Association of Adverse Childhood Experiences and Resilience With Depression and Anxiety During Pregnancy
This was a retrospective cohort study of pregnant individuals in the Kaiser Permanente Northern California system who were screened for adverse childhood experiences and resilience as part of standard prenatal care at about 16 weeks of gestation. Overall, 14,625 pregnancies were included; 17.0% had newly identified depression; 9.8% had newly identified depression symptoms; and 8.9% had newly identified anxiety during the pregnancy with no known preexisting diagnosis. We found that adverse childhood experiences and low resilience were independently associated with newly identified depressive disorders, depression symptoms, and anxiety disorders during pregnancy. When adverse childhood experiences and resilience were modeled in combination, the greatest odds of each outcome occurred in individuals with a combination of four or more adverse childhood experiences and low resilience (vs no adverse childhood experiences and high resilience): depression adjusted odds ratio (aOR) 6.43 (95% CI, 5.23-7.90), depression symptoms aOR 9.49 (95% CI, 7.50-12.0), and anxiety disorder aOR 4.79 (95% CI, 3.81-6.02). Routine screening for adverse childhood experiences and resilience may identify individuals at risk of developing prenatal depression and anxiety, allowing faster resource linkage and potentially improved maternal and child outcomes.
Authors: Watson, Carey R;Eaton, Abigail;Campbell, Cynthia I;Alexeeff, Stacey E;Avalos, Lyndsay A;Ridout, Kathryn K;Young-Wolff, Kelly C
Obstet Gynecol. 2024 May 01;143(5):707-710. Epub 2024-02-29.
Long-Term Risk of Reintervention After Surgical Leiomyoma Treatment in an Integrated Health Care System
To compare long-term risk of reintervention across four uterus-preserving surgical treatments for leiomyomas and to assess effect modification by sociodemographic factors in a prospective cohort study in an integrated health care delivery system. We studied a cohort of 10,324 patients aged 18-50 (19.9% Asian, 21.2% Black, 21.3% Hispanic, 32.5% White, 5.2% additional races and ethnicities) who had a first uterus-preserving procedure (abdominal, laparoscopic, or vaginal myomectomy [referred to as myomectomy]; hysteroscopic myomectomy; endometrial ablation; uterine artery embolization) after leiomyoma diagnosis in the 2009-2021 electronic health records of Kaiser Permanente Northern California. We followed up patients until reintervention (second uterus-preserving procedure or hysterectomy) or censoring. We used a Kaplan-Meier estimator to calculate the cumulative incidence of reintervention and Cox regression models to estimate hazard ratios and 95% CIs comparing rates of reintervention across procedures, adjusting for age, parity, race and ethnicity, body mass index (BMI), Neighborhood Deprivation Index, and year. We also assessed effect modification by demographic characteristics. Median follow-up was 3.8 years (interquartile range 1.8-7.4 years). Index procedures were 18.0% (1,857) hysteroscopic myomectomies, 16.2% (1,669) uterine artery embolizations, 21.4% (2,211) endometrial ablations, and 44.4% (4,587) myomectomies. Accounting for censoring, the 7-year reintervention risk was 20.6% for myomectomy, 26.0% for uterine artery embolization, 35.5% for endometrial ablation, and 37.0% for hysteroscopic myomectomy; 63.2% of reinterventions were hysterectomies. Within each procedure type, reintervention rates did not vary by BMI, race and ethnicity, or Neighborhood Deprivation Index. However, rates of reintervention after uterine artery embolization, endometrial ablation, and hysteroscopic myomectomy decreased with age, and reintervention rates for hysteroscopic myomectomy were higher for parous than nulliparous patients. Long-term reintervention risks for uterine artery embolization, endometrial ablation, and hysteroscopic myomectomy are greater than for myomectomy, with potential variation by patient age and parity but not BMI, race and ethnicity, or Neighborhood Deprivation Index.
Authors: Mitro, Susanna D;Xu, Fei;Lee, Catherine;Zaritsky, Eve;Waetjen, L Elaine;Wise, Lauren A;Hedderson, Monique M
Obstet Gynecol. 2024 May 01;143(5):619-626. Epub 2024-03-28.
Using Electronic Health Records to Improve HIV Preexposure Prophylaxis Care: A Randomized Trial
Preexposure prophylaxis (PrEP) use remains limited and inequitable, and strategies are needed to improve PrEP provision in primary care. We conducted a cluster randomized trial at Kaiser Permanente, San Francisco, to evaluate the effectiveness of a clinical decision support intervention guided by an electronic health record (EHR)-based HIV risk prediction model to improve PrEP provision. Primary care providers (PCPs) were randomized to usual care or intervention, with PCPs who provide care to people with HIV balanced between arms. PCPs in the intervention arm received an EHR-based staff message with prompts to discuss HIV prevention and PrEP before upcoming in-person or video visits with patients whose predicted 3-year HIV risk was above a prespecified threshold. The main study outcome was initiation of PrEP care within 90 days, defined as PrEP discussions, referrals, or prescription fills. One hundred twenty-one PCPs had 5051 appointments with eligible patients (2580 usual care; 2471 intervention). There was a nonsignificant increase in initiation of PrEP care in the intervention arm (6.0% vs 4.5%, HR 1.32, 95% CI: 0.84 to 2.1). There was a significant interaction by HIV provider status, with an intervention HR of 2.59 (95% CI: 1.30 to 5.16) for HIV providers and 0.89 (95% CI: 0.59 to 1.35) for non-HIV providers (P-interaction <0.001). An EHR-based intervention guided by an HIV risk prediction model substantially increased initiation of PrEP care among patients of PCPs who also care for people with HIV. Higher-intensity interventions may be needed to improve PrEP provision among PCPs less familiar with PrEP and HIV care.
Authors: Volk, Jonathan E;Leyden, Wendy A;Lea, Alexandra N;Lee, Catherine;Donnelly, Michelle C;Krakower, Douglas S;Lee, Kristine;Liu, Vincent X;Marcus, Julia L;Silverberg, Michael J
J Acquir Immune Defic Syndr. 2024 Apr 01;95(4):362-369.
Longitudinal Changes in Sex Hormone Binding Globulin (SHBG) and Risk of Incident Diabetes: The Study of Women’s Health Across the Nation (SWAN)
To investigate the associations of longitudinal changes in sex hormone binding globulin (SHBG) and testosterone (T) over the menopause transition with the risk of diabetes. We followed 2,952 participants in the Study of Women’s Health Across the Nation (SWAN) who were premenopausal or early perimenopausal and diabetes-free at baseline. SHBG,T, and estradiol (E2) levels were measured at up to 13 follow-up visits (over up to 17 years). We used complementary log-log-based discrete-time survival models anchored at baseline. Diabetes developed in 376 women. A 5-unit increase in time-varying SHBG was associated with a 10% reduced risk of diabetes (hazard ratio [HR] 0.91, 95% CI 0.87-0.95), adjusting for covariates, and baseline SHBG,T, and E2 levels. Time-varying T was not associated with diabetes risk. Compared with the lowest quartile for annual rate of change of SHBG since baseline (quartile 1 [Q1] -92.3 to -1.5 nmol/L), all other quartiles were associated with a decreased risk of diabetes adjusting for covariates and baseline SHBG; associations persisted after adjusting for rate of change of T and E2 (Q2 [> -1.5 to -0.2 nmol/L] HR 0.33, 95% CI 0.23-0.48; Q3 [> -0.2 to 1.3 nmol/L] HR 0.37, 95% CI 0.25-0.55; Q4 [>1.3 to 82.0 nmol/L] HR 0.43, 95% CI 0.30-0.63). Increasing levels of SHBG over the menopause transition were associated with a decreased risk of incident diabetes. Stable to increasing rates of change in SHBG were also independently associated with a decreased risk of diabetes compared with decreasing rates of change, suggesting SHBG may affect glucose through a mechanism beyond androgenicity.
Authors: Hedderson, Monique M;Capra, Angela;Lee, Catherine;Habel, Laurel A;Lee, Jennifer;Gold, Ellen B;Badon, Sylvia E;Mitro, Susanna D;El Khoudary, Samar R
Diabetes Care. 2024 Apr 01;47(4):676-682.
Interim Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccines Against COVID-19-Associated Hospitalization Among Adults Aged ≥18 Years with Immunocompromising Conditions – VISION Network, September 2023-February 2024
In September 2023, CDC’s Advisory Committee on Immunization Practices recommended updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccination for all persons aged ≥6 months to prevent COVID-19, including severe disease. As with past COVID-19 vaccines, additional doses may be considered for persons with immunocompromising conditions, who are at higher risk for severe COVID-19 and might have decreased response to vaccination. In this analysis, vaccine effectiveness (VE) of an updated COVID-19 vaccine dose against COVID-19-associated hospitalization was evaluated during September 2023-February 2024 using data from the VISION VE network. Among adults aged ≥18 years with immunocompromising conditions, VE against COVID-19-associated hospitalization was 38% in the 7-59 days after receipt of an updated vaccine dose and 34% in the 60-119 days after receipt of an updated dose. Few persons (18%) in this high-risk study population had received updated COVID-19 vaccine. All persons aged ≥6 months should receive updated 2023-2024 COVID-19 vaccination; persons with immunocompromising conditions may get additional updated COVID-19 vaccine doses ≥2 months after the last recommended COVID-19 vaccine.
Authors: Link-Gelles, Ruth;Klein, Nicola P;Zerbo, Ousseny;Fireman, Bruce;Payne, Amanda B;et al.
MMWR Morb Mortal Wkly Rep. 2024 Mar 28;73(12):271-276. Epub 2024-03-28.
Effectiveness of an Artificial Intelligence-Enabled Intervention for Detecting Clinical Deterioration
Inpatient clinical deterioration is associated with substantial morbidity and mortality but may be easily missed by clinicians. Early warning scores have been developed to alert clinicians to patients at high risk of clinical deterioration, but there is limited evidence for their effectiveness. To evaluate the effectiveness of an artificial intelligence deterioration model-enabled intervention to reduce the risk of escalations in care among hospitalized patients using a study design that facilitates stronger causal inference. This cohort study used a regression discontinuity design that controlled for confounding and was based on Epic Deterioration Index (EDI; Epic Systems Corporation) prediction model scores. Compared with other observational research, the regression discontinuity design facilitates causal analysis. Hospitalized adults were included from 4 general internal medicine units in 1 academic hospital from January 17, 2021, through November 16, 2022. An artificial intelligence deterioration model-enabled intervention, consisting of alerts based on an EDI score threshold with an associated collaborative workflow among nurses and physicians. The primary outcome was escalations in care, including rapid response team activation, transfer to the intensive care unit, or cardiopulmonary arrest during hospitalization. During the study, 9938 patients were admitted to 1 of the 4 units, with 963 patients (median [IQR] age, 76.1 [64.2-86.2] years; 498 males [52.3%]) included within the primary regression discontinuity analysis. The median (IQR) Elixhauser Comorbidity Index score in the primary analysis cohort was 10 (0-24). The intervention was associated with a -10.4-percentage point (95% CI, -20.1 to -0.8 percentage points; P = .03) absolute risk reduction in the primary outcome for patients at the EDI score threshold. There was no evidence of a discontinuity in measured confounders at the EDI score threshold. Using a regression discontinuity design, this cohort study found that the implementation of an artificial intelligence deterioration model-enabled intervention was associated with a significantly decreased risk of escalations in care among inpatients. These results provide evidence for the effectiveness of this intervention and support its further expansion and testing in other care settings.
Authors: Gallo, Robert J;Shieh, Lisa;Smith, Margaret;Marafino, Ben J;Geldsetzer, Pascal;Asch, Steven M;Shum, Kenny;Lin, Steven;Westphal, Jerri;Hong, Grace;Li, Ron Chen
JAMA Intern Med. 2024 Mar 25.
Vaccine Effectiveness Against Pediatric Influenza-A-Associated Urgent Care, Emergency Department, and Hospital Encounters During the 2022-2023 Season, VISION Network
During the 2022-2023 influenza season, the United States experienced the highest influenza-associated pediatric hospitalization rate since 2010-2011. Influenza A/H3N2 infections were predominant. We analyzed acute respiratory illness (ARI)-associated emergency department or urgent care (ED/UC) encounters or hospitalizations at 3 health systems among children and adolescents aged 6 months-17 years who had influenza molecular testing during October 2022-March 2023. We estimated influenza A vaccine effectiveness (VE) using a test-negative approach. The odds of vaccination among influenza-A-positive cases and influenza-negative controls were compared after adjusting for confounders and applying inverse-propensity-to-be-vaccinated weights. We developed overall and age-stratified VE models. Overall, 13 547 of 44 787 (30.2%) eligible ED/UC encounters and 263 of 1862 (14.1%) hospitalizations were influenza-A-positive cases. Among ED/UC patients, 15.2% of influenza-positive versus 27.1% of influenza-negative patients were vaccinated; VE was 48% (95% confidence interval [CI], 44-52%) overall, 53% (95% CI, 47-58%) among children aged 6 months-4 years, and 38% (95% CI, 30-45%) among those aged 9-17 years. Among hospitalizations, 17.5% of influenza-positive versus 33.4% of influenza-negative patients were vaccinated; VE was 40% (95% CI, 6-61%) overall, 56% (95% CI, 23-75%) among children ages 6 months-4 years, and 46% (95% CI, 2-70%) among those 5-17 years. During the 2022-2023 influenza season, vaccination reduced the risk of influenza-associated ED/UC encounters and hospitalizations by almost half (overall VE, 40-48%). Influenza vaccination is a critical tool to prevent moderate-to-severe influenza illness in children and adolescents.
Authors: Adams, Katherine;Klein, Nicola P;Fireman, Bruce;Zerbo, Ousseny;Tenforde, Mark W;et al.
Clin Infect Dis. 2024 Mar 20;78(3):746-755.
Initial antiretroviral therapy regimen and risk of heart failure
Heart failure risk is elevated in people with HIV (PWH). We investigated whether initial antiretroviral therapy (ART) regimens influenced heart failure risk. Cohort study. PWH who initiated an ART regimen between 2000 and 2016 were identified from three integrated healthcare systems. We evaluated heart failure risk by protease inhibitor, nonnucleoside reverse transcriptase inhibitors (NNRTI), and integrase strand transfer inhibitor (INSTI)-based ART, and comparing two common nucleotide reverse transcriptase inhibitors: tenofovir disoproxil fumarate (tenofovir) and abacavir. Follow-up for each pairwise comparison varied (i.e. 7 years for protease inhibitor vs. NNRTI; 5 years for tenofovir vs. abacavir; 2 years for INSTIs vs. PIs or NNRTIs). Hazard ratios were from working logistic marginal structural models, fitted with inverse probability weighting to adjust for demographics, and traditional cardiovascular risk factors. Thirteen thousand six hundred and thirty-four PWH were included (88% men, median 40 years of age; 34% non-Hispanic white, 24% non-Hispanic black, and 24% Hispanic). The hazard ratio (95% CI) were: 2.5 (1.5-4.3) for protease inhibitor vs. NNRTI-based ART (reference); 0.5 (0.2-1.8) for protease inhibitor vs. INSTI-based ART (reference); 0.1 (0.1-0.8) for NNRTI vs. INSTI-based ART (reference); and 1.7 (0.5-5.7) for tenofovir vs. abacavir (reference). In more complex models of cumulative incidence that accounted for possible nonproportional hazards over time, the only remaining finding was evidence of a higher risk of heart failure for protease inhibitor compared with NNRTI-based regimens (1.8 vs. 0.8%; P = 0.002). PWH initiating protease inhibitors may be at higher risk of heart failure compared with those initiating NNRTIs. Future studies with longer follow-up with INSTI-based and other specific ART are warranted.
Authors: Silverberg, Michael J;Ambrosy, Andrew P;Go, Alan S;Neugebauer, Romain;Neugebauer, Romain;et al.
AIDS. 2024 Mar 15;38(4):547-556. Epub 2023-11-14.
Mortality risk after COVID-19 vaccination: A self-controlled case series study
Although previous studies found no-increased mortality risk after COVID-19 vaccination, residual confounding bias might have impacted the findings. Using a modified self-controlled case series (SCCS) design, we assessed the risk of non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes after primary series COVID-19 vaccination. We analyzed all deaths between December 14, 2020, and August 11, 2021, among individuals from eight Vaccine Safety Datalink sites. Demographic characteristics of deaths in recipients of COVID-19 vaccines and unvaccinated individuals were reported. We conducted SCCS analyses by vaccine type and death outcomes and reported relative incidences (RI). The observation period for death spanned from the dates of emergency use authorization to the end of the study period (August 11, 2021) without censoring the observation period upon death. We pre-specified a primary risk interval of 28-day and a secondary risk interval of 14-day after each vaccination dose. Adjusting for seasonality in mortality analyses is crucial because death rates vary over time. Deaths among unvaccinated individuals were included in SCCS analyses to account for seasonality by incorporating calendar month in the models. For Pfizer-BioNTech (BNT162b2), RIs of non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes were below 1 and 95 % confidence intervals (CIs) excluded 1 across both doses and both risk intervals. For Moderna (mRNA-1273), RI point estimates of all outcomes were below 1, although the 95 % CIs of two RI estimates included 1: cardiac-related (RI = 0.78, 95 % CI, 0.58-1.04) and non-COVID-19 cardiac-related mortality (RI = 0.80, 95 % CI, 0.60-1.08) 14 days after the second dose in individuals without pre-existing cancer and heart disease. For Janssen (Ad26.COV2.S), RIs of four cardiac-related death outcomes ranged from 0.94 to 0.98 for the 14-day risk interval, and 0.68 to 0.72 for the 28-day risk interval and 95 % CIs included 1. Using a modified SCCS design and adjusting for temporal trends, no-increased risk was found for non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes among recipients of the three COVID-19 vaccines used in the US.
Authors: Xu, Stanley;Fireman, Bruce;Qian, Lei;et al.
Vaccine. 2024 Mar 07;42(7):1731-1737. Epub 2024-02-22.
On- and Off-Label Atypical Antipsychotic Prescription Trends Across a Nine-Year Period Among Adolescents Pre- to Post-COVID-19
This study examined atypical antipsychotic prescribing by Food and Drug Administration (FDA) approved-use (on-label) status for adolescents before and during the COVID-19 pandemic. Retrospective data were collected from electronic health records (EHRs) of adolescents aged 10-17 years in Kaiser Permanente Northern California. New outpatient atypical antipsychotic prescription orders during 2013-2021 were evaluated. Prescriptions were categorized as on-label if linked in EHRs to autism, psychosis, bipolar disorder, or Tourette’s diagnoses; otherwise, they were potentially off-label (herein, off-label). Trend analysis of monthly prescribing rates assessed slope change at pandemic onset for the cohort and by sex and age groups. Among 5828 patients, 74.5% of new antipsychotic orders were off-label in 2021. Overall prescribing decreased significantly until early 2020 (slope = -0.045, P < .01) but then significantly increased through 2021 (post-March 2020 slope change = 0.211, P = .01). Off-label prescriptions increased at a similar rate during the COVID-19 time period, but on-label prescriptions did not change significantly. Males and younger adolescents (ages 10-14 years) showed significant decreases until early 2020, while females and older adolescents (ages 15-17 years) did not. Females and younger adolescents exhibited significant increases in overall and off-label prescribing rates following pandemic onset; older adolescents exhibited increases in overall prescriptions while males had no detectable changes. Antipsychotic prescribing declined slightly but then increased significantly following COVID-19 onset for overall and off-label prescriptions. Pandemic onset differentially impacted antipsychotic prescribing by sex and age, with overall and off-label prescribing driven by increases among female and younger adolescents.
Authors: Costales, Brianna;Slama, Natalie E;Penfold, Robert B;Nugent, Joshua R;Spalding, Scott R;Sterling, Stacy A;Iturralde, Esti
Acad Pediatr. 2024 Mar 06.
Alanine aminotransferase elevation varies by ethnicity among Asian and Pacific Islander children with overweight or obesity
Limited research on alanine aminotransferase (ALT) screening for metabolic dysfunction-associated steatotic liver disease (MASLD) among US Asian/Pacific Islander (PI) children necessitates investigation in this heterogeneous population. Examine ALT elevation among Asian/PI children with overweight or obesity. Elevated ALT prevalence (clinical threshold) and association with body mass index ≥85th percentile were compared among 18 402 Asian/PI and 25 376 non-Hispanic White (NHW) children aged 9-17 years using logistic regression. ALT elevation was more prevalent among Asian/PI (vs. NHW) males with overweight (4.0% vs. 2.7%), moderate (7.8% vs. 5.3%) and severe obesity (16.6% vs. 11.5%), and females with moderate (5.1% vs. 3.0%) and severe obesity (10.2% vs. 5.2%). Adjusted odds of elevated ALT were 1.6-fold and ~2-fold higher for Asian/PI (vs. NHW) males and females (with obesity), respectively. Filipino, Chinese and Southeast Asian males had 1.7-2.1-fold higher odds, but Native Hawaiian/PI (NHPI) and South Asian males did not significantly differ (vs. NHW). Filipina and Chinese females with obesity had >2-fold higher odds, Southeast and South Asian females did not differ and NHPI findings were mixed (vs. NHW). High elevated ALT prevalence among Asian/PI children with overweight and obesity emphasizes the need for MASLD risk assessment and examination of ethnic subgroups.
Authors: Lee, Catherine;Schwimmer, Jeffrey B;Gunderson, Erica P;Goyal, Nidhi P;Darbinian, Jeanne A;Greenspan, Louise C;Lo, Joan C
Pediatr Obes. 2024 Mar 05:e13110.
Challenges of fracture risk assessment in Asian and Black women
Bone mineral density (BMD) and fracture risk calculators (eg, the Fracture Risk Assessment Tool [FRAX]) guide primary prevention care in postmenopausal women. BMD scores use non-Hispanic White (NHW) reference data for T-score classification, whereas FRAX incorporates BMD, clinical risk factors, and population differences when calculating risk. This study compares findings among Asian, Black, and NHW women who underwent osteoporosis screening in a US health care system. Retrospective cross-sectional study. Asian, Black, and NHW women aged 65 to 75 years who underwent BMD testing (with no recent fracture, osteoporosis therapy, metastatic cancer, multiple myeloma, metabolic bone disorders, or kidney replacement therapy) were compared across the following measures: femoral neck BMD (FN-BMD) T-score (normal ≥ -1, osteoporosis ≤ -2.5), high FRAX 10-year hip fracture risk (FRAX-Hip ≥ 3%), FRAX risk factors, and diabetes status. Among 3640 Asian women, 23.8% had osteoporosis and 8.7% had FRAX-Hip scores of at least 3% (34.5% among those with osteoporosis). Among 11,711 NHW women, 12.3% had osteoporosis and 17.2% had FRAX-Hip scores of at least 3% (84.8% among those with osteoporosis). Among 1711 Black women, 68.1% had normal FN-BMD, 4.1% had BMD-defined osteoporosis, and 1.8% had FRAX-Hip scores of at least 3% (32.4% among those with osteoporosis). Fracture risk factors differed by group. Diabetes was 2-fold more prevalent in Black and Asian (35% and 36%, respectively) vs NHW (16%) women. A large subset of Asian women have discordant BMD and FRAX scores, presenting challenges in osteoporosis management. Furthermore, FN-BMD and especially FRAX scores identified few Black women at high fracture risk warranting treatment. Studies should examine whether fracture risk assessment can be optimized in understudied racial minority populations, particularly when findings are discordant.
Authors: Lo, Joan C;Chandra, Malini;Yang, Wei;Thompson, Nailah;Lee, Catherine;Ramaswamy, Mohan;Khan, Mehreen;Wheeler, Amber
Am J Manag Care. 2024 Mar;30(3):140-144.
Behavior reallocations within 24-h movement profiles and change in cardiometabolic biomarkers during pregnancy
The goal of this study was to investigate associations of reallocations within 24-h movement profiles and changes in cardiometabolic biomarkers from early to late pregnancy. In 137 individuals with prepregnancy overweight/obesity, waking movement was measured using wrist-worn accelerometers, sleep was self-reported, and biomarkers were measured in fasting serum samples at 12 and 32 weeks’ gestation. We used compositional isotemporal substitution models. On average, biomarkers increased 21%-83% across pregnancy. For those with guideline-recommended moderate/vigorous-intensity physical activity (MVPA) in early pregnancy, reallocating 30 min from MVPA to sleep, sedentary behavior, or light-intensity physical activity (LPA) was associated with a 0.6 mmol/L greater increase in total cholesterol (95% CI: -0.1 to 1.2) and a 0.7 mmol/L greater increase in low-density lipoprotein (LDL) cholesterol (95% CI: 0.1 to 1.3) from early to late pregnancy. For those with low MVPA in early pregnancy, reallocating 30 min from sleep, sedentary behavior, or LPA to MVPA was associated with a 0.6 mmol/L lower increase in total cholesterol (95% CI: -1.3 to 0.1) and a 0.8 mmol/L lower increase in LDL cholesterol (95% CI: -1.4 to -0.1) from early to late pregnancy. There were no associations with change in glucose, insulin, homeostatic model assessment for insulin resistance, very low-density lipoprotein, or high-density lipoprotein cholesterol, triglycerides, or free fatty acids. Maintaining or achieving a 24-h movement profile with guideline-recommended amounts of MVPA may be beneficial for reducing pregnancy-induced increases in total and LDL cholesterol.
Authors: Badon, Sylvia E;Ferrara, Assiamira;Gabriel, Kelley Pettee;Dooley, Erin E;Quesenberry, Charles P;Avalos, Lyndsay A;Hedderson, Monique M
Obesity (Silver Spring). 2024 Mar;32(3):623-632. Epub 2024-01-28.
Racial and Ethnic Variation in Dementia Prevalence in a Diverse Cohort of Adults with Hip Fracture
Authors: Lee, David R;Lo, Joan C;Chandra, Malini;Lee, Catherine;Gilsanz, Paola
J Gen Intern Med. 2024 Mar;39(4):716-719. Epub 2023-12-24.
Interim Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccines Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalization Among Immunocompetent Adults Aged ≥18 Years – VISION and IVY Networks, September 2023-January 2024
In September 2023, CDC’s Advisory Committee on Immunization Practices recommended updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccination for all persons aged ≥6 months to prevent COVID-19, including severe disease. However, few estimates of updated vaccine effectiveness (VE) against medically attended illness are available. This analysis evaluated VE of an updated COVID-19 vaccine dose against COVID-19-associated emergency department (ED) or urgent care (UC) encounters and hospitalization among immunocompetent adults aged ≥18 years during September 2023-January 2024 using a test-negative, case-control design with data from two CDC VE networks. VE against COVID-19-associated ED/UC encounters was 51% (95% CI = 47%-54%) during the first 7-59 days after an updated dose and 39% (95% CI = 33%-45%) during the 60-119 days after an updated dose. VE estimates against COVID-19-associated hospitalization from two CDC VE networks were 52% (95% CI = 47%-57%) and 43% (95% CI = 27%-56%), with a median interval from updated dose of 42 and 47 days, respectively. Updated COVID-19 vaccine provided increased protection against COVID-19-associated ED/UC encounters and hospitalization among immunocompetent adults. These results support CDC recommendations for updated 2023-2024 COVID-19 vaccination. All persons aged ≥6 months should receive updated 2023-2024 COVID-19 vaccine.
Authors: DeCuir, Jennifer;Klein, Nicola P;Fireman, Bruce;CDC COVID-19 Vaccine Effectiveness Collaborators,;et al.
MMWR Morb Mortal Wkly Rep. 2024 Feb 29;73(8):180-188. Epub 2024-02-29.
Differences in Smoking Behavior by Nativity, Race/Ethnicity, and Education Among Women Diagnosed with Breast Cancer
We evaluated smoking differences across nativity and race/ethnicity among women diagnosed with breast cancer. In our Northern Californian pooled population of 5,653 [670 Asian, 690 Hispanic, and 4,300 Non-Hispanic White (White)] women diagnosed with breast cancer, we evaluated smoking differences across nativity, race/ethnicity, and acculturation and effect modification of nativity by race/ethnicity and education. Foreign-born women currently smoked less than US-born women [odds ratio (OR) = 0.46, 95% confidence limit (CL): 0.29, 0.72]. Hispanic (OR = 0.50, 95% CL: 0.32, 0.78) women currently smoked less than White women. Among those who ever smoked (n = 2,557), foreign-born women smoked 5.23 fewer pack-years (PY) than US-born women (95% CL: -2.75, -7.70). Furthermore, Asian (-4.60, 95% CL: -0.81, -8.39) and Hispanic (-6.79, 95% CL: -4.14, -9.43) women smoked fewer PY than White women. Associations were generally suggestive of greater smoking with greater acculturation (immigration age, US years, survey language). Finally, associations for nativity differed by education but not race/ethnicity, with a higher likelihood of smoking in US-born women only among those with less than a bachelor’s degree (OR = 2.84, 95% CL: 2.15, 3.77) (current smoking: p = 0.01, PY: p = 0.05). Asian and Hispanic (vs. White) and foreign-born (vs. US-born) breast cancer survivors reported fewer smoking behaviors. Smoking differences across nativity and education were driven by higher rates of smoking in US-born women with lower educational attainment. Smoking behavioral patterns were similar among breast cancer survivors and the general population, informing potential smoking interventions.
Authors: Uong, Stephen P;Torres, Jacqueline M;Alexeeff, Stacey E;Morey, Brittany N;Caan, Bette J;Kushi, Lawrence H;Kroenke, Candyce H
Cancer Epidemiol Biomarkers Prev. 2024 Feb 12.
Changes in Body Mass Index Over Time in People With and Without HIV Infection
Excess weight gain is an important health concern among people with HIV (PWH) on antiretroviral therapy (ART). The extent to which ART contributes to body mass index (BMI) changes is incompletely understood. We conducted a retrospective study of PWH initiating ART and demographically matched people without HIV (PWoH). Data on baseline BMI (kg/m2; categorized as underweight/normal, overweight, or obese) and ART class (integrase strand transfer inhibitor [INSTI], non-nucleoside reverse transcriptase inhibitor [NNRTI], protease inhibitor [PI]) were obtained from electronic health records. BMI was evaluated longitudinally using piecewise linear splines in mixed effects models by HIV status, baseline BMI, and ART class. Models were adjusted for sociodemographics, comorbidities, and substance use. The study included 8256 PWH and 129 966 PWoH (mean baseline age, 40.9 and 42.2 years, respectively; 88% men). In adjusted models, the average annual change in BMI in the first 2 years after ART initiation was 0.53 for PWH and 0.12 for PWoH (P < .001). BMI increases among PWH were observed for all ART classes: 0.69 for INSTIs, 0.69 for PIs, and 0.40 for NNRTIs vs 0.12 among PWoH. For PWH initiating INSTIs, BMI increases were observed regardless of baseline BMI. Overall BMI changes >2 years after ART initiation were similar by HIV status (0.02 average annual increase for PWH and PWoH). PWH initiating ART gained excess weight in the first 2 years, emphasizing the importance of monitoring weight and cardiometabolic health among ART-treated PWH.
Authors: Lam, Jennifer O;Alexeeff, Stacey;Silverberg, Michael J;Silverberg, Michael J;et al.
Open Forum Infect Dis. 2024 Feb;11(2):ofad611. Epub 2024-02-06.
Effectiveness of Recombinant Zoster Vaccine Against Herpes Zoster in a Real-World Setting
A 2-dose series of recombinant zoster vaccine (RZV) was 97% effective against herpes zoster (HZ) in a pivotal clinical trial. To evaluate real-world effectiveness of RZV against HZ. Prospective cohort study. Four health care systems in the Vaccine Safety Datalink. Persons aged 50 years or older. The outcome was incident HZ defined by a diagnosis with an antiviral prescription. Cox regression was used to estimate the hazard of HZ in vaccinated persons compared with unvaccinated persons, with adjustment for covariates. Vaccine effectiveness (VE) was calculated as 1 minus the adjusted hazard ratio and was estimated by time since the last RZV dose and by corticosteroid use. The study included nearly 2.0 million persons who contributed 7.6 million person-years of follow-up. After adjustment, VE of 1 dose was 64% and VE of 2 doses was 76%. After 1 dose only, VE was 70% during the first year, 45% during the second year, 48% during the third year, and 52% after the third year. After 2 doses, VE was 79% during the first year, 75% during the second year, and 73% during the third and fourth years. Vaccine effectiveness was 65% in persons who received corticosteroids before vaccination and 77% in those who did not. Herpes zoster could not be identified as accurately in these observational data as in the previous clinical trials. Two doses of RZV were highly effective, although less effective than in the previous clinical trials. Two-dose effectiveness waned very little during the 4 years of follow-up. However, 1-dose effectiveness waned substantially after 1 year, underscoring the importance of the second dose. Centers for Disease Control and Prevention.
Authors: Zerbo, Ousseny;Bartlett, Joan;Fireman, Bruce;Lewis, Ned;Goddard, Kristin;Dooling, Kathleen;Duffy, Jonathan;Glanz, Jason;Naleway, Allison;Donahue, James G;Klein, Nicola P
Ann Intern Med. 2024 Feb;177(2):189-195. Epub 2024-01-09.
Telehealth Collaborative Care Led by Clinical Pharmacists for People With Psychosis or Bipolar Disorder: A Propensity Weighted Comparison With Usual Psychiatric Care
Objective: People with psychosis or bipolar disorder (severe and persistent mental illness [SPMI]) are at high risk for poor psychiatric and chronic illness outcomes, which could be ameliorated through improved health care quality. This study assessed whether a telehealth, collaborative care program managed by psychiatric clinical pharmacists (SPMI Population Care) was associated with improved health care quality for adults with SPMI in a large California health system. Methods: This retrospective cohort study used electronic health record data to compare 968 program enrollees at 6 demonstration sites (Population Care) to 8,339 contemporaneous patients with SPMI at 6 non-program sites (Usual Care). SPMI diagnoses were based on ICD-10-CM diagnostic codes. Primary outcomes were optimal psychotropic medication adherence, guideline-recommended glycemic screening, annual psychiatrist visit, and emergency department use. Difference-in-difference analyses assessed change in outcomes from 12 months pre- to 12 months post-enrollment using overlap weighting with high dimensional propensity scores to balance participant characteristics across groups. Participant data were collected from January 1, 2020, to June 30, 2022. Results: From pre- to post-enrollment, Population Care was associated with greater achievement of psychotropic medication adherence and glycemic screening (+6 and +9 percentage points), but unexpectedly with a decrease in annual psychiatrist visits (-6 percentage points) and no significant change in emergency department use, relative to Usual Care. More than 75% of Population Care participants attended an intake and ≥ 1 follow-up visits. Participants with psychosis (26% of sample) had similar results as those with bipolar disorder. Conclusions: Clinical pharmacist-led telehealth collaborative care has potential to improve psychopharmacologic treatment adherence and recommended disease preventive screening for people with psychosis or bipolar disorder.
Authors: Iturralde, Esti;Fazzolari, Lisa;Slama, Natalie E;Alexeeff, Stacey E;Sterling, Stacy A;Awsare, Sameer;Koshy, Maria T;Shia, Macy
J Clin Psychiatry. 2024 Jan 29;85(1). Epub 2024-01-29.
Effect of home-based resistance training on chemotherapy relative dose intensity and tolerability in colon cancer: The FORCE randomized control trial
Many patients with colon cancer cannot fully adhere to postoperative chemotherapy due to dose-limiting toxicities, resulting in lower relative dose intensity (RDI) and potentially compromising overall survival. This study examined whether home-based resistance training (RT) during adjuvant chemotherapy improves RDI and patient-reported toxicities versus usual care (UC) in colon cancer patients. Multicenter, randomized control trial (RCT) conducted at community and academic practices. Enrollment of patients receiving postoperative chemotherapy for colon cancer occurred between February 23, 2018, and September 29, 2021; final follow-up was March 21, 2022. Participants were randomized to RT (n = 90) or UC (n = 91) for the duration of chemotherapy. Participants in the RT group engaged in twice weekly home-based progressive RT. At the end of the study, UC was given an online exercise program. Among 181 randomized patients (mean age, 55.2 [SD, 12.8] years, 95 [52.5%] were men), there were no differences in the mean RDI among those in RT (79% [SD, 19%]) and those in UC (82% [SD, 19%]); (mean difference -0.04 [95% confidence interval (CI), -0.09 to 0.02]). Assignment to RT did not significantly reduce the number of moderate/severe symptoms per week across follow-up (relative rate: 0.94 [95% CI, 0.72-1.22]). Additionally, time since randomization did not significantly modify the effect of RT on the overall number of symptoms (p = .06). Among patients with colon cancer, these results do not support home-based RT as an adjunct to chemotherapy specifically to improve planned treatment intensity.
Authors: Caan, Bette J;Lee, Catherine;Quesenberry, Charles P;Cespedes Feliciano, Elizabeth M;Schmitz, Kathryn H;et al.
Cancer. 2024 Jan 24.
A polygenic score associated with fracture risk in breast cancer patients treated with aromatase inhibitors
Identifying women at high risk of osteoporotic fracture from aromatase inhibitor (AI) therapy for breast cancer is largely based on known risk factors for healthy postmenopausal women, which might not accurately reflect the risk in breast cancer patients post-AI therapy. To determine whether a polygenic score associated with fracture in healthy women is also significant in women treated with AIs for breast cancer, we used data from a prospective observational cohort of 2152 women diagnosed with hormonal receptor positive breast cancer treated with AIs as the initial endocrine therapy and examined a polygenic score of heel quantitative ultrasound speed of sound (gSOS) in relation to incident osteoporotic fracture after AI therapy during a median 6.1 years of follow up after AI initiation. In multivariable models, patients with the second and third highest tertiles (T) versus the lowest tertile of gSOS had significantly lower risk of fracture (T2: adjusted HR = 0.61, 95% CI: 0.46-0.80; T3: adjusted HR = 0.53, 95% CI: 0.40-0.70). The lower risk of fracture in patients with the highest tertile of gSOS remained significant after further adjustment for BMD at the hip (T3: adjusted HR = 0.62, 95% CI: 0.42-0.91). In conclusion, our analysis showed gSOS as a novel genetic predictor for fracture risk independent of BMD among breast cancer patients treated with AIs. Future studies are warranted to evaluate the performance of incorporating gSOS in prediction models for the risk of AI-related fracture in breast cancer patients.
Authors: Hook, Christine;Lee, Catherine;Lo, Joan C;Kushi, Lawrence H;Kwan, Marilyn L;Yao, Song;et al.
NPJ Breast Cancer. 2024 Jan 20;10(1):9. Epub 2024-01-20.
Advances in Adherence Reporting of Resistance Training in a Clinical Trial during Adjuvant Chemotherapy for Colon Cancer
Detailed reporting of individually tailored exercise prescriptions (ExRx) used in clinical trials is essential to describe feasibility, tolerability, and efficacy of the intervention and to inform translation to clinical care. This paper outlines the methodology used to develop a resistance training (RT) ExRx for people with colon cancer receiving chemotherapy and reports adherence to the randomized controlled trial testing the impact of RT on relative dose intensity of chemotherapy and patient-reported toxicities. Participants randomized to the exercise arm (n = 90) were included. To promote muscle hypertrophy, the ExRx was twice-weekly, moderate to heavy loads (65-85% 1-RM), high sets (3-5), and intermediate repetitions (6-10) of five large multi-joint movements with adjustable dumbbells. Attendance (achieved frequency) and adherence (achieved volume) were calculated. Group-based trajectory modeling was used to identify clusters of individuals with similar adherence patterns and compared baseline characteristics across adherence groups. The median attendance was 69.1%. Adherence was 60.6%, but higher for those receiving 3 versus 6 months of chemotherapy (80.4 vs. 47.4%; p < 0.05). Participants engaged in a median of 1.4 days of RT each week, lifting 62% of the 1-RM load, for 3.0 sets and 7.5 repetitions per set. Three distinct adherence groups were identified: 13% "non-starter", 37% "tapered off", and 50% "consistent exercisers". Females were more likely to be in the "non-starter" and "tapered off" groups. This paper outlines suggested methods for reporting ExRx of RT in oncology clinical trials and provides insight into the tolerance of ExRx of RT during chemotherapy treatment for colon cancer. These findings aim to foster constructive dialogue, and offer a premise for designing future research to elucidate the benefits of exercise during chemotherapy.
Authors: Campbell, Kristin L;Lee, Catherine;Sternfeld, Barbara;Caan, Bette J;Schmitz, Kathryn H;et al.
Med Sci Sports Exerc. 2024 Jan 18.
Cardiovascular Disease Risk Factor Control in People With and Without Human Immunodeficiency Virus
Management of hypertension, dyslipidemia, diabetes and other modifiable factors may mitigate the cardiovascular disease (CVD) risk in people with human immunodeficiency virus (HIV, PWH) compared with people without HIV (PWoH). This was a retrospective cohort study of 8285 PWH and 170 517 PWoH from an integrated health system. Risk factor control was measured using a novel disease management index (DMI) accounting for amount/duration above treatment goals (0% to 100% [perfect control]), including 2 DMIs for hypertension (diastolic and systolic blood pressure), 3 for dyslipidemia (low-density lipoprotein, total cholesterol, triglycerides), and 1 for diabetes (HbA1c). CVD risk by HIV status was evaluated overall and in subgroups defined by DMIs, smoking, alcohol use, and overweight/obesity in adjusted Cox proportional hazards models. PWH and PWoH had similar DMIs (80%-100%) except for triglycerides (worse for PWH) and HbA1c (better for PWH). In adjusted models, PWH had an elevated risk of CVD compared with PWoH (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.07-1.31). This association was attenuated in subgroups with controlled dyslipidemia and diabetes but remained elevated for PWH with controlled hypertension or higher total cholesterol. The strongest HIV status association with CVD was seen in the subgroup with frequent unhealthy alcohol use (HR, 2.13; 95% CI, 1.04-4.34). Control of dyslipidemia and diabetes, but not hypertension, attenuated the HIV status association with CVD. The strong association of HIV and CVD with frequent unhealthy alcohol use suggests enhanced screening and treatment of alcohol problems in PWH is warranted.
Authors: Silverberg, Michael J;Alexeeff, Stacey E;Flamm, Jason A;Lam, Jennifer O;Sterling, Stacy A;Satre, Derek D;Satre, Derek D;et al.
Clin Infect Dis. 2024 Jan 16.
Community-Wide Universal Human Immunodeficiency Virus (HIV) Test and Treat Intervention Reduces Tuberculosis Transmission in Rural Uganda: A Cluster-Randomized Trial
Human immunodeficiency virus (HIV) treatment reduces tuberculosis (TB) disease and mortality; however, the population-level impact of universal HIV-test-and-treat interventions on TB infection and transmission remain unclear. In a sub-study nested in the SEARCH trial, a community cluster-randomized trial (NCT01864603), we assessed whether a universal HIV-test-and-treat intervention reduced population-level incident TB infection in rural Uganda. Intervention communities received annual, population-level HIV testing and patient-centered linkage. Control communities received population-level HIV testing at baseline and endline. We compared estimated incident TB infection by arms, defined by tuberculin skin test conversion in a cohort of persons aged 5 and older, adjusting for participation and predictors of infection, and accounting for clustering. Of the 32 trial communities, 9 were included, comprising 90 801 participants (43 127 intervention and 47 674 control). One-year cumulative incidence of TB infection was 16% in the intervention and 22% in the control; SEARCH reduced the population-level risk of incident TB infection by 27% (adjusted risk ratio = 0.73; 95% confidence interval [CI]: .57-.92, P = .005). In pre-specified analyses, the effect was largest among children aged 5-11 years and males. A universal HIV-test-and-treat intervention reduced incident TB infection, a marker of population-level TB transmission. Investments in community-level HIV interventions have broader population-level benefits, including TB reductions.
Authors: Marquez, Carina;Nugent, Joshua;Balzer, Laura B;et al.
Clin Infect Dis. 2024 Jan 16.
Reproductive Health Care in Adolescents with Autism and Other Developmental Disabilities
Adults with developmental disabilities often have less access to reproductive health services than adults without these disabilities. However, little is known about how adolescents with developmental disabilities, including autism, access reproductive health care. We aimed to characterize the utilization of reproductive health care services among autistic adolescents and adolescents with other developmental disabilities in comparison with typically developing adolescents. We conducted a cohort study of a sample of adolescents who were continuously enrolled members of Kaiser Permanente Northern California, an integrated healthcare system, from ages 14 to 18. The final analytic sample included 700 autistic adolescents, 836 adolescents with other developmental disabilities, and 2187 typically developing adolescents who sought care between 2000 and 2017. Using electronic health records, we obtained information on menstrual conditions, use of obstetric/gynecological care, and prescriptions of hormonal contraception. We compared utilization between groups using chi-squared tests and covariate-adjusted risk ratios estimated with modified Poisson regression. Autistic adolescents and adolescents with other developmental disabilities were significantly more likely to have diagnoses of menstrual disorders, polycystic ovary syndrome, and premenstrual syndrome than typically developing adolescents. These two groups also were less likely than typically developing peers to visit the OB/GYN or to use any form of hormonal contraception, including oral contraception, hormonal implants, and intrauterine devices. Adolescents in all three groups accessed hormonal contraception most frequently through their primary care provider, followed by an OB/GYN provider. Autistic adolescents and adolescents with other developmental disabilities are less likely than their typically developing peers to visit the OB/GYN and use hormonal contraception, suggesting possible care disparities that may persist into adulthood. Efforts to improve access to reproductive healthcare in these populations should target care delivered in both pediatric and OB/GYN settings.
Authors: Ames, Jennifer L;Anderson, Meredith C;Cronbach, Emily;Lee, Catherine;Giwa Onaiwu, Morénike;Vallerie, Amy M;Croen, Lisa A
Am J Obstet Gynecol. 2024 Jan 11.
Evaluation of an outreach programme for patients with COVID-19 in an integrated healthcare delivery system: a retrospective cohort study
In the first year of the COVID-19 pandemic, health systems implemented programmes to manage outpatients with COVID-19. The goal was to expedite patients’ referral to acute care and prevent overcrowding of medical centres. We sought to evaluate the impact of such a programme, the COVID-19 Home Care Team (CHCT) programme. Retrospective cohort. Kaiser Permanente Northern California. Adult members before COVID-19 vaccine availability (1 February 2020-31 January 2021) with positive SARS-CoV-2 tests. Virtual programme to track and treat patients with ‘CHCT programme’. The outcomes were (1) COVID-19-related emergency department visit, (2) COVID-19-related hospitalisation and (3) inpatient mortality or 30-day hospice referral. We estimated the average effect comparing patients who were and were not treated by CHCT. We estimated propensity scores using an ensemble super learner (random forest, XGBoost, generalised additive model and multivariate adaptive regression splines) and augmented inverse probability weighting. There were 98 585 patients with COVID-19. The majority were followed by CHCT (n=80 067, 81.2%). Patients followed by CHCT were older (mean age 43.9 vs 41.6 years, p<0.001) and more comorbid with COmorbidity Point Score, V.2, score ≥65 (1.7% vs 1.1%, p<0.001). Unadjusted analyses showed more COVID-19-related emergency department visits (9.5% vs 8.5%, p<0.001) and hospitalisations (3.9% vs 3.2%, p<0.001) in patients followed by CHCT but lower inpatient death or 30-day hospice referral (0.3% vs 0.5%, p<0.001). After weighting, there were higher rates of COVID-19-related emergency department visits (estimated intervention effect -0.8%, 95% CI -1.4% to -0.3%) and hospitalisation (-0.5%, 95% CI -0.9% to -0.1%) but lower inpatient mortality or 30-day hospice referral (-0.5%, 95% CI -0.7% to -0.3%) in patients followed by CHCT. Despite CHCT following older patients with higher comorbidity burden, there appeared to be a protective effect. Patients followed by CHCT were more likely to present to acute care and less likely to die inpatient.
Authors: Myers, Laura C;Lawson, Brian L;Escobar, Gabriel J;Daly, Kathleen A;Chen, Yi-Fen Irene;Dlott, Richard;Lee, Catherine;Liu, Vincent
BMJ Open. 2024 Jan 08;14(1):e073622. Epub 2024-01-08.
Randomized trial of patient outreach approaches to de-implement outdated colonoscopy surveillance intervals
Guidelines now recommend patients with low-risk adenomas receive colonoscopy surveillance in 7-10 years and those with the previously recommended 5-year interval be reevaluated. We tested three outreach approaches for transitioning patients to the 10-year interval recommendation. Design: 3-arm pragmatic randomized trial comparing telephone, secure messaging, and mailed letter outreach. Kaiser Permanente Northern California, a large integrated healthcare system. Patients aged 54-70 years with 1-2 small (<10 mm) tubular adenomas at baseline colonoscopy, due for 5-year surveillance in 2022, without high-risk conditions, and with access to all three outreach modalities. Patients were randomly assigned to outreach arm (telephone [n=200], secure message [n=203], and mailed letter [n=201]) stratified by age, sex, race, and ethnicity. Outreach in each arm was performed by trained medical assistants (unblinded) communicating in English with 1 reminder attempt at 2-4 weeks. Participants could change their assigned interval to 10 years or continue their planned 5-year interval. 60-day response rates were higher for telephone (64.5%) and secure messaging outreach (51.7%) versus mailed letter (31.3%). Also, more patients adopted the 10-year surveillance interval in the telephone (37.0%) and secure messaging arms (32.0%) compared to mailed letter (18.9%) and rate differences were significant for telephone (18.1%; 97.5% CI: 8.3%, 27.9%) and secure message outreach (13.1%; 97.5% CI: 3.5%, 22.7%) versus mailed letter outreach. Telephone and secure messaging were more effective than mailed letter outreach for de-implementing outdated colonoscopy surveillance recommendations among individuals with a history of low-risk adenomas in an integrated healthcare setting.
Authors: Lee, Jeffrey K;Velayos, Fernando S;Quesenberry, Charles P;Corley, Douglas A;Levin, Theodore R;Levin, Theodore R;et al.
Clin Gastroenterol Hepatol. 2024 Jan 06.
Inflammatory Conditions During Pregnancy and Risk of Autism and Other Neurodevelopmental Disorders
Maternal inflammation can result from immune dysregulation and metabolic perturbations during pregnancy. Whether conditions associated with inflammation during pregnancy increase the likelihood of autism spectrum disorder (ASD) or other neurodevelopmental disorders (DDs) is not well understood. We conducted a case-control study among children born in California from 2011 to 2016 to investigate maternal immune-mediated and cardiometabolic conditions during pregnancy and risk of ASD (n = 311) and DDs (n = 1291) compared with children from the general population (n = 967). Data on maternal conditions and covariates were retrieved from electronic health records. Maternal genetic data were used to assess a causal relationship. Using multivariable logistic regression, we found that mothers with asthma were more likely to deliver infants later diagnosed with ASD (odds ratio [OR] = 1.62, 95% CI: 1.15-2.29) or DDs (OR = 1.30, 95% CI: 1.02-1.64). Maternal obesity was also associated with child ASD (OR = 1.51, 95% CI: 1.07-2.13). Mothers with both asthma and extreme obesity had the greatest odds of delivering an infant later diagnosed with ASD (OR = 16.9, 95% CI: 5.13-55.71). These increased ASD odds were observed among female children only. Polygenic risk scores for obesity, asthma, and their combination showed no association with ASD risk. Mendelian randomization did not support a causal relationship between maternal conditions and ASD. Inflammatory conditions during pregnancy are associated with risk for neurodevelopmental disorders in children. These risks do not seem to be due to shared genetic risk; rather, inflammatory conditions may share nongenetic risk factors with neurodevelopmental disorders. Children whose mothers have both asthma and obesity during pregnancy may benefit from earlier screening and intervention.
Authors: Croen, Lisa A;Ames, Jennifer L;Qian, Yinge;Alexeeff, Stacey;Ashwood, Paul;Gunderson, Erica P;Wu, Yvonne W;Boghossian, Andrew S;Yolken, Robert;Van de Water, Judy;Weiss, Lauren A
Biol Psychiatry Glob Open Sci. 2024 Jan;4(1):39-50. Epub 2023-10-11.
Evaluation of the international Ki67 working group cut point recommendations for early breast cancer: comparison with 21-gene assay results in a large integrated health care system
The International Ki67 Working Group (IKWG) has developed training for immunohistochemistry (IHC) scoring reproducibility and recommends cut points of ≤ 5% and ≥ 30% for prognosis in ER+, HER2-, stage I/II breast cancer. We examined scoring reproducibility following IKWG training and evaluated these cut points for selecting patients for further testing with the 21-gene Recurrence Score (RS) assay. We included 307 women aged 50+ years with node-negative, ER+PR+HER2- breast cancer and with available RS results. Slides from the diagnostic biopsy were stained for Ki67 and scored using digital image analysis (IA). Two IHC pathologists underwent IKWG training and visually scored slides, blinded to each other and IA readings. Interobserver reproducibility was examined using intraclass correlation (ICC) and Kappa statistics. Depending on reader, 8.8-16.0% of our cohort had Ki67 ≤ 5% and 11.4-22.5% had scores ≥ 30%. The ICC for Ki67 scores by the two pathologists was 0.82 (95% CI 0.78-0.85); it was 0.79 (95% CI 0.74-0.83) for pathologist 1 and IA and 0.76 (95% CI 0.71-0.80) for pathologist 2 and IA. For Ki67 scores ≤ 5%, the percentages with RS < 26 were 92.6%, 91.8%, and 90.9% for pathologist 1, pathologist 2, and IA, respectively. For Ki67 scores ≥ 30%, the percentages with RS ≥ 26 were 41.5%, 51.4%, and 27.5%, respectively. The IKWG's Ki67 training resulted in moderate to strong reproducibility across readers but cut points had only moderate overlap with RS cut points, especially for Ki67 ≥ 30% and RS ≥ 26; thus, their clinical utility for a 21-gene assay testing pathway remains unclear.
Authors: Shim, Veronica C;Lee, Catherine;Habel, Laurel A;Habel, Laurel A;et al.
Breast Cancer Res Treat. 2024 Jan;203(2):281-289. Epub 2023-10-17.
Agreement Between Self-reports and Urine Toxicology Measures of Illicit Methamphetamine and Cocaine Use During Early Pregnancy
This study aimed to assess agreement between self-report and urine toxicology measures assessing use of 2 illicit simulants (methamphetamine and cocaine) during early pregnancy. This cross-sectional study of 203,053 pregnancies from 169,709 individuals receiving prenatal care at Kaiser Permanente Northern California between January 1, 2011, and December 31, 2019, assessed agreement ( κ , sensitivity, and specificity) between self-reported frequency and urine toxicology measures of methamphetamine and cocaine early in pregnancy. Prenatal use of the illicit stimulants was rare according to toxicology (n = 244 [0.12%]) and self-report measures (n = 294 [0.14%]). Agreement between these measures was low ( κ < 0.20). Of the 498 positive pregnancies, 40 (8.03%) screened positive on both measures, 204 (40.96%) screened positive on toxicology tests only, and 254 (51.00%) screened positive by self-report only. Relative to toxicology tests, sensitivity of any self-reported use was poor with 16.39% (95% confidence interval [CI], 11.75%-21.04%) of pregnancies with a positive toxicology test self-reporting any use in pregnancy. Relative to self-report, sensitivity of toxicology tests was also poor with 13.61% (95% CI, 9.69%-17.52%) of pregnancies who self-reported any use having positive urine toxicology tests. The sensitivity improved slightly at higher frequencies of self-reported use: daily, 17.50% (95% CI, 5.72%-29.29%); weekly, 25.00% (95% CI, 11.58%-38.42%); and monthly or less, 11.06% (95% CI, 6.89%-15.23%). Specificity was high (>99%), reflecting the high negative rate of use. Findings suggest that using self-report and toxicology measures in combination likely provides the most accurate information on methamphetamine and cocaine use in early pregnancy. Findings also highlight the need to provide supportive nonstigmatizing environments in which pregnant individuals feel comfortable disclosing substance use without fear of punishment.
Authors: Sujan, Ayesha C;Avalos, Lyndsay A;Young-Wolff, Kelly C;Young-Wolff, Kelly C;et al.
J Addict Med. 2024 Jan-Feb 01;18(1):28-32. Epub 2023-10-05.
Timing and level of educational attainment and late-life cognition in the KHANDLE study
The timing of educational attainment may modify its effects on late-life cognition, yet most studies evaluate education only at a single time point. Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study cohort participants (N = 554) reported educational attainment (dichotomized at any college education) at two time points, and we classified them as having low, high, or later-life high educational attainment. Linear mixed-effects models estimated associations between educational attainment change groups and domain-specific cognitive outcomes (z-standardized). Compared to low educational attainment, high (β= 0.59 SD units; 95% confidence interval [CI]: 0.39, 0.79) and later-life high educational attainment (β = 0.22; 95% CI: 0.00, 0.44) were associated with higher executive function. Only high educational attainment was associated with higher verbal episodic memory (β = 0.27; 95% CI: 0.06, 0.48). Level and timing of educational attainment are both associated with domain-specific cognition. A single assessment for educational attainment may inadequately characterize protective associations with late-life cognition. Few studies have examined both level and timing of educational attainment on cognition. Marginalized populations are more likely to attain higher education in adulthood. Higher educational attainment in late life is also associated with higher cognition.
Authors: Soh, Yenee;Quesenberry, Charles P;Gilsanz, Paola;Gilsanz, Paola;et al.
Alzheimers Dement. 2024 Jan;20(1):593-600. Epub 2023-09-26.
Clinical outcomes in hospitalized plasma and platelet transfusion recipients prior to and following widespread blood donor SARS-CoV-2 infection and vaccination
The safety of transfusion of SARS-CoV-2 antibodies in high plasma volume blood components to recipients without COVID-19 is not established. We assessed whether transfusion of plasma or platelet products during periods of increasing prevalence of blood donor SARS-CoV-2 infection and vaccination was associated with changes in outcomes in hospitalized patients without COVID-19. We conducted a retrospective cohort study of hospitalized adults who received plasma or platelet transfusions at 21 hospitals during pre-COVID-19 (3/1/2018-2/29/2020), COVID-19 pre-vaccine (3/1/2020-2/28/2021), and COVID-19 post-vaccine (3/1/2021-8/31/2022) study periods. We used multivariable logistic regression with generalized estimating equations to adjust for demographics and comorbidities to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Among 21,750 hospitalizations of 18,584 transfusion recipients without COVID-19, there were 697 post-transfusion thrombotic events, and oxygen requirements were increased in 1751 hospitalizations. Intensive care unit length of stay (n = 11,683) was 3 days (interquartile range 1-5), hospital mortality occurred in 3223 (14.8%), and 30-day rehospitalization in 4144 (23.7%). Comparing the pre-COVID, pre-vaccine and post-vaccine study periods, there were no trends in thromboses (OR 0.9 [95% CI 0.8, 1.1]; p = .22) or oxygen requirements (OR 1.0 [95% CI 0.9, 1.1]; p = .41). In parallel, there were no trends across study periods for ICU length of stay (p = .83), adjusted hospital mortality (OR 1.0 [95% CI 0.9-1.0]; p = .36), or 30-day rehospitalization (p = .29). Transfusion of plasma and platelet blood components collected during the pre-vaccine and post-vaccine periods of the COVID-19 pandemic was not associated with increased adverse outcomes in transfusion recipients without COVID-19.
Authors: Roubinian, Nareg H;Liu, Vincent X;Lee, Catherine;Mark, Dustin G;Vinson, David R;NHLBI Recipient Epidemiology and Donor Evaluation Study-IV-P (REDS-IV),;et al.
Transfusion. 2024 Jan;64(1):53-67. Epub 2023-12-06.
Recombinant or Standard-Dose Influenza Vaccine in Adults under 65 Years of Age
Quadrivalent recombinant influenza vaccines contain three times the amount of hemagglutinin protein as standard-dose egg-based vaccines, and the recombinant formulation is not susceptible to antigenic drift during manufacturing. Data are needed on the relative effectiveness of recombinant vaccines as compared with standard-dose vaccines against influenza-related outcomes in adults under the age of 65 years. In this cluster-randomized observational study, Kaiser Permanente Northern California facilities routinely administered either a high-dose recombinant influenza vaccine (Flublok Quadrivalent) or one of two standard-dose influenza vaccines during the 2018-2019 and 2019-2020 influenza seasons to adults 50 to 64 years of age (primary age group) and 18 to 49 years of age. Each facility alternated weekly between the two vaccine formulations. The primary outcome was influenza (A or B) confirmed by polymerase-chain-reaction (PCR) testing. Secondary outcomes included influenza A, influenza B, and influenza-related hospitalization outcomes. We used Cox regression analysis to estimate the hazard ratio of the recombinant vaccine as compared with the standard-dose vaccines against each outcome. We calculated the relative vaccine effectiveness as 1 minus the hazard ratio. The study population included 1,630,328 vaccinees between the ages of 18 and 64 years (632,962 in the recombinant-vaccine group and 997,366 in the standard-dose group). During this study period, 1386 cases of PCR-confirmed influenza were diagnosed in the recombinant-vaccine group and 2435 cases in the standard-dose group. Among the participants who were 50 to 64 years of age, 559 participants (2.00 cases per 1000) tested positive for influenza in the recombinant-vaccine group as compared with 925 participants (2.34 cases per 1000) in the standard-dose group (relative vaccine effectiveness, 15.3%; 95% confidence interval [CI], 5.9 to 23.8; P = 0.002). In the same age group, the relative vaccine effectiveness against influenza A was 15.7% (95% CI, 6.0 to 24.5; P = 0.002). The recombinant vaccine was not significantly more protective against influenza-related hospitalization than were the standard-dose vaccines. The high-dose recombinant vaccine conferred more protection against PCR-confirmed influenza than an egg-based standard-dose vaccine among adults between the ages of 50 and 64 years. (Funded by Sanofi; ClinicalTrials.gov number, NCT03694392.).
Authors: Hsiao, Amber;Yee, Arnold;Fireman, Bruce;Hansen, John;Lewis, Ned;Klein, Nicola P
N Engl J Med. 2023 Dec 14;389(24):2245-2255.
Environmental and Occupational Exposures and Prognosis in Patients with Non-Muscle Invasive Bladder Cancer in the Be-Well Study
Bladder cancer is primarily diagnosed as non-muscle invasive bladder cancer (NMIBC) with high recurrence and progression rates. Environmental and occupational exposures to carcinogens are well-known risk factors for developing bladder cancer, yet their effects on prognosis remain unknown. In the Be-Well Study, a population-based prospective cohort study of 1,472 patient with newly diagnosed NMIBC from 2015 to 2019, we examined history of environmental and occupational exposures in relation to tumor stage and grade at initial diagnosis by multivariable logistic regression, and subsequent recurrence and progression by Cox proportional hazards regression. Exposure to environmental and occupational carcinogens was significantly associated with increased risk of progression (HR = 1.79; 95% CI: 1.04, 3.09), specifically increased progression into muscle-invasive disease (HR = 2.28; 95% CI: 1.16, 4.50). Exposure to asbestos and arsenic were associated with increased odds of advanced stage at diagnosis (asbestos: OR = 1.43; 95% CI: 1.11, 1.84; arsenic, OR = 1.27; 95% CI: 1.01, 1.63), and formaldehyde exposure was associated with increased risk of recurrence (HR = 1.38; 95% CI: 1.12, 1.69). Our findings suggest that history of these exposures may benefit current risk stratification systems to tailor clinical care and improve prognosis in patients with NMIBC.
Authors: Wang, Zinian;Ergas, Isaac J;Quesenberry, Charles P;Kushi, Lawrence H;Tang, Li;et al.
Am J Epidemiol. 2023 Dec 05.
Influenza vaccine effectiveness against influenza-A-associated emergency department, urgent care, and hospitalization encounters among U.S. adults, 2022-2023
The 2022-2023 United States influenza season had unusually early influenza activity with high hospitalization rates. Vaccine-matched A(H3N2) viruses predominated, with lower levels of A(H1N1)pdm09 activity also observed. Using the test-negative design, we evaluated influenza vaccine effectiveness (VE) during the 2022-2023 season against influenza-A-associated emergency department/urgent care (ED/UC) visits and hospitalizations from October 2022-March 2023 among adults (age ≥18 years) with acute respiratory illness (ARI). VE was estimated by comparing odds of seasonal influenza vaccination among case-patients (influenza A test-positive by molecular assay) and controls (influenza test-negative), applying inverse-propensity-to-be-vaccinated weights. The analysis included 85,389 ED/UC ARI encounters (17.0% influenza-A-positive; 37.8% vaccinated overall) and 19,751 hospitalizations (9.5% influenza-A-positive; 52.8% vaccinated overall). VE against influenza-A-associated ED/UC encounters was 44% (95% confidence interval [95%CI]: 40-47%) overall and 45% and 41% among adults aged 18-64 and ≥65 years, respectively. VE against influenza-A-associated hospitalizations was 35% (95%CI: 27-43%) overall and 23% and 41% among adults aged 18-64 and ≥65 years, respectively. VE was moderate during the 2022-2023 influenza season, a season characterized with increased burden of influenza and co-circulation with other respiratory viruses. Vaccination is likely to substantially reduce morbidity, mortality, and strain on healthcare resources.
Authors: Tenforde, Mark W;Fireman, Bruce;Zerbo, Ousseny;Klein, Nicola P;Klein, Nicola P;et al.
J Infect Dis. 2023 Dec 02.
Fracture Risk and Association With TDF Use Among People With HIV in Large Integrated Health Systems
Greater decline in bone health among people with HIV (PWH) has been documented but fracture risk and the impact of specific antiretroviral therapy (ART) regimens remain unclear. Retrospective analyses of electronic health record data from 3 US integrated health care systems. Fracture incidence was compared between PWH aged 40 years or older without prior fracture and demographically matched people without HIV (PWoH), stratified by age, sex, and race/ethnicity. Multivariable Cox proportional hazards models were used to estimate fracture risk associated with HIV infection. The association of tenofovir disoproxil fumarate (TDF) use and fracture risk was evaluated in a subset of PWH initiating ART. Incidence of fracture was higher in PWH [13.6/1000 person-years, 95% confidence interval (CI): 13.0 to 14.3, n = 24,308] compared with PWoH (9.5, 95% CI: 9.4 to 9.7, n = 247,313). Compared with PWoH, the adjusted hazard ratio (aHR) for fracture among PWH was 1.24 (95% CI: 1.18 to 1.31). The association between HIV infection and fracture risk increased with age, with the lowest aHR (1.17, 95% CI: 1.10 to 1.25) among those aged 40-49 years and the highest aHR (1.89, 95% CI: 1.30 to 2.76) among those aged 70 years or older. Among PWH initiating ART (n = 6504), TDF was not associated with significant increase in fracture risk compared with non-TDF regimens (aHR: 1.18, 95% CI: 0.89 to 1.58). Among people aged 40 years or older, HIV infection is associated with increased risk of fractures. Bone health screening from the age of 40 years may be beneficial for PWH. Large cohort studies with longer follow-up are needed to evaluate TDF effect and the potential benefit of early screening.
Authors: Hechter, Rulin C;Lam, Jennifer O;Alexeeff, Stacey;Lo, Joan C;Silverberg, Michael J;Silverberg, Michael J;et al.
J Acquir Immune Defic Syndr. 2023 Dec 01;94(4):341-348.
Postpartum defects in inflammatory response after gestational diabetes precede progression to type 2 diabetes: a nested case-control study within the SWIFT study
Gestational diabetes (GDM) is a distinctive form of diabetes that first presents in pregnancy. While most women return to normoglycemia after delivery, they are nearly ten times more likely to develop type 2 diabetes than women with uncomplicated pregnancies. Current prevention strategies remain limited due to our incomplete understanding of the early underpinnings of progression. To comprehensively characterize the postpartum profiles of women shortly after a GDM pregnancy and identify key mechanisms responsible for the progression to overt type 2 diabetes using multi-dimensional approaches. We conducted a nested case-control study of 200 women from the Study of Women, Infant Feeding and Type 2 Diabetes After GDM Pregnancy (SWIFT) to examine biochemical, proteomic, metabolomic, and lipidomic profiles at 6-9 weeks postpartum (baseline) after a GDM pregnancy. At baseline and annually up to two years, SWIFT administered research 2-hour 75-gram oral glucose tolerance tests. Women who developed incident type 2 diabetes within four years of delivery (incident case group, n = 100) were pair-matched by age, race, and pre-pregnancy body mass index to those who remained free of diabetes for at least 8 years (control group, n = 100). Correlation analyses were used to assess and integrate relationships across profiling platforms. At baseline, all 200 women were free of diabetes. The case group was more likely to present with dysglycemia (e.g., impaired fasting glucose levels, glucose tolerance, or both). We also detected differences between groups across all omic platforms. Notably, protein profiles revealed an underlying inflammatory response with perturbations in protease inhibitors, coagulation components, extracellular matrix components, and lipoproteins, whereas metabolite and lipid profiles implicated disturbances in amino acids and triglycerides at individual and class levels with future progression. We identified significant correlations between profile features and fasting plasma insulin levels, but not with fasting glucose levels. Additionally, specific cross-omic relationships, particularly among proteins and lipids, were accentuated or activated in the case group but not the control group. Overall, we applied orthogonal, complementary profiling techniques to uncover an inflammatory response linked to elevated triglyceride levels shortly after a GDM pregnancy, which is more pronounced in women who progress to overt diabetes.
Authors: Van, Julie A D;Luo, Yihan;Danska, Jayne S;Dai, Feihan;Alexeeff, Stacey E;Gunderson, Erica P;Rost, Hannes;Wheeler, Michael B
Metabolism. 2023 Dec;149:155695. Epub 2023-10-05.
Intrinsic motivation for physical activity, healthy eating, and self-weighing in association with corresponding behaviors in early pregnancy
Healthy lifestyle behaviors influence maternal cardiovascular health, but motivation for them in pregnancy is poorly understood. We examined whether intrinsic motivation (assessed on 5-point scales for each behavior) is associated with three lifestyle behaviors in early pregnancy: physical activity, by intensity level; healthy eating, quantified with the Alternate Healthy Eating Index for Pregnancy (AHEI-P); and weight self-monitoring, a standard weight management technique. Participants in the Northern California Pregnancy, Lifestyle and Environment Study (PETALS) population-based cohort completed validated surveys in early pregnancy (2017-18; N = 472; 22 % Asian, 6 % Black, 30 % Hispanic, 13 % multiracial, 30 % White). Cross-sectional data were analyzed in 2021-22. Overall, 40.7 % (n = 192) met United States national physical activity guidelines; the average AHEI-P score was 62.3 out of 130 (SD 11.4); and 36.9 % reported regular self-weighing (≥once/week; n = 174). In models adjusted for participant characteristics, 1-unit increases in intrinsic motivation were associated with increased likelihood of meeting physical activity guidelines (risk ratio [95 % CI]: 1.66 [1.48, 1.86], p < 0.0001); meeting sample-specific 75th percentiles for vigorous physical activity (1.70 [1.44, 1.99], p < 0.0001) and AHEI-P (1.75 [1.33, 2.31], p < 0.0001); and regular self-weighing (2.13 [1.92, 2.37], p < 0.0001). A 1-unit increase in intrinsic motivation lowered the risk of meeting the 75th percentile for sedentary behavior (0.79 [0.67, 0.92], p < 0.003). Intrinsic motivation was not associated with reaching 75th percentiles for total, light, or moderate activity. Intrinsic motivation is associated with physical activity, healthy eating, and self-weighing among diverse individuals in early pregnancy. Results can inform intervention design to promote maternal health via increased enjoyment of lifestyle behaviors.
Authors: Brown, Susan D;Kiernan, Michaela;Ehrlich, Samantha F;Zhu, Yeyi;Hedderson, Monique M;Daredia, Saher;Feng, Juanran;Millman, Andrea;Quesenberry, Charles P;Ferrara, Assiamira
Prev Med Rep. 2023 Dec;36:102456. Epub 2023-10-04.
Neonatal Outcomes Associated with In Utero Cannabis Exposure: A Population-Based Retrospective Cohort Study
The full spectrum of associations between in utero cannabis exposure and adverse neonatal outcomes is still unclear. This study evaluates associations between in utero cannabis exposure and neonatal outcomes. This population-based retrospective cohort study of singleton births among Kaiser Permanente Northern California members (January 1, 2011- July 31, 2020) included parent-infant dyads in which the pregnant parent was screened for cannabis use as part of standard prenatal care, generally upon entrance into care. Data were ascertained from electronic health records. Generalized estimating equation models were adjusted for sociodemographic characteristics, other non-cannabis prenatal substance use, medical and mental health comorbidities, and adequacy of prenatal care. In utero cannabis exposure was defined as self-report since becoming pregnant and/or a positive urine toxicology test for cannabis at any time during pregnancy (yes/no; primary) and frequency of use (self-report daily, weekly, ≤ monthly, never, unknown; secondary). Neonatal outcomes included low birth weight (LBW), small for gestational age (SGA), preterm birth, neonatal intensive care unit (NICU) admission, and infant respiratory support. Of 364,924 infants, 22,624 (6.2%) were exposed to cannabis in utero. After adjustment for potential confounders including in utero exposure to other substances, in utero exposure to cannabis was associated with greater odds of LBW (adjusted odds ratio [aOR],1.20; 95%CI, 1.12-1.28), SGA (aOR, 1.24; 95%CI, 1.18-1.30), preterm birth (<37 weeks; aOR,1.06; 95%CI, 1.00-1.13), and NICU admission (aOR,1.06; 95%CI, 1.01-1.11). There was a suggestive association with early preterm birth (<34 weeks; aOR, 1.11; 95%CI, 1.00-1.23, P=.055), but no significant association with respiratory support (aOR,1.07; 95%CI, 0.97-1.18). Dose-response analysis found an increasing likelihood of LBW and SGA with increasing frequency of prenatal cannabis use by the pregnant individual. Sensitivity analyses further supported an increased likelihood of LBW and SGA although associations with other outcomes did not reach significance. In utero cannabis exposure was associated with an increased likelihood of LBW, SGA, preterm birth, and NICU admission. Clinicians should counsel individuals who are pregnant or considering pregnancy about the potential adverse neonatal health outcomes associated with prenatal cannabis use.
Authors: Avalos, Lyndsay A;Adams, Sara R;Alexeeff, Stacey E;Oberman, Nina R;Does, Monique B;Ansley, Deborah;Goler, Nancy;Padon, Alisa A;Silver, Lynn D;Young-Wolff, Kelly C
Am J Obstet Gynecol. 2023 Nov 18.
Effectiveness of the live zoster vaccine during the 10 years following vaccination: real world cohort study using electronic health records
To assess the effectiveness of live zoster vaccine during more than 10 years after vaccination; and to describe methods for ascertaining vaccine effectiveness in the context of waning. Real world cohort study using electronic health records. Kaiser Permanente Northern California, an integrated healthcare delivery system in the US, 1 January 2007 to 31 December 2018. More than 1.5 million people aged 50 years and older followed for almost 9.4 million person years. Vaccine effectiveness in preventing herpes zoster, postherpetic neuralgia, herpes zoster ophthalmicus, and admission to hospital for herpes zoster was assessed. Change in vaccine effectiveness by time since vaccination was examined using Cox regression with a calendar timeline. Time varying indicators were specified for each interval of time since vaccination (30 days to less than one year, one to less than two years, etc) and adjusted for covariates. Of 1 505 647 people, 507 444 (34%) were vaccinated with live zoster vaccine. Among 75 135 incident herpes zoster cases, 4982 (7%) developed postherpetic neuralgia, 4439 (6%) had herpes zoster ophthalmicus, and 556 (0.7%) were admitted to hospital for herpes zoster. For each outcome, vaccine effectiveness was highest in the first year after vaccination and decreased substantially over time. Against herpes zoster, vaccine effectiveness waned from 67% (95% confidence interval 65% to 69%) in the first year to 15% (5% to 24%) after 10 years. Against postherpetic neuralgia, vaccine effectiveness waned from 83% (78% to 87%) to 41% (17% to 59%) after 10 years. Against herpes zoster ophthalmicus, vaccine effectiveness waned from 71% (63% to 76%) to 29% (18% to 39%) during five to less than eight years. Against admission to hospital for herpes zoster, vaccine effectiveness waned from 90% (67% to 97%) to 53% (25% to 70%) during five to less than eight years. Across all follow-up time, overall vaccine effectiveness was 46% (45% to 47%) against herpes zoster, 62% (59% to 65%) against postherpetic neuralgia, 45% (40% to 49%) against herpes zoster ophthalmicus, and 66% (55% to 74%) against admission to hospital for herpes zoster. Live zoster vaccine was effective initially. Vaccine effectiveness waned substantially yet some protection remained 10 years after vaccination. After 10 years, protection was low against herpes zoster but higher against postherpetic neuralgia. ClinicalTrials.gov number NCT01600079; EU PAS register number EUPAS17502.
Authors: Klein, Nicola P;Bartlett, Joan;Fireman, Bruce;Marks, Morgan A;Hansen, John;Lewis, Edwin;Aukes, Laurie;Saddier, Patricia
BMJ. 2023 Nov 08;383:e076321. Epub 2023-11-08.
Effectiveness of COVID-19 vaccination during pregnancy by circulating viral variant
SARS-CoV-2 infection in pregnancy can result in a spectrum of asymptomatic to critical COVID-19 outcomes, including hospitalization, admission to the intensive care unit, or death. This study aimed to investigate the effectiveness of messenger RNA COVID-19 vaccination during pregnancy against both hospitalization and infection, stratified by different variant circulations and by time since the last vaccine dose. This was a retrospective cohort study among pregnant persons who were members of Kaiser Permanente Northern California and delivered between December 15, 2020, and September 30, 2022. Pregnant persons who received any vaccine dose before the pregnancy onset date were excluded. The primary outcome was hospitalization for COVID-19, and the secondary outcome was polymerase chain reaction-confirmed SARS-CoV-2 infection. Exposure was receipt of a messenger RNA vaccine during pregnancy. Poisson regression was used to estimate the risk ratio of hospitalization by comparing vaccinated pregnant persons with unvaccinated pregnant persons adjusted for sociodemographic factors and calendar time. Cox regression was used to estimate the hazard ratio of infection by comparing vaccinated pregnant persons with unvaccinated pregnant persons. Vaccine effectiveness was estimated as 1 minus the rate ratio or the hazard ratio multiplied by 100. Vaccine effectiveness was estimated overall and by variant periods (before Delta, Delta, Omicron, and subvariants). Of 57,688 pregnant persons, 16,153 (28%) received at least 1 dose of a messenger RNA COVID-19 vaccine during pregnancy; moreover, 4404 pregnant persons tested positive for SARS-CoV-2 infection, and 108 pregnant persons were hospitalized during pregnancy. Overall, 2-dose vaccine effectiveness against hospitalization was 91% within <150 days of vaccination and 48% >150 days after vaccination. The 2-dose vaccine effectiveness within <150 days after vaccination was 100% during the original virus strain and Delta variant periods of the virus; vaccine effectiveness was 51% during the Omicron period. Of the hospitalization cases, 97% of pregnant persons were unvaccinated. During hospitalization, none of the vaccinated pregnant persons required ventilation or were admitted to the intensive care unit. Moreover, 2-dose vaccine effectiveness against infection was 54% within <150 days after vaccination and 26% ≥150 days after vaccination. Messenger RNA COVID-19 vaccination during pregnancy was effective against hospitalization for COVID-19 and SARS-CoV-2 infection. COVID-19 was mild among pregnant persons who were vaccinated compared with those who were unvaccinated. Thus, all pregnant persons should be strongly encouraged to receive messenger RNA COVID-19 vaccines to prevent severe disease.
Authors: Zerbo, Ousseny;Ray, G Thomas;Fireman, Bruce;Layefsky, Evan;Goddard, Kristin;Ross, Pat;Greenberg, Mara;Klein, Nicola P
AJOG Glob Rep. 2023 Nov;3(4):100264. Epub 2023-08-25.
Neighborhood Disadvantage, Race and Ethnicity, and Postpartum Depression
Postpartum depression (PPD) is a debilitating condition with higher rates among Black individuals. Increasingly, neighborhood disadvantage is being recognized as a contributor to poor health and may be associated with adverse postpartum mental health; however, associations between neighborhood disadvantage, race and ethnicity, and PPD have not been examined. To investigate the association between neighborhood disadvantage and PPD and evaluate the extent to which these associations may differ by race and ethnicity. This population-based cross-sectional study included 122 995 postpartum Kaiser Permanente Northern California members 15 years or older with a live birth between October 7, 2012, and May 31, 2017, and an address in the electronic health record. Analyses were conducted from June 1, 2022, through June 30, 2023. Neighborhood disadvantage defined using quartiles of the Neighborhood Deprivation Index (NDI), a validated census-based socioeconomic status measure; self-reported race and ethnicity ascertained from Kaiser Permanente Northern California electronic health records. Multivariable Poisson regression was conducted to assess associations between neighborhood disadvantage, race and ethnicity, and a diagnosis of PPD. Of 122 995 included postpartum individuals, 17 554 (14.3%) were younger than 25 years, 29 933 (24.3%) were Asian, 8125 (6.6%) were Black, 31 968 (26.0%) were Hispanic, 47 527 (38.6%) were White, 5442 (4.4%) were of other race and ethnicity, and 15 436 (12.6%) had PPD. Higher neighborhood disadvantage and race and ethnicity were associated with PPD after covariate adjustment. Compared with White individuals, Black individuals were more likely to have PPD (adjusted relative risk [ARR], 1.30; 95% CI, 1.24-1.37), whereas Asian (ARR, 0.48; 95% CI, 0.46-0.50), and Hispanic (ARR, 0.92; 95% CI, 0.89-0.96) individuals and those identified as having other race and ethnicity (ARR, 95% CI, 0.90; 0.85-0.98) were less likely to have PPD. Associations between NDI and PPD differed by race and ethnicity (likelihood ratio test for interaction, χ212 = 41.36; P < .001). Among Black individuals, the risk of PPD was the greatest overall and increased with neighborhood disadvantage in a dose-response manner (quartile [Q] 2 ARR, 1.39 [95% CI, 1.13-1.71]; Q3 ARR, 1.50 [95% CI, 1.23-1.83]; Q4 ARR, 1.60 [95% CI, 1.32-1.93]; Cochrane-Armitage test for trend, P < .001). Neighborhood disadvantage was associated with PPD among Asian (Q2 ARR, 1.17 [95% CI, 1.04-1.31]; Q3 ARR, 1.20 [95% CI, 1.06-1.35]) and White (Q3 ARR, 1.14 [95% CI, 1.07-1.21]; Q4 ARR, 1.17 [95% CI, 1.09-1.26]) individuals and those of other race and ethnicity (Q3 ARR, 1.34 [95% CI, 1.09-1.63]; Q4 ARR, 1.28 [95% CI, 1.03-1.58]), but the magnitude of risk was lower. Neighborhood disadvantage was not associated with PPD among Hispanic individuals (eg, Q2 ARR, 1.04 [95% CI, 0.94-1.14]; Q3 ARR, 1.00 [95% CI, 0.91-1.10]; Q4 ARR, 0.98 [95% CI, 0.90-1.08]). In this cross-sectional study of postpartum individuals, residing in more disadvantaged neighborhoods was associated with PPD, except among Hispanic individuals. Neighborhood disadvantage may be associated with racial and ethnic differences in postpartum mental health. Geographic targeting of mental health interventions may decrease postpartum mental health inequities.
Authors: Onyewuenyi, Ticara L;Peterman, Kelli;Zaritsky, Eve;Ritterman Weintraub, Miranda L;Pettway, Bria L;Quesenberry, Charles P;Nance, Nerissa;Surmava, Ann-Marie;Avalos, Lyndsay A
JAMA Netw Open. 2023 Nov 01;6(11):e2342398. Epub 2023-11-01.
Patient-reported Primary Care Video and Telephone Telemedicine Preference Shifts During the COVID-19 Pandemic
Patient perceptions of primary care telephone and video telemedicine and whether COVID-19 pandemic-related telemedicine exposure shifted patients’ visit preference is unknown. We examined patient surveys to understand the health care experience of patients seeking primary care through telemedicine and how patients expected their preferences to shift as a result of the COVID-19 pandemic. In an integrated delivery system that shifted to a “telemedicine-first” health care model during the COVID-19 pandemic, we sampled monthly and collected 1000 surveys from adults with primary care telemedicine visits scheduled through the online patient portal between 3/16/2020 and 10/31/2020. Participants reported their preferred primary care visit modality (telephone, video, or in-person visits) across 3 time points: before, during and (hypothetically) after the COVID-19 pandemic, and reported their general assessment of primary care visits during the pandemic. The majority of participants preferred in-person visits before (69%) and after the COVID-19 pandemic (57%). However, most participants reported a preference for telemedicine visits during the pandemic and continue to prefer telemedicine visits at a 12% higher rate post-pandemic. Many participants (63%) expressed interest in using telemedicine at least some of the time. Among participants reporting a recent telemedicine visit, 85% agreed that the visit addressed their health needs. As primary care visit modality preferences continue to evolve, patients anticipate that they will continue to prefer telemedicine visits, both video and telephone, at an increased rate than before the COVID-19 pandemic.
Authors: Millman, Andrea;Huang, Jie;Graetz, Ilana;Lee, Catherine;Shan, Judy;Hsueh, Loretta;Muelly, Emilie;Gopalan, Anjali;Reed, Mary
Med Care. 2023 Nov 01;61(11):772-778. Epub 2023-09-19.
Independent Impact of Eat, Sleep, Console Assessment on Neonatal Opioid Withdrawal Syndrome
Compared with the Finnegan Neonatal Abstinence Scoring System (FNASS), the Eat, Sleep, Console (ESC) approach reduces pharmacotherapy and length of stay (LOS) for neonatal opioid withdrawal syndrome (NOWS) infants. The independent outcome contribution of ESC is unknown as the approach combines ESC assessment with additional management changes. Our objective was to evaluate ESC assessment’s independent impact on outcomes compared with FNASS. We conducted a retrospective cohort study of in utero opioid-exposed infants ≥35 weeks gestation managed with FNASS versus ESC. Outcomes included pharmacotherapy initiation, LOS, length of pharmacotherapy, and emergency department visit/readmissions. Among 151 FNASS and 100 ESC managed infants, pharmacotherapy initiation (P = .47), LOS for all infants (P = .49), and LOS for pharmacologically treated infants (P = .68) were similar. Length of pharmacotherapy did not differ (P = .84). Emergency department evaluation/NOWS readmission was equally rare (P = .65). Using equivalent models of care, comparison of ESC and FNASS assessment tools showed no difference in NOWS outcomes.
Authors: Chyi, Lisa J;Li, Sherian;Lee, Catherine;Walsh, Eileen M;Kuzniewicz, Michael W
Clin Pediatr (Phila). 2023 Oct 05:99228231204448.
Impact of a scalable training program on the quality of colonoscopy performance and risk of post-colonoscopy colorectal cancer
Endoscopist adenoma detection rates (ADRs) vary widely and are associated with patients’ risk of postcolonoscopy colorectal cancers (PCCRCs). However, few scalable physician-directed interventions demonstrably both improve ADR and reduce PCCRC risk. Among patients undergoing colonoscopy, we evaluated the influence of a scalable online training on individual-level ADRs and PCCRC risk. The intervention was a 30-minute, interactive, online training, developed using behavior change theory, to address factors that potentially impede detection of adenomas. Analyses included interrupted time series analyses for pretraining versus posttraining individual-physician ADR changes (adjusted for temporal trends) and Cox regression for associations between ADR changes and patients’ PCCRC risk. Across 21 endoscopy centers and all 86 eligible endoscopists, ADRs increased immediately by an absolute 3.13% (95% confidence interval [CI], 1.31-4.94) in the 3-month quarter after training compared with .58% per quarter (95% CI, .40-.77) and 0.33% per quarter (95% CI, .16-.49) in the 3-year pretraining and posttraining periods, respectively. Posttraining ADR increases were higher among endoscopists with pretraining ADRs below the median. Among 146,786 posttraining colonoscopies (all indications), each 1% absolute increase in screening ADR posttraining was associated with a 4% decrease in their patients’ PCCRC risk (hazard ratio, .96; 95% CI, .93-.99). An ADR increase of ≥10% versus <1% was associated with a 55% reduced risk of PCCRC (hazard ratio, .45; 95% CI, .24-.82). A scalable, online behavior change training intervention focused on modifiable factors was associated with significant and sustained improvements in ADR, particularly among endoscopists with lower ADRs. These ADR changes were associated with substantial reductions in their patients' risk of PCCRC.
Authors: Corley, Douglas A;Jensen, Christopher D;Lee, Jeffrey K;Contreras, Richard;Fireman, Bruce H;Quesenberry, Charles P;et al.
Gastrointest Endosc. 2023 Oct;98(4):609-617. Epub 2023-04-23.
Association between maternal prenatal cannabis use and missed child preventive care visits in an integrated health care delivery system in Northern California
The periodicity of well-child visits recommended by the American Academy of Pediatrics emphasizes the importance of continuity of care in health management. Exposure to cannabis in utero has been associated with adverse development, and adherence to well-child visits is critical for earlier detection and intervention. To assess whether maternal prenatal cannabis use was associated with missed well-child visits in the first three years after birth we conducted a longitudinal cohort study in Kaiser Permanente Northern California of pregnant individuals and their children born between January 1, 2011 and December 31, 2018. Maternal prenatal cannabis use was defined as any self-reported cannabis use since becoming pregnant and/or a positive urine toxicology test for cannabis during pregnancy. Well-child visits were defined as an encounter for a well-child visit or physical exam and categorized into seven time periods from birth to 36 months. Modified Poisson regression models were conducted. Of the 168,589 eligible pregnancies, 3.4% screened positive for maternal prenatal cannabis use. Compared to no use, maternal prenatal cannabis use was associated with more missed well-child visits at every time period; (missed 12-month visit: adjusted relative risk (aRR): 1.43, 95%CI: 1.32-1.54; missed 3-year visit: aRR: 1.15, 95%CI: 1.11-1.20). Maternal prenatal cannabis use was also associated with missing two or more well-child visits through 36 months of age (35.8% among cannabis users vs. 23.0% among non-users, Χ2p < .001). Educating pregnant individuals who use cannabis on the importance of well-child visits may benefit children's health and development.
Authors: Avalos, Lyndsay A;Oberman, Nina;Alexeeff, Stacey E;Croen, Lisa A;Adams, Sara R;Davignon, Meghan;Young-Wolff, Kelly C
Prev Med. 2023 Oct;175:107716. Epub 2023-09-28.
PFAS concentrations in early and mid-pregnancy and risk of gestational diabetes mellitus in a nested case-control study within the ethnically and racially diverse PETALS cohort
Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals and are commonly found in everyday items. PFAS have been linked to disrupting glucose homeostasis, however, whether they are associated with gestational diabetes mellitus (GDM) risk remains inconclusive. We examined prospective associations of PFAS concentrations measured twice in pregnancy with GDM risk. In the PETALS pregnancy cohort, a nested case-control study which included 41 GDM cases and 87 controls was conducted. PFAS analytes were measured in blood serum collected in both early and mid-pregnancy (mean [SD]: 13.9 [2.2] and 20.2 [2.2] gestational weeks, respectively), with cumulative exposure calculated by the area-under-the-curve (AUC) to integrate both the PFAS concentration and the timing of the exposure. Individual adjusted weighted unconditional logistic regression models examined seven PFAS in association with GDM risk. P-values were corrected using the false-discovery-rate (FDR). Mixture models were analyzed with Bayesian kernel machine regression (BKMR). PFDA, PFNA and PFOA were individually associated with higher GDM risk per interquartile range (IQR) in early pregnancy (OR [95% CI]: 1.23 [1.09, 1.38]), 1.40 [1.24, 1.58]), and 1.15 [1.04, 1.27], respectively), mid-pregnancy (1.28 [1.15, 1.43], 1.16 [1.05, 1.28], and 1.20 [1.09, 1.33], respectively), and with cumulative exposure (1.23 [1.09, 1.38], 1.21 [1.07, 1.37], and 1.19 [1.09, 1.31], respectively). PFOS in mid-pregnancy and with cumulative exposure was associated with increased GDM risk (1.41 [1.17, 1.71] and 1.33 [1.06, 1.58], respectively). PFUnDA in early pregnancy was associated with lower GDM risk (0.79 [0.64, 0.98]), whereas mid-pregnancy levels were associated with higher risk (1.49 [1.18, 1.89]). PFHxS was associated with decreased GDM risk in early and mid-pregnancy (0.48 [0.38, 0.60] and 0.48 [0.37, 0.63], respectively) and with cumulative exposure (0.49 [0.38,0.63]). PFPeA was not associated with GDM. Similar conclusions were observed in BKMR models; however, overall associations in these models were not statistically significant. Higher risk of GDM was consistently observed in association with PFDA, PFNA, and PFOA exposure in both early and mid-pregnancy. Results should be corroborated in larger population-based cohorts and individuals of reproductive age should potentially avoid known sources of PFAS.
Authors: Peterson, Alicia K;Zhu, Yeyi;Fuller, Sophia;Feng, Juanran;Alexeeff, Stacey;Mitro, Susanna D;Kannan, Kurunthachalam;Robinson, Morgan;Padula, Amy;Ferrara, Assiamira
BMC Pregnancy Childbirth. 2023 Sep 13;23(1):657. Epub 2023-09-13.
Challenges and Opportunities of Epidemiological Studies to Reduce the Burden of Cancers in Young Adults
There are >1.9 million survivors of adolescent and young adult cancers (AYA, diagnosed at ages 15-39) living in the U.S. today. Epidemiologic studies to address the cancer burden in this group have been a relatively recent focus of the research community. In this article, we discuss approaches and data resources for cancer epidemiology and health services research in the AYA population. We consider research that uses data from cancer registries, vital records, healthcare utilization, and surveys, and the accompanying challenges and opportunities of each. To illustrate the strengths of each data source, we present example research questions or areas that are aligned with these data sources and salient to AYAs. Integrating the respective strengths of cancer registry, vital records, healthcare data, and survey-based studies sets the foundation for innovative and impactful research on AYA cancer treatment and survivorship to inform a comprehensive understanding of diverse AYA needs and experiences.
Authors: Nichols, Hazel B;Lee, Catherine;Quesenberry, Charles P;Kushi, Lawrence H;Kushi, Lawrence H;et al.
Curr Epidemiol Rep. 2023 Sep;10(3):115-124. Epub 2022-03-29.
Individual and neighborhood factors associated with being unvaccinated against COVID-19 among pregnant persons
We investigated whether unvaccinated pregnant persons cluster geographically and determined factors associated with being unvaccinated using spatial and multivariate logistic regression analyses. Pregnant persons with deliveries from December 15, 2020, through September 30, 2022, at Kaiser Permanente Northern California were included. Of the 85,852 pregnant persons in the study, 46.6% were unvaccinated before and during pregnancy. Spatial analysis identified 5 clusters with high prevalence of unvaccinated pregnant persons. Within these clusters, the proportion of unvaccinated varied from 53% to 62% versus 39% outside the clusters. In covariate-adjusted analyses, residence in a cluster increased the odds of being unvaccinated by 1.64 (95% confidence interval (CI): 1.59,1.69). The odds of being unvaccinated increased among those aged 16-24 years (odds ratio [OR] = 2.69, CI: 2.55, 2.83), aged 25-34 years (OR = 1.59, CI: 1.54, 1.64) compared with age ≥ 35 years, black race (OR = 1.45, CI:1.37, 1.54), and subsidized insurance (OR = 1.32, CI: 1.26, 1.38). The odds of being unvaccinated also increased for pregnant persons living in neighborhoods where the proportion of adults with high school education or less was greater than 20%. Geographic clustering of unvaccinated pregnant persons suggests a need for population-specific-interventions to increase vaccine coverage.
Authors: Zerbo, Ousseny;Ray, G Thomas;Fireman, Bruce;Layefsky, Evan;Goddard, Kristin;Ross, Pat;Greenberg, Mara;Klein, Nicola P
Hum Vaccin Immunother. 2023 Aug 01;19(2):2256042.
A demonstration of Modified Treatment Policies to evaluate shifts in mobility and COVID-19 case rates in U.S. counties
Mixed evidence exists of associations between mobility data and coronavirus disease 2019 (COVID-19) case rates. We aimed to evaluate the county-level impact of reducing mobility on new COVID-19 cases in summer/fall of 2020 in the United States and to demonstrate modified treatment policies to define causal effects with continuous exposures. Specifically, we investigated the impact of shifting the distribution of 10 mobility indexes on the number of newly reported cases per 100,000 residents 2 weeks ahead. Primary analyses used targeted minimum loss-based estimation with Super Learner to avoid parametric modeling assumptions during statistical estimation and flexibly adjust for a wide range of confounders, including recent case rates. We also implemented unadjusted analyses. For most weeks, unadjusted analyses suggested strong associations between mobility indexes and subsequent new case rates. However, after confounder adjustment, none of the indexes showed consistent associations under mobility reduction. Our analysis demonstrates the utility of this novel distribution-shift approach to defining and estimating causal effects with continuous exposures in epidemiology and public health.
Authors: Nugent, Joshua R; Balzer, Laura B
Am J Epidemiol. 2023 May 05;192(5):762-771.
Blood donor, component, and recipient-specific factors associated with venous thromboembolism in transfused hospitalized adult patients: Data from the recipient epidemiology and donor evaluation Study-III (REDS-III)
Growing evidence suggests multiple pathophysiological mechanisms linking red blood cells (RBC) transfusions to thrombosis. This study examined blood donor, component, and recipient factors which may be associated with thromboembolic outcomes following RBC transfusion. We utilized the Recipient Epidemiology Donor Evaluation Study-III (REDS-III) database on patients transfused in 12 hospitals between 2013-2016. Stratified Cox proportional hazards regression models with time-dependent exposures were used to examine associations of donor and component modification characteristics on venous thromboembolism (VTE) in patients transfused RBC units. 59,603 patients were transfused 229,500 RBC units during 79,298 hospitalizations with post-transfusion VTE occurring in 1869 (2.4%) of patients. In adjusted regression analyses, a per RBC-unit risk of VTE was present for gamma irradiation (HR = 1.03; 95% CI: 1.02-1.03), female donor sex (HR = 1.01; 95% CI: 1.00-1.01), storage duration greater than 5 weeks (HR = 1.01; 95% CI: 1.01-1.02), AS-1 storage solution (HR = 1.01; 95% CI: 1.00-1.01), and apheresis-derived collections (HR = 1.01; 95% CI: 1.01-1.02). Among recipient factors, male sex (HR = 1.03; 95% CI: 1.02-1.04), pre-transfusion hemoglobin level (HR = 0.94; 95% CI: 0.94-0.94), body mass index strata (HR = 1.11; 95% CI: 1.08-1.14), and principal diagnoses including malignancy (HR = 1.13; 95% CI: 1.10-1.16), cardiac arrest (HR = 1.38; 95% CI:1.07-1.77) and hip fracture (HR = 1.59; 95% CI:1.53-1.66) were associated with VTE in adjusted analyses. We identified several donor, component, and recipient-specific factors associated with VTE in transfused hospitalized adult patients. In adjusted models, the dose-dependent associations of donor and component-specific factors with VTE were modest and unlikely to be clinically significant in the majority of transfused patients. Additional mechanistic and clinical studies linking blood donor and component factors with thrombotic outcomes are needed.
Authors: Goel, Ruchika; Plimier, Colleen; Lee, Catherine; Tobian, Aaron A R; Josephson, Cassandra D; Hod, Eldad A; Roubinian, Nareg H
Transfusion. 2023 May;63(5):925-932. Epub 2023-02-25.
Protection of 2 and 3 mRNA Vaccine Doses Against Severe Outcomes Among Adults Hospitalized with COVID-19 – VISION Network, August 2021 – March 2022
We assessed coronavirus disease 2019 (COVID-19) vaccination impact on illness severity among adults hospitalized with COVID-19, August 2021-March 2022. We evaluated differences in intensive care unit (ICU) admission, in-hospital death, and length of stay among vaccinated (2 or 3 mRNA vaccine doses) versus unvaccinated patients aged ≥18 years hospitalized for ≥24 hours with COVID-19-like illness and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) molecular testing. We calculated odds ratios (ORs) for ICU admission and death and subdistribution hazard ratios (SHR) for time to hospital discharge adjusted for age, geographic region, calendar time, and local virus circulation. We included 27 149 SARS-CoV-2-positive hospitalizations. During both Delta- and Omicron-predominant periods, protection against ICU admission was strongest among 3-dose vaccinees compared with unvaccinated patients (Delta OR, 0.52 [95% CI, .28-.96]; Omicron OR, 0.69 [95% CI, .54-.87]). During both periods, risk of in-hospital death was lower among vaccinated compared with unvaccinated patients but ORs overlapped across vaccination strata. We observed SHR >1 across all vaccination strata in both periods indicating faster discharge for vaccinated patients. COVID-19 vaccination was associated with lower rates of ICU admission and in-hospital death in both Delta and Omicron periods compared with being unvaccinated.
Authors: DeSilva, Malini B; Klein, Nicola P; Zerbo, Ousseny; Fireman, Bruce; Gaglani, Manjusha; et al.
J Infect Dis. 2023 Apr 18;227(8):961-969.
The prospective association of hyperandrogenism, oligomenorrhea and polycystic ovary syndrome with incident gestational diabetes: The coronary artery risk development in young adults women’s study
In this 28-year prospective study of 455 women (mean age: 26 years), polycystic ovary syndrome (PCOS) was associated with a 2.6-fold elevated risk of gestational diabetes (GDM). However, hyperandrogenism or oligomenorrhea in the absence of PCOS was not associated with GDM.
Authors: Appiah, Duke; Hedderson, Monique M; Kim, Catherine; Sidney, Stephen; Sternfeld, Barbara; Quesenberry, Charles P; Wellons, Melissa F; Gunderson, Erica P
Diabetes Res Clin Pract. 2023 Apr;198:110593. Epub 2023-03-02.
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.
Development of cardiometabolic risk factors following endocrine therapy in women with breast cancer
Studies comparing the effect of aromatase inhibitor (AI) and tamoxifen use on cardiovascular disease (CVD) risk factors in hormone-receptor positive breast cancer (BC) survivors report conflicting results. We examined associations of endocrine therapy use with incident diabetes, dyslipidemia, and hypertension. The Pathways Heart Study examines cancer treatment exposures with CVD-related outcomes in Kaiser Permanente Northern California members with BC. Electronic health records provided sociodemographic and health characteristics, BC treatment, and CVD risk factor data. Hazard ratios (HR) and 95% confidence intervals (CI) of incident diabetes, dyslipidemia, and hypertension in hormone-receptor positive BC survivors using AIs or tamoxifen compared with survivors not using endocrine therapy were estimated using Cox proportional hazards regression models adjusted for known confounders. In 8,985 BC survivors, mean baseline age and follow-up time was 63.3 and 7.8 years, respectively; 83.6% were postmenopausal. By treatment, 77.0% used AIs, 19.6% used tamoxifen, and 16.0% used neither. Postmenopausal women who used tamoxifen had an increased rate (HR: 1.43, 95% CI: 1.06-1.92) of developing hypertension relative to those who did not use endocrine therapy. Tamoxifen use was not associated with incident diabetes, dyslipidemia, or hypertension in premenopausal BC survivors. Postmenopausal AI users had higher hazard rates of developing diabetes (HR: 1.37, 95% CI: 1.05-1.80), dyslipidemia (HR: 1.58, 95% CI: 1.29-1.92) and hypertension (HR: 1.50, 95% CI: 1.24-1.82) compared with non-endocrine therapy users. Hormone-receptor positive BC survivors treated with AIs may have higher rates of developing diabetes, dyslipidemia, and hypertension over an average 7.8 years post-diagnosis.
Authors: Rillamas-Sun, Eileen; Kwan, Marilyn L; Iribarren, Carlos; Neugebauer, Romain; Rana, Jamal S; Nguyen-Huynh, Mai; Kushi, Lawrence H; Greenlee, Heather; et al.
Res Sq. 2023 Mar 22.
Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19-Associated Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompetent Adults – VISION Network, Nine States, September-November 2022
During June-October 2022, the SARS-CoV-2 Omicron BA.5 sublineage accounted for most of the sequenced viral genomes in the United States, with further Omicron sublineage diversification through November 2022.* Bivalent mRNA vaccines contain an ancestral SARS-CoV-2 strain component plus an updated component of the Omicron BA.4/BA.5 sublineages. On September 1, 2022, a single bivalent booster dose was recommended for adults who had completed a primary vaccination series (with or without subsequent booster doses), with the last dose administered ≥2 months earlier (1). During September 13-November 18, the VISION Network evaluated vaccine effectiveness (VE) of a bivalent mRNA booster dose (after 2, 3, or 4 monovalent doses) compared with 1) no previous vaccination and 2) previous receipt of 2, 3, or 4 monovalent-only mRNA vaccine doses, among immunocompetent adults aged ≥18 years with an emergency department/urgent care (ED/UC) encounter or hospitalization for a COVID-19-like illness.† VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated ED/UC encounters was 56% compared with no vaccination, 32% compared with monovalent vaccination only with last dose 2-4 months earlier, and 50% compared with monovalent vaccination only with last dose ≥11 months earlier. VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated hospitalizations was 59% compared with no vaccination, 42% compared with monovalent vaccination only with last dose 5-7 months earlier, and 48% compared with monovalent vaccination only with last dose ≥11 months earlier. Bivalent vaccines administered after 2, 3, or 4 monovalent doses were effective in preventing medically attended COVID-19 compared with no vaccination and provided additional protection compared with past monovalent vaccination only, with relative protection increasing with time since receipt of the last monovalent dose. All eligible persons should stay up to date with recommended COVID-19 vaccinations, including receiving a bivalent booster dose. Persons should also consider taking additional precautions to avoid respiratory illness this winter season, such as masking in public indoor spaces, especially in areas where COVID-19 community levels are high.
Authors: Tenforde, Mark W; Klein, Nicola P; Fireman, Bruce; Zerbo, Ousseny; Link-Gelles, Ruth; et al.
MMWR Morb Mortal Wkly Rep. 2023 Mar 17;71(53):1637-1646. Epub 2023-03-17.
TRENDS IN SMOKING-SPECIFIC LUNG CANCER INCIDENCE RATES WITHIN A U.S. INTEGRATED HEALTH SYSTEM, 2007-2018
At least 10% of lung cancers arise in adults who have never smoked. Data remain inconclusive on whether lung cancer incidence has been increasing among never-smoking adults. How have age-adjusted incidence rates of lung cancer changed temporally, especially among never-smoking adults? Trends in lung cancer incidence were examined using linked electronic health record and cancer registry data on a dynamic cohort of adults aged ≥30 years at risk for incident lung cancer between 1/1/2007 and 12/31/2018 from an integrated healthcare system in northern California. Truncated age-adjusted lung cancer incidence rates and average annual percentage change (AAPC) in rates were estimated, overall and separately for ever- and never-smoking adults by age, sex, and race/ethnicity. Our cohort included 3,751,348 (52.5% female; 48.0% non-Hispanic White; 63.1% never-smoking) adults, among whom 18,627 (52.7% female; 68.6% non-Hispanic White; 15.4% never-smoking) were diagnosed with lung cancer. The overall lung cancer incidence rate declined from 91.1 to 63.7 per 100,000 person-years between 2007-2009 and 2016-2018 (AAPC, -3.9%; 95% CI, -4.2%, -3.6%). Among ever-smoking adults, incidence rates declined overall from 167.0 to 113.4 per 100,000 person-years (AAPC, -4.2%; 95% CI, -4.4%, -3.9%) and, to varying degrees, within all age, sex, and racial/ethnic groups. Among never-smoking adults, incidence rates were relatively constant, with three-year period estimates ranging from 19.9 to 22.6 per 100,000 person-years (AAPC, 0.9%; 95% CI, -0.3%, 2.1%). Incidence rates for never-smoking adults appeared stable over time within age, sex, and racial/ethnic groups, except for those of Asian and Pacific Islander (API) origin (AAPC, 2.0%; 95% CI, 0.1%, 3.9%), whose rates were about twice as high compared to their counterparts. These observed trends underscore the need to further elucidate the etiology of lung cancer in never-smoking adults, including why incidence is higher and rising in never-smoking API adults.
Authors: Sakoda, Lori C; Alabaster, Amy; Sumner, Eric T; Gordon, Nancy P; Quesenberry, Charles P; Velotta, Jeffrey B
Chest. 2023 Mar 17.
Rates of malignancies among patients with moderate to severe atopic dermatitis: a retrospective cohort study
Patients with atopic dermatitis (AD), also known as eczema, may be at an increased risk for malignancies compared with patients without AD; however, incidence rates (IRs) of malignancies in patients with moderate to severe AD are largely unknown. The objective of this study was to evaluate and compare IRs of malignancies in adults with moderate to severe AD (aged ≥18 years). Retrospective cohort study using data from a Kaiser Permanente Northern California (KPNC) cohort. AD severity classification was adjudicated with medical chart review. Covariates and stratification variables included age, sex and smoking status. Data were obtained from the KPNC healthcare delivery system in northern California, USA. Cases of AD were defined by outpatient dermatologist-rendered codes and prescriptions of topical therapy or phototherapy (moderate) or systemic treatment (severe). KPNC health plan members with moderate or severe AD (2007-2018). Malignancy IRs and 95% CIs per 1000 person-years were calculated. 7050 KPNC health plan members with moderate and severe AD met eligibility criteria for inclusion. IRs (95% CI) were highest for non-melanoma skin cancer (NMSC) in patients with moderate and severe AD (4.6 (95% CI 3.9 to 5.5) and 5.9 (95% CI 3.8 to 9.2), respectively) and breast cancer (2.2 (95% CI 1.6 to 3.0) and 0.5 (95% CI 0.1 to 3.9), respectively). Except for breast cancer, which was only evaluated in women, malignancies were higher (with non-overlapping CIs) in patients with moderate and moderate to severe AD in men versus women for basal cell carcinoma and NMSC and in former versus never smokers for NMSC and squamous cell carcinoma. This study estimated IRs of malignancies in patients with moderate and severe AD and provides valuable information for dermatology clinicians and ongoing clinical trials in these populations.
Authors: Hedderson, Monique M;Asgari, Maryam M;Xu, Fei;Quesenberry, Charles P;Sridhar, Sneha;Geier, Jamie;Lemeshow, Adina R
BMJ Open. 2023 Mar 10;13(3):e071172. Epub 2023-03-10.
Associations between antidepressant use patterns during pregnancy and birth outcomes among periconception antidepressant users
Little is known about antidepressant medication use patterns during pregnancy among periconception (before and immediately following conception) users. Additionally, the associations between these patterns and birth outcomes is unclear, after taking into account underlying depression severity. This study describes patterns of antidepressant use among periconception users and examines associations between usage patterns and birth outcomes. This retrospective cohort study included pregnant Kaiser Permanente Northern California (KPNC) members with a live birth between 2014 and 2017 and an antidepressant medication fill that overlapped the 8th week of pregnancy. Outcomes were preterm birth and neonatal intensive care unit (NICU) admission. Data were extracted from KPNC’s electronic health records. Modified Poisson regression was conducted. Of the 3637 pregnancies meeting inclusion criteria, 33% (n = 1204) continued antidepressant use throughout the pregnancy (refilled throughout pregnancy), 47% (n = 1721) discontinued use (no refills), and 20% (n = 712) stopped and reinitiated use (refill after 30+ day gap in supply). Women who continued use had 1.86 (95% confidence interval (CI) 1.53, 2.27) times the risk of preterm birth and 1.76 (95% CI: 1.42, 2.19) times the risk of NICU admission, compared to women who discontinued use during pregnancy. Similarly, women with continued use had 1.66 (95% CI: 1.27, 2.18) times the risk of preterm birth and 1.85 (95% CI: 1.39, 2.46) times the risk of NICU admission, compared to women who stopped and reinitiated use. This relationship held when examining continuous exposure; the relationship between continuous exposure and preterm delivery was stronger in later trimesters. Periconception antidepressant users who continue use during pregnancy, particularly into the second and third trimesters, may be at higher risk of adverse birth outcomes. This evidence should be considered alongside the risks associated with depression relapse.
Authors: Nance, Nerissa; Badon, Sylvia E; Ridout, Kathryn; Ahern, Jennifer; Li, De-Kun; Quesenberry, Charles; Avalos, Lyndsay A
Pharmacotherapy. 2023 Mar 05.
Human Immunodeficiency Virus Status, Tenofovir Exposure, and the Risk of Poor Coronavirus Disease 19 (COVID-19) Outcomes: Real-World Analysis From 6 United States Cohorts Before Vaccine Rollout
People with human immunodeficiency virus (HIV) (PWH) may be at increased risk for severe coronavirus disease 2019 (COVID-19) outcomes. We examined HIV status and COVID-19 severity, and whether tenofovir, used by PWH for HIV treatment and people without HIV (PWoH) for HIV prevention, was associated with protection. Within 6 cohorts of PWH and PWoH in the United States, we compared the 90-day risk of any hospitalization, COVID-19 hospitalization, and mechanical ventilation or death by HIV status and by prior exposure to tenofovir, among those with severe acute respiratory syndrome coronavirus 2 infection between 1 March and 30 November 2020. Adjusted risk ratios (aRRs) were estimated by targeted maximum likelihood estimation, with adjustment for demographics, cohort, smoking, body mass index, Charlson comorbidity index, calendar period of first infection, and CD4 cell counts and HIV RNA levels (in PWH only). Among PWH (n = 1785), 15% were hospitalized for COVID-19 and 5% received mechanical ventilation or died, compared with 6% and 2%, respectively, for PWoH (n = 189 351). Outcome prevalence was lower for PWH and PWoH with prior tenofovir use. In adjusted analyses, PWH were at increased risk compared with PWoH for any hospitalization (aRR, 1.31 [95% confidence interval, 1.20-1.44]), COVID-19 hospitalizations (1.29 [1.15-1.45]), and mechanical ventilation or death (1.51 [1.19-1.92]). Prior tenofovir use was associated with reduced hospitalizations among PWH (aRR, 0.85 [95% confidence interval, .73-.99]) and PWoH (0.71 [.62-.81]). Before COVID-19 vaccine availability, PWH were at greater risk for severe outcomes than PWoH. Tenofovir was associated with a significant reduction in clinical events for both PWH and PWoH.
Authors: Lea, Alexandra N; Marafino, Ben J; Skarbinski, Jacek; Silverberg, Michael J; et al.
Clin Infect Dis. 2023 Mar 02.
Estimation of COVID-19 mRNA Vaccine Effectiveness and COVID-19 Illness and Severity by Vaccination Status During Omicron BA.4 and BA.5 Sublineage Periods
Recent SARS-CoV-2 Omicron variant sublineages, including BA.4 and BA.5, may be associated with greater immune evasion and less protection against COVID-19 after vaccination. To evaluate the estimated vaccine effectiveness (VE) of 2, 3, or 4 doses of COVID-19 mRNA vaccination among immunocompetent adults during a period of BA.4 or BA.5 predominant circulation; and to evaluate the relative severity of COVID-19 in hospitalized patients across Omicron BA.1, BA.2 or BA.2.12.1, and BA.4 or BA.5 sublineage periods. This test-negative case-control study was conducted in 10 states with data from emergency department (ED) and urgent care (UC) encounters and hospitalizations from December 16, 2021, to August 20, 2022. Participants included adults with COVID-19-like illness and molecular testing for SARS-CoV-2. Data were analyzed from August 2 to September 21, 2022. mRNA COVID-19 vaccination. The outcomes of interest were COVID-19 ED or UC encounters, hospitalizations, and admission to the intensive care unit (ICU) or in-hospital death. VE associated with protection against medically attended COVID-19 was estimated, stratified by care setting and vaccine doses (2, 3, or 4 doses vs 0 doses as the reference group). Among hospitalized patients with COVID-19, demographic and clinical characteristics and in-hospital outcomes were compared across sublineage periods. During the BA.4 and BA.5 predominant period, there were 82 229 eligible ED and UC encounters among patients with COVID-19-like illness (median [IQR] age, 51 [33-70] years; 49 682 [60.4%] female patients), and 19 114 patients (23.2%) had test results positive for SARS-CoV-2; among 21 007 hospitalized patients (median [IQR] age, 71 [58-81] years; 11 209 [53.4%] female patients), 3583 (17.1 %) had test results positive for SARS-CoV-2. Estimated VE against hospitalization was 25% (95% CI, 17%-32%) for receipt of 2 vaccine doses at 150 days or more after receipt, 68% (95% CI, 50%-80%) for a third dose 7 to 119 days after receipt, and 36% (95% CI, 29%-42%) for a third dose 120 days or more (median [IQR], 235 [204-262] days) after receipt. Among patients aged 65 years or older who had received a fourth vaccine dose, VE was 66% (95% CI, 53%-75%) at 7 to 59 days after vaccination and 57% (95% CI, 44%-66%) at 60 days or more (median [IQR], 88 [75-105] days) after vaccination. Among hospitalized patients with COVID-19, ICU admission or in-hospital death occurred in 21.4% of patients during the BA.1 period vs 14.7% during the BA.4 and BA.5 period (standardized mean difference: 0.17). In this case-control study of COVID-19 vaccines and illness, VE associated with protection against medically attended COVID-19 illness was lower with increasing time since last dose; estimated VE was higher after receipt of 1 or 2 booster doses compared with a primary series alone.
Authors: Link-Gelles, Ruth; Klein, Nicola P; Zerbo, Ousseny; Fireman, Bruce; Tenforde, Mark W; et al.
JAMA Netw Open. 2023 Mar 01;6(3):e232598. Epub 2023-03-01.
Practice Patterns and Outcomes Associated With Anticoagulation Use Following Sepsis Hospitalizations With New-Onset Atrial Fibrillation
Practice patterns and outcomes associated with the use of oral anticoagulation for arterial thromboembolism prevention following a hospitalization with new-onset atrial fibrillation (AF) during sepsis are unclear. Retrospective, observational cohort study of patients ≥40 years of age discharged alive following hospitalization with new-onset AF during sepsis across 21 hospitals in the Kaiser Permanente Northern California health care delivery system, years 2011 to 2018. Primary outcomes were ischemic stroke/transient ischemic attack (TIA), with a safety outcome of major bleeding events, both within 1 year of discharge alive from sepsis hospitalization. Adjusted risk differences for outcomes between patients who did and did not receive oral anticoagulation within 30 days of discharge were estimated using marginal structural models fitted by inverse probability weighting using Super Learning within a target trial emulation framework. Among 82 748 patients hospitalized with sepsis, 3992 (4.8%) had new-onset AF and survived to hospital discharge; mean age was 78±11 years, 53% were men, and 70% were White. Patients with new-onset AF during sepsis averaged 45±33% of telemetry monitoring entries with AF, and 27% had AF present on the day of hospital discharge. Within 1 year of hospital discharge, 89 (2.2%) patients experienced stroke/TIA, 225 (5.6%) had major bleeding, and 1011 (25%) died. Within 30 days of discharge, 807 (20%) patients filled oral anticoagulation prescriptions, which were associated with higher 1-year adjusted risks of ischemic stroke/TIA (5.69% versus 2.32%; risk difference, 3.37% [95% CI, 0.36-6.38]) and no significant difference in 1-year adjusted risks of major bleeding (6.51% versus 7.10%; risk difference, -0.59% [95% CI, -3.09 to 1.91]). Sensitivity analysis of ischemic stroke-only outcomes showed a risk difference of 0.15% (95% CI, -1.72 to 2.03). After hospitalization with new-onset AF during sepsis, oral anticoagulation use was uncommon and associated with potentially higher stroke/TIA risk. Further research to inform mechanisms of stroke and TIA and management of new-onset AF after sepsis is needed.
Authors: Walkey, Allan J; Myers, Laura C; Thai, Khanh K; Kipnis, Patricia; Desai, Manisha; Go, Alan S; Lu, Yun; Clancy, Heather; Devis, Ycar; Neugebauer, Romain; Liu, Vincent X
Circ Cardiovasc Qual Outcomes. 2023 Mar;16(3):e009494. Epub 2023-02-28.
Perinatal Outcomes After Bariatric Surgery Compared With a Matched Control Group
To evaluate perinatal outcomes associated with pregnancy after bariatric surgery within a large integrated health care system using propensity score matching. We conducted a retrospective cohort study that evaluated perinatal outcomes in pregnant patients after bariatric surgery from January 2012 through December 2018. History of bariatric surgery was identified by using International Classification of Diseases codes and a clinical database. Primary outcomes were preterm birth (PTB), gestational hypertension, preeclampsia, impaired glucose tolerance or gestational diabetes, a large-for-gestational-age (LGA) or small-for-gestational-age (SGA) neonates, and cesarean birth. Propensity scores were estimated by using logistic regression that accounted for age at delivery, prepregnancy body mass index, year of delivery, parity, neighborhood deprivation index, race and ethnicity, insurance status, initiation of prenatal visit in the first trimester, smoking during pregnancy, chronic hypertension, and preexisting diabetes. Five patients in the control group were matched to each patient in the case group on linear propensity score, and modified Poisson regression was used to adjust for covariates. Sensitivity analyses by timing and type of surgery were performed. We identified a case cohort of 1,591 pregnancies in patients after bariatric surgery and a matched cohort of 7,955 pregnancies in patients who had not undergone bariatric surgery. Demographic characteristics were similar in both groups. In multivariate models, pregnancy after bariatric surgery was associated with a decreased risk of preeclampsia (7.5% vs 10.2%, adjusted relative risk [aRR] 0.72, 95% CI 0.60-0.86), gestational diabetes or impaired fasting glucose (23.5% vs 35.0%, aRR 0.73, 95% CI 0.66-0.80), and LGA (10.6% vs 19.9%, aRR 0.56, 95% CI 0.48-0.65) and an increased risk of SGA (10.9% vs 6.6%, aRR 1.51, 95% CI 1.28-1.78). No significant differences were observed in PTB, gestational hypertension and cesarean delivery. Pregnancy after bariatric surgery in a racially and ethnically diverse cohort of patients is associated with decreased risk of preeclampsia, gestational diabetes or impaired fasting glucose, and LGA neonates; it is also associated with an increased risk of SGA neonates compared with pregnant patients in a matched control group.
Authors: Boller, Marie J; Xu, Fei; Lee, Catherine; Sridhar, Sneha; Greenberg, Mara B; Hedderson, Monique M
Obstet Gynecol. 2023 Mar 01;141(3):583-591. Epub 2023-02-02.
Long-term Trajectories of Physical Function Decline in Women With and Without Cancer
Patients with cancer experience acute declines in physical function, hypothesized to reflect accelerated aging driven by cancer-related symptoms and effects of cancer therapies. No study has examined long-term trajectories of physical function by cancer site, stage, or treatment compared with cancer-free controls. Examine trajectories of physical function a decade before and after cancer diagnosis among older survivors and cancer-free controls. This prospective cohort study enrolled patients from 1993 to 1998 and followed up until December 2020. The Women’s Health Initiative, a diverse cohort of postmenopausal women, included 9203 incident cancers (5989 breast, 1352 colorectal, 960 endometrial, and 902 lung) matched to up to 5 controls (n = 45 358) on age/year of enrollment and study arm. Cancer diagnosis (site, stage, and treatment) via Medicare and medical records. Trajectories of self-reported physical function (RAND Short Form 36 [RAND-36] scale; range: 0-100, higher scores indicate superior physical function) estimated from linear mixed effects models with slope changes at diagnosis and 1-year after diagnosis. This study included 9203 women with cancer and 45 358 matched controls. For the women with cancer, the mean (SD) age at diagnosis was 73.0 (7.6) years. Prediagnosis, physical function declines of survivors with local cancers were similar to controls; after diagnosis, survivors experienced accelerated declines relative to controls, whose scores declined 1 to 2 points per year. Short-term declines in the year following diagnosis were most severe in women with regional disease (eg, -5.3 [95% CI, -6.4 to -4.3] points per year in regional vs -2.8 [95% CI, -3.4 to -2.3] for local breast cancer) or who received systemic therapy (eg, for local endometrial cancer, -7.9 [95% CI, -12.2 to -3.6] points per year with any chemotherapy; -3.1 [95% CI, -6.0 to -0.3] with radiation therapy alone; and -2.6 [95% CI, -4.2 to -1.0] with neither, respectively). While rates of physical function decline slowed in the later postdiagnosis period (eg, women with regional colorectal cancer declined -4.3 [95% CI, -5.9 to -2.6] points per year in the year following diagnosis vs -1.4 [95% CI, -1.7 to -1.0] points per year in the decade thereafter), survivors had estimated physical function significantly below that of age-matched controls 5 years after diagnosis. In this prospective cohort study, survivors of cancer experienced accelerated declines in physical function after diagnosis, and physical function remained below that of age-matched controls even years later. Patients with cancer may benefit from supportive interventions to preserve physical functioning.
Authors: Cespedes Feliciano, Elizabeth M; Quesenberry, Charles; Caan, Bette J; Anderson, Garnet L; et al.
JAMA Oncol. 2023 Mar 01;9(3):395-403.
Natural history of multiple recurrences in intermediate-risk non-muscle invasive bladder cancer: lessons from a prospective cohort
To describe the risk of multiple recurrences in intermediate-risk non-muscle invasive bladder cancer (IR-NMIBC) and their impact on progression. Prognostic studies of IR-NMIBC have focused on initial recurrences, yet little is known about subsequent recurrences and their impact on progression. IR-NMIBC patients from the Be-Well Study, a prospective cohort study of NMIBC patients diagnosed from 2015 to 2019 at Kaiser Permanente Northern California, were identified. The frequency of first, second, and third intravesical recurrences of urothelial carcinoma were characterized using conditional Kaplan-Meier analyses and random-effects shared-frailty models. The association of multiple recurrences with progression was examined. In 291 patients with IR-NMIBC (median follow-up 38 months), the 5-year risk of initial recurrence was 54.4%. After initial recurrence (n = 137), 60.1% of patients had a second recurrence by 2 years. After second recurrence (n = 70), 51.5% of patients had a third recurrence by 3 years. In multivariable analysis, female sex (Hazard Ratio 1.51, P< .01), increasing tumor size (HR 1.14, P< .01) and number of prior recurrences (HR 1.24, P< .01) were associated with multiple recurrences; whereas maintenance BCG (HR 0.66, P = .03) was associated with reduced recurrences. The 5-year risk of progression varied significantly (P< .01) by number of recurrences: 9.5%, 21.9%, and 37.9% for patients with 1, 2, and 3+ recurrences, respectively. Multiple recurrences are common in IR-NMIBC and are associated with progression. Female sex, larger tumors, number of prior recurrences, and lack of maintenance BCG were associated with multiple recurrences. Multiple recurrences may prove useful as a clinical trial endpoint for IR-NMIBC.
Authors: Sharma, Vidit; Kushi, Lawrence H; Quesenberry, Charles P; Kwan, Marilyn L; et al.
Urology. 2023 Mar;173:134-141. Epub 2022-12-24.
Maternal SARS-CoV-2 vaccination and infant protection against SARS-CoV-2 during the first six months of life
We examined the effectiveness of maternal vaccination against SARS-CoV-2 infection in 30,311 infants born at Kaiser Permanente Northern California from December 15, 2020, to May 31, 2022. Using Cox regression, the effectiveness of ≥2 doses of COVID-19 vaccine received during pregnancy was 84% (95% confidence interval [CI]: 66, 93), 62% (CI: 39, 77) and 56% (CI: 34,71) during months 0-2, 0-4 and 0- 6 of a child’s life, respectively, in the Delta variant period. In the Omicron variant period, the effectiveness of maternal vaccination in these three age intervals was 21% (CI: -21,48), 14% (CI: -9,32) and 13% (CI: -3,26), respectively. Over the entire study period, the incidence of hospitalization for COVID-19 was lower during the first 6 months of life among infants of vaccinated mothers compared with infants of unvaccinated mothers (21/100,000 person-years vs. 100/100,000 person-years). Maternal vaccination was protective, but protection was lower during Omicron than during Delta. Protection during both periods decreased as infants aged.
Authors: Zerbo, Ousseny; Ray, G Thomas; Fireman, Bruce; Layefsky, Evan; Goddard, Kristin; Lewis, Edwin; Ross, Pat; Omer, Saad; Greenberg, Mara; Klein, Nicola P
Nat Commun. 2023 Feb 28;14(1):894. Epub 2023-02-28.
Protection from COVID-19 mRNA vaccination and prior SARS-CoV-2 infection against COVID-19-associated encounters in adults during Delta and Omicron predominance
Data assessing protection conferred from COVID-19 mRNA vaccination and/or prior SARS-CoV-2 infection during Delta and Omicron predominance periods in the U.S. are limited. This cohort study included persons ≥18 years who had ≥1 healthcare encounter across four health systems and had been tested for SARS-CoV-2 before August 26, 2021. COVID-19 mRNA vaccination and prior SARS-CoV-2 infection defined the exposure. Cox regression estimated hazard ratios (HRs) for the Delta and Omicron periods; protection was calculated as (1-HR)x100%. Compared to unvaccinated and previously uninfected persons, during Delta predominance, protection against COVID-19-associated hospitalizations was high for those 2- or 3-dose vaccinated and previously infected, 3-dose vaccinated alone, and prior infection alone (range:91%-97%, with overlapping 95% confidence intervals (95%CIs)); during Omicron predominance, estimates were lower (range:77%-90%). Protection against COVID-19-associated emergency department/urgent care (ED/UC) encounters during Delta predominance was high for those exposure groups (range:86%-93%); during Omicron predominance, protection remained high for those 3-dose vaccinated with or without a prior infection (76% (95%CI=67%-83%) and 71% (95%CI=67%-73%), respectively). COVID-19 mRNA vaccination and/or prior SARS-CoV-2 infection provided protection against COVID-19-associated hospitalizations and ED/UC encounters regardless of variant. Staying up-to-date with COVID-19 vaccination still provides protection against severe COVID-19 disease, regardless of prior infection.
Authors: Bozio, Catherine H; Fireman, Bruce; Stenehjem, Edward; et al.
J Infect Dis. 2023 Feb 18.
Sex- and ethnic-specific patterns in the incidence of hip fracture among older US Asian and non-Hispanic White adults
Asian and Pacific Islander (Asian/PI) adults have lower hip fracture incidence than non-Hispanic White (NHW) adults, but data regarding Asian/PI subgroups are limited. We compared hip fracture incidence among older US Asian/PI and NHW populations, including ethnic subgroup differences. Using observational data from a California healthcare system, we identified Asian/PI and NHW adults aged ≥50 years (2000-2019) and followed subjects to 2021 for hip fracture determined by principal/primary hospital diagnosis or by secondary hospital diagnosis with hip/femur procedure codes. Age-adjusted hip fracture incidence was calculated with 95% confidence intervals (CIs). Log-Poisson regression was used to determine fracture incidence rate ratios (IRRs, [CI]; NHW or Chinese as reference) adjusting for age and year. Among 215,359 Asian/PI and 776,839 NHW women, hip fracture incidence was 1.34 (1.28-1.40) and 2.97 (2.94-3.01) per 1000 person-years, respectively, with IRR 0.45 (0.43-0.47). Among 188,328 Asian/PI and 697,046 NHW men, hip fracture incidence was 0.62 (0.58-0.67) and 1.81 (1.78-1.84) per 1000 person-years, respectively, with IRR 0.34 (0.32-0.37). For the four largest Asian/PI subgroups, Filipina women (IRR 0.85 [0.75-0.96]) had lower, and Japanese (IRR 1.36 [1.20-1.54]) and South Asian (IRR 1.36 [1.07-1.72]) women had higher hip fracture incidence compared to Chinese women. Hip fracture incidence was only higher among South Asian (IRR 1.61 [1.21-2.14]) compared to Chinese men. Hip fracture incidence among US Asian/PI adults was 55% (women) and 66% (men) lower than NHW adults, but incidence varied by Asian/PI subgroup. The heterogeneity among Asian/PI adults highlights the importance of examining fracture risk by ethnic subgroup.
Authors: Lo, Joan C; Chandra, Malini; Lee, David R; Darbinian, Jeanne A; Gordon, Nancy P; Zeltser, David W; Grimsrud, Christopher D; Lee, Catherine
J Am Geriatr Soc. 2023 Feb 15.
Maternal and neonatal outcomes associated with treating hypertension in pregnancy at different thresholds
In the United States, there has been controversy over whether treatment of mild-to-moderate hypertension during pregnancy conveys more benefit than risk. The objective of the study was to compare risks and benefits of treatment of mild-to-moderate hypertension during pregnancy. This retrospective cohort study included 11,871 pregnant women with mild-to-moderate hypertension as defined by blood pressure (BP) values from three Kaiser Permanente regions between 2005 and 2014. Data were extracted from electronic health records. Dynamic marginal structural models with inverse probability weighting and informative censoring were used to compare risks of adverse outcomes when beginning antihypertensive medication treatment at four BP thresholds (≥155/105, ≥150/100, ≥145/95, ≥140/90 mm Hg) compared with the recommended threshold in the United States at that time, ≥160/110 mm Hg. Outcomes included preeclampsia, preterm birth, small-for-gestational-age (SGA), Neonatal Intensive Care Unit (NICU) care, and stillbirth. Primary analyses allowed 2 weeks for medication initiation after an elevated BP. Several sensitivity and subgroup (i.e., race/ethnicity and pre-pregnancy body mass index) analyses were also conducted. In primary analyses, medication initiation at lower BP thresholds was associated with greater risk of most outcomes. Comparing the lowest (≥140/90 mm Hg) to the highest BP threshold (≥160/110 mm Hg), we found an excess risk of preeclampsia (adjusted Risk Difference (aRD) 38.6 per 100 births, 95% Confidence Interval (CI): 30.6, 46.6), SGA (aRD: 10.2 per 100 births, 95% CI: 2.6, 17.8), NICU admission (aRD: 20.2 per 100 births, 95% CI: 12.6, 27.9), and stillbirth (1.18 per 100 births, 95% CI: 0.27, 2.09). The findings did not reach statistical significance for preterm birth (aRD: 2.5 per 100 births, 95% CI: -0.4, 5.3). These relationships were attenuated and did not always reach statistically significance when comparing higher BP treatment thresholds to the highest threshold (i.e., ≥160/110 mm Hg). Sensitivity and subgroup analyses produced similar results. Initiation of antihypertensive medication at mild-to-moderate BP thresholds (140-155/90-105 mm Hg; with the largest risk consistently associated with treatment at 140/90 mm Hg) may be associated with adverse maternal and neonatal outcomes. Limitations include inability to measure medication adherence.
Authors: Avalos, Lyndsay A; Neugebauer, Romain S; Nance, Nerissa; Badon, Sylvia E; Cheetham, T Craig; Easterling, Thomas R; Reynolds, Kristi; Idu, Abisola; Bider-Canfield, Zoe; Holt, Victoria L; Dublin, Sascha
Pharmacotherapy. 2023 Feb 13.
Risk of venous thromboembolism in non-respiratory and respiratory presentations of COVID-19 in critically ill patients
Authors: Roubinian, Nareg H; Vinson, David R; Pai, Ashok P; Myers, Laura C; Skarbinski, Jacek; Lee, Catherine; Mark, Dustin G; Liu, Vincent X
Chest. 2023 Feb 12.
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.
Association of Long-term Exposure to Particulate Air Pollution With Cardiovascular Events in California
Long-term exposure to fine particulate air pollution (PM2.5) is a known risk factor for cardiovascular events, but controversy remains as to whether the current National Ambient Air Quality Standard (12 μg/m3 for 1-year mean PM2.5) is sufficiently protective. To evaluate the associations between long-term fine particulate air pollution and cardiovascular events using electronic health record and geocoded address data. This retrospective cohort study included adults in the Kaiser Permanente Northern California integrated health care system during 2007 to 2016 and followed for up to 10 years. Study participants had no prior stroke or acute myocardial infarction (AMI), and lived in Northern California for at least 1 year. Analyses were conducted January 2020 to December 2022. Long-term exposure to PM2.5. Individual-level time-varying 1-year mean PM2.5 exposures for every study participant were updated monthly from baseline through the end of follow-up, accounting for address changes. Incident AMI, ischemic heart disease (IHD) mortality, and cardiovascular disease (CVD) mortality. Cox proportional hazards models were fit with age as time scale, adjusted for sex, race and ethnicity, socioeconomic status, smoking, body mass index, baseline comorbidities, and baseline medication use. Associations below the current regulation limit were also examined. The study cohort included 3.7 million adults (mean [SD] age: 41.1 [17.2] years; 1 992 058 [52.5%] female, 20 205 [0.5%] American Indian or Alaskan Native, 714 043 [18.8%] Asian, 287 980 [7.6%] Black, 696 796 [18.4%] Hispanic, 174 261 [4.6%] multiracial, 1 904 793 [50.2%] White). There was a 12% (95% CI, 7%-18%) increased risk of incident AMI, a 21% (95% CI, 13%-30%) increased risk of IHD mortality, and an 8% (95% CI, 3%-13%) increased risk of CVD mortality associated with a 10 μg/m3 increase in 1-year mean PM2.5. PM2.5 exposure at moderate concentrations (10.0 to 11.9 μg/m3) was associated with increased risks of incident AMI (6% [95% CI, 3%-10%]) and IHD mortality (7% [95% CI, 2%-12%]) compared with low concentrations (less than 8 μg/m3). In this study, long-term PM2.5 exposure at moderate concentrations was associated with increased risks of incident AMI, IHD mortality, and CVD mortality. This study’s findings add to the evidence that the current regulatory standard is not sufficiently protective.
Authors: Alexeeff, Stacey E; Deosaransingh, Kamala; Van Den Eeden, Stephen; Schwartz, Joel; Liao, Noelle S; Sidney, Stephen
JAMA Netw Open. 2023 Feb 01;6(2):e230561. Epub 2023-02-01.
High-dimensional propensity scores for empirical covariate selection in secondary database studies: Planning, implementation, and reporting
Real-world evidence used for regulatory, payer, and clinical decision-making requires principled epidemiology in design and analysis, applying methods to minimize confounding given the lack of randomization. One technique to deal with potential confounding is propensity score (PS) analysis, which allows for the adjustment for measured preexposure covariates. Since its first publication in 2009, the high-dimensional propensity score (hdPS) method has emerged as an approach that extends traditional PS covariate selection to include large numbers of covariates that may reduce confounding bias in the analysis of healthcare databases. hdPS is an automated, data-driven analytic approach for covariate selection that empirically identifies preexposure variables and proxies to include in the PS model. This article provides an overview of the hdPS approach and recommendations on the planning, implementation, and reporting of hdPS used for causal treatment-effect estimations in longitudinal healthcare databases. We supply a checklist with key considerations as a supportive decision tool to aid investigators in the implementation and transparent reporting of hdPS techniques, and to aid decision-makers unfamiliar with hdPS in the understanding and interpretation of studies employing this approach. This article is endorsed by the International Society for Pharmacoepidemiology.
Authors: Rassen, Jeremy A; Blin, Patrick; Kloss, Sebastian; Neugebauer, Romain S; Platt, Robert W; Pottegård, Anton; Schneeweiss, Sebastian; Toh, Sengwee
Pharmacoepidemiol Drug Saf. 2023 Feb;32(2):93-106. Epub 2022-11-22.
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 prospective study of lifestyle factors and bone health in breast cancer patients who received aromatase inhibitors in an integrated healthcare setting
Fracture and osteoporosis are known side effects of aromatase inhibitors (AIs) for postmenopausal hormone receptor positive (HR+) breast cancer (BC) patients. How modifiable lifestyle factors impact fracture risk in these patients is relatively unknown. We conducted a prospective cohort study to examine the association of lifestyle factors, focusing on physical activity, with risk of incident major osteoporotic fracture and osteoporosis in 2152 HR+ BC patients diagnosed from 2006 to 2013 at Kaiser Permanente Northern California and who received AIs. Patients self-reported lifestyle factors at study entry and at 6-month follow-up. Fracture and osteoporosis outcomes were prospectively ascertained by physician-adjudication and bone mineral density (BMD) values, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated from multivariable proportional hazards regression. Models were adjusted for age, menopausal status, race/ethnicity, body mass index (BMI), AJCC stage, breast cancer treatment, prior osteoporosis, and prior major fracture. Over a median 6.1 years of follow-up after AI initiation, 165 women experienced an incident osteoporotic fracture and 243 women had osteoporosis. No associations were found between overall moderate-vigorous physical activity and fracture risk, although < 150 min/week of aerobic exercise in the 6 months after BC diagnosis was associated with increased fracture risk (HR=2.42; 95% CI: 1.34, 4.37) compared with ≥ 150 min/week (meeting physical activity guidelines). Risk was also higher for never or infrequently engaging in aerobic exercise (HR=1.90; 95% CI: 1.05, 3.44). None or infrequent overall moderate-vigorous physical activity in the 6 months before BC diagnosis was associated with increased risk of osteoporosis (HR=1.94; 95% CI: 1.11; 3.37). Moderate-vigorous physical activity during the immediate period after BC diagnosis, particularly aerobic exercise, was associated with lower risk of major osteoporotic fractures in women on AI therapy. Findings may inform fracture prevention in women on AI therapy through non-pharmacologic lifestyle-based strategies.
Authors: Kwan, Marilyn L; Lo, Joan C; Laurent, Cecile A; Roh, Janise M; Tang, Li; Ambrosone, Christine B; Kushi, Lawrence H; Quesenberry, Charles P; Yao, Song
J Cancer Surviv. 2023 Feb;17(1):139-149. Epub 2021-02-09.
Vaccine effectiveness against influenza-associated urgent care, emergency department, and hospital encounters during the 2021-2022 season, VISION Network
Following historically low influenza activity during the 2020-2021 season, the United States saw an increase in influenza circulating during the 2021-2022 season. Most viruses belonged to the influenza A(H3N2) 3C.2a1b 2a.2 subclade. We conducted a test-negative case-control analysis among adults ≥18 years of age at three sites within the VISION Network. Encounters included emergency department/urgent care (ED/UC) visits or hospitalizations with ≥1 acute respiratory illness (ARI) discharge diagnosis codes and molecular testing for influenza. Vaccine effectiveness (VE) was calculated by comparing the odds of influenza vaccination ≥14 days before the encounter date between influenza-positive cases (type A) and influenza-negative and SARS-CoV-2-negative controls, applying inverse probability-to-be-vaccinated weights, and adjusting for confounders. 86,732 ED/UC ARI-associated encounters (7,696 [9%] cases) and 16,805 hospitalized ARI-associated encounters (649 [4%] cases) were included. VE against influenza-associated ED/UC encounters was 25% (95% confidence interval (CI): 20-29%) and 25% (95%CI: 11-37%) against influenza-associated hospitalizations. VE against ED/UC encounters was lower in adults ≥65 years of age (7%; CI: -5-17%) or with immunocompromising conditions (4%, CI:-45-36%). During an influenza A(H3N2)-predominant influenza season, modest VE was observed. These findings highlight the need for improved vaccines, particularly for A(H3N2) viruses that are historically associated with lower VE.
Authors: Tenforde, Mark W; Fireman, Bruce; Zerbo, Ousseny; Klein, Nicola P; et al.
J Infect Dis. 2023 Jan 23.
MiXcan: a framework for cell-type-aware transcriptome-wide association studies with an application to breast cancer
Human bulk tissue samples comprise multiple cell types with diverse roles in disease etiology. Conventional transcriptome-wide association study approaches predict genetically regulated gene expression at the tissue level, without considering cell-type heterogeneity, and test associations of predicted tissue-level expression with disease. Here we develop MiXcan, a cell-type-aware transcriptome-wide association study approach that predicts cell-type-level expression, identifies disease-associated genes via combination of cell-type-level association signals for multiple cell types, and provides insight into the disease-critical cell type. As a proof of concept, we conducted cell-type-aware analyses of breast cancer in 58,648 women and identified 12 transcriptome-wide significant genes using MiXcan compared with only eight genes using conventional approaches. Importantly, MiXcan identified genes with distinct associations in mammary epithelial versus stromal cells, including three new breast cancer susceptibility genes. These findings demonstrate that cell-type-aware transcriptome-wide analyses can reveal new insights into the genetic and cellular etiology of breast cancer and other diseases.
Authors: Song, Xiaoyu; Alexeeff, Stacey E; Sakoda, Lori C; Habel, Laurel A; Sieh, Weiva; et al.
Nat Commun. 2023 Jan 23;14(1):377. Epub 2023-01-23.
A broad assessment of covid-19 vaccine safety using tree-based data-mining in the vaccine safety datalink
Except for spontaneous reporting systems, vaccine safety monitoring generally involves pre-specifying health outcomes and post-vaccination risk windows of concern. Instead, we used tree-based data-mining to look more broadly for possible adverse events after Pfizer-BioNTech, Moderna, and Janssen COVID-19 vaccination. Vaccine Safety Datalink enrollees receiving ≥1 dose of COVID-19 vaccine in 2020-2021 were followed for 70 days after Pfizer-BioNTech or Moderna and 56 days after Janssen vaccination. Incident diagnoses in inpatient or emergency department settings were analyzed for clustering within both the hierarchical ICD-10-CM code structure and the post-vaccination follow-up period. We used the self-controlled tree-temporal scan statistic and TreeScan software. Monte Carlo simulation was used to estimate p-values; p = 0.01 was the pre-specified cut-off for statistical significance of a cluster. There were 4.1, 2.6, and 0.4 million Pfizer-BioNTech, Moderna, and Janssen vaccinees, respectively. Clusters after Pfizer-BioNTech vaccination included: (1) unspecified adverse effects, (2) common vaccine reactions, such as fever, myalgia, and headache, (3) myocarditis/pericarditis, and (4) less specific cardiac or respiratory symptoms, all with the strongest clusters generally after Dose 2; and (5) COVID-19/viral pneumonia/sepsis/respiratory failure in the first 3 weeks after Dose 1. Moderna results were similar but without a significant myocarditis/pericarditis cluster. Further investigation suggested the fifth signal group was a manifestation of mRNA vaccine effectiveness after the first 3 weeks. Janssen vaccinees had clusters of unspecified or common vaccine reactions, gait/mobility abnormalities, and muscle weakness. The latter two were deemed to have arisen from confounding related to practices at one site. We detected post-vaccination clusters of unspecified adverse effects, common vaccine reactions, and, for the mRNA vaccines, chest pain and palpitations, as well as myocarditis/pericarditis after Pfizer-BioNTech Dose 2. Unique advantages of this data mining are its untargeted nature and its inherent adjustment for the multiplicity of diagnoses and risk intervals scanned.
Authors: Yih, W Katherine; Fireman, Bruce; Maro, Judith C; et al.
Vaccine. 2023 Jan 16;41(3):826-835. Epub 2022-12-16.
A safety study evaluating non-COVID-19 mortality risk following COVID-19 vaccination
The safety of COVID-19 vaccines plays an important role in addressing vaccine hesitancy. We conducted a large cohort study to evaluate the risk of non-COVID-19 mortality after COVID-19 vaccination while adjusting for confounders including individual-level demographics, clinical risk factors, health care utilization, and community-level socioeconomic risk factors. The retrospective cohort study consisted of members from seven Vaccine Safety Datalink sites from December 14, 2020 through August 31, 2021. We conducted three separate analyses for each of the three COVID-19 vaccines used in the US. Crude non-COVID-19 mortality rates were reported by vaccine type, age, sex, and race/ethnicity. The counting process model for survival analyses was used to analyze non-COVID-19 mortality where a new observation period began when the vaccination status changed upon receipt of the first dose and the second dose. We used calendar time as the basic time scale in survival analyses to implicitly adjust for season and other temporal trend factors. A propensity score approach was used to adjust for the potential imbalance in confounders between the vaccinated and comparison groups. For each vaccine type and across age, sex, and race/ethnicity groups, crude non-COVID-19 mortality rates among COVID-19 vaccinees were lower than those among comparators. After adjusting for confounders with the propensity score approach, the adjusted hazard ratios (aHRs) were 0.46 (95% confidence interval [CI], 0.44-0.49) after dose 1 and 0.48 (95% CI, 0.46-0.50) after dose 2 of the BNT162b2 vaccine, 0.41 (95% CI, 0.39-0.44) after dose 1 and 0.38 (95% CI, 0.37-0.40) after dose 2 of the mRNA-1273 vaccine, and 0.55 (95% CI, 0.51-0.59) after receipt of Ad26.COV2.S. While residual confounding bias remained after adjusting for several individual-level and community-level risk factors, no increased risk was found for non-COVID-19 mortality among recipients of three COVID-19 vaccines used in the US.
Authors: Xu, Stanley; Klein, Nicola P; Fireman, Bruce; Qian, Lei; et al.
Vaccine. 2023 Jan 16;41(3):844-854. Epub 2022-12-20.
A mid-level health manager intervention to promote uptake of isoniazid preventive therapy among people with HIV in Uganda: a cluster randomised trial.
BACKGROUND: Despite longstanding guidelines endorsing isoniazid preventive therapy (IPT) for people with HIV, uptake is low across sub-Saharan Africa. Mid-level health managers oversee IPT programmes nationally; interventions aimed at this group have not been tested. We aimed to establish whether providing structured leadership and management training and facilitating subregional collaboration and routine data feedback to mid-level managers could increase IPT initiation among people with HIV compared with standard practice. METHODS: We conducted a cluster randomised trial in Uganda among district-level health managers. We randomly assigned clusters of between four and seven managers in a 1:1 ratio to intervention or control groups. Our intervention convened managers into mini-collaboratives facilitated by Ugandan experts in tuberculosis and HIV, and provided business leadership and management training, SMS platform access, and data feedback. The control was standard practice. Participants were not masked to trial group, but study statisticians were masked until trial completion. The primary outcome was IPT initiation rates among adults with HIV in facilities overseen by participants over a period of 2 years (2019-21). We conducted prespecified analyses that excluded the third quarter of 2019 (Q3-2019) to understand intervention effects independent of a national 100-day IPT push tied to a financial contingency during Q3-2019. This trial is registered with ClinicalTrials.gov (NCT03315962), and is ongoing. FINDINGS: Between Nov 15, 2017, and March 14, 2018, managers from 82 of 82 eligible districts (61% of Uganda’s 135 districts) were enrolled and randomised: 43 districts to intervention, 39 to control. Intervention delivery took place between Dec 6, 2017, and Feb 2, 2022. Over 2 years, IPT initiation rates were 0.74 versus 0.65 starts per person-year in intervention versus control groups (incidence rate ratio [IRR] 1.14, 95% CI 0.88-1.46; p=0.16). Excluding Q3-2019, IPT initiation was higher in the intervention group versus the control group: 0.32 versus 0.25 starts per person-year (IRR 1.27, 95% CI 1.00-1.61; p=0.026). INTERPRETATION: Following an intervention targeting managers in more than 60% of Uganda’s districts, IPT initiation rates were not significantly higher in intervention than control groups. After accounting for large increases in IPT from a 100-day push in both groups, the intervention led to significantly increased IPT rates, sustained after the push and during the COVID-19 pandemic. Our findings suggest that interventions centred on mid-level health managers can improve IPT implementation on a large, subnational scale, and merit further exploration to address key public health challenges for which strong evidence exists but implementation remains suboptimal. FUNDING: National Institute of Allergy and Infectious Diseases.
Authors: Kakande, Elijah; Christian, Canice; Balzer, Laura B; Owaraganise, Asiphas; Nugent, Joshua R; DiIeso, William; Rast, Derek; Kabami, Jane; Johnson Peretz, Jason; Camlin, Carol S; Shade, Starley B; Geng, Elvin H; Kwarisiima, Dalsone; Kamya, Moses R; Havlir, Diane V; Chamie, Gabriel
Lancet HIV. 2022 Sep;9(9):e607-e616. doi: 10.1016/S2352-3018(22)00166-7. Epub 2022 Jul 28.
HIV incidence after pre-exposure prophylaxis initiation among women and men at elevated HIV risk: A population-based study in rural Kenya and Uganda.
BACKGROUND: Oral pre-exposure prophylaxis (PrEP) is highly effective for HIV prevention, but data are limited on HIV incidence among PrEP users in generalized epidemic settings, particularly outside of selected risk groups. We performed a population-based PrEP study in rural Kenya and Uganda and sought to evaluate both changes in HIV incidence and clinical and virologic outcomes following seroconversion on PrEP. METHODS AND FINDINGS: During population-level HIV testing of individuals >/=15 years in 16 communities in the Sustainable East Africa Research in Community Health (SEARCH) study (NCT01864603), we offered universal access to PrEP with enhanced counseling for persons at elevated HIV risk (based on serodifferent partnership, machine learning-based risk score, or self-identified HIV risk). We offered rapid or same-day PrEP initiation and flexible service delivery with follow-up visits at facilities or community-based sites at 4, 12, and every 12 weeks up to week 144. Among participants with incident HIV infection after PrEP initiation, we offered same-day antiretroviral therapy (ART) initiation and analyzed HIV RNA, tenofovir hair concentrations, drug resistance, and viral suppression (<1,000 c/ml based on available assays) after ART start. Using Poisson regression with cluster-robust standard errors, we compared HIV incidence among PrEP initiators to incidence among propensity score-matched recent historical controls (from the year before PrEP availability) in 8 of the 16 communities, adjusted for risk group. Among 74,541 individuals who tested negative for HIV, 15,632/74,541 (21%) were assessed to be at elevated HIV risk; 5,447/15,632 (35%) initiated PrEP (49% female; 29% 15-24 years; 19% in serodifferent partnerships), of whom 79% engaged in >/=1 follow-up visit and 61% self-reported PrEP adherence at >/=1 visit. Over 7,150 person-years of follow-up, HIV incidence was 0.35 per 100 person-years (95% confidence interval [CI] 0.22-0.49) among PrEP initiators. Among matched controls, HIV incidence was 0.92 per 100 person-years (95% CI 0.49-1.41), corresponding to 74% lower incidence among PrEP initiators compared to matched controls (adjusted incidence rate ratio [aIRR] 0.26, 95% CI 0.09-0.75; p = 0.013). Among women, HIV incidence was 76% lower among PrEP initiators versus matched controls (aIRR 0.24, 95% CI 0.07-0.79; p = 0.019); among men, HIV incidence was 40% lower, but not significantly so (aIRR 0.60, 95% CI 0.12-3.05; p = 0.54). Of 25 participants with incident HIV infection (68% women), 7/25 (28%) reported taking PrEP
Authors: Koss, Catherine A; Havlir, Diane V; Ayieko, James; Kwarisiima, Dalsone; Kabami, Jane; Chamie, Gabriel; Atukunda, Mucunguzi; Mwinike, Yusuf; Mwangwa, Florence; Owaraganise, Asiphas; Peng, James; Olilo, Winter; Snyman, Katherine; Awuonda, Benard; Clark, Tamara D; Black, Douglas; Nugent, Joshua; Brown, Lillian B; Marquez, Carina; Okochi, Hideaki; Zhang, Kevin; Camlin, Carol S; Jain, Vivek; Gandhi, Monica; Cohen, Craig R; Bukusi, Elizabeth A; Charlebois, Edwin D; Petersen, Maya L; Kamya, Moses R; Balzer, Laura B
PLoS Med. 2021 Feb 9;18(2):e1003492. doi: 10.1371/journal.pmed.1003492. eCollection 2021 Feb.
Type I error control for cluster randomized trials under varying small sample structures.
BACKGROUND: Linear mixed models (LMM) are a common approach to analyzing data from cluster randomized trials (CRTs). Inference on parameters can be performed via Wald tests or likelihood ratio tests (LRT), but both approaches may give incorrect Type I error rates in common finite sample settings. The impact of different combinations of cluster size, number of clusters, intraclass correlation coefficient (ICC), and analysis approach on Type I error rates has not been well studied. Reviews of published CRTs find that small sample sizes are not uncommon, so the performance of different inferential approaches in these settings can guide data analysts to the best choices. METHODS: Using a random-intercept LMM stucture, we use simulations to study Type I error rates with the LRT and Wald test with different degrees of freedom (DF) choices across different combinations of cluster size, number of clusters, and ICC. RESULTS: Our simulations show that the LRT can be anti-conservative when the ICC is large and the number of clusters is small, with the effect most pronouced when the cluster size is relatively large. Wald tests with the between-within DF method or the Satterthwaite DF approximation maintain Type I error control at the stated level, though they are conservative when the number of clusters, the cluster size, and the ICC are small. CONCLUSIONS: Depending on the structure of the CRT, analysts should choose a hypothesis testing approach that will maintain the appropriate Type I error rate for their data. Wald tests with the Satterthwaite DF approximation work well in many circumstances, but in other cases the LRT may have Type I error rates closer to the nominal level.
Authors: Nugent, Joshua R; Kleinman, Ken P
BMC Med Res Methodol. 2021 Apr 3;21(1):65. doi: 10.1186/s12874-021-01236-7.
Risk of posthospital venous thromboembolism in patients with COVID-19 varies by SARS-CoV-2 period and vaccination status
Authors: Roubinian, Nareg H;Vinson, David R;Knudson-Fitzpatrick, Tess Wheeler;Mark, Dustin G;Skarbinski, Jacek;Lee, Catherine;Liu, Vincent X;Pai, Ashok P
Blood Adv. 2023 Jan 10;7(1):141-144.
Tree-based data mining for safety assessment of first COVID-19 booster doses in the Vaccine Safety Datalink
The Centers for Disease Control and Prevention’s Vaccine Safety Datalink (VSD) has been performing safety surveillance for COVID-19 vaccines since their earliest authorization in the United States. Complementing its real-time surveillance for pre-specified health outcomes using pre-specified risk intervals, the VSD conducts tree-based data-mining to look for clustering of a broad range of health outcomes after COVID-19 vaccination. This study’s objective was to use this untargeted, hypothesis-generating approach to assess the safety of first booster doses of Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), and Janssen (Ad26.COV2.S) COVID-19 vaccines. VSD enrollees receiving a first booster of COVID-19 vaccine through April 2, 2022 were followed for 56 days. Incident diagnoses in inpatient or emergency department settings were analyzed for clustering within both the hierarchical ICD-10-CM code structure and the follow-up period. The self-controlled tree-temporal scan statistic was used, conditioning on the total number of cases for each diagnosis. P-values were estimated by Monte Carlo simulation; p = 0.01 was pre-specified as the cut-off for statistical significance of clusters. More than 2.4 and 1.8 million subjects received Pfizer-BioNTech and Moderna boosters after an mRNA primary series, respectively. Clusters of urticaria/allergy/rash were found during Days 10-15 after the Moderna booster (p = 0.0001). Other outcomes that clustered after mRNA boosters, mostly with p = 0.0001, included unspecified adverse effects, common vaccine-associated reactions like fever and myalgia, and COVID-19. COVID-19 clusters were in Days 1-10 after booster receipt, before boosters would have become effective. There were no noteworthy clusters after boosters following primary Janssen vaccination. In this untargeted data-mining study of COVID-19 booster vaccination, a cluster of delayed-onset urticaria/allergy/rash was detected after the Moderna booster, as has been reported after Moderna vaccination previously. Other clusters after mRNA boosters were of unspecified or common adverse effects and COVID-19, the latter evidently reflecting immunity to COVID-19 after 10 days.
Authors: Katherine Yih, W; Fireman, Bruce; Maro, Judith C; et al.
Vaccine. 2023 Jan 09;41(2):460-466. Epub 2022-11-24.
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.
Pregnancy post-bariatric surgery: Improved outcomes with telephonic nutritional management program
Pregnancies post-bariatric surgery are increasingly common. It is important to understand how to manage prenatal care in this high-risk population to optimize perinatal outcomes. To determine among pregnancies post-bariatric surgery whether participation in a telephonic nutritional management program was associated with improved perinatal outcomes and nutritional adequacy. Retrospective cohort study of pregnancies post-bariatric surgery from 2012 to 2018. Participation in a telephonic management program with nutritional counseling, monitoring and nutritional supplement adjustment. Modified Poisson Regression estimated the relative risk using propensity score methods to account for baseline differences between the patients who participated in the program and patients who did not. 1575 pregnancies occurred post-bariatric surgery, of which 1142 (72.5 % of pregnancies) participated in the telephonic nutritional management program. Participants in the program were less likely than non-participants to have a preterm birth (aRR 0.48, 95 % CI 0.35-0.67), preeclampsia (aRR 0.43, 95 % CI (0.27-0.69)), gestational hypertension (aRR 0.62, 95 % CI 0.41-0.93), and to have neonates admitted to a Level 2 or 3 (aRR 0.61, 95 % CI0.39-0.94; aRR 0.66, 95 % CI 0.45-0.97, respectively), after adjusting for the propensity score to account for baseline differences. Risk of cesarean delivery, gestational weight gain, glucose intolerance and birthweight did not differ by participation. Among 593 pregnancies with nutritional labs available, participants in the telephonic program were less likely to have nutritional inadequacy in late pregnancy (aRR 0.91, 95 % CI 0.88-0.94). Participation in a telephonic nutritional management program post-bariatric surgery was associated with improved perinatal outcomes and nutritional adequacy.
Authors: Hedderson, Monique M; Boller, Marie; Xu, Fei; Lee, Catherine; Sridhar, Sneha; Greenberg, Mara
Obes Res Clin Pract. 2023 Mar-Apr;17(2):144-150. Epub 2023-03-10.
Association between anaemia and hospital readmissions in patients undergoing major surgery requiring postoperative intensive care
Anaemia is a common sequela of surgery, although its relationship with patient recovery is unclear. The goal of this investigation was to assess the associations between haemoglobin concentrations at the time of hospital discharge following major surgery and early post-hospitalisation outcomes, with a primary outcome of 30 day unanticipated hospital readmissions. This investigation includes data from two independent population-based observational cohorts of adult surgical patients (aged ≥ 18 years) requiring postoperative intensive care unit admission between 1 January 2010 and 31 December 2019 in hospitals in Olmsted County, Minnesota, and between 1 July 2010 and 30 June 2017 in the Kaiser Permanente Northern California integrated healthcare system, California. Cox proportional hazards models assessed the associations between discharge haemoglobin concentrations (per 10 g.l-1 ) and outcomes, with prespecified multivariable adjustment. A total of 3260 patients were included from Olmsted County hospitals and 29,452 from Kaiser Permanente Northern California. In adjusted analyses, each 10 g.l-1 decrease in haemoglobin at hospital discharge was associated with a 9% (hazard ratio 1.09, 95%CI 1.02-1.18; p = 0.014) and 8% increase (hazard ratio 1.08, 95%CI 1.06-1.11; p < 0.001) in the hazard for readmission within 30 days in Olmsted County and Kaiser Permanente Northern California, respectively. In a sensitivity analysis exploring relationships across varying levels of pre-operative anaemia severity, these associations remained consistent, with lower discharge haemoglobin concentrations associated with higher readmissions irrespective of pre-operative anaemia severity. Anaemia at hospital discharge in surgical patients requiring postoperative intensive care is associated with increased rates of hospital readmission in two large independent cohorts. Future studies are necessary to evaluate strategies to prevent and/or treat anaemia in these patients for the improvement of post-hospitalisation outcomes.
Authors: Warner, M A; Hanson, A C; Plimier, C; Lee, C; Liu, V X; Richards, T; Kor, D J; Roubinian, N H
Anaesthesia. 2023 Jan;78(1):45-54. Epub 2022-09-08.
Predicting Post-Sepsis Cardiovascular Events with Death as a Competing Risk
Authors: Myers, Laura C; Lee, Catherine; Go, Alan S; Liu, Vincent X; Walkey, Allan J; et al.
Ann Am Thorac Soc. 2023 Jan;20(1):145-148.
Survival Associated With Consolidated Multidisciplinary Care in Head and Neck Cancer: A Retrospective Cohort Study
To compare survival among patients with head and neck cancer before and after implementing a weekly multidisciplinary clinic and case conference. A retrospective cohort study with chart review was conducted of 3081 patients (1431 preimplementation, 1650 postimplementation) diagnosed with stage I-IVB tumors in the oral cavity, oropharynx, hypopharynx, nasopharynx, or larynx. Pre- and postimplementation differences in overall and disease-specific survival 1, 2, and 3 years after diagnosis were assessed with unadjusted Kaplan-Meier curves and multivariable Cox proportional hazard regression models adjusted for demographic characteristics, comorbidity burden, smoking status, tumor site and stage, p16 status for oropharyngeal squamous cell cancer, and initial treatment modality. Patients less commonly presented with oropharyngeal squamous cell cancer and advanced tumors (III-IVB) and received primary treatment with surgery alone or with adjuvant therapy preimplementation than postimplementation. Overall survival at 3 years was 77.1% and 79.9% (P = .07) and disease-specific survival was 84.9% and 87.5% (P = .05) among pre- and postimplementation patients, respectively. At 3 years, preimplementation patients had slightly poorer overall (hazard ratio, 1.20; 95% CI, 1.02-1.40) and disease-specific (hazard ratio, 1.26; 95% CI, 1.03-1.54) adjusted survival than postimplementation patients. In unadjusted and adjusted analyses, survival improvements were more pronounced among patients with advanced disease. A multidisciplinary clinic and case conference were associated with improved outcomes among patients with head and neck cancer, especially those with advanced tumors. All patients with head and neck cancer should receive multidisciplinary team management, especially those with advanced tumors.
Authors: Meltzer, Charles; Nguyen, Nathalie T; Zhang, Jie; Aguilar, Jillian; Blatchins, Maruta A; Quesenberry, Charles P; Wang, Yan; Sakoda, Lori C
Otolaryngol Head Neck Surg. 2023 Jan;168(1):82-90.
An application of the Causal Roadmap in two safety monitoring case studies: Causal inference and outcome prediction using electronic health record data
Real-world data, such as administrative claims and electronic health records, are increasingly used for safety monitoring and to help guide regulatory decision-making. In these settings, it is important to document analytic decisions transparently and objectively to assess and ensure that analyses meet their intended goals. The Causal Roadmap is an established framework that can guide and document analytic decisions through each step of the analytic pipeline, which will help investigators generate high-quality real-world evidence. In this paper, we illustrate the utility of the Causal Roadmap using two case studies previously led by workgroups sponsored by the Sentinel Initiative – a program for actively monitoring the safety of regulated medical products. Each case example focuses on different aspects of the analytic pipeline for drug safety monitoring. The first case study shows how the Causal Roadmap encourages transparency, reproducibility, and objective decision-making for causal analyses. The second case study highlights how this framework can guide analytic decisions beyond inference on causal parameters, improving outcome ascertainment in clinical phenotyping. These examples provide a structured framework for implementing the Causal Roadmap in safety surveillance and guide transparent, reproducible, and objective analysis.
Authors: Williamson, Brian D;Wyss, Richard;Stuart, Elizabeth A;Dang, Lauren E;Mertens, Andrew N;Neugebauer, Romain S;Wilson, Andrew;Gruber, Susan
J Clin Transl Sci. 2023;7(1):e208. Epub 2023-09-21.
Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19-Associated Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompetent Adults – VISION Network, Nine States, September-November 2022
During June-October 2022, the SARS-CoV-2 Omicron BA.5 sublineage accounted for most of the sequenced viral genomes in the United States, with further Omicron sublineage diversification through November 2022.* Bivalent mRNA vaccines contain an ancestral SARS-CoV-2 strain component plus an updated component of the Omicron BA.4/BA.5 sublineages. On September 1, 2022, a single bivalent booster dose was recommended for adults who had completed a primary vaccination series (with or without subsequent booster doses), with the last dose administered ≥2 months earlier (1). During September 13-November 18, the VISION Network evaluated vaccine effectiveness (VE) of a bivalent mRNA booster dose (after 2, 3, or 4 monovalent doses) compared with 1) no previous vaccination and 2) previous receipt of 2, 3, or 4 monovalent-only mRNA vaccine doses, among immunocompetent adults aged ≥18 years with an emergency department/urgent care (ED/UC) encounter or hospitalization for a COVID-19-like illness.† VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated ED/UC encounters was 56% compared with no vaccination, 31% compared with monovalent vaccination only with last dose 2-4 months earlier, and 50% compared with monovalent vaccination only with last dose ≥11 months earlier. VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated hospitalizations was 57% compared with no vaccination, 38% compared with monovalent vaccination only with last dose 5-7 months earlier, and 45% compared with monovalent vaccination only with last dose ≥11 months earlier. Bivalent vaccines administered after 2, 3, or 4 monovalent doses were effective in preventing medically attended COVID-19 compared with no vaccination and provided additional protection compared with past monovalent vaccination only, with relative protection increasing with time since receipt of the last monovalent dose. All eligible persons should stay up to date with recommended COVID-19 vaccinations, including receiving a bivalent booster dose. Persons should also consider taking additional precautions to avoid respiratory illness this winter season, such as masking in public indoor spaces, especially in areas where COVID-19 community levels are high.
Authors: Tenforde, Mark W; Klein, Nicola P; Fireman, Bruce; Zerbo, Ousseny; Link-Gelles, Ruth; et al.
MMWR Morb Mortal Wkly Rep. 2022 Dec 30;71(5152):1616-1624. Epub 2022-12-30.
Metabolic abnormalities and survival among patients with non-metastatic breast cancer
Research on the impact of metabolic abnormalities on breast cancer prognosis is limited by small samples and assessment of laboratory values at a single time point, often prior to cancer diagnosis and treatment. In this population-based cohort, time-updated laboratory values were adjusted for cancer treatment to assess the association between metabolic risk factors (glucose, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides) and breast cancer survival. 13,434 women diagnosed with stage I-III breast cancer from 2005-15 at Kaiser Permanente were included. All outpatient fasting glucose, HDL-C, LDL-C, and triglyceride values from diagnosis through 2019 or death were extracted from electronic medical records. Risk of breast cancer-specific mortality was evaluated with Cox proportional hazards models adjusted for metabolic labs, demographics, body mass index, diabetes, dyslipidemia and anti-hypertensive medications, tumor characteristics (stage, ER and HER2 receptor status) and cancer treatment (use of chemotherapy, tamoxifen, and aromatase inhibitors). Mean (SD) age at diagnosis was 62.3 (11.8) years. Over a median follow-up of 8.6 years, 2,876 patients died; 1,080 of breast cancer. Patients with low HDL-C (≤ 45 vs. > 45 mg/dL) had higher breast cancer-specific mortality (HR, 1.77; 95% CI, 1.53-2.05), as did those with elevated fasting glucose (> 99 vs. 60-99 mg/dL) (HR, 1.19; 95% CI, 1.03-1.37). Elevated levels of triglycerides and LDL-C were not associated with breast cancer-specific mortality. High fasting glucose and low HDL-C evaluated over time after cancer diagnosis were associated with higher breast cancer mortality independent of cancer treatments and changes in other metabolic risk factors. Future studies should address whether pharmacologic or lifestyle treatment of glucose and lipids after breast cancer diagnosis can optimize survival outcomes.
Authors: Zimbalist, Alexa S; Caan, Bette J; Chen, Wendy Y; Mittendorf, Elizabeth A; Dillon, Deborah A R; Quesenberry, Charles; Cespedes Feliciano, Elizabeth M
BMC Cancer. 2022 Dec 29;22(1):1361. Epub 2022-12-29.
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.
High-sensitivity troponin I is associated with cardiovascular outcomes but not with breast arterial calcification among postmenopausal women
Prior studies support the utility of high sensitivity troponin I (hsTnI) for cardiovascular disease (CVD) risk stratification among asymptomatic populations; however, only two prior studies examined women separately. The association between hsTnI and breast arterial calcification is unknown. Cohort study of 2896 women aged 60-79 years recruited after attending mammography screening between 10/2012 and 2/2015. BAC status (presence versus absence) and quantity (calcium mass mg) was determined using digital mammograms. Pre-specified endpoints were incident coronary heart disease (CHD), ischemic stroke, heart failure and its subtypes and all CVD. After 7.4 (SD = 1.7) years of follow-up, 51 CHD, 30 ischemic stroke and 46 heart failure events were ascertained. At a limit of detection of 1.6 ng/L, 98.3 of the cohort had measurable hsTnI concentration. HsTnI in the 4-10 ng/L range were independently associated of CHD (adjusted hazard ratio[aHR] = 2.78; 95% CI, 1.48-5.22; p = 0.002) and all CVD (aHR = 2.06; 95% CI, 1.37-3.09; p = 0.0005) and hsTnI over 10 ng/L was independently associated with CHD (aHR = 4.75; 95% CI, 1.83-12.3; p = 0.001), ischemic stroke (aHR = 3.81; 95% CI, 1.22-11.9; p = 0.02), heart failure (aHR = 3.29; 95% CI, 1.33-8.13; p = 0.01) and all CVD (aHR = 4.78; 95% CI, 2.66-8.59; p < 0.0001). No significant association was found between hsTnI and BAC. Adding hsTnI to a model containing the Pooled Cohorts Equation resulted in significant and clinical important improved calibration, discrimination (Δ Cindex = 6.5; p = 0.02) and reclassification (bias-corrected clinical NRI = 0.18; 95% CI, -0.13-0.49 after adding hsTnI categories). Our results support the consideration of hsTnI as a risk enhancing factor for CVD in asymptomatic women that could drive preventive or therapeutic decisions.
Authors: Iribarren, Carlos; Chandra, Malini; Lee, Catherine; Sanchez, Gabriela; Sam, Danny L; Azamian, Farima Faith; Cho, Hyo-Min; Ding, Huanjun; Wong, Nathan D; Molloi, Sabee
Int J Cardiol Cardiovasc Risk Prev. 2022 Dec;15:200157. Epub 2022-11-01.
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.
Incidence of Myocarditis/Pericarditis Following mRNA COVID-19 Vaccination Among Children and Younger Adults in the United States
Authors: Goddard, Kristin; Hanson, Kayla E; Lewis, Ned; Weintraub, Eric; Fireman, Bruce; Klein, Nicola P
Ann Intern Med. 2022 Dec;175(12):1169-1771. Epub 2022-10-04.
Urinary Phenols in Early to Mid-Pregnancy and Risk of Gestational Diabetes: A Longitudinal Study in a Multiracial Cohort
Environmental phenols are ubiquitous endocrine disruptors and putatively diabetogenic. However, data during pregnancy are scant. We investigated the prospective associations between pregnancy phenol concentrations and gestational diabetes mellitus (GDM) risk. In a nested matched case-control study of 111 individuals with GDM and 222 individuals without GDM within the prospective PETALS cohort, urinary bisphenol A (BPA), BPA substitutes (bisphenol F and bisphenol S [BPS]), benzophenone-3, and triclosan were quantified during the first and second trimesters. Cumulative concentrations across the two times were calculated using the area under the curve (AUC). Multivariable conditional logistic regression examined the association of individual phenols with GDM risk. We conducted mixture analysis using Bayesian kernel machine regression. We a priori examined effect modification by Asian/Pacific Islander (A/PI) race/ethnicity resulting from the case-control matching and highest GDM prevalence among A/PIs. Overall, first-trimester urinary BPS was positively associated with increased risk of GDM (adjusted odds ratio comparing highest vs. lowest tertile [aORT3 vs. T1] 2.12 [95% CI 1.00-4.50]). We identified associations among non-A/Ps, who had higher phenol concentrations than A/PIs. Among non-A/PIs, first-trimester BPA, BPS, and triclosan were positively associated with GDM risk (aORT3 vs. T1 2.91 [95% CI 1.05-8.02], 4.60 [1.55-13.70], and 2.88 [1.11-7.45], respectively). Triclosan in the second trimester and AUC were positively associated with GDM risk among non-A/PIs (P < 0.05). In mixture analysis, triclosan was significantly associated with GDM risk. Urinary BPS among all and BPA, BPS, and triclosan among non-A/PIs were associated with GDM risk. Pregnant individuals should be aware of these phenols' potential adverse health effects.
Authors: Zhu, Yeyi; Hedderson, Monique M; Calafat, Antonia M; Alexeeff, Stacey E; Feng, Juanran; Quesenberry, Charles P; Ferrara, Assiamira
Diabetes. 2022 Dec 01;71(12):2539-2551.
A large genome-wide association study of QT interval length utilizing electronic health records
QT interval length is an important risk factor for adverse cardiovascular outcomes; however, the genetic architecture of QT interval remains incompletely understood. We conducted a genome-wide association study of 76,995 ancestrally diverse Kaiser Permanente Northern California members enrolled in the Genetic Epidemiology Research on Adult Health and Aging cohort using 448,517 longitudinal QT interval measurements, uncovering 9 novel variants, most replicating in 40,537 individuals in the UK Biobank and Population Architecture using Genomics and Epidemiology studies. A meta-analysis of all 3 cohorts (n = 117,532) uncovered an additional 19 novel variants. Conditional analysis identified 15 additional variants, 3 of which were novel. Little, if any, difference was seen when adjusting for putative QT interval lengthening medications genome-wide. Using multiple measurements in Genetic Epidemiology Research on Adult Health and Aging increased variance explained by 163%, and we show that the ≈6 measurements in Genetic Epidemiology Research on Adult Health and Aging was equivalent to a 2.4× increase in sample size of a design with a single measurement. The array heritability was estimated at ≈17%, approximately half of our estimate of 36% from family correlations. Heritability enrichment was estimated highest and most significant in cardiovascular tissue (enrichment 7.2, 95% CI = 5.7-8.7, P = 2.1e-10), and many of the novel variants included expression quantitative trait loci in heart and other relevant tissues. Comparing our results to other cardiac function traits, it appears that QT interval has a multifactorial genetic etiology.
Authors: Hoffmann, Thomas J; Lu, Meng; Oni-Orisan, Akinyemi; Lee, Catherine; Risch, Neil; Iribarren, Carlos
Genetics. 2022 Nov 30;222(4).
Associations between childhood obesity and pubertal timing stratified by sex and race/ethnicity
Earlier puberty has been associated with numerous adverse mental, emotional, and physical health outcomes. Obesity is a known risk factor for earlier puberty in girls, but research with boys has yielded inconsistent findings. We examined sex- and race/ethnicity-specific associations between childhood obesity and puberty in a multiethnic cohort of 129,824 adolescents born at a Kaiser Permanente Northern California medical facility between 2003 and 2011. We used Weibull regression models to explore associations between childhood obesity and breast development onset (thelarche) in girls, testicular enlargement onset (gonadarche) in boys, and pubic hair development onset (pubarche) in both sexes, adjusting for important confounders. Clear dose-response relationships were observed. Boys with severe obesity had the greatest risk for earlier gonadarche (hazard ratio = 1.23, 95% confidence limit: 1.15, 1.32) and pubarche (hazard ratio = 1.44, 95% confidence limit: 1.34, 1.55), while underweight boys had delayed puberty compared with peers with normal body mass index. A similar dose-response relationship was observed in girls. There were significant interactions between childhood body mass index and race/ethnicity. Childhood obesity is associated with earlier puberty in both boys and girls, and the magnitude of the associations may vary by race/ethnicity. Prevention of childhood obesity may delay pubertal timing and mitigate health risks associated with both conditions.
Authors: Aghaee, Sara; Deardorff, Julianna; Quesenberry, Charles P; Greenspan, Louise C; Kushi, Lawrence H; Kubo, Ai
Am J Epidemiol. 2022 Nov 19;191(12):2026-2036.
Association of serum folate levels during pregnancy and prenatal depression
To evaluate the association between serum folate levels during pregnancy and prenatal depression and the extent to which obesity may modify this relationship. This secondary data analysis leveraged data from a previous study of pregnant Kaiser Permanente Northern California participants who completed a survey and provided a serum sample between 2011 and 2013. Serum folate was assessed using the Center for Disease Control’s Total Folate Serum/Whole Blood Microbiological Assay Method. A score of 15 or greater on the Center for Epidemiologic Studies Depression Scale was defined as prenatal depression. We used Poisson regression to estimate risk of prenatal depression given prenatal serum folate status (low/medium tertiles vs. high tertile) in the full sample and in subsamples of women with pre-pregnancy body mass index in the (a) normal range and (b) overweight/obese range. Of the sample, 13% had prenatal depression. Combined low/medium folate tertiles was associated with prenatal depression (adjusted relative risk [aRR]?=?1.97, 95% confidence interval [CI]: 0.93-4.18), although results did not reach statistical significance. This relationship was stronger among women with overweight/obesity than women with normal weight (aRR: 2.61, 95% CI: 1.01-6.71 and aRR: 1.50, 95% CI: 0.34-6.66, respectively). Results suggest an association between lower pregnancy folate levels and prenatal depression that may be stronger among women with overweight or obesity. Future studies need to clarify the temporal sequence of these associations.
Authors: Avalos, Lyndsay A; Nance, Nerissa; Caan, Bette; Sujan, Ayesha C; Uriu-Adams, Janet Y; Li, De-Kun; Quesenberry, Charles P; Hedderson, Monique M
J Matern Fetal Neonatal Med. 2023 Dec;36(1):1-4. Epub 2022-11-17.
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.
Association of Thoracic Aortic Aneurysm Size With Long-term Patient Outcomes: The KP-TAA Study
The risk of adverse events from ascending thoracic aorta aneurysm (TAA) is poorly understood but drives clinical decision-making. To evaluate the association of TAA size with outcomes in nonsyndromic patients in a large non-referral-based health care delivery system. The Kaiser Permanente Thoracic Aortic Aneurysm (KP-TAA) cohort study was a retrospective cohort study at Kaiser Permanente Northern California, a fully integrated health care delivery system insuring and providing care for more than 4.5 million persons. Nonsyndromic patients from a regional TAA safety net tracking system were included. Imaging data including maximum TAA size were merged with electronic health record (EHR) and comprehensive death data to obtain demographic characteristics, comorbidities, medications, laboratory values, vital signs, and subsequent outcomes. Unadjusted rates were calculated and the association of TAA size with outcomes was evaluated in multivariable competing risk models that categorized TAA size as a baseline and time-updated variable and accounted for potential confounders. Data were analyzed from January 2018 to August 2021. TAA size. Aortic dissection (AD), all-cause death, and elective aortic surgery. Of 6372 patients with TAA identified between 2000 and 2016 (mean [SD] age, 68.6 [13.0] years; 2050 female individuals [32.2%] and 4322 male individuals [67.8%]), mean (SD) initial TAA size was 4.4 (0.5) cm (828 individuals [13.0% of cohort] had initial TAA size 5.0 cm or larger and 280 [4.4%] 5.5 cm or larger). Rates of AD were low across a mean (SD) 3.7 (2.5) years of follow-up (44 individuals [0.7% of cohort]; incidence 0.22 events per 100 person-years). Larger initial aortic size was associated with higher risk of AD and all-cause death in multivariable models, with an inflection point in risk at 6.0 cm. Estimated adjusted risks of AD within 5 years were 0.3% (95% CI, 0.3-0.7), 0.6% (95% CI, 0.4-1.3), 1.5% (95% CI, 1.2-3.9), 3.6% (95% CI, 1.8-12.8), and 10.5% (95% CI, 2.7-44.3) in patients with TAA size of 4.0 to 4.4 cm, 4.5 to 4.9 cm, 5.0 to 5.4 cm, 5.5 to 5.9 cm, and 6.0 cm or larger, respectively, in time-updated models. Rates of the composite outcome of AD and all-cause death were higher than for AD alone, but a similar inflection point for increased risk was observed at 6.0 cm. In a large sociodemographically diverse cohort of patients with TAA, absolute risk of aortic dissection was low but increased with larger aortic sizes after adjustment for potential confounders and competing risks. Our data support current consensus guidelines recommending prophylactic surgery in nonsyndromic individuals with TAA at a 5.5-cm threshold.
Authors: Solomon, Matthew D; Lee, Catherine; Chang, Robert; Go, Alan S; Kaiser Permanente Northern California Center for Thoracic Aortic Disease ,; et al.
JAMA Cardiol. 2022 Nov 01;7(11):1160-1169.
Retrospective cohort study to assess the association between treatment with tocilizumab and mortality among mechanically ventilated patients with COVID-19
Assess the association between tocilizumab administration and clinical outcomes among mechanically ventilated patients with COVID-19 pneumonia. Retrospective cohort study. Large integrated health system with 9 million members in California, USA. 4185 Kaiser Permanente members hospitalised with COVID-19 pneumonia requiring invasive mechanical ventilation (IMV). Receipt of tocilizumab within 10 days of initiation of IMV. Using a retrospective cohort of consecutive patients hospitalised with COVID-19 pneumonia who required IMV in a large integrated health system in California, USA, we assessed the association between tocilizumab administration and 28-day mortality, time to extubation from IMV and time to hospital discharge. Among 4185 patients, 184 received tocilizumab and 4001 patients did not receive tocilizumab within 10 days of initiation of IMV. After inverse probability weighting, baseline characteristics were well balanced between groups. Patients treated with tocilizumab had a similar risk of death in the 28 days after intubation compared with patients not treated with tocilizumab (adjusted HR (aHR), 1.21, 95% CI 0.98 to 1.50), but did have a significantly longer time-to-extubation (aHR 0.71; 95% CI 0.57 to 0.88) and time-to-hospital-discharge (aHR 0.66; 95% CI 0.50 to 0.88). However, patients treated with tocilizumab ≤2 days after initiation of IMV had a similar risk of mortality (aHR 1.47; 95% CI 0.96 to 2.26), but significantly shorter time-to-extubation (aHR 0.37; 95% CI 0.23 to 0.58) and time-to-hospital-discharge (aHR 0.31; 95% CI CI 0.17 to 0.56) compared with patients treated with tocilizumab 3-10 days after initiation of IMV. Among mechanically ventilated patients with COVID-19, the risk of death in the 28-day follow-up period was similar, but time-to-extubation and time-to-hospital-discharge were longer in patients who received tocilizumab within 10 days of initiation of IMV compared with patients who did not receive tocilizumab.
Authors: Skarbinski, Jacek; Fireman, Bruce H; Tartof, Sara Y; et al.
BMJ Open. 2022 10 31;12(10):e060358. Epub 2022-10-31.
Prescribing for different antibiotic classes across age groups in the Kaiser Permanente Northern California population in association with influenza incidence, 2010-2018
There is limited information on the volume of antibiotic prescribing that is influenza-associated, resulting from influenza infections and their complications (such as streptococcal pharyngitis). We estimated that for the Kaiser Permanente Northern California population during 2010-2018, 3.4% (2.8%-4%) of all macrolide prescriptions (fills), 2.7% (2.3%-3.2%) of all aminopenicillin prescriptions, 3.1% (2.4%-3.9%) of all 3rd generation cephalosporins prescriptions, 2.2% (1.8%-2.6%) of all protected aminopenicillin prescriptions and 1.3% (1%-1.6%) of all quinolone prescriptions were influenza-associated. The corresponding proportions were higher for select age groups, e.g. 4.3% of macrolide prescribing in ages over 50 years, 5.1% (3.3%-6.8%) of aminopenicillin prescribing in ages 5-17 years and 3.3% (1.9%-4.6%) in ages <5 years was influenza-associated. The relative contribution of influenza to antibiotic prescribing for respiratory diagnoses without a bacterial indication in ages over 5 years was higher than the corresponding relative contribution to prescribing for all diagnoses. Our results suggest a modest benefit of increasing influenza vaccination coverage for reducing prescribing for the five studied antibiotic classes, particularly for macrolides in ages over 50 years and aminopenicillins in ages <18 years, and the potential benefit of other measures to reduce unnecessary antibiotic prescribing for respiratory diagnoses with no bacterial indication, both of which may contribute to the mitigation of antimicrobial resistance.
Authors: Goldstein, Edward; Fireman, Bruce H; Klein, Nicola P; Lipsitch, Marc; Ray, G Thomas
Epidemiol Infect. 2022 Oct 26;150:e180. Epub 2022-10-26.
Effectiveness of COVID-19 mRNA Vaccines Against COVID-19-Associated Hospitalizations Among Immunocompromised Adults During SARS-CoV-2 Omicron Predominance – VISION Network, 10 States, December 2021-August 2022
Persons with moderate-to-severe immunocompromising conditions might have reduced protection after COVID-19 vaccination, compared with persons without immunocompromising conditions (1-3). On August 13, 2021, the Advisory Committee on Immunization Practices (ACIP) recommended that adults with immunocompromising conditions receive an expanded primary series of 3 doses of an mRNA COVID-19 vaccine. ACIP followed with recommendations on September 23, 2021, for a fourth (booster) dose and on September 1, 2022, for a new bivalent mRNA COVID-19 vaccine booster dose, containing components of the BA.4 and BA.5 sublineages of the Omicron (B.1.1.529) variant (4). Data on vaccine effectiveness (VE) of monovalent COVID-19 vaccines among persons with immunocompromising conditions since the emergence of the Omicron variant in December 2021 are limited. In the multistate VISION Network,§ monovalent 2-, 3-, and 4-dose mRNA VE against COVID-19-related hospitalization were estimated among adults with immunocompromising conditions¶ hospitalized with COVID-19-like illness,** using a test-negative design comparing odds of previous vaccination among persons with a positive or negative molecular test result (case-patients and control-patients) for SARS-CoV-2 (the virus that causes COVID-19). During December 16, 2021-August 20, 2022, among SARS-CoV-2 test-positive case-patients, 1,815 (36.3%), 1,387 (27.7%), 1,552 (31.0%), and 251 (5.0%) received 0, 2, 3, and 4 mRNA COVID-19 vaccine doses, respectively. Among test-negative control-patients during this period, 6,928 (23.7%), 7,411 (25.4%), 12,734 (43.6%), and 2,142 (7.3%) received these respective doses. Overall, VE against COVID-19-related hospitalization among adults with immunocompromising conditions hospitalized for COVID-like illness during Omicron predominance was 36% ≥14 days after dose 2, 69% 7-89 days after dose 3, and 44% ≥90 days after dose 3. Restricting the analysis to later periods when Omicron sublineages BA.2/BA.2.12.1 and BA.4/BA.5 were predominant and 3-dose recipients were eligible to receive a fourth dose, VE was 32% ≥90 days after dose 3 and 43% ≥7 days after dose 4. Protection offered by vaccination among persons with immunocompromising conditions during Omicron predominance was moderate even after a 3-dose monovalent primary series or booster dose. Given the incomplete protection against hospitalization afforded by monovalent COVID-19 vaccines, persons with immunocompromising conditions might benefit from updated bivalent vaccine booster doses that target recently circulating Omicron sublineages, in line with ACIP recommendations. Further, additional protective recommendations for persons with immunocompromising conditions, including the use of prophylactic antibody therapy, early access to and use of antivirals, and enhanced nonpharmaceutical interventions such as well-fitting masks or respirators, should also be considered.
Authors: Britton, Amadea; Klein, Nicola P; Zerbo, Ousseny; Fireman, Bruce; Tenforde, Mark W; et al.
MMWR Morb Mortal Wkly Rep. 2022 Oct 21;71(42):1335-1342. Epub 2022-10-21.
Maternal SARS-CoV-2 Vaccination and Infant Protection Against SARS-CoV-2 During the First 6 Months of Life
We examined the effectiveness of maternal vaccination against SARS-CoV-2 infection in 30,288 infants born at Kaiser Permanente Northern California from December 15, 2020, to May 31, 2022. Using Cox regression, the effectiveness of maternal vaccination was 85% (95% confidence interval [CI]: 67, 93), 64% (CI: 43, 78) and 57% (CI: 36,71) during the first 2, 4 and 6 months of life, respectively, in the Delta variant period. In the Omicron variant period, the effectiveness of maternal vaccination in these three age intervals was 22% (CI: -18,48), 14% (CI: -10,32) and 12% (CI: -4,26), respectively. Over the entire study period, the incidence of hospitalization for COVID-19 was lower during the first 6 months of life among infants of vaccinated mothers compared with infants of unvaccinated mothers (21/100,000 person-years vs. 100/100,000 person-years). Maternal vaccination was protective, but protection was lower during Omicron than during Delta. Protection during both periods decreased as infants aged.
Authors: Zerbo, Ousseny; Ray, G Thomas; Fireman, Bruce; Layefsky, Evan; Goddard, Kristin; Lewis, Edwin; Ross, Pat; Omer, Saad; Greenberg, Mara; Klein, Nicola
Res Sq. 2022 Oct 18.
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.
Assessment of genetic susceptibility to multiple primary cancers through whole-exome sequencing in two large multi-ancestry studies
Up to one of every six individuals diagnosed with one cancer will be diagnosed with a second primary cancer in their lifetime. Genetic factors contributing to the development of multiple primary cancers, beyond known cancer syndromes, have been underexplored. To characterize genetic susceptibility to multiple cancers, we conducted a pan-cancer, whole-exome sequencing study of individuals drawn from two large multi-ancestry populations (6429 cases, 165,853 controls). We created two groupings of individuals diagnosed with multiple primary cancers: (1) an overall combined set with at least two cancers across any of 36 organ sites and (2) cancer-specific sets defined by an index cancer at one of 16 organ sites with at least 50 cases from each study population. We then investigated whether variants identified from exome sequencing were associated with these sets of multiple cancer cases in comparison to individuals with one and, separately, no cancers. We identified 22 variant-phenotype associations, 10 of which have not been previously discovered and were significantly overrepresented among individuals with multiple cancers, compared to those with a single cancer. Overall, we describe variants and genes that may play a fundamental role in the development of multiple primary cancers and improve our understanding of shared mechanisms underlying carcinogenesis.
Authors: Cavazos, Taylor B; Alexeeff, Stacey; Van Den Eeden, Stephen; Corley, Douglas A; Kushi, Lawrence H; Habel, Laurel A; Sakoda, Lori C; Witte, John S; et al.
BMC Med. 2022 10 06;20(1):332. Epub 2022-10-06.
Waning of vaccine effectiveness against moderate and severe covid-19 among adults in the US from the VISION network: test negative, case-control study
To estimate the effectiveness of mRNA vaccines against moderate and severe covid-19 in adults by time since second, third, or fourth doses, and by age and immunocompromised status. Test negative case-control study. Hospitals, emergency departments, and urgent care clinics in 10 US states, 17 January 2021 to 12 July 2022. 893 461 adults (≥18 years) admitted to one of 261 hospitals or to one of 272 emergency department or 119 urgent care centers for covid-like illness tested for SARS-CoV-2. The main outcome was waning of vaccine effectiveness with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine during the omicron and delta periods, and the period before delta was dominant using logistic regression conditioned on calendar week and geographic area while adjusting for age, race, ethnicity, local virus circulation, immunocompromised status, and likelihood of being vaccinated. 45 903 people admitted to hospital with covid-19 (cases) were compared with 213 103 people with covid-like illness who tested negative for SARS-CoV-2 (controls), and 103 287 people admitted to emergency department or urgent care with covid-19 (cases) were compared with 531 168 people with covid-like illness who tested negative for SARS-CoV-2. In the omicron period, vaccine effectiveness against covid-19 requiring admission to hospital was 89% (95% confidence interval 88% to 90%) within two months after dose 3 but waned to 66% (63% to 68%) by four to five months. Vaccine effectiveness of three doses against emergency department or urgent care visits was 83% (82% to 84%) initially but waned to 46% (44% to 49%) by four to five months. Waning was evident in all subgroups, including young adults and individuals who were not immunocompromised; although waning was morein people who were immunocompromised. Vaccine effectiveness increased among most groups after a fourth dose in whom this booster was recommended. Effectiveness of mRNA vaccines against moderate and severe covid-19 waned with time after vaccination. The findings support recommendations for a booster dose after a primary series and consideration of additional booster doses.
Authors: Ferdinands, Jill M; Klein, Nicola P; Zerbo, Ousseny; Fireman, Bruce; et al.
BMJ. 2022 10 03;379:e072141. Epub 2022-10-03.
Sociodemographic and clinical characteristics associated with never-smoking status in patients with lung cancer: findings from a large integrated health system
Evidence is limited characterizing sociodemographically diverse patient populations with lung cancer in relation to smoking status. In a cross-sectional analysis of adults diagnosed with lung cancer at ages ≥30 years from 2007-2018 within an integrated healthcare system, overall and sex-specific prevalence of never smoking were estimated according to sociodemographic and clinical characteristics. Adjusted prevalence ratio (aPR) and 95% confidence interval (CI) were also estimated using modified Poisson regression to identify patient characteristics associated with never smoking, overall and by sex. Similar analyses were conducted to explore whether prevalence and association patterns differed between non-Hispanic White and Asian/Pacific Islander patients. Among 17,939 patients with lung cancer, 2,780 (15.5%) never smoked and 8,698 (48.5%) had adenocarcinoma. Overall prevalence of never smoking was higher among females than males (21.2% vs. 9.2%, aPR 2.13, 95% CI: 1.98-2.29); Asian/Pacific Islander (aPR 2.85, 95% CI: 2.65-3.07) and Hispanic (aPR 1.72, 95% CI: 1.51-1.95) than non-Hispanic White patients; patients who primarily spoke Spanish (aPR 1.60, 95% CI: 1.32-1.94), any Asian language (aPR 1.20, 95% CI: 1.10-1.30), or other languages (aPR 1.84, 95% CI: 1.27-2.65) than English; patients living in the least vs. most deprived neighborhoods (aPR 1.36, 95% CI: 1.24-1.50); and patients with adenocarcinoma (aPR 2.57, 95% CI: 2.18-3.03), other non-small cell lung cancer (NSCLC) (aPR 2.00, 95% CI: 1.63-2.45), or carcinoid (aPR 3.60, 95% CI: 2.96-4.37) than squamous cell carcinoma tumors. Patterns of never smoking associated with sociodemographic, but not clinical factors, differed by sex. The higher prevalence of never smoking associated with Asian/Pacific Islander race/ethnicity was more evident among females (aPR 3.30, 95% CI: 2.95-3.47) than males (aPR 2.25, 95% CI: 1.92-2.63), whereas the higher prevalence of never smoking associated with living in the least deprived neighborhoods was more evident among males (aPR 1.93, 95% CI: 1.56-2.38) than females (aPR 1.18, 95% CI: 1.06-1.31). Associations between primary language and never-smoking status were found only among females. Overall and sex-specific prevalence and association patterns differed between Asian/Pacific Islander and non-Hispanic white patients. Our findings suggest that patterns of never-smoking status associated with sociodemographic and clinical characteristics are different across sex and race/ethnicity among patients with lung cancer. Such data are critical to increasing awareness and expediting diagnosis of this disease.
Authors: Banks, Kian C; Sumner, Eric T; Alabaster, Amy; Hsu, Diana S; Quesenberry, Charles P; Sakoda, Lori C; Velotta, Jeffrey B
Transl Cancer Res. 2022 Oct;11(10):3522-3534.
Disparities in the Incidence of Ectopic Pregnancy in a Large Health Care System in California, 2010-2019
IntroductionEctopic pregnancy leads to reproductive health morbidity, including greater risk of another ectopic pregnancy, infertility, and, in rare cases, mortality. Information on trends in the incidence of ectopic pregnancy in the last decade is limited. MethodsA population-based cross-sectional study of women aged 15-44 years enrolled at Kaiser Permanente Northern and Southern California 2010-2019 was conducted. Electronic health records were used to identify ectopic pregnancies. The crude ectopic pregnancy incidence per 1000 pregnancies (live births, induced abortions, and ectopic pregnancies) and 95% confidence interval (CI) was estimated per study year, overall, and stratified by age group. The age-adjusted incidence and 95% CI was estimated per study year, overall, and stratified by race/ethnicity. Temporal trend was assessed using Poisson regression. ResultsThere were 15,537 ectopic pregnancies among 979,027 pregnancies. The overall age-adjusted ectopic pregnancy incidence was 15.8 per 1000 pregnancies, 95% CI: 15.6, 16.1. The annual incidence increased from 15.2, 95% CI: 14.4, 16.1, in 2010 to 16.4, 95% CI: 15.6, 17.2, in 2019 (p < 0.001). The overall incidence was highest among women aged 40-44 years (24.2, 95% CI: 22.7, 25.6) and non-Hispanic Black women (21.9, 95% CI: 21.0, 22.8); compared to 30-34-year-old (16.2, 95% CI: 15.7, 16.6) and non-Hispanic White (14.6, 95% CI: 14.1, 15.0) women, respectively. DiscussionThe increase in ectopic pregnancy incidence during the studied period was largely driven by increasing incidence in younger women. However, disparities in the incidence by age and race/ethnicity persisted. ConclusionEctopic pregnancy remains a significant source of reproductive health morbidity, especially for older ( >40 years) and non-Hispanic Black women.
Authors: Raine-Bennett, Tina; Fassett, Michael J; Chandra, Malini; Armstrong, Mary Anne; Xie, Fagen; Shi, Jiaxiao M; Alexeeff, Stacey; Chiu, Vicki Y; Im, Theresa M; Asiimwe, Alex; Getahun, Darios
Perm J. 2022 Sep 14;26(3):61-68. Epub 2022-08-01.
Estimation of COVID-19 mRNA Vaccine Effectiveness Against Medically Attended COVID-19 in Pregnancy During Periods of Delta and Omicron Variant Predominance in the United States
Pregnant people are at high risk for severe COVID-19 but were excluded from mRNA vaccine trials; data on COVID-19 vaccine effectiveness (VE) are needed. To evaluate the estimated effectiveness of mRNA vaccination against medically attended COVID-19 among pregnant people during Delta and Omicron predominance. This test-negative, case-control study was conducted from June 2021 to June 2022 in a network of 306 hospitals and 164 emergency department and urgent care (ED/UC) facilities across 10 US states, including 4517 ED/UC encounters and 975 hospitalizations among pregnant people with COVID-19-like illness (CLI) who underwent SARS-CoV-2 molecular testing. Two doses (14-149 and ≥150 days prior) and 3 doses (7-119 and ≥120 days prior) of COVID-19 mRNA vaccine (≥1 dose received during pregnancy) vs unvaccinated. Estimated VE against laboratory-confirmed COVID-19-associated ED/UC encounter or hospitalization, based on the adjusted odds ratio (aOR) for prior vaccination; VE was calculated as (1 - aOR) × 100%. Among 4517 eligible CLI-associated ED/UC encounters and 975 hospitalizations, 885 (19.6%) and 334 (34.3%) were SARS-CoV-2 positive, respectively; the median (IQR) patient age was 28 (24-32) years and 31 (26-35) years, 537 (12.0%) and 118 (12.0%) were non-Hispanic Black and 1189 (26.0%) and 240 (25.0%) were Hispanic. During Delta predominance, the estimated VE against COVID-19-associated ED/UC encounters was 84% (95% CI, 69% to 92%) for 2 doses within 14 to 149 days, 75% (95% CI, 5% to 93%) for 2 doses 150 or more days prior, and 81% (95% CI, 30% to 95%) for 3 doses 7 to 119 days prior; estimated VE against COVID-19-associated hospitalization was 99% (95% CI, 96% to 100%), 96% (95% CI, 86% to 99%), and 97% (95% CI, 79% to 100%), respectively. During Omicron predominance, for ED/UC encounters, the estimated VE of 2 doses within 14 to 149 days, 2 doses 150 or more days, 3 doses within 7 to 119 days, and 3 doses 120 or more days prior was 3% (95% CI, -49% to 37%), 42% (95% CI, -16% to 72%), 79% (95% CI, 59% to 89%), and -124% (95% CI, -414% to 2%), respectively; for hospitalization, estimated VE was 86% (95% CI, 41% to 97%), 64% (95% CI, -102% to 93%), 86% (95% CI, 28% to 97%), and -53% (95% CI, -1254% to 83%), respectively. In this study, maternal mRNA COVID-19 vaccination, including booster dose, was associated with protection against medically attended COVID-19. VE estimates were higher against COVID-19-associated hospitalization than ED/UC visits and lower against the Omicron variant than the Delta variant. Protection waned over time, particularly during Omicron predominance.
Authors: Schrag, Stephanie J; Zerbo, Ousseny; Klein, Nicola P; Fireman, Bruce; Naleway, Allison L; et al.
JAMA Netw Open. 2022 09 01;5(9):e2233273. Epub 2022-09-01.
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.
Maternal autoantibody profiles as biomarkers for ASD and ASD with co-occurring intellectual disability
Maternal autoantibody-related ASD (MAR ASD) is a subtype of autism in which pathogenic maternal autoantibodies (IgG) cross the placenta, access the developing brain, and cause neurodevelopmental alterations and behaviors associated with autism in the exposed offspring. We previously reported maternal IgG response to eight proteins (CRMP1, CRMP2, GDA LDHA, LDHB, NSE, STIP1, and YBOX) and that reactivity to nine specific combinations of these proteins (MAR ASD patterns) was predictive of ASD risk. The aim of the current study was to validate the previously identified MAR ASD patterns (CRMP1 + GDA, CRMP1 + CRMP2, NSE + STIP1, CRMP2 + STIP1, LDHA + YBOX, LDHB + YBOX, GDA + YBOX, STIP1 + YBOX, and CRMP1 + STIP1) and their accuracy in predicting ASD risk in a prospective cohort employing maternal samples collected prior to parturition. We used prenatal plasma from mothers of autistic children with or without co-occurring intellectual disability (ASD = 540), intellectual disability without autism (ID = 184) and general population controls (GP = 420) collected by the Early Markers for Autism (EMA) study. We found reactivity to one or more of the nine previously identified MAR ASD patterns in 10% of the ASD group compared with 4% of the ID group and 1% of the GP controls (ASD vs GP: Odds Ratio (OR) = 7.81, 95% Confidence Interval (CI) 3.32 to 22.43; ASD vs ID: OR = 2.77, 95% CI (1.19-7.47)) demonstrating that the MAR ASD patterns are strongly associated with the ASD group and could be used to assess ASD risk prior to symptom onset. The pattern most strongly associated with ASD was CRMP1 + CRMP2 and increased the odds for an ASD diagnosis 16-fold (3.32 to >999.99). In addition, we found that several of these specific MAR ASD patterns were strongly associated with ASD with intellectual disability (ASD + ID) and others associated with ASD without ID (ASD-no ID). Prenatal screening for these MAR patterns may lead to earlier identification of ASD and facilitate access to the appropriate early intervention services based on each child’s needs.
Authors: Ramirez-Celis, Alexandra; Croen, Lisa A; Yoshida, Cathleen K; Alexeeff, Stacey E; Schauer, Joseph; Yolken, Robert H; Ashwood, Paul; Van de Water, Judy
Mol Psychiatry. 2022 Sep;27(9):3760-3767. Epub 2022-05-26.
Risk of myocarditis and pericarditis following BNT162b2 and mRNA-1273 COVID-19 vaccination
Evidence indicates that mRNA COVID-19 vaccination is associated with risk of myocarditis and possibly pericarditis, especially in young males. It is not clear if risk differs between mRNA-1273 versus BNT162b2. We assessed if risk differs using comprehensive health records on a diverse population. Members 18-39 years of age at eight integrated healthcare-delivery systems were monitored using data updated weekly and supplemented with medical record review of myocarditis and pericarditis cases. Incidence of myocarditis and pericarditis events that occurred among vaccine recipients 0 to 7 days after either dose 1 or 2 of a messenger RNA (mRNA) vaccine was compared with that of vaccinated concurrent comparators who, on the same calendar day, had received their most recent dose 22 to 42 days earlier. Rate ratios (RRs) were estimated by conditional Poisson regression, adjusted for age, sex, race and ethnicity, health plan, and calendar day. Head-to-head comparison directly assessed risk following mRNA-1273 versus BNT162b2 during 0-7 days post-vaccination. From December 14, 2020 – January 15, 2022 there were 41 cases after 2,891,498 doses of BNT162b2 and 38 cases after 1,803,267 doses of mRNA-1273. Cases had similar demographic and clinical characteristics. Most were hospitalized for ≤1 day; none required intensive care. During days 0-7 after dose 2 of BNT162b2, the incidence was 14.3 (CI: 6.5-34.9) times higher than the comparison interval, amounting to 22.4 excess cases per million doses; after mRNA-1273 the incidence was 18.8 (CI: 6.7-64.9) times higher than the comparison interval, amounting to 31.2 excess cases per million doses. In head-to-head comparisons 0-7 days after either dose, risk was moderately higher after mRNA-1273 than after BNT162b2 (RR: 1.61, CI 1.02-2.54). Both vaccines were associated with increased risk of myocarditis and pericarditis in 18-39-year-olds. Risk estimates were modestly higher after mRNA-1273 than after BNT162b2.
Authors: Goddard, Kristin; Fireman, Bruce; Zerbo, Ousseny; Klein, Nicola P; et al.
Vaccine. 2022 Aug 19;40(35):5153-5159. Epub 2022-07-12.
Prolactin and maternal metabolism in women with a recent GDM pregnancy and links to future T2D: the SWIFT study
Prolactin is a multifaceted hormone known to regulate lactation. In women with gestational diabetes mellitus (GDM) history, intensive lactation has been associated with lower relative risk of future type 2 diabetes (T2D). However, the role of prolactin in T2D development and maternal metabolism in women with a recent GDM pregnancy has not been ascertained. We examined the relationships among prolactin, future T2D risk, and key clinical and metabolic parameters. We utilized a prospective GDM research cohort (the SWIFT study) and followed T2D onset by performing 2-hour 75-g research oral glucose tolerance test (OGTT) at study baseline (6-9 weeks postpartum) and again annually for 2 years, and also by retrieving clinical diagnoses of T2D from 2 years through 10 years of follow up from electronic medical records. Targeted metabolomics and lipidomics were applied on fasting plasma samples collected at study baseline from 2-hour 75-g research OGTTs in a nested case-control study (100 future incident T2D cases vs 100 no T2D controls). Decreasing prolactin quartiles were associated with increased future T2D risk (adjusted odds ratio 2.48; 95% CI, 0.81-7.58; P = 0.05). In women who maintained normoglycemia during the 10-year follow-up period, higher prolactin at baseline was associated with higher insulin sensitivity (P = 0.038) and HDL-cholesterol (P = 0.01), but lower BMI (P = 0.001) and leptin (P = 0.002). Remarkably, among women who developed future T2D, prolactin was not correlated with a favorable metabolic status (all P > 0.05). Metabolomics and lipidomics showed that lower circulating prolactin strongly correlated with a T2D-high risk lipid profile, with elevated circulating neutral lipids and lower concentrations of specific phospholipids/sphingolipids. In women with recent GDM pregnancy, low circulating prolactin is associated with specific clinical and metabolic parameters and lipid metabolites linked to a high risk of developing T2D.
Authors: Zhang, Ziyi; Piro, Anthony L; Allalou, Amina; Alexeeff, Stacey E; Dai, Feihan F; Gunderson, Erica P; Wheeler, Michael B
J Clin Endocrinol Metab. 2022 Aug 18;107(9):2652-2665.
Risk of severe COVID-19 infection among adults with prior exposure to children
Susceptibility and severity of COVID-19 infection vary widely. Prior exposure to endemic coronaviruses, common in young children, may protect against SARS-CoV-2. We evaluated risk of severe COVID-19 among adults with and without exposure to young children in a large, integrated healthcare system. Adults with children 0-5 years were matched 1:1 to adults with children 6-11 years, 12-18 years, and those without children based upon a COVID-19 propensity score and risk factors for severe COVID-19. COVID-19 infections, hospitalizations, and need for intensive care unit (ICU) were assessed in 3,126,427 adults, of whom 24% (N = 743,814) had children 18 years or younger, and 8.8% (N = 274,316) had a youngest child 0-5 years. After 1:1 matching, propensity for COVID-19 infection and risk factors for severe COVID-19 were well balanced between groups. Rates of COVID-19 infection were slightly higher for adults with exposure to older children (incident risk ratio, 1.09, 95% confidence interval, [1.05-1.12] and IRR 1.09 [1.05-1.13] for adults with children 6-11 and 12-18, respectively), compared to those with children 0-5 years, although no difference in rates of COVID-19 illness requiring hospitalization or ICU admission was observed. However, adults without exposure to children had lower rates of COVID-19 infection (IRR 0.85, [0.83-0.87]) but significantly higher rates of COVID-19 hospitalization (IRR 1.49, [1.29-1.73]) and hospitalization requiring ICU admission (IRR 1.76, [1.19-2.58]) compared to those with children aged 0-5. In a large, real-world population, exposure to young children was associated with less severe COVID-19 illness. Endemic coronavirus cross-immunity may play a role in protection against severe COVID-19.
Authors: Solomon, Matthew D; Escobar, Gabriel J; Lu, Yun; Schlessinger, David; Steinman, Jonathan B; Steinman, Lawrence; Lee, Catherine; Liu, Vincent X
Proc Natl Acad Sci U S A. 2022 Aug 16;119(33):e2204141119. Epub 2022-07-27.
Safety of COVID-19 Vaccination in US Children Ages 5-11 Years
Limited postauthorization safety data for the Pfizer-BioNTech coronavirus disease 2019 vaccination among children ages 5 to 11 years are available, particularly for the adverse event myocarditis, which has been detected in adolescents and young adults. We describe adverse events observed during the first 4 months of the United States coronavirus disease 2019 vaccination program in this age group. We analyzed data from 3 United States safety monitoring systems: v-safe, a voluntary smartphone-based system that monitors reactions and health effects; the Vaccine Adverse Events Reporting System (VAERS), the national spontaneous reporting system comanaged by the Centers for Disease Control and Prevention and Food and Drug Administration; and the Vaccine Safety Datalink, an active surveillance system that monitors electronic health records for prespecified events, including myocarditis. Among 48 795 children ages 5 to 11 years enrolled in v-safe, most reported reactions were mild-to-moderate, most frequently reported the day after vaccination, and were more common after dose 2. VAERS received 7578 adverse event reports; 97% were nonserious. On review of 194 serious VAERS reports, 15 myocarditis cases were verified; 8 occurred in boys after dose 2 (reporting rate 2.2 per million doses). In the Vaccine Safety Datalink, no safety signals were detected in weekly sequential monitoring after administration of 726 820 doses. Safety findings for Pfizer-BioNTech vaccine from 3 United States monitoring systems in children ages 5 to 11 years show that most reported adverse events were mild and no safety signals were observed in active surveillance. VAERS reporting rates of myocarditis after dose 2 in this age group were substantially lower than those observed among adolescents ages 12 to 15 years.
Authors: Hause, Anne M; Klein, Nicola P; Fireman, Bruce; Zerbo, Ousseny; Shimabukuro, Tom T; et al.
Pediatrics. 2022 08 01;150(2).
Predictive Metabolomic Markers in Early to Mid-Pregnancy for Gestational Diabetes: A Prospective Test and Validation Study
Gestational diabetes mellitus (GDM) predisposes pregnant individuals to perinatal complications and long-term diabetes and cardiovascular diseases. We developed and validated metabolomic markers for GDM in a prospective test-validation study. In a case-control sample within the PETALS cohort (GDM n = 91 and non-GDM n = 180; discovery set), a random PETALS subsample (GDM n = 42 and non-GDM n = 372; validation set 1), and a case-control sample within the GLOW trial (GDM n = 35 and non-GDM n = 70; validation set 2), fasting serum untargeted metabolomics were measured by gas chromatography/time-of-flight mass spectrometry. Multivariate enrichment analysis examined associations between metabolites and GDM. Ten-fold cross-validated LASSO regression identified predictive metabolomic markers at gestational weeks (GW) 10-13 and 16-19 for GDM. Purinone metabolites at GW 10-13 and 16-19 and amino acids, amino alcohols, hexoses, indoles, and pyrimidine metabolites at GW 16-19 were positively associated with GDM risk (false discovery rate <0.05). A 17-metabolite panel at GW 10-13 outperformed the model using conventional risk factors, including fasting glycemia (area under the curve: discovery 0.871 vs. 0.742, validation 1 0.869 vs. 0.731, and validation 2 0.972 vs. 0.742; P < 0.01). Similar results were observed with a 13-metabolite panel at GW 17-19. Dysmetabolism is present early in pregnancy among individuals progressing to GDM. Multimetabolite panels in early pregnancy can predict GDM risk beyond conventional risk factors.
Authors: Zhu, Yeyi; Barupal, Dinesh K; Ngo, Amanda L; Quesenberry, Charles P; Feng, Juanran; Fiehn, Oliver; Ferrara, Assiamira
Diabetes. 2022 08 01;71(8):1807-1817.
Adults hospitalized with breakthrough COVID-19 have lower mortality than matched unvaccinated adults
Coronavirus disease 2019 (COVID-19) breakthrough infections are common. Evaluate in-hospital mortality of patients with COVID-19 by vaccination status using retrospective cohort study. We generated propensity scores for receipt of full vaccination in adults requiring supplemental oxygen hospitalized at Kaiser Permanente Northern California (1 April 2021 to 30 November 2021) with positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction tests. Optimal matching of fully vaccinated/unvaccinated patients was performed comparing in-hospital mortality. Of 7305 patients, 1463 (20.0%) were full, 138 (1.9%) were partial, and 5704 (78.1%) were unvaccinated. Fully vaccinated were older than partial or unvaccinated (71.0, 63.0, and 54.0 years, respectively, p < 0.001) with more comorbidities (Comorbidity Point Scores 33.0, 22.0, and 10.0, p < 0.001) and immunosuppressant (11.5%, 8.7%, and 3.0%, p < 0.001) or chemotherapy exposure (2.8%, 0.7%, and 0.4%, p < 0.001). Fewer fully vaccinated patients died compared to matched unvaccinated (9.0% vs. 16.3%, p < 0.0001). Fully vaccinated patients are less likely to die compared to matched unvaccinated patients.
Authors: Myers, Laura C; Kipnis, Patricia; Greene, John; Lawson, Brian; Escobar, Gabriel J; Fireman, Bruce H; Klein, Nicola P; Liu, Vincent X
J Intern Med. 2022 08;292(2):377-384. Epub 2022-05-17.
Myocarditis and/or pericarditis risk after mRNA COVID-19 vaccination: A Canadian head to head comparison of BNT162b2 and mRNA-1273 vaccines
Canadian and international data suggest the risk of myocarditis and/or pericarditis is elevated during the week after mRNA COVID-19 vaccination, particularly in younger age groups, in males, and after second doses. This article examines whether there is a product-specific difference in the risk for myocarditis and/or pericarditis between the two mRNA vaccines administered in Canada: BNT162b2 (Pfizer-BioNTech Comirnaty) and mRNA-1273 (Moderna Spikevax). Reporting rates of myocarditis and/or pericarditis were calculated from reports received by the Canadian Adverse Events Following Immunization Surveillance System from December 2020-March 2022. Excess cases and attributable incidence among individuals aged 18-39 were estimated for each vaccine in comparison with background rates from 2015 to 2019. Head-to-head comparisons used Poisson regression, conditioned on week of vaccine administration, to estimate rate ratios for the week after mRNA-1273 vaccination versus the week after BNT162b2, by age and sex as well as overall. Analyses were restricted to May 30-March 13, 2021, when heightened media awareness was unlikely to have affected reporting rates for the two products differentially. In 18-29 year-old males who received a second dose of mRNA COVID-19 vaccine, attributable risk of myocarditis and/or pericarditis was found to be 5.69 (95% CI: 4.07 – 7.95; p < 0.001) times higher among mRNA-1273 recipients (n = 106) as compared to BNT162b2 recipients (n = 33). In the same group, Poisson regression modelling estimated that the risk of myocarditis and/or pericarditis was 4.72 (p-value = <0.001) times higher after mRNA-1723 compared to BNT162b2 vaccination. The risk of myocarditis and/or pericarditis is higher after mRNA-1723 vaccination than BNT162b2 vaccination in those aged 18-39 years, especially in males aged 18-29 years, where the risk is several times higher.
Authors: Abraham, Natalia; Spruin, Sarah; Rossi, Tanya; Fireman, Bruce; Zafack, Joseline; Blaser, Christine; Shaw, Amanda; Hutchings, Kimberley; Ogunnaike-Cooke, Susanna
Vaccine. 2022 07 30;40(32):4663-4671. Epub 2022-05-25.
Effectiveness of 2, 3, and 4 COVID-19 mRNA Vaccine Doses Among Immunocompetent Adults During Periods when SARS-CoV-2 Omicron BA.1 and BA.2/BA.2.12.1 Sublineages Predominated – VISION Network, 10 States, December 2021-June 2022
The Omicron variant (B.1.1.529) of SARS-CoV-2, the virus that causes COVID-19, was first identified in the United States in November 2021, with the BA.1 sublineage (including BA.1.1) causing the largest surge in COVID-19 cases to date. Omicron sublineages BA.2 and BA.2.12.1 emerged later and by late April 2022, accounted for most cases.* Estimates of COVID-19 vaccine effectiveness (VE) can be reduced by newly emerging variants or sublineages that evade vaccine-induced immunity (1), protection from previous SARS-CoV-2 infection in unvaccinated persons (2), or increasing time since vaccination (3). Real-world data comparing VE during the periods when the BA.1 and BA.2/BA.2.12.1 predominated (BA.1 period and BA.2/BA.2.12.1 period, respectively) are limited. The VISION network† examined 214,487 emergency department/urgent care (ED/UC) visits and 58,782 hospitalizations with a COVID-19-like illness§ diagnosis among 10 states during December 18, 2021-June 10, 2022, to evaluate VE of 2, 3, and 4 doses of mRNA COVID-19 vaccines (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) compared with no vaccination among adults without immunocompromising conditions. VE against COVID-19-associated hospitalization 7-119 days and ≥120 days after receipt of dose 3 was 92% (95% CI = 91%-93%) and 85% (95% CI = 81%-89%), respectively, during the BA.1 period, compared with 69% (95% CI = 58%-76%) and 52% (95% CI = 44%-59%), respectively, during the BA.2/BA.2.12.1 period. Patterns were similar for ED/UC encounters. Among adults aged ≥50 years, VE against COVID-19-associated hospitalization ≥120 days after receipt of dose 3 was 55% (95% CI = 46%-62%) and ≥7 days (median = 27 days) after a fourth dose was 80% (95% CI = 71%-85%) during BA.2/BA.2.12.1 predominance. Immunocompetent persons should receive recommended COVID-19 booster doses to prevent moderate to severe COVID-19, including a first booster dose for all eligible persons and second booster dose for adults aged ≥50 years at least 4 months after an initial booster dose. Booster doses should be obtained immediately when persons become eligible.¶.
Authors: Link-Gelles, Ruth; Klein, Nicola P; Fireman, Bruce; Zerbo, Ousseny; Tenforde, Mark W; et al.
MMWR Morb Mortal Wkly Rep. 2022 Jul 22;71(29):931-939. Epub 2022-07-22.
Reach, acceptability, and perceived success of a telehealth diabetes prevention program among racially and ethnically diverse patients with gestational diabetes: the GEM cluster-randomized trial
Patients with gestational diabetes mellitus and from racial/ethnic minority groups face disproportionate risk for type 2 diabetes. Lifestyle interventions, if accessible and acceptable to diverse patients, could advance diabetes prevention and mitigate racial/ethnic disparities. Here we describe overall and race/ethnicity-specific reach, acceptability, and perceived success from an effective telehealth diabetes prevention lifestyle program for patients with gestational diabetes mellitus, implemented in the Gestational Diabetes Effects on Moms (GEM) cluster-randomized controlled trial. GEM tested a program of 13 telephone sessions and behavior change techniques (BCTs, e.g., goal setting) in a healthcare system. We evaluated participation (completing ≥1 session), acceptability of BCTs, and perceived success reaching program goals. Among 1,087 patients (75.2% from minority groups), 50.3% participated. Participation rates were 61.7% among Black, 56.4% among Hispanic, 55.6% among multiracial/other, 53.0% among White, and 43.7% among Asian/Pacific Islander patients. Evaluation survey respondents (n = 433/547; 79.2%) largely rated BCTs as very helpful (range 40.9%-58.4%) or moderately helpful (27.3%-34.9%). Respondents from minority groups largely rated goal setting for weight management as very or moderately helpful, with fewer minority respondents rating it as only a little/not at all helpful than White respondents (p = .02). Black and White respondents reported more limited success reaching a healthy weight than Asian/Pacific Islander, Hispanic, and multiracial/other women (p = .005). A telehealth diabetes prevention lifestyle program demonstrated reach and acceptability across racial/ethnic groups. While perceived success can be improved among Black and White participants, such programs could promote access to preventive care and help mitigate disparities in diabetes risk.
Authors: Brown, Susan D; Hedderson, Monique M; Gordon, Nancy; Albright, Cheryl L; Tsai, Ai-Lin; Quesenberry, Charles P; Ferrara, Assiamira
Transl Behav Med. 2022 Jul 18;12(7):793-799.
Lessons from a mature acellular pertussis vaccination program and strategies to overcome suboptimal vaccine effectiveness
Despite high vaccination coverage among children and adolescents, pertussis remains a public health problem, with large outbreaks occurring periodically in the US and other developed countries. We examine lessons learned more than 20 years after implementation of programs which use only acellular pertussis vaccines and propose avenues for possible effective use of acellular pertussis vaccine to prevent large outbreaks. Acellular pertussis vaccines were introduced more than 20 years ago, yet the incidence of pertussis has been increasing over the past decade, with periodic large outbreaks marked by notable shifts in disease burden from infants and young children toward fully vaccinated adolescents and young adults. This age shift is mainly driven by the waning of vaccine immunity. To better protect adolescents against pertussis, modification of the current acellular pertussis vaccination schedule or adoption of new vaccination strategies should be considered. For infants not yet eligible to be vaccinated, maternal vaccination against pertussis during pregnancy is an effective way to protect infants from infection, severe disease and death. Implementation of maternal vaccination programs should be encouraged in countries without one or efforts to improve coverage should be supported in countries with existing program.
Authors: Zerbo, Ousseny; Fireman, Bruce; Klein, Nicola P
Expert Rev Vaccines. 2022 07;21(7):899-907. Epub 2021-10-08.
A Web-Based mHealth Intervention With Telephone Support to Increase Physical Activity Among Pregnant Patients With Overweight or Obesity: Feasibility Randomized Controlled Trial
Pregnant patients with overweight or obesity are at high risk for perinatal complications. Excess gestational weight gain (GWG) further exacerbates this risk. Mobile health (mHealth) lifestyle interventions that leverage technology to facilitate self-monitoring and provide just-in-time feedback may motivate behavior change to reduce excess GWG, reduce intervention costs, and increase scalability by improving access. This study aimed to test the acceptability and feasibility of a pilot mHealth lifestyle intervention for pregnant patients with overweight or obesity to promote moderate intensity physical activity (PA), encourage guideline-concordant GWG, and inform the design of a larger pragmatic cluster randomized controlled trial. We conducted a mixed methods acceptability and feasibility randomized controlled trial among pregnant patients with a prepregnancy BMI of 25 to 40 kg/m2. Patients with singletons at 8 to 15 weeks of gestation who were aged ≥21 years and had Wi-Fi access were recruited via email from 2 clinics within Kaiser Permanente Northern California and randomized to receive usual prenatal care or an mHealth lifestyle intervention. Participants in the intervention arm received wireless scales, access to an intervention website, activity trackers to receive automated feedback on weight gain and activity goals, and monthly calls from a lifestyle coach. Surveys and focus groups with intervention participants assessed intervention satisfaction and ways to improve the intervention. PA outcomes were self-assessed using the Pregnancy Physical Activity Questionnaire, and GWG was assessed using electronic health record data for both arms. Overall, 33 patients were randomly assigned to the intervention arm, and 35 patients were randomly assigned to the usual care arm. All participants in the intervention arm weighed themselves at least once a week, compared with 20% (7/35) of the participants in the usual care arm. Participants in the intervention arm wore the activity tracker 6.4 days per week and weighed themselves 5.3 times per week, and 88% (29/33) of them rated the program “good to excellent.” Focus groups found that participants desired more nutrition-related support to help them manage GWG and would have preferred an app instead of a website. Participants in the intervention arm had a 23.46 metabolic equivalent of task hours greater change in total PA per week and a 247.2-minute greater change in moderate intensity PA per week in unadjusted models, but these effects were attenuated in adjusted models (change in total PA: 15.55 metabolic equivalent of task hours per week; change in moderate intensity PA: 199.6 minutes per week). We found no difference in total GWG (mean difference 1.14 kg) compared with usual care. The pilot mHealth lifestyle intervention was feasible, highly acceptable, and promoted self-monitoring. Refined interventions are needed to effectively affect PA and GWG among pregnant patients with overweight or obesity. ClinicalTrials.gov NCT03936283; https://clinicaltrials.gov/ct2/show/NCT03936283.
Authors: Thomas, Tainayah; Xu, Fei; Sridhar, Sneha; Sedgwick, Tali; Nkemere, Linda; Badon, Sylvia E; Quesenberry, Charles; Ferrara, Assiamira; Mandel, Sarah; Brown, Susan D; Hedderson, Monique
JMIR Form Res. 2022 Jun 22;6(6):e33929. Epub 2022-06-22.
Risk of severe clinical outcomes among persons with SARS-CoV-2 infection with differing levels of vaccination during widespread Omicron (B.1.1.529) and Delta (B.1.617.2) variant circulation in Northern California: A retrospective cohort study
The incidence of and risk factors for severe clinical outcomes with the Omicron (B.1.1.529) SARS-CoV-2 variant have not been well-defined. We conducted a retrospective cohort study to assess risks of severe clinical outcomes within 21 days after SARS-CoV-2 diagnosis in a large, diverse, integrated health system. Among 118,078 persons with incident SARS-CoV-2 infection, 48,101 (41%) were during the Omicron period and 69,977 (59%) during the Delta (B.1.617.2) period. Cumulative incidence of any hospitalization (2.4% versus 7.8%; adjusted hazard ratio [aHR] 0.55; 95% confidence interval [CI] (0.51-0.59), with low-flow oxygen support (1.6% versus 6.4%; aHR 0.46; CI 0.43-0.50), with high-flow oxygen support (0.6% versus 2.8%; aHR 0.47; CI 0.41-0.54), with invasive mechanical ventilation (0.1% versus 0.7%; aHR 0.43; CI 0.33-0.56), and death (0.2% versus 0.7%; aHR 0.54; CI 0.42-0.70) were lower in the Omicron than the Delta period. The risk of hospitalization was higher among unvaccinated persons (aHR 8.34; CI 7.25-9.60) and those who completed a primary COVID-19 vaccination series (aHR 1.72; CI 1.49-1.97) compared with those who completed a primary vaccination series and an additional dose. The strongest risk factors for all severe clinical outcomes were older age, higher body mass index and select comorbidities. Persons with SARS-CoV-2 infection were significantly less likely to develop severe clinical outcomes during the Omicron period compared with the Delta period. COVID-19 primary vaccination and additional doses were associated with reduced risk of severe clinical outcomes among those with SARS-CoV-2 infection. National Cancer Institute and The Permanente Medical Group.
Authors: Skarbinski, Jacek; Wood, Mariah S; Chervo, Tyler C; Schapiro, Jeffrey M; Elkin, Eric P; Valice, Emily; Amsden, Laura B; Hsiao, Crystal; Quesenberry, Charles; Corley, Douglas A; Kushi, Lawrence H
Lancet Reg Health Am. 2022 Jun 16:100297.
Association of Physician Adenoma Detection Rates With Postcolonoscopy Colorectal Cancer
Although colonoscopy is frequently performed in the United States, there is limited evidence to support threshold values for physician adenoma detection rate as a quality metric. To evaluate the association between physician adenoma detection rate values and risks of postcolonoscopy colorectal cancer and related deaths. Retrospective cohort study in 3 large integrated health care systems (Kaiser Permanente Northern California, Kaiser Permanente Southern California, and Kaiser Permanente Washington) with 43 endoscopy centers, 383 eligible physicians, and 735 396 patients aged 50 to 75 years who received a colonoscopy that did not detect cancer (negative colonoscopy) between January 2011 and June 2017, with patient follow-up through December 2017. The adenoma detection rate of each patient’s physician based on screening examinations in the calendar year prior to the patient’s negative colonoscopy. Adenoma detection rate was defined as a continuous variable in statistical analyses and was also dichotomized as at or above vs below the median for descriptive analyses. The primary outcome (postcolonoscopy colorectal cancer) was tumor registry-verified colorectal adenocarcinoma diagnosed at least 6 months after any negative colonoscopy (all indications). The secondary outcomes included death from postcolonoscopy colorectal cancer. Among 735 396 patients who had 852 624 negative colonoscopies, 440 352 (51.6%) were performed on female patients, median patient age was 61.4 years (IQR, 55.5-67.2 years), median follow-up per patient was 3.25 years (IQR, 1.56-5.01 years), and there were 619 postcolonoscopy colorectal cancers and 36 related deaths during more than 2.4 million person-years of follow-up. The patients of physicians with higher adenoma detection rates had significantly lower risks for postcolonoscopy colorectal cancer (hazard ratio [HR], 0.97 per 1% absolute adenoma detection rate increase [95% CI, 0.96-0.98]) and death from postcolonoscopy colorectal cancer (HR, 0.95 per 1% absolute adenoma detection rate increase [95% CI, 0.92-0.99]) across a broad range of adenoma detection rate values, with no interaction by sex (P value for interaction = .18). Compared with adenoma detection rates below the median of 28.3%, detection rates at or above the median were significantly associated with a lower risk of postcolonoscopy colorectal cancer (1.79 vs 3.10 cases per 10 000 person-years; absolute difference in 7-year risk, -12.2 per 10 000 negative colonoscopies [95% CI, -10.3 to -13.4]; HR, 0.61 [95% CI, 0.52-0.73]) and related deaths (0.05 vs 0.22 cases per 10 000 person-years; absolute difference in 7-year risk, -1.2 per 10 000 negative colonoscopies [95%, CI, -0.80 to -1.69]; HR, 0.26 [95% CI, 0.11-0.65]). Within 3 large community-based settings, colonoscopies by physicians with higher adenoma detection rates were significantly associated with lower risks of postcolonoscopy colorectal cancer across a broad range of adenoma detection rate values. These findings may help inform recommended targets for colonoscopy quality measures.
Authors: Schottinger, Joanne E; Lee, Jeffrey K; Fireman, Bruce H; Quesenberry, Charles P; Corley, Douglas A; et al.
JAMA. 2022 06 07;327(21):2114-2122.
Uptake of guideline-recommended postpartum diabetes screening among diverse women with gestational diabetes: associations with patient factors in an integrated health system in USA
Clinical guidelines urge timely postpartum screening for diabetes among women with gestational diabetes mellitus (GDM), yet patient factors associated with screening uptake remain unclear. We aimed to identify patient factors associated with completed postpartum diabetes screening (2-hour oral glucose tolerance test within 4-12 weeks postpartum), as recommended by the American Diabetes Association (ADA). Within the context of Gestational Diabetes’ Effects on Moms (GEM), a pragmatic cluster randomized trial (2011-2012), we examined survey and electronic health record data to assess clinical and sociodemographic factors associated with uptake of ADA-recommended postpartum screening. Participants included 1642 women (76% racial/ethnic minorities) identified with GDM according to the Carpenter and Coustan criteria in a health system that deploys population-level strategies to promote screening. To contextualize these analyses, screening rates derived from the GEM trial were compared with those in the health system overall using registry data from a concurrent 10-year period (2007-2016, n=21 974). Overall 52% (n=857) completed recommended postpartum screening in the analytic sample, comparable to 45.7% (n=10 040) in the registry. Screening in the analytic sample was less likely among women at elevated risk for type 2 diabetes, assessed using items from an ADA risk test (vs non-elevated; adjusted rate ratio (aRR)=0.86 (95% CI 0.75 to 0.98)); perinatal depression (0.88 (0.79 to 0.98)); preterm delivery (0.84 (0.72 to 0.98)); parity ≥2 children (vs 0; 0.80 (0.69 to 0.93)); or less than college education (0.79 (0.72 to 0.86)). Screening was more likely among Chinese Americans (vs White; 1.31 (1.15 to 1.49)); women who attended a routine postpartum visit (5.28 (2.99 to 9.32)); or women who recalled receiving healthcare provider advice about screening (1.31 (1.03 to 1.67)). Guideline-recommended postpartum diabetes screening varied by patient clinical and sociodemographic factors. Findings have implications for developing future strategies to improve postpartum care.
Authors: Brown, Susan D; Hedderson, Monique M; Zhu, Yeyi; Tsai, Ai-Lin; Feng, Juanran; Quesenberry, Charles P; Ferrara, Assiamira
BMJ Open Diabetes Res Care. 2022 06;10(3).
Effect of Electronic and Mail Outreach From Primary Care Physicians for COVID-19 Vaccination of Black and Latino Older Adults: A Randomized Clinical Trial
COVID-19 morbidity is highest in Black and Latino older adults. These racial and ethnic groups initially had lower vaccination uptake than others, and rates in Black adults continue to lag. To evaluate the effect of outreach via electronic secure messages and mailings from primary care physicians (PCPs) on COVID-19 vaccination uptake among Black and Latino older adults and to compare the effects of culturally tailored and standard PCP messages. This randomized clinical trial was conducted from March 29 to May 20, 2021, with follow-up surveys through July 31, 2021. Latino and Black individuals aged 65 years and older from 4 Kaiser Permanente Northern California (KPNC) service areas were included. Data were analyzed from May 27, 2021, to September 28, 2021. Individuals who had not received COVID-19 vaccination after previous outreach were randomized to electronic secure message and/or mail outreach from their PCP, similar outreach with additional culturally tailored content, or usual care. Outreach groups were sent a secure message or letter in their PCP’s name, followed by a postcard to those still unvaccinated after 4 weeks. The primary outcome was time to receipt of COVID-19 vaccination during the 8 weeks after initial study outreach. KPNC data were supplemented with state data from external sources. Intervention effects were evaluated via proportional hazards regression. Of 8287 included individuals (mean [SD] age, 72.6 [7.0] years; 4665 [56.3%] women), 2434 (29.4%) were Black, 3782 (45.6%) were Latino and preferred English-language communications, and 2071 (25.0%) were Latino and preferred Spanish-language communications; 2847 participants (34.4%) had a neighborhood deprivation index at the 75th percentile or higher. A total of 2767 participants were randomized to culturally tailored PCP outreach, 2747 participants were randomized to standard PCP outreach, and 2773 participants were randomized to usual care. Culturally tailored PCP outreach led to higher COVID-19 vaccination rates during follow-up compared with usual care (664 participants [24.0%] vs 603 participants [21.7%]; adjusted hazard ratio (aHR), 1.22; 95% CI, 1.09-1.37), as did standard PCP outreach (635 participants [23.1%]; aHR, 1.17; 95% CI, 1.04-1.31). Individuals who were Black (aHR, 1.19; 95% CI, 1.06-1.33), had high neighborhood deprivation (aHR, 1.17; 95% CI, 1.03-1.33), and had medium to high comorbidity scores (aHR, 1.19; 95% CI, 1.09-1.31) were more likely to be vaccinated during follow-up. This randomized clinical trial found that PCP outreach using electronic and mailed messages increased COVID-19 vaccination rates among Black and Latino older adults. ClinicalTrials.gov Identifier: NCT05096026.
Authors: Lieu, Tracy A; Klein, Nicola P; Quesenberry, Charles P; Chen, Yi-Fen Irene; et al.
JAMA Netw Open. 2022 Jun 01;5(6):e2217004. Epub 2022-06-01.
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.
Perspectives on Postpartum Diabetes Screening among Patients with Gestational Diabetes in an Integrated Healthcare System
Authors: Glaser, Katherine; Ferrara, Assiamira; Ritchie, Jenna L; Tsai, Ai-Lin; Greenberg, Mara; Quesenberry, Charles P; Brown, Susan D
Am J Obstet Gynecol. 2022 06;226(6):857-859.e1. Epub 2022-02-12.
Predicting obstructive sleep apnea severity in children referred for polysomnography: use of the Pediatric Sleep Questionnaire and Subscales
This study evaluated the role of the Pediatric Sleep Questionnaire (PSQ) and associated subscales in predicting the severity of obstructive sleep apnea (OSA) in children referred for attended polysomnography (PSG). This is a retrospective study of children (0-18 years) who completed PSQs the night of their initial diagnostic PSG (2019-2020). We excluded children with previous PSG, positive airway pressure titrations, or underlying genetic or craniofacial syndromes. Area under the receiver operating characteristic curve (AUC [95%CIs]) were estimated for prediction of varying severities of obstructive apnea-hypopnea index (oAHI > 2, 5, 10, and 25/h) by the PSQ’s sleep-related breathing disorders (SRBD) scale and subscales. Of 477 children, median (IQR) age at PSG was 5.7 (4.3); 60% of children were male, 21% were obese, and 4% had oAHI > 25/h. SRBD score did not improve discrimination of OSA cases at any oAHI threshold, with AUC CI that crossed 50% at all severities. Snoring subscale scores were predictive at oAHI > 2/h (AUC = 64.5% [59.5-69.5%]), oAHI > 5/h (AUC = 64.3% [59.6-69.0%]), and oAHI > 10 (AUC = 67.2% [62.0-72.4%]) thresholds, but were not predictive at oAHI > 25/h. The addition of demographic data (age and gender) improved the classification of the SRBD scale. When utilized in children referred for attended PSG due to concerns for an underlying sleep disorder, the PSQ snoring subscale was more predictive of OSA at varying thresholds than the SRBD scale. While the original intent of the PSQ was not for the purpose of predicting severity in children referred for PSG, future directions include augmenting the questionnaire with additional clinical variables.
Authors: Bseikri, Mustafa; Zhang, Jie; Kirley, Jocelyn; Lee, Catherine; Castillo, Adrienne; Feliciano, Elizabeth M Cespedes
Sleep Breath. 2022 May 28.
Risk of Cardiovascular Disease in Women With and Without Breast Cancer: The Pathways Heart Study
To examine cardiovascular disease (CVD) and mortality risk in women with breast cancer (BC) by cancer therapy received relative to women without BC. The study population comprised Kaiser Permanente Northern California members. Cases with invasive BC diagnosed from 2005 to 2013 were matched 1:5 to controls without BC on birth year and race/ethnicity. Cancer treatment, CVD outcomes, and covariate data were from electronic health records. Multivariable Cox proportional hazards models estimated hazard ratios (HRs) and 95% CIs of CVD incidence and mortality by receipt of chemotherapy treatment combinations, radiation therapy, and endocrine therapy. A total of 13,642 women with BC were matched to 68,202 controls without BC. Over a 7-year average follow-up (range < 1-14 years), women who received anthracyclines and/or trastuzumab had high risk of heart failure/cardiomyopathy relative to controls, with the highest risk seen in women who received both anthracyclines and trastuzumab (HR, 3.68; 95% CI, 1.79 to 7.59). High risk of heart failure and/or cardiomyopathy was also observed in women with BC with a history of radiation therapy (HR, 1.38; 95% CI, 1.13 to 1.69) and aromatase inhibitor use (HR, 1.31; 95% CI, 1.07 to 1.60), relative to their controls. Elevated risks for stroke, arrhythmia, cardiac arrest, venous thromboembolic disease, CVD-related death, and death from any cause were also observed in women with BC on the basis of cancer treatment received. Women with BC had increased incidence of CVD events, CVD-related mortality, and all-cause mortality compared with women without BC, and risks varied according to the history of cancer treatment received. Studies are needed to determine how women who received BC treatment should be cared for to improve cardiovascular outcomes.
Authors: Greenlee, Heather; Rana, Jamal S; Cheng, Richard; Rillamas-Sun, Eileen; Neugebauer, Romain; Kwan, Marilyn L; Kwan, Marilyn L; et al.
J Clin Oncol. 2022 05 20;40(15):1647-1658. Epub 2022-04-06.
Risk of Cardiometabolic Risk Factors in Women With and Without a History of Breast Cancer: The Pathways Heart Study
The incidence of cardiometabolic risk factors in breast cancer (BC) survivors has not been well described. Thus, we compared risk of hypertension, diabetes, and dyslipidemia in women with and without BC. Women with invasive BC diagnosed from 2005 to 2013 at Kaiser Permanente Northern California (KPNC) were identified and matched 1:5 to noncancer controls on birth year, race, and ethnicity. Cumulative incidence rates of hypertension, diabetes, and dyslipidemia were estimated with competing risk of overall death. Subdistribution hazard ratios (sHRs) were estimated by Fine and Gray regression, adjusted for cardiovascular disease-related risk factors, and stratified by treatment and body mass index (BMI). A total of 14,942 BC cases and 74,702 matched controls were identified with mean age 61.2 years and 65% non-Hispanic White. Compared with controls, BC cases had higher cumulative incidence rates of hypertension (10.9% v 8.9%) and diabetes (2.1% v 1.7%) after 2 years, with higher diabetes incidence persisting after 10 years (9.3% v 8.8%). In multivariable models, cases had higher risk of diabetes (sHR, 1.16; 95% CI, 1.07 to 1.26) versus controls. Cases treated with chemotherapy (sHR, 1.23; 95% CI, 1.11 to 1.38), left-sided radiation (sHR, 1.29; 95% CI, 1.13 to 1.48), or endocrine therapy (sHR, 1.23; 95% CI, 1.12 to 1.34) continued to have higher diabetes risk. Hypertension risk was higher for cases receiving left-sided radiation (sHR, 1.11; 95% CI, 1.02 to 1.21) or endocrine therapy (sHR, 1.10; 95% CI, 1.03 to 1.16). Normal-weight (BMI < 24.9 kg/m2) cases had higher risks overall and within treatment subgroups versus controls. BC survivors at KPNC experienced elevated risks of diabetes and hypertension compared with women without BC depending on treatments received and BMI. Future studies should examine strategies for cardiometabolic risk factor prevention in BC survivors.
Authors: Kwan, Marilyn L; Iribarren, Carlos; Neugebauer, Romain; Rana, Jamal S; Nguyen-Huynh, Mai; Kushi, Lawrence H; Greenlee, Heather; et al.
J Clin Oncol. 2022 05 20;40(15):1635-1646. Epub 2022-01-13.
Exploratory analysis of novel electronic health record variables for quantification of healthcare delivery strain, prediction of mortality, and prediction of imminent discharge
To explore the relationship between novel, time-varying predictors for healthcare delivery strain (eg, counts of patient orders per hour) and imminent discharge and in-hospital mortality. We conducted a retrospective cohort study using data from adults hospitalized at 21 Kaiser Permanente Northern California hospitals between November 1, 2015 and October 31, 2020 and the nurses caring for them. Patient data extracted included demographics, diagnoses, severity measures, occupancy metrics, and process of care metrics (eg, counts of intravenous drip orders per hour). We linked these data to individual registered nurse records and created multiple dynamic, time-varying predictors (eg, mean acute severity of illness for all patients cared for by a nurse during a given hour). All analyses were stratified by patients’ initial hospital unit (ward, stepdown unit, or intensive care unit). We used discrete-time hazard regression to assess the association between each novel time-varying predictor and the outcomes of discharge and mortality, separately. Our dataset consisted of 84 162 161 hourly records from 954 477 hospitalizations. Many novel time-varying predictors had strong associations with the 2 study outcomes. However, most of the predictors did not merely track patients’ severity of illness; instead, many of them only had weak correlations with severity, often with complex relationships over time. Increasing availability of process of care data from automated electronic health records will permit better quantification of healthcare delivery strain. This could result in enhanced prediction of adverse outcomes and service delays. New conceptual models will be needed to use these new data elements.
Authors: Lee, Catherine; Lawson, Brian L; Mann, Ariana J; Liu, Vincent X; Myers, Laura C; Schuler, Alejandro; Escobar, Gabriel J
J Am Med Inform Assoc. 2022 05 11;29(6):1078-1090.
Effect of Lifestyle Coaching or Enhanced Pharmacotherapy on Blood Pressure Control Among Black Adults With Persistent Uncontrolled Hypertension: A Cluster Randomized Clinical Trial
Greater difficulty in controlling blood pressure (BP) and adverse lifestyle practices such as higher salt intake or less physical activity may account for some of the differences between BP control rates in Black vs White adults, thereby exposing Black adults to a higher risk of vascular events. To determine whether a lifestyle coaching intervention or an enhanced pharmacotherapy protocol is more effective than usual care in improving BP control rates in Black adults treated within an integrated health care delivery system. Shake, Rattle & Roll, a cluster randomized clinical trial, was conducted from June 5, 2013, to June 11, 2018, in a large integrated health care delivery system. Enrollment was completed during a 12-month period and interventions were implemented for 12 months. Follow-up lasted 48 months after enrollment. Panels of Black adult members of the health care delivery system with BP of at least 140/90 mm Hg from 98 adult primary care physicians were randomly assigned at the primary care physician level to usual care (UC group [n = 1129]), enhanced pharmacotherapy monitoring (EP group [n = 346]) of current BP management protocol, or diet and lifestyle coaching consisting of photographs, stories, and recipes, for example, that are appropriate for Black adults (LC group [n = 286]) focused on the Dietary Approaches to Stop Hypertension (DASH) diet. Data were analyzed from June 1, 2016, to March 25, 2022. The UC group received care per customary protocol. The EP group was contacted by a research nurse and/or a clinical pharmacist to discuss barriers to hypertension control, and drug therapy emphasized the use of thiazide diuretic intensification and addition of spironolactone as needed. The LC group received as many as 16 telephone sessions with a lifestyle coach and an emphasis on implementing reduction of sodium intake and the DASH diet. Intention-to-treat analysis of BP control rates at end of the 12-month intervention. Among the 1761 participants, the mean (SD) age was 61 (13) years, and 1214 (68.9%) were women. At the end of the 12-month intervention period, there was no significant difference in BP control rate among study groups (UC, 61.8% [95% CI, 58.8%-64.9%]; EP, 64.5% [95% CI, 59.0%-69.4%]; LC, 67.8% [95% CI, 62.1%-73.2%]; LC vs EP, P = .07). However, greater BP control was present in the LC group vs UC at 24 months (UC, 61.2% [95% CI, 57.3%-64.7%]; EP, 67.6% [95% CI, 61.9%-72.8%]; LC, 72.4% [95% CI, 66.9%-78.1%]; LC vs UC, P = .001), and 48 months (UC, 64.5% [95% CI, 61.6%-67.2%]; EP, 66.5% [95% CI, 61.3%-71.3%]; LC, 73.1% [95% CI, 67.6%-77.9%]; LC vs UC, P = .006) after enrollment. The contribution of BP medication adherence to explain group differences was inconclusive. In this cluster randomized clinical trial including Black adults with persistent uncontrolled hypertension, a 12-month LC intervention was more effective at controlling BP than UC at 24 and 48 months after enrollment. Further research is needed to explore the potential implementation of this intervention into clinical practice. ClinicalTrials.gov Identifier: NCT01892592.
Authors: Nguyen-Huynh, Mai N; Young, Joseph D; Ovbiagele, Bruce; Alexander, Janet G; Alexeeff, Stacey; Lee, Catherine; Blick, Noelle; Caan, Bette J; Go, Alan S; Sidney, Stephen
JAMA Netw Open. 2022 May 02;5(5):e2212397. Epub 2022-05-02.
Contribution of Maternal Cardiometabolic Risk Factors to Racial-Ethnicity Disparities in Preterm Birth Subtypes
There are recognized racial-ethnic disparities in preterm birth and in maternal cardiometabolic risk factors likely linked to systemic racism. However, it is unclear the extent to which cardiometabolic risk factors contribute to the higher rates of preterm birth among minoritized populations. This study aimed to evaluate racial-ethnic disparities in preterm birth subtypes and the role of maternal cardiometabolic risk factors as mediators of the association between maternal race-ethnicity and preterm birth subtypes. This was a retrospective cohort study of 295,210 singleton live births from 2011 to 2018. Preterm birth subtypes were defined as medically indicated and spontaneous preterm birth. Poisson regression with robust standard errors were used to provide estimates of the relative risks and 95% confidence intervals for preterm birth subtypes. Causal mediation analysis used logistic regression models to estimate the natural direct and natural indirect (mediated) effects of maternal cardiometabolic risk factors. Compared with White individuals, Black, Asian, and Hispanic individuals were at increased risk for having both medically indicated preterm birth (1.45, 1.30-1.61; 1.21, 1.12-1.31; and 1.13, 1.05-1.22, respectively) (risk ratios, 95% confidence intervals, respectively) and spontaneous preterm birth (1.20, 1.08-1.34; 1.34, 1.26-1.43; and 1.16, (1.08-1.23), independent of established risk factors. The extent to which cardiometabolic risk factors mediated the associations between race-ethnicity (each group vs White in separate analyses) and preterm birth subtypes varied by race-ethnicity. Hypertensive disorders mediated 30.1% of the association between Black race-ethnicity and medically indicated preterm birth, but it did not mediate the association for other racial-ethnic groups or for spontaneous preterm birth. Any glucose disorder in pregnancy was a mediator of medically indicated preterm birth and spontaneous preterm birth for Asian (65.8% and 13.9%, respectively) and Hispanic (17.3% and 11.9%) race-ethnicity but not for Black race-ethnicity. Overweight or obesity mediated the association between race-ethnicity and medically indicated preterm birth (15.5% among Black individuals and 25.1% among Hispanic individuals) and spontaneous preterm birth (10.7% among Hispanic individuals) but was not a mediator among Asian individuals. Black, Asian, and Hispanic individuals are at increased risk for preterm birth. Maternal cardiometabolic risk factors partially mediate the associations between race-ethnicity and preterm birth subtypes but the extent varies by race-ethnicity. These findings suggest that strategies that improve and diminish differences in cardiometabolic health between race-ethnicity populations may diminish disparities in preterm birth.
Authors: Hedderson, Monique M; Xu, Fei; Dayo, Olumayowa M; Liu, Emily; Sridhar, Sneha; Lee, Catherine; Greenberg, Mara
Am J Obstet Gynecol MFM. 2022 05;4(3):100608. Epub 2022-03-04.
Association between residential green cover and direct healthcare costs in Northern California: An individual level analysis of 5 million persons
Prior studies have shown higher green cover levels are associated with beneficial health outcomes. We sought to determine if residential green cover was also associated with direct healthcare costs. We linked residential Normalized Difference Vegetation Index (NDVI) satellite data for 5,189,303 members of Kaiser Permanente Northern California (KPNC) to direct individual healthcare costs for 2003-2015. Using generalized linear regression to adjust for confounding, we examined the association between direct healthcare costs and green cover within250, 500, and 1000 meters (m) of an individual’s residence. Costs were determined from an internal cost accounting system that captures administrative and patient care costs for each clinical encounter. Sensitivity analyses included adjustments for comorbidity and an alternative measure of green cover, tree canopy. We observed a significant inverse association between higher levels of residential green cover and lower direct healthcare costs. The relative rate of total cost for the highest compared to the lowest decile of NDVI was 0.92 (95% CI 0.90-0.93) for the 500 m buffer. The association was robust to adjustment from a broad array of confounders, found at each buffer size, and largely driven by hospitalization, and emergency department visits. Individuals in the top decile of residential green cover had adjusted healthcare costs of $374.04 (95% CI $307.31-$439.41) per person per year less than individuals living in the bottom or least green decile. Sensitivity analyses including tree canopy cover as the green space measure yielded similar findings. Analyses that included adjustment for comorbidity were consistent with the hypothesis that green cover reduces healthcare costs by improving health status. Green cover was associated with lower direct healthcare costs, raising the possibility that residential greening can have a significant healthcare cost impact across the population.
Authors: Van Den Eeden, Stephen K; H E M Browning, Matthew; Becker, Douglas A; Shan, Jun; Alexeeff, Stacey E; Thomas Ray, G; Quesenberry, Charles P; Kuo, Ming
Environ Int. 2022 05;163:107174. Epub 2022-03-17.
Perinatal Complications in Individuals in California With or Without SARS-CoV-2 Infection During Pregnancy
Additional research from population-based studies is needed to inform the treatment of SARS-CoV-2 infection during pregnancy and to provide health risk information to pregnant individuals. To assess the risk of perinatal complications associated with SARS-CoV-2 infection and to describe factors associated with hospitalizations. This population-based cohort study included 43 886 pregnant individuals with longitudinal electronic health record data from preconception to delivery who delivered at Kaiser Permanente Northern California between March 1, 2020, and March 16, 2021. Individuals with diagnostic codes for COVID-19 that did not have a confirmatory polymerase chain reaction test for SARS-CoV-2 were excluded. SARS-CoV-2 infection detected by polymerase chain reaction test (from 30 days before conception to 7 days after delivery) as a time varying exposure. Severe maternal morbidity including 21 conditions (eg, acute myocardial infarction, acute renal failure, acute respiratory distress syndrome, and sepsis) that occurred at any time during pregnancy or delivery; preterm birth; pregnancy hypertensive disorders; gestational diabetes; venous thromboembolism (VTE); stillbirth; cesarean delivery; and newborn birth weight and respiratory conditions. Standardized mean differences between individuals with and without SARS-CoV-2 were calculated. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% CIs for the association between SARS-CoV-2 infection and perinatal complications and hospitalization and to consider the timing of SARS-CoV-2 infection relative to outcomes. In this study of 43 886 pregnant individuals (mean [SD] age, 30.7 [5.2] years), individuals with a SARS-CoV-2 infection (1332 [3.0%]) were more likely to be younger, Hispanic, multiparous individuals with a higher neighborhood deprivation index and obesity or chronic hypertension. After adjusting for demographic characteristics, comorbidities, and smoking status, individuals with SARS-CoV-2 infection had higher risk for severe maternal morbidity (HR, 2.45; 95% CI, 1.91-3.13), preterm birth (<37 weeks; HR, 2.08; 95% CI, 1.75-2.47), and VTE (HR, 3.08; 95% CI, 1.09-8.74) than individuals without SARS-CoV-2. SARS-CoV-2 infection was also associated with increased risk of medically indicated preterm birth (HR, 2.56; 95% CI, 2.06-3.19); spontaneous preterm birth (HR, 1.61; 95% CI, 1.22-2.13); and early (HR, 2.52; 95% CI, 1.49-4.24), moderate (HR, 2.18; 95% CI, 1.25-3.80), and late (HR, 1.95; 95% CI, 1.61-2.37) preterm birth. Among individuals with SARS-CoV-2 infection, 76 (5.7%) had a hospitalization; pregestational diabetes (HR, 7.03; 95% CI, 2.22-22.2) and Asian or Pacific Islander (HR, 2.33; 95% CI, 1.06-5.11) and Black (HR, 3.14; 95% CI, 1.24-7.93) race and ethnicity were associated with an increased risk of hospitalization. In this cohort study, SARS-CoV-2 infection was associated with increased risk of severe maternal morbidity, preterm birth, and VTE. The study findings inform clinicians and patients about the risk of perinatal complications associated with SARS-CoV-2 infection in pregnancy and support vaccination of pregnant individuals and those planning conception.
Authors: Ferrara, Assiamira; Hedderson, Monique M; Zhu, Yeyi; Avalos, Lyndsay A; Kuzniewicz, Michael W; Myers, Laura C; Ngo, Amanda L; Gunderson, Erica P; Ritchie, Jenna L; Quesenberry, Charles P; Greenberg, Mara
JAMA Intern Med. 2022 05 01;182(5):503-512.
Safety of measles and pertussis-containing vaccines in children with autism spectrum disorders
To determine whether children aged 4-7 years with a diagnosis of autism spectrum disorders (ASD) were at increased risk of fever, febrile seizures, or emergency department (ED) visits following measles- or pertussis-containing vaccines compared with children without ASD. The study included children born between 1995-2012, aged 4-7 years at vaccination, and members of six healthcare delivery systems within Vaccine Safety Datalink. We conducted self-controlled risk interval analyses comparing rates of outcomes in risk and control intervals within each group defined by ASD status, and then compared outcome rates between children with and without ASD, in risk and control intervals, by estimating difference-in-differences using logistic regressions. The study included 14,947 children with ASD and 1,650,041 children without ASD. After measles- or pertussis-containing vaccination, there were no differences in association between children with and without ASD for fever (ratio of rate ratio for measles-containing vaccine = 1.07, 95% CI 0.58-1.96; for pertussis-containing vaccine = 1.16, 95% CI 0.63-2.15) or ED visits (ratio of rate ratio for measles-containing vaccine = 1.11, 95% CI 0.80-1.54; for pertussis-containing vaccine = 0.87, 95% CI 0.59-1.28). Febrile seizures were rare. Pertussis-containing vaccines were associated with small increased risk of febrile seizures in children without ASD. Children with ASD were not at increased risk for fever or ED visits compared with children without ASD following measles- or pertussis-containing vaccines. These results may provide further reassurance that these vaccines are safe for all children, including those with ASD.
Authors: Zerbo, Ousseny; Fireman, Bruce; Klein, Nicola P; et al.
Vaccine. 2022 04 20;40(18):2568-2573. Epub 2022-03-18.
Incidence of Guillain-Barré Syndrome After COVID-19 Vaccination in the Vaccine Safety Datalink
Postauthorization monitoring of vaccines in a large population may detect rare adverse events not identified in clinical trials such as Guillain-Barré syndrome (GBS), which has a background rate of 1 to 2 per 100 000 person-years. To describe cases and incidence of GBS following COVID-19 vaccination and assess the risk of GBS after vaccination for Ad.26.COV2.S (Janssen) and mRNA vaccines. This cohort study used surveillance data from the Vaccine Safety Datalink at 8 participating integrated health care systems in the United States. There were 10 158 003 participants aged at least 12 years. Data analysis was performed from November 2021 to February 2022. Ad.26.COV2.S, BNT162b2 (Pfizer-BioNTech), or mRNA-1273 (Moderna) COVID-19 vaccine, including mRNA vaccine doses 1 and 2, December 13, 2020, to November 13, 2021. GBS with symptom onset in the 1 to 84 days after vaccination, confirmed by medical record review and adjudication. Descriptive characteristics of confirmed cases, GBS incidence rates during postvaccination risk intervals after each type of vaccine compared with the background rate, rate ratios (RRs) comparing GBS incidence in the 1 to 21 vs 22 to 42 days postvaccination, and RRs directly comparing risk of GBS after Ad.26.COV2.S vs mRNA vaccination, using Poisson regression adjusted for age, sex, race and ethnicity, site, and calendar day. From December 13, 2020, through November 13, 2021, 15 120 073 doses of COVID-19 vaccines were administered to 7 894 989 individuals (mean [SE] age, 46.5 [0.02] years; 8 138 318 doses received [53.8%] by female individuals; 3 671 199 doses received [24.3%] by Hispanic or Latino individuals, 2 215 064 doses received [14.7%] by Asian individuals, 6 266 424 doses received [41.4%] by White individuals), including 483 053 Ad.26.COV2.S doses, 8 806 595 BNT162b2 doses, and 5 830 425 mRNA-1273 doses. Eleven cases of GBS after Ad.26.COV2.S were confirmed. The unadjusted incidence rate of GBS per 100 000 person-years in the 1 to 21 days after Ad.26.COV2.S was 32.4 (95% CI, 14.8-61.5), significantly higher than the background rate, and the adjusted RR in the 1 to 21 vs 22 to 42 days following Ad.26.COV2.S was 6.03 (95% CI, 0.79-147.79). Thirty-six cases of GBS after mRNA vaccines were confirmed. The unadjusted incidence rate per 100 000 person-years in the 1 to 21 days after mRNA vaccines was 1.3 (95% CI, 0.7-2.4) and the adjusted RR in the 1 to 21 vs 22 to 42 days following mRNA vaccines was 0.56 (95% CI, 0.21-1.48). In a head-to-head comparison of Ad.26.COV2.S vs mRNA vaccines, the adjusted RR was 20.56 (95% CI, 6.94-64.66). In this cohort study of COVID-19 vaccines, the incidence of GBS was elevated after receiving the Ad.26.COV2.S vaccine. Surveillance is ongoing.
Authors: Hanson, Kayla E; Fireman, Bruce; Klein, Nicola P; et al.
JAMA Netw Open. 2022 Apr 01;5(4):e228879. Epub 2022-04-01.
Joint associations between neighborhood walkability, greenness, and particulate air pollution on cardiovascular mortality among adults with a history of stroke or acute myocardial infarction
Fine particulate matter (PM2.5) is a known risk factor for cardiovascular disease (CVD). Neighborhood walkability and greenness may also be associated with CVD, but there is limited evidence on their joint or interacting effects with PM2.5. Cox proportional hazard models were used to estimate the risk of CVD mortality among adults with a history of acute myocardial infarction and/or stroke living in Northern California. We assessed the independent and joint effects of walkability, greenness (Normalized Differentiated Vegetation Index [NDVI]), and PM2.5 at residential addresses, controlling for age, sex, race/ethnicity, comorbidities, BMI, smoking, revascularization, medications, and socioeconomic status. Greenness had a nonlinear association with CVD mortality (P = 0.038), with notably protective effects (HR = 0.87 [95% confidence interval {CI} = 0.78, 0.97]) at higher greenness levels (NDVI ≥ 0.3) and moderate attenuation after adjusting for PM2.5 (HR = 0.92 [95% CI = 0.82, 1.03]) per 0.1 increase in NDVI. Walkability had no independent effect on CVD mortality. PM2.5 had a strong independent effect in models adjusted for greenness and walkability (HR = 1.20 [95% CI = 1.08, 1.33)) per 10 μg/m3 increase in PM2.5. There was an interaction between walkability and PM2.5 (P = 0.037), where PM2.5 had slightly stronger associations in more walkable than less walkable neighborhoods (HR = 1.23 [95% CI = 1.06, 1.42] vs. 1.17 [95% CI = 1.04, 1.32]) per 10 μg/m3 increase in PM2.5. Greenness had no interaction with PM2.5 (P = 0.768) nor walkability (P = 0.385). High greenness may be protective of CVD mortality among adults with CVD history. PM2.5 associated CVD mortality risk varies slightly by level of neighborhood walkability, though these small differences may not be clinically meaningful.
Authors: Liao NS; Van Den Eeden SK; Sidney S; Deosaransingh K; Schwartz J; Uong SP; Alexeeff SE
Environ Epidemiol. 2022 Apr;6(2):e200. Epub 2022-02-18.
Effectiveness of Homologous and Heterologous COVID-19 Booster Doses Following 1 Ad.26.COV2.S (Janssen [Johnson & Johnson]) Vaccine Dose Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults – VISION Network, 10 States, December 2021-March 2022
CDC recommends that all persons aged ≥18 years receive a single COVID-19 vaccine booster dose ≥2 months after receipt of an Ad.26.COV2.S (Janssen [Johnson & Johnson]) adenovirus vector-based primary series vaccine; a heterologous COVID-19 mRNA vaccine is preferred over a homologous (matching) Janssen vaccine for booster vaccination. This recommendation was made in light of the risks for rare but serious adverse events following receipt of a Janssen vaccine, including thrombosis with thrombocytopenia syndrome and Guillain-Barré syndrome† (1), and clinical trial data indicating similar or higher neutralizing antibody response following heterologous boosting compared with homologous boosting (2). Data on real-world vaccine effectiveness (VE) of different booster strategies following a primary Janssen vaccine dose are limited, particularly during the period of Omicron variant predominance. The VISION Network§ determined real-world VE of 1 Janssen vaccine dose and 2 alternative booster dose strategies: 1) a homologous booster (i.e., 2 Janssen doses) and 2) a heterologous mRNA booster (i.e., 1 Janssen dose/1 mRNA dose). In addition, VE of these booster strategies was compared with VE of a homologous booster following mRNA primary series vaccination (i.e., 3 mRNA doses). The study examined 80,287 emergency department/urgent care (ED/UC) visits¶ and 25,244 hospitalizations across 10 states during December 16, 2021-March 7, 2022, when Omicron was the predominant circulating variant.** VE against laboratory-confirmed COVID-19-associated ED/UC encounters was 24% after 1 Janssen dose, 54% after 2 Janssen doses, 79% after 1 Janssen/1 mRNA dose, and 83% after 3 mRNA doses. VE for the same vaccination strategies against laboratory-confirmed COVID-19-associated hospitalizations were 31%, 67%, 78%, and 90%, respectively. All booster strategies provided higher protection than a single Janssen dose against ED/UC visits and hospitalizations during Omicron variant predominance. Vaccination with 1 Janssen/1 mRNA dose provided higher protection than did 2 Janssen doses against COVID-19-associated ED/UC visits and was comparable to protection provided by 3 mRNA doses during the first 120 days after a booster dose. However, 3 mRNA doses provided higher protection against COVID-19-associated hospitalizations than did other booster strategies during the same time interval since booster dose. All adults who have received mRNA vaccines for their COVID-19 primary series vaccination should receive an mRNA booster dose when eligible. Adults who received a primary Janssen vaccine dose should preferentially receive a heterologous mRNA vaccine booster dose ≥2 months later, or a homologous Janssen vaccine booster dose if mRNA vaccine is contraindicated or unavailable. Further investigation of the durability of protection afforded by different booster strategies is warranted.
Authors: Natarajan, Karthik; Klein, Nicola P; Fireman, Bruce; Zerbo, Ousseny; Dixon, Brian E; et al.
MMWR Morb Mortal Wkly Rep. 2022 Apr 01;71(13):495-502. Epub 2022-04-01.
Primary care telemedicine during the COVID-19 pandemic: patient’s choice of video versus telephone visit
The aim of this study is to examine the association between patient characteristics and primary care telemedicine choice among integrated delivery system patients self-scheduling visits during the COVID-19 pandemic. We used multivariate logistic regression to examine the association between the choice of video versus telephone and patient sociodemographic characteristics and technology access among patient-initiated primary care telemedicine visits scheduled online from March to October 2020. Among 978 272 patient-scheduled primary care telemedicine visits, 39% were video visits. Patients of Black or Hispanic race/ethnicity, or living in low socioeconomic status or low internet access neighborhoods were less likely to schedule video visits. Patients 65 years or older, with prior video visit experience or mobile portal access, or visiting their own personal provider were more likely to schedule video visits. While video adoption was substantial in all patient groups examined, differences in telemedicine choice suggest the persistence of a digital divide, emphasizing the importance of maintaining a telephone telemedicine option.
Authors: Huang, Jie; Graetz, Ilana; Millman, Andrea; Gopalan, Anjali; Lee, Catherine; Muelly, Emilie; Reed, Mary E
JAMIA Open. 2022 Apr;5(1):ooac002. Epub 2022-01-19.
Association of teledermatology workflows with standardising co-management of rashes by primary care physicians and dermatologists
For patients with a rash, the effect of teledermatology workflow on utilization has not been defined. We compared utilization across four teledermatology workflows in patients with a rash. The observational longitudinal cohort study included 28,857 Kaiser Permanente Northern California members with a new rash diagnosis seen in primary care and with dermatology advice obtained using teledermatology. The workflows differed in camera and image quality; who took the picture; how the image was forwarded; and synchronicity and convenience. On average, 23% of patients had a follow-up office visit in dermatology within 90 days of their primary care visit. In multivariable analysis, the four technologies differed substantially in the likelihood of a follow-up dermatology office visit. In contrast, the likelihood was only negligibly related to medical centre or primary care provider. Technologies and workflows that offer the mobility of a smartphone with a high level of synchronicity in communication were associated with standardised co-management of rashes.
Authors: Dusendang JR; Marwaha S; Alexeeff SE; Crowley E; Haiman M; Pham N; Tuerk MJ; Wudka D; Hartmann M; Herrinton LJ
J Telemed Telecare. 2022 Apr;28(3):182-187. Epub 2020-06-26.
Associations between infant growth and pubertal onset timing in a multiethnic prospective cohort of girls
Early puberty increases risk of adverse health conditions throughout the life course. US girls are experiencing earlier puberty without clear reasons. Studies suggest early life factors, such as infant growth, may influence pubertal timing. We assessed the associations between infant growth and onset of breast development (thelarche), pubic hair development (pubarche), and menarche in girls. A prospective cohort of girls born at a Kaiser Permanente Northern California medical facility in 2005-11 was used. Weight-for-age z-scores were calculated at birth and 24 months. Difference in z-scores greater than 0.67 represent rapid “catch-up” growth, less than -0.67 represent delayed “catch-down” growth, and between -0.67 and 0.67 represent “normal” growth. Pubertal onset was measured using clinician-assessed sexual maturity ratings (SMRs) and defined as the age at transition from SMR 1 to SMR 2 + for both thelarche and pubarche. SMR data was collected through June 2020. Menarche was analyzed as a secondary outcome. Weibull and modified Poisson regression models were used. Models were adjusted for potential confounders. There were 15,196 girls included in the study. Approximately 30.2% experienced catch-up growth, 25.8% experienced catch-down growth, and 44% had normal growth. Girls with catch-up growth had increased risk of earlier thelarche (hazard ratio = 1.26, 95% confidence interval (CI): 1.18, 1.35), pubarche (1.38, 95% CI: 1.28, 1.48), and menarche (< 12y, relative risk = 1.52, 95% CI: 1.36, 1.69) compared to those with normal growth, after adjusting for covariates. These associations were partially mediated by childhood body mass index. Catch-down growth was associated with later pubertal onset. Girls who experience infant catch-up growth have higher risk of earlier pubertal development compared to girls with normal growth and the associations are partially explained by childhood obesity. This information may help clinicians to monitor girls who are at high risk of developing earlier.
Authors: Aghaee, Sara; Quesenberry, Charles P; Deardorff, Julianna; Kushi, Lawrence H; Greenspan, Louise C; Ferrara, Assiamira; Kubo, Ai
BMC Pediatr. 2022 Mar 31;22(1):171. Epub 2022-03-31.
Effectiveness of COVID-19 Pfizer-BioNTech BNT162b2 mRNA Vaccination in Preventing COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Nonimmunocompromised Children and Adolescents Aged 5-17 Years – VISION Network, 10 States, April 2021-January 2022
The efficacy of the BNT162b2 (Pfizer-BioNTech) vaccine against laboratory-confirmed COVID-19 exceeded 90% in clinical trials that included children and adolescents aged 5-11, 12-15, and 16-17 years (1-3). Limited real-world data on 2-dose mRNA vaccine effectiveness (VE) in persons aged 12-17 years (referred to as adolescents in this report) have also indicated high levels of protection against SARS-CoV-2 (the virus that causes COVID-19) infection and COVID-19-associated hospitalization (4-6); however, data on VE against the SARS-CoV-2 B.1.1.529 (Omicron) variant and duration of protection are limited. Pfizer-BioNTech VE data are not available for children aged 5-11 years. In partnership with CDC, the VISION Network* examined 39,217 emergency department (ED) and urgent care (UC) encounters and 1,699 hospitalizations† among persons aged 5-17 years with COVID-19-like illness across 10 states during April 9, 2021-January 29, 2022,§ to estimate VE using a case-control test-negative design. Among children aged 5-11 years, VE against laboratory-confirmed COVID-19-associated ED and UC encounters 14-67 days after dose 2 (the longest interval after dose 2 in this age group) was 46%. Among adolescents aged 12-15 and 16-17 years, VE 14-149 days after dose 2 was 83% and 76%, respectively; VE ≥150 days after dose 2 was 38% and 46%, respectively. Among adolescents aged 16-17 years, VE increased to 86% ≥7 days after dose 3 (booster dose). VE against COVID-19-associated ED and UC encounters was substantially lower during the Omicron predominant period than the B.1.617.2 (Delta) predominant period among adolescents aged 12-17 years, with no significant protection ≥150 days after dose 2 during Omicron predominance. However, in adolescents aged 16-17 years, VE during the Omicron predominant period increased to 81% ≥7 days after a third booster dose. During the full study period, including pre-Delta, Delta, and Omicron predominant periods, VE against laboratory-confirmed COVID-19-associated hospitalization among children aged 5-11 years was 74% 14-67 days after dose 2, with wide CIs that included zero. Among adolescents aged 12-15 and 16-17 years, VE 14-149 days after dose 2 was 92% and 94%, respectively; VE ≥150 days after dose 2 was 73% and 88%, respectively. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations, including a booster dose for those aged 12-17 years.
Authors: Klein, Nicola P; Fireman, Bruce; Zerbo, Ousseny; Verani, Jennifer R; et al.
MMWR Morb Mortal Wkly Rep. 2022 Mar 04;71(9):352-358. 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.
Age-Adjusted Mortality Rates and Age and Risk-Associated Contributions to Change in Heart Disease and Stroke Mortality, 2011-2019 and 2019-2020
Authors: Sidney, Stephen; Lee, Catherine; Liu, Jennifer; Khan, Sadiya S; Lloyd-Jones, Donald M; Rana, Jamal S
JAMA Netw Open. 2022 03 01;5(3):e223872. Epub 2022-03-01.
Breast Arterial Calcification: a Novel Cardiovascular Risk Enhancer Among Postmenopausal Women
Breast arterial calcification (BAC), a common incidental finding in mammography, has been shown to be associated with angiographic coronary artery disease and cardiovascular disease (CVD) outcomes. We aimed to (1) examine the association of BAC presence and quantity with hard atherosclerotic CVD (ASCVD) and global CVD; (2) ascertain model calibration, discrimination and reclassification of ASCVD risk; (3) assess the joint effect of BAC presence and 10-year pooled cohorts equations risk on ASCVD. A cohort study of 5059 women aged 60-79 years recruited after attending mammography screening between October 2012 and February 2015 was conducted in a large health plan in Northern California, United States. BAC status (presence versus absence) and quantity (calcium mass mg) was determined using digital mammograms. Prespecified end points were incident hard ASCVD and a composite of global CVD. Twenty-six percent of women had BAC >0 mg. After a mean (SD) follow-up of 6.5 (1.6) years, we ascertained 155 (3.0%) ASCVD events and 427 (8.4%) global CVD events. In Cox regression adjusted for traditional CVD risk factors, BAC presence was associated with a 1.51 (95% CI, 1.08-2.11; P=0.02) increased hazard of ASCVD and a 1.23 (95% CI, 1.002-1.52; P=0.04) increased hazard of global CVD. While there was no evidence of dose-response association with ASCVD, a threshold effect was found for global CVD at very high BAC burden (95th percentile when BAC present). BAC status provided additional risk stratification of the pooled cohorts equations risk. We noted improvements in model calibration and reclassification of ASCVD: the overall net reclassification improvement was 0.12 (95% CI, 0.03-0.14; P=0.01) and the bias-corrected clinical-net reclassification improvement was 0.11 (95% CI, 0.01-0.22; P=0.04) after adding BAC status. Our results indicate that BAC has potential utility for primary CVD prevention and, therefore, support the notion that BAC ought to be considered a risk-enhancing factor for ASCVD among postmenopausal women.
Authors: Iribarren, Carlos; Chandra, Malini; Lee, Catherine; Sanchez, Gabriela; Sam, Danny L; Azamian, Farima Faith; Cho, Hyo-Min; Ding, Huanjun; Wong, Nathan D; Molloi, Sabee
Circ Cardiovasc Imaging. 2022 03;15(3):e013526. Epub 2022-03-15.
Association of Glyburide and Subcutaneous Insulin With Perinatal Complications Among Women With Gestational Diabetes
Nearly 30% of individuals with gestational diabetes (GDM) do not achieve glycemic control with lifestyle modification alone and require medication treatment. Oral agents, such as glyburide, have several advantages over insulin for the treatment of GDM, including greater patient acceptance; however, the effectiveness of glyburide for the treatment of GDM remains controversial. To compare the perinatal and neonatal outcomes associated with glyburide vs insulin using causal inference methods in a clinical setting with information on glycemic control. The population-based cohort study included patients with GDM who required medication treatment from 2007 to 2017 in Kaiser Permanente Northern California. Machine learning and rigorous casual inference methods with time-varying exposures were used to evaluate associations of exposure to glyburide vs insulin with perinatal outcomes. Data analysis was conducted from March 2018 to July 2017. Time-varying exposure to glyburide vs insulin during pregnancy. Outcomes evaluated separately included neonatal hypoglycemia, jaundice, shoulder dystocia, respiratory distress syndrome (RDS), neonatal intensive care unit (NICU) admission, size-for-gestational age, and cesarean delivery. Inverse probability weighting (IPW) estimation was used to separately compare perinatal outcomes between those initiating glyburide and insulin. This approach was combined with Super Learning for propensity score estimation to account for both baseline and time-dependent confounding in both per-protocol (primary) and intention-to-treat (secondary) analyses to evaluate sustained exposure to the same therapy. From 2007 to 2017, 11 321 patients with GDM (mean [SD] age, 32.9 [4.9] years) initiated glyburide or insulin during pregnancy. In multivariate models, the risk of neonatal respiratory distress was 2.03 (95% CI, 0.13-3.92) per 100 births lower and the risk of NICU admission was 3.32 (95% CI, 0.20-6.45) per 100 births lower after continuous exposure to glyburide compared with insulin. There were no statistically significant differences in glyburide vs insulin initiation in risk for neonatal hypoglycemia (0.85 [95% CI, -1.17 to 2.86] per 100 births), jaundice (0.02 [95% CI, -1.46 to 1.51] per 100 births), shoulder dystocia (-1.05 [95% CI, -2.71 to 0.62] per 100 births), or large-for-gestational age categories (-2.75 [95% CI, -6.31 to 0.80] per 100 births). Using data from a clinical setting and contemporary causal inference methods, our findings do not provide evidence of a difference in the outcomes examined between patients with GDM initiating glyburide compared with those initiating insulin.
Authors: Hedderson, Monique M; Badon, Sylvia E; Pimentel, Noel; Xu, Fei; Regenstein, Anne; Ferrara, Assiamira; Neugebauer, Romain
JAMA Netw Open. 2022 03 01;5(3):e225026. Epub 2022-03-01.
Early Pregnancy Blood Pressure Patterns Identify Risk of Hypertensive Disorders of Pregnancy Among Racial and Ethnic Groups
Hypertensive disorders of pregnancy are a leading cause of severe maternal morbidity and mortality and confer 4-fold higher perinatal mortality in Black women. Early pregnancy blood pressure patterns may differentiate risk of hypertensive disorders of pregnancy. This study identified distinct blood pressure trajectories from 0 to 20 weeks’ gestation to evaluate subsequent pregnancy-related hypertension in a retrospective cohort of 174 925 women with no prior hypertension or history of preeclampsia, prenatal care entry ≤14 weeks, and a stillborn or live singleton birth delivered at Kaiser Permanente Northern California hospitals in 2009 to 2019. We used electronic health records to obtain clinical outcomes, covariables, and longitudinal outpatient blood pressure measurements ≤20 weeks’ gestation (mean 4.1 measurements). Latent class trajectory modeling identified 6 blood pressure groups: ultra-low-declining(referent), low-declining, moderate-fast-decline, low-increasing, moderate-stable, and elevated-stable. Multivariable logistic regression evaluated trajectory group-associations with the odds of preeclampsia/eclampsia and gestational hypertension’ and effect modification by race-ethnicity and prepregnancy body size. Compared with ultra-low-declining, adjusted odds ratios (95% confidence intervals [CIs]) for low-increasing, moderate-stable, and elevated-stable groups were 3.25 (2.7-3.9), 5.3 (4.5-6.3), and 9.2 (7.7-11.1) for preeclampsia/eclampsia’ and 6.4 (4.9-8.3), 13.6 (10.5-17.7), and 30.2 (23.2-39.4) for gestational hypertension. Race/ethnicity, and prepregnancy obesity modified the trajectory-group associations with preeclampsia/eclampsia (interaction P<0.01), with highest risks for Black, then Hispanic and Asian women for all blood pressure trajectories, and with increasing obesity class. Early pregnancy blood pressure patterns revealed racial and ethnic differences in associations with preeclampsia/eclampsia risk within equivalent levels and patterns. These blood pressure patterns may improve individual risk stratification permitting targeted surveillance and early mitigation strategies.
Authors: Gunderson, Erica P; Greenberg, Mara; Nguyen-Huynh, Mai N; Tierney, Cassidy; Roberts, James M; Go, Alan S; Tao, Wei; Alexeeff, Stacey E
Hypertension. 2022 03;79(3):599-613. Epub 2021-12-29.
Impact of the Affordable Care Act on Colorectal Cancer Incidence and Mortality
The Patient Protection and Affordable Care Act eliminated cost sharing for preventive services, including colorectal cancer screening for individuals aged 50-75 years with private health insurance. This study examines the impact of the Affordable Care Act’s removal of cost sharing for colorectal cancer screening on colorectal cancer incidence and mortality. Trends in colorectal cancer incidence and colorectal cancer‒related mortality were modeled among 2,113,283 Kaiser Permanente Northern California members aged ≥50 years between 2003 and 2016 using an interrupted time-series design. As a sensitivity analysis, a controlled analysis utilized a comparison group of members covered with pre‒Affordable Care Act zero cost sharing for colorectal cancer screening. Analyses were performed in 2019 and 2020. The colorectal cancer incidence dropped by 17% around the time the Affordable Care Act was enacted (change in level incidence rate ratio; 95% CI=0.77, 0.90, 2-sided p-value <0.0001), followed by a 3% further decrease per year (95% CI=0.93, 1.00, p=0.05). A similar pattern was observed for colorectal cancer‒related mortality. The controlled results indicated that the elimination of cost sharing for screening due to the Affordable Care Act was associated with greater improvements in colorectal cancer outcomes among members previously covered by health plans with out-of-pocket costs for screening than among those with health plans with zero cost sharing for screening before the Affordable Care Act. The elimination of cost sharing for colorectal cancer screening due to the Affordable Care Act was associated with a decrease in age-, race/ethnicity-, and sex-adjusted colorectal cancer incidence and colorectal cancer‒related mortality, implying that policies that remove barriers to screening, particularly financial burden from cost sharing, can result in improved colorectal cancer outcomes.
Authors: Lee, Catherine; Kushi, Lawrence H; Reed, Mary E; Eldridge, Elizabeth H; Lee, Jeffrey K; Zhang, Jie; Spiegelman, Donna
Am J Prev Med. 2022 03;62(3):387-394. Epub 2021-11-08.
Cohort and Nested Case-Control Study of Cutaneous Squamous Cell Carcinoma in Solid Organ Transplant Recipients, by Medication
Knowledge is needed about the risk of cutaneous squamous cell carcinoma (cSCC) in solid organ transplant recipients (SOTRs) using contemporary immunosuppressive regimens. Evaluate the risk of cSCC in relation to medications used by SOTRs. The cohort and nest case-control study included 3308 SOTRs and 65,883 persons without transplantation during 2009-2019. Incident cSCC was identified from pathology data, and medications were identified from pharmacy data. Adjusted hazard ratios and 95% confidence intervals (CIs) were estimated using Cox proportional hazards analysis, with voriconazole examined as a time-dependent variable. The annual incidence of cSCC was 1.69% in SOTRs and 0.30% in persons without transplantation. The adjusted hazard ratio of cSCC associated with lung transplant was 14.83 (95% CI, 9.85-22.33) for lung and 6.53-10.69 for other organs. Risk in Latinx persons was higher than in other non-White groups. Among lung recipients, the hazard ratio was 1.14 for each month of voriconazole use (95% CI, 1.04-1.26). Azathioprine use for ≥7 months, relating to mycophenolate mofetil intolerance, was associated with a 4.22-fold increased risk of cSCC (95% CI, 1.90-9.40). Belatacept and other immunsuppressive medications were not associated with risk. The number of events was somewhat small. The knowledge of risks and benefits in diverse patients can translate to improvements in care.
Authors: Dusendang, Jennifer R; Carlson, Ekama; Lee, David S; Marwaha, Sangeeta; Madani, Shabnam; Alexeeff, Stacey E; Webber, Allison; Goes, Nelson B; Herrinton, Lisa J
J Am Acad Dermatol. 2022 03;86(3):598-606. Epub 2021-08-09.
Antibiotic prescribing across age groups in the Kaiser Permanente Northern California population in association with different diagnoses, and with influenza incidence, 2010-2018
There is limited information on the volume of antibiotic prescribing that is influenza-associated, resulting from influenza infections and their complications (such as streptococcal pharyngitis and otitis media). Here, we estimated age/diagnosis-specific proportions of antibiotic prescriptions (fills) for the Kaiser Permanente Northern California population during 2010-2018 that were influenza-associated. The proportion of influenza-associated antibiotic prescribing among all antibiotic prescribing was higher in children aged 5-17 years compared to children aged under 5 years, ranging from 1.4% [95% CI (0.7-2.1)] in aged <1 year to 2.7% (1.9-3.4) in aged 15-17 years. For adults aged over 20 years, the proportion of influenza-associated antibiotic prescribing among all antibiotic prescribing was lower, ranging from 0.7% (0.5-1) for aged 25-29 years to 1.6% (1.2-1.9) for aged 60-64 years. Most of the influenza-associated antibiotic prescribing in children aged under 10 years was for ear infections, while for age groups over 25 years, 45-84% of influenza-associated antibiotic prescribing was for respiratory diagnoses without a bacterial indication. This suggests a modest benefit of increasing influenza vaccination coverage for reducing antibiotic prescribing, as well as the potential benefit of other measures to reduce unnecessary antibiotic prescribing for respiratory diagnoses with no bacterial indication in persons aged over 25 years, both of which may further contribute to the mitigation of antimicrobial resistance.
Authors: Goldstein, Edward; Fireman, Bruce H; Klein, Nicola P; Lipsitch, Marc; Ray, G Thomas
Epidemiol Infect. 2022 Feb 24;150:e85. Epub 2022-02-24.
Waning 2-Dose and 3-Dose Effectiveness of mRNA Vaccines Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominance – VISION Network, 10 States, August 2021-January 2022
CDC recommends that all persons aged ≥12 years receive a booster dose of COVID-19 mRNA vaccine ≥5 months after completion of a primary mRNA vaccination series and that immunocompromised persons receive a third primary dose.* Waning of vaccine protection after 2 doses of mRNA vaccine has been observed during the period of the SARS-CoV-2 B.1.617.2 (Delta) variant predominance† (1-5), but little is known about durability of protection after 3 doses during periods of Delta or SARS-CoV-2 B.1.1.529 (Omicron) variant predominance. A test-negative case-control study design using data from eight VISION Network sites§ examined vaccine effectiveness (VE) against COVID-19 emergency department/urgent care (ED/UC) visits and hospitalizations among U.S. adults aged ≥18 years at various time points after receipt of a second or third vaccine dose during two periods: Delta variant predominance and Omicron variant predominance (i.e., periods when each variant accounted for ≥50% of sequenced isolates).¶ Persons categorized as having received 3 doses included those who received a third dose in a primary series or a booster dose after a 2 dose primary series (including the reduced-dosage Moderna booster). The VISION Network analyzed 241,204 ED/UC encounters** and 93,408 hospitalizations across 10 states during August 26, 2021-January 22, 2022. VE after receipt of both 2 and 3 doses was lower during the Omicron-predominant than during the Delta-predominant period at all time points evaluated. During both periods, VE after receipt of a third dose was higher than that after a second dose; however, VE waned with increasing time since vaccination. During the Omicron period, VE against ED/UC visits was 87% during the first 2 months after a third dose and decreased to 66% among those vaccinated 4-5 months earlier; VE against hospitalizations was 91% during the first 2 months following a third dose and decreased to 78% ≥4 months after a third dose. For both Delta- and Omicron-predominant periods, VE was generally higher for protection against hospitalizations than against ED/UC visits. All eligible persons should remain up to date with recommended COVID-19 vaccinations to best protect against COVID-19-associated hospitalizations and ED/UC visits.
Authors: Ferdinands, Jill M; Klein, Nicola P; Zerbo, Ousseny; Fireman, Bruce; et al.
MMWR Morb Mortal Wkly Rep. 2022 Feb 18;71(7):255-263. Epub 2022-02-18.
Self-controlled assessment of thromboembolic event (TEE) risk following intravenous immune globulin (IGIV) in the U.S. (2006-2012)
Since 2013, the U.S. Food and Drug administration (FDA) has required that intravenous immune globulin (IGIV) products carry a boxed warning concerning the risk of thromboembolic events (TEEs). This study assessed the incidence of TEEs attributable to IGIV in a large population-based cohort. A self-controlled risk interval design was used to quantify the transient increase in TEE risk during the risk interval (days 0-2 and 0-13 following IGIV for arterial and venous TEEs, respectively) relative to a later control interval (days 14-27 following IGIV). Potential IGIV-exposed TEE cases from 2006 to 2012 were identified from the FDA-sponsored Sentinel Distributed Database and confirmed through medical record review. Inpatient IGIV exposures were not included in the venous TEE analysis due to concerns about time-varying confounding. 19,069 new users of IGIV who received 93,555 treatment episodes were included. Charts were retrieved for 62% and 70% of potential venous and arterial cases, respectively. There was a transient increase in the risk of arterial TEEs during days 0-2 following IGIV treatment (RR = 4.69; 95% CI 1.87, 11.90; absolute increase in risk = 8.86 events per 10,000 patients, 95% CI 3.25, 14.6), but no significant increase in venous TEE risk during days 0-13 following outpatient IGIV treatments (RR = 1.07, 95% CI 0.34, 3.48). Our results suggest there is a small increase in the absolute risk of arterial TEEs following IGIV. However, lower-than-expected chart retrieval rates and the possibility of time-varying confounding mean that our results should be interpreted cautiously. Continued pharmacovigilance efforts are warranted.
Authors: Ammann, Eric M; Fuller, Candace C; Winiecki, Scott K; et al.
J Thromb Thrombolysis. 2022 Feb;53(2):264-272. Epub 2021-11-24.
Effectiveness of a Third Dose of mRNA Vaccines Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominance – VISION Network, 10 States, August 2021-January 2022
Estimates of COVID-19 mRNA vaccine effectiveness (VE) have declined in recent months (1,2) because of waning vaccine induced immunity over time,* possible increased immune evasion by SARS-CoV-2 variants (3), or a combination of these and other factors. CDC recommends that all persons aged ≥12 years receive a third dose (booster) of an mRNA vaccine ≥5 months after receipt of the second mRNA vaccine dose and that immunocompromised individuals receive a third primary dose.† A third dose of BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine increases neutralizing antibody levels (4), and three recent studies from Israel have shown improved effectiveness of a third dose in preventing COVID-19 associated with infections with the SARS-CoV-2 B.1.617.2 (Delta) variant (5-7). Yet, data are limited on the real-world effectiveness of third doses of COVID-19 mRNA vaccine in the United States, especially since the SARS-CoV-2 B.1.1.529 (Omicron) variant became predominant in mid-December 2021. The VISION Network§ examined VE by analyzing 222,772 encounters from 383 emergency departments (EDs) and urgent care (UC) clinics and 87,904 hospitalizations from 259 hospitals among adults aged ≥18 years across 10 states from August 26, 2021¶ to January 5, 2022. Analyses were stratified by the period before and after the Omicron variant became the predominant strain (>50% of sequenced viruses) at each study site. During the period of Delta predominance across study sites in the United States (August-mid-December 2021), VE against laboratory-confirmed COVID-19-associated ED and UC encounters was 86% 14-179 days after dose 2, 76% ≥180 days after dose 2, and 94% ≥14 days after dose 3. Estimates of VE for the same intervals after vaccination during Omicron variant predominance were 52%, 38%, and 82%, respectively. During the period of Delta variant predominance, VE against laboratory-confirmed COVID-19-associated hospitalizations was 90% 14-179 days after dose 2, 81% ≥180 days after dose 2, and 94% ≥14 days after dose 3. During Omicron variant predominance, VE estimates for the same intervals after vaccination were 81%, 57%, and 90%, respectively. The highest estimates of VE against COVID-19-associated ED and UC encounters or hospitalizations during both Delta- and Omicron-predominant periods were among adults who received a third dose of mRNA vaccine. All unvaccinated persons should get vaccinated as soon as possible. All adults who have received mRNA vaccines during their primary COVID-19 vaccination series should receive a third dose when eligible, and eligible persons should stay up to date with COVID-19 vaccinations.
Authors: Thompson, Mark G; Klein, Nicola P; Fireman, Bruce; Zerbo, Ousseny; Ong, Toan C; et al.
MMWR Morb Mortal Wkly Rep. 2022 Jan 21;71(4):139-145. Epub 2022-01-21.
TP53 Gain-of-Function and Non-Gain-of-Function Mutations Are Differentially Associated With Sidedness-Dependent Prognosis in Metastatic Colorectal Cancer
To examine the association of gain-of-function (GOF) and non-gain-of-function (non-GOF) TP53 mutations with prognosis of metastatic right-sided (RCC) versus left-sided colorectal cancer (LCC). This cohort study included patients with metastatic colorectal cancer (CRC) who had next-generation sequencing performed from November 2017 to January 2021. We defined R175H, R248W, R248Q, R249S, R273H, R273L, and R282W as GOF and all other mutp53 as non-GOF. We used Cox regression modeling to examine the association between GOF and non-GOF mutp53 and overall survival (OS), adjusting for age, sex, ethnicity, performance status, Charlson comorbidity index and receipt of chemotherapy. Of total 1,043 patients, 735 had tumors with mutp53 and 308 had wild-type p53 (wtp53). GOF was associated with worse OS than non-GOF mutp53 only in LCC (hazard ratio [HR] = 1.66 [95% CI, 1.20 to 2.29]), but not in RCC (HR = 0.79 [95% CI, 0.49 to 1.26]). Importantly, RCC was associated with worse OS than LCC only in the subset of patients whose CRC carried non-GOF (HR = 1.76 [95% CI, 1.30 to 2.39]), but not GOF mutp53 (HR = 0.92 [95% CI, 0.55 to 1.53]) or wtp53 (HR = 0.88 [95% CI, 0.60 to 1.28]). These associations were largely unchanged after also adjusting for RAS, BRAF, and PIK3CA mutations, and microsatellite instability-high. Poorer survival of patients with metastatic RCC versus LCC appeared to be restricted to the subset with non-GOF mutp53, whereas GOF versus non-GOF mutp53 was associated with poorer survival only among patients with LCC. This approach of collectively classifying mutp53 into GOF and non-GOF provides new insight for prognostic stratification and for understanding the mechanism of sidedness-dependent prognosis. If confirmed, future CRC clinical trials may benefit from incorporating this approach.
Authors: Pan, Minggui; Solorzano, Aleyda V; Habel, Laurel A; et al.
J Clin Oncol. 2022 01 10;40(2):171-179. Epub 2021-11-29.
Identifying hypertensive disorders of pregnancy, a comparison of two epidemiologic definitions
Studies of hypertension in pregnancy that use electronic health care data generally identify hypertension using hospital diagnosis codes alone. We sought to compare results from this approach to an approach that included diagnosis codes, antihypertensive medications and blood pressure (BP) values. We conducted a retrospective cohort study of 1,45,739 pregnancies from 2009 to 2014 within an integrated healthcare system. Hypertensive pregnancies were identified using the “BP-Inclusive Definition” if at least one of three criteria were met: (1) two elevated outpatient BPs, (2) antihypertensive medication fill plus an outpatient hypertension diagnosis, or (3) hospital discharge diagnosis for preeclampsia or eclampsia. The “Traditional Definition” considered only delivery hospitalization discharge diagnoses. Outcome event analyses compared rates of preterm delivery and small for gestational age (SGA) between the two definitions. The BP-Inclusive Definition identified 14,225 (9.8%) hypertensive pregnancies while the Traditional Definition identified 13,637 (9.4%); 10,809 women met both definitions. Preterm delivery occurred in 20.9% of BP-Inclusive Definition pregnancies, 21.8% of Traditional Definition pregnancies and 6.6% of non-hypertensive pregnancies; for SGA the numbers were 15.6, 16.3, and 8.6%, respectively (p < 0.001 for all events compared to non-hypertensive pregnancies). Analyses in women meeting only one hypertension definition (21-24% of positive cases) found much lower rates of both preterm delivery and SGA. Prevalence of hypertension in pregnancy was similar between the two study definitions. However, a substantial number of women met only one of the study definitions. Women who met only one of the hypertension definitions had much lower rates of adverse neonatal events than women meeting both definitions.
Authors: Cheetham, T Craig; Avalos, Lyndsay A; Neugebauer, Romain S; Dublin, Sascha; et al.
Front Cardiovasc Med. 2022;9:1006104. Epub 2022-11-23.
Maternal and neonatal outcomes of antihypertensive treatment in pregnancy: A retrospective cohort study
To compare maternal and infant outcomes with different antihypertensive medications in pregnancy. Retrospective cohort study. Kaiser Permanente, a large healthcare system in the United States. Women aged 15-49 years with a singleton birth from 2005-2014 treated for hypertension. We identified medication exposure from automated pharmacy data based on the earliest dispensing after the first prenatal visit. Using logistic regression, we calculated weighted outcome prevalences, adjusted odds ratios (aORs) and 95% confidence intervals, with inverse probability of treatment weighting to address confounding. Small for gestational age, preterm delivery, neonatal and maternal intensive care unit (ICU) admission, preeclampsia, and stillbirth or termination at > 20 weeks. Among 6346 deliveries, 87% with chronic hypertension, the risk of the infant being small for gestational age (birthweight < 10th percentile) was lower with methyldopa than labetalol (prevalence 13.6% vs. 16.6%; aOR 0.77, 95% CI 0.63 to 0.92). For birthweight < 3rd percentile the aOR was 0.57 (0.39 to 0.80). Compared with labetalol (26.0%), risk of preterm delivery was similar for methyldopa (26.5%; aOR 1.10 [0.95 to 1.27]) and slightly higher for nifedipine (28.5%; aOR 1.25 [1.06 to 1.46]) and other β-blockers (31.2%; aOR 1.58 [1.07 to 2.23]). Neonatal ICU admission was more common with nifedipine than labetalol (25.9% vs. 23.3%, aOR 1.21 [1.02 to 1.43]) but not elevated with methyldopa. Risks of other outcomes did not differ by medication. Risk of most outcomes was similar comparing labetalol, methyldopa and nifedipine. Risk of the infant being small for gestational age was substantially lower for methyldopa, suggesting this medication may warrant further consideration.
Authors: Dublin, Sascha; Avalos, Lyndsay A; Neugebauer, Romain S; Badon, Sylvia E; Shortreed, Susan M; et al.
PLoS One. 2022;17(5):e0268284. Epub 2022-05-16.
Rates of cardiovascular events among patients with moderate-to-severe atopic dermatitis in an integrated health care system: A retrospective cohort study
Patients with versus without atopic dermatitis may have a greater risk of cardiovascular events, and the risk increases with severity of atopic dermatitis. The incidence of cardiovascular events in the population of patients with moderate-to-severe atopic dermatitis is largely unknown. This retrospective study evaluates incidence rates of cardiovascular events in patients aged ≥12 years with moderate-to-severe atopic dermatitis in a cohort of Kaiser Permanente Northern California health care system members without recognized risk factors for adverse events. Patients with moderate-to-severe atopic dermatitis, as defined by dermatologist-rendered code and prescription history between 2007 and 2018, were included. Major adverse cardiovascular events, venous thrombotic events, deep vein thrombosis, and pulmonary embolisms were identified via International Classification of Diseases codes. Stratification variables included age, sex, race, smoking history, and diabetes. Incidence rates per 1000 person-years were calculated by the number of patients with an incident event divided by the total person-years of observation. Among 8197 patients with moderate-to-severe atopic dermatitis, incidence rates per 1000 person-years (95% confidence interval) for major adverse cardiovascular events, venous thrombotic events, deep vein thrombosis, and pulmonary embolism were: 2.6 (2.1-3.2), 2.0 (1.5-2.5), 1.6 (1.2-2.1), and 0.7 (0.5-1.0), respectively. Incidence rates for all events were higher for older versus younger patients, patients with versus without diabetes, former smokers versus patients who had never smoked, and men versus women, except for pulmonary embolisms, which were higher in women. This study estimated the incidence of cardiovascular events in patients with moderate-to-severe atopic dermatitis and provides valuable information for clinicians.
Authors: Hedderson, Monique M; Asgari, Maryam M; Xu, Fei; Quesenberry, Charles P; Sridhar, Sneha; Geier, Jamie; Lemeshow, Adina R
PLoS One. 2022;17(11):e0277469. Epub 2022-11-17.
Effectiveness of two-dose vaccination with mRNA COVID-19 vaccines against COVID-19-associated hospitalizations among immunocompromised adults-Nine States, January-September 2021
Authors: Embi, Peter J; Klein, Nicola P; Fireman, Bruce; Zerbo, Ousseny; DeSilva, Malini B; et al.
Am J Transplant. 2022 01;22(1):306-314.
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.
Ectopic Pregnancy Prevention: Further Evidence of Benefits of Prescription Contraceptives
To estimate the incidence of ectopic pregnancy (EP) associated with prescription contraceptive use. We performed a retrospective cohort study of women aged 15 to 44 years at Kaiser Permanente Northern and Southern California during 2010 to 2019. We identified EPs and prescription contraceptive use from diagnosis, procedural, and medication codes, and natural language processing of clinical notes from electronic health records. Contraceptive use categories included combined hormonal contraceptives, intrauterine devices, depot-medroxyprogesterone acetate (DMPA), progestin-only pills (POPs), implants, no method after recent discontinuation of a prescription contraceptive in the last 12 months, and no method after discontinuation of a prescription contraceptive more than 12 months ago or no use of prescription contraceptives during the study period. Contraceptive use was updated as women started, stopped, or changed methods. An EP was attributed to a contraceptive method if it occurred 14 days after starting and up to 42 days after stopping a method. Age-adjusted EP incidence and 95% confidence intervals (CI) were estimated per 10,000 woman-years overall and by contraceptive category. There were 11,436 EPs among 3,204,118 women with 11,909,842 woman-years of follow-up for an overall EP incidence of 9.5 per 10,000 woman-years (95%CI 9.3-9.6). The majority of EPs (9662; 84.5%) occurred during no prescription contraceptive use. EP incidence was lowest during DMPA (1.8 per 10,000 woman-years [95%CI 1.2-2.5]) or implant (2.0 per 10,000 woman-years [95%CI 1.2-3.3]) use, and higher during POP use at 15.2 (95%CI 12.2-19.6); however, incidence was highest after recent discontinuation of a prescription contraceptive (20.6 per 10,000 woman-years [95%CI 19.7-21.4]). EP incidence is lower with prescription contraceptive use than with nonuse. All prescription contraceptives, including POPs are protective of EP.
Authors: Raine-Bennett, Tina; Alexeeff, Stacey; Getahun, Darios; et al.
Contraception. 2022 01;105:19-25. Epub 2021-09-20.
Torsade de pointes: A nested case-control study in an integrated healthcare delivery system
TdP is a form of polymorphic ventricular tachycardia which develops in the setting of a prolonged QT interval. There are limited data describing risk factors, treatment, and outcomes of this potentially fatal arrhythmia. Our goals were as follows: (1) to validate cases presenting with Torsade de Pointes (TdP), (2) to identify modifiable risk factors, and (3) to describe the management strategies used for TdP and its prognosis in a real-world healthcare setting. Case-control study (with 2:1 matching on age, sex, and race/ethnicity) nested within the Genetic Epidemiology Research on Aging (GERA) cohort. Follow-up of the cohort for case ascertainment was between January 01, 2005 and December 31, 2018. A total of 56 cases of TdP were confirmed (incidence rate = 3.6 per 100,000 persons/years). The average (SD) age of the TdP cases was 74 (13) years, 55 percent were female, and 16 percent were non-white. The independent predictors of TdP were potassium concentration <3.6 mEq/L (OR = 10.6), prior history of atrial fibrillation/flutter (OR = 6.2), QTc >480 ms (OR = 4.4) and prior history of coronary artery disease (OR = 2.6). Exposure to furosemide and amiodarone was significantly greater in cases than in controls. The most common treatment for TdP was IV magnesium (78.6%) and IV potassium repletion (73.2%). The in-hospital and 1-year mortality rates for TdP cases were 10.7% and 25.0% percent, respectively. These findings may inform quantitative multivariate risk indices for the prediction of TdP and could guide practitioners on which patients may qualify for continuous ECG monitoring and/or electrolyte replacement therapy.
Authors: Mantri, Neha; Lu, Meng; Zaroff, Jonathan G; Risch, Neil; Hoffmann, Thomas; Oni-Orisan, Akinyemi; Lee, Catherine; Iribarren, Carlos
Ann Noninvasive Electrocardiol. 2022 01;27(1):e12888. Epub 2021-09-21.
Population-based assessment of risks for severe COVID-19 disease outcomes
Among approximately 4.6 million members of Kaiser Permanente Northern California, we examined associations of severe COVID-19 with demographic factors and comorbidities. As of July 23, 2021, 16 182 had been hospitalized, 2416 admitted to an ICU, and 1525 died due to COVID-19. Age was strongly associated with hospitalization, ICU admission, and death. Black persons and Hispanic ethnicity had higher risk of death compared with Whites. Among the comorbidities examined, Alzheimer’s disease was associated with the highest risk for hospitalization (aHR 3.19, CI: 2.88-3.52) and death (aHR 4.04, CI: 3.32-4.91). Parkinson’s disease had the second highest risk of death (aHR = 2.07, CI: 1.50-2.87).
Authors: Zerbo, Ousseny; Lewis, Ned; Fireman, Bruce; Goddard, Kristin; Skarbinski, Jacek; Sejvar, James J; Azziz-Baumgartner, Eduardo; Klein, Nicola P
Influenza Other Respir Viruses. 2022 01;16(1):159-165. Epub 2021-08-25.
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.
Comanagement of Rashes by Primary Care Providers and Dermatologists: A Retrospective Study
There is a high demand for managing skin disease, and dermatologists are in short supply. To better understand how rashes and other specific skin conditions are co-managed by primary care providers (PCPs) and dermatologists, we estimated the frequency with which PCPs sought consultation with or referral to dermatology and the proportion of patients who had a follow-up dermatology office visit in the following 90 days. The retrospective longitudinal study included 106,459 patients with a skin condition diagnosed by 3,830 PCPs, from January 2017 to March 2017. Comprehensive electronic medical record data with generalized linear mixed modeling accounted for patient factors including diagnosis and clustering by medical center and PCP. PCPs escalated 9% of patients to dermatology through consultation or referral, while 5% required a follow-up dermatology office visit within 90 days. Patients with bullous, hair, or pigment conditions or psoriasis were most likely to be escalated. Clustering of escalation and follow-up visits was minimal in relation to medical center (intraclass correlation, 0.04 for both outcomes) or PCP (escalation, intraclass correlation, 0.16; follow-up visits, 0.09). Improving primary care education in skin disease and, for certain skin conditions, standardizing approaches to workup, treatment, and escalation may further streamline care and reduce pressure on the dermatologist workforce. PCPs managed 91% of rashes without consultation or referral to dermatology, and the frequency of patients scheduled for dermatology office visits after primary care was similar from one PCP to another.
Authors: Marwaha, Sangeeta; Dusendang, Jennifer R; Alexeeff, Stacey E; Crowley, Eileen; Haiman, Michael; Pham, Ngoc; Tuerk, Melanie J; Wudka, Danny; Hartmann, Michael; Herrinton, Lisa J
Perm J. 2021 12 13;25. Epub 2021-12-13.
Cancer in people with and without hepatitis C virus infection: comparison of risk before and after introduction of direct-acting antivirals
Chronic hepatitis C virus (HCV) infection is a leading cause of liver cancer. The association of HCV infection with extrahepatic cancers, and the impact of direct-acting antiviral (DAA) treatment on these cancers, is less well known. We conducted a cohort study in a healthcare delivery system. Using electronic health record data from 2007 to 2017, we determined cancer incidence, overall and by type, in people with HCV infection and by DAA treatment status. All analyses included comparisons with a reference population of people without HCV infection. Covariate-adjusted Poisson models were used to estimate incidence rate ratios. 2,451 people with HCV and 173,548 people without HCV were diagnosed with at least one type of cancer. Compared with people without HCV, those with HCV were at higher risk for liver cancer [adjusted incidence rate ratio (aIRR) = 31.4, 95% confidence interval (CI) = 28.9-34.0], hematologic cancer (aIRR = 1.3, 95% CI = 1.1-1.5), lung cancer (aIRR = 1.3, 95% CI = 1.2-1.5), pancreatic cancer (aIRR = 2.0, 95% CI = 1.6-2.5), oral/oropharynx cancer (aIRR = 1.4, 95% CI = 1.1-1.8), and anal cancer (aIRR = 1.6, 95% CI = 1.1-2.4). Compared with people without HCV, the aIRR for liver cancer was 31.9 (95% CI = 27.9-36.4) among DAA-untreated and 21.2 (95% CI = 16.8-26.6) among DAA-treated, and the aIRR for hematologic cancer was 1.5 (95% CI = 1.1-2.0) among DAA-untreated and 0.6 (95% CI = 0.3-1.2) among DAA-treated. People with HCV infection were at increased risk of liver cancer, hematologic cancer, and some other extrahepatic cancers. DAA treatment was associated with reduced risk of liver cancers and hematologic cancers. DAA treatment is important for reducing cancer incidence among people with HCV infection.
Authors: Lam, Jennifer O; Champsi, Jamila H; Silverberg, Michael J; et al.
Cancer Epidemiol Biomarkers Prev. 2021 12;30(12):2188-2196. Epub 2021-09-28.
Hypotonic-hyporesponsive Episodes After Diphtheria, Tetanus and Acellular Pertussis Vaccination
Hypotonic-hyporesponsive episode (HHE) after whole cell pertussis vaccination is a known adverse event. Less is known about the risk of HHE after administration of acellular pertussis vaccines. Using parental interviews, this study actively surveyed for HHE among infants after doses 1 and 2 of acellular pertussis vaccine. We interviewed the parents of 52,531 infants. HHE was reported at a rate of 22.8 per 100,000 doses (95% CI: 11.8-39.9) of acellular pertussis vaccine, approximately 45 episodes per 100,000 children. These rates are lower than HHE rates reported after whole cell pertussis vaccines and within the range of HHE rates reported in other studies of acellular pertussis vaccines.
Authors: Hansen, John; Decker, Michael D; Lewis, Edwin; Fireman, Bruce; Pool, Vitali; Greenberg, David P; Johnson, David R; Black, Steven; Klein, Nicola P
Pediatr Infect Dis J. 2021 12 01;40(12):1122-1126.
Laboratory-Confirmed COVID-19 Among Adults Hospitalized with COVID-19-Like Illness with Infection-Induced or mRNA Vaccine-Induced SARS-CoV-2 Immunity – Nine States, January-September 2021
Previous infection with SARS-CoV-2 (the virus that causes COVID-19) or COVID-19 vaccination can provide immunity and protection from subsequent SARS-CoV-2 infection and illness. CDC used data from the VISION Network* to examine hospitalizations in adults with COVID-19-like illness and compared the odds of receiving a positive SARS-CoV-2 test result, and thus having laboratory-confirmed COVID-19, between unvaccinated patients with a previous SARS-CoV-2 infection occurring 90-179 days before COVID-19-like illness hospitalization, and patients who were fully vaccinated with an mRNA COVID-19 vaccine 90-179 days before hospitalization with no previous documented SARS-CoV-2 infection. Hospitalized adults aged ≥18 years with COVID-19-like illness were included if they had received testing at least twice: once associated with a COVID-19-like illness hospitalization during January-September 2021 and at least once earlier (since February 1, 2020, and ≥14 days before that hospitalization). Among COVID-19-like illness hospitalizations in persons whose previous infection or vaccination occurred 90-179 days earlier, the odds of laboratory-confirmed COVID-19 (adjusted for sociodemographic and health characteristics) among unvaccinated, previously infected adults were higher than the odds among fully vaccinated recipients of an mRNA COVID-19 vaccine with no previous documented infection (adjusted odds ratio [aOR] = 5.49; 95% confidence interval [CI] = 2.75-10.99). These findings suggest that among hospitalized adults with COVID-19-like illness whose previous infection or vaccination occurred 90-179 days earlier, vaccine-induced immunity was more protective than infection-induced immunity against laboratory-confirmed COVID-19. All eligible persons should be vaccinated against COVID-19 as soon as possible, including unvaccinated persons previously infected with SARS-CoV-2.
Authors: Bozio, Catherine H; Klein, Nicola P; Fireman, Bruce; Zerbo, Ousseny; Stenehjem, Edward; et al.
MMWR Morb Mortal Wkly Rep. 2021 Nov 05;70(44):1539-1544. Epub 2021-11-05.
Effectiveness of 2-Dose Vaccination with mRNA COVID-19 Vaccines Against COVID-19-Associated Hospitalizations Among Immunocompromised Adults – Nine States, January-September 2021
Immunocompromised persons, defined as those with suppressed humoral or cellular immunity resulting from health conditions or medications, account for approximately 3% of the U.S. adult population (1). Immunocompromised adults are at increased risk for severe COVID-19 outcomes (2) and might not acquire the same level of protection from COVID-19 mRNA vaccines as do immunocompetent adults (3,4). To evaluate vaccine effectiveness (VE) among immunocompromised adults, data from the VISION Network* on hospitalizations among persons aged ≥18 years with COVID-19-like illness from 187 hospitals in nine states during January 17-September 5, 2021 were analyzed. Using selected discharge diagnoses,† VE against COVID-19-associated hospitalization conferred by completing a 2-dose series of an mRNA COVID-19 vaccine ≥14 days before the index hospitalization date§ (i.e., being fully vaccinated) was evaluated using a test-negative design comparing 20,101 immunocompromised adults (10,564 [53%] of whom were fully vaccinated) and 69,116 immunocompetent adults (29,456 [43%] of whom were fully vaccinated). VE of 2 doses of mRNA COVID-19 vaccine against COVID-19-associated hospitalization was lower among immunocompromised patients (77%; 95% confidence interval [CI] = 74%-80%) than among immunocompetent patients (90%; 95% CI = 89%-91%). This difference persisted irrespective of mRNA vaccine product, age group, and timing of hospitalization relative to SARS-CoV-2 (the virus that causes COVID-19) B.1.617.2 (Delta) variant predominance in the state of hospitalization. VE varied across immunocompromising condition subgroups, ranging from 59% (organ or stem cell transplant recipients) to 81% (persons with a rheumatologic or inflammatory disorder). Immunocompromised persons benefit from mRNA COVID-19 vaccination but are less protected from severe COVID-19 outcomes than are immunocompetent persons, and VE varies among immunocompromised subgroups. Immunocompromised persons receiving mRNA COVID-19 vaccines should receive 3 doses and a booster, consistent with CDC recommendations (5), practice nonpharmaceutical interventions, and, if infected, be monitored closely and considered early for proven therapies that can prevent severe outcomes.
Authors: Embi, Peter J; Klein, Nicola P; Fireman, Bruce; Zerbo, Ousseny; DeSilva, Malini B; et al.
MMWR Morb Mortal Wkly Rep. 2021 Nov 05;70(44):1553-1559. Epub 2021-11-05.
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.
Treatment and Follow-up Care Associated With Patient-Scheduled Primary Care Telemedicine and In-Person Visits in a Large Integrated Health System
Telemedicine visits can offer patients convenient access to a clinician, but it is unclear whether treatment differs from that with in-person visits or how often patients require in-person follow-up. To examine whether physician prescribing and orders differ between telemedicine and office visits, whether physicians conducting telemedicine visits are more likely to require in-person follow-up, and whether telemedicine visits are associated with more health events. This cohort study included all patients who scheduled primary care appointments through the patient portal of a large integrated health care delivery system newly implementing patient-scheduled video telemedicine visits from January 2016 to May 2018. Adjusted rates of any medication prescribed or laboratory tests or imaging ordered and rates of follow-up health care utilization (in-person visits, emergency department visits, and hospitalizations) within 7 days after the index visit, stratified by index primary care visit type, were generated using multivariable adjustment for patient, access, and clinical characteristics. This study included 1 131 722 patients (611 821 [54%] female; mean [SD] age, 43 [22] years) with 2 178 440 total appointments (307 888 [14%] telemedicine), of which 13.5% were for patients younger than 18 years, 22.2% were for patients 65 years or older, and 54.9% were for female patients. After adjustment, 38.6% (95% CI, 38.0%-39.3%) of video visits, 34.7% (95% CI, 34.5%-34.9%) of telephone visits, and 51.9% (95% CI, 51.8%-52.0%) of office visits had any medication prescribed; laboratory tests or imaging were ordered for 29.2% (95% CI, 28.5%-29.8%) of video visits, 27.3% (95% CI, 27.1%-27.5%) of telephone visits, and 59.3% (95% CI, 59.3%-59.4%) of clinic visits. After adjustment, follow-up visits within 7 days occurred after 25.4% (95% CI, 24.7%-26.0%) of video visits, 26.0% (95% CI, 25.9%-26.2%) of telephone visits, and 24.5% (95% CI, 24.5%-24.6%) of office visits. Adjusted emergency department visits and rates of hospitalizations were not statistically significantly different by primary care index visit type. In this cohort study of patient self-scheduled primary care telemedicine visits within ongoing patient-physician relationships, prescribing and orders were significantly lower for telemedicine visits than for clinic visits, with slightly higher follow-up office visits for telemedicine but no difference in health events (emergency department visits or hospitalizations). Video or telephone visits may be a convenient and efficient way to access primary care and address patient needs.
Authors: Reed, Mary; Huang, Jie; Graetz, Ilana; Muelly, Emilie; Millman, Andrea; Lee, Catherine
JAMA Netw Open. 2021 11 01;4(11):e2132793. Epub 2021-11-01.
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.
Surveillance for Adverse Events After COVID-19 mRNA Vaccination
Safety surveillance of vaccines against COVID-19 is critical to ensure safety, maintain trust, and inform policy. To monitor 23 serious outcomes weekly, using comprehensive health records on a diverse population. This study represents an interim analysis of safety surveillance data from Vaccine Safety Datalink. The 10 162 227 vaccine-eligible members of 8 participating US health plans were monitored with administrative data updated weekly and supplemented with medical record review for selected outcomes from December 14, 2020, through June 26, 2021. Receipt of BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) COVID-19 vaccination, with a risk interval of 21 days for individuals after vaccine dose 1 or 2 compared with an interval of 22 to 42 days for similar individuals after vaccine dose 1 or 2. Incidence of serious outcomes, including acute myocardial infarction, Bell palsy, cerebral venous sinus thrombosis, Guillain-Barré syndrome, myocarditis/pericarditis, pulmonary embolism, stroke, and thrombosis with thrombocytopenia syndrome. Incidence of events that occurred among vaccine recipients 1 to 21 days after either dose 1 or 2 of a messenger RNA (mRNA) vaccine was compared with that of vaccinated concurrent comparators who, on the same calendar day, had received their most recent dose 22 to 42 days earlier. Rate ratios (RRs) were estimated by Poisson regression, adjusted for age, sex, race and ethnicity, health plan, and calendar day. For a signal, a 1-sided P < .0048 was required to keep type I error below .05 during 2 years of weekly analyses. For 4 additional outcomes, including anaphylaxis, only descriptive analyses were conducted. A total of 11 845 128 doses of mRNA vaccines (57% BNT162b2; 6 175 813 first doses and 5 669 315 second doses) were administered to 6.2 million individuals (mean age, 49 years; 54% female individuals). The incidence of events per 1 000 000 person-years during the risk vs comparison intervals for ischemic stroke was 1612 vs 1781 (RR, 0.97; 95% CI, 0.87-1.08); for appendicitis, 1179 vs 1345 (RR, 0.82; 95% CI, 0.73-0.93); and for acute myocardial infarction, 935 vs 1030 (RR, 1.02; 95% CI, 0.89-1.18). No vaccine-outcome association met the prespecified requirement for a signal. Incidence of confirmed anaphylaxis was 4.8 (95% CI, 3.2-6.9) per million doses of BNT162b2 and 5.1 (95% CI, 3.3-7.6) per million doses of mRNA-1273. In interim analyses of surveillance of mRNA COVID-19 vaccines, incidence of selected serious outcomes was not significantly higher 1 to 21 days postvaccination compared with 22 to 42 days postvaccination. While CIs were wide for many outcomes, surveillance is ongoing.
Authors: Klein, Nicola P; Fireman, Bruce; Zerbo, Ousseny; Weintraub, Eric S; et al.
JAMA. 2021 10 12;326(14):1390-1399.
Intensive lactation among women with recent gestational diabetes significantly alters the early postpartum circulating lipid profile: the SWIFT study
Women with a history of gestational diabetes mellitus (GDM) have a 7-fold higher risk of developing type 2 diabetes (T2D). It is estimated that 20-50% of women with GDM history will progress to T2D within 10 years after delivery. Intensive lactation could be negatively associated with this risk, but the mechanisms behind a protective effect remain unknown. In this study, we utilized a prospective GDM cohort of 1010 women without T2D at 6-9 weeks postpartum (study baseline) and tested for T2D onset up to 8 years post-baseline (n=980). Targeted metabolic profiling was performed on fasting plasma samples collected at both baseline and follow-up (1-2 years post-baseline) during research exams in a subset of 350 women (216 intensive breastfeeding, IBF vs. 134 intensive formula feeding or mixed feeding, IFF/Mixed). The relationship between lactation intensity and circulating metabolites at both baseline and follow-up were evaluated to discover underlying metabolic responses of lactation and to explore the link between these metabolites and T2D risk. We observed that lactation intensity was strongly associated with decreased glycerolipids (TAGs/DAGs) and increased phospholipids/sphingolipids at baseline. This lipid profile suggested decreased lipogenesis caused by a shift away from the glycerolipid metabolism pathway towards the phospholipid/sphingolipid metabolism pathway as a component of the mechanism underlying the benefits of lactation. Longitudinal analysis demonstrated that this favorable lipid profile was transient and diminished at 1-2 years postpartum, coinciding with the cessation of lactation. Importantly, when stratifying these 350 women by future T2D status during the follow-up (171 future T2D vs. 179 no T2D), we discovered that lactation induced robust lipid changes only in women who did not develop incident T2D. Subsequently, we identified a cluster of metabolites that strongly associated with future T2D risk from which we developed a predictive metabolic signature with a discriminating power (AUC) of 0.78, superior to common clinical variables (i.e., fasting glucose, AUC 0.56 or 2-h glucose, AUC 0.62). In this study, we show that intensive lactation significantly alters the circulating lipid profile at early postpartum and that women who do not respond metabolically to lactation are more likely to develop T2D. We also discovered a 10-analyte metabolic signature capable of predicting future onset of T2D in IBF women. Our findings provide novel insight into how lactation affects maternal metabolism and its link to future diabetes onset. ClinicalTrials.gov NCT01967030 .
Authors: Zhang, Ziyi; Lai, Mi; Piro, Anthony L; Alexeeff, Stacey E; Allalou, Amina; Röst, Hannes L; Dai, Feihan F; Wheeler, Michael B; Gunderson, Erica P
BMC Med. 2021 10 08;19(1):241. Epub 2021-10-08.
Effectiveness of Covid-19 Vaccines in Ambulatory and Inpatient Care Settings
There are limited data on the effectiveness of the vaccines against symptomatic coronavirus disease 2019 (Covid-19) currently authorized in the United States with respect to hospitalization, admission to an intensive care unit (ICU), or ambulatory care in an emergency department or urgent care clinic. We conducted a study involving adults (≥50 years of age) with Covid-19-like illness who underwent molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed 41,552 admissions to 187 hospitals and 21,522 visits to 221 emergency departments or urgent care clinics during the period from January 1 through June 22, 2021, in multiple states. The patients’ vaccination status was documented in electronic health records and immunization registries. We used a test-negative design to estimate vaccine effectiveness by comparing the odds of a positive test for SARS-CoV-2 infection among vaccinated patients with those among unvaccinated patients. Vaccine effectiveness was adjusted with weights based on propensity-for-vaccination scores and according to age, geographic region, calendar time (days from January 1, 2021, to the index date for each medical visit), and local virus circulation. The effectiveness of full messenger RNA (mRNA) vaccination (≥14 days after the second dose) was 89% (95% confidence interval [CI], 87 to 91) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization, 90% (95% CI, 86 to 93) against infection leading to an ICU admission, and 91% (95% CI, 89 to 93) against infection leading to an emergency department or urgent care clinic visit. The effectiveness of full vaccination with respect to a Covid-19-associated hospitalization or emergency department or urgent care clinic visit was similar with the BNT162b2 and mRNA-1273 vaccines and ranged from 81% to 95% among adults 85 years of age or older, persons with chronic medical conditions, and Black or Hispanic adults. The effectiveness of the Ad26.COV2.S vaccine was 68% (95% CI, 50 to 79) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization and 73% (95% CI, 59 to 82) against infection leading to an emergency department or urgent care clinic visit. Covid-19 vaccines in the United States were highly effective against SARS-CoV-2 infection requiring hospitalization, ICU admission, or an emergency department or urgent care clinic visit. This vaccine effectiveness extended to populations that are disproportionately affected by SARS-CoV-2 infection. (Funded by the Centers for Disease Control and Prevention.).
Authors: Thompson, Mark G; Fireman, Bruce; Zerbo, Ousseny; Klein, Nicola P; et al.
N Engl J Med. 2021 10 07;385(15):1355-1371. Epub 2021-09-08.
QT Interval Dynamics and Cardiovascular Outcomes: A Cohort Study in an Integrated Health Care Delivery System
Background Long QT has been associated with ventricular dysrhythmias, cardiovascular disease (CVD) mortality, and sudden cardiac death. However, no studies to date have investigated the dynamics of within-person QT change over time in relation to risk of incident CVD and all-cause mortality in a real-world setting. Methods and Results A cohort study among members of an integrated health care delivery system in Northern California including 61 455 people (mean age, 62 years; 60% women, 42% non-White) with 3 or more ECGs (baseline in 2005-2009; mean±SD follow-up time, 7.6±2.6 years). In fully adjusted models, tertile 3 versus tertile 1 of average QT corrected (using the Fridericia correction) was associated with cardiac arrest (hazard ratio [HR], 1.66), heart failure (HR, 1.62), ventricular dysrhythmias (HR, 1.56), all CVD (HR, 1.31), ischemic heart disease (HR, 1.28), total stroke (HR, 1.18), and all-cause mortality (HR, 1.24). Tertile 3 versus tertile 2 of the QT corrected linear slope was associated with cardiac arrest (HR, 1.22), ventricular dysrhythmias (HR, 1.12), and all-cause mortality (HR, 1.09). Tertile 3 versus tertile 1 of the QT corrected root mean squared error was associated with ventricular dysrhythmias (HR, 1.34), heart failure (HR, 1.28), all-cause mortality (HR, 1.20), all CVD (HR, 1.14), total stroke (HR, 1.08), and ischemic heart disease (HR, 1.07). Conclusions Our results demonstrate improved predictive ability for CVD outcomes using longitudinal information from serial ECGs. Long-term average QT corrected was more strongly associated with CVD outcomes than the linear slope or the root mean squared error. This new evidence is clinically relevant because ECGs are frequently used, noninvasive, and inexpensive.
Authors: Mantri, Neha; Lu, Meng; Zaroff, Jonathan G; Risch, Neil; Hoffmann, Thomas; Oni-Orisan, Akinyemi; Lee, Catherine; Jorgenson, Eric; Iribarren, Carlos
J Am Heart Assoc. 2021 10 05;10(19):e018513. Epub 2021-09-28.
Hydrochlorothiazide and risk of melanoma subtypes
Hydrochlorothiazide (HCTZ), a common diuretic known to be photosensitizing and previously associated with non-melanoma skin cancer, was recently reported to be associated with two melanoma subtypes, nodular and lentigo, among residents of Denmark. Our goal was to examine whether Danish findings could be replicated in a US cohort, using a similar study design and analysis. Among non-Hispanic White enrollees of Kaiser Permanente Northern California, we conducted an analysis of 9176 melanoma cases and 264 781 controls, matched on age, sex and time in health plan. We examined use of HCTZ prior to cancer diagnosis (cases) or comparable date for controls, categorized as never use, ever use and high use (≥50 000 mg). Electronic health records provided data on prescriptions, cancer diagnoses, and covariates. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for education, income and number of dermatology, internal medicine and urgent care visits. We observed a small increase in risk of melanoma, all types combined, associated with high use (≥50 000 mg) of HCTZ (OR = 1.11, 95% CI 1.00-1.23) and no evidence of a dose-response. Risk was more elevated for lentigo subtype (OR = 1.57, 95% CI 1.01-2.42). The somewhat elevated risk for nodular subtype was not statistically significant (OR = 1.22, 95% CI 0.78-1.90). There was very little association of high use with the superficial spreading subtype (OR = 1.05, 95% CI 0.80-1.37). Our findings support a recent report of an association between high use of HCTZ and increased risk of the lentigo subtype of melanoma.
Authors: Habel, Laurel A; Achacoso, Ninah; Fireman, Bruce; Pedersen, Sidsel Arnspang; Pottegård, Anton
Pharmacoepidemiol Drug Saf. 2021 10;30(10):1396-1401. Epub 2021-05-26.
Association of Cardiovascular Outcomes and Mortality With Sustained Long-Acting Insulin Only vs Long-Acting Plus Short-Acting Insulin Treatment
Cardiovascular events and mortality are the principal causes of excess mortality and health care costs for people with type 2 diabetes. No large studies have specifically compared long-acting insulin alone with long-acting plus short-acting insulin with regard to cardiovascular outcomes. To compare cardiovascular events and mortality in adults with type 2 diabetes receiving long-acting insulin who do or do not add short-acting insulin. This retrospective cohort study emulated a randomized experiment in which adults with type 2 diabetes who experienced a qualifying glycated hemoglobin A1c (HbA1c) level of 6.8% to 8.5% with long-acting insulin were randomized to continuing treatment with long-acting insulin (LA group) or adding short-acting insulin within 1 year of the qualifying HbA1c level (LA plus SA group). Retrospective data in 4 integrated health care delivery systems from the Health Care Systems Research Network from January 1, 2005, to December 31, 2013, were used. Analysis used inverse probability weighting estimation with Super Learner for propensity score estimation. Analyses took place from April 1, 2018, to June 30, 2019. Long-acting insulin alone or with added short-acting insulin within 1 year from the qualifying HbA1c level. Mortality, cardiovascular mortality, acute myocardial infarction, stroke, and hospitalization for heart failure. Among 57 278 individuals (39 279 with data on cardiovascular mortality) with a mean (SD) age of 60.6 (11.5) years, 53.6% men, 43.5% non-Hispanic White individuals, and 4 years of follow-up (median follow-up of 11 [interquartile range, 5-20] calendar quarters), the LA plus SA group was associated with increased all-cause mortality compared with the LA group (hazard ratio, 1.27; 95% CI, 1.05-1.49) and a decreased risk of acute myocardial infarction (hazard ratio, 0.89; 95% CI, 0.81-0.97). Treatment with long-acting plus short-acting insulin was not associated with increased risks of congestive heart failure, stroke, or cardiovascular mortality. Findings of this retrospective cohort study suggested an increased risk of all-cause mortality and a decreased risk of acute myocardial infarction for the LA plus SA group compared with the LA group. Given the lack of an increase in major cardiovascular events or cardiovascular mortality, the increased all-cause mortality with long-acting plus short-acting insulin may be explained by noncardiovascular events or unmeasured confounding.
Authors: Schroeder, Emily B; Neugebauer, Romain; Schmittdiel, Julie A; O'Connor, Patrick J; et al.
JAMA Netw Open. 2021 09 01;4(9):e2126605. Epub 2021-09-01.
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.
Lifestyle-related education and counseling resource utilization and cardiovascular biomarkers in midlife women with low physical activity
Health plan-based resources are promising avenues for decreasing cardiovascular disease risk. This study examined associations of lifestyle-related resource utilization within a healthcare delivery system and cardiovascular biomarkers among midlife women with low physical activity. Midlife women (45-55 years old) with <10 min/week of reported physical activity at a primary care visit within a large integrated healthcare delivery system in Northern California in 2015 (n = 55,393) were identified. Within this cohort, subsequent lifestyle-related health education and individual coaching resource utilization, and the next recorded physical activity, weight, systolic blood pressure, plasma glucose, HDL and LDL cholesterol measures up to 2 years after the index primary care visit were identified from electronic health records. We used a multilevel linear model to estimate associations. About 3% (n = 1587) of our cohort had ≥1 lifestyle-related resource encounter; 0.3% (n = 178) had ≥ 4 encounters. Participation in ≥4 lifestyle-related resource encounters (compared to none) was associated with 51 more minutes/week of physical activity (95% CI: 33,69) at the next clinical measurement in all women, 6.2 kg lower weight (95% CI: -7.0,-5.5) at the next measurement in women with obesity, and 8-10 mg/dL lower plasma glucose (95% CI: -30,14 and -23,2, respectively) at the next measurement in women with diabetes or prediabetes. Our results support the sustained utilization of health plan-based lifestyle-related resources for improving physical activity, weight, and plasma glucose in high-risk midlife women. Given the observed low utilization, health system-wide efforts may be warranted to increase utilization of lifestyle-related resources in this population.
Authors: Badon, Sylvia E; Nance, Nerissa; Fogelberg, Renee; Quesenberry, Charles; Hedderson, Monique M; Avalos, Lyndsay A
Prev Med Rep. 2021 Sep;23:101401. Epub 2021-05-17.
Healthy preconception and early-pregnancy lifestyle and risk of preterm birth: a prospective cohort study
Preterm birth (PTB) remains a leading cause of neonatal mortality and long-term morbidity. Individual factors have been linked to PTB risk. The impact of a healthy lifestyle, with multiple modifiable prenatal factors, remains unknown. We aimed to examine the associations of preconceptional and early-pregnancy low-risk modifiable factors (individually and in combination) with PTB risk. This prospective cohort study included 2449 women with singleton pregnancies in the Pregnancy Environment and Lifestyle Study. PTB was defined as ultrasound-confirmed obstetric estimate-based gestational age at delivery <37 wk. A set of low-risk modifiable factors were identified: healthy weight (prepregnancy BMI: 18.5-24.9 kg/m2) based on clinical measurements and high-quality diet (Alternate Healthy Eating Index-Pregnancy score ≥75th percentile) and low-to-moderate stress during early pregnancy (Perceived Stress Scale score <75th percentile) assessed at gestational weeks 10-13. Poisson regression estimated adjusted relative risk (aRR) of PTB in association with individual and combined low-risk modifiable prenatal factors, adjusting for sociodemographic, clinical, and other prenatal factors. One hundred and sixty women (6.5%) delivered preterm. Risk of PTB was lower among women who had a healthy weight (aRR: 0.58; 95% CI: 0.39, 0.86), high-quality diet (aRR: 0.68; 95% CI: 0.39, 0.99), and low-to-moderate stress (aRR: 0.60; 95% CI: 0.41, 0.88). Women with 1, 2, or 3 low-risk modifiable prenatal factors compared with none had a 38% (aRR: 0.72; 95% CI: 0.45, 1.16), 51% (aRR: 0.49; 95% CI: 0.29, 0.84), or 70% (aRR: 0.30; 95% CI: 0.13, 0.70) lower PTB risk, respectively. Associations of having ≥1 low-risk factor with PTB risk were more pronounced for medically indicated than for spontaneous PTB and for late than for early or moderate PTB. Associations also varied by race or ethnicity, although with overlapping 95% CIs. A healthy prenatal lifestyle with multiple low-risk modifiable factors was associated with lower risk of PTB. Our findings may inform multicomponent preconceptional or early-pregnancy prevention strategies to mitigate PTB risk.
Authors: Zhu, Yeyi; Hedderson, Monique M; Brown, Susan D; Badon, Sylvia E; Feng, Juanran; Quesenberry, Charles P; Ferrara, Assiamira
Am J Clin Nutr. 2021 08 02;114(2):813-821.
AUTOMATED ALERTS IN OBSTETRICS
Authors: Escobar, Gabriel J; Schuler, Alejandro; Lee, Catherine
Am J Obstet Gynecol. 2021 08;225(2):208. Epub 2021-04-23.
COVID-19 Vaccination Coverage Among Insured Persons Aged ≥16 Years, by Race/Ethnicity and Other Selected Characteristics – Eight Integrated Health Care Organizations, United States, December 14, 2020-May 15, 2021
COVID-19 vaccination is critical to ending the COVID-19 pandemic. Members of minority racial and ethnic groups have experienced disproportionate COVID-19-associated morbidity and mortality (1); however, COVID-19 vaccination coverage is lower in these groups (2). CDC used data from CDC’s Vaccine Safety Datalink (VSD)* to assess disparities in vaccination coverage among persons aged ≥16 years by race and ethnicity during December 14, 2020-May 15, 2021. Measures of coverage included receipt of ≥1 COVID-19 vaccine dose (i.e., receipt of the first dose of the Pfizer-BioNTech or Moderna COVID-19 vaccines or 1 dose of the Janssen COVID-19 vaccine [Johnson & Johnson]) and full vaccination (receipt of 2 doses of the Pfizer-BioNTech or Moderna COVID-19 vaccines or 1 dose of Janssen COVID-19 vaccine). Among 9.6 million persons aged ≥16 years enrolled in VSD during December 14, 2020-May 15, 2021, ≥1-dose coverage was 48.3%, and 38.3% were fully vaccinated. As of May 15, 2021, coverage with ≥1 dose was lower among non-Hispanic Black (Black) and Hispanic persons (40.7% and 41.1%, respectively) than it was among non-Hispanic White (White) persons (54.6%). Coverage was highest among non-Hispanic Asian (Asian) persons (57.4%). Coverage with ≥1 dose was higher among persons with certain medical conditions that place them at higher risk for severe COVID-19 (high-risk conditions) (63.8%) than it was among persons without such conditions (41.5%) and was higher among persons who had not had COVID-19 (48.8%) than it was among those who had (42.4%). Persons aged 18-24 years had the lowest ≥1-dose coverage (28.7%) among all age groups. Continued monitoring of vaccination coverage and efforts to improve equity in coverage are critical, especially among populations disproportionately affected by COVID-19.
Authors: Pingali, Cassandra; Klein, Nicola P; Fireman, Bruce; Zerbo, Ousseny; Patel, Suchita A; et al.
MMWR Morb Mortal Wkly Rep. 2021 Jul 16;70(28):985-990. Epub 2021-07-16.
Particulate Matter and Cardiovascular Risk in Adults with Chronic Obstructive Pulmonary Disease
Rationale: People with chronic obstructive pulmonary disease (COPD) have an increased risk of cardiovascular disease and may be more susceptible to air pollution exposure. However, no study has examined the association between long-term fine particulate matter exposure (≤2.5 μm in aerodynamic diameter) and risk of cardiovascular events in this potentially vulnerable population. Objectives: To estimate the association between long-term fine particulate matter and risk of cardiovascular events among adults with COPD. Methods: This retrospective cohort study included 169,714 adults with COPD who were members of the Kaiser Permanente Northern California health plan during 2007-2016. Electronic health record data were linked to 1 km modeled particulate matter ≤2.5 μm in aerodynamic diameter exposure estimates. We fit Cox proportional hazard models, adjusting for age, sex, race/ethnicity, calendar year, smoking, body mass index, comorbidities, medications, and socioeconomic status. In low exposure analyses, we examined effects below the current regulation limit (12 μg/m3). Measurements and Main Results: Among adults with COPD, a 10-μg/m3 increase in 1-year mean fine particulate matter exposure was associated with an elevated risk of cardiovascular mortality (hazard ratio, 1.10; 95% confidence interval [CI], 1.01-1.20). Effects were stronger in low exposure analyses (hazard ratio, 1.88; 95% CI, 1.56-2.27). Fine particulate matter exposure was not associated with acute myocardial infarction or stroke in overall analyses. Conclusions: Long-term fine particulate matter exposure was associated with an increased risk of cardiovascular mortality among adults with COPD. Current regulations may not sufficiently protect those with COPD.
Authors: Alexeeff, Stacey E; Deosaransingh, Kamala; Liao, Noelle S; Van Den Eeden, Stephen K; Schwartz, Joel; Sidney, Stephen
Am J Respir Crit Care Med. 2021 07 15;204(2):159-167.
The effect of mail order pharmacy outreach on older patients with diabetes
Authors: Gong, Chelsea; Dyer, Wendy; Yassin, Maher; Neugebauer, Romain; Karter, Andrew J; Schmittdiel, Julie A
J Am Geriatr Soc. 2021 07;69(7):2028-2030. Epub 2021-03-26.
Mediating Effects of Cardiometabolic Risk Factors on the Association Between Maternal Race-Ethnicity and Cesarean Delivery Among Low-Risk Women
Background: While racial-ethnic disparities in cesarean delivery rates among nulliparous women delivering a term singleton in the vertex position (NTSV) exist, it remains unclear the extent to which potentially modifiable maternal cardiometabolic risk factors (obesity, maternal hyperglycemia and hypertensive disorders) underlie these disparities. We examined race-ethnicity and risk of NTSV cesarean deliveries and whether the associations were mediated by maternal cardiometabolic risk factors. Materials and Methods: A cohort study of 62,048 NTSV deliveries in Kaiser Permanente Northern California. The outcome was cesarean delivery. Results: Black, Asian, and Hispanic women were at increased risk of having a NTSV cesarean delivery compared with White women (relative risks and 95% confidence intervals: 1.37 [1.28-1.45]; 1.11 [1.07-1.16]; 1.12 [1.07-1.16], respectively), independent of established risk factors and prenatal care utilization. The extent to which cardiometabolic risk factors mediated the associations between race-ethnicity (each group vs. White, in separate analyses) and NTSV cesarean delivery varied by race-ethnicity. Maternal overweight/obesity (body mass index ≥25.0) mediated the association between Black and Hispanic race-ethnicity and NTSV cesarean delivery (21.1% [15.8-26.4] and 24.7% [14.6-34.8, respectively), but not for Asian race. Maternal hyperglycemia (gestational diabetes mellitus or preexisting diabetes) mediated the association between Asian and Hispanic race and NTSV cesarean delivery (18.5% [9.8-27.2] and 9.8% [5.0-14.7], respectively), but not for Black race. Hypertensive disorders mediated 3.2% (0.70-5.8) of the association between Black race and cesarean delivery, but not for other race-ethnicities. Conclusion: Black, Asian, and Hispanic women are at increased risk for NTSV cesarean deliveries. Maternal cardiometabolic risk factors only partially mediate the associations between race-ethnicity and NSTV cesarean deliveries.
Authors: Hedderson, Monique M; Xu, Fei; Liu, Emily; Sridhar, Sneha B; Quesenberry, Charles P; Flanagan, Tracy A
J Womens Health (Larchmt). 2021 07;30(7):1028-1037. Epub 2021-02-11.
Separating Algorithms from Questions and Causal Inference with Unmeasured Exposures: An Application to Birth Cohort Studies of Early BMI Rebound
Observational studies reporting on adjusted associations between childhood body mass index (BMI; weight (kg)/height (m)2) rebound and subsequent cardiometabolic outcomes have often not paid explicit attention to causal inference, including definition of a target causal effect and assumptions for unbiased estimation of that effect. Using data from 649 children in a Boston, Massachusetts-area cohort recruited in 1999-2002, we considered effects of stochastic interventions on a chosen subset of modifiable yet unmeasured exposures expected to be associated with early ( Authors: Aris, Izzuddin M; Sarvet, Aaron L; Stensrud, Mats J; Neugebauer, Romain; Li, Ling-Jun; Hivert, Marie-France; Oken, Emily; Young, Jessica G Am J Epidemiol. 2021 07 01;190(7):1414-1423.
Visual Outcomes After Cataract Surgery: Topical NSAID Prophylaxis Compared with Prednisolone
To compare visual outcomes in patients without a history of macular edema after phacoemulsification using combination topical nonsteroidal anti-inflammatory drug plus prednisolone with prednisolone alone. Kaiser Permanente Northern California, USA. Retrospective cohort study. Information was obtained from the electronic health record. The first measure of corrected distance visual acuity (CDVA) recorded during the period 3 weeks to 1 year after phacoemulsification was obtained. Confounding factors and clustering of eyes within patients were adjusted using linear mixed effects regression models for the continuous outcome of CDVA improvement and general estimating equations for the dichotomous outcome of 20/20 or better vs 20/25 or worse. The study included 62 700 health plan members of whom 26,309 (42%) used topical prednisolone alone, whereas 36,391 (58%) used combination treatment. The mean within-person change in CDVA from the preoperative measurement to the postoperative measurement was the same (-0.43 logMAR) for patients in the 2 groups. However, the group that received combination treatment was somewhat more likely to achieve CDVA of 20/20 or better (odds ratio 1.24 with 95% CI, 1.20-1.28). In this large study of cataract surgery patients, a small statistically significant association of combination treatment compared with prednisolone alone was observed.
Authors: Shorstein, Neal H; Carolan, James; Liu, Liyan; Alexeeff, Stacey E; Amsden, Laura B; Herrinton, Lisa J
J Cataract Refract Surg. 2021 Jul 01;47(7):870-877.
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.
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.
A prognostic information system for real-time personalized care: Lessons for embedded researchers
Embedded researchers could play a central role in developing tools to personalize care using electronic medical records (EMRs). However, few studies have described the steps involved in developing such tools, or evaluated the key factors in success and failure. This case study describes how we used an EMR-derived data warehouse to develop a prototype informatics tool to help oncologists counsel patients with pancreatic cancer about their prognosis. The tool generated real-time prognostic information based on tumor type and stage, age, comorbidity status and lab tests. Our multidisciplinary team included embedded researchers, application developers, user experience experts, and an oncologist leader.This prototype succeeded in establishing proof of principle, but did not reach adoption into actual practice. In pilot testing, oncologists succeeded in generating prognostic information in real time. A few found it helpful in patient encounters, but all identified critical areas for further development before implementation. Generalizable lessons included the need to (1) include a wide range of potential use cases and stakeholders when selecting use cases for such tools; (2) develop talking points for clinicians to explain results from predictive tools to patients; (3) develop ways to reduce lag time between events and data availability; and (4) keep the options presented in the user interface very simple. This case demonstrates that embedded researchers can lead collaborations using EMR-derived data to create systems for real-time personalized patient counseling, and highlights challenges that such teams can anticipate.
Authors: Lieu, Tracy A; Neugebauer, Romain; Van Den Eeden, Stephen K; Baer, David M; et al.
Healthc (Amst). 2021 Jun;8 Suppl 1:100486. Epub 2021-06-23.
Is Shelter-in-Place Policy Related to Mail Order Pharmacy Use and Racial/Ethnic Disparities for Patients With Diabetes?
Authors: Thomas, Tainayah W; Dyer, Wendy T; Yassin, Maher; Neugebauer, Romain; Karter, Andrew J; Schmittdiel, Julie A
Diabetes Care. 2021 06;44(6):e113-e114. Epub 2021-04-13.
Racial Disparities in COVID-19 Testing and Outcomes : Retrospective Cohort Study in an Integrated Health System
Racial disparities exist in outcomes after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To evaluate the contribution of race/ethnicity in SARS-CoV-2 testing, infection, and outcomes. Retrospective cohort study (1 February 2020 to 31 May 2020). Integrated health care delivery system in Northern California. Adult health plan members. Age, sex, neighborhood deprivation index, comorbid conditions, acute physiology indices, and race/ethnicity; SARS-CoV-2 testing and incidence of positive test results; and hospitalization, illness severity, and mortality. Among 3 481 716 eligible members, 42.0% were White, 6.4% African American, 19.9% Hispanic, and 18.6% Asian; 13.0% were of other or unknown race. Of eligible members, 91 212 (2.6%) were tested for SARS-CoV-2 infection and 3686 had positive results (overall incidence, 105.9 per 100 000 persons; by racial group, White, 55.1; African American, 123.1; Hispanic, 219.6; Asian, 111.7; other/unknown, 79.3). African American persons had the highest unadjusted testing and mortality rates, White persons had the lowest testing rates, and those with other or unknown race had the lowest mortality rates. Compared with White persons, adjusted testing rates among non-White persons were marginally higher, but infection rates were significantly higher; adjusted odds ratios [aORs] for African American persons, Hispanic persons, Asian persons, and persons of other/unknown race were 2.01 (95% CI, 1.75 to 2.31), 3.93 (CI, 3.59 to 4.30), 2.19 (CI, 1.98 to 2.42), and 1.57 (CI, 1.38 to 1.78), respectively. Geographic analyses showed that infections clustered in areas with higher proportions of non-White persons. Compared with White persons, adjusted hospitalization rates for African American persons, Hispanic persons, Asian persons, and persons of other/unknown race were 1.47 (CI, 1.03 to 2.09), 1.42 (CI, 1.11 to 1.82), 1.47 (CI, 1.13 to 1.92), and 1.03 (CI, 0.72 to 1.46), respectively. Adjusted analyses showed no racial differences in inpatient mortality or total mortality during the study period. For testing, comorbid conditions made the greatest relative contribution to model explanatory power (77.9%); race only accounted for 8.1%. Likelihood of infection was largely due to race (80.3%). For other outcomes, age was most important; race only contributed 4.5% for hospitalization, 12.8% for admission illness severity, 2.3% for in-hospital death, and 0.4% for any death. The study involved an insured population in a highly integrated health system. Race was the most important predictor of SARS-CoV-2 infection. After infection, race was associated with increased hospitalization risk but not mortality. The Permanente Medical Group, Inc.
Authors: Escobar, Gabriel J; Adams, Alyce S; Liu, Vincent X; Soltesz, Lauren; Chen, Yi-Fen Irene; Parodi, Stephen M; Ray, G Thomas; Myers, Laura C; Ramaprasad, Charulata M; Dlott, Richard; Lee, Catherine
Ann Intern Med. 2021 06;174(6):786-793. Epub 2021-02-09.
Design of the Association of Uterine Perforation and Expulsion of IUD (APEX-IUD) Study: A Multisite Retrospective Cohort Study
Intrauterine devices are effective and safe, long-acting reversible contraceptives, but the risk of uterine perforation occurs with an estimated incidence of 1 to 2 per 1000 insertions. The European Active Surveillance Study for Intrauterine Devices, a European prospective observational study that enrolled 61,448 participants (2006-2012), found that women breastfeeding at the time of device insertion or with the device inserted at ≤36 weeks after delivery had a higher risk of uterine perforation. The Association of Uterine Perforation and Expulsion of Intrauterine Device (APEX-IUD) study was a Food and Drug Administration-mandated study designed to reflect current United States clinical practice. The aims of the APEX-IUD study were to evaluate the risk of intrauterine device-related uterine perforation and device expulsion among women who were breastfeeding or within 12 months after delivery at insertion. We aimed to describe the APEX-IUD study design, methodology, and analytical plan and present population characteristics, size of risk factor groups, and duration of follow-up. APEX-IUD study was a retrospective cohort study conducted in 4 organizations with access to electronic health records: Kaiser Permanente Northern California, Kaiser Permanente Southern California, Kaiser Permanente Washington, and Regenstrief Institute in Indiana. Variables were identified through structured data (eg, diagnostic, procedural, medication codes) and unstructured data (eg, clinical notes) via natural language processing. Outcomes include uterine perforation and device expulsion; potential risk factors were breastfeeding at insertion, postpartum timing of insertion, device type, and menorrhagia diagnosis in the year before insertion. Covariates include demographic characteristics, clinical characteristics, and procedure-related variables, such as difficult insertion. The first potential date of inclusion for eligible women varies by research site (from January 1, 2001 to January 1, 2010). Follow-up begins at insertion and ends at first occurrence of an outcome of interest, a censoring event (device removal or reinsertion, pregnancy, hysterectomy, sterilization, device expiration, death, disenrollment, last clinical encounter), or end of the study period (June 30, 2018). Comparisons of levels of exposure variables were made using Cox regression models with confounding adjusted by propensity score weighting using overlap weights. The study population includes 326,658 women with at least 1 device insertion during the study period (Kaiser Permanente Northern California, 161,442; Kaiser Permanente Southern California, 123,214; Kaiser Permanente Washington, 20,526; Regenstrief Institute, 21,476). The median duration of continuous enrollment was 90 (site medians 74-177) months. The mean age was 32 years, and the population was racially and ethnically diverse across the 4 sites. The mean body mass index was 28.5 kg/m2, and of the women included in the study, 10.0% had menorrhagia ≤12 months before insertion, 5.3% had uterine fibroids, and 10% were recent smokers; furthermore, among these women, 79.4% had levonorgestrel-releasing devices, and 19.5% had copper devices. Across sites, 97,824 women had an intrauterine device insertion at ≤52 weeks after delivery, of which 94,817 women (97%) had breastfeeding status at insertion determined; in addition, 228,834 women had intrauterine device insertion at >52 weeks after delivery or no evidence of a delivery in their health record. Combining retrospective data from multiple sites allowed for a large and diverse study population. Collaboration with clinicians in the study design and validation of outcomes ensured that the APEX-IUD study results reflect current United States clinical practice. Results from this study will provide valuable information based on real-world evidence about risk factors for intrauterine devices perforation and expulsion for clinicians.
Authors: Anthony, Mary S; Getahun, Darios; Asiimwe, Alex; et al.
Am J Obstet Gynecol. 2021 06;224(6):599.e1-599.e18. Epub 2021-01-15.
Timing of Antiretroviral Therapy Initiation and Risk of Cancer among Persons Living with HIV
Persons living with human immunodeficiency virus (HIV; PLWH) experience a high burden of cancer. It remains unknown which cancer types are reduced in PLWH with earlier initiation of antiretroviral therapy (ART). We evaluated AIDS-free, ART-naive PLWH during 1996-2014 from 22 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. PLWH were followed from first observed CD4 of 350-500 cells/µL (baseline) until incident cancer, death, lost-to-follow-up, or December 2014. Outcomes included 6 cancer groups and 5 individual cancers that were confirmed by chart review or cancer registry linkage. We evaluated the effect of earlier (in the first 6 months after baseline) versus deferred ART initiation on cancer risk. Marginal structural models were used with inverse probability weighting to account for time-dependent confounding and informative right-censoring, with weights informed by subject’s age, sex, cohort, baseline year, race/ethnicity, HIV transmission risk, smoking, viral hepatitis, CD4, and AIDS diagnoses. Protective results for earlier ART were found for any cancer (adjusted hazard ratio [HR] 0.57; 95% confidence interval [CI], .37-.86), AIDS-defining cancers (HR 0.23; 95% CI, .11-.49), any virus-related cancer (HR 0.30; 95% CI, .16-.54), Kaposi sarcoma (HR 0.25; 95% CI, .10-.61), and non-Hodgkin lymphoma (HR 0.22; 95% CI, .06-.73). By 15 years, there was also an observed reduced risk with earlier ART for virus-related NADCs (0.6% vs 2.3%; adjusted risk difference -1.6; 95% CI, -2.8, -.5). Earlier ART initiation has potential to reduce the burden of virus-related cancers in PLWH but not non-AIDS-defining cancers (NADCs) without known or suspected viral etiology.
Authors: Silverberg, Michael J; Neugebauer, Romain S; et al.
Clin Infect Dis. 2021 06 01;72(11):1900-1909.
Particulate Air Pollution and Risk of Cardiovascular Events Among Adults With a History of Stroke or Acute Myocardial Infarction
Background Previous studies have found associations between fine particulate matter <2.5 µm in diameter (PM2.5) and increased risk of cardiovascular disease (CVD) among populations with no CVD history. Less is understood about susceptibility of adults with a history of CVD and subsequent PM2.5-related CVD events and whether current regulation levels for PM2.5 are protective for this population. Methods and Results This retrospective cohort study included 96 582 Kaiser Permanente Northern California adults with a history of stroke or acute myocardial infarction. Outcome, covariate, and address data obtained from electronic health records were linked to time-varying 1-year mean PM2.5 exposure estimates based on residential locations. Cox proportional hazard models estimated risks of stroke, acute myocardial infarction, and cardiovascular mortality associated with PM2.5 exposure, adjusting for multiple covariates. Secondary analyses estimated risks below federal and state regulation levels (12 µg/m3 for 1-year mean PM2.5). A 10-µg/m3 increase in 1-year mean PM2.5 exposure was associated with an increase in risk of cardiovascular mortality (hazard ratio [HR], 1.20; 95% CI, 1.11-1.30), but no increase in risk of stroke or acute myocardial infarction. Analyses of <12 µg/m3 showed increased risk for CVD mortality (HR, 2.31; 95% CI, 1.96-2.71), stroke (HR, 1.41; 95% CI, 1.09-1.83]), and acute myocardial infarction (HR, 1.51; 95% CI, 1.21-1.89) per 10-µg/m3 increase in 1-year mean PM2.5. Conclusions Adults with a history of CVD are susceptible to the effects of PM2.5 exposure, particularly on CVD mortality. Increased risks observed at exposure levels <12 µg/m3 highlight that current PM2.5 regulation levels may not be protective for this susceptible population.
Authors: Liao, Noelle S; Sidney, Stephen; Deosaransingh, Kamala; Van Den Eeden, Stephen K; Schwartz, Joel; Alexeeff, Stacey E
J Am Heart Assoc. 2021 05 18;10(10):e019758. Epub 2021-05-04.
The Association of Lactation Duration with Visceral and Pericardial Fat Volumes in Parous Women: the CARDIA Study
Lactation is associated with lower risks for cardiovascular disease in women. Organ-related adiposity, which plays significant roles in the development of cardiometabolic diseases, could help explain this observation. We evaluated the association of lactation duration with visceral (VAT) and pericardial (PAT) fat volumes in women. Data were obtained from 910 women enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study (1985-1986) without diabetes prior to pregnancy who had ≥1 birth during 25 years of follow-up and had VAT and PAT measured from computed tomographic scans in 2010-2011. Cumulative lactation duration across all births since baseline was calculated from self-reports collected at periodic exams. At baseline, the average age of women (48% black, 52% white) was 24 ± 3.7 years. After controlling for baseline age, race, smoking status, body mass index, fasting glucose, family history of diabetes, fat intake, total cholesterol, physical activity, and follow-up covariates (parity, gestational diabetes), the mean fat volumes across categories of lactation [none (n = 221), 1-5 months (n = 306), 6-11 months (n = 210), and ≥12 months (n = 173)] were 122.0, 113.7 105.0, and 110.1 cm3 for VAT and 52.2, 46.7, 44.5, and 43.4 cm3 for PAT, respectively. Changes in body weight from the first post-baseline birth to the end of follow-up mediated 21% and 18% of the associations of lactation with VAT and PAT, respectively. In this prospective study, longer cumulative lactation duration was associated with lower VAT and PAT volumes, with weight gain partially mediating these associations.
Authors: Appiah, Duke; Lewis, Cora E; Jacobs, David R; Shikany, James M; Quesenberry, Charles P; Gross, Myron; Carr, Jeff; Sidney, Stephen; Gunderson, Erica P
J Clin Endocrinol Metab. 2021 05 13;106(6):1821-1831.
Ten-Year Follow-up of Persons With Sun-Damaged Skin Associated With Subsequent Development of Cutaneous Squamous Cell Carcinoma
Risk of cutaneous squamous cell carcinoma (cSCC) after the diagnosis of actinic keratosis (AK) has not been studied during long follow-up periods. To estimate the risk up to 10 years and identify risk factors for cSCC development. This longitudinal cohort study, performed from January 1, 2009, to February 29, 2020, examined Kaiser Permanente Northern California patients with AK and control patients matched 1:1 on age, sex, race/ethnicity, medical center, and date of the initial diagnosis plus 30 days in the patients with AK. Patients with AK and control participants were followed up for up to 10 years for incidence of cSCC. Incident cSCC was obtained from pathologic data, and subdistribution hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression analysis, accounting for competing risks, calendar year, demographic factors, and number of AKs. The study included 220 236 patients with AK and 220 236 matched control patients (mean [SD] age, 64.1 [12.2] years; 231 248 [52.5%] female). After losses to follow-up were accounted for, risk of cSCC increased with each year of follow-up by 1.92% (95% CI, 1.89%-1.95%) in patients with AK and 0.83% (95% CI, 0.81%-0.85%) in matched control patients (subdistribution HR, 1.90; 95% CI, 1.85-1.95). However, among patients 49 years or younger, those diagnosed with AK were nearly 7 times more likely to be diagnosed with cSCC than those without AK (HR, 6.77; 95% CI, 5.50-8.32). At 10 years, the cumulative incidence of cSCC reached 17.1% (95% CI, 16.9%-17.4%) in patients with AK and 5.7% (95% CI, 5.5%-5.9%) in control patients. Increased numbers of AKs were modestly associated with increased cSCC risk (≥15 AKs vs 1 AK: subdistribution HR, 1.89; 95% CI, 1.75-2.04). Older patients had much higher risk of cSCC than younger patients (compared with those ≤49 years of age at AK diagnosis; ≥80 years of age: subdistribution HR, 8.18; 95% CI, 7.62-8.78). Other than AK, risk factors for cSCC included older age, White race (a proxy for skin type), history of basal cell carcinoma, and male sex. Risk decreased between 2009 and 2019 (2018-2019 vs 2009-2010: subdistribution HR, 0.67; 95% CI, 0.63-0.72). The results of this longitudinal cohort study can be used to develop recommendations to increase early detection of cSCC. Additional research is needed to understand the effect of AK treatment on cSCC risk and outcomes of cSCC.
Authors: Madani, Shabnam; Marwaha, Sangeeta; Dusendang, Jennifer R; Alexeeff, Stacey; Pham, Ngoc; Chen, Elbert H; Han, Sandra; Herrinton, Lisa J
JAMA Dermatol. 2021 05 01;157(5):559-565.
Intraocular Pressure Reduction After Phacoemulsification: A Matched Cohort Study
Phacoemulsification has been linked to lowered intraocular pressure (IOP) in patients with glaucoma, ocular hypertension, anatomic narrow angles, and in glaucoma suspects, but the magnitude of change has varied. Retrospective cohort study. Patients with glaucoma treated from June 2010 through May 2015 who underwent phacoemulsification (surgical group) were matched to patients who did not (nonsurgical group) for age, gender, type of glaucoma, baseline IOP, and number and type of glaucoma medications. Electronic medical record information was used to compare the matched surgical and nonsurgical groups. Change in IOP, change in number of glaucoma medications, and likelihood of a glaucoma procedure within 36 months after phacoemulsification. Intraocular pressure measures were obtained from Goldmann applanation tonometry when available (45%), and otherwise with the iCare tonometer (iCare USA, Raleigh, NC), the Tono-Pen (Reichert Technologies, Depew, NY), noncontact tonometry, and pneumotonometry. Among 16 169 matched pairs, average IOP after the index date was lower in the surgical than nonsurgical group throughout follow-up to 36 months. The difference was greatest during months 1 through 18, during which IOP increased by 0.22 mmHg from 16.49 mmHg in the average nonsurgical patient and decreased by 0.99 mmHg from 16.50 mmHg in the average surgical patient (difference in difference, 1.21 mmHg; 95% confidence interval [CI], 1.12-1.30 mmHg). The difference in difference was greatest for patients with ocular hypertension (2.00 mmHg) and for patients with preoperative IOP of 20 mmHg or more (2.46 mmHg). By 30 to 36 months, 5% (95% CI, 4%-6%) fewer surgical patients used an ophthalmic medication. In the surgical group, the odds of selective laser trabeculoplasty were reduced in patients with ocular hypertension (odds ratio [OR], 0.27; 95% CI, 0.10-0.74) or glaucoma suspects (OR, 0.31; 95% CI, 0.20-0.47), whereas the odds of glaucoma surgery were elevated in surgical patients with primary open-angle glaucoma (OR, 1.48; 95% CI, 1.08-2.01). The association of phacoemulsification for cataract with IOP reduction was lower than in past referral-based studies. Surgeons should expect to reduce IOP approximately 1 to 2 mmHg with phacoemulsification in patients with preoperative IOP of less than 20 mmHg.
Authors: Carolan, James A; Liu, Liyan; Alexeeff, Stacey E; Amsden, Laura B; Shorstein, Neal H; Herrinton, Lisa J
Ophthalmol Glaucoma. 2021 May-Jun;4(3):277-285. Epub 2020-10-10.
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.
Patterns and Factors Associated With Adherence to Lung Cancer Screening in Diverse Practice Settings
For lung cancer screening to confer mortality benefit, adherence to annual screening with low-dose computed tomography scans is essential. Although the National Lung Screening Trial had an adherence rate of 95%, current data are limited on screening adherence across diverse practice settings in the United States. To evaluate patterns and factors associated with adherence to annual screening for lung cancer after negative results of a baseline examination, particularly in centralized vs decentralized screening programs. This observational cohort study was conducted at 5 academic and community-based sites in North Carolina and California among 2283 individuals screened for lung cancer between July 1, 2014, and March 31, 2018, who met US Preventive Services Task Force eligibility criteria, had negative results of a baseline screening examination (American College of Radiology Lung Imaging Reporting and Data System category 1 or 2), and were eligible to return for a screening examination in 12 months. To identify factors associated with adherence, the association of adherence with selected baseline demographic and clinical characteristics, including type of screening program, was estimated using multivariable logistic regression. Screening program type was classified as centralized if individuals were referred through a lung cancer screening clinic or program and as decentralized if individuals had a direct clinician referral for the baseline low-dose computed tomography scan. Adherence to annual lung cancer screening, defined as a second low-dose computed tomography scan within 11 to 15 months after baseline screening. Among the 2283 eligible individuals (1294 men [56.7%]; mean [SD] age, 64.9 [5.8] years; 1160 [50.8%] aged ≥65 years) who had negative screening results at baseline, overall adherence was 40.2% (n = 917), with higher adherence among those who underwent screening through centralized (46.0% [478 of 1039]) vs decentralized (35.3% [439 of 1244]) programs. The independent factor most strongly associated with adherence was type of screening program, with a 2.8-fold increased likelihood of adherence associated with centralized screening (adjusted odds ratio [aOR], 2.78; 95% CI, 1.99-3.88). Another associated factor was age (65-69 vs 55-59 years: aOR, 1.38; 95% CI, 1.07-1.77; 70-74 vs 55-59 years: aOR, 1.47; 95% CI, 1.10-1.96). After negative results of a baseline examination, adherence to annual lung cancer screening was suboptimal, although adherence was higher among individuals who were screened through a centralized program. These results support the value of centralized screening programs and the need to further implement strategies that improve adherence to annual screening for lung cancer.
Authors: Sakoda, Lori C; Quesenberry, Charles P; Henderson, Louise M; et al.
JAMA Netw Open. 2021 04 01;4(4):e218559. Epub 2021-04-01.
Clustering of Social and Physical Pain Variables and Their Association With Mortality in Two Population-Based Cohorts
Social pain and physical pain are related bidirectionally, but how these variables cluster in the population is unknown. This study included 2833 women from the Study of Women’s Health Across the Nation (SWAN), a community-based cohort of middle-aged women, and 3972 women from the Pathways Study, a population-based cohort of women diagnosed with American Joint Committee on Cancer stages I-IV breast cancer diagnosed between 2005 and 2013. Women provided data on measures related to social pain (social network size, social support, loneliness, social well-being) and physical pain (sensitivity to pain, bodily pain) at study baseline. Analyzing each cohort separately, we used latent class analysis to evaluate social-physical pain clusters, logistic regression to evaluate predictors of categorization into clusters, and Cox proportional hazards models to evaluate associations of clusters with all-cause mortality. We also performed a meta-analysis to combine cohort mortality associations. Each cluster analysis produced a “low social-physical pain” cluster (SWAN, 48.6%; Pathways, 35.2%) characterized by low social and pain symptoms, a “high social-physical pain” cluster (SWAN, 17.9%; Pathways, 17.9%) characterized by high symptoms, and a “low social/high physical pain” cluster of women with high pain and compromised social functioning but otherwise low social symptoms (SWAN, 33.5%; Pathways, 46.9%). In meta-analysis, categorization into the high social-physical pain cluster was associated with elevated mortality (adjusted hazard ratio = 1.34, 95% confidence interval = 1.05-1.71, Q statistic = 0.782), compared with those in the low social-physical pain cluster. In two cohorts of women, latent class analysis produced similar sets of social-physical pain clusters, with the same proportion having both high social and pain symptoms; women in this cluster had elevated mortality.
Authors: Kroenke, Candyce H; Alexeeff, Stacey; Kushi, Lawrence H; Kwan, Marilyn L; Matthews, Karen A
Psychosom Med. 2021 04 01;83(3):228-238.
Dual trajectories of physical activity and blood lipids in midlife women: The Study of Women’s Health Across the Nation
Physical activity (PA) has the potential to attenuate cardiovascular disease risk in midlife women through multiple pathways, including improving lipid profiles. Longitudinal patterns of PA and blood lipid levels have not been studied in midlife women. Our study identified trajectories of PA and blood lipids across midlife and characterized the associations between these trajectories. We evaluated 2,789 participants from the Study of Women’s Health Across the Nation (SWAN), a longitudinal cohort study with follow-up over the menopause transition. Women reported PA using the Kaiser Physical Activity Survey at seven study visits across 17 years of follow-up. Serum high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides were measured at eight study visits across the same 17-year follow-up period. We used group-based trajectory models to characterize trajectories of PA and blood lipids over midlife and dual trajectory models to determine the association between PA and blood lipid trajectories adjusted for race/ethnicity, body mass index category, smoking, and lipid-lowering medication use. Women were 46 years old, on average, at study entry. Forty-nine percent were non-Hispanic white; 32 % were Black; 10 % were Japanese; and 9 % were Chinese. We identified four PA trajectories, three HDL cholesterol trajectories, four LDL cholesterol trajectories, and two triglyceride trajectories. The most frequently occurring trajectories were the consistently low PA trajectory (69 % of women), the low HDL cholesterol trajectory (43 % of women), the consistently moderate LDL cholesterol trajectory (45 % of women), and the consistently low triglycerides trajectory (90 % of women). In dual trajectory analyses, no clear associations were observed between PA trajectories and HDL cholesterol, LDL cholesterol, or triglycerides trajectories. The most frequently observed trajectories across midlife were characterized by low physical activity, low HDL cholesterol, moderate LDL cholesterol, and low triglycerides. Despite the absence of an association between long-term trajectories of PA and blood lipids in this study, a large body of evidence has established the importance of clinical and public health messaging and interventions targeted at midlife women to promote regular and sustained PA during midlife to achieve other cardiovascular and metabolic benefits.
Authors: Badon, Sylvia E; Gabriel, Kelley Pettee; Karvonen-Gutierrez, Carrie; Sternfeld, Barbara; Gold, Ellen B; Waetjen, L Elaine; Lee, Catherine; Avalos, Lyndsay A; El Khoudary, Samar R; Hedderson, Monique M
Maturitas. 2021 Apr;146:49-56. Epub 2021-02-06.
mHealth Mindfulness Intervention for Women with Moderate-to-Moderately-Severe Antenatal Depressive Symptoms: a Pilot Study Within an Integrated Health Care System
Traditional mindfulness-based interventions have been shown to reduce depression symptoms in pregnant women, although in-person classes may pose significant accessibility barriers, particularly during the COVID-19 pandemic. Mobile technology offers greater convenience, but little is known regarding the efficacy of self-paced, mobile-delivered (mHealth) mindfulness interventions in this population. This study tested the feasibility and acceptability of offering such an intervention for pregnant women with moderate-to-moderately-severe depression symptoms. We conducted a single-arm trial within Kaiser Permanente Northern California (KPNC). Participants were identified through KPNC’s universal perinatal depression screening program. Eligible participants included English-speaking pregnant women (<28 weeks of gestation) with moderate-to-moderately-severe depressive symptoms without a regular (<3 times/week) mindfulness/meditation practice. Participants were asked to follow a self-paced, 6-week mindfulness meditation program using a mobile app, Headspace™, 10-20 min/day. Outcome measures included feasibility, acceptability, and patient-reported outcomes (e.g., depression symptoms). Of the 27 women enrolled, 20 (74%) completed the study. Over half (55%) of participants used the app ≥50% of the days during the 6-week intervention. Responses to the semi-structured interviews indicated that women appreciated the convenience of the intervention and the ability to engage without having to attend classes or arrange childcare. We observed significant improvements in pre-postintervention scores for depression symptoms, perceived stress, sleep disturbance, and mindfulness. Our study demonstrates the feasibility and acceptability of an mHealth mindfulness intervention for women with moderate-to-moderately-severe antenatal depression symptoms. The preliminary data further suggest that an efficacy trial is warranted.
Authors: Kubo, Ai; Aghaee, Sara; Kurtovich, Elaine M; Nkemere, Linda; Quesenberry, Charles P; McGinnis, MegAnn K; Avalos, Lyndsay A
Mindfulness (N Y). 2021 Mar 11:1-11.
Editorial Expression of Concern: Exposure to Magnetic Field Non-Ionizing Radiation and the Risk of Miscarriage: A Prospective Cohort Study
Authors: Li DK; Chen H; Ferber JR; Odouli R; Quesenberry C
Sci Rep. 2021 03 10;11(1):6021. Epub 2021-03-10.
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.
A Risk Score to Predict Clostridioides difficile Infection
Clostridioides difficile infection (CDI) is a major cause of severe diarrhea. In this retrospective study, we identified CDI risk factors by comparing demographic and clinical characteristics for Kaiser Permanente Northern California members ≥18 years old with and without laboratory-confirmed incident CDI. We included these risk factors in logistic regression models to develop 2 risk scores that predict future CDI after an Index Date for Risk Score Assessment (IDRSA), marking the beginning of a period for which we estimated CDI risk. During May 2011 to July 2014, we included 9986 CDI cases and 2 230 354 members without CDI. The CDI cases tended to be older, female, white race, and have more hospitalizations, emergency department and office visits, skilled nursing facility stays, antibiotic and proton pump inhibitor use, and specific comorbidities. Using hospital discharge as the IDRSA, our risk score model yielded excellent performance in predicting the likelihood of developing CDI in the subsequent 31-365 days (C-statistic of 0.848). Using a random date as the IDRSA, our model also predicted CDI risk in the subsequent 31-365 days reasonably well (C-statistic 0.722). These results can be used to identify high-risk populations for enrollment in C difficile vaccine trials and facilitate study feasibility regarding sample size and time to completion.
Authors: Aukes, Laurie; Fireman, Bruce; Lewis, Edwin; Timbol, Julius; Hansen, John; Yu, Holly; Cai, Bing; Gonzalez, Elisa; Lawrence, Jody; Klein, Nicola P
Open Forum Infect Dis. 2021 Mar;8(3):ofab052. 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.
Cross-cancer evaluation of polygenic risk scores for 16 cancer types in two large cohorts
Even distinct cancer types share biological hallmarks. Here, we investigate polygenic risk score (PRS)-specific pleiotropy across 16 cancers in European ancestry individuals from the Genetic Epidemiology Research on Adult Health and Aging cohort (16,012 cases, 50,552 controls) and UK Biobank (48,969 cases, 359,802 controls). Within cohorts, each PRS is evaluated in multivariable logistic regression models against all other cancer types. Results are then meta-analyzed across cohorts. Ten positive and one inverse cross-cancer associations are found after multiple testing correction. Two pairs show bidirectional associations; the melanoma PRS is positively associated with oral cavity/pharyngeal cancer and vice versa, whereas the lung cancer PRS is positively associated with oral cavity/pharyngeal cancer, and the oral cavity/pharyngeal cancer PRS is inversely associated with lung cancer. Overall, we validate known, and uncover previously unreported, patterns of pleiotropy that have the potential to inform investigations of risk prediction, shared etiology, and precision cancer prevention strategies.
Authors: Graff, Rebecca E; Alexeeff, Stacey E; Corley, Douglas A; Kushi, Lawrence H; Van Den Eeden, Stephen K; Habel, Laurel A; Sakoda, Lori C; et al.
Nat Commun. 2021 02 12;12(1):970. Epub 2021-02-12.
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.
Recruitment strategies and design considerations in a trial of resistance training to prevent dose-limiting toxicities in colon cancer patients undergoing chemotherapy
Low muscle is associated with an increased risk of chemotherapy-related dose limiting toxicities (DLT) in cancer patients. Resistance training (RT) improves muscle mass; however, the effects of RT on preventing DLTs and dose reductions in colon cancer patients has not been investigated. FOcus on Reducing dose-limiting toxicities in Colon cancer with resistance Exercise (FORCE) is a multicenter, randomized clinical trial examining the effects of RT on relative dose intensity (RDI; primary outcome) and moderate and severe chemotoxicities (primary outcome) in non-metastatic colon cancer patients receiving adjuvant chemotherapy. Patients (N = 180) will be recruited from Kaiser Permanente Northern California, Dana-Farber Cancer Institute, and Penn State Cancer Institute. This paper describes recruitment strategies and design considerations. Patients will be randomized in equal numbers to RT intervention or control. Patients have baseline and post completion of chemotherapy visits where information on anthropometry, physical function, body composition, quality of life, physical activity and dietary behaviors, and inflammatory blood markers will be collected. Patient-reported outcomes of chemotherapy side effects will be collected around the time of chemotherapy throughout the duration of the trial. Intervention participants will be prescribed a progressive RT program consisting of 4-6 visits with a certified exercise trainer, delivered either in-person or remotely by video conference, and will be asked to engage twice weekly in-home training sessions. Control patients at the end of the study receive a consult with a FORCE exercise trainer, an online exercise RT training program and a set of resistance bands. Results of this trial will provide information on the benefit of resistance exercise as a treatment to increase RDI.
Authors: Caan, Bette J; Meyerhardt, Jeffrey A; Brown, Justin C; Campbell, Kristin L; Cespedes Feliciano, Elizabeth M; Lee, Catherine; Ross, Michelle C; Quinney, Sara; Quesenberry, Charles; Sternfeld, Barbara; Schmitz, Kathryn H
Contemp Clin Trials. 2021 02;101:106242. Epub 2020-12-07.
Exercise During the First Trimester of Pregnancy and the Risks of Abnormal Screening and Gestational Diabetes Mellitus
To estimate the effects of exercise during the first trimester on the risks of abnormal screening and gestational diabetes mellitus (GDM). Data come from PETALS, a prospectively followed pregnancy cohort (n = 2,246, 79% minorities) receiving care at Kaiser Permanente Northern California. A Pregnancy Physical Activity Questionnaire was used to assess exercise. Glucose testing results for screening and diagnostic tests were obtained from electronic health records. Inverse probability of treatment weighting and targeted maximum likelihood with data-adaptive estimation (machine learning) of propensity scores and outcome regressions were used to obtain causal risk differences adjusted for potential confounders, including prepregnancy BMI, exercise before pregnancy, and gestational weight gain. Exercise was dichotomized at 1) the cohort’s 75th percentile for moderate- to vigorous-intensity exercise (≥13.2 MET-h per week or ≥264 min per week of moderate exercise), 2) current recommendations (≥7.5 MET-h per week or ≥150 min per week of moderate exercise), and 3) any vigorous exercise. Overall, 24.3% and 6.5% had abnormal screening and GDM, respectively. Exercise meeting or exceeding the 75th percentile decreased the risks of abnormal screening and GDM by 4.8 (95% CI 1.1, 8.5) and 2.1 (0.2, 4.1) fewer cases per 100, respectively, in adjusted analyses. Exercise reduces the risks of abnormal screening and GDM, but the amount needed to achieve these risk reductions is likely higher than current recommendations. Future interventions may consider promoting ≥38 min per day of moderate-intensity exercise to prevent GDM.
Authors: Ehrlich, Samantha F; Ferrara, Assiamira; Hedderson, Monique M; Feng, Juanran; Neugebauer, Romain
Diabetes Care. 2021 02;44(2):425-432. Epub 2020-12-21.
PREDICTION OF OBSTETRIC AND FETAL COMPLICATIONS USING AUTOMATED ELECTRONIC HEALTH RECORD DATA
An increasing number of delivering women experience major morbidity and mortality. Limited work has been done on automated predictive models that could be used for prevention. Using only routinely collected obstetrical data, this study aimed to develop a predictive model suitable for real-time use with an electronic medical record. We used a retrospective cohort study design with split validation. The denominator consisted of women admitted to a delivery service. The numerator consisted of women who experienced a composite outcome that included both maternal (eg, uterine rupture, postpartum hemorrhage), fetal (eg, stillbirth), and neonatal (eg, hypoxic ischemic encephalopathy) adverse events. We employed machine learning methods, assessing model performance using the area under the receiver operator characteristic curve and number needed to evaluate. A total of 303,678 deliveries took place at 15 study hospitals between January 1, 2010, and March 31, 2018, and 4130 (1.36%) had ≥1 obstetrical complication. We employed data from 209,611 randomly selected deliveries (January 1, 2010, to March 31, 2017) as a derivation dataset and validated our findings on data from 52,398 randomly selected deliveries during the same time period (validation 1 dataset). We then applied our model to data from 41,669 deliveries from the last year of the study (April 1, 2017, to March 31, 2018 [validation 2 dataset]). Our model included 35 variables (eg, demographics, vital signs, laboratory tests, progress of labor indicators). In the validation 2 dataset, a gradient boosted model (area under the receiver operating characteristic curve or c statistic, 0.786) was slightly superior to a logistic regression model (c statistic, 0.778). Using an alert threshold of 4.1%, our final model would flag 16.7% of women and detect 52% of adverse outcomes, with a number needed to evaluate of 20.9 and 0.455 first alerts per day per 1000 annual deliveries. In conclusion, electronic medical record data can be used to predict obstetrical complications. The clinical utility of these automated models has not yet been demonstrated. To conduct interventions to assess whether using these models results in patient benefit, future work will need to focus on the development of clinical protocols suitable for use in interventions.
Authors: Escobar, Gabriel J; Soltesz, Lauren; Schuler, Alejandro; Niki, Hamid; Malenica, Ivana; Lee, Catherine
Am J Obstet Gynecol. 2021 02;224(2):137-147.e7. Epub 2020-10-22.
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.
Long-Term PM2.5 Exposure and Risks of Ischemic Heart Disease and Stroke Events: Review and Meta-Analysis
Background Fine particulate matter <2.5 µm in diameter (PM2.5) has known effects on cardiovascular morbidity and mortality. However, no study has quantified and compared the risks of incident myocardial infarction, incident stroke, ischemic heart disease (IHD) mortality, and cerebrovascular mortality in relation to long-term PM2.5 exposure. Methods and Results We sought to quantitatively summarize studies of long-term PM2.5 exposure and risk of IHD and stroke events by conducting a review and meta-analysis of studies published by December 31, 2019. The main outcomes were myocardial infarction, stroke, IHD mortality, and cerebrovascular mortality. Random effects meta-analyses were used to estimate the combined risk of each outcome among studies. We reviewed 69 studies and included 42 studies in the meta-analyses. In meta-analyses, we found that a 10-µg/m3 increase in long-term PM2.5 exposure was associated with an increased risk of 23% for IHD mortality (95% CI, 15%-31%), 24% for cerebrovascular mortality (95% CI, 13%-36%), 13% for incident stroke (95% CI, 11%-15%), and 8% for incident myocardial infarction (95% CI, -1% to 18%). There were an insufficient number of studies of recurrent stroke and recurrent myocardial infarction to conduct meta-analyses. Conclusions Long-term PM2.5 exposure is associated with increased risks of IHD mortality, cerebrovascular mortality, and incident stroke. The relationship with incident myocardial infarction is suggestive of increased risk but not conclusive. More research is needed to understand the relationship with recurrent events.
Authors: Alexeeff, Stacey E; Liao, Noelle S; Liu, Xi; Van Den Eeden, Stephen K; Sidney, Stephen
J Am Heart Assoc. 2021 01 05;10(1):e016890. Epub 2020-12-31.
Building Predictive Models for Clinical Care-Where to Build and What to Predict?
Authors: Selby, Joe V; Fireman, Bruce H
JAMA Netw Open. 2021 01 04;4(1):e2032539. Epub 2021-01-04.
Incidence and predictors of type 1 diabetes among younger adults aged 20-45 years: The diabetes in young adults (DiYA) study
To estimate incidence of type 1 diabetes (T1D) and to develop a T1D prediction model among young adults. Adults 20-45 years newly-diagnosed with diabetes in 2017 were identified within Kaiser Permanente’s healthcare systems in California and invited for diabetes autoantibody (DAA) testing. Multiple imputation was conducted to assign missing DAA status. The primary outcome for incidence rates (IR) and the prediction model was T1D defined by ≥1 positive DAA. Among 2,347,989 persons at risk, 7862 developed diabetes, 2063 had DAA measured, and 166 (8.0%) had ≥1 positive DAA. T1D IR (95% CI) per 100,000 person-years was 15.2 (10.2-20.1) for ages 20-29 and 38.2 (28.6-47.8) for ages 30-44 years. The age-standardized IRs were 32.5 (22.2-42.8) for men and 27.2 (21.0-34.5) for women. The age/sex-standardized IRs were 30.1 (23.5-36.8) overall; 41.4 (25.3-57.5) for Hispanics, 37.0 (11.6-62.4) for Blacks, 21.4 (14.3-28.6) for non-Hispanic Whites, and 19.4 (8.5-30.2) for Asians. Predictors of T1D among cases included female sex, younger age, lower BMI, insulin use and having T1D based on diagnostic codes. T1D may account for up to 8% of incident diabetes cases among young adults. Follow-up is needed to establish the clinical course of patients with one DAA at diagnosis.
Authors: Lawrence, Jean M; Quesenberry, Charles; Ferrara, Assiamira; et al.
Diabetes Res Clin Pract. 2021 Jan;171:108624. Epub 2020-12-15.
A Randomized Encouragement Trial to Increase Mail Order Pharmacy Use and Medication Adherence in Patients with Diabetes
Mail order pharmacy (MOP) use has been linked to improved medication adherence and health outcomes among patients with diabetes. However, no large-scale intervention studies have assessed the effect of encouraging MOP use on medication adherence. To assess an intervention to encourage MOP services to increase its use and medication adherence. Randomized encouragement trial. 63,012 diabetes patients from three health care systems: Kaiser Permanente Northern California (KPNC), Kaiser Permanente Hawaii (KPHI), and Harvard Pilgrim Health Care (HPHC) who were poorly adherent to at least one class of cardiometabolic medications and had not used MOP in the prior 12 months. Patients were randomized to receive either usual care (control arm) or outreach encouraging MOP use consisting of a mailed letter, secure email message, and automated telephone call outlining the potential benefits of MOP use (intervention arm). HPHC intervention patients received the letter only. We compared the percentages of patients that began using MOP and that became adherent to cardiometabolic medication classes during a 12-month follow-up period. We also conducted a race/ethnicity-stratified analysis. During follow-up, 10.6% of intervention patients began using MOP vs. 9.3% of controls (p < 0.01); the percent of cardiometabolic medication delivered via mail was 42.1% vs. 39.8% (p < 0.01). Metformin adherence improved in the intervention arm relative to control at the two KP sites (52% vs. 49%, p < 0.01). Stratified analyses suggested a significant positive effect of the intervention in White (RR: 1.12, 95% CI: 1.03, 1.22) and Asian (RR: 1.30, 95% CI: 1.17, 1.45) patients. This pragmatic trial showed that simple outreach to encourage MOP modestly increased its use and improved adherence measured by refills to a key class of diabetes medications in some settings. Given its minimal cost, clinicians and health systems should consider outreach interventions to actively promote MOP use among diabetes patients. ClinicalTrials.gov registration number: NCT02621476.
Authors: Ramachandran, Bharathi; Neugebauer, Romain S; Brown, Susan D; Karter, Andrew J; Schmittdiel, Julie A; et al.
J Gen Intern Med. 2021 01;36(1):154-161. Epub 2020-10-01.
Maternal immune response and air pollution exposure during pregnancy: insights from the Early Markers for Autism (EMA) study
Perinatal exposure to air pollution and immune system dysregulation are two factors consistently associated with autism spectrum disorders (ASD) and other neurodevelopmental outcomes. However, little is known about how air pollution may influence maternal immune function during pregnancy. To assess the relationship between mid-gestational circulating levels of maternal cytokines/chemokines and previous month air pollution exposure across neurodevelopmental groups, and to assess whether cytokines/chemokines mediate the relationship between air pollution exposures and risk of ASD and/or intellectual disability (ID) in the Early Markers for Autism (EMA) study. EMA is a population-based, nested case-control study which linked archived maternal serum samples collected during weeks 15-19 of gestation for routine prenatal screening, birth records, and Department of Developmental Services (DDS) records. Children receiving DDS services for ASD without intellectual disability (ASD without ID; n = 199), ASD with ID (ASD with ID; n = 180), ID without ASD (ID; n = 164), and children from the general population (GP; n = 414) with no DDS services were included in this analysis. Serum samples were quantified for 22 cytokines/chemokines using Luminex multiplex analysis technology. Air pollution exposure for the month prior to maternal serum collection was assigned based on the Environmental Protection Agency’s Air Quality System data using the maternal residential address reported during the prenatal screening visit. Previous month air pollution exposure and mid-gestational maternal cytokine and chemokine levels were significantly correlated, though weak in magnitude (ranging from - 0.16 to 0.13). Ten pairs of mid-pregnancy immune markers and previous month air pollutants were significantly associated within one of the child neurodevelopmental groups, adjusted for covariates (p < 0.001). Mid-pregnancy air pollution was not associated with any neurodevelopmental outcome. IL-6 remained associated with ASD with ID even after adjusting for air pollution exposure. This study suggests that maternal immune activation is associated with risk for neurodevelopmental disorders. Furthermore, that prenatal air pollution exposure is associated with small, but perhaps biologically relevant, effects on maternal immune system function during pregnancy. Additional studies are needed to better evaluate how prenatal exposure to air pollution affects the trajectory of maternal immune activation during pregnancy, if windows of heightened susceptibility can be identified, and how these factors influence neurodevelopment of the offspring.
Authors: Volk, Heather E; Alexeeff, Stacey E; Croen, Lisa A; et al.
J Neurodev Disord. 2020 12 16;12(1):42. Epub 2020-12-16.
Risk of complete atypical femur fracture with Oral bisphosphonate exposure beyond three years
Bisphosphonate (BP) therapy has been associated with atypical femur fracture (AFF). However, the threshold of treatment duration leading to increased AFF risk is unclear. In a retrospective cohort of older women initiating BP, we compared the AFF risk associated with treatment for at least three years to the risk associated with treatment less than three years. We used observational data from a large population of female members of an integrated healthcare system who initiated oral BP during 2002-2014. Women were retrospectively followed for incident AFF confirmed by radiologic adjudication. Demographic data, pharmacologic exposures, comorbidity, bone density, and fracture history were ascertained from electronic health records. Inverse probability weighting was used to estimate risk differences comparing the cumulative incidence (risk) of AFF if women discontinued BP within three years to the cumulative incidence of AFF if women continued BP for three or more years, adjusting for potential time-dependent confounding by the aforementioned factors. Among 87,820 women age 45-84 years who initiated BP (mean age 68.6, median T-score - 2.6, 14% with prior major osteoporotic fracture), 16,180 continued BP for three or more years. Forty-six confirmed AFFs occurred during follow-up in the two groups. AFF-free survival was greater for BP treatment < 3 years compared to treatment ≥3 years (p = 0.004 comparing areas under survival curves). At five years, the risk of AFF was 27 per 100,000 (95% confidence interval, CI: 8-46) if women received BP treatment < 3 years and 120 per 100,000 (95% CI: 56-183) if women received BP treatment ≥3 years (risk difference 93 per 100,000, 95% CI: 30-160). By ten years, the risks were 27 (95% CI: 8-46) and 363 (95% CI: 132-593) per 100,000 for BP treatment < 3 and ≥ 3 years, respectively (risk difference 336 per 100,000, 95% CI: 110-570). Bisphosphonate treatment for 3 or more years was associated with greater risk of AFF than treatment for less than 3 years. Although AFFs are uncommon among BP-treated women, this increased risk should be considered when counseling women about long-term BP use. Future studies should further characterize the dose-response relationship between BP duration and incident AFF and identify patients at highest risk.
Authors: Lo, Joan C; Neugebauer, Romain S; Ettinger, Bruce; Chandra, Malini; Hui, Rita L; Ott, Susan M; Grimsrud, Christopher D; Izano, Monika A
BMC Musculoskelet Disord. 2020 Dec 03;21(1):801. Epub 2020-12-03.
Development and Validation of Machine Learning Models: Electronic Health Record Data To Predict Visual Acuity After Cataract Surgery
To develop predictive models of final corrected distance visual acuity (CDVA) following cataract surgery using machine learning algorithms and electronic health record data. In this predictive modeling study we used decision tree, random forest, and gradient boosting. We included the first surgical eye of 64,768 members of Kaiser Permanente Northern California who underwent cataract surgery from June 1, 2010 through May 31, 2015. We measured discrimination and calibration of machine learning models for predicting postoperative CDVA 20/50 or worse vs 20/40 or better. The training set included 51,712 patients, and the validation set included 13,056 patients. We compared 3 machine learning models and found that the gradient boosting model provided the best discrimination ability for CDVA. The most important variables for predicting final CDVA 20/50 or worse were preoperative CDVA, age, and age-related macular degeneration, which together accounted for 41% of the gain in optimization of the gradient boosting model. Other important variables in the model included dispensed glaucoma medication, epiretinal membrane, cornea disorder, cataract surgery operating time, surgeon experience, and census block neighborhood characteristics (household income, family income, family poverty, college education, and home residence by owner). For predicting CDVA after cataract surgery, gradient boosting had the best ability to discriminate patients with postoperative CDVA 20/50 or worse from patients with postoperative CDVA 20/40 or better. Machine learning has the potential to improve prognosis and can improve patient information when making decisions to undergo cataract surgery.
Authors: Alexeeff, Stacey E; Uong, Stephen; Liu, Liyan; Shorstein, Neal H; Carolan, James; Amsden, Laura B; Herrinton, Lisa J
Perm J. 2020 12;25:1.
Validation Study of Kaiser Permanente Bedside Dysphagia Screening Tool in Acute Stroke Patients
Dysphagia occurs in up to 50% of patients with acute stroke symptoms, resulting in increased aspiration pneumonia rates and mortality. The purpose of this study was to validate a health system’s dysphagia (swallow) screening tool used since 2007 on all patients with suspected stroke symptoms. Annual rates of aspiration pneumonia for ischemic stroke patients have ranged from 2% to 3% since 2007. From August 17, 2015 through September 30, 2015, a bedside dysphagia screening was prospectively performed by 2 nurses who were blinded to all patients age 18 years or older admitted through the emergency department with suspected stroke symptoms at 21 Joint Commission accredited primary stroke centers in an integrated health system. The tool consists of 3 parts: pertinent history, focused physical examination, and progressive testing from ice chips to 90 mL of water. A speech language pathologist blinded to the nurse’s screening results performed a formal swallow evaluation on the same patient. The end study population was 379 patients. Interrater reliability between 2 nurses of the dysphagia screening was excellent at 93.7% agreement (Ƙ = 0.83). When the dysphagia screenings were compared with the gold standard speech language pathologist professional swallow evaluation, the tool demonstrated both high sensitivity (86.4%; 95% confidence interval = 73.3-93.6) and high negative predictive value (93.8%; 95% confidence interval = 87.2-97.1). This tool is highly reliable and valid. The dysphagia screening tool requires minimal training and is easily administered in a timely manner.
Authors: Finnegan, Barbara Schumacher; Meighan, Melissa M; Warren, Noelani C; Hatfield, Meghan K; Alexeeff, Stacey; Lipiz, Jorge; Nguyen-Huynh, Mai
Perm J. 2020 12;24:1.
Bisphosphonate Treatment Beyond 5 Years and Hip Fracture Risk in Older Women
Clinical trials have demonstrated the antifracture efficacy of bisphosphonate drugs for the first 3 to 5 years of therapy. However, the efficacy of continuing bisphosphonate for as long as 10 years is uncertain. To examine the association of discontinuing bisphosphonate at study entry, discontinuing at 2 years, and continuing for 5 additional years with the risk of hip fracture among women who had completed 5 years of bisphosphonate treatment at study entry. This cohort study included women who were members of Kaiser Permanente Northern and Southern California, 2 integrated health care delivery systems, and who had initiated oral bisphosphonate and completed 5 years of treatment by January 1, 2002, to September 30, 2014. Data analysis was conducted from January 2018 to August 2020. Discontinuation of bisphosphonate at study entry (within a 6-month grace period), discontinuation at 2 years (within a 6-month grace period), and continuation for 5 additional years. The outcome was hip fracture determined by principal hospital discharge diagnoses. Demographic, clinical, and pharmacological data were ascertained from electronic health records. Among 29 685 women (median [interquartile range] age, 71 [64-77] years; 17 778 [60%] non-Hispanic White individuals), 507 incident hip fractures were identified. Compared with bisphosphonate discontinuation at study entry, there were no differences in the cumulative incidence (ie, risk) of hip fracture if women remained on therapy for 2 additional years (5-year risk difference [RD], -2.2 per 1000 individuals; 95% CI, -20.3 to 15.9 per 1000 individuals) or if women continued therapy for 5 additional years (5-year RD, 3.8 per 1000 individuals; 95% CI, -7.4 to 15.0 per 1000 individuals). While 5-year differences in hip fracture risk comparing continuation for 5 additional years with discontinuation at 2 additional years were not statistically significant (5-year RD, 6.0 per 1000 individuals; 95% CI, -9.9 to 22.0 per 1000 individuals), interim hip fracture risk appeared lower if women discontinued after 2 additional years (3-year RD, 2.8 per 1000 individuals; 95% CI, 1.3 to 4.3 per 1000 individuals; 4-year RD, 9.3 per 1000 individuals; 95% CI, 6.3 to 12.3 per 1000 individuals) but not without a 6-month grace period to define discontinuation. In this study of women treated with bisphosphonate for 5 years, hip fracture risk did not differ if they discontinued treatment compared with continuing treatment for 5 additional years. If women continued for 2 additional years and then discontinued, their risk appeared lower than continuing for 5 additional years. Discontinuation at other times and fracture rates during intervening years should be further studied.
Authors: Izano, Monika A; Lo, Joan C; Adams, Annette L; Ettinger, Bruce; Ott, Susan M; Chandra, Malini; Hui, Rita L; Niu, Fang; Li, Bonnie H; Neugebauer, Romain S
JAMA Netw Open. 2020 12 01;3(12):e2025190. Epub 2020-12-01.
Associations between spousal caregiving and health among older adults in Mexico: A targeted estimation approach
To evaluate associations between spousal caregiving and mental and physical health among older adults in Mexico. Data come from the Mexican Health & Aging Study, a national population-based study of adults ≥50 years and their spouses (2001-2015). We compared outcomes for spousal caregivers to outcomes for those whose spouses had difficulty with at least one basic or instrumental activity of daily living (I/ADL) but were not providing care; the control group conventionally includes all married respondents regardless of spouse’s need for care. We used targeted maximum likelihood estimation to evaluate the associations with past-week depressive symptoms, lower-body functional limitations, and chronic health conditions. At baseline, 846 women and 629 men had a spouse with ≥1 I/ADL. Of these, 60.9% of women and 52.6% of men were spousal caregivers. Spousal caregiving was associated with more past-week depressive symptoms for men (Marginal Risk Difference (RD): 0.27, 95% confidence internal [CI]: 0.03, 0.51) and women (RD: 0.15, 95% CI: 0.07, 0.23). We could not draw conclusions about associations with lower-body functional limitations and chronic health conditions. On average, all respondents whose spouses had caregiving needs had poorer health than the overall sample. We found evidence of an association between spousal caregiving and mental health among older Mexican adults with spouses who had need for care. However, our findings suggest that older adults who are both currently providing or at risk of providing spousal care may need targeted programs and policies to support health and long-term care needs.
Authors: Torres JM; Mitchell UA; Sofrygin O; Rudolph KE; López-Ortega M; Sharif MZ; Wong R; Glymour MM
Int J Geriatr Psychiatry. 2020 Dec 01.
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.
Association of Valproic Acid Use, a Potent Histone Deacetylase Inhibitor, and Melanoma Risk
Histone deacetylase inhibitors, including valproic acid, selectively induce cellular differentiation and apoptosis in melanoma cells. No published pharmacoepidemiologic studies have explored the association between valproic acid use and melanoma risk. We conducted a retrospective cohort study of adult white Kaiser Permanente Northern California members (n = 2,213,845) from 1997 to 2012 to examine the association between valproic acid use and melanoma risk. Melanoma hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, adjusted for age, sex, calendar year, and healthcare use. Melanoma incidence was lower among exposed individuals (64.0 exposed vs. 96.2 unexposed per 100,000 person-years, P < 0.001). Exposed individuals had a lower incident melanoma risk (HR = 0.64; 95% CI = 0.51-0.79) in unadjusted analysis, and the estimate was attenuated but significant in adjusted analysis (HR = 0.76, 95% CI = 0.61-0.94). Cumulative exposure based on the number of fills revealed a biologically implausible inverse dose-effect. Exposed individuals were more likely to present with local than regional or distant disease at diagnosis (80/82; 97.6% exposed vs. 12,940/13,971; 92.6% unexposed). Our findings suggest that valproic acid exposure may be associated with decreased melanoma risk and progression, but the cumulative exposure analyses suggest that the observation may be owing to residual confounding.
Authors: Chavez A; Quesenberry CP; Darbinian J; Asgari MM
J Invest Dermatol. 2020 12;140(12):2353-2358. Epub 2020-04-28.
Identifying Ectopic Pregnancy in a Large Integrated Health Care Delivery System: Algorithm Validation
Surveillance of ectopic pregnancy (EP) using electronic databases is important. To our knowledge, no published study has assessed the validity of EP case ascertainment using electronic health records. We aimed to assess the validity of an enhanced version of a previously validated algorithm, which used a combination of encounters with EP-related diagnostic/procedure codes and methotrexate injections. Medical records of 500 women aged 15-44 years with membership at Kaiser Permanente Southern and Northern California between 2009 and 2018 and a potential EP were randomly selected for chart review, and true cases were identified. The enhanced algorithm included diagnostic/procedure codes from the International Classification of Diseases, Tenth Revision, used telephone appointment visits, and excluded cases with only abdominal EP diagnosis codes. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall performance (Youden index and F-score) of the algorithm were evaluated and compared to the validated algorithm. There were 334 true positive and 166 true negative EP cases with available records. True positive and true negative EP cases did not differ significantly according to maternal age, race/ethnicity, and smoking status. EP cases with only one encounter and non-tubal EPs were more likely to be misclassified. The sensitivity, specificity, PPV, and NPV of the enhanced algorithm for EP were 97.6%, 84.9%, 92.9%, and 94.6%, respectively. The Youden index and F-score were 82.5% and 95.2%, respectively. The sensitivity and NPV were lower for the previously published algorithm at 94.3% and 88.1%, respectively. The sensitivity of surgical procedure codes from electronic chart abstraction to correctly identify surgical management was 91.9%. The overall accuracy, defined as the percentage of EP cases with correct management (surgical, medical, and unclassified) identified by electronic chart abstraction, was 92.3%. The performance of the enhanced algorithm for EP case ascertainment in integrated health care databases is adequate to allow for use in future epidemiological studies. Use of this algorithm will likely result in better capture of true EP cases than the previously validated algorithm.
Authors: Getahun, Darios; Alexeeff, Stacey; Raine-Bennett, Tina; et al.
JMIR Med Inform. 2020 Nov 30;8(11):e18559. Epub 2020-11-30.
A Mobile Health Mindfulness Intervention for Women With Moderate to Moderately Severe Postpartum Depressive Symptoms: Feasibility Study
Approximately 20% of women suffer from postpartum depression (PPD). Due to barriers such as limited access to care, half of the women with PPD do not receive treatment. Therefore, it is critical to identify effective and scalable interventions. Traditional mindfulness programs have been effective in reducing depressive symptoms, however access remains a barrier. A self-paced mobile health (mHealth) mindfulness program may fit the lifestyle of busy mothers who are unable to attend in-person classes. However, little is known regarding the feasibility or efficacy of mHealth mindfulness interventions in postpartum women with depressive symptoms. This study aims to assess the feasibility, acceptability, and preliminary efficacy of an mHealth mindfulness intervention for postpartum women with moderate to moderately severe depressive symptoms. We conducted a single-arm feasibility trial of an mHealth mindfulness intervention within Kaiser Permanente Northern California (KPNC), a large integrated health care system. Participants were identified through clinician referral and electronic health records via KPNC’s universal perinatal depression screening program and recruited by the study team. Inclusion criteria included the following: English-speaking, up to 6 months postpartum with a Patient Health Questionnaire (PHQ-8) score of 10 to 19, and no regular mindfulness/meditation practice. Participants were asked to use a mindfulness app, Headspace, 10 to 20 min/day for 6 weeks. Baseline and postintervention surveys captured data on patient-reported outcomes (depression and stress symptoms, sleep quality, and mindfulness). Semistructured interviews captured acceptability. Retention and adherence were used to assess feasibility. Of the 115 women who were contacted and met the eligibility criteria or declined participation before eligibility assessment, 27 (23%) were enrolled. In addition, 70% (19/27) completed the study. The mean age of participants was 31 years (SD 5.2), 30% (8/27) were non-Hispanic White, and, on average, participants were 12.3 weeks postpartum (SD 5.7). Of the women who completed the study, 100% (19/19) used the Headspace app at least once, and nearly half (9/19, 47%) used the app on ≥50% of the days during the 6-week intervention period. Of the 16 participants who completed the postintervention interview, 69% (11/16) reported that they were very or extremely satisfied with the app. Interviews indicated that women appreciated the variety of meditations and felt that the program led to reduced anxiety and improved sleep. Significant improvements in pre- and postintervention scores were observed for depressive symptoms (PHQ-8: -3.8, P=.004), perceived stress (10-item Perceived Stress Scale: -6.0, P=.005), and sleep quality (Pittsburgh Sleep Quality Index: -2.1, P=.02, indicating less sleep disturbance). Improvements in mindfulness were also significant (Five Facet Mindfulness Questionnaire-Short Form: 10.9, P=.01). An mHealth mindfulness intervention for postpartum women with moderate to moderately severe depressive symptoms is feasible and acceptable. An efficacy trial is warranted.
Authors: Avalos, Lyndsay A; Aghaee, Sara; Kurtovich, Elaine; Quesenberry, Charles; Nkemere, Linda; McGinnis, MegAnn K; Kubo, Ai
JMIR Ment Health. 2020 Nov 12;7(11):e17405. Epub 2020-11-12.
Individual and Neighborhood Factors Associated with Failure to Vaccinate against Influenza during Pregnancy
Uptake of influenza vaccine among pregnant women remains low. We investigated whether unvaccinated pregnant women were clustered geographically and determined factors associated with failure to vaccinate using spatial and multivariate logistic regression analyses. Pregnant women who were members of Kaiser Permanente Northern California in 2015 or 2016 were included in the study. More than half (53%) of the 77,607 included pregnant women were unvaccinated. Spatial analysis identified 5 clusters with a high prevalence of unvaccinated pregnant women. The proportion of unvaccinated women ranged from 57% to 75% within clusters as compared with 51% outside clusters. In covariate-adjusted analyses, residence in a cluster was associated with a 41% increase in the odds of being unvaccinated (odds ratio (OR) = 1.41, 95% confidence interval (CI): 1.36, 1.46). The odds of being unvaccinated were greater for Black women (OR = 1.58, 95% CI: 1.49, 1.69), Hispanic women (OR = 1.15, 95% CI: 1.05, 1.25), women with subsidized health insurance (OR = 1.18, 95% CI: 1.11, 1.24), women with fewer than 5 prenatal-care visits (OR = 1.85, 95% CI: 1.60, 2.16), and neighborhoods with a high deprivation index (fourth quartile vs. first: OR = 1.14, 95% CI: 1.07, 1.21). In conclusion, unvaccinated pregnant women were clustered geographically and by key sociodemographic factors. These findings suggest that interventions to increase influenza vaccine coverage among pregnant women are needed, particularly in vulnerable populations.
Authors: Zerbo, Ousseny; Ray, G Thomas; Zhang, Lea; Goddard, Kristin; Fireman, Bruce; Adams, Alyce; Omer, Saad; Kulldorff, Martin; Klein, Nicola P
Am J Epidemiol. 2020 11 02;189(11):1379-1388.
Presentation of Rash in a Community-Based Health System
Coordination of care between primary care providers and dermatologists is important to ensure high quality and cost efficiency. In our integrated care setting, we used a retrospective cohort study to assess which patients self-refer to dermatology and which returned for a follow-up visit in dermatology. We identified 107,832 patients with a new rash diagnosis who presented to primary care or dermatology between January and March 2017. We compared patients who self-referred to dermatology with those who used primary care, using multi-level generalized estimating equations with adjustment for patient-level covariables and medical center. We also characterized patients who returned for a follow-up visit in dermatology. Among patients with a new rash diagnosis, 99% were originally seen in primary care. Patients with a history of a dermatological condition were more likely to present to dermatology. Patients with a history of a dermatological condition or with psoriasis, pigment, hair, bullous, or multiple conditions were more likely to have a follow-up visit with a dermatologist. For each outcome, initial location of care and return for a follow-up visit, we found minimal clustering by medical center or provider. One percent of patients with a new rash diagnosis self-refer to dermatology in this setting. Patients with a history of a dermatological condition were more likely to self-refer to dermatology and to have a follow-up visit with a dermatologist. Individual dermatologists and primary care providers had little impact on a patient’s odds of returning for a follow-up visit.
Authors: Dusendang, Jennifer R; Marwaha, Sangeeta; Alexeeff, Stacey E; Herrinton, Lisa J
Perm J. 2020 11;24:1-4.
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.
Bone Mineral Density in Older U.S. Filipino, Chinese, Japanese, and White Women
Bone mineral density (BMD) reference data exist for U.S. White, Black, and Hispanic (Mexican American) populations but not for U.S. Asians. Few studies have compared BMD findings among different U.S. Asian ethnicities. Retrospective observational study. Large northern California healthcare system. Asian and White women aged 50 to 79 years with BMD testing from 1998 to 2017 excluding those with estrogen or osteoporosis treatment, recent fracture, or select disorders affecting skeletal health. Femoral neck (FN)-BMD and height data. Differences in FN-BMD were examined by ethnicity and age, comparing Filipino, Chinese, and Japanese women and non-Hispanic White women. Differences in BMD were also examined after adjustment for height. There were 37,224 Asian women (including 11,147 Filipino, 10,648 Chinese, and 2,519 Japanese) and 115,318 non-Hispanic White women. Mean height was similar among the Asian subgroups and about 6 to 8 cm lower than Whites. Mean FN-BMDs differed by less than 3% for Filipino, Chinese, and Japanese and all were lower than Whites, with smaller Asian-White differences among younger women (<3%; ages 50-59) and larger differences among older women (6-8%; ages 65-79). Adjusting FN-BMD for height reduced White-Asian differences by about 30% to 40%. Mean FN-BMD and height for Filipino, Chinese, and Japanese women were similar but consistently lower than White women, especially among older women. Although Asian-White BMD differences were substantially attenuated after height adjustment; some differences persisted for older women. Future studies should investigate potential age-cohort effects and the extent to which these BMD differences influence fracture risk and clinical care.
Authors: Lo, Joan C; Chandra, Malini; Lee, Catherine; Darbinian, Jeanne A; Ramaswamy, Mohan; Ettinger, Bruce
J Am Geriatr Soc. 2020 11;68(11):2656-2661. Epub 2020-10-12.
Consequences of depletion of susceptibles for hazard ratio estimators based on propensity scores
We use simulated data to examine the consequences of depletion of susceptibles for hazard ratio (HR) estimators based on a propensity score (PS). First, we show that the depletion of susceptibles attenuates marginal HRs toward the null by amounts that increase with the incidence of the outcome, the variance of susceptibility, and the impact of susceptibility on the outcome. If susceptibility is binary then the Bross bias multiplier, originally intended to quantify bias in a risk ratio from a binary confounder, also quantifies the ratio of the instantaneous marginal HR to the conditional HR as susceptibles are depleted differentially. Second, we show how HR estimates that are conditioned on a PS tend to be between the true conditional and marginal HRs, closer to the conditional HR if treatment status is strongly associated with susceptibility and closer to the marginal HR if treatment status is weakly associated with susceptibility. We show that associations of susceptibility with the PS matter to the marginal HR in the treated (ATT) though not to the marginal HR in the entire cohort (ATE). Third, we show how the PS can be updated periodically to reduce depletion-of-susceptibles bias in conditional estimators. Although marginal estimators can hit their ATE or ATT targets consistently without updating the PS, we show how their targets themselves can be misleading as they are attenuated toward the null. Finally, we discuss implications for the interpretation of HRs and their relevance to underlying scientific and clinical questions. See video Abstract: https://links.lww.com/EDE/B727.
Authors: Fireman, Bruce; Wyss, Richard; et al.
Epidemiology. 2020 11;31(6):806-814.
Early Screening of African Americans (45-50 Years Old) in a Fecal Immunochemical Test-based Colorectal Cancer Screening Program
Some guidelines recommend starting colorectal cancer (CRC) screening before age 50 years for African Americans, but there are few data on screening uptake and yield in this population. We performed a prospective study of fecal immunochemical test (FIT) screening among African American members of the Kaiser Permanente Northern California health plan. We compared data from African American members screened when they were 45-50 years old (early screening group) in 2018 with data from previously unscreened African American, white, Hispanic, and Asian/Pacific Islander health plan members who were 51-56 years old. Screening outreach was performed with mailed FIT kits. Logistic regression models, adjusted for sex, were used to evaluate differences among groups in screening uptake, colonoscopy follow-up of abnormal test results, and test yield. Among 10,232 African Americans in the early screening group who were mailed a FIT, screening was completed by 33.1%. Among the 4% with positive test results, 85.3% completed a follow-up colonoscopy: 57.8% had any adenoma, 33.6% had an advanced adenoma (adenoma with advanced histology or polyp ≥10 mm), and 2.6% were diagnosed with CRC. African Americans in the early screening group were modestly more likely to have completed screening than previously unscreened African Americans, whites, and Hispanics 51-56 years old. The groups did not differ significantly in positive results from the FIT (range, 3.8%-4.6%) and more than 74% received a follow-up colonoscopy after a positive test result. The test yields for any adenoma (range, 56.7%-70.7%), advanced adenoma (range, 20.0%-33.6%), and CRC (range, 0%-7.1%) were similar. Proportions of African Americans who participated in early (aged 45-50 years) FIT screening and test yield were comparable to those of previously unscreened African Americans, whites, Hispanics, and Asian/Pacific Islanders who were 51-56 years old.
Authors: Levin TR; Jensen CD; Chawla NM; Sakoda LC; Lee JK; Zhao WK; Landau MA; Herm A; Eby E; Quesenberry CP; Corley DA
Gastroenterology. 2020 11;159(5):1695-1704.e1. Epub 2020-07-20.
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.
Standardized reporting and management of suspicious findings on chest computed tomography is associated with improved lung cancer diagnosis in an observational study
Follow-up of chest CT scan findings suspicious for lung cancer may be delayed because of inadequate documentation. Standardized reporting and follow-up may reduce time to diagnosis and care for lung cancer. We implemented a reporting system that standardizes tagging of chest CT scan reports by classifying pulmonary findings. The system also automates referral of patients with findings suspicious for lung cancer to a multidisciplinary care team for rapid review and follow-up. The system was designed to reduce the time to diagnosis, particularly for early-stage lung cancer. We evaluated the effectiveness of this system, using a quasi-experimental stepped wedge cluster design, examining 99,148 patients who underwent diagnostic (nonscreening) chest CT imaging from 2015 to 2017 and who had not received a chest CT scan in the preceding 24 months. We evaluated the association of the intervention with the incidence of diagnosis and surgical treatment of early-stage (I, II) and late-stage (III, IV) lung cancer within 120 days of chest CT imaging. Forty percent of patients received the intervention. Among 2,856 patients (2.9%) who received diagnoses of lung cancer, 28% had early-stage disease. In multivariable analyses, the intervention was associated with 24% greater odds of early-stage diagnosis (OR, 1.24; 95% CI, 1.09-1.41) and no change in the odds of late-stage diagnosis (OR, 1.04; 95% CI, 0.95-1.14). The intervention was not associated with the rate of surgical treatment within 120 days. In this large quasi-experimental community-based observational study, implementation of a system that combines standardized tagging of chest CT scan reports with clinical navigation was effective for increasing the diagnosis of early-stage lung cancer.
Authors: Urbania TH; Dusendang JR; Herrinton LJ; Alexeeff S; Corley DA; Ely S; Patel A; Osinski T; Sakoda LC
Chest. 2020 11;158(5):2211-2220. Epub 2020-06-17.
Early life household intactness and timing of pubertal onset in girls: a prospective cohort study
Girls who experience early-life familial stress may have heightened risk of early puberty, which has adverse implications for adolescent and adult health. We assessed the association between household intactness and pubertal onset using a racially/ethnically diverse cohort of girls from Northern California. A prospective cohort study of 26,044 girls born in 2003-10. Girls living with both parents from birth up to 6 years were considered to come from “intact” households while others constituted “non-intact” households. Pubertal development was measured using pediatrician-assessed Tanner staging for breast and pubic hair. Pubertal onset was defined as the transition from Tanner Stage 1 to 2+ for breast (thelarche) and pubic hair (pubarche). Menarche data was collected from routine well-child questionnaires. Weibull regression models accommodating left, right, and interval censoring were used to determine risk of earlier thelarche and pubarche, and logistic regressions were used to assess the risk of early menarche (age < 12). Girls exposed to non-intact households before age 2 years were at increased risk for earlier thelarche and pubarche with significant effect modification by race/ethnicity, compared with girls from intact households. The associations were strongest among Black girls (adjusted hazard ratio [HR]: 1.60, 95% confidence interval [CI]: 1.29,1.98; HR: 1.42, 95%CI: 1.15,1.77 for thelarche and pubarche, respectively). There were no significant associations among Asian/Pacific Islanders. Girls who lived in non-intact households before age 2 years were also at increased risk for earlier menarche, but without race/ethnic interaction. Adjustment for prepubertal obesity did not change these associations. Associations between living in non-intact households after age 2 years and early puberty were weaker but still significant. Exposure to a non-intact household early in life may increase the risk of early puberty in girls. Future psychosocial interventions focused on improving family cohesiveness and efforts to reduce childhood stress among families that are non-intact may mitigate these negative associations, thereby preventing future adverse health effects of early puberty and health disparities.
Authors: Aghaee, Sara; Deardorff, Julianna; Greenspan, Louise C; Quesenberry, Charles P; Kushi, Lawrence H; Kubo, Ai
BMC Pediatr. 2020 10 28;20(1):464. Epub 2020-10-28.
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.
Inpatient-outpatient shared electronic health records: telemedicine and laboratory follow-up after hospital discharge
Continuity of patient information across settings can improve transitions after hospital discharge, but outpatient clinicians often have limited access to complete information from recent hospitalizations. We examined whether providers’ timely access to clinical information through shared inpatient-outpatient electronic health records (EHRs) was associated with follow-up visits, return emergency department (ED) visits, or readmissions after hospital discharge in patients with diabetes. Stepped-wedge observational study. As an integrated delivery system staggered implementation of a shared inpatient-outpatient EHR, we studied 241,510 hospital discharges in patients with diabetes (2005-2011), examining rates of outpatient follow-up office visits, telemedicine (phone visits and asynchronous secure messages), laboratory tests, and return ED visits or readmissions (as adverse events). We used multivariate logistic regression adjusting for time trends, patient characteristics, and medical center and accounting for patient clustering to calculate adjusted follow-up rates. For patients with diabetes, provider use of a shared inpatient-outpatient EHR was associated with a statistically significant shift toward follow-up delivered through a combination of telemedicine and outpatient laboratory tests, without a traditional in-person visit (from 22.9% with an outpatient-only EHR to 27.0% with a shared inpatient-outpatient EHR; P < .05). We found no statistically significant differences in 30-day return ED visits (odds ratio, 1.02; 95% CI, 0.96-1.09) or readmissions (odds ratio, 0.98; 95% CI, 0.91-1.06) with the shared EHR compared with the outpatient-only EHR. Real-time clinical information availability during transitions between health care settings, along with robust telemedicine access, may shift the method of care delivery without adversely affecting patient health outcomes. Efforts to expand interoperability and information exchange may support follow-up care efficiency.
Authors: Reed, Mary; Huang, Jie; Brand, Richard; Graetz, Ilana; Jaffe, Marc G; Ballard, Dustin; Neugebauer, Romain; Fireman, Bruce; Hsu, John
Am J Manag Care. 2020 10 01;26(10):e327-e332. Epub 2020-10-01.
Gestational weight gain, birthweight and early-childhood obesity: between- and within-family comparisons
Associations of excessive gestational weight gain (GWG) with greater birthweight and childhood obesity may be confounded by shared familial environment or genetics. Sibling comparisons can minimize variation in these confounders because siblings grow up in similar environments and share the same genetic predisposition for weight gain. We identified 96 289 women with live births in 2008-2014 at Kaiser Permanente Northern California. Fifteen percent of women (N = 14 417) had at least two births during the study period for sibling analyses. We assessed associations of GWG according to the Institute of Medicine (IOM) recommendations with birthweight and obesity at age 3 years, using conventional analyses comparing outcomes between mothers and sibling analyses comparing outcomes within mothers, which control for stable within-family unmeasured confounders such as familial environment and genetics. We used generalized estimating-equations and fixed-effects models. In conventional analyses, GWG above the IOM recommendations was associated with 88% greater odds of large-for-gestational age birthweight [95% confidence interval (CI): 1.80, 1.97] and 30% greater odds of obesity at 3 years old (95% CI: 1.24, 1.37) compared with GWG within the IOM recommendations. In sibling analyses, GWG above the IOM recommendations was also associated with greater odds of large-for-gestational age [odds ratio (OR): 1.36; 95% CI: 1.20, 1.54], but was not associated with obesity at 3 years old (OR = 0.98; 95% CI: 0.84, 1.15). GWG likely has a direct impact on birthweight; however, shared environmental and lifestyle factors within families may play a larger role in determining early-childhood weight status and obesity risk than GWG.
Authors: Badon, Sylvia E; Quesenberry, Charles P; Xu, Fei; Avalos, Lyndsay A; Hedderson, Monique M
Int J Epidemiol. 2020 10 01;49(5):1682-1690.
Association of Low Muscle Mass and Low Muscle Radiodensity With Morbidity and Mortality for Colon Cancer Surgery
Given the risks of postoperative morbidity and its consequent economic burden and impairment to patients undergoing colon resection, evaluating risk factors associated with complications will allow risk stratification and the targeting of supportive interventions. Evaluation of muscle characteristics is an emerging area for improving preoperative risk stratification. To examine the associations of muscle characteristics with postoperative complications, length of hospital stay (LOS), readmission, and mortality in patients with colon cancer. This population-based retrospective cohort study was conducted among 1630 patients who received a diagnosis of stage I to III colon cancer from January 2006 to December 2011 at Kaiser Permanente Northern California, an integrated health care system. Preliminary data analysis started in 2017. Because major complication data were collected between 2018 and 2019, the final analysis using the current cohort was conducted between 2019 and 2020. Low skeletal muscle index (SMI) and/or low skeletal muscle radiodensity (SMD) levels were assessed using preoperative computerized tomography images. Length of stay, any complication (≥1 predefined complications) or major complications (Clavien-Dindo classification score ≥3), 30-day mortality and readmission up to 30 days postdischarge, and overall mortality. The mean (SD) age at diagnosis was 64.0 (11.3) years and 906 (55.6%) were women. Patients with low SMI or low SMD were more likely to remain hospitalized 7 days or longer after surgery (odds ratio [OR], 1.33; 95% CI, 1.05-1.68; OR, 1.39; 95% CI, 1.05-1.84, respectively) and had higher risks of overall mortality (hazard ratio, 1.40; 95% CI, 1.13-1.74; hazard ratio, 1.44; 95% CI, 1.12-1.85, respectively). Additionally, patients with low SMI were more likely to have 1 or more postsurgical complications (OR, 1.31; 95% CI, 1.04-1.65) and had higher risk of 30-day mortality (OR, 4.85; 95% CI, 1.23-19.15). Low SMD was associated with higher odds of having major complications (OR, 2.41; 95% CI, 1.44-4.04). Low SMI and low SMD were associated with longer LOS, higher risk of postsurgical complications, and short-term and long-term mortality. Research should evaluate whether targeting potentially modifiable factors preoperatively, such as preserving muscle mass, could reverse the observed negative associations with postoperative outcomes.
Authors: Xiao, Jingjie; Cespedes Feliciano, Elizabeth M; Meyerhardt, Jeffrey A; Kwan, Marilyn L; Alexeeff, Stacey E; Castillo, Adrienne L; Prado, Carla M; et al.
JAMA Surg. 2020 10 01;155(10):942-949.
Determining Which of Several Simultaneously Administered Vaccines Increase Risk of an Adverse Event
Childhood immunization schedules often involve multiple vaccinations per visit. When increased risk of an adverse event is observed after simultaneous (same-day) vaccinations, it can be difficult to ascertain which triggered the adverse event. This methods paper discusses a systematic process to determine which of the simultaneously administered vaccine(s) are most likely to have caused an observed increase in risk of an adverse event. We use an example from the literature where excess risk of seizure was observed 1 day after vaccination, but same-day vaccination patterns made it difficult to discern which vaccine(s) may trigger the adverse event. We illustrate the systematic identification process using a simulation that retained the observed pattern of simultaneous vaccination in an empirical cohort of vaccinated children. We simulated “true” effects for diphtheria-tetanus-acellular pertussis (DTaP) and pneumococcal conjugate (PCV) on risk of seizure the day after vaccination. We varied the independent and interactive effects of vaccines (on the multiplicative scale). After applying the process to simulated data, we evaluated risk of seizure 1 day after vaccination in the empirical cohort. In all simulations, we were able to determine which vaccines contributed to excess risk. In the empirical data, we narrowed the association with seizure from all vaccines in the schedule to three likely candidates, DTaP, PCV, and/or Haemophilus influenzae type B (HiB) (p < 0.01, attributable risk when all three were administered together: five per 100,000). Disentangling their associations with seizure would require a larger sample or more variation in the combinations administered. When none of these three were administered, no excess risk was observed. The process outlined could provide valuable information on the magnitude of potential risk from individual and simultaneousvaccinations. Associations should be further investigated with independent data as well as biologically based, statistically independent hypotheses.
Authors: Wang SV; Stefanini K; Lewis E; Newcomer SR; Fireman B; Daley MF; Glanz JM; Duffy J; Weintraub E; Kulldorff M
Drug Saf. 2020 10;43(10):1057-1065.
Feasibility of Measuring Preferences for Chemotherapy Among Early-Stage Breast Cancer Survivors Using a Direct Rank Ordering Multicriteria Decision Analysis Versus a Time Trade-Off
Chemotherapy is increasingly a preference-based choice among women diagnosed with early-stage breast cancer. Multicriteria decision analysis (MCDA) is a promising but underutilized method to facilitate shared decision making. We explored the feasibility of conducting an MCDA using direct rank ordering versus a time trade-off (TTO) to assess chemotherapy choice in a large population-based sample. We surveyed 904 early-stage breast cancer survivors who were within 5 years of diagnosis and reported to the Western Washington State Cancer System and Kaiser Permanente Northern California registries. Direct rank ordering of 11 criteria and TTO surveys were conducted from September 2015 to July 2016; clinical data were obtained from registries or medical records. Multivariable regressions estimated post hoc associations between the MCDA, TTO, and self-reported chemotherapy receipt, considering covariates. Survivors ranged in age from 25 to 74 years and 73.9% had stage I tumors. The response rate for the rank ordering was 81.0%; TTO score was 94.2%. A one-standard deviation increase in the difference between the chemotherapy and no chemotherapy MCDA scores was associated with a 75.1% (95% confidence interval 43.9-109.7%; p < 0.001) increase in the adjusted odds of having received chemotherapy; no association was found between the TTO score and chemotherapy receipt. A rank-order-based MCDA was feasible and was associated with chemotherapy choice. Future research should consider developing and testing this MCDA for use in clinical encounters. Additional research is required to develop a TTO-based model and test its properties against a pragmatic MCDA to inform future shared decision-making tools.
Authors: Panattoni L; Phelps CE; Lieu TA; Alexeeff S; O'Neill S; Mandelblatt JS; Ramsey SD
Patient. 2020 10;13(5):557-566.
Conducting prospective sequential surveillance in real-world dynamic distributed databases
Authors: Maro JC; Eworuke E; Hou L; Welch EC; Goulding MR; Izem R; Lee JY; Toh S; Fireman B; Nguyen MD
Pharmacoepidemiol Drug Saf. 2020 10;29(10):1331-1335. Epub 2020-05-25.
History of Early Childhood Infections and Acute Lymphoblastic Leukemia Risk Among Children in a U.S. Integrated Health Care System
Surrogate measures of infectious exposures have been consistently associated with lower childhood acute lymphoblastic leukemia (ALL) risk. However, recent reports have suggested that physician-diagnosed early-life infections increase ALL risk, thereby raising the possibility that stronger responses to infections might promote risk. We examined whether medically diagnosed infections were related to childhood ALL risk in an integrated health-care system in the United States. Cases of ALL (n = 435) diagnosed between 1994-2014 among children aged 0-14 years, along with matched controls (n = 2,170), were identified at Kaiser Permanente Northern California. Conditional logistic regression was used to estimate risk of ALL associated with history of infections during first year of life and across the lifetime (up to diagnosis). History of infection during first year of life was not associated with ALL risk (odds ratio (OR) = 0.85, 95% confidence interval (CI): 0.60, 1.21). However, infections with at least 1 medication prescribed (i.e., more “severe” infections) were inversely associated with risk (OR = 0.42, 95% CI: 0.20, 0.88). Similar associations were observed when the exposure window was expanded to include medication-prescribed infections throughout the subjects’ lifetime (OR = 0.52, 95% CI: 0.32, 0.85).
Authors: Morimoto LM; Kwan ML; Deosaransingh K; Munneke JR; Kang AY; Quesenberry C; Kogan S; de Smith AJ; Metayer C; Wiemels JL
Am J Epidemiol. 2020 10 01;189(10):1076-1085.
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.
Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts
Deciphering the shared genetic basis of distinct cancers has the potential to elucidate carcinogenic mechanisms and inform broadly applicable risk assessment efforts. Here, we undertake genome-wide association studies (GWAS) and comprehensive evaluations of heritability and pleiotropy across 18 cancer types in two large, population-based cohorts: the UK Biobank (408,786 European ancestry individuals; 48,961 cancer cases) and the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging cohorts (66,526 European ancestry individuals; 16,001 cancer cases). The GWAS detect 21 genome-wide significant associations independent of previously reported results. Investigations of pleiotropy identify 12 cancer pairs exhibiting either positive or negative genetic correlations; 25 pleiotropic loci; and 100 independent pleiotropic variants, many of which are regulatory elements and/or influence cross-tissue gene expression. Our findings demonstrate widespread pleiotropy and offer further insight into the complex genetic architecture of cross-cancer susceptibility.
Authors: Rashkin, Sara R; Alexeeff, Stacey E; Corley, Douglas A; Kushi, Lawrence H; Van Den Eeden, Stephen K; Habel, Laurel A; Sakoda, Lori C; Witte, John S; et al.
Nat Commun. 2020 09 04;11(1):4423. Epub 2020-09-04.
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.
Evaluation of a Vaccine-Communication Tool for Physicians
To evaluate a Kaiser Permanente Northern California physician training tool entitled “Effective Communication without Confrontation” aimed at improving communication with vaccine-hesitant parents, building trust, and alleviating physician stress surrounding vaccination visits. Trainings were held May to July 2015. Pre- and post-training surveys assessed physician comfort and perceived effectiveness in communicating with vaccine-hesitant parents. We measured vaccination coverage at the 2-, 4-, and 6-month well-child visits, and days undervaccinated at 9 months of age. We compared vaccination rates before and after the training. Of 415 physicians who received training, 249 completed post-training surveys. Physicians reported that the training helped them feel “much more or more” comfortable talking with parents who are unsure (72.3%), want to delay (73.9%), or refuse (63.5%) vaccinations and “much more or more” effective at persuading parents who are unsure (67.5%) or want to delay vaccinations (61.4%). They reported feeling “the same or less” effective persuading parents who refuse vaccinations (66.3%). Vaccine coverage remained unchanged and high from before to after the training (95%-96%), as did parent satisfaction with his or her child’s provider (4.73/5.00). The Effective Communication without Confrontation training did not increase vaccine coverage, but did improve physicians’ comfort and perceived effectiveness communicating with most vaccine-hesitant parents and may help to ease potentially stressful vaccination visits.
Authors: Glanternik JR; McDonald JC; Yee AH; Howell Ba A; Saba KN; Mellor RG; Fireman B; Klein NP
J Pediatr. 2020 09;224:72-78.e1. Epub 2020-06-06.
The Covid-19 Pandemic and the Incidence of Acute Myocardial Infarction
Authors: Solomon MD; McNulty EJ; Rana JS; Leong TK; Lee C; Sung SH; Ambrosy AP; Sidney S; Go AS
N Engl J Med. 2020 08 13;383(7):691-693. Epub 2020-05-19.
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.
Increased Risk of Colorectal Cancer in Individuals With a History of Serrated Polyps
Serrated polyp (SPs) are precursors to 20% to 30% of cases of colorectal tumors, but patients’ long-term risk after removal of SPs is poorly understood. We investigated the risk of colorectal cancer (CRC) in individuals with a history of SPs. We performed a retrospective cohort study of Kaiser Permanente Northern California members who underwent colonoscopy from 2006 through 2016. Study participants were categorized based on the size and location of SPs. We used Cox proportional hazards modeling to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association of CRC diagnosed more than 1 year after colonoscopy, with polyp type vs no polyp after adjustment for year of colonoscopy, age, sex, race/ethnicity, and smoking history. The study included 233,393 individuals, of whom 445 developed incident CRC. At 10 years, the cumulative incidence rates of CRC for individuals with no polyp, proximal small SPs, proximal large SPs, and distal SPs were 4.7 (95% CI, 4.0-5.6), 14.8 (95% CI, 9.0-24.3), 30.2 (95% CI, 13.2-68.4), and 5.9 (95% CI, 3.6-9.5) per 1000 persons, respectively. In patients with SPs, risk of CRC was not increased until 3 years or more after the first colonoscopy (HR for small proximal SPs 2.6; 95% CI, 1.7-3.9 and HR for large proximal SPs 8.0; 95% CI, 3.6-16.1). The presence of synchronous adenomas increased the risk for CRC (HR for proximal SPs with synchronous adenomas 4.0; 95% CI, 3.0-5.5 and HR for distal SPs with synchronous adenomas 2.4; 95% CI, 1.7-3.4). In a retrospective analysis of a large cohort of individuals examined by colonoscopy, we found that risk of incident CRC increased in individuals with proximal SPs (large SPs in particular) 3 years or more after the colonoscopy. These findings support guidelines that recommend surveillance colonoscopy for individuals with SPs.
Authors: Li D; Liu L; Fevrier HB; Alexeeff SE; Doherty AR; Raju M; Amsden LB; Lee JK; Levin TR; Corley DA; Herrinton LJ
Gastroenterology. 2020 08;159(2):502-511.e2. Epub 2020-04-08.
Cesarean Delivery and the Risk of Atopic Dermatitis in Children
Caesarean delivery (C-section) may disrupt maternal-infant microbial transfer and alter immune system development and subsequent risk for atopic dermatitis. Investigate the association between C-section and atopic dermatitis by age four and examine potential sources of bias in the relationship in a large cohort study. Maternal and child information was collected through Kaiser Permanente Northern California’s (KPNC) integrated healthcare system. Data sources included electronic medical records, pharmacy databases, state birth records, and prospectively collected breastfeeding surveys. Children were eligible if they were born in a KPNC or contracting hospital between 2005 and 2014 and had continuous enrolment in the KPNC system for at least four years (n = 173 105). Modified Poisson regression with robust variance estimation was used to estimate the association between C-section and atopic dermatitis overall and when stratified by demographic and labour and delivery characteristics. Although unadjusted analyses showed a positive association between C-section and atopic dermatitis [RR(95%CI): 1.06(1.03, 1.10)], this effect was attenuated towards the null after adjustment [aRR(95%CI): 1.02(0.99, 1.05)]. In stratified analyses, there was evidence that C-section increased atopic dermatitis risk among certain subgroups (eg firstborns, overweight/obese pre-pregnancy BMI), but associations were weak. C-section delivery conditions indicative of the least exposure to maternal microbiome (ie no labour, short interval between membrane rupture and delivery) showed no evidence of association with atopic dermatitis. Estimated associations were not strongly influenced by intrapartum antibiotics, breastfeeding, missing data, or familial factors. Caesarean delivery was not associated with atopic dermatitis by age four in this large US cohort. This association did not appear to be biased by intrapartum antibiotics, breastfeeding behaviour, C-section indication, missing covariates, or familial factors.
Authors: Richards M; Ferber J; Chen H; Swor E; Quesenberry CP; Li DK; Darrow LA
Clin Exp Allergy. 2020 07;50(7):805-814. Epub 2020-06-11.
Comparison of Overall and Comorbidity-Free Life Expectancy Between Insured Adults With and Without HIV Infection, 2000-2016
Antiretroviral therapy (ART) has improved life expectancy for individuals with HIV infection, but recent data comparing life span and comorbidity-free years by HIV status are lacking. To quantify the gap in life span and comorbidity-free years by HIV status among adults with access to care. This matched cohort study used data from insured adults with and without HIV infection (aged ≥21 years) matched 1:10 at medical centers of Kaiser Permanente in northern and southern California and the mid-Atlantic states of Washington DC, Maryland, and Virginia from January 1, 2000, through December 31, 2016. Data were analyzed from September 1, 2019, through March 31, 2020. HIV status and, for individuals with HIV infection, ART initiation at a CD4 cell count of 500/μL or greater. Overall life expectancy and expected years free of major chronic comorbidities, including chronic liver disease, chronic kidney disease, chronic lung disease, diabetes, cancer, and cardiovascular disease. Of 39 000 individuals with HIV infection and 387 785 matched uninfected adults, 374 421 (87.7%) were male, with a mean (SD) age of 41.4 (10.8) years. Among 359 244 individuals with known race/ethnicity, 90 177 (25.1%) were non-Hispanic black and 87 191 (24.3%) were Hispanic. From 2000 to 2003, overall life expectancy at age 21 years of age was 37.6 years among individuals with HIV infection and 59.7 years among uninfected adults, (difference, 22.1 years; 95% CI, 20.2-24.0 years). From 2014 to 2016, overall life expectancy at 21 years of age among individuals with HIV infection increased to 56.0 years compared with 65.1 years among uninfected adults (difference, 9.1 years; 95% CI, 7.9-10.2 years). During 2011 to 2016, individuals with HIV infection who initiated ART with a CD4 cell count of 500/μL or greater had a life expectancy at 21 years of age of 57.4 years compared with 64.2 years among uninfected adults (difference, 6.8 years; 95% CI, 5.0-8.5 years). From 2000 to 2003, the expected number of comorbidity-free years remaining at 21 years of age was 11.3 for individuals with HIV infection and 26.6 years for uninfected adults (difference, 15.3 years; 95% CI, 13.9-16.6 years). This difference in comorbidity-free years persisted over time but decreased to 9.5 years (95% CI, 7.7-11.2 years) for individuals with HIV infection who initiated ART at a CD4 cell count of 500/μL or greater. The results suggest that life expectancy of adults with HIV infection may be near that of life expectancy of individuals without HIV infection, but greater attention is needed to prevention of comorbidities among individuals with HIV infection.
Authors: Marcus JL; Leyden WA; Alexeeff SE; Anderson AN; Hechter RC; Hu H; Lam JO; Towner WJ; Yuan Q; Horberg MA; Silverberg MJ
JAMA Netw Open. 2020 06 01;3(6):e207954. Epub 2020-06-01.
Association of Azithromycin Use With Cardiovascular Mortality
Azithromycin is one of the most commonly prescribed antibiotics in the US. It has been associated with an increased risk of cardiovascular death in some observational studies. To estimate the relative and absolute risks of cardiovascular and sudden cardiac death after an outpatient azithromycin prescription compared with amoxicillin, an antibiotic not known to increase cardiovascular events. This retrospective cohort study included 2 large, diverse, community-based integrated care delivery systems with comprehensive capture of encounters and prescriptions from January 1, 1998, to December 31, 2014. The cohort included patients aged 30 to 74 years who had at least 12 months of health-plan enrollment prior to antibiotic exposure. The exclusion criteria were absence of prescription benefits, prescription for more than 1 type of study antibiotic within 10 days, hospitalization or nursing home residence, and serious medical conditions. Risk of cardiovascular death associated with azithromycin vs amoxicillin exposure was calculated after controlling for confounding factors using a propensity score. Data were analyzed from December 1, 2016, to March 30, 2020. Outpatient prescription of azithromycin or amoxicillin. The primary outcomes were cardiovascular death and sudden cardiac death. An a priori subgroup analysis quantified the effects of azithromycin exposure among patients with increased baseline cardiovascular risk. The secondary outcomes were noncardiovascular death and all-cause mortality. The study included 7 824 681 antibiotic exposures, including 1 736 976 azithromycin exposures (22.2%) and 6 087 705 amoxicillin exposures (77.8%), among 2 929 008 unique individuals (mean [SD] age, 50.7 [12.3] years; 1 810 127 [61.8%] women). Azithromycin was associated with a significantly increased hazard of cardiovascular death (hazard ratio [HR], 1.82; 95% CI, 1.23-2.67) but not sudden cardiac death (HR, 1.59; 95% CI, 0.90-2.81) within 5 days of exposure. No increases in risk were found 6 to 10 days after exposure. Similar results were observed in patients within the top decile of cardiovascular risk (HR, 1.71; 95% CI, 1.06-2.76). Azithromycin was also associated with an increased risk of noncardiovascular death (HR, 2.17; 95% CI, 1.44-3.26) and all-cause mortality (HR, 2.00; 95% CI, 1.51-2.63) within 5 days of exposure. These findings suggest that outpatient azithromycin use was associated with an increased risk of cardiovascular death and noncardiovascular death. Causality cannot be established, particularly for noncardiovascular death, owing to the likelihood of residual confounding.
Authors: Zaroff JG; Cheetham TC; Palmetto N; Almers L; Quesenberry C; Schneider J; Gatto N; Corley DA
JAMA Netw Open. 2020 06 01;3(6):e208199. Epub 2020-06-01.
Patient Characteristics Associated With Choosing a Telemedicine Visit vs Office Visit With the Same Primary Care Clinicians
Video or telephone telemedicine can offer patients access to a clinician without arranging for transportation or spending time in a waiting room, but little is known about patient characteristics associated with choosing between telemedicine or office visits. To examine patient characteristics associated with choosing a telemedicine visit vs office visit with the same primary care clinicians. This cross-sectional study included data from 1 131 722 patients who scheduled a primary care appointment through the Kaiser Permanente Northern California patient portal between January 1, 2016, and May 31, 2018. All completed primary care appointments booked via the patient portal were identified. Only index visits without any other clinical visits within 7 days were included to define a relatively distinct patient-initiated care-seeking episode. Visits for routine physical, which are not telemedicine-eligible, were excluded. Data were analyzed from July 1, 2018, to December 31, 2019. Patient choice between an office, video, or telephone visit. Relative risk ratios (RRRs) for patient sociodemographic characteristics (age, sex, race/ethnicity, neighborhood socioeconomic status, language preference), technology access (neighborhood residential internet, mobile portal use), visiting the patient’s own personal primary care clinician, and in-person visit barriers (travel-time, parking, cost-sharing), associated with choice of video or telephone telemedicine (vs office visit). Of 2 178 440 patient-scheduled primary care visits scheduled by 1 131 722 patients, 86% were scheduled as office visits and 14% as telemedicine visits, with 7% of the telemedicine visits by video. Choosing telemedicine was statistically significantly associated with patient sociodemographic characteristics. For example, patients aged 65 years and over were less likely than patients aged 18 to 44 years to choose telemedicine (RRR, 0.24; 95% CI, 0.22-0.26 for video visit; RRR 0.55; 95% CI, 0.54-0.57 for telephone visit). Choosing telemedicine was also statistically significantly associated with technology access (patients living in a neighborhood with high rates of residential internet access were more likely to choose a video visit than patients whose neighborhoods had low internet access: RRR, 1.10; 95% CI, 1.06-1.14); as well as in-person visit barriers (patients whose clinic had a paid parking structure were more likely to choose a telemedicine visit than patients whose facility had free parking: RRR, 1.70; 95% CI, 1.41-2.05 for video visit; and RRR, 1.73, 95% CI, 1.61-1.86 for telephone visit). In this cross-sectional study, patients usually chose an in-person visit when scheduling an appointment online through the portal. Telemedicine may offer the potential to reach vulnerable patient groups and improve access for patients with transportation, parking, or cost barriers to clinic visits.
Authors: Reed ME; Huang J; Graetz I; Lee C; Muelly E; Kennedy C; Kim E
JAMA Netw Open. 2020 06 01;3(6):e205873. Epub 2020-06-01.
A telehealth lifestyle intervention to reduce excess gestational weight gain in pregnant women with overweight or obesity (GLOW): a randomised, parallel-group, controlled trial
Excess gestational weight gain (GWG) among women with overweight or obesity synergistically increases their already elevated risk of having gestational diabetes, a caesarean delivery, a large for gestational age infant, and post-partum weight retention, and increases their child’s risk of obesity. We investigated whether a primarily telehealth lifestyle intervention reduced excess GWG among women with overweight or obesity. We did a randomised controlled trial in five antenatal clinics of Kaiser Permanente; Oakland, San Leandro, Walnut Creek, Fremont, and Santa Clara, CA, USA. Women at 8-15 weeks’ gestation with singletons, pre-pregnancy BMI 25·0-40·0 kg/m2, and aged 18 years or older were randomly assigned (1:1) to receive the telehealth lifestyle intervention or usual antenatal care. Randomisation was adaptively balanced for age, BMI, and race and ethnicity. Data collectors and investigators were masked to group assignments. The core lifestyle intervention consisted of two in-person and 11 telephone sessions on behavioural strategies to improve weight, diet, and physical activity, and stress management to help women meet a trial goal of gaining at the lower limit of the Institute of Medicine (IOM) guidelines range for total GWG: 7 kg for women with overweight and 5 kg for women with obesity. Usual antenatal care included an antenatal visit at 7-10 weeks’ gestation, an additional seven antenatal visits, on average, and periodic health education newsletters, including the IOM GWG guidelines and information on healthy eating and physical activity in pregnancy. The primary outcome was weekly rate of GWG expressed as excess GWG, per Institute of Medicine guidelines and mean assessed in the intention-to-treat population. The trial is registered at ClinicalTrials.gov, NCT02130232. Between March 24, 2014, and Sept 26, 2017, 5329 women were assessed for eligibility and 200 were randomly assigned to the lifestyle intervention group and 198 to the usual care group. Analyses included 199 women in the lifestyle intervention group (one lost to follow-up) and 195 in the usual care group (three lost to follow-up). 96 (48%) women in the lifestyle intervention group and 134 (69%) women in the usual care group exceeded Institute of Medicine guidelines for rate of GWG per week (relative risk 0·70, 95% CI 0·59 to 0·83). Compared with usual care, women in the lifestyle intervention had reduced weekly rate of GWG (mean 0·26 kg per week [SD 0·15] vs 0·32 kg per week [0·13]; mean between-group difference -0·07 kg per week, 95% CI -0·09 to -0·04). No between-group differences in perinatal complications were observed. Our evidence-based programme showed that health-care delivery systems could further adapt to meet the needs of their clinical settings to prevent excess GWG and improve healthy behaviours and markers of insulin resistance among women with overweight or obesity by using telehealth lifestyle interventions. US National Institutes of Health.
Authors: Ferrara A; Hedderson MM; Brown SD; Ehrlich SF; Tsai AL; Feng J; Galarce M; Marcovina S; Catalano P; Quesenberry CP
Lancet Diabetes Endocrinol. 2020 06;8(6):490-500.
Prenatal Depression and Diet Quality During Pregnancy
Maternal nutrition during pregnancy has a significant effect on the health of the offspring and mother, highlighting the need for identifying factors that may affect diet during pregnancy. Research in nonpregnant and pregnant populations suggest depression may play a role. To investigate the relationship between prenatal depression and diet quality during pregnancy overall and by race/ethnicity and to explore the relationships between prenatal depression and the 12 Healthy Eating Index 2010 dietary components. A cross-sectional secondary analysis of a cohort study of Kaiser Permanente Northern California women entering prenatal care between October 2011 and April 2013. Participants included 1,160 adult pregnant women. Poor diet quality was defined as a Healthy Eating Index 2010 score in the lowest quartile. Logistic regression was used to assess the relationship between prenatal depression (defined as a depression diagnosis, Patient Health Questionnaire score of 10 or greater or antidepressant medication dispensing between the last menstrual period and completion of the food frequency questionnaire) and poor diet quality overall and by race/ethnicity. Relationships between prenatal depression and each of the 12 Healthy Eating Index 2010 dietary components were assessed using t-tests and linear regression analyses. One hundred fifty-nine (14%) participants had prenatal depression. Women with prenatal depression had nearly two times the odds of poor diet quality (odds ratio 1.80, 95% CI 1.23 to 2.60) compared with women without prenatal depression, after adjusting for potential confounders. Differences emerged by race/ethnicity; after adjusting for potential confounders the adjusted odds of poor diet quality were significant only among Hispanic women. Hispanic women with prenatal depression had an increased odds of poor diet quality compared with Hispanic women without prenatal depression (odds ratio 2.66, 95% CI 1.15 to 6.06). Women with prenatal depression had a higher consumption of empty calories (from solid fats, alcohol, and added sugars; threshold for counting alcohol >13 g/1,000 kcal) (P=0.01) and lower consumption of greens and beans (P<0.05), total fruit (P<0.01), and whole fruit (P<0.01), compared with women without prenatal depression. Except for empty calories, these findings remained after adjusting for potential confounders. Study findings suggest that women with prenatal depression are at a higher risk of poor diet quality compared with women without prenatal depression, and the relationship is stronger among Hispanic women. Nutrition counseling interventions for women with depression should consider the use of culturally sensitive materials and target limiting empty calories from solid fats, alcohol, and added sugars and encourage eating more greens, beans, and fruit.
Authors: Avalos LA; Caan B; Nance N; Zhu Y; Li DK; Quesenberry C; Hyde RJ; Hedderson MM
J Acad Nutr Diet. 2020 06;120(6):972-984. Epub 2020-02-13.
Time-to-event analysis when the event is defined on a finite time interval
Acute graft-versus-host disease (GVHD) is a frequent complication following hematopoietic cell transplantation (HCT). Research on risk factors for acute GVHD has tended to ignore two important clinical issues. First, post-transplant mortality is high. In our motivating data, 100-day post-HCT mortality was 15.4%. Second, acute GVHD in its classic form is only diagnosed within 100 days of the transplant; beyond 100 days, a patient may be diagnosed with late onset acute or chronic GVHD. Standard modeling of time-to-event outcomes, however, generally conceive of patients being able to experience the event at any point on the time scale. In this paper, we propose a novel multi-state model that simultaneously: (i) accounts for mortality through joint modeling of acute GVHD and death, and (ii) explicitly acknowledges the finite time interval during which the event of interest can take place. The observed data likelihood is derived, with estimation and inference via maximum likelihood. Additionally, we provide methods for estimating the absolute risk of acute GVHD and death simultaneously. The proposed framework is compared via comprehensive simulations to a number of alternative approaches that each acknowledge some but not all aspects of acute GVHD, and illustrated with an analysis of HCT data that motivated this work.
Authors: Lee C; Lee SJ; Haneuse S
Stat Methods Med Res. 2020 06;29(6):1573-1591. Epub 2019-08-22.
Inverse probability weighted Cox model in multi-site studies without sharing individual-level data
The inverse probability weighted Cox proportional hazards model can be used to estimate the marginal hazard ratio. In multi-site studies, it may be infeasible to pool individual-level datasets due to privacy and other considerations. We propose three methods for making inference on hazard ratios without the need for pooling individual-level datasets across sites. The first method requires a summary-level eight-column risk-set table to produce the same hazard ratio estimate and robust sandwich variance estimate as those from the corresponding pooled individual-level data analysis (reference analysis). The second and third methods, which are based on two bootstrap re-sampling strategies, require a summary-level four-column risk-set table and bootstrap-based risk-set tables from each site to produce the same hazard ratio and bootstrap variance estimates as those from their reference analyses. All three methods require only one file transfer between the data-contributing sites and the analysis center. We justify these methods theoretically, illustrate their use, and demonstrate their statistical performance using both simulated and real-world data.
Authors: Shu D; Yoshida K; Fireman BH; Toh S
Stat Methods Med Res. 2020 06;29(6):1668-1681. Epub 2019-08-26.
Comparative Effectiveness of 2 Diabetes Prevention Lifestyle Programs in the Workplace: The City and County of San Francisco Diabetes Prevention Trial
Data on the comparative effectiveness of Diabetes Prevention Programs (DPPs) in the workplace are limited. Between September 2015 and July 2016, employees of the City and County of San Francisco who were at risk for type 2 diabetes (N = 158) were randomly assigned to one of 2 DPP-derived programs recognized by the Centers for Disease Control and Prevention: an in-person YMCA-DPP (n = 78) or an online virtual lifestyle management DPP (VLM-DPP) offered through Canary Health (n = 80). The primary outcome was change in body weight assessed at 6 and 12 months. Follow-up ended in August 2017. Both the YMCA-DPP and VLM-DPP yielded a significant reduction in percentage body weight at 6 months. For the YMCA-DPP, mean percentage change at 6 months was -2.70% (95% confidence interval [CI], -3.91% to -1.48%) and at 12 months was -2.46% (95% CI, -4.24% to -0.68%). For the VLM-DPP, mean percentage change at 6 months was -2.41% (95% CI, -4.07% to -0.77%) and at 12 months was -1.59% (95% CI, -3.51% to 0.33%). The mean between-condition difference at 6 months was -0.25% (95% CI, -2.04% to 1.55%) and at 12 months was -0.84% (95% CI, -3.03% to 1.34%). No significant differences were observed between conditions. The YMCA-DPP had a slightly higher reduction in waist circumference than VLM-DDP at 6 months (mean between-condition difference -2.00 cm [95% CI, -4.24 to 0.25 cm]). Participant engagement, expressed as mean number of completed core program sessions, was significantly higher for the YMCA-DPP than the VLM-DPP. Participants of the YMCA-DPP completed an average of 10.2 sessions (95% CI, 9.0 to 11.4), and participants of the VLM-DPP completed an average of 5.9 sessions (95% CI, 4.7 to 7.1). The adjusted mean between-condition difference was 4.2 sessions (95% CI, 2.54 to 5.99). Both the YMCA-DPP and VLM-DPP yielded weight loss at 6 months, which was maintained at 12 months in the YMCA-DPP. The workplace may be an effective setting to offer DPPs.
Authors: Ferrara A; McDonald JC; Brown SD; Alexander JG; Christian-Herman JL; Fisher S; Quesenberry CP
Prev Chronic Dis. 2020 May 28;17:E38. Epub 2020-05-28.
Additive effects of blood donor smoking and gamma irradiation on outcome measures of red blood cell transfusion
Recent publications have reported conflicting results regarding the role of blood donor tobacco use on hemoglobin (Hb) levels in patients after red blood cell (RBC) transfusion. We examined associations and interactions between donor, component, and recipient factors to better understand the impact of donor smoking on transfusion outcomes. We linked blood donor and component manufacturing data, including self-reported cigarette smoking, with a cohort of patients transfused RBCs between 2013 and 2016. Using multivariable regression, we examined Hb increments and subsequent transfusion requirements after single-unit RBC transfusion episodes, adjusting for donor, component, and recipient factors. We linked data on 4038 transfusion recipients who received one or more single-unit RBC transfusions (n = 5086 units) to donor demographic and component manufacturing characteristics. Among RBC units from smokers (n = 326), Hb increments were reduced after transfusion of gamma-irradiated units (0.76 g/dL; p = 0.033) but not unirradiated units (1.04 g/dL; p = 0.54) compared to those from nonsmokers (1.01 g/dL; n = 4760). In parallel with changes in Hb levels, donor smoking was associated with the receipt of additional RBC transfusions for irradiated (odds ratio [OR], 2.49; p = 0.01) but not unirradiated RBC units (OR, 1.10; p = 0.52). Donor smoking was associated with reduced Hb increments and the need for additional transfusions in recipients of gamma-irradiated RBC units. Additional research is needed to better understand interactions between donor, component, and recipient factors on efficacy measures of RBC transfusion.
Authors: DeSimone RA; Plimier C; Lee C; Kanias T; Cushing MM; Sachais BS; Kleinman S; Busch MP; Roubinian NH
Transfusion. 2020 May 01.
Proton Pump Inhibitor Use and Risk of Gastric, Colorectal, Liver, and Pancreatic Cancers in a Community-Based Population
Proton pump inhibitors (PPIs) are commonly used for gastrointestinal disorders; given they increase the systemic levels of gastrin, a trophic hormone, there is a concern about their carcinogenicity. This study evaluated the association between PPI use and gastrointestinal cancers. We performed a nested case-control study in a large, community-based integrated healthcare setting. Cases were adults with gastric (n = 1,233), colorectal (n = 18,595), liver (n = 2,329), or pancreatic cancers (n = 567). Each case was matched with up to 10 controls by age, sex, race/ethnicity, medical facility, and enrollment duration. The primary exposure was defined as ≥2-year cumulative PPI supply. Data were obtained from pharmacy, cancer registry, and electronic medical record databases. Associations were evaluated using conditional logistic regression and adjusted for multiple confounders. We also evaluated the cancer risks separately by PPI dose, duration of use, and dose and duration. PPI use of ≥2-years was not associated with the risks of gastric (odds ratio [OR]: 1.07, 95% confidence interval [CI]: 0.81-1.42), colorectal (OR: 1.05, 95% CI: 0.99-1.12), liver (OR: 1.14, 95% CI: 0.91-1.43), or pancreatic cancers (OR: 1.22, 95% CI: 0.89-1.67), compared to non-users. In exploratory analyses, elevated cancer risks were primarily restricted to those with ≥10 years of PPI use, but no consistent associations were found for increasing PPI dose and/or duration of use. PPI use of ≥2 years was not associated with increased risks of gastrointestinal cancers. The cancer risks associated with PPI use of ≥10 years requires further study.
Authors: Lee JK; Merchant SA; Schneider JL; Jensen CD; Fireman BH; Quesenberry CP; Corley DA
Am J Gastroenterol. 2020 05;115(5):706-715.
Initial Glycemic Control and Care Among Younger Adults Diagnosed With Type 2 Diabetes
The prevalence of type 2 diabetes is increasing among adults under age 45. Onset of type 2 diabetes at a younger age increases an individual’s risk for diabetes-related complications. Given the lasting benefits conferred by early glycemic control, we compared glycemic control and initial care between adults with younger onset (21-44 years) and mid-age onset (45-64 years) of type 2 diabetes. Using data from a large, integrated health care system, we identified 32,137 adults (aged 21-64 years) with incident diabetes (first HbA1c ≥6.5% [≥48 mmol/mol]). We excluded anyone with evidence of prior type 2 diabetes, gestational diabetes mellitus, or type 1 diabetes. We used generalized linear mixed models, adjusting for demographic and clinical variables, to examine differences in glycemic control and care at 1 year. Of identified individuals, 26.4% had younger-onset and 73.6% had mid-age-onset type 2 diabetes. Adults with younger onset had higher initial mean HbA1c values (8.9% [74 mmol/mol]) than adults with onset in mid-age (8.4% [68 mmol/mol]) (P < 0.0001) and lower odds of achieving an HbA1c <7% (<53 mmol/mol) 1 year after the diagnosis (adjusted odds ratio [aOR] 0.70 [95% CI 0.66-0.74]), even after accounting for HbA1c at diagnosis. Adults with younger onset had lower odds of in-person primary care contact (aOR 0.82 [95% CI 0.76-0.89]) than those with onset during mid-age, but they did not differ in telephone contact (1.05 [0.99-1.10]). Adults with younger onset had higher odds of starting metformin (aOR 1.20 [95% CI 1.12-1.29]) but lower odds of adhering to that medication (0.74 [0.69-0.80]). Adults with onset of type 2 diabetes at a younger age were less likely to achieve glycemic control at 1 year following diagnosis, suggesting the need for tailored care approaches to improve outcomes for this high-risk patient population.
Authors: Gopalan A; Mishra P; Alexeeff SE; Blatchins MA; Kim E; Man A; Karter AJ; Grant RW
Diabetes Care. 2020 05;43(5):975-981. Epub 2020-03-04.
Alcohol and tobacco use in relation to mammographic density in 23,456 women
Percent density (PD) is a strong risk factor for breast cancer that is potentially modifiable by lifestyle factors. PD is a composite of the dense (DA) and nondense (NDA) areas of a mammogram, representing predominantly fibroglandular or fatty tissues, respectively. Alcohol and tobacco use have been associated with increased breast cancer risk. However, their effects on mammographic density (MD) phenotypes are poorly understood. We examined associations of alcohol and tobacco use with PD, DA, and NDA in a population-based cohort of 23,456 women screened using full-field digital mammography machines manufactured by Hologic or General Electric. MD was measured using Cumulus. Machine-specific effects were estimated using linear regression, and combined using random effects meta-analysis. Alcohol use was positively associated with PD (P trend = 0.01), unassociated with DA (P trend = 0.23), and inversely associated with NDA (P trend = 0.02) adjusting for age, body mass index, reproductive factors, physical activity, and family history of breast cancer. In contrast, tobacco use was inversely associated with PD (P trend = 0.0008), unassociated with DA (P trend = 0.93), and positively associated with NDA (P trend<0.0001). These trends were stronger in normal and overweight women than in obese women. These findings suggest that associations of alcohol and tobacco use with PD result more from their associations with NDA than DA. PD and NDA may mediate the association of alcohol drinking, but not tobacco smoking, with increased breast cancer risk. Further studies are needed to elucidate the modifiable lifestyle factors that influence breast tissue composition, and the important role of the fatty tissues on breast health.
Authors: McBride RB; Alexeeff SE; Sakoda LC; Habel LA; Sieh W; et al.
Cancer Epidemiol Biomarkers Prev. 2020 05;29(5):1039-1048. Epub 2020-02-17.
Prediction of Occult Uterine Sarcoma prior to Hysterectomy for Women with Leiomyoma or Abnormal Bleeding
To develop a risk prediction model for occult uterine sarcoma using preoperative clinical characteristics in women undergoing hysterectomy for presumed uterine leiomyomata. Cases of uterine sarcoma were identified from the electronic medical records. Age/race-matched controls were selected at a 2:1 ratio (controls:cases) from a cohort of 45 188 women who underwent hysterectomy for uterine leiomyomata or abnormal bleeding during the same time interval. Unadjusted conditional logistic regression was performed to identify risk factors for occult uterine sarcomas, defined as no preoperative suspicion for malignancy. A risk prediction model was developed using a weighted logistic regression model, and the performance of the model was assessed using the receiver operator characteristic curve and corresponding area under the curve. A large integrated health care system in California PATIENTS: Women 18 years of age and older who underwent a hysterectomy and were diagnosed with a uterine sarcoma and matched controls from 2006 to 2013. None. There were 117 cases of occult uterine sarcomas that met inclusion criteria during the study period. The final risk prediction model included age, race/ethnicity, number of myomas, uterine weight, uterine size increase, degree of pelvic pain, and recent history of blood transfusion. The risk prediction model showed high accuracy based on the receiver operating characteristic curve method (area under the curve = 0.83; 95% confidence interval, 0.77-0.90); however, the positive predictive values were low (0.048 or less) at all risk thresholds. Multiple clinical features are associated with the presence of a uterine sarcoma, but when incorporated into a prediction model, they fail to provide significantly more information about women who may have an unrecognized sarcoma and only marginally improve the certainty about women who are not likely to have sarcoma.
Authors: Lentz SE; Zaritsky E; Tucker LY; Lee C; Lazo IM; Niihara A; Yamamoto M; Raine-Bennett T
J Minim Invasive Gynecol. 2020 May - Jun;27(4):930-937.e1. Epub 2019-07-25.
Exploiting nonsystematic covariate monitoring to broaden the scope of evidence about the causal effects of adaptive treatment strategies
In studies based on electronic health records (EHR), the frequency of covariate monitoring can vary by covariate type, across patients, and over time, which can limit the generalizability of inferences about the effects of adaptive treatment strategies. In addition, monitoring is a health intervention in itself with costs and benefits, and stakeholders may be interested in the effect of monitoring when adopting adaptive treatment strategies. This paper demonstrates how to exploit nonsystematic covariate monitoring in EHR-based studies to both improve the generalizability of causal inferences and to evaluate the health impact of monitoring when evaluating adaptive treatment strategies. Using a real world, EHR-based, comparative effectiveness research (CER) study of patients with type II diabetes mellitus, we illustrate how the evaluation of joint dynamic treatment and static monitoring interventions can improve CER evidence and describe two alternate estimation approaches based on inverse probability weighting (IPW). First, we demonstrate the poor performance of the standard estimator of the effects of joint treatment-monitoring interventions, due to a large decrease in data support and concerns over finite-sample bias from near-violations of the positivity assumption (PA) for the monitoring process. Second, we detail an alternate IPW estimator using a no direct effect assumption. We demonstrate that this estimator can improve efficiency but at the potential cost of increase in bias from violations of the PA for the treatment process.
Authors: Kreif N; Sofrygin O; Schmittdiel JA; Adams AS; Grant RW; Zhu Z; van der Laan MJ; Neugebauer R
Biometrics. 2020 Apr 15.
If Influenza Vaccines Wane Can We Delay Vaccination Without Compromising Coverage?
Authors: Klein NP; Fireman B
Clin Infect Dis. 2020 04 10;70(8):1560-1561.
Cumulative Adherence to Secondary Prevention Guidelines and Mortality After Acute Myocardial Infarction
Background The survival benefit associated with cumulative adherence to multiple clinical and lifestyle-related guideline recommendations for secondary prevention after acute myocardial infarction (AMI) is not well established. Methods and Results We examined adults with AMI (mean age 68 years; 64% men) surviving at least 30 (N=25 778) or 90 (N=24 200) days after discharge in a large integrated healthcare system in Northern California from 2008 to 2014. The association between all-cause death and adherence to 6 or 7 secondary prevention guideline recommendations including medical treatment (prescriptions for β-blockers, renin-angiotensin-aldosterone system inhibitors, lipid medications, and antiplatelet medications), risk factor control (blood pressure <140/90 mm Hg and low-density lipoprotein cholesterol <100 mg/dL), and lifestyle approaches (not smoking) at 30 or 90 days after AMI was evaluated with Cox proportional hazard models. To allow patients time to achieve low-density lipoprotein cholesterol <100 mg/dL, this metric was examined only among those alive 90 days after AMI. Overall guideline adherence was high (35% and 34% met 5 or 6 guidelines at 30 days; and 31% and 23% met 6 or 7 at 90 days, respectively). Greater guideline adherence was independently associated with lower mortality (hazard ratio, 0.57 [95% CI, 0.49-0.66] for those meeting 7 and hazard ratio, 0.69 [95% CI, 0.61-0.78] for those meeting 6 guidelines versus 0 to 3 guidelines in 90-day models, with similar results in the 30-day models), with significantly lower mortality per each additional guideline recommendation achieved. Conclusions In a large community-based population, cumulative adherence to guideline-recommended medical therapy, risk factor control, and lifestyle changes after AMI was associated with improved long-term survival. Full adherence was associated with the greatest survival benefit.
Authors: Solomon MD; Leong TK; Levin E; Rana JS; Jaffe MG; Sidney S; Sung SH; Lee C; DeMaria A; Go AS
J Am Heart Assoc. 2020 03 17;9(6):e014415. Epub 2020-03-05.
Depletion of Susceptibles Bias in Analyses of Intra-season Waning of Influenza Vaccine Effectiveness
Bias arises in studies of waning vaccine effectiveness when higher-risk individuals are depleted from the at-risk population at different rates between study groups. We examined how this bias arises and how to avoid it. A reanalysis of data from California confirmed a finding of intra-season waning of influenza vaccine effectiveness.
Authors: Ray GT; Lewis N; Klein NP; Daley MF; Lipsitch M; Fireman B
Clin Infect Dis. 2020 03 17;70(7):1484-1486.
Association of immunosuppression and HIV viremia with anal cancer risk in persons living with HIV in the United States and Canada
People living with human immunodeficiency virus (HIV; PLWH) have a markedly elevated anal cancer risk, largely due to loss of immunoregulatory control of oncogenic human papillomavirus infection. To better understand anal cancer development and prevention, we determined whether recent, past, cumulative, or nadir/peak CD4+ T-cell count (CD4) and/or HIV-1 RNA level (HIV RNA) best predict anal cancer risk. We studied 102 777 PLWH during 1996-2014 from 21 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. Using demographics-adjusted, cohort-stratified Cox models, we assessed associations between anal cancer risk and various time-updated CD4 and HIV RNA measures, including cumulative and nadir/peak measures during prespecified moving time windows. We compared models using the Akaike information criterion. Cumulative and nadir/peak CD4 or HIV RNA measures from approximately 8.5 to 4.5 years in the past were generally better predictors for anal cancer risk than their corresponding more recent measures. However, the best model included CD4 nadir (ie, the lowest CD4) from approximately 8.5 years to 6 months in the past (hazard ratio [HR] for <50 vs ≥500 cells/µL, 13.4; 95% confidence interval [CI], 3.5-51.0) and proportion of time CD4 <200 cells/µL from approximately 8.5 to 4.5 years in the past (a cumulative measure; HR for 100% vs 0%, 3.1; 95% CI, 1.5-6.6). Our results are consistent with anal cancer promotion by severe, prolonged HIV-induced immunosuppression. Nadir and cumulative CD4 may represent useful markers for identifying PLWH at higher anal cancer risk.
Authors: Hernández-Ramírez RU; Neugebauer RS; Silverberg MJ; North American AIDS Cohort Collaboration on Research and Design of the International Epidemiologic Databases to Evaluate AIDS; et al.
Clin Infect Dis. 2020 03 03;70(6):1176-1185.
Long-term Risk of Colorectal Cancer and Related Death After Adenoma Removal in a Large, Community-based Population
The long-term risks of colorectal cancer (CRC) and CRC-related death following adenoma removal are uncertain. Data are needed to inform evidence-based surveillance guidelines, which vary in follow-up recommendations for some polyp types. Using data from a large, community-based integrated health care setting, we examined the risks of CRC and related death by baseline colonoscopy adenoma findings. Participants at 21 medical centers underwent baseline colonoscopies from 2004 through 2010; findings were categorized as no-adenoma, low-risk adenoma, or high-risk adenoma. Participants were followed until the earliest of CRC diagnosis, death, health plan disenrollment, or December 31, 2017. Risks of CRC and related deaths among the high- and low-risk adenoma groups were compared with the no-adenoma group using Cox regression adjusting for confounders. Among 186,046 patients, 64,422 met eligibility criteria (54.3% female; mean age, 61.6 ± 7.1 years; median follow-up time, 8.1 years from the baseline colonoscopy). Compared with the no-adenoma group (45,881 patients), the high-risk adenoma group (7563 patients) had a higher risk of CRC (hazard ratio [HR] 2.61; 95% confidence interval [CI] 1.87-3.63) and related death (HR 3.94; 95% CI 1.90-6.56), whereas the low-risk adenoma group (10,978 patients) did not have a significant increase in risk of CRC (HR 1.29; 95% CI 0.89-1.88) or related death (HR 0.65; 95% CI 0.19-2.18). With up to 14 years of follow-up, high-risk adenomas were associated with an increased risk of CRC and related death, supporting early colonoscopy surveillance. Low-risk adenomas were not associated with a significantly increased risk of CRC or related deaths. These results can inform current surveillance guidelines for high- and low-risk adenomas.
Authors: Lee JK; Levin TR; Fireman BH; Quesenberry CP; Corley DA; et al.
Gastroenterology. 2020 03;158(4):884-894.e5. Epub 2019-10-04.
Risk of Mortality between Untreated and Treated Papillary Thyroid Cancer: A Matched Cohort Analysis
To examine the association between treatment status and mortality risk among patients with papillary thyroid cancer (PTC). We identified 3,679 adults with PTC. Thirty-one untreated patients were matched to 155 treated patients. Hazards ratios (HR) and 95% confidence intervals (CIs) were calculated to estimate all-cause and disease-specific mortality. A low-risk subgroup was analyzed for differences in all-cause mortality. The adjusted HRs (95% CIs) for all-cause mortality at 5 and 10 years were 4.2 (1.7-10.3) and 4.1 (1.9-9.4) and for disease- specific mortality were 14.1 (3.4-59.3) and 10.2 (2.9-36.4), respectively, for untreated versus treated patients. The adjusted HRs (95% CIs) for all- cause mortality was 0.7 (0.1-6.4) for low-risk untreated versus matched treated patients. Compared to treated patients, untreated PTC patients were at higher risk of death while low-risk untreated PTC patients had comparable rate of metastasis and no increased risk of all-cause mortality. Level of evidence: 3.
Authors: Lin JK; Sakoda LC; Darbinian J; Socarras M; Chiao W; Calixto N; Quesenberry C; Gurushanthaiah D; Wang KH; Durr M
Ann Otol Rhinol Laryngol. 2020 Mar;129(3):265-272. Epub 2019-10-28.
Exercise During the First Trimester and Infant Size at Birth: Targeted Maximum Likelihood Estimation of the Causal Risk Difference
This cohort study sought to estimate the differences in risk of delivering infants who were small or large for gestational age (SGA or LGA, respectively) according to exercise during the first trimester of pregnancy (vs. no exercise) among 2,286 women receiving care at Kaiser Permanente Northern California in 2013-2017. Exercise was assessed by questionnaire. SGA and LGA were determined by the sex- and gestational-age-specific birthweight distributions of the 2017 US Natality file. Risk differences were estimated by targeted maximum likelihood estimation, with and without data-adaptive prediction (machine learning). Analyses were also stratified by prepregnancy weight status. Overall, exercise at the cohort-specific 75th percentile was associated with an increased risk of SGA of 4.5 (95% CI: 2.1, 6.8) per 100 births, and decreased risk of LGA of 2.8 (95% CI: 0.5, 5.1) per 100 births; similar findings were observed among the underweight and normal-weight women, but no associations were found among those with overweight or obesity. Meeting Physical Activity Guidelines was associated with increased risk of SGA and decreased risk of LGA but only among underweight and normal-weight women. Any vigorous exercise reduced the risk of LGA in underweight and normal-weight women only and was not associated with SGA risk.
Authors: Ehrlich SF; Neugebauer RS; Feng J; Hedderson MM; Ferrara A
Am J Epidemiol. 2020 02 28;189(2):133-145.
Learning to learn from data: Using deep adversarial learning to construct optimal statistical procedures
Traditionally, statistical procedures have been derived via analytic calculations whose validity often relies on sample size growing to infinity. We use tools from deep learning to develop a new approach, adversarial Monte Carlo meta-learning, for constructing optimal statistical procedures. Statistical problems are framed as two-player games in which Nature adversarially selects a distribution that makes it difficult for a statistician to answer the scientific question using data drawn from this distribution. The players’ strategies are parameterized via neural networks, and optimal play is learned by modifying the network weights over many repetitions of the game. Given sufficient computing time, the statistician’s strategy is (nearly) optimal at the finite observed sample size, rather than in the hypothetical scenario where sample size grows to infinity. In numerical experiments and data examples, this approach performs favorably compared to standard practice in point estimation, individual-level predictions, and interval estimation.
Authors: Luedtke A; Carone M; Simon N; Sofrygin O
Sci Adv. 2020 Feb;6(9):eaaw2140. Epub 2020-02-26.
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.
Association of Mobile Patient Portal Access With Diabetes Medication Adherence and Glycemic Levels Among Adults With Diabetes
Online patient portals support self-management, and mobile devices expand portal access, but whether this translates to improvements in diabetes outcomes is unclear. To examine the association of adding mobile patient portal access with diabetes medication adherence and glycemic levels among adults with diabetes. This retrospective cohort study included patients with diabetes treated at Kaiser Permanente Northern California, a large, integrated health care delivery system, from April 1, 2015, to December 31, 2017. Inclusion criteria were adults with diabetes with an oral diabetes prescription at baseline and no insulin use. Data were analyzed from March 2018 to March 2019. Patient portal access status for each calendar month from April 2015 to December 2017, categorized as never used, used from a computer only, used from a mobile device only, or used from both computer and mobile device. Medication adherence, measured by monthly percentage of days covered (PDC), and glycemic levels, measured by changes in glycated hemoglobin A1c (HbA1c) levels. The association of portal access with study outcomes was assessed using linear regression with patient-level fixed effects and adjusting for time-changing variables, stratified by baseline HbA1c level. Among 111 463 included patients (mean [SD] age, 63.79 [12.93] years; 59 918 [53.76%] men), the number of patients using the portal from both a computer and mobile device increased over time from 38 371 patients (34.42%) in April 2015 to 57 920 patients (61.71%) in December 2017. Among patients with no prior portal access, adding computer-only portal access was associated with an increase in PDC of 1.16 (95% CI, 0.63 to 1.70) percentage points and a change of -0.06 (95% CI, -0.08 to -0.03) percentage points in HbA1c level, and adding both mobile and computer portal access was associated with an increase in PDC of 1.67 (95% CI, 1.10 to 2.23) percentage points and a change of -0.13 (95% CI, -0.16 to -0.10) percentage points in HbA1c level. Among patients with higher baseline HbA1c level (>8.0%), changing from no portal access to both computer and mobile access was associated with an increase in PDC of 5.09 (95% CI, 3.78 to 6.40) percentage points and a change of -0.19 (95% CI, -0.27 to -0.15) percentage points in HbA1c level. These findings suggest that providing patients with computer patient portal access and combining it with mobile patient portal access are associated with significa