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Rationale: Decreased lung function has been linked to increased inflammation and oxidative stress. Statins have demonstrated antiinflammatory and antioxidant properties.Objectives: We investigated the effect of statin use on decline in lung function in the elderly, and whether smoking modified this effect.Methods: Our study population included 2,136 measurements on 803 elderly men from the Normative Aging Study whose lung function (FVC and FEV(1)) was measured two to four times between 1995 and 2005. Subjects indicated statin use and smoking history at each visit. We used mixed linear models to estimate the effects of each covariate, adjusting for subject and possible confounders.Measurements and Main Results: For those not using statins, the estimated decline in FEV(1) was 23.9 ml/year (95% confidence interval [CI], -27.8 to -20.1 ml/yr), whereas those taking statins had an estimated 10.9-ml/year decline in FEV(1) (95% CI, -16.9 to -5.0 ml/yr). We also examined the effect of statins with smoking by dividing the cohort into four groups: never-smokers, longtime quitters (quit >or= 10 yr ago), recent quitters (quit < 10 yr ago), and current smokers. We found a significant three-way interaction between time since first visit, statin use, and smoking status (P < 0.001). Within each smoking category, the effect of statins was always estimated to be beneficial, but the size of the improvement in the decline rate varied among smoking groups. We found similar results for FVC decline.Conclusions: Our results indicate that statin use attenuates decline in lung function in the elderly, with the size of the beneficial effect modified by smoking status. [ABSTRACT FROM AUTHOR]

Importance: It is unknown whether state recreational cannabis legalization (RCL) is related to increased rates of prenatal cannabis use or whether RCL-related changes vary with cannabis screening methods or the local policy environment., Objective: To test whether RCL in California was associated with changes in prenatal cannabis use rates, whether changes were evident in both self-report and urine toxicology testing, and whether rates varied by local policies banning vs allowing adult-use retailers post-RCL., Design, Setting, and Participants: This population-based time-series study used data from pregnancies in Kaiser Permanente Northern California universally screened for cannabis use during early pregnancy by self-report and toxicology testing from January 1, 2012, to December 31, 2019. Analyses were conducted from September 2022 to August 2024., Exposures: California state RCL passage (November 9, 2016) and implementation of legal sales (January 1, 2018) were examined with a 1-month lag. Local policies allowing vs banning medical retailers pre-RCL and adult-use retailers post-RCL were also examined., Main Outcomes and Measures: Any prenatal cannabis use was based on screening at entrance to prenatal care (typically at 8-10 weeks' gestation) and defined as (1) a positive urine toxicology test result or self-report, (2) a positive urine toxicology test result, or (3) self-report. Interrupted time series models were fit using Poisson regression, adjusting for age, race and ethnicity, and neighborhood deprivation index., Results: The sample of 300 993 pregnancies (236 327 unique individuals) comprised 25.9% Asian individuals, 6.4% Black individuals, 26.0% Hispanic individuals, 37.7% White individuals, and 4.1% individuals of other, multiple, or unknown race, with a mean (SD) age of 30.3 (5.4) years. Before RCL implementation, rates of prenatal cannabis use rose steadily from 4.5% in January 2012 to 7.1% in January 2018. There was no change in use rates at the time of RCL passage (level change rate ratio [RR], 1.03; 95% CI, 0.96-1.11) and a statistically significant increase in rates in the first month after RCL implementation, increasing to 8.6% in February 2018 (level change RR, 1.10; 95% CI, 1.04-1.16). Results were similar when defining prenatal cannabis use by (1) a toxicology test or (2) self-report. In local policy analyses, the post-RCL implementation increase in use was only found among those in jurisdictions allowing adult-use cannabis retailers (allowed RR, 1.21; 95% CI, 1.10-1.33; banned RR, 1.01; 95% CI, 0.93-1.10)., Conclusions and Relevance: In this time-series study, RCL implementation in California was associated with an increase in rates of cannabis use during early pregnancy, defined by both self-report and toxicology testing, driven by individuals living in jurisdictions that allowed adult-use retailers.

Objectives. To examine whether local cannabis policies and retail availability are associated with cannabis use and problematic cannabis use (PCU) among adolescents in Northern California. Methods. The sample comprised adolescents aged 13 to 17 years screened for past-year cannabis use during well-child visits in 2021. Exposures included local bans on cannabis storefront retailers, policy protectiveness, and retail proximity and density. Outcomes included self-reported past-year cannabis use and PCU diagnoses. Modified Poisson regression models adjusted for sociodemographics. Results. The sample (n = 103 134) was 51.1% male with a median age of 15 years (interquartile range [IQR] = 14-16 years); 5.5% self-reported cannabis use, and 0.3% had diagnosed PCU. Adolescents had a lower prevalence of cannabis use in jurisdictions that banned storefront retailers (adjusted prevalence rate [APR] = 0.857; 95% confidence interval [CI] = 0.814, 0.903 vs allowed), banned delivery (APR = 0.751; 95% CI = 0.710, 0.795 vs allowed), or had more policy protections (APR range = 0.705-0.800). Lower PCU prevalence was also found among those in jurisdictions that banned (vs allowed) storefront retailers (APR = 0.786; 95% CI = 0.629, 0.983) or delivery (APR = 0.783; 95% CI = 0.616, 0.996). Longer drive time and lower density of storefront retailers were associated with a lower cannabis use prevalence. Conclusions. More protective cannabis policies and less retail availability were associated with a lower prevalence of adolescent cannabis use and PCU. ( Am J Public Health . 2024;114(S8):S654-S663. https://doi.org/10.2105/AJPH.2024.307787).

Aims: To estimate the strength of association between psychiatric disorders and substance use disorders (SUD), and cannabis use and cannabis use disorder (CUD) during early pregnancy., Design: Observational study., Setting: Kaiser Permanente Northern California, USA., Participants: 299 496 pregnancies from 227 555 individuals screened for cannabis use by self-report and a urine toxicology test at entrance to prenatal care in Kaiser Permanente Northern California during January 2011-December 2021 (excepting year 2020). The sample was 62.5% non-White, with a mean (standard deviation) age of 31.1 (5.5) years; 6.8% used cannabis; 0.2% had a CUD., Measurements: Exposure variables included electronic health record-based psychiatric diagnoses of attention deficit hyperactivity, anxiety, bipolar, depressive, personality, posttraumatic stress and psychotic disorders; and alcohol, opioid, stimulant and tobacco use disorders, during the two years prior to pregnancy up to the day before the prenatal substance use screening date. Outcome variables were any cannabis use, frequency of self-reported cannabis use and CUD during early pregnancy., Findings: Psychiatric disorder prevalence ranged from 0.2% (psychotic) to 14.3% (anxiety), and SUD ranged from 0.3% (stimulant/opioid) to 3.8% (tobacco). Psychiatric disorders were associated with cannabis use and CUD, with the strongest association for any use found for bipolar disorder (adjusted odds ratio [aOR] = 2.83; 95% confidence interval [CI] = 2.53-3.17) and the strongest association for CUD found for psychotic disorders (aOR = 10.01, 95% CI = 6.52-15.37). SUDs were associated with cannabis use and CUD, with the strongest association for any use found for tobacco use disorder (aOR = 4.03, 95% CI = 3.82-4.24) and the strongest association for CUD found for stimulant use disorder (aOR = 21.99, 95% CI = 16.53-29.26). Anxiety, bipolar, depressive disorders and tobacco use disorder were associated with greater odds of daily than monthly or less cannabis use., Conclusions: Psychiatric disorders and substance use disorders appear to be associated with elevated odds of any and frequent cannabis use as well as cannabis use disorder during early pregnancy. In most cases, the associations with cannabis outcomes were stronger for substance use disorders than other psychiatric disorders., (© 2024 Society for the Study of Addiction.)

Introduction: Organophosphate esters (OPEs) are increasing in use as flame retardants and plasticizers and concerns have been raised given their endocrine-disrupting activities and possible obesogenic consequences. However, longitudinal studies on gestational OPE exposure and childhood obesity are scarce. This study examined whether OPE levels in maternal urine during pregnancy were associated with the risk of childhood obesity., Methods: OPEs were analyzed in pregnancy urine samples of 5,087 individuals from 14 studies contributing to the Environmental influences on Child Health Outcomes (ECHO) Cohort. BDCPP, DBUP/DIBP, and DPHP, detected in > 80 % of the samples, were modeled continuously and by tertiles; whereas BCPP, BBOEP, and BCETP, detected in 50-80 % of samples, were modeled categorically (not-detected, low, and high). Childhood obesity was defined by BMI z-score ≥ 95th percentile according to WHO (<2 years) and the CDC (≥2 years) metrics. Adjusted modified Poisson regression models assessed childhood obesity risk and the mixture effect was assessed using Bayesian kernel machine regression (BKMR)., Results: BMI measurements were available for 3,827 children in infancy (0.5-1.9 years), 3,921 children in early childhood (2.0-4.9 years), and 2,541 children in mid-childhood (5.0-10.0 years). Obesity was present in 16-21 % of children across age groups. In mid-childhood DBUP/DIBP second and third versus first tertiles were associated with increased obesity risk (RR 1.14; 95 % CI: 1.02, 1.28; and RR 1.11; 95 % CI: 0.97, 1.27; respectively); whereas BDCPP second and third versus first tertiles reflected an inverse association with obesity risk (RR 0.85; 95 % CI: 0.80, 0.91 and RR 0.91; 95 % CI: 0.77, 1.07; respectively). No association with obesity risk was observed for DPHP, BCPP, BBOEP, and BCETP. Directions observed were consistent with those seen in BKMR models., Conclusions: This study identified mixed associations between gestational OPE exposure and childhood obesity. Further investigation across a comprehensive range of OPE exposures is warranted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To examine whether maternal cannabis use during early pregnancy is associated with offspring attention deficit hyperactivity disorder (ADHD) and disruptive behavior disorders (DBD)., Methods: We conducted a population-based retrospective birth cohort study of children (N = 141,570) born between 2011 and 2018 to pregnant individuals (N = 117,130) in Kaiser Permanente Northern California universally screened for any prenatal cannabis use at the entrance to prenatal care (at ∼8-10 wk gestation). Prenatal cannabis use was defined as (1) self-reported use and/or a positive toxicology test, (2) self-reported use, (3) a positive toxicology test, and (4) self-reported use frequency. Cox proportional hazards regression models adjusting for maternal characteristics (sociodemographics, other substance use and substance use disorders, prenatal care initiation, comorbidities) examined associations between prenatal cannabis use and offspring ADHD and DBD diagnosed by age 11 years., Results: The sample of pregnant individuals was 27.2% Asian/Pacific Islander, 5.7% Black, 24.5% Hispanic, and 38.8% non-Hispanic White, with a mean (SD) age of 30.9 (5.2) years; 4.6% screened positive for any cannabis use (0.4% daily, 0.5% weekly, 1.1% monthly or less, 2.7% unknown frequency); 3.92% had a positive toxicology test and 1.8% self-reported use; 7.7% of offspring had ADHD and 6.8% had DBD. Maternal prenatal cannabis use was not associated with ADHD (adjusted hazard ratio [aHR]: 0.84, 95% CI, 0.70-1.01), and there was an inverse association with DBD (aHR: 0.83, 95% CI, 0.71-0.97), which remained when cannabis was defined by toxicology testing but not by self-report. Frequency of use was not associated with outcomes., Conclusion: Maternal prenatal cannabis use was not associated with an increased risk of offspring ADHD or DBD., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Importance: Maternal prenatal cannabis use is associated with adverse neonatal health effects, yet little is known about its association with child developmental outcomes., Objective: To evaluate associations between maternal prenatal cannabis use in early pregnancy and child early developmental delays., Design, Setting, and Participants: This cohort study included 119 976 children born to 106 240 unique individuals between January 2015 and December 2019 and followed up to aged 5.5 years or younger (through December 31, 2021) at Kaiser Permanente Northern California. Individuals were screened for prenatal cannabis use via self-report and urine toxicology at entrance into prenatal care (approximately 8- to 10-weeks' gestation). Data were analyzed from February 2023 to March 2024., Exposure: Maternal prenatal cannabis use defined as any use (self-reported or by urine toxicology testing) and use frequency., Main Outcomes: Early developmental delays (speech and language disorders, motor delays, global delays) in children up to age 5.5 years defined by International Statistical Classification of Diseases and Related Health Problems, Ninth Revision and Tenth Revision diagnoses codes ascertained from electronic health records., Results: In this cohort of 119 976 pregnancies among 106 240 unique pregnant individuals, there were 29 543 Hispanic pregnancies (24.6%), 6567 non-Hispanic Black pregnancies (5.5%), 46 823 non-Hispanic White pregnancies (39.0%), 12 837 pregnancies (10.7%) to individuals aged 24 years or younger, and 10 365 pregnancies (8.6%) to individuals insured by Medicaid. Maternal prenatal cannabis use was documented for 6778 pregnancies (5.6%). Daily maternal prenatal cannabis use was reported for 618 pregnancies (0.5%), weekly for 722 pregnancies (0.6%), and monthly or less for 1617 pregnancies (1.3%). No association was observed between maternal prenatal cannabis use and child speech and language disorders (HR, 0.93; 95% CI, 0.84-1.03), global developmental delays (HR, 1.04; 95% CI, 0.68-1.59), or motor delays (HR, 0.86; 95% CI, 0.69-1.06). No association was detected between the frequency of maternal prenatal cannabis use and child early developmental delays., Conclusions and Relevance: In this cohort study, maternal prenatal cannabis use was not associated with an increased risk of child early developmental delays. Future research is needed to assess different patterns of cannabis use throughout pregnancy. Given the association between maternal prenatal cannabis use and other adverse outcomes, pregnant individuals should be educated on those risks.

Importance: Despite an increase in maternal prenatal cannabis use and associations with adverse neonatal outcomes, research on child neurodevelopmental outcomes is limited., Objective: To evaluate the association between maternal cannabis use in early pregnancy and child autism spectrum disorder (ASD)., Design, Setting, and Participants: This population-based retrospective birth cohort study included children born between 2011 and 2019 to pregnant Kaiser Permanente Northern California members screened for prenatal cannabis use during pregnancy. Statistical analysis was conducted February 2023 to March 2024., Exposures: Maternal prenatal cannabis use was assessed at entrance to prenatal care (approximately 8- to 10-weeks' gestation) via self-report and/or positive urine toxicology test. Use frequency was assessed., Main Outcomes and Measures: Child ASD was defined by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis codes ascertained from the electronic health record. Associations between maternal prenatal cannabis use and child ASD were modeled using Cox proportional hazards regression adjusted for maternal sociodemographic, other substance use and disorders, prenatal care initiation, comorbidities, and clustering among maternal siblings., Results: The study cohort included 178 948 singleton pregnancies among 146 296 unique pregnant individuals, including 48 880 (27.3%) Asian or Pacific Islander, 42 799 (23.9%) Hispanic, 9742 (5.4%) non-Hispanic Black, and 70 733 (39.5%) non-Hispanic White pregnancies. The median (IQR) maternal age at pregnancy onset was 31 (6) years; 8486 (4.7%) screened positive for cannabis use, 7054 (3.9%) via urine toxicology testing and 3662 (2.0%) by self-report. In the total study population, the frequency of self-reported use was monthly or less for 2003 pregnancies (1.1%), weekly for 918 pregnancies (0.5%), daily for 741 pregnancies (0.4%), and unknown for 4824 pregnancies (2.7%). ASD was diagnosed in 3.6% of children. After adjustment for maternal characteristics, maternal prenatal cannabis use was not associated with child ASD (hazard ratio [HR], 1.05; 95% CI, 0.84-1.32). When self-reported frequency of use was assessed, no statistically significant associations were observed after confounder adjustment. No sex-specific associations were documented (males: HR, 1.01; 95% CI, 0.77-1.32; and females: HR, 1.19; 95% CI, 0.77-1.85)., Conclusions and Relevance: In this cohort study, maternal cannabis use assessed in early pregnancy was not associated with child ASD. Additional studies are needed to evaluate different patterns of use throughout pregnancy. Given the known adverse neonatal health effects of maternal prenatal cannabis use, clinicians should follow national guidelines and advise against use.

This population-based cross-sectional study analyzed electronic health record data of pregnant individuals in an integrated health care delivery system in California to examine changes in prenatal cannabis use through self-report and urine toxicology testing during standard prenatal care between 2012 (n=33,546) and 2022 (n=43,415), and to test whether trends differed by race and ethnicity or age. The prevalence of prenatal cannabis use increased from 5.5% (95% CI, 5.3-5.8%) in 2012 to 9.0% (95% CI, 8.7-9.2%) in 2022 (adjusted prevalence ratio [aPR] 1.82, 95% CI, 1.72-1.92), with similar increases by toxicology test (aPR 1.70, 95% CI, 1.60-1.81) and self-report (aPR 2.12, 95% CI, 1.95-2.30). The increase in prevalence varied significantly across racial and ethnic and age groups, with the highest prevalence among Black individuals and those aged 13-24 across years. Although rates increased more slowly among groups with the highest prevalence of use, disparities persisted over time., Competing Interests: Financial Disclosure Cynthia I. Campbell and Monique B. Does have received support managed through their institution from the Industry PMR Consortium, a consortium of companies working together to conduct post-marketing studies required by the U.S. Food and Drug Administration that assess risks related to opioid analgesic use. The other authors did not report any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: With extended lifespans for people with human immunodeficiency virus (PWH), there is a corresponding increased burden of chronic illnesses, including cancer. Our objective was to estimate the excess mortality for PWH with cancer compared with people without HIV (PWoH), accounting for the higher background mortality in the general PWH population., Methods: We identified 39,000 PWH and 387,767 demographically-matched PWoH in three integrated healthcare systems from 2000-2016. We estimated excess mortality for PWH with cancer, computed as the cancer mortality rate difference-in-difference comparing PWH and PWoH. We evaluated five cancer groups: any cancer; virus-, human papillomavirus-, and Epstein-Barr virus (EBV)-related cancers; virus-unrelated cancers, and common individual cancers. We fitted a multivariable additive Poisson model to estimate excess mortality for PWH with cancer., Results: PWH with any cancer had excess mortality compared with PWoH (41.3/1000 person-years [py], 95% Confidence Interval [CI] 34.0, 48.7). The highest excess mortality was observed for EBV-related cancers (63.2/1000 py, 95% CI 47.8, 78.7), lung cancer (147.7/1000 py, 95% CI 41.1, 254.3) and non-Hodgkin lymphoma (70.5/1000 py, 95% CI 51.4, 89.6). Excess mortality for PWH was attenuated 2009-2016, and PWH with cancer had no excess mortality 5 years after diagnosis., Conclusions: PWH in care may have excess mortality from certain cancer types, although disparities may have attenuated over time and do not persist beyond 5 years after diagnosis., Impact: Findings may guide improved clinical practice, and suggest further research is needed to investigate whether cancer treatment or other factors contribute to mortality disparities for PWH with cancer.

Importance: Many studies have evaluated whether in utero cannabis exposure is associated with fetal and neonatal outcomes, yet little is known about whether prenatal cannabis use is associated with maternal health outcomes during pregnancy., Objective: To evaluate whether prenatal cannabis use is associated with maternal health outcomes during pregnancy., Design, Setting, and Participants: This population-based retrospective cohort study included pregnancies in Northern California from January 2011 to December 2019 that lasted 20 weeks or longer and were screened for prenatal cannabis use., Exposures: Prenatal cannabis use was defined as any self-reported use during early pregnancy or a positive toxicology test result based on universal screening at entrance to prenatal care (approximately 8-10 weeks' gestation). Self-reported frequency of use (daily, weekly, monthly or less, never, unknown), use defined only by self-report, and use defined only by toxicology test results were examined., Main Outcomes and Measures: Electronic health record data were used to define the following outcomes: gestational hypertension, preeclampsia, eclampsia, gestational diabetes, gestational weight gain greater and less than guidelines, placenta previa, placental abruption, placenta accreta, and severe maternal morbidity. Adjusted risk ratios (aRRs) were calculated using a modified Poisson regression., Results: The sample (n = 316 722 pregnancies; 250 221 unique individuals) included 84 039 (26.5%) Asian/Pacific Islander, 20 053 (6.3%) Black, 83 145 (26.3%) Hispanic, and 118 333 (37.4%) White individuals; the mean (SD) age was 30.6 (5.4) years. Overall, 20 053 (6.3%) screened positive for prenatal cannabis use; 2.9% were positive by self-report, 5.3% by toxicology testing, and 1.8% by both. The frequency of cannabis use was 1930 (0.6%) daily, 2345 (0.7%) weekly, 4892 (1.5%) monthly or less, and 10 886 (3.4%) unknown. Prenatal cannabis use was associated with greater risk of gestational hypertension (aRR, 1.17; 95% CI, 1.13-1.21), preeclampsia (aRR, 1.08; 95% CI, 1.01-1.15), weight gain less than (aRR, 1.05; 95% CI, 1.01-1.08) and greater than (aRR, 1.09; 95% CI, 1.08-1.10) guidelines, and placental abruption (aRR, 1.19; 95% CI, 1.05-1.36). The pattern of results was similar when defining prenatal cannabis use only by self-report or only by toxicology testing, and associations between the frequency of prenatal cannabis use and outcomes varied with outcome., Conclusions and Relevance: The results of this cohort study suggest that prenatal cannabis use was associated with several adverse maternal health outcomes during pregnancy. Continued research is needed to understand whether characteristics of prenatal cannabis use (eg, dose, mode, and timing) moderate these associations.

Ethnic enclaves influence the health of Asian American and Hispanic or Latinx/a/o populations, likely via neighborhood social, economic, and built environments. To facilitate studies aiming to disentangle these specific neighborhood mechanisms, we describe the creation and validation of two novel measures-Asian-serving and Hispanic-serving sociocultural institutions (SCIs)-to estimate the social, cultural, and economic character of ethnic enclaves in California. Business listing data were used to identify SCIs or businesses that promote cultural and social identity, including arts, civic, historical, religious, social service, and membership organizations. Keyword searches of business names were used to identify potential Asian- or Hispanic-serving SCIs. An online audit of 1,627 businesses within 12 cities confirmed the validity of using keyword searches to assess whether census tracts were high or low in Asian- or Hispanic-serving SCIs (sensitivity: 63%-100%, specificity: 86%-95%; positive predictive value: 63%-89%). In exploratory regression analyses, high presence of SCIs (compared to low presence) may be associated with neighborhood-level health indicators, including greater percentages of residents who had an annual checkup in majority Asian census tracts and lower percentages of residents who were current smokers in majority Asian and Hispanic census tracts. This approach advances methodology in measurement of neighborhood sociocultural environments., Competing Interests: Declarations of interest This research does not necessarily represent the views of the funders or institutions affiliated with this work. Aside from the funding sources listed above, there are no financial interests to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: As more states legalize cannabis, studies are needed to understand the potential impacts of recreational cannabis legalization (RCL) on adolescents from the perspective of clinicians who care for them., Methods: This qualitative study characterized clinician perspectives on whether cannabis legalization is associated with changes in adolescents' cannabis use beliefs, behaviors, and consequences. Semi-structured qualitative interviews were conducted with 32 clinicians in a large healthcare organization from 9/6/2022-12/21/2022. Video-recorded interviews were transcribed and analyzed using thematic analysis., Results: The 32 participants (56.3 % female, mean [SD] age, 45.9 [7.6] years; 65.3 % non-Hispanic White) were from Addiction Medicine (n = 13), Psychiatry/Mental Health (n = 7), Pediatrics (n = 5), and the Emergency Department (n = 7). Clinicians described post-RCL increases in adolescent cannabis use, use of non-combustible modes and high-potency products, and younger age of first use. Clinicians reported social, physical, and policy changes, including changes in social norms, appealing advertisements, marketing, and easier access. Many noted fewer perceived harms among adolescents and greater self-medication post-RCL. They described how RCL contributed to increased parental cannabis use and permissiveness around adolescent use. Finally, many described post-RCL increases in cannabis hyperemesis syndrome, and several noted increased cannabis-related psychosis and acute intoxication, and decreased court-mandated treatment., Conclusions: Clinicians from diverse specialties described post-RCL increases in adolescent cannabis use and cannabis-related consequences, alongside changes in social norms, access, marketing and advertisements, and decreased perceptions of harms. Findings can inform strategies to support adolescents in the context of increased cannabis availability and acceptability post-legalization and support the development of hypotheses for broader-scale quantitative work., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Food insecurity is associated with poor glycemic control and increased risk for diabetes-related complications. The clinical benefit of addressing these challenges through a medically supportive grocery prescription (GRx) program in patients with type 2 diabetes mellitus (T2D) remains unclear. We report the aims and design of a randomized clinical trial to evaluate the effectiveness of a 6-month GRx intervention on hemoglobin A1c (HbA1c) levels among low-income adults with T2D., Methods: The Kaiser Permanente Evaluating Nutritional Interventions in Food-Insecure High-Risk Adults (KP ENRICH) Study is a pragmatic randomized trial enrolling 1100 participants within Kaiser Permanente Northern California and Southern California, two integrated health care delivery systems serving >9 million members. Medicaid-insured adults with T2D and baseline HbA1c ≥7.5% will be randomized at a 1:1 ratio to either GRx, delivered as $100 per month for select items from among a curated list of healthful food groups in an online grocery ordering and home-delivery platform along with biweekly digital nutrition educational materials, or control, consisting of free membership and deliveries from the online grocery platform but without curated food groups or purchasing dollars. The primary outcome is 6-month change in HbA1c. Secondary outcomes include 12-month change in HbA1c, and 6- and 12-month change in medical resource utilization, food security, nutrition security, dietary habits, diabetes-related quality of life, and dietary self-efficacy., Conclusions: The results of this large randomized clinical trial of GRx will help inform future policy and health system-based initiatives to improve food and nutrition security, disease management, and health equity among patients with T2D., Competing Interests: Declaration of competing interest Dr. Mozaffarian reports research funding from the National Institutes of Health, Gates Foundation, Kaiser Permanente Fund, National Association of Chain Drug Stores Foundation, and Rockefeller Foundation; personal fees from Acasti Pharma (ended); scientific advisory board, Beren Therapeutics, Brightseed, Calibrate, Elysium Health, Filtricine, HumanCo, Instacart Health, January Inc., Season Health, Validation Institute (ended: Perfect Day, Tiny Organics); an unrestricted gift from Google; stock ownership in Calibrate and HumanCo; and chapter royalties from UpToDate. Others at the Food is Medicine Institute have received research funding or gifts for investigator-initiated research from About Fresh, the American Diabetes Association, Kroger, and family foundations. The remaining authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: The full spectrum of associations between in utero cannabis exposure and adverse neonatal outcomes is still unclear., Objective: This study aimed to evaluate the associations between in utero cannabis exposure and neonatal outcomes., Study Design: 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-reported use since becoming pregnant and/or a positive urine toxicology test for cannabis at any time during pregnancy (yes/no; primary exposure). Frequency of use was self-reported and categorized as daily, weekly, monthly or less, never, or unknown (secondary exposure). Neonatal outcomes included low birthweight, small for gestational age, preterm birth, neonatal intensive care unit admission, and infant respiratory support., Results: 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 low birthweight (adjusted odds ratio, 1.20; 95% confidence interval, 1.12-1.28), small for gestational age (adjusted odds ratio, 1.24; 95% confidence interval, 1.18-1.30), preterm birth (<37 weeks; adjusted odds ratio, 1.06; 95% confidence interval, 1.00-1.13), and neonatal intensive care unit admission (adjusted odds ratio, 1.06; 95% confidence interval, 1.01-1.11). There was a suggestive association with early preterm birth (<34 weeks; adjusted odds ratio, 1.11; 95% confidence interval, 1.00-1.23; P=.055), but no significant association with respiratory support (adjusted odds ratio, 1.07; 95% confidence interval, 0.97-1.18). Dose-response analysis found an increasing likelihood of low birthweight and small for gestational age with increasing frequency of prenatal cannabis use by the pregnant individual. Sensitivity analyses further supported an increased likelihood of low birthweight and small for gestational age, although associations with other outcomes did not reach statistical significance., Conclusion: In utero cannabis exposure was associated with increased likelihood of low birthweight, small for gestational age, preterm birth, and neonatal intensive care unit admission. Clinicians should counsel individuals who are pregnant or considering pregnancy about the potential adverse neonatal health outcomes associated with prenatal cannabis use., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: 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)., Methods: 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., Results: 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)., Conclusions: 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., Competing Interests: Potential conflicts of interest. M. C. reports research grants from Gilead, MSD, and ViiV (paid to institution); payment for expert testimony from Gilead, MSD, and ViiV Healthcare (paid to institution); and support for attending meetings and/or travel from Gilead (paid to institution). C. B. H. reports grants or contracts from Gilead (payments to institution for unrelated research). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The unexplained protective effect of childhood adiposity on breast cancer risk may be mediated via mammographic density (MD). Here, we investigate a complex relationship between adiposity in childhood and adulthood, puberty onset, MD phenotypes (dense area (DA), non-dense area (NDA), percent density (PD)), and their effects on breast cancer. We use Mendelian randomization (MR) and multivariable MR to estimate the total and direct effects of adiposity and age at menarche on MD phenotypes. Childhood adiposity has a decreasing effect on DA, while adulthood adiposity increases NDA. Later menarche increases DA/PD, but when accounting for childhood adiposity, this effect is attenuated. Next, we examine the effect of MD on breast cancer risk. DA/PD have a risk-increasing effect on breast cancer across all subtypes. The MD SNPs estimates are heterogeneous, and additional analyses suggest that different mechanisms may be linking MD and breast cancer. Finally, we evaluate the role of MD in the protective effect of childhood adiposity on breast cancer. Mediation MR analysis shows that 56% (95% CIs [32%-79%]) of this effect is mediated via DA. Our finding suggests that higher childhood adiposity decreases mammographic DA, subsequently reducing breast cancer risk. Understanding this mechanism is important for identifying potential intervention targets., (© 2024. The Author(s).)

Background: We evaluated smoking differences across nativity and race/ethnicity among women diagnosed with breast cancer., Methods: 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., Results: 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 to -7.70). Furthermore, Asian (-4.60, 95% CL: -0.81 to -8.39) and Hispanic (-6.79, 95% CL: -4.14 to -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)., Conclusions: 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., Impact: Smoking behavioral patterns were similar among breast cancer survivors and the general population, informing potential smoking interventions., (©2024 American Association for Cancer Research.)

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., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

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., (© Copyright 2024 Physicians Postgraduate Press, Inc.)

Objective: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 American Society of Addiction Medicine.)

Background: 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., Aim: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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, Χ 2 p < .001). Educating pregnant individuals who use cannabis on the importance of well-child visits may benefit children's health and development., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Breast density is strongly associated with breast cancer risk. Fully automated quantitative density assessment methods have recently been developed that could facilitate large-scale studies, although data on associations with long-term breast cancer risk are limited. We examined LIBRA assessments and breast cancer risk and compared results to prior assessments using Cumulus, an established computer-assisted method requiring manual thresholding., Methods: We conducted a cohort study among 21,150 non-Hispanic white female participants of the Research Program in Genes, Environment and Health of Kaiser Permanente Northern California who were 40-74 years at enrollment, followed for up to 10 years, and had archived processed screening mammograms acquired on Hologic or General Electric full-field digital mammography (FFDM) machines and prior Cumulus density assessments available for analysis. Dense area (DA), non-dense area (NDA), and percent density (PD) were assessed using LIBRA software. Cox regression was used to estimate hazard ratios (HRs) for breast cancer associated with DA, NDA and PD modeled continuously in standard deviation (SD) increments, adjusting for age, mammogram year, body mass index, parity, first-degree family history of breast cancer, and menopausal hormone use. We also examined differences by machine type and breast view., Results: The adjusted HRs for breast cancer associated with each SD increment of DA, NDA and PD were 1.36 (95% confidence interval, 1.18-1.57), 0.85 (0.77-0.93) and 1.44 (1.26-1.66) for LIBRA and 1.44 (1.33-1.55), 0.81 (0.74-0.89) and 1.54 (1.34-1.77) for Cumulus, respectively. LIBRA results were generally similar by machine type and breast view, although associations were strongest for Hologic machines and mediolateral oblique views. Results were also similar during the first 2 years, 2-5 years and 5-10 years after the baseline mammogram., Conclusion: Associations with breast cancer risk were generally similar for LIBRA and Cumulus density measures and were sustained for up to 10 years. These findings support the suitability of fully automated LIBRA assessments on processed FFDM images for large-scale research on breast density and cancer risk., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background Clinical risk factors, a single blood pressure (BP) measurement, current biomarkers, and biophysical parameters can effectively identify risk of early-onset preeclampsia but have limited ability to predict later-onset preeclampsia and gestational hypertension. Clinical BP patterns hold promise to improve early risk stratification for hypertensive disorders of pregnancy. Methods and Results After excluding preexisting hypertension, heart, kidney, or liver disease, or prior preeclampsia, the retrospective cohort (n=249 892) all had systolic BP <140 mm Hg and diastolic BP <90 mm Hg or a single BP elevation ≤20 weeks' gestation, prenatal care at <14 weeks' gestation, and a still or live birth delivery at Kaiser Permanente Northern California hospitals (2009-2019). The sample was randomly split into development (N=174 925; 70%) and validation (n=74 967; 30%) data sets. Predictive performance of multinomial logistic regression models for early-onset (<34 weeks) preeclampsia, later-onset (≥34 weeks) preeclampsia, and gestational hypertension was evaluated in the validation data set. There were 1008 (0.4%), 10 766 (4.3%), and 11 514 (4.6%) patients with early-onset preeclampsia, later-onset preeclampsia, and gestation hypertension, respectively. Models with 6 systolic BP trajectory groups (0-20 weeks' gestation) plus standard clinical risk factors performed substantially better than risk factors alone to predict early- and later-onset preeclampsia and gestational hypertension, with C-statistics (95% CIs) of 0.747 (0.720-0.775), 0.730 (0.722-0.739), and 0.768 (0.761-0.776) versus 0.688 (0.659-0.717), 0.695 (0.686-0.704) and 0.692 (0.683-0.701), respectively, with excellent calibration (Hosmer-Lemeshow P =0.99, 0.99, and 0.74, respectively). Conclusions Early pregnancy BP patterns up to 20 weeks' gestation plus clinical, social, and behavioral factors more accurately discriminate hypertensive disorders of pregnancy risk among low-to-moderate risk pregnancies. Early pregnancy BP trajectories improve risk stratification to reveal higher-risk individuals hidden within ostensibly low-to-moderate risk groups and lower-risk individuals considered at higher risk by US Preventive Services Task Force criteria.

Importance: Older patients using many prescription drugs (hyperpolypharmacy) may be at increased risk of adverse drug effects., Objective: To test the effectiveness and safety of a quality intervention intended to reduce hyperpolypharmacy., Design, Setting, and Participants: This randomized clinical trial allocated patients 76 years or older who used 10 or more prescription medications to a deprescribing intervention or to usual care (1:1 ratio) at an integrated health system with multiple preexisting deprescribing workflows. Data were collected from October 15, 2020, to July 29, 2022., Intervention: Physician-pharmacist collaborative drug therapy management, standard-of-care practice recommendations, shared decision-making, and deprescribing protocols administered by telephone over multiple cycles for a maximum of 180 days after allocation., Main Outcomes and Measures: Primary end points were change in the number of medications and in the prevalence of geriatric syndrome (falls, cognition, urinary incontinence, and pain) from 181 to 365 days after allocation compared with before randomization. Secondary outcomes were use of medical services and adverse drug withdrawal effects., Results: Of a random sample of 2860 patients selected for potential enrollment, 2470 (86.4%) remained eligible after physician authorization, with 1237 randomized to the intervention and 1233 to usual care. A total of 1062 intervention patients (85.9%) were reached and agreed to enroll. Demographic variables were balanced. The median age of the 2470 patients was 80 (range, 76-104) years, and 1273 (51.5%) were women. In terms of race and ethnicity, 185 patients (7.5%) were African American, 234 (9.5%) were Asian or Pacific Islander, 220 (8.9%) were Hispanic, 1574 (63.7%) were White (63.7%), and 257 (10.4%) were of other (including American Indian or Alaska Native, Native Hawaiian, or >1 race or ethnicity) or unknown race or ethnicity. During follow-up, both the intervention and usual care groups had slight reductions in the number of medications dispensed (mean changes, -0.4 [95% CI, -0.6 to -0.2] and -0.4 [95% CI, -0.6 to -0.3], respectively), with no difference between the groups (P = .71). There were no significant changes in the prevalence of a geriatric condition in the usual care and intervention groups at the end of follow-up and no difference between the groups (baseline prevalence: 47.7% [95% CI, 44.9%-50.5%] vs 42.9% [95% CI, 40.1%-45.7%], respectively; difference-in-differences, 1.0 [95% CI, -3.5 to 5.6]; P = .65). No differences in use of medical services or adverse drug withdrawal effects were observed., Conclusions and Relevance: In this randomized clinical trial from an integrated care setting with various preexisting deprescribing workflows, a bundled hyperpolypharmacy deprescribing intervention was not associated with reduction in medication dispensing, prevalence of geriatric syndrome, utilization of medical services, or adverse drug withdrawal effects. Additional research is needed in less integrated settings and in more targeted populations., Trial Registration: ClinicalTrials.gov Identifier: NCT05616689.

Our recently published study of >2.4 million adults in Northern California indicated that current versus never-tobacco smoking was associated with lower risk of SARS-CoV-2 infection and less severe coronavirus disease 2019 (COVID-19). We extended this research by evaluating whether these associations were moderated by socio-demographic factors and medical comorbidities. This retrospective cohort study of 1,885,826 adults with current or never-smoking status in Kaiser Permanente Northern California from 3/5/2020 (baseline) to 12/31/2020 (pre-vaccine) included electronic health record-based socio-demographics (sex, age, race/ethnicity, neighborhood deprivation index (NDI)) and medical comorbidities (obesity, cardiovascular conditions, diabetes, renal disease, respiratory conditions). We estimated the adjusted risk of SARS-CoV-2 infection and hospitalization (≤30 days of infection) associated with smoking status using Cox proportional hazard regression models. We estimated associations within subgroups of socio-demographics and comorbidities, and tested for effect modification using interaction terms. During the study, 35,627 patients had SARS-CoV-2 infection. Current versus never-smoking status was associated with lower adjusted rates of SARS-CoV-2 infection (aHR ranging from 0.51 to 0.89) and hospitalization (aHR ranging from 0.32 to 0.70) within nearly every socio-demographic and comorbidity subgroup. Statistically significant interactions showed that the magnitude of protection for SARS-CoV-2 infection varied by sex, age, race/ethnicity, NDI, cardiovascular conditions and diabetes, and for SARS-CoV-2 hospitalization by age and renal disease. Taken together, results indicated that while some socio-demographics and comorbidities moderated the associations, the lower risk of SARS-CoV-2 infection and hospitalization associated with current versus never-smoking status persisted among patients regardless of socio-demographics or comorbidities., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Judith J. Prochaska, PhD, MPH, has provided consultation to pharmaceutical and technology companies that make medications and other treatments for quitting smoking and has served as an expert witness in lawsuits against the tobacco companies. All other authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 American Society of Addiction Medicine.)

Importance: 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., Objective: To evaluate the associations between long-term fine particulate air pollution and cardiovascular events using electronic health record and geocoded address data., Design, Setting, and Participants: 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., Exposure: 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., Main Outcomes and Measures: 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., Results: 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)., Conclusions and Relevance: 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.

Importance: 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., Objective: To investigate trends in unstable and/or unsafe living situations and IPV among pregnant individuals prior to and during the COVID-19 pandemic., Design, Setting, and Participants: 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., Exposures: COVID-19 pandemic (prepandemic period: January 1, 2019, to March 31, 2020; during pandemic period: April 1 to December 31, 2020)., Main Outcomes and Measures: 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., Results: 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., Conclusions and Relevance: 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.

Background and Aims: 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., Design: This is a retrospective cohort study., Setting: The study was conducted in California, USA., Participants: 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., Measurements: 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., Findings: 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)., Conclusions: Current cannabis use appears to be associated with a reduced risk of SARS-CoV-2 infection among pregnant individuals., (© 2022 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

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., (© 2023. The Author(s).)

Introduction: 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., Aims and Methods: 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., Results: 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., Conclusions: 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., Implications: 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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© 2022 by the American Diabetes Association.)

Competing Interests: None.

Importance: 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., Objective: 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., Design, Setting, and Participants: 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., Exposures: The COVID-19 pandemic., Main Outcomes and Measures: Prenatal cannabis use based on universal urine toxicology tests conducted during early pregnancy at entrance to prenatal care., Results: 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)., Conclusions and Relevance: 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.

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., (© 2022. The Author(s).)

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., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Context: 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., Objective: We examined the relationships among prolactin, future T2D risk, and key clinical and metabolic parameters., Methods: 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)., Results: 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., Conclusion: 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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: 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., Objectives: 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., Design, Setting, and Participants: 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., Exposures: Time (calendar year)., Main Outcomes and Measures: 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., Results: 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., Conclusions and Relevance: 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.

Background and Objective: 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., Methods: 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., Results: 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., Conclusion: 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., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: 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., Methods: 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., Results: 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., Discussion: 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.

Background: Knowledge is needed about the risk of cutaneous squamous cell carcinoma (cSCC) in solid organ transplant recipients (SOTRs) using contemporary immunosuppressive regimens., Objective: Evaluate the risk of cSCC in relation to medications used by SOTRs., Methods: 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., Results: 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., Limitation: The number of events was somewhat small., Conclusions: The knowledge of risks and benefits in diverse patients can translate to improvements in care., Competing Interests: Conflicts of interest Authors Dusendang, Carlson, Lee, Marwaha, Madani, Alexeeff, Webber, Goes, and Herrinton are partners or staff of The Permanente Medical Group. Dr Webber is an employee of the University of California at San Francisco., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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.

Fine particulate matter (PM 2.5 ) 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 PM 2.5 ., Methods: 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 PM 2.5 at residential addresses, controlling for age, sex, race/ethnicity, comorbidities, BMI, smoking, revascularization, medications, and socioeconomic status., Results: 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 PM 2.5 (HR = 0.92 [95% CI = 0.82, 1.03]) per 0.1 increase in NDVI. Walkability had no independent effect on CVD mortality. PM 2.5 had a strong independent effect in models adjusted for greenness and walkability (HR = 1.20 [95% CI = 1.08, 1.33)) per 10 μg/m 3 increase in PM 2.5 . There was an interaction between walkability and PM 2.5 ( P = 0.037), where PM 2.5 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/m 3 increase in PM 2.5 . Greenness had no interaction with PM 2.5 ( P = 0.768) nor walkability ( P = 0.385)., Conclusions: High greenness may be protective of CVD mortality among adults with CVD history. PM 2.5 associated CVD mortality risk varies slightly by level of neighborhood walkability, though these small differences may not be clinically meaningful., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Background: Low socioeconomic status (SES) has been associated with a higher risk of aggressive breast cancer (BC) subtypes, but few studies have examined the independent effects of both neighborhood-level socioeconomic status (nSES) and individual-level SES measures., Methods: This study included 5547 women from the Pathways and Life After Cancer Epidemiology cohorts who were diagnosed with invasive BC. Generalized estimating equation models were used to examine associations of nSES (a composite score based on income, poverty, education, occupation, employment, rent, and house value) and individual-level SES (income and education) with BC subtypes: luminal B (LumB), Her2-enriched (Her2-e), and triple-negative breast cancer (TNBC) relative to luminal A (LumA). Models controlled for age, race, nativity, stage, days from diagnosis to survey, and study cohort and simultaneously for nSES and individual-level SES., Results: In fully adjusted models, low nSES was significantly associated with the LumB (odds ratio for quartile 1 vs quartile 4 [OR Q1vQ4 ], 1.31; 95% confidence interval [CI], 1.11-1.54; P for trend = .005) and TNBC subtypes (OR Q1vQ4 , 1.32; 95% CI, 1.02-1.71; P for trend = .037) relative to LumA. Conversely, individual education was significantly associated with only the Her2-e subtype (odds ratio for high school degree or less vs postgraduate, 1.68; 95% CI, 1.03-2.75; P for trend = .030) relative to LumA. Individual income was not significantly associated with any BC subtype., Conclusions: nSES and individual-level SES are independently associated with different BC subtypes; specifically, low nSES and individual-level education are independent predictors of more aggressive BC subtypes relative to LumA., (© 2021 American Cancer Society.)

Background: There is a high demand for managing skin disease, and dermatologists are in short supply., Objectives: 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., Design and Setting: The retrospective longitudinal study included 106,459 patients with a skin condition diagnosed by 3,830 PCPs, from January 2017 to March 2017., Methods: Comprehensive electronic medical record data with generalized linear mixed modeling accounted for patient factors including diagnosis and clustering by medical center and PCP., Results: 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)., Discussion: 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., Conclusion: 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.