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.
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.
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.
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.
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.
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.
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.
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.
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.
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.