bleeding. DATA SOURCES: We searched MEDLINE, EMBASE, IBIDS, and the Cochrane Collaboration Database from 1966 to October 2004 with no language restrictions. REVIEW METHODS: Published case reports of bleeding events in persons using ginkgo were selected. Two reviewers independently abstracted a standard set of information to assess whether ginkgo caused the bleeding event. RESULTS: Fifteen published case reports described a temporal association between using ginkgo and a bleeding event. Most cases involved serious medical conditions, including 8 episodes of intracranial bleeding. However, 13 of the case reports identified other risk factors for bleeding. Only 6 reports clearly described that ginkgo was stopped and that bleeding did not recur. Bleeding times, measured in 3 reports, were elevated when patients were taking ginkgo. CONCLUSION: A structured assessment of published case reports suggests a possible causal association between using ginkgo and bleeding events. Given the widespread use of this herb and the serious nature of the reported events, further studies are needed. Patients using ginkgo, particularly those with known bleeding risks, should be counseled about a possible increase in bleeding risk.
Authors: Bent S; Goldberg H; Padula A; Avins AL
J Gen Intern Med. 2005 Jul;20(7):657-61.
Obesity in middle age and future risk of dementia: a 27 year longitudinal population based study
OBJECTIVE: To evaluate any association between obesity in middle age, measured by body mass index and skinfold thickness, and risk of dementia later in life. DESIGN: Analysis of prospective data from a multiethnic population based cohort. SETTING: Kaiser Permanente Northern California Medical Group, a healthcare delivery organisation. PARTICIPANTS: 10,276 men and women who underwent detailed health evaluations from 1964 to 1973 when they were aged 40-45 and who were still members of the health plan in 1994. MAIN OUTCOME MEASURES: Diagnosis of dementia from January 1994 to April 2003. Time to diagnosis was analysed with Cox proportional hazard models adjusted for age, sex, race, education, smoking, alcohol use, marital status, diabetes, hypertension, hyperlipidaemia, stroke, and ischaemic heart disease. RESULTS: Dementia was diagnosed in 713 (6.9%) participants. Obese people (body mass index > or = 30) had a 74% increased risk of dementia (hazard ratio 1.74, 95% confidence interval 1.34 to 2.26), while overweight people (body mass index 25.0-29.9) had a 35% greater risk of dementia (1.35, 1.14 to 1.60) compared with those of normal weight (body mass index 18.6-24.9). Compared with those in the lowest fifth, men and women in the highest fifth of the distribution of subscapular or tricep skinfold thickness had a 72% and 59% greater risk of dementia, respectively (1.72, 1.36 to 2.18, and 1.59, 1.24 to 2.04). CONCLUSIONS: Obesity in middle age increases the risk of future dementia independently of comorbid conditions.
Authors: Whitmer RA; Gunderson EP; Barrett-Connor E; Quesenberry CP Jr; Yaffe K
BMJ. 2005 Jun 11;330(7504):1360. Epub 2005 Apr 29.
Hazardous drinkers and drug users in HMO primary care: prevalence, medical conditions, and costs
BACKGROUND: There exists substantial evidence that individuals with alcohol and drug disorders have heightened comorbidities and health care costs. However, little is known about the larger population of ‘hazardous’ drinkers (those whose consumption increases their ‘risk of physical and psychological harm’) and drug users. METHODS: A sample of 1,419 patients from HMO primary care clinics was screened for hazardous drinking and drug use. Health plan databases were used to examine medical conditions and health care costs of hazardous drinkers and drug users in the year prior to screening, in comparison to 13,347 patients from the same clinics, excluding those screened. RESULTS: We found a prevalence of 7.5% for hazardous drinking and 3.2% for drug use in primary care (10% had at least one of the two problems). Hazardous drinkers and drug users had heightened prevalences for eight medical conditions, including costly conditions such as injury and hypertension, and psychiatric conditions. Medical costs for the year examined were not higher, except for those who also had psychiatric conditions. CONCLUSIONS: The prevalence of hazardous drinking and drug use was similar to hypertension and diabetes. Hazardous drinkers and drug users’ heightened medical conditions, especially those related to alcohol and drug abuse, indicate that screening and brief intervention at this lower threshold of hazardous drinking and drug use will detect individuals with health risks sooner. Optimal treatment and prevention of some medical disorders may require identification and intervention of underlying hazardous alcohol or drug use.
Authors: Mertens JR; Weisner C; Ray GT; Fireman B; Walsh K
Alcohol Clin Exp Res. 2005 Jun;29(6):989-98.
Health services for women in outpatient substance abuse treatment
OBJECTIVE: To evaluate how a sample of outpatient substance abuse treatment units respond to organizational and environmental influences by adopting and implementing treatment services for women. DATA SOURCES: The National Drug Abuse Treatment System Survey from 1995 and 2000, a national survey of outpatient substance abuse treatment units. STUDY DESIGN: Health services for women are the dependent variables. The predictors include organizational and environmental factors that represent resource dependence and institutional pressures for the treatment unit. Logistic regression and Heckman selection models were used to test hypotheses. DATA COLLECTION: Program directors and clinical supervisors at each treatment unit were interviewed by telephone in 1995 and 2000. PRINCIPAL FINDINGS: Units that depended on specific funding for women’s programs and that depended on government funds were more likely to adopt, but not necessarily implement, women’s services. Methadone units and units that train more staff to work with women were more likely to adopt as well as implement women’s services. Private not-for-profit units were more likely to adopt some services, while for-profit units were less so. However, in general, neither for-profit nor not-for-profit units significantly implemented services. There was evidence that the odds of adopting services were greater in 2000 than 1995 for two services, but were otherwise stable. CONCLUSIONS: There is considerable variation in the adoption and implementation of women’s services. In addition, not all adopted services were significantly implemented, which could reflect limited organizational resources and/or conflicting expectations. This also suggests that referral mechanisms to these services, and therefore access, may not be adequate. Government funds and specific funds for women’s programs are important resources for the provision of these services. Women’s services appear more available in methadone units, suggesting that regulation has been influential and that the recent methadone accreditation system should be evaluated. Staff training may be one strategy to encourage implementation of these services. For the most part, the adoption of services for women did not change between 1995 and 2000.
Authors: Campbell CI; Alexander JA
Health Serv Res. 2005 Jun;40(3):781-810.
Use of an embedded N-of-1 trial to improve adherence and increase information from a clinical study
Withdrawal of participants from randomized trials can occur because of symptoms thought to be related to the study medicine, but the causal relationship between the study medicine and the symptoms is often unclear. Single-patient trials (‘N-of-1 trials’), developed to identify optimal therapy for an individual patient in the clinical setting, may provide a means of resolving some of these dilemmas. We describe here the use of an N-of-1 study embedded within a placebo-controlled trial of saw palmetto for a participant who considered withdrawing because he believed the study medication caused an increase in his blood pressure. In this case, the N-of-1 study not only reassured the patient, who decided to remain in the study, but provided potentially useful new information regarding the study medication. Wider use of formal N-of-1 studies may be a valuable tool for improving adherence and determining whether observed side effects are caused by study medication in clinical trials.
Authors: Avins AL; Bent S; Neuhaus JM
Contemp Clin Trials. 2005 Jun;26(3):397-401. Epub 2005 Mar 28.
Chemical dependency and psychiatric services for adolescents in private managed care: implications for outcomes
BACKGROUND: Many adolescents with alcohol and drug problems have mental health comorbidities. The literature suggests that patients entering chemical dependency (CD) treatment with co-occurring problems have less successful outcomes, including treatment dropout and relapse. We examined the impact of psychiatric services on treatment initiation, retention, and alcohol and drug abstinence outcomes for adolescents in CD treatment. METHODS: Participants were 419 adolescents aged 12-18 years who were seeking treatment at four CD programs of a nonprofit, managed care, group model health system and a parent or guardian for each adolescent. We surveyed participants at intake and 6 months and examined clinical and administrative data on diagnoses and CD and psychiatric utilization. Six-month response rates were 91% for adolescents and 93% for parents. RESULTS: Fifty-five percent of the patients with treatment intakes had at least one psychiatric diagnosis in addition to a substance use disorder. Compared with matched controls, patients with CD intakes had higher rates of depression, anxiety, eating disorders, attention deficit hyperactivity disorder, conduct disorder, and conduct disorder including oppositional defiant disorder. Thirty-one percent of the full sample had psychiatric visits in the 6 months after intake; among those with a psychiatric diagnosis, 54% had a psychiatric visit. Girls and those with higher Youth Self-Report internalizing scores were more likely to have a psychiatric visit (OR = 2.27, p < 0.001 and OR = 1.05, p < 0.0001, respectively). Adolescents receiving psychiatric services were more likely to be abstinent from both alcohol and drugs than those not receiving these services (OR = 1.57, 95% CI = 0.98-2.5) and more likely to be alcohol abstinent (OR = 1.68, 95% CI = 1.00-2.85). Those adolescents at colocated clinics had higher odds of abstinence from both alcohol and drugs (OR = 1.57, 95% CI = 1.03-2.39) and drugs (OR = 1.84, 95% CI = 1.87-2.85) and of returning after intake to initiate CD treatment (OR = 2.28, 95% CI = 1.44-3.61, p < 0.001) than others. CONCLUSIONS: Our results demonstrate the need for psychiatric treatment of adolescents in CD treatment and highlight the importance of their receiving such services.
Authors: Sterling S; Weisner C
Alcohol Clin Exp Res. 2005 May;29(5):801-9.
Maternal exposure to toxoplasmosis and risk of schizophrenia in adult offspring
OBJECTIVE: The authors examined the relationship between maternal antibody to toxoplasmosis and the risk of schizophrenia and other schizophrenia spectrum disorders in offspring. Toxoplasmosis is known to adversely affect fetal brain development. METHOD: In a nested case-control design of a large birth cohort born between 1959 and 1967, the authors conducted serological assays for Toxoplasma antibody on maternal serum specimens from pregnancies giving rise to 63 cases of schizophrenia and other schizophrenia spectrum disorders and 123 matched comparison subjects. Toxoplasma immunoglobulin (Ig)G antibody was quantified by using the Sabin-Feldman dye test. The Ig titers were classified into three groups: negative (<1:16) (reference), moderate (1:16-1:64), and high (> or =1:128). RESULTS: The adjusted odds ratio of schizophrenia/schizophrenia spectrum disorders for subjects with high maternal Toxoplasma IgG antibody titers was 2.61 (95% confidence interval=1.00-6.82). There was no association between moderate Toxoplasma Ig antibody titers and the risk of schizophrenia/spectrum disorders. CONCLUSIONS: These findings suggest that maternal exposure to toxoplasmosis may be a risk factor for schizophrenia. The findings may be explained by reactivated infection or an effect of the antibody on the developing fetus. Given that toxoplasmosis is a preventable infection, the findings, if replicated, may have implications for reducing the incidence of schizophrenia.
Authors: Brown AS; Schaefer CA; Quesenberry CP Jr; Liu L; Babulas VP; Susser ES
Am J Psychiatry. 2005 Apr;162(4):767-73.
Improving depression care for older, minority patients in primary care
OBJECTIVE: Few older minorities receive adequate treatment of depression in primary care. This study examines whether a collaborative care model for depression in primary care is as effective in older minorities as it is in nonminority elderly patients in improving depression treatment and outcomes. STUDY DESIGN: A multisite randomized clinical trial of 1801 older adults comparing collaborative care for depression with treatment as usual in primary care. Twelve percent of the sample were black (n = 222), 8% were Latino (n = 138), and 3% (n = 53) were from other minority groups. We compared the 3 largest ethnic groups (non-Latino white, black, and Latino) on depression severity, quality of life, and mental health service use at baseline, 3, 6, and 12 months after randomization to collaborative care or usual care. PRINCIPAL FINDINGS: Compared with care as usual, collaborative care significantly improved rates and outcomes of depression care in older adults from ethnic minority groups and in older whites. At 12 months, intervention patients from ethnic minorities (blacks and Latinos) had significantly greater rates of depression care for both antidepressant medication and psychotherapy, lower depression severity, and less health-related functional impairment than usual care participants (64%, 95% confidence interval [CI] 55-72 versus 45%, CI 36-55, P = 0.003 for antidepressant medication; 37%, CI 28-47 versus 13%, CI 6-19, P = 0.002 for psychotherapy; mean = 0.9, CI 0.8-1.1 versus mean = 1.4, CI 1.3-1.5, P < 0.001 for depression severity, range 0-4; mean = 3.7, CI 3.2-4.1, versus mean = 4.7, CI 4.3-5.1, P < 0.0001 for functional impairment, range 0-10). CONCLUSIONS: Collaborative Care is significantly more effective than usual care for depressed older adults, regardless of their ethnicity. Intervention effects in ethnic minority participants were similar to those observed in whites.
Authors: Arean PA; Ayalon L; Hunkeler E; Lin EH; Tang L; Harpole L; Hendrie H; Williams JW Jr; Unutzer J; IMPACT Investigators
Med Care. 2005 Apr;43(4):381-90.
Treatment of depression improves physical functioning in older adults
OBJECTIVES: To determine the effect of collaborative care management for depression on physical functioning in older adults. DESIGN: Multisite randomized clinical trial. SETTING: Eighteen primary care clinics from eight healthcare organizations. PARTICIPANTS: One thousand eight hundred one patients aged 60 and older with major depressive disorder. INTERVENTION: Patients were randomized to the Improving Mood: Promoting Access to Collaborative Treatment (IMPACT) intervention (n=906) or to a control group receiving usual care (n=895). Control patients had access to all health services available as part of usual care. Intervention patients had access for 12 months to a depression clinical specialist who coordinated depression care with their primary care physician. MEASUREMENTS: The 12-item short form Physical Component Summary (PCS) score (range 0-100) and instrumental activities of daily living (IADLs) (range 0-7). RESULTS: The mean patient age was 71.2, 65% were women, and 77% were white. At baseline, the mean PCS was 40.2, and the mean number of IADL dependencies was 0.7; 45% of participants rated their health as fair or poor. Intervention patients experienced significantly better physical functioning at 1 year than usual-care patients as measured using between-group differences on the PCS of 1.71 (95% confidence interval (CI)=0.96-2.46) and IADLs of -0.15 (95% CI=-0.29 to -0.01). Intervention patients were also less likely to rate their health as fair or poor (37.3% vs 52.4%, P<.001). Combining both study groups, patients whose depression improved were more likely to experience improvement in physical functioning. CONCLUSION: The IMPACT collaborative care model for late-life depression improves physical function more than usual care.
Authors: Callahan CM; Kroenke K; Counsell SR; Hendrie HC; Perkins AJ; Katon W; Noel PH; Harpole L; Hunkeler EM; Unutzer J; IMPACT Investigators
J Am Geriatr Soc. 2005 Mar;53(3):367-73.
Treatment with stimulants among youths in a large California health plan
OBJECTIVE: The aim of this study was to examine the use of stimulants among youths in a large and diverse health plan in California from 1996-2000. METHODS: Computerized pharmacy, outpatient visit, and membership files were used to conduct a population-based analysis of stimulant use among over 500,000 enrollees aged 2-18 years. Annual prevalence rates of stimulant use were estimated by calendar year, age, gender, and geographic area. RESULTS: The annual percentage of continuously enrolled 2- through 18-year-olds receiving at least one prescription for a stimulant rose from 1.86% (95% confidence interval (CI) 1.82-1.90) in 1996 to 1.93% (95% CI, 1.90-1.96) in 2000. An increase was observed only among girls 8 years of age or older and among boys 12 years or older. Use of methylphenidate decreased, whereas use of extended-release amphetamine products increased. Stimulant use was lower and use of other psychotropic drugs was higher among children with visits for attention-deficit/hyperactivity disorder (ADHD) and a coexisting psychiatric disorder than among those seen for ADHD alone. Of the 11,698 children receiving at least one stimulant in 2000, 24% of these children received a single prescription. Approximately 55% of stimulant prescriptions were written by physicians in pediatrics and 45% by physicians in psychiatry. CONCLUSIONS: The prevalence of treatment with stimulants was lower than what generally has been reported in other parts of the United States; it increased by approximately 4% between 1996 and 2000, and was frequently short term or intermittent.
Authors: Habel LA; Schaefer CA; Levine P; Bhat AK; Elliott G
J Child Adolesc Psychopharmacol. 2005 Feb;15(1):62-7.
Relationship between use of psychiatric services and five-year alcohol and drug treatment outcomes
OBJECTIVE: The objective of this study was to examine the relationship between use of psychiatric services and alcohol and drug treatment outcomes five years after such treatment. It was anticipated that receipt of psychiatric services would predict long-term abstinence. METHODS: A sample of 604 outpatients from a managed care organization’s chemical dependency program was interviewed about substance use and severity of psychiatric symptoms at baseline and at five years. Patients were required to have at least three years of membership in the health plan during the five years after intake. Severity of psychiatric symptoms was categorized as zero, low, middle, or high. Use of psychiatric services was ascertained on the basis of administrative data from the health plan. Logistic regression analysis was used to assess the relationship between receipt of psychiatric services during the five years after intake and abstinence at five years. Results were adjusted for individual, treatment, and extra-treatment characteristics; severity of psychiatric symptoms at baseline; and other contacts with the health system. RESULTS: Patients who received a threshold level of psychiatric services (an average of at least 2.1 hours a year) were significantly more likely to be abstinent at five years than patients who received less than 2.1 hours a year. CONCLUSIONS: The use of psychiatric services among patients with chemical dependency is associated with enhanced long-term outcomes.
Authors: Ray GT; Weisner CM; Mertens JR
Psychiatr Serv. 2005 Feb;56(2):164-71.
Trends in use of antidepressants, lithium, and anticonvulsants in Kaiser Permanente-insured youths, 1994-2003
In view of the current controversy regarding the use of antidepressants in children and adolescents, we examined trends from 1994 to 2003 in the use of antidepressants, lithium, and anticonvulsants by enrollees, aged 5-17 years, of Kaiser Permanente in Northern California. We found that the use of antidepressants more than doubled from 9.4 per 1000 enrollees to 21.3 per 1000. Most of this increase is associated with selective serotonin reuptake inhibitors (SSRIs), which increased from 4.6 to 14.5 per 1000. The use of tricyclic antidepressants (TCAs) decreased markedly, while the increase of other newer antidepressants rose from 1.3 to 6.5 per 1000. The use of anticonvulsants nearly doubled, from 3.5 to 6.9 per 1000, while lithium use was relatively stable at a rate of nearly 1 per 1000. Use of SSRIs, newer antidepressants, and anticonvulsants increased in boys as well as girls in each of three age groups: 5-9, 10-14, and 15-17 years. An increasing percentage of the antidepressant users had a diagnosis of depression, and an increasing percentage of anticonvulsant users had a diagnosis of bipolar disorder. Although the safety and efficacy of antidepressants in youths needs to be more firmly established, these findings may reflect progress in the diagnosis and treatment of mental illness.
Authors: Hunkeler EM; Fireman B; Lee J; Diamond R; Hamilton J; He CX; Dea R; Nowell WB; Hargreaves WA
J Child Adolesc Psychopharmacol. 2005 Feb;15(1):26-37.
Midlife cardiovascular risk factors and risk of dementia in late life
OBJECTIVE: To evaluate if midlife cardiovascular risk factors are associated with risk of late-life dementia in a large, diverse cohort. METHOD: The authors conducted a retrospective cohort study of 8,845 participants of a health maintenance organization who underwent health evaluations from 1964 to 1973 when they were between the ages of 40 and 44. Midlife cardiovascular risk factors included total cholesterol, diabetes, hypertension, and smoking. Diagnoses of dementia were ascertained by medical records from January 1994 to April 2003. RESULTS: The authors identified 721 participants (8.2%) with dementia. Smoking, hypertension, high cholesterol, and diabetes at midlife were each associated with a 20 to 40% increase in risk of dementia (fully adjusted Cox proportional hazards model: HR 1.24, 95% CI 1.04 to 1.48 for hypertension, HR 1.26, 95% CI 1.08 to 1.47 for smoking, HR 1.42, 95% CI 1.22 to 1.66 for high cholesterol, and HR 1.46, 95% CI 1.19 to 1.79 for diabetes). A composite cardiovascular risk score was created using all four risk factors and was associated with dementia in a dose-dependent fashion. Compared with participants having no risk factors, the risk for dementia increased from 1.27 for having one risk factor to 2.37 for having all four risk factors (fully adjusted model: HR 2.37, 95% CI 1.10 to 5.10). CONCLUSION: The presence of multiple cardiovascular risk factors at midlife substantially increases risk of late-life dementia in a dose dependent manner.
Authors: Whitmer RA; Sidney S; Selby J; Johnston SC; Yaffe K
Neurology. 2005 Jan 25;64(2):277-81.
Substance misuse: what place for women-only treatment programs?
Authors: Weisner C
Addiction. 2005 Jan;100(1):7-8.
Substance abuse and HIV risk behaviours amongst primary health care service users in Cape Town
Objective: To document prevalence of, and association between, substance use and HIV risk behaviours among primary care patients. Method: Cross-sectional survey. Four primary care clinics in Cape Town. We selected clinics using stratified sampling, and systematically selected 131 patients from attendance logs. We assessed substance use with the Alcohol, Smoking and Substance Involvement Screening Test, and HIV risk with items addressing injection drug use, blood-sharing rituals, and sexual risk behaviours. Results: Substances most used at hazardous levels were tobacco (28.2%) and alcohol (14.8%). Among possible HIV risk factors, highest prevalence was participation in blood-sharing rituals (25%), and having had an STI (19.8%). An association between substance use and sexual risk behaviours was only found among those aged 18-24. Conclusion: In younger patients, presence of substance use or HIV risk behaviours increases the probability that the other is present.
Authors: Ward CL; Mertens JR; Flisher AJ; Bresick GF; Sterling S; Distiller GB; Weisner CM
S Afr Psychiatry Rev. 2005;8:160-5.
Pathways to chemical dependency treatment for adolescents in an HMO
This study examines pathways to chemical dependency (CD) treatment for adolescents in a prepaid health plan, including factors influencing treatment referral and access. Data were collected from 419 adolescent CD treatment intakes ages 13 to 18 in a large, private health plan. The study examines predictors of referral from different sources and of mental health treatment prior to CD treatment. Referral patterns, problem severity, and psychiatric comorbidity differed by gender. Being male (p < .05) and higher scores on the Youth Self-Report (YSR) externalizing scale (p < .01) predicted a justice system referral. Using more types of substances predicted referral by medical and mental health providers (p < .05) and self-referral (p < .01). Higher YSR internalizing scores predicted referral from mental health (p < .01) and self-referral (p <.01). Being White versus African American (p < .05) or Latino (p < .01), older (p < .05), and having higher YSR internalizing scores (p < .05), a conduct disorder (p < .01), or a family member with a substance use problem (p < .01) predicted a mental health visit prior to CD intake. The findings raise questions regarding the role of health plans, clinicians, families, schools, and community agencies in referring and treating adolescents with substance use problems. They suggest that improved coordination of care may promote more integrated treatment practices, which could decrease substance use, mental health, and medical problem severity.
Authors: Sterling S; Kohn C; Lu Y; Weisner C
J Psychoactive Drugs. 2004 Dec;36(4):439-53.
Depression and comorbid illness in elderly primary care patients: impact on multiple domains of health status and well-being
PURPOSE: Our objective was to examine the relative association of depression severity and chronicity, other comorbid psychiatric conditions, and coexisting medical illnesses with multiple domains of health status among primary care patients with clinical depression. METHODS: We collected cross-sectional data as part of a treatment effectiveness trial that was conducted in 8 diverse health care organizations. Patients aged 60 years and older (N = 1,801) who met diagnostic criteria for major depression or dysthymia participated in a baseline survey. A survey instrument included questions on sociodemographic characteristics, depression severity and chronicity, neuroticism, and the presence of 11 common chronic medical illnesses, as well as questions screening for panic disorder and posttraumatic stress disorder. Measures of 4 general health indicators (physical and mental component scales of the SF-12, Sheehan Disability Index, and global quality of life) were included. We conducted separate mixed-effect regression linear models predicting each of the 4 general health indicators. RESULTS: Depression severity was significantly associated with all 4 indicators of general health after controlling for sociodemographic differences, other psychological dysfunction, and the presence of 11 chronic medical conditions. Although study participants had an average of 3.8 chronic medical illnesses, depression severity made larger independent contributions to 3 of the 4 general health indicators (mental functional status, disability, and quality of life) than the medical comorbidities. CONCLUSIONS: Recognition and treatment of depression has the potential to improve functioning and quality of life in spite of the presence of other medical comorbidities.
Authors: Noel PH; Williams JW Jr; Unutzer J; Worchel J; Lee S; Cornell J; Katon W; Harpole LH; Hunkeler E
Ann Fam Med. 2004 Nov-Dec;2(6):555-62.
Five-year alcohol and drug treatment outcomes of older adults versus middle-aged and younger adults in a managed care program
AIMS: This study compared 5-year treatment outcomes of older adults to those of middle-aged and younger adults in a large managed care chemical dependency program. We examined age group differences in individual, treatment and extra-treatment factors, which may influence long-term outcome. DESIGN: Seventy-seven per cent of original study participants completed a telephone interview 5 years after out-patient chemical dependency treatment at Kaiser Permanente. This sample (N = 925) included 65 patients aged 55-77, 296 patients aged 40-54 and 564 patients aged 18-39 (age at baseline). MEASUREMENTS: Measures at follow-up included alcohol and drug use, Addiction Severity Index (ASI), Alcoholics Anonymous Affiliation Scale, social resource and self-reported health questions. Mortality data were obtained from contact with family members of patients as well as automated health plan records. FINDINGS: Older adults were less likely to be drug-dependent at baseline than younger and middle-aged adults, and had longer retention in treatment than younger adults. At 5 years, older adults were less likely than younger adults to have close family or friends who encouraged alcohol or drug use. Fifty-two per cent of older adults reported total abstinence from alcohol and drugs in the previous 30 days versus 40% of younger adults. Older women had higher 30-day abstinence than older men or younger women. Among participants dependent only on alcohol, there were no significant age differences in 30-day abstinence. In logistic regression analysis, age group was not significant. Variables associated with greater age that independently predicted 30-day abstinence in the logistic regression model included longer retention in treatment and having no close family or friends who encouraged alcohol or drug use at 5 years; female gender was also significant. CONCLUSIONS: Results indicate that older adults have favorable long-term outcome following treatment relative to younger adults, but these differences may be accounted for by variables associated with age such as type of substance dependence, treatment retention, social networks and gender. Age differences in these characteristics inform intervention strategies to support long-term recovery of older adults and provide direction for investigation of how age affects outcome.
Authors: Satre DD; Mertens JR; Arean PA; Weisner C
Addiction. 2004 Oct;99(10):1286-97.
Incidence and duration of side effects and those rated as bothersome with selective serotonin reuptake inhibitor treatment for depression: patient report versus physician estimate
BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are widely used as the first-line treatment for depression. Information regarding their side effects is mostly based on controlled clinical trials. METHOD: Patients who received an SSRI for a new or recurrent case of depression (ICD-9 code 296.2 or 311) between December 15, 1999, and May 31, 2000 were interviewed by telephone 75 to 105 days after initiation of SSRI therapy. Using closed-ended questions, investigators asked patients if they experienced any of 17 side effects commonly associated with SSRIs, how bothersome they were, and what their duration was. Prescribing physicians completed a written survey providing their estimates about frequency of side effects associated with SSRIs and how bothersome those side effects are. RESULTS: Of 401 patients who completed the phone interview, 344 patients (86%) reported at least 1 side effect, and 219 patients (55%) experienced 1 or more bothersome side effect(s). The most common bothersome side effects were sexual dysfunction and drowsiness (17% each). While most side effects first occurred within the first 2 weeks of treatment, the majority of patients were still experiencing the same side effects at the time of interview, most notably blurred vision (85%) and sexual dysfunction (83%). Overall, physicians (N = 137) significantly underestimated the occurrence of the 17 side effects explored, and they tended to underrate how bothersome those side effects were to their patients. CONCLUSION: Side effects associated with SSRIs are common and bothersome to patients. Treatment-emergent side effects tend to persist during the first 3 months of treatment.
Authors: Hu XH; Bull SA; Hunkeler EM; Ming E; Lee JY; Fireman B; Markson LE
J Clin Psychiatry. 2004 Jul;65(7):959-65.
The effectiveness of depression care management on diabetes-related outcomes in older patients
BACKGROUND: Depression frequently occurs in combination with diabetes mellitus, adversely affecting the course of illness. OBJECTIVE: To determine whether enhancing care for depression improves affective and diabetic outcomes in older adults with diabetes and depression. DESIGN: Preplanned subgroup analysis of the Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) randomized, controlled trial. SETTING: 18 primary care clinics from 8 health care organizations in 5 states. PATIENTS: 1801 patients 60 years of age or older with depression; 417 had coexisting diabetes mellitus. INTERVENTION: A care manager offered education, problem-solving treatment, or support for antidepressant management by the patient’s primary care physician; diabetes care was not specifically enhanced. MEASUREMENTS: Assessments at baseline and at 3, 6, and 12 months for depression, functional impairment, and diabetes self-care behaviors. Hemoglobin A(1c) levels were obtained for 293 patients at baseline and at 6 and 12 months. RESULTS: At 12 months, diabetic patients who were assigned to intervention had less severe depression (range, 0 to 4 on a checklist of 20 depression items; between-group difference, -0.43 [95% CI, -0.57 to -0.29]; P < 0.001) and greater improvement in overall functioning (range, 0 [none] to 10 [unable to perform activities]; between-group difference, -0.89 [CI, -1.46 to -0.32]) than did participants who received usual care. In the intervention group, weekly exercise days increased (between-group difference, 0.50 day [CI, 0.12 to 0.89 day]; P = 0.001); other self-care behaviors were not affected. At baseline, mean (+/-SD) hemoglobin A1c levels were 7.28% +/- 1.43%; follow-up values were unaffected by the intervention (P > 0.2). LIMITATIONS: Because patients had good glycemic control at baseline, power to detect small but clinically important improvements in glycemic control was limited. CONCLUSIONS: Collaborative care improves affective and functional status in older patients with depression and diabetes; however, among patients with good glycemic control, such care minimally affects diabetes-specific outcomes.
Authors: Williams JW Jr; Hunkeler E; IMPACT Investigators; et al.
Ann Intern Med. 2004 Jun 15;140(12):1015-24.
Dependent and problem drinking over 5 years: a latent class growth analysis
Understanding the long-term course of problematic drinking is a fundamental concern for health services research in the alcohol field. The stability of, or change in, the course of drinking–especially heavy drinking–has both theoretical and applied relevance to alcohol research. We explore the application of latent class growth modeling to 5 years of survey data collected from dependent and problem drinkers–some not in treatment at baseline–in an attempt to uncover prototypical longitudinal drinking patterns. Results indicated that five profiles of drinkers can be used to represent their longitudinal course of alcohol consumption: early quitters (N = 88), light/non-drinkers (N = 76), gradual improvers (N = 129), moderate drinkers (N = 229), and heavy drinkers (N = 572). Significant baseline factors included ASI drug severity, dependence symptoms, and marital status. Attendance at AA meetings, the size of one’s heavy drinking and drug using social network, past treatment, receiving suggestions about one’s drinking, and contacts with the medical system were significant influences. The size of heavy drinking and drug using social networks was noticeably larger for the heavy drinkers. Findings also support the usefulness of a semi-parametric latent group-based approach as a tool for analyzing alcohol-related behaviors.
Authors: Delucchi KL; Matzger H; Weisner C
Drug Alcohol Depend. 2004 Jun 11;74(3):235-44.
Family environment factors and substance abuse severity in an HMO adolescent treatment population
To examine how parental limit setting, family conflict, and perception of family experience influence severity of alcohol and drug problems, and important gender differences in these relationships, we interviewed consecutive intakes, aged 12 to 18 years, at 4 chemical dependency programs of a large group-model nonprofit health maintenance organization (HMO) (n=419). The Family Conflict, Limit Setting, and Positive Family Experience scales correlated with substance dependence (p<0.01, p<0.01, p<0.05, respectively). Depression also correlated with family conflict (p<0.01), absence of limit setting (p<0.01), poor family experience (p<0.01) and dependence symptoms (p<0.01). Number of substance-using friends correlated with number of dependence symptoms (p<0.01). Gender differences included the following: (1) girls scoring higher in family conflict (p=0.0002), negative perceptions of family experience (p<0.0017), and lower in absence of limit setting (p<0.0001); (2) how family environment predicted problem severity: absence of limit setting was significant for boys and girls but family conflict for boys only; (3) girls had more dependence symptoms (p=<0.0001), psychiatric diagnoses (e.g., depression (p<0.0003), anxiety (p<0.0002), conduct disorder (p=0.07)), and substance-abusing family members (53 % versus 39%; p=0.006). To conclude, family and peers influence severity of alcohol and drug problems in adolescents.
Authors: Wu NS; Lu Y; Sterling S; Weisner C
Clin Pediatr (Phila). 2004 May;43(4):323-33.
Detection of postpartum depression and anxiety in a large health plan
To determine the prevalence of diagnosed and/or treated postpartum depression and anxiety, records were extracted for 1 year after delivery from databases of outpatient diagnoses and prescriptions, for women in a health maintenance organization who had delivered a child from July 1997 through June 1998. For comparison, telephone interviews were conducted 5 to 9 months after delivery with random samples of women who delivered at 2 facilities from June 1998 through January 1999. Of the women interviewed, 11% met criteria for major depression during the first 4 months postpartum, and an additional 13% met criteria for probable depression at 5 to 9 months postpartum. In contrast 7.0% of the large cohort had a visit or prescription for depression. The 1-year prevalence rate for diagnosed and/or treated anxiety without depression was 3.8%; the rate at time of interview was 14.7%. Overall, less than 33% of women with substantial depression or anxiety symptoms were detected.
Authors: Coates AO; Schaefer CA; Alexander JL
J Behav Health Serv Res. 2004 Apr-Jun;31(2):117-33.
Adolescents with substance diagnoses in an HMO: factors associated with medical provider referrals to substance abuse and mental health treatment
This study examines the factors related to referrals of adolescents with substance use disorders to substance abuse or mental health treatment by their medical providers. Administrative and chart review data from the membership of a large private health maintenance organization (HMO) were collected from a probability sample of 400 adolescents, ages 13-18, who were diagnosed with a substance use disorder in 1999. Logistic regression analyses examined referral to substance abuse treatment and referral to mental health treatment in the aggregate and stratified by gender. Documented use of both alcohol and another illicit drug, and legal problems increased likelihood of referral to substance abuse and mental health treatment, whereas diagnoses of alcohol and marijuana use disorders decreased likelihood of referral to substance abuse treatment. Mental health diagnoses played a limited role in both types of referrals, although specific psychosocial problems were associated with increased likelihood of referrals. Treatment history and location of first mention of problem were significant predictors of referral. There were no gender differences in referral rates to either substance abuse or mental health treatment; however predictors of referral differed by gender. These findings extend our knowledge about factors that influence clinicians’ treatment referrals of adolescents with substance abuse diagnoses and have implications for influencing clinician referral behavior within health plans.
Authors: Scott M; Parthasarathy S; Kohn C; Hinman A; Sterling S; Weisner C
Ment Health Serv Res. 2004 Mar;6(1):47-60.
Does marital status predict long-term drinking? Five-year observations of dependent and problem drinkers
OBJECTIVE: Married individuals have lower rates of problem drinking, but little is known about this relationship in the context of other factors. This longitudinal analysis examines marital status with other individual predisposing, problem severity and social predisposing characteristics to understand its strength in predicting alcohol consumption over 5 years. METHOD: A probability sample of dependent (n = 600) and problem (n = 992) drinkers was recruited through consecutive adult intakes from a Northern California county’s alcohol and drug treatment programs and through a general population survey. Annual volume of drinks consumed over a 5-year period-measured at baseline, and at 1, 3 and 5 years later-was estimated in four nested models using maximum likelihood estimation via PROC MIXED. RESULTS: In simpler models that examined only marital status, married individuals drank significantly less than those never married (p < .01 for problem drinkers and p < .05 for dependent drinkers); however, when our models added individual predisposing, problem severity and social predisposing characteristics, marital status was no longer significant in predicting a trajectory of decreased drinking. For problem drinkers, the following characteristics were more important than marital status in predicting alcohol consumption over the 5 years: individual predisposing characteristics (age, p < .001; income, p < .001; education, p < .001; and age of initiation of regular alcohol use, p < .001), problem severity (number of alcohol dependence symptoms, p < .001; number of alcohol-related social consequences, p < .001; and higher drug severity, p < .05) and social predisposing characteristics (family member with an alcohol problem, p < .05; the size of heavy alcohol- and drug-using social network, p < .05; and chemical dependency treatment in the prior year, p < .001). For those who were alcohol dependent, income (p < .05), number of alcohol dependence symptoms (p < .001), higher drug severity (p < .05) and a heavy alcohol- and drug-using social network (p < .05 ) were more important than marital status in predicting consumption. CONCLUSIONS: In longitudinal models, individual predisposing, problem severity and social predisposing characteristics are more important than marital status in predicting alcohol consumption.
Authors: Matzger H; Delucchi K; Weisner C; Ammon L
J Stud Alcohol. 2004 Mar;65(2):255-65.
A naturalistic comparison of outcomes at social and clinical model substance abuse treatment programs
Since the 1970s, much of the public treatment system in California has been based on a social model orientation to recovery for alcoholics, but there has been minimal research on program outcomes. This article reports on follow-up interviews conducted with a representative sample of 722 people who had entered treatment about a year earlier in public and private programs, including publicly-funded social model detoxification and residential programs, and clinical model programs in hospitals and HMO clinics. Social model clients came to treatment with more severe legal and employment problems, whereas those seeking treatment at clinical programs reported more severe family problems. At follow-up, clients at both types of programs reported attending a similar number of Alcoholics Anonymous (AA) meetings, but social model clients reported going to more Narcotics Anonymous (NA) meetings and being involved in more AA activities. Social model clients were less likely than clinical model clients to report problems with alcohol or drugs at follow-up, but the odds of reporting other problems (e.g., medical, psychological, legal, family/social) were similar. The program effect for better alcohol outcomes at the social model programs was partially explained by their clients’ higher levels of 12-step program involvement during follow-up, which strongly predicted an absence of alcohol problems. Social networks supportive of abstinence also were predictive of reporting no alcohol problems at follow-up. In contrast, subsequent detoxification treatment events between baseline and follow-up were associated with a higher odds of reporting alcohol, drug, psychiatric and family/social problems at follow-up. These findings are consistent with the growing body of literature reporting higher rates of abstinence among those who are able to construct more positive social networks, and who attend and become involved in 12-step programs during and following treatment. It is important that these results be replicated, as they suggest that social model programs are successful in engaging their clients in AA activities and in NA meeting attendance, and could represent for some an effective alternative to clinical model treatment programs.
Authors: Kaskutas LA; Ammon L; Weisner C
Int J Self Help Self Care. 2004;2(2):111-133.
Sources of informal pressure on problematic drinkers to cut down or seek treatment
Objective: To examine how patterns of expressions of concern about drinking from family members and friends differ according to the demographic characteristics of the drinker. Method: A probability sample of adult treated (n=926) and untreated (n=672) problem?drinking individuals from a Northern California county. Logistic regression analysis was used to predict having received pressure about drinking from a specific family member or friend. Results: Spouses and significant others were the most common relations to have said anything about the respondent’s drinking, suggested they cut down or given an ultimatum to enter treatment. When controlling for severity, the respondent’s degree of dependence and number of social consequences strongly predicted pressure from all sources. Having a higher income remained a strong predictor of pressure by a spouse, while having a lower income was significant in receiving pressure from siblings and other relatives and friends. Younger respondents were more likely to be pressed by a father or mother, while older respondents were more likely to be pressed by sons and daughters. Conclusions: Results show the importance of family relationships other than that with a spouse or significant other, in the efforts at informal control of drinking and efforts to seek treatment.
Authors: Room R; Matzger H; Weisner C
J Subst Use. 2004;9(6):280-95.
Effect of improving depression care on pain and functional outcomes among older adults with arthritis: a randomized controlled trial
CONTEXT: Depression and arthritis are disabling and common health problems in late life. Depression is also a risk factor for poor health outcomes among arthritis patients. OBJECTIVE: To determine whether enhancing care for depression improves pain and functional outcomes in older adults with depression and arthritis. DESIGN, SETTING, AND PARTICIPANTS: Preplanned subgroup analyses of Improving Mood-Promoting Access to Collaborative Treatment (IMPACT), a randomized controlled trial of 1801 depressed older adults (> or =60 years), which was performed at 18 primary care clinics from 8 health care organizations in 5 states across the United States from July 1999 to August 2001. A total of 1001 (56%) reported coexisting arthritis at baseline. INTERVENTION: Antidepressant medications and/or 6 to 8 sessions of psychotherapy (Problem-Solving Treatment in Primary Care). MAIN OUTCOME MEASURES: Depression, pain intensity (scale of 0 to 10), interference with daily activities due to arthritis (scale of 0 to 10), general health status, and overall quality-of-life outcomes assessed at baseline, 3, 6, and 12 months. RESULTS: In addition to reduction in depressive symptoms, the intervention group compared with the usual care group at 12 months had lower mean (SE) scores for pain intensity (5.62 [0.16] vs 6.15 [0.16]; between-group difference, -0.53; 95% confidence interval [CI], -0.92 to -0.14; P =.009), interference with daily activities due to arthritis (4.40 [0.18] vs 4.99 [0.17]; between-group difference, -0.59; 95% CI, -1.00 to -0.19; P =.004), and interference with daily activities due to pain (2.92 [0.07] vs 3.17 [0.07]; between-group difference, -0.26; 95% CI, -0.41 to -0.10; P =.002). Overall health and quality of life were also enhanced among intervention patients relative to control patients at 12 months. CONCLUSIONS: In a large and diverse population of older adults with arthritis (mostly osteoarthritis) and comorbid depression, benefits of improved depression care extended beyond reduced depressive symptoms and included decreased pain as well as improved functional status and quality of life.
Authors: Lin EH; Hunkeler E; IMPACT Investigators; et al.
JAMA. 2003 Nov 12;290(18):2428-9.
Medical and psychiatric conditions of alcohol and drug treatment patients in an HMO: comparison with matched controls
BACKGROUND: Substance abuse and health problems seem to be inextricably related. Yet, prior research on the health conditions related to substance abuse is largely focused on alcohol and is from patients treated in publicly funded programs, inpatients, and the general population. METHODS: This study compares the prevalence of medical and psychiatric conditions among 747 substance abuse patients and 3690 demographically matched controls from the same health maintenance organization, and examines whether any heightened prevalence for substance abuse patients (relative to controls) varies according to demographic subgroups and type of substance. RESULTS: Approximately one third of the conditions examined were more common among substance abuse patients than among matched controls, and many of these conditions were among the most costly. We also found that pain-related diagnoses, including arthritis, headache, and lower back pain, were more prevalent among such patients, particularly those dependent on narcotic analgesics. CONCLUSIONS: Our findings point to the importance of examining comorbid medical conditions and substance abuse in both primary and specialty care. Our findings regarding pain-related diagnoses among patients dependent on narcotic analgesics highlight the need for linkages between primary care and substance abuse treatment. Moreover, optimal treatment of many common medical disorders may require identification, intervention, and treatment of an underlying substance abuse disorder.
Authors: Mertens JR; Lu YW; Parthasarathy S; Moore C; Weisner CM
Arch Intern Med. 2003 Nov 10;163(20):2511-7.
Nonvitamin, nonmineral supplement use over a 12-month period by adult members of a large health maintenance organization
OBJECTIVE: National survey data show an increase in the prevalence of nonvitamin, nonmineral (NVNM) supplement use among adults over the past 10 years. Concern over this trend is based in part on reports of potential drug-supplement interactions. The type and prevalence of supplement use by demographic and behavior characteristics were examined among members of a large group model health plan, including those with selected health conditions. DESIGN: Data on the use of herbal medicines and dietary supplements among survey respondents were analyzed. Questions employed a checklist for six specific NVNM supplements with optional write-ins. SUBJECTS/SETTING: A stratified random sample of 15,985 adult members of a large group model health maintenance organization in northern California, who were respondents to a 1999 general health survey. STATISTICAL ANALYSES PERFORMED: Analyses were conducted with poststratification weighted data to reflect the actual age, gender, and geographic distribution of the adult membership from which the sample was drawn. RESULTS: An estimated 32.7% of adult health plan members used at least one NVNM supplement. The most frequently used herbs were Echinacea (14.7%) and Gingko biloba (10.9%). Use of all NVNM supplements was highest among females, 45 to 64 years of age, whites, college graduates, and among those with selected health conditions. APPLICATIONS: Dietetics professionals need to uniformly screen clients for dietary supplement use and provide accurate information and appropriate referrals to users.
Authors: Schaffer DM; Gordon NP; Jensen CD; Avins AL
J Am Diet Assoc. 2003 Nov;103(11):1500-5.
The role of community services and informal support on five-year drinking trajectories of alcohol dependent and problem drinkers
OBJECTIVE: The purpose of this study was to examine how informal support and community services impact the course of alcohol disorders by examining the trajectories of alcohol consumption over 5 years in dependent and problem drinkers. METHOD: Alcohol dependent adults (n = 600) and problem drinkers (n = 992) were identified through probability surveys in the general population and in public and private treatment programs throughout a California county. Participants were interviewed at baseline and again 1, 3 and 5 years later. Models controlling for demographic characteristics, problem severity, community services and recovery-oriented social networks were estimated, using a multi-level, mixed model to predict alcohol consumption over time. RESULTS: A significant trend of reduced drinking over time was observed for both dependent and problem drinkers. Recovery-oriented social networks and AA participation predicted decreased consumption for both groups. Contacts with medical, mental health, welfare and legal systems were predictive of reduced consumption for problem drinkers. In the dependent group, only contacts with mental health agencies marginally predicted decreased consumption. CONCLUSIONS: Findings point to the importance of developing mechanisms for better identifying problem drinkers in the course of contacts with health and social service systems and for facilitating use of self-help groups and positive changes in social networks. Development of recovery-oriented social networks should be emphasized to extend the benefits of treatment for dependent individuals.
Authors: Weisner C; Delucchi K; Matzger H; Schmidt L
J Stud Alcohol. 2003 Nov;64(6):862-73.
Suicide risk in bipolar disorder during treatment with lithium and divalproex
CONTEXT: Several studies have suggested that lithium treatment reduces risk of suicide in bipolar disorder, but no research has examined suicide risk during treatment with divalproex, the most commonly prescribed mood-stabilizing drug in the United States. OBJECTIVE: To compare risk of suicide attempt and suicide death during treatment with lithium with that during treatment with divalproex. DESIGN AND SETTING: Retrospective cohort study conducted at 2 large integrated health plans in California and Washington. PATIENTS: Population-based sample of 20 638 health plan members aged 14 years or older who had at least 1 outpatient diagnosis of bipolar disorder and at least 1 filled prescription for lithium, divalproex, or carbamazepine between January 1, 1994, and December 31, 2001. Follow-up for each individual began with first qualifying prescription and ended with death, disenrollment from the health plan, or end of the study period. MAIN OUTCOME MEASURES: Suicide attempt, recorded as a hospital discharge diagnosis or an emergency department diagnosis; suicide death, recorded on death certificate. RESULTS: In both health plans, unadjusted rates were greater during treatment with divalproex than during treatment with lithium for emergency department suicide attempt (31.3 vs 10.8 per 1000 person-years; P<.001), suicide attempt resulting in hospitalization (10.5 vs 4.2 per 1000 person-years; P<.001), and suicide death (1.7 vs 0.7 per 1000 person-years; P =.04). After adjustment for age, sex, health plan, year of diagnosis, comorbid medical and psychiatric conditions, and concomitant use of other psychotropic drugs, risk of suicide death was 2.7 times higher (95% confidence interval [CI], 1.1-6.3; P =.03) during treatment with divalproex than during treatment with lithium. Corresponding hazard ratios for nonfatal attempts were 1.7 (95% CI, 1.2-2.3; P =.002) for attempts resulting in hospitalization and 1.8 (95% CI, 1.4-2.2; P<.001) for attempts diagnosed in the emergency department. CONCLUSION: Among patients treated for bipolar disorder, risk of suicide attempt and suicide death is lower during treatment with lithium than during treatment with divalproex.
Authors: Goodwin FK; Fireman B; Simon GE; Hunkeler EM; Lee J; Revicki D
JAMA. 2003 Sep 17;290(11):1467-73.
Short-term alcohol and drug treatment outcomes predict long-term outcome
INTRODUCTION: Although addiction is recognized as a chronic, relapsing condition, few treatment studies, and none in a commercially insured managed care population, have measured long-term outcomes. We examined the relationship of 6-month treatment outcomes to abstinence 5 years post-treatment, and whether the predictors of abstinence at 5 years were different for those who were, and were not, abstinent at 6 months. METHODS: The sample (N=784) is from an outpatient (day hospital and traditional outpatient) managed care chemical dependency program. Subjects were interviewed at baseline, 6 months, and 5 years. Logistic regression analysis was used to assess which individual, treatment and extra-treatment characteristics predicted alcohol and drug abstinence at 5 years. RESULTS: Abstinence at 6 months was an important predictor of abstinence at 5 years. Among those abstinent at 6 months, predictors of abstinence at 5 years were older age, being female, 12-step meeting attendance, and recovery-oriented social networks. Among those not abstinent at 6 months, being alcohol dependent rather than drug dependent, 12-step meeting attendance, treatment readmission, and recovery-oriented social networks predicted abstinence at 5 years. CONCLUSION: Our findings demonstrate a clear association between short-term and long-term treatment success. In addition, these results strongly support the importance of recovery-oriented social networks for those with good short-term outcomes, and the beneficial impact of readmission for those not initially successful in treatment.
Authors: Weisner C; Ray GT; Mertens JR; Satre DD; Moore C
Drug Alcohol Depend. 2003 Sep 10;71(3):281-94.
Contrasting outcomes of older versus middle-aged and younger adult chemical dependency patients in a managed care program
OBJECTIVE: This study examined how well older chemical dependency patients succeed in treatment relative to middle-aged and younger patients in a mixed-age private HMO outpatient program. To predict successful outcome, we tested a model incorporating age group differences in individual, treatment and extratreatment factors. METHOD: The sample included 89 patients aged 55 and over, 379 patients aged 40 to 54, and 736 patients aged 18-39 (N = 1,204). Baseline measures included DSM-IV substance misuse diagnoses, Addiction Severity Index (ASI), psychiatric symptom checklist, sources of suggestion to enter treatment, treatment history and motivation. Outcome measures were abstinence rates and ASI score 6 months posttreatment. RESULTS: At baseline, older adults showed higher levels of alcohol dependence, lower rates of drug dependence and lower psychiatric symptoms relative to younger individuals. Source of suggestions to enter treatment differed by age. Older and middle-aged patients were more likely to have an abstinence goal and to stay in treatment longer than younger adults. At 6 months posttreatment, 55% of older adults reported abstinence in the preceding 30 days, versus 59% of middle-aged adults and 50% of younger adults (p = .035). CONCLUSIONS: Lower rates of dependence and hostility, and greater abstinence motivation and length of stay in treatment–all of which were associated with greater age–positively affect prognosis of older adults in treatment.
Authors: Satre DD; Mertens J; Arean PA; Weisner C
J Stud Alcohol. 2003 Jul;64(4):520-30.
How important is treatment? One-year outcomes of treated and untreated alcohol-dependent individuals
AIMS: To compare representative treatment and untreated samples of alcohol-dependent individuals in rates of abstinence and non-problematic use at 1-year follow-up. PARTICIPANTS AND DESIGN: A total of 482 alcohol-dependent adults in a northern California county identified through a probability survey of problem drinkers in the general population (n = 111) or a survey of consecutive admissions to public and private substance abuse programs (n = 371) were interviewed in person at baseline and by telephone at 1 year. MEASUREMENTS: Logistic regression models were used to predict 30-day abstinence and 12-month non-problematic alcohol use. RESULTS: At follow-up, alcohol-dependent individuals in the treatment sample had higher abstinence rates and non-problematic use outcomes than those in the untreated general population sample. In logistic regression models of the merged samples, being in the treatment sample was related strongly and positively to abstinence and non-problematic use. Having more drug users and heavy drinkers in one’s social network, higher psychiatric comorbidity, and more social consequences were inversely related to abstinence and non-problematic use in the treatment sample. The number of drug users and heavy drinkers in one’s social network was also inversely related to abstinence in both the treatment and untreated general population samples. Results predicting non-problematic use were similar. CONCLUSIONS: These results are consistent with other studies that examine treatment effectiveness in the absence of a controlled trial. Although natural recovery also occurs, alcohol-dependent individuals benefit from treatment. Co-occurring psychiatric problems continue to be major barriers to treatment effectiveness. An emphasis on changing social networks to be conducive to recovery could heighten both clinical effectiveness and prevention efforts within communities.
Authors: Weisner C; Matzger H; Kaskutas LA
Addiction. 2003 Jul;98(7):901-11.
The persistent influence of social networks and alcoholics anonymous on abstinence
OBJECTIVE: The role of changes in Alcoholics Anonymous (AA) involvement and social networks in relation to abstinence following substance abuse treatment is studied. Specifically, the role of AA and network support for abstinence are examined in relation to their effect on changes in abstinence states between follow-ups. METHOD: Study sites were 10 representative public and private alcohol treatment programs in a northern California county. A recruitment of 367 men and 288 women seeking treatment were interviewed at intake and re-interviewed 1 and 3 years later to collect information about alcohol consumption, dependence symptoms, social support for reducing drinking, number of heavy drinkers in the social network and AA involvement. RESULTS: Significant predictors of 90-day abstinence at both the 1- and 3-year follow-up interviews included AA involvement in the last year, percentage of heavy or problem drinkers in the social network, percentage encouraging alcohol reduction and AA-based support for reducing drinking. Panel models estimated an increase in AA participation between 12 and 36 months posttreatment increased the odds of abstinence at 3 years by 35% above those at 12 months. The only significant mediator of AA’s effect on abstinence was the number of AA-based contacts supporting reduced drinking, which reduced the magnitude of the relationship by 16%. CONCLUSIONS: AA involvement and the type of support received from AA members were consistent contributors to abstinence 3 years following a treatment episode. The enduring effects observed from supportive networks demonstrate the importance of ongoing mechanisms of action that contribute to an abstinent lifestyle.
Authors: Bond J; Kaskutas LA; Weisner C
J Stud Alcohol. 2003 Jul;64(4):579-88.
Missed opportunities in addressing drinking behavior in medical and mental health services
BACKGROUND: Epidemiological and clinical literature point to the importance of screening for alcohol problems in medical and psychiatric settings. However, little is known about which problem drinkers seek help from those services or about the characteristics of those who have their drinking addressed. METHODS: We interviewed a probability sample of adult dependent and problem drinkers in the general population (n = 672) and consecutive admissions to chemical dependency programs in a northern California county (n = 926). We reinterviewed them 1 year later and measured medical and mental health visits and whether their drinking was addressed during the visit. RESULTS: Almost two-thirds of problem drinkers had a medical visit, and approximately one-third had a mental health visit, yet drinking was not often discussed, especially during medical visits. Many of those more likely to have a visit were not more likely to have their drinking addressed. Women and individuals older than 40 years had more medical and mental health visits [odds ratio (OR), 1.71; p < 0.001 and OR, 1.55; p < 0.001, respectively, for women; OR, 1.57; p < 0.05 and OR, 1.64; p < 0.05, respectively, for age >/=40 years], but were not more likely to have their drinking addressed in either setting, and women were less likely than men to have their drinking addressed in mental health settings (OR, 0.62; p < 0.05). Those with higher alcohol severity and those who had attended chemical dependency treatment during the previous year were more likely to have their drinking addressed in each setting. Insurance status predicted medical, but not mental health, visits and was not related to having drinking addressed in either setting. CONCLUSIONS: Drinking behavior was not routinely addressed by medical and mental health practitioners for dependent and problem-drinking men and women who presented in public and private medical and mental health settings.
Authors: Weisner C; Matzger H
Alcohol Clin Exp Res. 2003 Jul;27(7):1132-41.
Natural variation in human membrane transporter genes reveals evolutionary and functional constraints
Membrane transporters maintain cellular and organismal homeostasis by importing nutrients and exporting toxic compounds. Transporters also play a crucial role in drug response, serving as drug targets and setting drug levels. As part of a pharmacogenetics project, we screened exons and flanking intronic regions for variation in a set of 24 membrane transporter genes (96 kb; 57% coding) in 247 DNA samples from ethnically diverse populations. We identified 680 single nucleotide polymorphisms (SNPs), of which 175 were synonymous and 155 caused amino acid changes, and 29 small insertions and deletions. Amino acid diversity (pi(NS)) in transmembrane domains (TMDs) was significantly lower than in loop domains, suggesting that TMDs have special functional constraints. This difference was especially striking in the ATP-binding cassette superfamily and did not parallel evolutionary conservation: there was little variation in the TMDs, even in evolutionarily unconserved residues. We used allele frequency distribution to evaluate different scoring systems (Grantham, blosum62, SIFT, and evolutionarily conservedevolutionarily unconserved) for their ability to predict which SNPs affect function. Our underlying assumption was that alleles that are functionally deleterious will be selected against and thus under represented at high frequencies and over represented at low frequencies. We found that evolutionary conservation of orthologous sequences, as assessed by evolutionarily conservedevolutionarily unconserved and SIFT, was the best predictor of allele frequency distribution and hence of function. European Americans had an excess of high frequency alleles in comparison to African Americans, consistent with a historic bottleneck. In addition, African Americans exhibited a much higher frequency of population specific medium-frequency alleles than did European Americans.
Authors: Leabman MK; de la Cruz M; Pharmacogenetics Of Membrane Transporters Investigators; et al.
Proc Natl Acad Sci U S A. 2003 May 13;100(10):5896-901. Epub 2003 Apr 28.
Psychiatric symptoms, impaired function, and medical care costs in an HMO setting
More information is needed regarding the medical care utilization and costs of individuals who report depressed mood, persistent anxiety, brief anxiety, panic, and trouble controlling violent behavior. We present findings from a 1-year prospective follow-up study of a stratified random sample of adult HMO enrollees (N = 10,377) originally interviewed by telephone. A strong association was observed between these psychiatric symptoms, associated impaired function, and general medical care costs during the year following the interview. After controlling for age, gender, race, medical conditions, and smoking, the mean costs of general medical care were $1,948 for respondents who reported none of the psychiatric symptoms or impaired function: $3,006 for respondents with all 5 symptoms but no impaired function; and $3,906 for those with all 5 symptoms and pervasive functional impairment. Persistent anxiety and depressed mood had the greatest impact on total general medical costs, while impaired function was associated with increased likelihood of hospital admission and emergency room use. We conclude that depressed mood, persistent anxiety, and related impaired function are associated with substantial increases in the use and cost of general medical care.
Authors: Hunkeler EM; Spector WD; Fireman B; Rice DP; Weisner C
Gen Hosp Psychiatry. 2003 May-Jun;25(3):178-84.
Depression treatment in a sample of 1,801 depressed older adults in primary care
OBJECTIVES: To examine rates and predictors of lifetime and recent depression treatment in a sample of 1,801 depressed older primary care patients DESIGN: Cross sectional survey data collected from 1999 to 2001 as part of a treatment effectiveness trial. SETTING: Eighteen primary care clinics belonging to eight organizations in five states. PARTICIPANTS: One thousand eight hundred one clinic users aged 60 and older who met diagnostic criteria for major depression or dysthymia. MEASUREMENTS: Lifetime depression treatment was defined as ever having received a prescription medication, counseling, or psychotherapy for depression. Potentially effective recent depression treatment was defined as 2 or more months of antidepressant medications or four or more sessions of counseling or psychotherapy for depression in the past 3 months. RESULTS: The mean age +/- standard deviation was 71.2 +/- 7.5; 65% of subjects were women. Twenty-three percent of the sample came from ethnic minority groups (12% were African American, 8% were Latino, and 3% belonged to other ethnic minorities). The median household income was $23,000. Most study participants (83%) reported depressive symptoms for 2 or more years, and most (71%) reported two or more prior depressive episodes. About 65% reported any lifetime depression treatment, and 46% reported some depression treatment in the past 3 months, although only 29% reported potentially effective recent depression treatment. Most of the treatment provided consisted of antidepressant medications, with newer antidepressants such as selective serotonin reuptake inhibitors constituting the majority (78%) of antidepressants used. Most participants indicated a preference for counseling or psychotherapy over antidepressant medications, but only 8% had received such treatment in the past 3 months, and only 1% reported four or more sessions of counseling. Men, African Americans, Latinos, those without two or more prior episodes of depression, and those who preferred counseling to antidepressant medications reported significantly lower rates of depression care. CONCLUSION: The findings suggest that there is considerable opportunity to improve care for older adults with depression. Particular efforts should be focused on improving access to depression care for older men, African Americans, Latinos, and patients who prefer treatments other than antidepressants.
Authors: Unutzer J; Hunkeler E; Oishi S; et al.
J Am Geriatr Soc. 2003 Apr;51(4):505-14.
Marijuana use and injury events resulting in hospitalization
PURPOSE: Information on the potential relation between marijuana use and the incidence of hospitalized injury is extremely limited. The purpose of this effort was to investigate the potential for this association. METHODS: A retrospective study was conducted in a large prepaid Northern California health care program cohort (n = 64,657) that completed baseline questionnaires about health behaviors, including marijuana use, and health status between 1979 and 1985. All injury hospitalizations through December 31, 1991, (n = 965) were identified and validated. RESULTS: Using Poisson regression modeling, increased rate-ratios and 95% confidence intervals were identified for all-cause injury hospitalizations for both men and women among current users (1.28; 1.01 to 1.61 and 1.37; 1.04 to 1.79, respectively) relative to nonusers, adjusted for age, cigarette and alcohol use, and other potential confounders. Increased rates of motor vehicle (1.96; 1.23 to 3.14), and assault (1.90, 1.16 to 3.15), injuries were identified among men who were current users; an increased rate of assault was suggestive in women (2.21; 0.92 to 5.19). CONCLUSIONS: Though the results must be viewed cautiously, they suggest that marijuana use may be independently associated with increased risk of hospitalized injury. Further study of the physiological and behavioral mechanisms is warranted [corrected].
Authors: Gerberich SG; Sidney S; Braun BL; Tekawa IS; Tolan KK; Quesenberry CP
Ann Epidemiol. 2003 Apr;13(4):230-7.
Hormone replacement therapy and cognitive performance: the role of homocysteine
BACKGROUND: Clinical trials have shown that estrogen reduces levels of homocysteine, and recent work has shown that elevated homocysteine increases the risk of incident dementia. However, no studies have investigated whether reduction of homocysteine is a mechanism by which estrogen enhances cognitive functioning. The aim of this study was to examine whether the association between homocysteine and cognitive functioning varies by use of hormone replacement therapy (HRT) in postmenopausal women. METHODS: Serum values of homocysteine, HRT status, and two measures of cognitive functioning, the Modified Mini-Mental State Exam (3MSE) and the Delayed Word Recall Test (DELREC), were measured in 1041 elderly women of Latino background. Multiple linear regression models were done to examine whether HRT could modify the effect of homocysteine on cognitive functioning. RESULTS: All findings were adjusted for age, education, income, acculturation, and hysterectomy status. Those subjects on HRT (21%) had 3MSE scores 1.88 points higher (p <.001), DELREC scores 0.12 points higher (p =.06), and homocysteine levels 1.19 micro mol/L lower (p <.001) than those not on HRT. Among those not on HRT, the 3MSE was 11.8 points lower and DELREC 1.98 points lower for every 10 micro mol/L increase in homocysteine. Among those on HRT, homocysteine was not associated with cognitive functioning. This interaction was not attenuated by further adjustment for lipids, blood pressure, creatinine, folate, Vitamin B(12), and cardiovascular disease (p <.001, interaction term coefficient for 3MSE and for DELREC). CONCLUSIONS: Women taking HRT may modify the effects of homocysteine levels on cognitive functioning. Further work in randomized clinical trials is needed to examine whether reducing homocysteine levels with HRT can prevent cognitive decline or incident dementia.
Authors: Whitmer RA; Haan MN; Miller JW; Yaffe K
J Gerontol A Biol Sci Med Sci. 2003 Apr;58(4):324-30.
Utilization and cost impact of integrating substance abuse treatment and primary care
OBJECTIVE: To examine the impact of integrating medical and substance abuse treatment on health care utilization and cost. RESEARCH DESIGN: Randomized clinical trial assigning patients to one of two treatment modalities: an Integrated Care model where primary health care is provided along with substance abuse treatment within the unit and an Independent Care model where medical care is provided in the HMO’s primary care clinics independently from substance abuse treatment. SUBJECTS: Adult patients entering treatment at the outpatient Chemical Dependency Recovery Program in Kaiser Sacramento. MEASURES: Medical utilization and cost for 12 months pretreatment and 12 months after treatment entry. RESULTS: For the full, randomized cohort, there were no statistically significant differences between the two treatment groups over time. However, among the subset of patients with substance abuse related medical conditions (SAMC), Integrated Care patients had significant decreases in hospitalization rates (P = 0.04), inpatient days (P = 0.05) and ER use (P = 0.02). Total medical costs per member-month declined from 431.12 US dollars to 200.03 US dollars (P = 0.02). Among SAMC Independent Care patients, there was a downward trend in inpatient days (P = 0.08) and ER costs (P = 0.05) but no statistically significant decrease in total medical cost. CONCLUSIONS: (Non)findings for the full sample suggest that integrating substance abuse treatment with primary care, may not be necessary or appropriate for all patients. However, it may be beneficial to refer patients with substance abuse related medical conditions to a provider also trained in addiction medicine. There appear to be large cost impacts of providing integrated care for such patients.
Authors: Parthasarathy S; Mertens J; Moore C; Weisner C
Med Care. 2003 Mar;41(3):357-67.
Services integration and cost-effectiveness
Alcohol treatment services are increasingly combined with other health and social services to address the needs of multiple-problem clients. Hence, it has been of growing policy interest to find the most effective and the most cost-effective ways of linking these services. This symposium presents some recent studies in this area. The small but growing body of studies in this area has great potential to inform public policy debates.
Authors: Hilton ME; Sterling S; Weisner C; et al.
Alcohol Clin Exp Res. 2003 Feb;27(2):271-80.
Changes in smoking status among substance abusers: baseline characteristics and abstinence from alcohol and drugs at 12-month follow-up
The impact of change in smoking status on 12-month substance abuse (SA) treatment outcomes was examined among an HMO population seeking SA treatment. Of the 749 participants who entered the study at baseline, 649 (86.9%) were retained at the 12-month follow-up. At treatment entry, 395 participants were smokers and 254 were nonsmokers. At 12-month follow-up, 13% of the 395 baseline smokers reported quitting smoking and 12% of the 254 baseline nonsmokers reported starting/relapsing to smoking. Those who quit smoking were less likely to be diagnosed as alcohol dependent compared to those that remained smokers. Those who started/resumed smoking were more likely to be diagnosed as both alcohol and drug dependent at treatment entry compared to all other groups. Total days abstinent from alcohol and illicit drugs was greatest for individuals who quit smoking (adjusted M=310.6) or who were nonsmokers (adjusted M=294.7) and lowest for those who started/resumed smoking (adjusted M=246.6) or remained smokers (adjusted M=258.2), even after controlling for demographic (i.e. age, income), psychosocial (ASI psychiatric severity), and other treatment characteristics (length of treatment stay, prescribed bupropion) that were associated with days abstinent at 12 months. Self-initiated smoking cessation does not appear to be detrimental to SA treatment outcomes, and may be beneficial. Starting/resuming smoking after entering SA treatment may be a clinical marker for individuals at greater risk of relapse. Future studies may want to measure the smoking status of all participants at all time points in order to include this higher-risk group of substance using smokers.
Authors: Kohn CS; Tsoh JY; Weisner CM
Drug Alcohol Depend. 2003 Jan 24;69(1):61-71.
The role of religion, spirituality and alcoholics anonymous in sustained sobriety
Spirituality or belief in a higher being is an integral part of Alcoholics Anonymous (AA). This study examines the role of religiosity in AA involvement and long-term sobriety in a representative sample of 587 men and women interviewed upon entering treatment and re-interviewed 1 and 3 years later. Religiosity is defined as spiritual, religious, secular (atheist or agnostic) and unsure, using the Religious Beliefs and Practices Scale employed in Project MATCH. Similar proportions within each religiosity group reported prior 12-month AA exposure at baseline; and over 40% of the unsure, spiritual and religious respondents and 25% of the secular respondents reported having gone to at least one AA meeting in the 12 months before the year 3 interview. Those who reported a spiritual awakening at year 3 were at the highest odds of continuous sobriety for the last year; notably, religious self-definition was not associated with a significantly higher odds of sobriety at year 3 after controlling for other considered influences. An increase in AA activities, other than AA meetings, between baseline and the year 1 follow-up was also associated with a higher odds of sobriety, highlighting the importance of increased AA involvement in the period immediately following treatment episodes.
Authors: Kaskutas LA; Turk N; Bond J; Weisner C
Alcohol Treat Q. 2003;21(1):1-16. Epub 2008 Oct 2.
Evidence-based care for depression in Maine: dissemination of the Kaiser Permanente Nurse Telecare Program
This paper describes the program model, implementation and preliminary results from a dissemination of a nurse case management program for treating depression in primary care. The program design was modeled after the Kaiser Permanente Nurse TeleCare program, which in a randomized clinical trial had previously demonstrated significant improvement in depression outcomes and patient satisfaction over usual care. As illustrated in this pilot by patient outcomes measured using the Hamilton Depression Rating Scale, the SF-12 Mental Health Composite Score, and the Work Role, Household and Leisure Time Functioning, the authors believe that it is possible to implement successful interventions in smaller primary care practices in community-based settings.
Authors: Pearson B; Katz SE; Soucie V; Hunkeler E; Meresman J; Rooney T; Amick BC 3rd
Psychiatr Q. 2003 Spring;74(1):91-102.
A case report: implementing a nurse telecare program for treating depression in primary care
The treatment of depression in primary care needs improvement. Previously, we reported that a nurse telecare intervention for treating depression in primary care clinics significantly improved treatment outcomes. The usefulness of nurse telecare, however, depends upon the feasibility of dissemination. In this report we describe nurse telecare and the steps required for implementation, and describe its dissemination in various settings. In addition to medication, which is managed by a primary care physician, the key elements of nurse telecare are focused behavioral activation, emotional support, patient education, promotion of treatment adherence, and monitoring of progress, delivered in ten brief telephone appointments over four months by primary care nurses. Support from key administrators and clinical champions is crucial to success. Nurses need ‘dedicated’ scheduled time for telecare activities. Nurse telecare has been piloted and disseminated in diverse settings. The model required only small modifications for dissemination, and was implemented with minimal investment of resources and no negative impact on clinic operations.
Authors: Meresman JF; Hunkeler EM; Hargreaves WA; Kirsch AJ; Robinson P; Green A; Mann EZ; Getzell M; Feigenbaum P
Psychiatr Q. 2003 Spring;74(1):61-73.
Reaching out and linking up
Authors: Leutz W; Hillier M; Hunkeler E; Nguyen H
In: Leutz W, Greenlick MR, Nonnenkamp L, editors. Linking medical care and community services: Practical models for bridging the gap. New York, NY: Springer Publishing Co; 2003.
Collaborative care management of late-life depression in the primary care setting: a randomized controlled trial
CONTEXT: Few depressed older adults receive effective treatment in primary care settings. OBJECTIVE: To determine the effectiveness of the Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) collaborative care management program for late-life depression. DESIGN: Randomized controlled trial with recruitment from July 1999 to August 2001. SETTING: Eighteen primary care clinics from 8 health care organizations in 5 states. PARTICIPANTS: A total of 1801 patients aged 60 years or older with major depression (17%), dysthymic disorder (30%), or both (53%). INTERVENTION: Patients were randomly assigned to the IMPACT intervention (n = 906) or to usual care (n = 895). Intervention patients had access for up to 12 months to a depression care manager who was supervised by a psychiatrist and a primary care expert and who offered education, care management, and support of antidepressant management by the patient’s primary care physician or a brief psychotherapy for depression, Problem Solving Treatment in Primary Care. MAIN OUTCOME MEASURES: Assessments at baseline and at 3, 6, and 12 months for depression, depression treatments, satisfaction with care, functional impairment, and quality of life. RESULTS: At 12 months, 45% of intervention patients had a 50% or greater reduction in depressive symptoms from baseline compared with 19% of usual care participants (odds ratio [OR], 3.45; 95% confidence interval [CI], 2.71-4.38; P<.001). Intervention patients also experienced greater rates of depression treatment (OR, 2.98; 95% CI, 2.34-3.79; P<.001), more satisfaction with depression care (OR, 3.38; 95% CI, 2.66-4.30; P<.001), lower depression severity (range, 0-4; between-group difference, -0.4; 95% CI, -0.46 to -0.33; P<.001), less functional impairment (range, 0-10; between-group difference, -0.91; 95% CI, -1.19 to -0.64; P<.001), and greater quality of life (range, 0-10; between-group difference, 0.56; 95% CI, 0.32-0.79; P<.001) than participants assigned to the usual care group. CONCLUSION: The IMPACT collaborative care model appears to be feasible and significantly more effective than usual care for depression in a wide range of primary care practices.
Authors: Unutzer J; Hunkeler E; IMPACT Investigators.Improving Mood-Promoting Access to Collaborative Treatment; et al.
JAMA. 2002 Dec 11;288(22):2836-45.
Who goes to alcohol and drug treatment? Understanding utilization within the context of insurance
OBJECTIVE: This study assesses the differential roles of demographic characteristics, problem severity, motivational factors and insurance in entrance into alcohol and drug treatment. METHOD: A probability sample of adult problem and dependent drinkers from a Northem California county (N = 672) and consecutive adult intakes from the county’s public (n = 298) and private (n = 628) alcohol and drug treatment programs. Interviewers conducted telephone screening for individuals meeting problem-drinking criteria in the general population; in-person interviews were conducted for those who screened positive, and also for individuals entering treatment. RESULTS: Insurance did not play an independent role in treatment entry. In logistic regression analysis, using a model from the medical utilization literature, black ethnicity (odds ratio [OR] = 2.98, p < .001); older age (OR = 4.67, p < .001); less education (OR = 1.81, p < .01); legal (OR = 7.46, p < .001) and work (OR = 3.57,p <.001) pressures; higher psychiatric (OR = 4.03,p <.001) and drug (OR = 3.04,p <.001) severity; and social consequences (OR = 1.35, p < .01) predicted treatment entry. Interventions from legal sources (OR = 6.22, p < .01) were related to entering treatment for the uninsured; legal (OR = 7.02, p < .001), workplace (OR = 6.01, p < .001) and family (OR = 1.62, p < .05) pressures were related for the insured. CONCLUSIONS: Social consequences, rather than severity of dependence, in both insured and uninsured problem drinkers are important predictors of treatment entry when traditional utilization measures are controlled. Public programs play a crucial part in the alcohol and drug treatment system, and their viability is important as health policy changes.
Authors: Weisner C; Matzger H; Tam T; Schmidt L
J Stud Alcohol. 2002 Nov;63(6):673-82.
Discontinuation of use and switching of antidepressants: influence of patient-physician communication
CONTEXT: Although current depression treatment guidelines recommend continuing antidepressant therapy for at least 4 to 9 months, many patients discontinue treatment prematurely, within 3 months. OBJECTIVES: To investigate the relationship between patient-physician communication and the continuation of treatment with antidepressants and to explore the demographics, adverse effects, therapeutic response, and frequency of follow-up visits. DESIGN, SETTING, AND PATIENTS: A total of 401 telephone interviews of depressed patients being treated with selective serotonin reuptake inhibitor (SSRI) therapy between December 15, 1999, and May 31, 2000, were conducted and 137 prescribing physicians completed written surveys from Northern California Kaiser Permanente health maintenance organization outpatient clinics. MAIN OUTCOME MEASURES: Patient-physician communication about therapy duration and about adverse effects; therapy discontinuation or medication switching within 3 months after start of SSRI therapy. RESULTS: Ninety-nine physicians (72%) reported that they usually ask patients to continue using antidepressants for at least 6 months, but 137 patients (34%) reported that their physicians asked them to continue using antidepressants for this duration and 228 (56%) reported receiving no instructions. Patients who said they were told to take their medication for less than 6 months were 3 times more likely to discontinue therapy (odds ratio [OR], 3.12; 95% confidence interval [CI], 1.21-8.07) compared with patients who said they were told to continue therapy longer. Patients who discussed adverse effects with their physicians were less likely to discontinue therapy than patients who did not discuss them (OR, 0.49; 95% CI, 0.25-0.95). Patients who reported discussing adverse effects with their physicians were more likely to switch medications (OR, 5.60; 95% CI, 2.31-13.60). Fewer than 3 follow-up visits for depression, adverse effects, and lack of therapeutic response to medication were also associated with patients’ discontinuing therapy. CONCLUSIONS: Discrepancies exist between instructions that physicians report they communicate to patients and what patients remember being told. Explicit instructions about expected duration of therapy and discussions about medication adverse effects throughout treatment may reduce discontinuation of SSRI use. Our finding that patients with 3 or more follow-up visits were more likely to continue using the initially prescribed antidepressant medication suggests that frequent patient-physician contact may increase the probability that patients will continue therapy.
Authors: Bull SA; Hu XH; Hunkeler EM; Lee JY; Ming EE; Markson LE; Fireman B
JAMA. 2002 Sep 18;288(11):1403-9.
Coping among individuals seeking private chemical dependence treatment: gender differences and impact on length of stay in treatment
BACKGROUND: Length of stay in treatment and coping skills are both predictive of chemical dependence and abuse treatment outcomes. However, little is known about whether coping strategies are related to length of stay in treatment. Because predictors of length of stay in treatment vary by gender, it also may be reasonable to expect gender differences in coping strategies as well as in the relationship between coping and LOS in treatment. METHODS: We examined gender differences in baseline coping strategies, and coping strategies as predictors of length of stay in treatment, among 747 (433 men, 314 women) individuals who entered chemical dependence and abuse treatment in a private, managed care facility. RESULTS: Women reported using more emotional discharge (behavioral attempts to reduce tension by expression of negative feelings), cognitive avoidance (cognitive attempts to avoid thinking realistically about the problem), resigned acceptance (cognitive attempts to react to the problem by accepting it), and seeking support/guidance (behavioral attempts to seek information, guidance, or support). Gender differences for emotional discharge disappeared after we controlled for depressive symptom and drug problem severities. Greater use of seeking alternative rewards (behavioral attempts to get involved in substitute activities and create new sources of satisfaction), less use of emotional discharge, and older age were significant predictors of longer length of stay, with no gender differences found. CONCLUSIONS: This study provides evidence for identifying and decreasing the use of emotional discharge early in treatment, possibly through the use of intervention strategies such as anger management, cognitive restructuring, or motivational interviewing, as well as encouraging an increase in participation in alternative activities.
Authors: Kohn CS; Mertens JR; Weisner CM
Alcohol Clin Exp Res. 2002 Aug;26(8):1228-33.
A prospective study of the factors influencing entry to alcohol and drug treatment
Much is known about factors related to entering alcohol and drug treatment, but most research comprises cross-sectional ‘snapshots’ in time. It is not known whether the reasons for entering treatment endure when problem drinkers are studied over time. This study contracts characteristics predicting treatment entry in a cross-sectional analysis at baseline with a longitudinal perspective at 1- and 3-year follow-up interviews. Sociodemographic characteristics were less important in the longitudinal analysis. In contrast to the social consequences important at the baseline interview, physiologic symptoms of alcohol dependence and interventions by medical professionals were prominent at later interview points. The findings have implications for interventions by health professionals, both for the development of early interventions targeting individuals to treatment and for a continuing care service model.
Authors: Weisner C; Matzger H
J Behav Health Serv Res. 2002 May;29(2):126-37.
Discontinuing or switching selective serotonin-reuptake inhibitors
OBJECTIVE: To describe reasons for discontinuing or switching selective serotonin-reuptake inhibitors (SSRIs) at 3 and 6 months after starting treatment, and to identify information provided to patients that may help prevent premature discontinuation of medication. METHODS: Telephone surveys were conducted at 3 and 6 months after patients (n = 672) were started on an SSRI for a new or recurrent case of depression. RESULTS: Significantly more patients discontinued or switched their SSRI because of an adverse effect within the first 3 months of starting (43%) compared with the second 3 months (27%; p = 0.023). The adverse effect most frequently reported as the reason for early discontinuation or switching was drowsiness/fatigue (10.2%), followed by anxiety, headache, and nausea – all at just over 5%. The odds ratio for discontinuation was 61% less in patients who recalled being told to take the medication for at least 6 months compared with those who did not (OR 0.39; p < 0.001). Patients who recalled being informed of potential adverse effects increased their reported incidence of mild to moderate adverse effects by 55% (OR 1.55; p < 0.05) without affecting rates of premature discontinuation (OR 1.06; p = 0.77). CONCLUSIONS: Adverse effects are the most frequent reason for discontinuing or switching SSRIs within the first 3 months of treatment. Patients are more likely to continue taking their antidepressant if they fully understand how long to take the medication. Informing patients of potential adverse effects does not appear to prevent premature discontinuation, but may increase the patient's awareness and reporting of mild to moderate adverse effects.
Authors: Bull SA; Hunkeler EM; Lee JY; Rowland CR; Williamson TE; Schwab JR; Hurt SW
Ann Pharmacother. 2002 Apr;36(4):578-84.
Effects of managed care on alcohol and other drug (AOD) treatment
The article represents the proceedings of a symposium at the 2001 RSA Meeting in Montreal, Canada. The organizer/chair was Stephen Magura. The presentations examined: (1) How managed care organization policies may affect enrollees’ use of alcohol and other drug (AOD) treatment, by Constance Horgan and associates; (2) The determinants of patients’ access to and utilization of AOD treatment in a large health maintenance organization, by Jennifer R. Mertens and Constance Weisner; (3) The impact on treatment access and costs of a statewide carve-out for AOD treatment for Medicaid, by Donald Shepard and associates; and (4) The predictive validity of a new patient assessment technology developed, in part, to better justify AOD treatment in response to the demands of managed care, by Stephen Magura and associates.
Authors: Magura S; Horgan CM; Mertens JR; Shepard DS
Alcohol Clin Exp Res. 2002 Mar;26(3):416-22.
Women referred for on-site domestic violence services in a managed care organization
BACKGROUND: Limited data about victims of domestic violence in health care settings hinder development of appropriate services. A comprehensive program was established in a managed care organization to increase identification and referral of domestically abused female patients. METHODS: Female victims of domestic abuse were referred to a trained social worker for further assessment. Information about the women was obtained from clinical consultation forms; initial interviews conducted by social workers; a survey administered to a convenience sample of women seen by the program; and medical chart review. RESULTS: Of 265 women who agreed to a domestic violence referral, 177 (67%) were contacted for further evaluation. The study sample was ethnically diverse and included female victims seen for routine care, women who had been assaulted, women who had depression, and women with various somatic symptoms. Responses from 51 of the 177 women showed the most cited reasons for accepting referral were unhappiness with current situation, wanting to leave or change the situation, concern about children who witnessed abuse, and the suggestion by a health care practitioner that the patient’s symptoms could be related to the abuse. Most reported having symptoms of depression in the previous year. CONCLUSIONS: Comprehensive programs in the health care setting can increase identification of victims of domestic abuse. This descriptive report provides a greater understanding of victims of domestic abuse, their presentation in the medical setting, their motivation for accepting referral, and issues which affect their recovery. Links between health care and community resources are necessary for effective intervention.
Authors: McCaw B; Bauer HM; Berman WH; Mooney L; Holmberg M; Hunkeler E
Women Health. 2002;35(2-3):23-40.
What is the scope of the problem and its impact on health and social systems?
Authors: Weisner C
In: Miller WR, Weisner C, editors. Changing substance abuse through health and social systems. New York: Kluwer Academic/Plenum; 2002.
Changing substance abuse through health and social systems
Authors: Miller WR; Weisner C
New York: Kluwer Academic/Plenum; 2002.
Integrating primary medical care with addiction treatment: a randomized controlled trial
CONTEXT: The prevalence of medical disorders is high among substance abuse patients, yet medical services are seldom provided in coordination with substance abuse treatment. OBJECTIVE: To examine differences in treatment outcomes and costs between integrated and independent models of medical and substance abuse care as well as the effect of integrated care in a subgroup of patients with substance abuse-related medical conditions (SAMCs). DESIGN: Randomized controlled trial conducted between April 1997 and December 1998. SETTING AND PATIENTS: Adult men and women (n = 592) who were admitted to a large health maintenance organization chemical dependency program in Sacramento, Calif. INTERVENTIONS: Patients were randomly assigned to receive treatment through an integrated model, in which primary health care was included within the addiction treatment program (n = 285), or an independent treatment-as-usual model, in which primary care and substance abuse treatment were provided separately (n = 307). Both programs were group based and lasted 8 weeks, with 10 months of aftercare available. MAIN OUTCOME MEASURES: Abstinence outcomes, treatment utilization, and costs 6 months after randomization. RESULTS: Both groups showed improvement on all drug and alcohol measures. Overall, there were no differences in total abstinence rates between the integrated care and independent care groups (68% vs 63%, P =.18). For patients without SAMCs, there were also no differences in abstinence rates (integrated care, 66% vs independent care, 73%; P =.23) and there was a slight but nonsignificant trend of higher costs for the integrated care group ($367.96 vs $324.09, P =.19). However, patients with SAMCs (n = 341) were more likely to be abstinent in the integrated care group than the independent care group (69% vs 55%, P =.006; odds ratio [OR], 1.90; 95% confidence interval [CI], 1.22-2.97). This was true for both those with medical (OR, 3.38; 95% CI, 1.68-6.80) and psychiatric (OR, 2.10; 95% CI, 1.04-4.25) SAMCs. Patients with SAMCs had a slight but nonsignificant trend of higher costs in the integrated care group ($470.81 vs $427.95, P =.14). The incremental cost-effectiveness ratio per additional abstinent patient with an SAMC in the integrated care group was $1581. CONCLUSIONS: Individuals with SAMCs benefit from integrated medical and substance abuse treatment, and such an approach can be cost-effective. These findings are relevant given the high prevalence and cost of medical conditions among substance abuse patients, new developments in medications for addiction, and recent legislation on parity of substance abuse with other medical benefits.
Authors: Weisner C; Mertens J; Parthasarathy S; Moore C; Lu Y
JAMA. 2001 Oct 10;286(14):1715-23.
Beyond screening for domestic violence: a systems model approach in a managed care setting
BACKGROUND: Implementation of screening guidelines for domestic violence has been challenging. The multifaceted ‘systems model’ may provide an effective means to improve domestic violence screening, identification, and intervention in the healthcare setting. METHODS: We developed: (1) a systems model approach using tools for effective referral, evaluation, and reporting of domestic violence; (2) materials for distribution to female patients; (3) training for social service and mental health clinicians to provide domestic violence evaluation; and (4) strong links to the community. SETTING: A nonprofit, managed care facility in Richmond, California. PARTICIPANTS: Staff and members of the managed care plan. MAIN OUTCOME MEASURES: (1) Increased screening for domestic violence by clinicians; (2) increased awareness of the healthcare facility as a resource for domestic violence assistance; and (3) increased member satisfaction with the health plan’s efforts to address domestic violence. RESULTS: The number of clinician referrals and patient self-referrals to an on-site domestic violence evaluator increased more than twofold. A pre-intervention and post-intervention phone survey of members seen for routine checkup showed an increase in member recall of being asked about domestic violence. After intervention, statistically significant increases were seen in members’ perception that the health plan was concerned about the health effects of domestic violence (p<0.0001) and about members' satisfaction with the health plan's efforts to address this issue (p<0.0001). CONCLUSIONS: A systems model approach improved domestic violence services in a managed care health setting within 1 year and affected clinicians' behavior as well as health plan members' experience. This successful implementation makes it possible to address critical research questions about the impact of a healthcare intervention for victims of domestic violence in a managed healthcare setting.
Authors: McCaw B; Berman WH; Syme SL; Hunkeler EF
Am J Prev Med. 2001 Oct;21(3):170-6.
Alcohol consumption patterns and health care costs in an HMO
We examined the relationship between patterns of alcohol consumption and health care costs among adult members of the Kaiser Permanente Medical Care Program (KPMCP) in Northern California. A telephone survey of a random sample of the KPMCP membership aged 18 and over was conducted between June 1994 and February 1996 (n=10,175). The survey included questions on sociodemographic characteristics, general and mental health status, patterns of past and current alcohol consumption; inpatient and outpatient costs were obtained from Kaiser Permanentes cost management information system. Results showed that current non-drinkers with a history of heavy drinking had higher health costs than other non-drinkers and current drinkers. The per person per year costs for non-drinkers with a heavy drinking history were $2421 versus $1706 for other non-drinkers and $1358 for current drinkers in 1995 US dollars. A history of heavy drinking has a significant effect on costs after controlling for sociodemographic characteristics, health status and health practices. Current drinkers have the lowest costs, suggesting that they may be more likely than non-drinkers to delay seeking care until they are sick and require expensive medical care.
Authors: Hunkeler EM; Hung YY; Rice DP; Weisner C; Hu T
Drug Alcohol Depend. 2001 Oct 1;64(2):181-90.
Improving primary care for depression in late life: the design of a multicenter randomized trial
BACKGROUND: Late life depression can be successfully treated with antidepressant medications or psychotherapy, but few depressed older adults receive effective treatment. RESEARCH DESIGN: A randomized controlled trial of a disease management program for late life depression. SUBJECTS: Approximately 1,750 older adults with major depression or dysthymia are recruited from seven national study sites. INTERVENTION: Half of the subjects are randomly assigned to a collaborative care program where a depression clinical specialist supervised by a psychiatrist and a primary care expert supports the patient’s regular primary care provider to treat depression. Intervention services are provided for 12 months using antidepressant medications and Problem Solving Treatment in Primary Care according to a stepped care protocol that varies intervention intensity according to clinical needs. The other half of the subjects are assigned to care as usual. EVALUATION: Subjects are independently assessed at baseline, 3 months, 6 months, 12 months, 18 months, and 24 months. The evaluation assesses the incremental cost-effectiveness of the intervention compared with care as usual. Specific outcomes examined include care for depression, depressive symptoms, health-related quality of life, satisfaction with depression care, health care costs, patient time costs, market and nonmarket productivity, and household income. CONCLUSIONS: The study blends methods from health services and clinical research in an effort to protect internal validity while maximizing the generalizability of results to diverse health care systems. We hope that this study will show the cost-effectiveness of a new model of care for late life depression that can be applied in a range of primary care settings.
Authors: Unutzer J; Hunkeler EM; Langston CA; et al.
Med Care. 2001 Aug;39(8):785-99.
Applications of health services research in the treatment and prevention of alcohol abuse. Introduction
Authors: McCarty D; Weisner C; Huebner RB
J Behav Health Serv Res. 2001 May;28(2):115-7.
The provision of services for alcohol problems: a community perspective for understanding access
Alcohol use is related to numerous health and social problems. The article describes the prevalence of alcohol problems and dependence across a county and its institutions. While high rates of problem drinking were found across health, mental health, criminal justice, welfare, drug, and alcohol programs, the proportion was highest for primary health clinics, the criminal justice system, and welfare agencies. This also was the case when the county’s most serious alcohol problem cases–individuals who were alcohol dependent–were examined. Thus it may be useful to develop screening procedures, mainstream treatment interventions in non-alcohol specialty agencies, and include non-specialty agencies in services research on access.
Authors: Weisner C
J Behav Health Serv Res. 2001 May;28(2):130-42.
Factors affecting the initiation of substance abuse treatment in managed care
AIMS: A long-standing concern of clinicians in addiction treatment is that a large number of individuals who are admitted to treatment do not return to actually begin the program. We identified characteristics that predict treatment initiation. DESIGN: In-person structured interviews were conducted with consecutive admissions to a large outpatient program (N = 1204), and the health plan’s automated registration data were used to determine treatment attendance. We compared those who returned to begin treatment with those who did not. SETTING: The study was conducted at the Chemical Dependency program of a large group model health maintenance organization (HMO). PARTICIPANTS: Study subjects were individuals age 18 or over admitted to the program. MEASUREMENT: Study variables included DSM-IV alcohol and drug dependence and abuse, Addiction Severity Index problem severity, motivation and treatment entry measures. FINDINGS: Those who were drug-dependent were less likely to begin treatment than those dependent only on alcohol. Measures of motivation, such as work-place pressures and the patient’s perception of the importance of alcohol treatment, predicted starting treatment for individuals who were alcohol-dependent only or alcohol- and drug-dependent. Among patients who were dependent only on alcohol, women were more likely than men to start treatment, and for those who were drug-dependent, being employed and having higher drug severity scores predicted starting treatment. CONCLUSIONS: Screening at intake may identify those at risk of not returning after admission to start treatment. Clinicians may consider making additional efforts during the intake process to engage individuals who are unemployed and have drug (as opposed to alcohol) disorders and less motivation.
Authors: Weisner C; Mertens J; Tam T; Moore C
Addiction. 2001 May;96(5):705-16.
Association of outpatient alcohol and drug treatment with health care utilization and cost: revisiting the offset hypothesis
OBJECTIVE: This study examines the hypothesis that treatment reduces medical utilization and costs of patients with substance use problems. METHOD: Adult patients (N = 1.011; 67% men) entering the outpatient chemical dependency recovery program at Sacramento Kaiser Permanente over a 2-year period were recruited into the study. Medical utilization and costs were examined for 18 months prior and 18 months after intake. To account for overall changes in utilization and cost, an age, gender and length-of-enrollment matched nonpatient control group (N = 4,925) was selected from health-plan members living in the same service area. Multivariate analyses controlling for age and gender were conducted using generalized estimating equation methods, allowing for correlation between repeated measures and nonnormal distributions of the outcome variable. RESULTS: The treatment cohort was less likely to be hospitalized (odds ratio [OR] = 0.59; p < .01) and there was a trend for having spent fewer days (rate ratio [RR] = 0.77; p < .10) in the hospital in the posttreatment period compared to pretreatment period. These patients were also less likely to visit the emergency room (ER) (OR = 0.64; p < .01) and had fewer ER visits (RR = 0.81; p < .01) following treatment. Inpatient, ER and total medical costs declined by 35%, 39% and 26%, respectively (p < .01). Reductions in cost were greater for the treatment cohort when compared with the matched sample (p < .05). Among women, there were significant reductions (p < .05) in inpatient, ER and total costs for the study cohort when compared with the matched sample; among men, the reductions in inpatient and ER cost (but not total cost) were significantly larger (p < .05) for the study cohort when compared with the matched sample. For the treatment cohort, the change in medical cost was not significantly different by gender. Changes in cost were significantly different across the various age groups (p < .05) for the study cohort and the matched sample. Among those in the group aged 40-49 years, the decline in cost for study cohort was significantly larger (p < .05) than for the matched sample. CONCLUSIONS: For patients with substance use disorders entering treatment, there was a substantial decline in inappropriate utilization and cost (hospital and ER) in the posttreatment period. The disaggregated pattern of posttreatment decline in utilization and cost is suggestive of long-term reductions that warrant a longer follow-up.
Authors: Parthasarathy S; Weisner C; Hu TW; Moore C
J Stud Alcohol. 2001 Jan;62(1):89-97.
Improving alcoholism treatment across the spectrum of services
This article represents the proceedings of a symposium at the 2000 RSA Meeting in Denver, Colorado. The chair was Michael E. Hilton. The presentations were (1) The effects of brief advice and motivational enhancement on alcohol use and related variables in primary care, by Stephen A. Maisto, Joseph Conigliaro, Melissa McNiel, Kevin Kraemer, Mary E. Kelley, and Rosemarie Conigliaro; (2) Enhanced linkage of alcohol dependent persons to primary medical care: A randomized controlled trial of a multidisciplinary health evaluation in a detoxification unit, by Jeffrey H. Samet, Mary Jo Larson, Jacqueline Savetsky, Michael Winter, Lisa M. Sullivan, and Richard Saitz; (3) Cost-effectiveness of day hospital versus traditional alcohol and drug outpatient treatment in a health maintenance organization: Randomized and self-selected samples, by Constance Weisner, Jennifer Mertens, Sujaya Parthasarathy, Charles Moore, Enid Hunkeler, Teh-Wei Hu, and Joe Selby; and (4) Case monitoring for alcoholics: One year clinical and health cost effects, by Robert L. Stout, William Zywiak, Amy Rubin, William Zwick, Mary Jo Larson, and Don Shepard.
Authors: Hilton ME; Weisner C; Hunkeler E; Shepard D; et al.
Alcohol Clin Exp Res. 2001 Jan;25(1):128-35.
Rethinking access to alcohol treatment
Authors: Weisner C; Schmidt LA
Recent Dev Alcohol. 2001;15:107-36.
Access to alcohol treatment in the 21st century. Old worries and new optimism. Overview
Authors: Weisner C
Recent Dev Alcohol. 2001;15:99-105.
Pharmacotherapy of obsessive-compulsive disorder in a health maintenance organization
The adequacy of pharmacotherapy for patients with obsessive-compulsive disorder (OCD) in a large, prepaid HMO was studied. An analysis was made of the computerized records for December 1, 1994, through April 30, 1998, for members of a Kaiser Permanente plan in northern California who were six years of age or older and had had continuous membership during an index year (May 1, 1995, to April 30, 1996) (1,728 million members). A total of 880 adults and 168 children and adolescents with chart-review-confirmed OCD and a pharmacy benefit were identified. The percentage of patients with an adequate drug trial, defined as > or = 56 days of continuous treatment with a serotonin-reuptake inhibitor or phenelzine at dosages at or above established minimal effective dosages, was determined. Forty-three percent of the adults and 28% of the children and adolescents who were newly diagnosed with OCD in the index year had an adequate trial of medication in the year after their first visit for OCD. By the second six months after the index year, only 75.2% of newly treated adults and 60.9% of newly treated children and adolescents continuing in the health plan filled at least one anti-OCD prescription. During the second follow-up year, these figures fell to 60.4% and 38.9%, respectively. Continuing-care patients filling a prescription in the index year were more likely than newly diagnosed patients to fill prescriptions in the two-year follow-up period, but their treatment still decreased substantially. Despite the typically chronic course of OCD, many patients with OCD who were enrolled in a large HMO appeared not to receive an adequate trial of pharmacotherapy or ongoing pharmacotherapy.
Authors: Koran LM; Leventhal JL; Fireman B; Jacobson A
Am J Health Syst Pharm. 2000 Nov 1;57(21):1972-8.
Predictors of substance abuse treatment retention among women and men in an HMO
BACKGROUND: Although prior research has examined predictors of treatment retention in public alcohol and drug treatment programs, little is known about factors that influence treatment retention in an insured outpatient population. Because there is growing evidence that the factors which influence treatment retention may differ by gender, we identify sex-specific predictors. METHODS: We recruited all eligible intakes to a health maintenance organization’s outpatient alcohol and drug treatment program during a 2-year period and obtained a sample of 317 women and 599 men. The programs, day hospital and traditional outpatient modalities, were abstinence based. We separated our sample by sex and used least squares and logistic regression to identify independent predictors of length of stay and program completion, respectively. RESULTS: One general pattern of predictors of increased retention was shared by women and men in this alcohol and drug treatment program–fewer and less severe drug problems. However, most predictors were sex-specific. Among women, retention was predicted by having higher incomes, belonging to ethnic categories other than African American, being unemployed, being married, and having lower levels of psychiatric severity. Among men, predictors of higher retention included being older, receiving employer suggestions to enter treatment, and having abstinence goals. CONCLUSIONS: These findings highlight the importance of examining aspects of the course of treatment separately by sex. They also suggest treatment factors that may enhance retention among insured populations, including employer referrals, psychiatric services, and drug-related services.
Authors: Mertens JR; Weisner CM
Alcohol Clin Exp Res. 2000 Oct;24(10):1525-33.
The outcome and cost of alcohol and drug treatment in an HMO: day hospital versus traditional outpatient regimens
OBJECTIVE: To compare outcome and cost-effectiveness of the two primary addiction treatment options, day hospitals (DH) and traditional outpatient programs (OP) in a managed care organization, in a population large enough to examine patient subgroups. DATA SOURCES: Interviews with new admissions to a large HMO’s chemical dependency program in Sacramento, California between April 1994 and April 1996, with follow-up interviews eight months later. Computerized utilization and cost data were collected from 1993 to 1997. STUDY DESIGN: Design was a randomized control trial of adult patients entering the HMO’s alcohol and drug treatment program (N = 668). To examine the generalizability of findings as well as self-selection factors, we also studied patients presenting during the same period who were unable or unwilling to be randomized (N = 405). Baseline interviews characterized type of substance use, addiction severity, psychiatric status, and motivation. Follow-up interviews were conducted at eight months following intake. Breathanalysis and urinalysis were conducted. Program costs were calculated. DATA COLLECTION: Interview data were merged with computerized utilization and cost data. PRINCIPAL FINDINGS: Among randomized subjects, both study arms showed significant improvement in all drug and alcohol measures. There were no differences overall in outcomes between DH and OP, but DH subjects with midlevel psychiatric severity had significantly better outcomes, particularly in regard to alcohol abstinence (OR = 2.4; 95% CI = 1.2, 4.9). The average treatment costs were $1,640 and $895 for DH and OP programs, respectively. In the midlevel psychiatric severity group, the cost of obtaining an additional person abstinent from alcohol in the DH cohort was approximately $5,464. Among the 405 self-selected subjects, DH was related to abstinence (OR = 2.1; 95% CI = 1.3, 3.5). CONCLUSIONS: Although significant benefits of the DH program were not found in the randomized study, DH treatment was associated with better outcomes in the self-selected group. However, for subjects with mid-level psychiatric severity in both the randomized and self-selected samples, the DH program produced higher rates of abstention and was more cost-effective. Self-selection in studies that randomize patients to services requiring very different levels of commitment may be important in interpreting findings for clinical practice.
Authors: Weisner C; Mertens J; Parthasarathy S; Moore C; Hunkeler EM; Hu T; Selby JV
Health Serv Res. 2000 Oct;35(4):791-812.
Addiction severity index data from general membership and treatment samples of HMO members. One case of norming the ASI
The Addiction Severity Index (ASI) is a widely used interview among substance-dependent populations in treatment. Its value as a treatment planning and evaluation tool has been diminished by the lack of comparative data from nonclinical samples. The present study included four scales from the ASI collected on samples of adult subscribers to a large health maintenance organization (HMO) in northern California, as well as an adult clinical sample from the same geographic region with the same HMO insurance, thereby offering informative contrasts. Interviews (N = 9,398) of non-alcohol-dependent or abuse adults from a random sample of members of a large HMO were analyzed. We collected complete ASI data on the alcohol, drug, medical, and psychiatric composite scales and partial data on the employment scale. A sample of 327 adult members of the same HMO from one of the counties included in the survey, who were admitted to treatment for alcohol and/or drug addiction, was administered the same ASI items at treatment admission. Analyses compare problem severities in the two samples by age and gender. The general membership reported some problems in most of the ASI problem areas, although at levels of severity that were typically far below those seen in the clinical sample. General membership and clinical samples were somewhat similar in medical status and in employment. As expected, alcohol, drug, and psychiatric status were much more severe in the clinical sample. The data from the HMO general membership sample provide one potential comparison group against which to judge the severity of problems presented by drug- and alcohol-dependent patients at treatment admission and at posttreatment follow-up. The authors discuss the implications for treatment planning and the evaluation of treatment outcome.
Authors: Weisner C; McLellan AT; Hunkeler EM
J Subst Abuse Treat. 2000 Sep;19(2):103-9.
Hospitalization for suicide attempt and completed suicide: epidemiological features in a managed care population
BACKGROUND: Understanding factors that contribute to high suicide ris