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Background: The potential risks of prenatal cannabis use may vary depending on how cannabis is administered, but little is known about modes of prenatal cannabis use. This study characterized prevalence and sociodemographic correlates of modes of prenatal cannabis use in California., Methods: This cross-sectional study included patients with pregnancies between January 1, 2021 and December 31, 2022 in a large healthcare system (3507 pregnancies [3454 individuals]) who self-reported prenatal cannabis use and mode of use (smoke, vape, edibles, dabs, and topicals) during universal screening at entrance to prenatal care. Multivariable regression models examined the relationship between sociodemographic characteristics and modes of use., Results: Smoking was the most common mode (71.1 %), followed by edibles (32.6 %), vaping (22.2 %), dabs (9.9 %), and topicals (4.6 %); 29.9 % endorsed multiple modes. Those who used edibles were the least likely to use daily (28.2 %), while those who dabbed (54.3 %) or used > 1 mode (45.3 %) were the most likely to use daily. In multivariable models, smoking was generally more common and edibles less common among those who were younger, non-Hispanic Black, and living in more deprived neighborhoods, vaping was more common among Hispanic individuals and less common among non-Hispanic Black individuals and those living in more deprived neighborhoods, and dabbing was more common among those who were younger and Hispanic., Conclusion: Modes of cannabis use during early pregnancy varied by sociodemographic characteristics. Future research is needed to test whether the risks of adverse outcomes or likelihood of persistent use during pregnancy vary depending on how cannabis is administered during pregnancy., Competing Interests: Declaration of Competing Interest Dr. Campbell and Ms. 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 Food and Drug Administration that assess risks related to opioid analgesic use. All remaining authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Mechanistic studies are needed to understand why depressive symptoms are associated with poorer physical health. The objective of this study was to examine whether behavioural, cognitive and physiological factors mediated an association between depressive symptoms, measured in early adulthood, and lower urinary tract symptoms (LUTS) and their impact, a composite variable measured in mid-life adulthood, among women in the Coronary Artery Risk Development in Young Adults study, conducted in four regions of the United States., Design: Prospective cohort study., Methods: Data were examined for 871 women. Depressive symptoms were measured and averaged across Years 5, 10 and 15. Year 20 health behaviour combined information about smoking, physical activity and diet. Year 25 cognitive function combined performance on different cognitive tests. Year 25 metabolic syndrome combined standard risk criteria for waist circumference, triglycerides, high-density lipoprotein, blood pressure and glucose. A cluster analysis of urinary incontinence, other LUTS and impact data-collected two years after Year 25-was used to group women into one of four categories: no or very mild symptoms with no impact (bladder health) versus mild, moderate or severe symptoms/impact., Results: Structural equation modelling showed a statistically significant direct path between depressive symptoms and LUTS/impact. Tests of indirect paths showed that health behaviours, cognitive function and metabolic syndrome did not mediate the association between depressive symptoms and LUTS/impact., Conclusions: Depressive symptoms in early adulthood appear to be associated with LUTS and their impact in mid-life adulthood over and above health behaviours, cognitive function and metabolic syndrome., (© 2025 The Author(s). British Journal of Health Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Objective: To investigate the effects of the Affordable Care Act (ACA) and its elimination of cost sharing on contraception utilization, pregnancy rates, and abortion rates., Methods: We conducted a retrospective cohort study within a health care system serving more than 4.5 million insured members across 21 medical centers and 250 clinics. The study included women aged 18-45 years with continuous health plan membership for at least 2 years in the pre-ACA (2007-2012) and post-ACA (2013-2018) periods. We analyzed out-of-pocket (OOP) costs for contraception, including oral contraceptives and long-acting reversible contraception (LARC), before and after the ACA's implementation. We then examined how the elimination of OOP costs affected contraception use, pregnancy rates, and abortion rates., Results: The study identified 1,523,962 women of childbearing age. In 2013, cost sharing for contraception sharply declined, with average annual OOP costs dropping from $88-94 pre-ACA to nearly zero post-ACA. Contraceptive use increased overall, rising from 30.2% pre-ACA to 31.9% by the study's end, with a notable rise in LARC use. In interrupted time-series analyses, contraception use continued to increase post-ACA, new pregnancy rates declined at a faster rate than pre-ACA, and abortion rates continued to fall, though at a slightly slower pace than pre-ACA ( P <.05 for all trends)., Conclusion: The ACA's elimination of contraception cost sharing led to increased contraception use, particularly LARC methods, and contributed to declines in both pregnancy and abortion rates. This suggests that improving access to effective contraception is a key strategy in reducing unintended pregnancies., Competing Interests: Financial Disclosure Matthew Solomon reports his institution received funding from Kaiser Permanente Community Health. Mary Reed reports her institution received funding from Kaiser Permanente Community Health, NIDDK, NIA, and the AHRQ. They also received a PCORI grant. The other authors did not report any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: To understand the role of hypertensive disorders of pregnancy (HDP), including preeclampsia and gestational hypertension (GH), in brain health earlier in life, we investigated the association of HDP with midlife cognition and brain health., Methods: We studied a prospective cohort of women, baseline age 18 to 30 years, who were assessed at study years 25 and 30 with a cognitive battery and a subset with brain magnetic resonance imaging. A history of HDP was defined based on self-report. We conducted linear regression to assess the association of a history of preeclampsia, GH, or no HDP with cognition and brain magnetic resonance imaging white matter hyperintensities., Results: Among 1441 women (mean age, 55.2±3.6 years), 202 reported preeclampsia and 112 reported GH. GH was associated with worse cognitive performance: global cognition (mean score, 23.2 versus 24.0; P =0.018), processing speed (67.5 versus 71.3; P =0.01), verbal fluency (29.5 versus 31.1; P =0.033), and a trend for executive function (24.3 versus 22.6; P =0.09), after multivariable adjustment. GH was associated with a greater 5-year decline in processing speed (mean change, -4.9 versus -2.7; P =0.049) and executive function (-1.7 versus 0.3; P =0.047); preeclampsia was associated with a greater 5-year decline on delayed verbal memory (-0.3 versus 0.1; P =0.041). GH and preeclampsia were associated with greater white matter hyperintensities in the parietal and frontal lobes, respectively., Conclusions: GH and preeclampsia are associated with cognition and white matter hyperintensities during midlife, with differences in cognitive domains and brain lobes. Women with HDP may need to be closely monitored for adverse brain outcomes starting in midlife., Competing Interests: None.

Competing Interests: Disclosure: The authors has nothing to disclose

Background: Older adults with cancer are at an increased risk of treatment related toxicities and early death. Routinely collected clinico-demographic characteristics inadequately explain this increased risk limiting accurate prognostication. Prior studies have suggested that altered body composition and frailty are independently associated with worse survival among older adults with cancer; however, their combined influence remains unclear., Methods: We used data from a single-institution prospective cohort study of older adults (≥ 60 years) who underwent geriatric assessment (GA) at the time of initial consultation with a medical oncologist from September 2017 to December 2020 and available baseline abdominal computed tomography within 60 days of GA. Using multi-slice CT images from T12 to L5 level, we assessed volumetric measures of skeletal muscle (SMV), visceral adipose tissue (VATV), subcutaneous adipose tissue (SATV) and averaged skeletal muscle density (SMD), computing sex-specific z for each measure. Frailty was measured using a 44-item frailty index using the deficit accumulation approach. Primary outcome of interest was overall survival (OS) defined as time from GA to death or last follow up. We used multivariable Cox regression model to study the independent association between the above four body composition measurements and OS adjusted for baseline confounders and frailty., Results: We included 459 patients with a mean age of 69.7 ± 7.5 years, 60% males and 77% non-Hispanic Whites. Most had colorectal (27%) or pancreatic cancer (20%) and 48% had stage IV disease. Over a median follow up of 39.4 months, 209 patients (46%) died. In multivariable Cox regression models adjusted for age, sex, race, cancer type, cancer stage and frailty, skeletal muscle volume (HR 0.74; 95% CI 0.58-0.96; p = 0.02, per 1 SD increment) was independently associated with OS. The addition of body composition variables to baseline clinico-demographic variables and frailty led to a slightly improved model discrimination., Conclusions: SMV is independently associated with OS among older adults with newly diagnosed gastrointestinal cancers. Capturing body composition measurements in oncology practice may provide additional prognostic information for older adults with cancer above and beyond what is captured in routine clinical assessment including frailty., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Objective: To investigate differences in health care utilization between immediate (within 10 minutes of placental delivery) and delayed (after 24 hours) intrauterine device (IUD) placement., Methods: This retrospective cohort study was conducted with data from Kaiser Permanente Northern California from 2017 to 2019 and included patients with an IUD placed between 0 and 63 days postpartum. The primary outcome for health care utilization was the number of obstetrician-gynecologist (ob-gyn) or women's health office visits within 1 year. Secondary outcomes included formal imaging studies, surgical intervention, and hospitalizations related to IUD complications within 1 year. An additional secondary outcome was live births at 120 days and 1 year., Results: Among 1,543 immediate and 10,332 delayed postpartum IUD placements, the number of visits to an ob-gyn or women's health office within 1 year was slightly increased with delayed placement (mean 2.30 vs 2.47, P <.001). Imaging was increased in the immediate compared with the delayed group (10.5% vs 4.1%, P <.001). Laparoscopy was decreased in the immediate compared with the delayed group (0.0% vs 0.4%, P =.005), with no significant difference in hysteroscopy (0.2% vs 0.1%, P =.413). Hospitalizations were rare and increased in the immediate group (0.4% vs 0.02%, P <.001). Lastly, there was no difference in repeat pregnancies between groups at 120 days (both 0.2%) or at 1 year (2.9% vs 2.5%, P =.342)., Conclusion: Compared with delayed placement, immediate postpartum IUD placement is not associated with increased office visits. Immediate placement is associated with an increase in imaging but a decrease in laparoscopic surgery to manage IUD-related complications. There was no difference in live birth rates at 6 months or 1 year between groups., 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.)

Concerns persist about the potential impact of prenatal exposure to bisphenols (BP) and their replacement analogues on childhood asthma and allergies. Previous studies on single and small cohorts had limited statistical power, few investigated analogues BPF and BPS, and even fewer examined atopic outcomes. Our objective was to assess whether prenatal exposures to individual environmental bisphenols (BPA, BPF, BPS) influence risk of childhood asthma, allergic rhinitis, and atopic dermatitis. Data from the U.S. Environmental Influences on Child Health Outcomes (ECHO) consortium were harmonized on measures of prenatal urinary BPA, BPF and BPS and asthma and allergic rhinitis (ages 5-9 years) and atopic dermatitis (up to age 3 years) from 1905 mother-child pairs that were collected between 1998 and 2017. Across the 2012 federal ban of BPA from certain infant products, median BPA levels decreased from 1.11 ng/ml to 0.86 ng/ml; median BPF levels decreased from 0.51 ng/ml to 0.39 ng/ml; and median BPS levels increased from 0.23 ng/ml to 0.31 ng/ml (dilution adjusted; p < 0.001 for all three median comparisons). Prenatal measures of BPA, BPF, and BPS were unrelated to the risk of childhood asthma, allergic rhinitis, or atopic dermatitis in the total population. Modest sex-dependent effects were observed: only among girls, second tertile levels of BPF was associated with a reduced odds of asthma (odds ratio (OR) 0.27, 95% confidence interval (CI) 0.08, 0.93); a continuous index of prenatal BPS was associated with reduced odds of atopic dermatitis (OR 0.64, 95% CI 0.44, 0.93). The ongoing and changing patterns of exposure to bisphenols in the U.S. population require further study with additional attention to time windows of exposure and co-occurring social determinants of health, to continue to inform current policies and evaluate the importance of limiting exposure to BPA and its analogues on childhood asthma, allergic rhinitis, and atopic dermatitis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Scott Weiss reports financial support was provided by National Institutes of Health. Scott Weiss reports financial support was provided by UptoDate Inc. Rachel L. Miller reports financial support was provided by National Institutes of Health. Yuyan Wang reports financial support was provided by National Institutes of Health. Jenny Aalborg reports financial support was provided by National Institutes of Health. Akram N. Alshawabkeh reports financial support was provided by National Institutes of Health. Deborah H. Bennett reports financial support was provided by National Institutes of Health. Carrie V. Breton reports financial support was provided by National Institutes of Health. Jessie P. Buckley reports financial support was provided by National Institutes of Health. Dana Dabelea reports financial support was provided by National Institutes of Health. Anne L. Dunlop reports financial support was provided by National Institutes of Health. Assiamira Ferrara reports financial support was provided by National Institutes of Health. Griffith Gao reports financial support was provided by National Institutes of Health. Abigail Gaylord reports financial support was provided by National Institutes of Health. Diane R. Gold reports financial support was provided by National Institutes of Health. Tina Hartert reports financial support was provided by National Institutes of Health. Irva Hertz-Picciotto reports financial support was provided by National Institutes of Health. Lori A. Hoepner reports financial support was provided by National Institutes of Health. Margaret Karagas reports financial support was provided by National Institutes of Health. Catherine J. Karr reports financial support was provided by National Institutes of Health. Rachel S. Kelly reports financial support was provided by National Institutes of Health. Camilo Khatchikian reports financial support was provided by National Institute of Health. Mengling Liu reports financial support was provided by National Institutes of Health. John D. Meeker reports financial support was provided by National Institutes of Health. Thomas G. OConnor reports financial support was provided by National Institutes of Health. Alicia K. Peterson reports financial support was provided by National Institutes of Health. Sheela Sathyanarayana reports financial support was provided by National Institutes of Health. Joanne Sordillo reports financial support was provided by National Institutes of Health. Leonardo Trasande reports financial support was provided by National Institutes of Health. Yeyi Zhu reports financial support was provided by National Institutes of Health. Rachel L. Miller reports a relationship with UptoDate Inc that includes: consulting or advisory. Scott Weiss is on the Board of Histolix a digital pathology company. If there are other authors, they 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.)

Introduction: Polycystic ovary syndrome is associated with hypertension in women, but few population studies have examined findings among adolescents. This retrospective study examines PCOS and hypertensive blood pressure in a large adolescent population receiving routine healthcare., Methods: Among females aged 13-17 years who had a well-child visit with systolic/diastolic blood pressure measured in a Northern California healthcare system (2013-2019), the outcome of hypertensive blood pressure (≥130/80 mmHg) was examined. Polycystic ovary syndrome was based on clinical diagnosis (ICD-9/10 256.4/E28.2) within 1 year of the visit. Overweight and obesity were defined by BMI 85th to <95th percentile and ≥95th percentile, respectively; 1.7% with underweight (<5th percentile) were excluded. Multivariable logistic regression was used to examine the association of polycystic ovary syndrome and hypertensive blood pressure, adjusting for age, race/ethnicity, BMI category, and estimated neighborhood deprivation index. Analyses were conducted in 2023-2024., Results: The cohort included 224,418 females (mean age 14.9±1.4 years; 34.3% non-Hispanic White, 30.1% Hispanic, 19.5% Asian/Pacific Islander, and 9.7% Black). Overall, 18.7% had overweight and 15.8% had obesity. The prevalence of hypertensive blood pressure was 7.2%, much higher for those with polycystic ovary syndrome (18.2%) versus no polycystic ovary syndrome (7.1%, p<0.001). In adjusted analyses, polycystic ovary syndrome was associated with 1.25-fold greater odds of hypertensive blood pressure (95% CI=1.10, 1.42). Similar findings were seen among the subset with obesity (OR=1.23 [95% CI=1.06, 1.42])., Conclusions: Nearly 1 in 5 adolescents with polycystic ovary syndrome had hypertensive blood pressure. Polycystic ovary syndrome was associated with 25% increased adjusted odds of hypertensive blood pressure, emphasizing the importance of blood pressure surveillance in this population with higher cardiometabolic risk., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Cannabis use among adolescents is prevalent, and clinicians who work with adolescents have unique insights about how to treat cannabis use in this population., Methods: This qualitative study interviewed 32 clinicians from addiction medicine recovery services (AMRS), the emergency department (ED), mental health (MH), and pediatrics in an integrated healthcare system to understand their perspectives and experiences regarding barriers and facilitators to treating adolescent cannabis use. The analysis was developed using thematic analysis of interviews., Results: Thirty-two clinicians (Mean age = 45.9, SD =7.6; 56.3 % Female; 56.3 % White) were recruited from AMRS (n = 13; 41.6 %), the ED (n = 7; 21.9 %), MH (n = 7; 21.9 %) and pediatrics (n = 5; 15.6 %). Clinicians discussed several key barriers and facilitators of treating adolescent cannabis use. Facilitators include the use of multiple screening tools for adolescent cannabis use (i.e., self-report and toxicology testing) which provide more comprehensive information; patient-centered treatment approaches; and discussing cannabis use in the context of adolescents' mental health. Barriers discussed included adolescents' and parents' minimization of adolescent cannabis use risks. Several factors were discussed as potential facilitators or barriers, depending on context, including the influence of peers, virtual treatment, and parental involvement or lack thereof in treatment., Conclusions: Interviews with clinicians who work with adolescents across settings highlighted factors that serve as barriers and facilitators to treating adolescent cannabis use. These findings have important implications for guiding future research and intervention efforts, including the inclusion of universal screening practices, addressing stigma, reducing adolescents' and parents' minimization of cannabis use-related harms, and improving adolescent and parent engagement in treatment., Competing Interests: Declaration of competing interest All authors report no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: There are limited data on duration of aromatase inhibitor (AI) and cardiovascular disease (CVD) risk in breast cancer (BC) survivors. We examined risk of CVD and mortality associated with duration of AI use in postmenopausal women with early-stage hormone receptor-positive BC., Methods: Postmenopausal women diagnosed with hormone receptor-positive BC (n = 5,853) who used an AI were included. Cause-specific hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between AI use duration (short-term: >0 and <2 years; intermediate-term: ≥2 and <5 years; long-term: ≥5 years) and CVD and mortality outcomes. The landmark method was used to avoid immortal time bias; the selected landmark was 6 years after BC diagnosis., Results: Anastrozole was the AI predominantly prescribed (95.4%). Over a median follow-up of 3 years for women who survived 6 years after BC diagnosis, a lower risk of stroke was observed in intermediate-term AI users (HR = 0.60, 95% CI: 0.37-0.96) and long-term AI users (HR = 0.51, 95% CI: 0.30-0.85), than in short-term AI users. The longer duration of AI use was also associated with lower risk of all-cause mortality and non-CVD-related mortality. In addition, long-term AI users were at 37% lower risk of CVD-related mortality than short-term AI users. No significant differences were observed in risks of major adverse cardiovascular events, ischemic heart disease, and heart failure across the three groups., Conclusion: Among postmenopausal women with early-stage hormone receptor-positive BC who survived to 6 years after BC diagnosis, longer duration of AI use was not associated with elevated CVD risk., (© The Author(s) 2025. Published by Oxford University Press.)

Background: Patients with cancer who report social needs have worse quality of life, lower healthcare access, and suboptimal health outcomes. However, screening for social needs does not happen systematically and successful screening tools, strategies, and workflows have seldom been described. The downstream effects of screening including resource navigation have also not been well characterized. This objective of this narrative review was to fill these gaps., Methods: Two investigators searched Pubmed and Embase for studies that implemented a patient-facing social screening tool among patients with cancer between 2008-2023 using search terms including "social screening," "social needs," and "cancer.", Results: We identified 19 articles that met study inclusion criteria. The most common tool used was the validated Health Leads Social Toolkit. Most often, screening tools were administered electronically, sent directly to patients, and captured needs at a single time point during a patient's diagnosis. Screening response rates ranged between 10-60%. Less than half of the studies described downstream resource navigation for patients who screened positive for social needs Only one study evaluated the impact of screening on clinical outcomes and quality of life. Screening for patients who do not speak English or who belong to historically racial, ethnic, and gender minority groups was limited., Conclusions: Screening for social needs has been shown to be feasible across delivery systems with numerous validated tools available. However, gaps remain in generalizability to diverse patient populations. Future work must identify how screening workflows can be successfully incorporated into routine clinical workflows., (© The Author(s) 2025. Published by Oxford University Press.)

Objective: Rapid patient referral to epilepsy centers may facilitate subsequent disease-modifying surgical and non-surgical treatments. Delays of 15-18 years have been reported from time of epilepsy diagnosis to surgical evaluation in some settings, though patterns for timely guideline-concordant referrals within integrated care models are not well known and could inform strategies for optimizing guideline-concordant access., Methods: We performed a retrospective cohort study of 1088 patients undergoing epilepsy center evaluation from January 1, 2008 through June 30, 2023 in a Northern California integrated healthcare delivery system (IDS) with a Level 4 Epilepsy Center. Using electronic health record (EHR) data, we summarized time from diagnosis and other major care time points until first visit at the epilepsy center. A multivariate linear model was used to evaluate the relationship of select demographic, socioeconomic, and clinical characteristics with the time to first epilepsy center visit., Results: The mean times to epilepsy center visit from first prescription of an anti-seizure medication (ASM), diagnosis of epilepsy or seizures, and first visit with a general neurologist, were 3.9 years (SD = 4.5), 3.2 years (SD = 3.2) and 2.7 years (SD = 3.2), respectively, for the full cohort of patients prescribed any number of ASMs. Comparable time frames were seen for patients prescribed two or more ASMs at the time of first visit. Significantly longer time to epilepsy center visit was seen in patients with multiple ASMs prescribed, a concordant diagnosis of developmental delay, and those age 40 and above. Longer times to epilepsy center visit were not seen among patients with psychiatric comorbidities, public health insurance coverage, and among patients in traditionally underserved groups., Conclusions: Patients evaluated at an epilepsy clinic within an IDS system did so within less than four years of diagnosis and initial treatment, with few disparities by demographics or comorbidities. Future studies can identify specific health system features that are key to shorter time frames to test transferable strategies to reduce time to epilepsy centers., 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 © 2025 Elsevier Inc. All rights reserved.)

Background: Multiple studies have demonstrated associations between psychiatric conditions and Parkinson's disease (PD) development; fewer have examined psychotic-spectrum disorders and PD development., Objective: The objective was to assess the prevalence of psychotic-spectrum disorders with and without depression and anxiety preceding a PD diagnosis., Methods: In this retrospective, case-control study of adults > 60 years of age, cases were identified by PD diagnosis and controls were identified in a 3:1 ratio by ambulatory encounter from 2015 to 2020. Psychiatric conditions were identified by diagnosis code up to 5 years prior to the index date. Conditional logistic regression was conducted to assess associations., Results: Among 13,998 patients, the odds of PD were 76% (95% confidence interval = 1.39-2.22) higher among those with psychotic-spectrum diagnoses. An additional anxiety diagnosis was associated with 166% (95% confidence interval = 1.35-5.25) higher odds of PD., Conclusions: Awareness of psychiatric conditions, including psychotic-spectrum disorders with comorbid anxiety, can stratify individuals at higher risk of developing PD.

Gestational diabetes mellitus (GDM), a transient form of diabetes that resolves postpartum, is a major risk factor for type 2 diabetes (T2D) in women. While the progression from GDM to T2D is not fully understood, it involves both genetic and environmental components. By integrating clinical, metabolomic, and genome-wide association study (GWAS) data, we identified associations between decreased sphingolipid biosynthesis and future T2D, in part through the rs267738 allele of the CERS2 gene in Hispanic women shortly after a GDM pregnancy. To understand the impact of the CERS2 gene and risk allele on glucose regulation, we examined whole-body Cers2 knockout and rs267738 knock-in mice. Both models exhibited glucose intolerance and impaired insulin secretion in vivo. Islets isolated from these models also demonstrated reduced β cell function, as shown by decreased insulin secretion ex vivo. Overall, reduced circulating sphingolipids may indicate a high risk of GDM-to-T2D progression and reflect deficits in CERS2 activity that negatively affect glucose homeostasis and β cell function.

Competing Interests: Declarations. Conflict of interest: Dr. Mario Enrico Canonico receives salary support from CPC Clinical Research. Dr. Andrew P. Ambrosy has received relevant research support through grants to his institution from the National Heart, Lung, and Blood Institute (K23HL150159), the American Heart Association (2nd Century Early Faculty Independence Award), The Permanente Medical Group, Northern California Community Benefits Programs, Garfield Memorial Fund, Abbott Laboratories, Amarin Pharma, Inc., Bayer, Cordio Medical, Edwards Lifesciences LLC, Esperion Therapeutics, Inc., Merck, and Novartis. Dr. Marc D. Samsky has no disclosures to report. The authors are members of Heart Failure Reviews editorial board.

Background: Alcohol use is measured in diverse ways across settings. Harmonization of measures is necessary to assess effects of alcohol use in multi-cohort collaborations, such as studies of people with HIV (PWH)., Methods: Data were combined from 14 HIV cohort studies (nine European, five North American) participating in the Antiretroviral Therapy Cohort Collaboration. We analyzed data on adult PWH with measured alcohol use at any time from 6 months before starting antiretroviral therapy. Five cohorts measured alcohol use with AUDIT-C and others used cohort-specific measures. We harmonized alcohol use as grams/day, calculated using country-level definitions of a standard drink. For Alcohol Use Disorders Identification Test (AUDIT-C), we used Items 1 (frequency) and 2 (number of drinks on a typical day). Where alcohol was measured in categories, we used the mid-point to calculate grams/day. We used multivariable Cox models to estimate associations of alcohol use with mortality., Results: Alcohol use data were available for 83,424 PWH, 22,447 (27%) had AUDIT-C measures and 60,977 (73%) recorded the number of drinks/units per week/day. Of the sample, 19,150 (23%) were female, 54,006 (65%) had White ethnicity, and median age was 42 years. Median alcohol use was 0.3 g/day (interquartile range [IQR] 0-4.8) and 0 g/day (IQR 0-20) for those with and without AUDIT-C. There was a J-shaped relationship between grams/day and mortality, with higher mortality for PWH reporting no alcohol use (adjusted hazard ratio [aHR] 1.46; 95% CI: 1.23-1.72) and heavier (>61.0 g/day) alcohol use (aHR 1.92; 1.41-2.59) compared with 0.1-5.5 g/day among those with AUDIT-C measures. Associations were similar among those with non-AUDIT-C measures., Conclusions: Grams/day is a useful metric to harmonize diverse measures of alcohol use. Magnitudes of associations of alcohol use with mortality may differ by setting and measurement method. Higher mortality among those with heavier alcohol use strengthens the case for interventions to reduce drinking., (© 2025 The Author(s). Alcohol, Clinical and Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcohol.)

Prevalence of autism diagnosis has historically differed by demographic factors. Using data from 8224 participants drawn from the Environmental influences on Child Health Outcomes (ECHO) Program, we examined relationships between demographic factors and parent-reported autism-related traits as captured by the Social Responsiveness Scale (SRS; T score > 65) and compared these to relations with parent-reported clinician diagnosis of ASD, in generalized linear mixed effects regression analyses. Results suggested lower odds of autism diagnosis, but not of SRS T > 65, for non-Hispanic Black children (adjusted odds ratio [OR] = 0.76, 95% CI 0.55, 1.06) relative to non-Hispanic White children. Higher maternal education was associated with reduced odds of both outcomes (OR = 0.73, 95% CI 0.51, 1.05 for ASD autism diagnosis and 0.4, 95% CI 0.29, 0.55 for SRS score). In addition, results suggested a lower likelihood of autism diagnosis but a higher likelihood of an SRS score > 65 in Black girls. Findings suggest lower diagnostic recognition of autism in non-Hispanic Black children, despite a similar degree of SRS-assessed autism-related traits falling in the clinically elevated range. Further work is needed to address this disparity., (© 2025 International Society for Autism Research and Wiley Periodicals LLC.)

Epidemiologic studies frequently use risk ratios to quantify associations between exposures and binary outcomes. When the data are physically stored at the sites of multiple data partners, it can be challenging to perform individual-level analysis if data cannot be pooled centrally due to privacy constraints. Existing methods either require multiple file transfers between each data partner and an analysis center (eg, distributed regression) or only provide approximate estimation of the risk ratio (eg, meta-analysis). Here we develop a practical method that requires a single transfer of 8 summary-level quantities from each data partner. Our approach leverages an existing risk-set method and software originally developed for Cox regression. Sharing only summary-level information, the proposed method provides risk ratio estimates and 95% CIs identical to those that would be provided-if individual-level data were pooled-by the modified Poisson regression. We justify the method theoretically, confirm its performance using simulated data, and implement it in a distributed analysis of COVID-19 data from the US Food and Drug Administration's Sentinel System. This article is part of a Special Collection on Pharmacoepidemiology., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To evaluate race and ethnicity differences in rates of cesarean delivery on maternal request (CDMR) in nulliparous, term, singleton, vertex presentation (NTSV) cesarean deliveries., Methods: We conducted a retrospective cohort study of NTSV cesarean deliveries within our institution from 2016 to 2020. The primary outcome was CDMR and the primary predictor was maternal race and ethnicity. Multivariable logistic regression models were used to evaluate associations between race and ethnicity, CDMR, and various maternal and perinatal factors., Results: Among 12,351 NTSV cesarean deliveries, 594 (4.81%) underwent CDMR; 4605 (37.28%) identified as non-Hispanic White, 3731 (30.21%) as Asian/Hawaiian/Pacific Islander, 2840 (22.99%) as Hispanic, 785 (6.36%) as Black, and 390 (3.16%) as multiple races/American Indian/Alaskan Native. Adjusted models showed increased odds of CDMR among non-Hispanic White people. Multiple races/American Indian/Alaskan Native people had the lowest odds of CDMR compared to non-Hispanic White people (adjusted OR [aOR] = 0.48, 95% CI 0.26-0.82), followed by Asian/Hawaiian/Pacific Islander (aOR = 0.58, 95% CI 0.47-0.72), Black (aOR = 0.61, 95% CI 0.40-0.89), and Hispanic (aOR = 0.70, 95% CI 0.55-0.88) people., Conclusion: Non-Hispanic White people undergo CDMR more frequently compared to Asian/Hawaiian/Pacific Islander, Black, and Hispanic people. Our findings are notable in light of the growing body of research demonstrating that White people have the lowest odds of cesarean delivery overall., Significance: Profound racial disparities in maternal obstetric outcomes exist in the United States. It is well established that non-Hispanic Black people have disproportionately higher cesarean birth rates and higher rates of birth complications, including maternal death. Racial and ethnic differences in rates of primary elective cesarean delivery, or cesarean delivery on maternal request, are not well understood. This research shows that non-Hispanic White people have more cesarean deliveries on maternal request than other racial and ethnic groups among low-risk nulliparous patients., Competing Interests: Declarations. Ethics Approval and Consent to Participate: This study was approved with a waiver of consent by our institution’s Institutional Review Board. This is an observational study. The Kaiser Permanente IRB has confirmed that no ethical approval is required. Conflict of Interest: The authors declare no competing interests., (© 2025. W. Montague Cobb-NMA Health Institute.)

Introduction: Colorectal cancer (CRC) screening relies primarily on colonoscopy and fecal immunochemical testing (FIT). Aligning utilization of these options with individual CRC risk may optimize benefit with lower risks, individual burden, and societal costs. We studied the effect of communicating personalized CRC risk and corresponding screening recommendations on risk-appropriate screening uptake in an organized screening setting., Methods: Randomized controlled trial among residents aged 50-69 years not yet invited for screening in Vaud, Switzerland. The intervention was a mailed brochure communicating individual 15-year CRC risk and screening recommendation. The control group received a usual brochure comparing FIT and colonoscopy. The primary outcome was self-reported risk-appropriate screening (FIT if <3% risk, FIT or colonoscopy if ≥3% and <6%, colonoscopy if ≥6%) at 6 months. A secondary outcome was overall screening uptake., Results: Of 5396 invitations, 1059 people responded (19%), of whom 258 were randomized to intervention and 257 to control materials (average 15-year risk 1.4% (SD=0.5), age 52.2 years (SD=2.2), 51% women). Risk-appropriate screening completion was 37% in the intervention group and 23% in the control group (absolute difference 14%, 95%CI 6%-22%). Overall screening uptake was 50% in the intervention and 49% in the control group (absolute difference 1%, 95CI -7%-10%)., Conclusions: In a population not known to be at elevated CRC risk, brochures providing personalized CRC risk and screening recommendations improved risk-appropriate screening without impacting overall screening uptake. This approach could be helpful for aligning screening methods, risks, and benefits with cancer risk and resource allocation., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Purpose: Our goals were to: 1) examine the occurrence of behavioral and emotional symptoms in children on the autism spectrum in a large national sample, stratifying by sex, and 2) evaluate whether children with increased autism-related social communication deficits also experience more behavioral and emotional problems., Methods:  Participants (n = 7,998) were from 37 cohorts from the Environmental influences on Child Health Outcomes (ECHO) Program. Cross-sectional information on demographic factors, parent-report of an ASD diagnosis by clinician, Social Responsiveness Scale (SRS) scores, and Child Behavior Checklist (CBCL) scores were obtained for children aged 2.5-18 years by surveys. We examined mean differences in CBCL Total Problems and DSM-oriented subscale scores by autism diagnosis and by child sex. Analyses using logistic regression were conducted to examine whether autism was associated with higher CBCL scores. We further examined if these relationships differed by child age category (< 6 years, 6-11 years, 12 + years). The relationships between SRS score and CBCL total and subscale scores were examined using quantile regression models, with analyses adjusted for child sex and age., Results:  In ECHO, 553 youth were reported by a parent to have a clinician diagnosis of autism spectrum disorder (ASD) (432 [78%] boys and 121 [22%] girls). Youth on the spectrum had higher mean CBCL raw scores on Total Problems and all DSM-oriented subscales compared to those not on the spectrum (all p < 0.0001). Analyses adjusted for sex and stratified by age group indicated that higher odds of autism diagnosis were associated with total, depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD) scales in the top 30% of the CBCL score distribution. Autistic girls were more likely to have parent-reported depression and anxiety compared to autistic boys. In quantile regression analyses, we observed evidence of stronger associations between SRS and CBCL for those in higher quantiles of CBCL total problems scale score (beta representing 1-unit change in SRS associated with 1-unit increase in CBCL total problems scale score), among children in the 70-90th percentile (β = 1.60, p < 0.01), or top 10th percentile (β = 2.43, p < 0.01) of the CBCL total problems scale score distribution. Similar findings were seen for the DSM-oriented depression, anxiety, and ADHD subscales., Conclusion:  Results from this large national sample suggest increased behavioral and emotional problems among autistic children compared to non-autistic children throughout early life. Among children on the spectrum this may warrant increased monitoring for co-occurring behavioral and emotional problems., Competing Interests: Declarations. Conflict of interests: The following authors have nothing to declare (HEV, CAC, JBS, RMJ, DPK, TMB, YSK, LDL, ALD)., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: Moderate-to-vigorous-intensity physical activity (MVPA), cardiorespiratory fitness (CRF), and coronary artery calcification (CAC) are associated with cardiovascular disease (CVD) risk. While a U-shaped relationship between CRF or MVPA and CAC has been reported, the presence of CAC among highly fit individuals might be benign. We examined interactive associations of CRF or MVPA and CAC with outcomes and evaluated the relationship of CRF and MVPA to CAC incidence., Methods and Results: CARDIA participants with CAC assessed in 2005-06 were included (n = 3,141, mean age 45). MVPA was assessed by self-report and accelerometer. CRF was estimated with a maximal graded exercise test. Adjudicated CVD events and mortality data were obtained through 2019. CAC was reassessed in 2010-11. Cox models were constructed to assess hazard ratios (HRs) for CVD, coronary heart disease (CHD), and mortality in groups defined by CAC presence/absence and lower/higher CRF or MVPA levels. Logistic models were constructed to assess associations with CAC incidence. Adjustment was made for sociodemographic and CVD risk factors. Relative to participants with no CAC and higher CRF, the adjusted HRs for CVD were 4.68 for CAC and higher CRF, 2.22 for no CAC and lower CRF, and 3.72 for CAC and lower CRF. For CHD, the respective HRs were 9.98, 2.28, and 5.52. For mortality, the HRs were 1.15, 1.58, and 3.14, respectively. Similar findings were observed when MVPA measured either by self-report or accelerometer was substituted for CRF. A robust inverse association of CRF and accelerometer-derived MVPA with CAC incidence was partly accounted for by adjusting for CVD risk factors., Conclusion: In middle-aged adults, CRF and MVPA demonstrated an inverse association with CAC incidence, but did not mitigate the increased cardiovascular risk associated with CAC, indicating that CAC is not benign in individuals with higher CRF or MVPA levels., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Importance: Doxycycline postexposure prophylaxis (doxyPEP) has been shown to decrease the incidence of bacterial sexually transmitted infections (STIs) among people assigned male sex at birth in clinical trials, but data from clinical practice are limited., Objective: To describe early uptake of doxyPEP and evaluate changes in STI incidence following doxyPEP initiation., Design, Setting, and Participants: This retrospective cohort study of adults (aged ≥18 years) dispensed HIV preexposure prophylaxis (PrEP) at Kaiser Permanente Northern California during November 1, 2022, to December 31, 2023, examined electronic health record data to compare HIV PrEP users dispensed and not dispensed doxyPEP and rates of bacterial STIs before and after starting doxyPEP. Individuals were followed up from their first recorded STI test on or after November 1, 2020, until December 31, 2023, or discontinuation of health plan membership., Exposure: Pharmacy dispensing data were used to define doxyPEP recipients., Main Outcomes and Measures: Demographic and clinical characteristics were compared between individuals dispensed and not dispensed doxyPEP. Primary outcomes were incident chlamydia, gonorrhea, or infectious syphilis measured as quarterly STI positivity (proportion of individuals testing positive at least once per quarter). Among doxyPEP recipients, rate ratios (RRs) compared mean quarterly STI positivity from 24 months before to 12 months after starting doxyPEP. In an exploratory analysis, STI trends were evaluated for the full cohort, stratified by receipt of doxyPEP., Results: Among 11 551 HIV PrEP users (mean [SD] age, 39.9 [12.1] years; 95.1% male), 2253 (19.5%) were dispensed doxyPEP, of whom 2228 (98.9%) were male and 1096 (48.6%) had an STI in the year before starting doxyPEP. Compared with individuals not dispensed doxyPEP, doxyPEP recipients were older (mean [SD] age, 40.4 [10.8] vs 39.8 [12.4] years; P = .04) and had used HIV PrEP longer (mean [SD], 4.2 [2.8] vs 3.4 [2.6] years; P < .001), and a higher proportion were commercially insured (2091 [92.8%] vs 8270 [88.9%]; P < .001). Among doxyPEP recipients, quarterly chlamydia positivity decreased from 9.6% (95% CI, 9.0%-10.3%) before starting doxyPEP to 2.0% (95% CI, 1.5%-2.6%) after starting doxyPEP (RR, 0.21; 95% CI, 0.16-0.27; P < .001), with significant declines for each anatomic site of infection. Quarterly gonorrhea positivity decreased from 10.2% (95% CI, 9.6%-10.9%) before starting doxyPEP to 9.0% (95% CI, 8.0%-10.1%) after starting doxyPEP (RR, 0.88; 95% CI, 0.77-1.00; P = .048); site-specific declines were significant for rectal (RR, 0.81; 95% CI, 0.67-0.97; P = .02) and urethral (RR, 0.56; 95% CI, 0.40-0.79; P = .001) gonorrhea, but not pharyngeal gonorrhea. Quarterly syphilis positivity decreased from 1.7% (95% CI, 1.4%-1.9%) before starting doxyPEP to 0.3% (95% CI, 0.2%-0.6%) after starting doxyPEP (RR, 0.20; 95% CI, 0.11-0.37; P < .001). Positivity for STIs remained stable in individuals not dispensed doxyPEP., Conclusions and Relevance: This study found that receipt of doxyPEP was associated with substantial declines in chlamydia and syphilis incidence and modest declines in urethral and rectal gonorrhea incidence among individuals using HIV PrEP. These findings suggest that doxyPEP may offer substantial benefits for reducing population-level STI transmission with broader implementation.

Background: Breast cancer survivors experience higher rates of cardiovascular disease (CVD) than women without breast cancer, due in part to cardiotoxic cancer treatments and shared lifestyle risk factors. Physical activity is associated with lower mortality risk in breast cancer survivors, but associations with CVD have not been examined in detail., Methods: The Pathways Study is a prospective cohort study of 4504 women diagnosed with invasive breast cancer between 2005 and 2013. At enrollment, women self-reported their physical activities during the previous 6 months, which were dichotomized as meeting the Centers for Disease Control and Prevention's Physical Activity Guidelines for Americans (≥150 minutes of moderate-intensity or ≥75 minutes of vigorous-intensity activity per week) vs not. Incident CVD events (heart failure, cardiomyopathy, cardiac arrest, ischemic heart disease, stroke) occurring between enrollment and December 2021 were identified from electronic health records. Covariate-adjusted, competing-risks Cox regression models estimated associations between meeting physical activity guidelines and CVD risk., Results: Compared with women who did not meet physical activity guidelines at their diagnosis, those who did had a 25% lower risk of CVD (HR = 0.75, 95% CI = 0.60 to 0.94). Among the individual CVD outcomes, meeting physical activity guidelines was protective against incident cardiomyopathy (hazard ratio [HR] = 0.54, 95% CI = 0.31 to 0.95), heart failure (HR = 0.66, 95% CI = 0.50 to 0.87), and cardiac arrest (HR = 0.68, 95% CI = 0.49 to 0.99)., Conclusions: Meeting physical activity guidelines at breast cancer diagnosis was associated with lower risk of CVD after diagnosis. Studies investigating changes in physical activity after a breast cancer diagnosis and CVD risk are warranted., (© The Author(s) 2024. Published by Oxford University Press.)

Importance: Chronic hypertension and preeclampsia are leading risk enhancers for maternal-neonatal morbidity and mortality. Severe maternal morbidity (SMM) indicators include heart, kidney, and liver disease, but studies have not excluded patients with preexisting diseases that define SMM. Thus, SMM risks for uncomplicated chronic hypertension specific to preeclampsia remain unclear., Objective: To determine SMM rates and estimate relative risks associated with hypertensive disorders of pregnancy among patients with and without chronic hypertension unencumbered by preexisting vascular or end organ diseases., Design, Setting, and Participants: This retrospective cohort study used longitudinal health data from electronic health records from patients within a community-based, integrated health care system in northern California. The study cohort selected 263 518 pregnant patients without pregestational heart, kidney, or liver disease entering prenatal care at 14 weeks' gestation or earlier and delivering a singleton stillbirth or live birth in 2009 to 2019. The data were analyzed between February 2022 and March 2024., Exposures: Five joint subgroups combining chronic hypertension status and the hypertensive disorders developing during pregnancy, defined as follows: (1) chronic hypertension with superimposed preeclampsia, (2) chronic hypertension and no preeclampsia, (3) no chronic hypertension with preeclampsia, (4) gestational hypertension, and (5) no chronic hypertension and no preeclampsia or gestational hypertension (reference group)., Main Outcomes and Measures: The main outcome was SMM rates at delivery hospitalization (cases per 10 000 births) using the Centers for Disease Control and Prevention criteria (≥1 of 21 indicators to define SMM) obtained from electronic health records. Modified Poisson regression models estimated crude and adjusted relative risks (aRRs) and 95% CIs of SMM associated with the chronic hypertension and developing hypertensive disorders of pregnancy groups vs the reference group (no chronic hypertension and no preeclampsia or gestational hypertension) adjusted for clinical, sociodemographic, social, and behavioral covariates., Results: The analysis included a total of 263 518 pregnant patients (mean [SD] age at delivery, 31.0 [5.3] years), including 249 892 patients without chronic hypertension (4.7% developed preeclampsia) and 13 626 patients with chronic hypertension (31.5% developed superimposed preeclampsia). The highest SMM rates occurred in the no chronic hypertension with preeclampsia (934.3 [95% CI, 882.3-988.3] cases per 10 000 births) and the chronic hypertension with superimposed preeclampsia (898.3 [95% CI, 814.5-987.8] cases per 10,000 births) groups. Lower SMM rates occurred in the chronic hypertension and no preeclampsia (195.1 [95% CI, 168.0-225.2] cases per 10,000 births), gestational hypertension (312.7 [95% CI, 281.6-346.1] cases per 10,000 births), and no chronic hypertension and no preeclampsia or gestational hypertension (165.8 [95% CI, 160.6-171.2] cases per 10,000 births) groups (P < .001). Compared with the no chronic hypertension and no preeclampsia or gestational hypertension group, risks of SMM were significantly higher for the chronic hypertension with superimposed preeclampsia group (aRR, 4.97 [95% CI, 4.46-5.54]), no chronic hypertension with preeclampsia group (aRR, 5.12 [95% CI, 4.79-5.48]), chronic hypertension and no preeclampsia group (aRR, 1.17 [95% CI, 1.003-1.36]; P = .046), and the gestational hypertension group (aRR, 1.78 [95% CI 1.60-1.99])., Conclusions and Relevance: This cohort study found that the highest SMM rates at delivery hospitalization occurred for preeclampsia superimposed on chronic hypertension and preeclampsia without chronic hypertension, while gestational hypertension had intermediate rates of SMM. The patients with chronic hypertension who did not develop preeclampsia had SMM rates that were nearly the same as the lowest-risk patients without chronic hypertension who did not develop preeclampsia or gestational hypertension. These findings provide evidence that prevention of preeclampsia among patients with uncomplicated chronic hypertension is paramount to mitigating maternal morbidity.

Importance: Sugar-sweetened beverage (SSB) excise taxes are popular policy interventions aimed at decreasing SSB purchasing and consumption to improve cardiometabolic health and generate revenue for public health initiatives. There is limited evidence that these taxes in the US are associated with weight-related outcomes in adults, a primary contributor to cardiometabolic health., Objective: To determine the association between SSB excise taxes and adult body mass index (BMI) and proportion of adults with overweight or obesity among California cities and assess whether associations vary by demographic characteristics., Design, Setting, and Participants: This cohort study compared California cities with SSB taxes (Albany, Berkeley, Oakland, and San Francisco) and demographically matched cities without SSB excise taxes from 6 years before the tax and 4 to 6 years after the tax from January 2009 through December 2020 using electronic health record data. Participants were Kaiser Permanente (KP) members aged 20 to 65 years at cohort entry with at least 1 pretax and 1 posttax BMI measurement. Data were analyzed from January 2021 to May 2023., Exposure: Implementation of city-level SSB excise taxes., Main Outcomes and Measures: Mean BMI and proportion of adults with overweight or obesity. Analysis used the differences-in-differences (DID) method., Results: The cohort had a total of 1 044 272 members (178 931 participants in 4 cities with excise taxes; mean [SD] age, 39.7 [11.2] years; 99 501 [55.6%] female; 865 343 participants in 40 control cities without excise taxes; mean [SD] age, 39.9 [11.6] years; 480 155 [55.5%] female). DID estimates for mean BMI showed a modest decrease among adults aged 20 to 39 years (20-25 years: -0.30; 95% CI, -0.51 to -0.08; 26-39 years: -0.19; 95% CI, -0.37 to -0.20), female participants (-0.19; 95% CI, -0.26 to -0.11), and White participants (-0.19; 95% CI, -0.35 to -0.04) living in cities with SSB excise taxes. There was a statistically significant reduction in mean BMI in Berkeley (-0.16; 95% CI, -0.27 to -0.04). There were no overall differences in BMI or proportion with overweight or obesity., Conclusions and Relevance: In this cohort study, SSB excise taxes were associated with reduced mean BMI among adults in demographic subgroups, including in young adults who consumed the most SSBs, and in Berkeley. Future research should examine the mechanisms of these associations to inform how SSB taxes could be more equitable for weight-related outcomes.

Importance: Food insecurity is a growing public health concern, but its association with perinatal complications remains unclear., Objective: To examine whether food insecurity in pregnancy was associated with the risk of perinatal complications and determine whether these potential associations differed by receipt of food assistance., Design, Setting, and Participants: This cohort study used data from a pregnancy survey conducted between June 22, 2020, and September 9, 2022, at Kaiser Permanente Northern California, an integrated health care system serving a diverse population of 4.6 million. Participants included individuals who delivered singletons. Data were analyzed from December 2023 to June 2024., Exposure: Food insecurity in pregnancy assessed using the validated 2-item Hunger Vital Sign screener., Main Outcomes and Measures: Maternal (gestational diabetes, gestational hypertension, preeclampsia, cesarean delivery) and neonatal (preterm birth, neonatal intensive care unit [NICU] admission, small-for-gestational age [SGA], and large-for-gestational age [LGA]) complications extracted from the electronic health records, and a composite adverse perinatal outcome (APO) of maternal and neonatal complications. Modified Poisson regression models were adjusted for covariates and stratified by receipt of food assistance in pregnancy., Results: Among 19 338 individuals, 2707 (14.0%) reported food insecurity in pregnancy. Individuals with food insecurity in pregnancy had a higher risk of gestational diabetes (adjusted relative risk [aRR], 1.13 [95% CI, 1.01-1.29]), preeclampsia (aRR, 1.28 [95% CI, 1.11-1.49]), preterm birth (aRR, 1.19 [95% CI, 1.02-1.38]), NICU admission (aRR, 1.23 [95% CI, 1.07-1.42]), and APO (aRR, 1.07 [95% CI, 1.02-1.13]) compared with individuals without food insecurity. Among 1471 individuals (7.6%) who received food assistance in pregnancy, associations of food insecurity in pregnancy with perinatal complications were attenuated to the null, except for preeclampsia (aRR, 1.64 [95% CI, 1.06-2.53]). On the contrary, the associations persisted among individuals who did not receive food assistance: gestational diabetes (aRR, 1.20 [95% CI, 1.04-1.37]), preeclampsia (aRR, 1.24 [95% CI, 1.06-1.46]), preterm birth (aRR, 1.23 [95% CI, 1.05-1.46]), NICU admission (aRR, 1.31 [95% CI, 1.12-1.52]), and APO (aRR, 1.12 [95% CI, 1.06-1.18])., Conclusions and Relevance: In this cohort study, food insecurity in pregnancy was associated with a higher risk of perinatal complications, and these associations were overall attenuated to the null among individuals who received food assistance in pregnancy. These findings support clinical guidelines of screening for food insecurity in pregnancy and provide evidence to expand food assistance programs that may help improve maternal and neonatal outcomes.

Importance: Adolescent and young adult (AYA) patients with advanced cancer often die in hospital settings. Data characterizing the degree to which this pattern of care is concordant with patient goals are sparse., Objective: To evaluate the extent of concordance between the preferred and actual location of death among AYA patients with cancer., Design, Setting, and Participants: This multicenter retrospective cohort study included AYA patients (aged 12-39 years) with cancer who died between January 1, 2003, and December 31, 2019, after receiving care at Dana-Farber Cancer Institute and Kaiser Permanente Northern California or who died between January 1, 2009, and December 31, 2019, after receiving care at Kaiser Permanente Southern California. Data were analyzed from January 12 to July 1, 2024., Exposure: Death due to cancer., Main Outcomes and Measures: Medical record documentation of discussions about preferred location of death, actual location of death, and concordance between preferred and actual location of death., Results: The analytic population included 1929 AYA decedents, of whom 1049 (54.4%) were female; 227 (11.8%), Asian; 157 (8.1%), Black; 514 (26.6%), Hispanic; and 1184 (61.4%), White. Median age at death was 32 (IQR, 25-37) years. A total of 1226 AYA patients (63.6%) had a documented discussion about preferred location of death. Among those with a documented discussion, 594 (48.5%) did not have a documented preference, 402 (32.8%) wanted to die at home, 177 (14.4%) preferred a hospital death, and 48 (3.9%) desired inpatient hospice. Eight hundred and thirty patients (43.0%) died in acute care settings (256 [13.3%] intensive care unit [ICU], 548 [28.4%] hospital [non-ICU], and 26 [1.3%] emergency department), while 643 (33.3%) died at home and 47 (2.4%) in an inpatient hospice. Among the 528 patients with both a documented preferred death location of home, hospital, or inpatient hospice and documented death in one of these locations, the concordance between preferred and actual location of death was 401 (75.9%). One hundred and sixty-four of 172 patients (95.3%) who preferred a hospital death died there; 224 of 317 (70.7%) who preferred a home death died at home, and 13 of 39 (33.3%) who desired to die in inpatient hospice did so., Conclusions and Relevance: Although many AYA patients with cancer died in their preferred location, over one-quarter of those who desired to die at home did not realize this goal. These findings highlight the need for effective solutions to enable goal-concordant care for this population.

Importance: Despite guideline recommendations to use low-molecular-weight heparins (LMWHs) or direct oral anticoagulants in the treatment of most patients with acute pulmonary embolism (PE), US-based studies have found increasing use of unfractionated heparin (UFH) in hospitalized patients., Objective: To identify barriers and facilitators of guideline-concordant anticoagulation in patients hospitalized with acute PE., Design, Setting, and Participants: This qualitative study conducted semistructured interviews from February 1 to June 3, 2024, that were recorded, transcribed, and analyzed in an iterative process using reflexive thematic analysis. Interview participants were physicians in emergency medicine, hospital medicine (hospitalist), interventional cardiology, and interventional radiology. Participants were recruited using maximum variation sampling targeting UFH-dominant vs LMWH-dominant approaches in hospitalized patients with acute PE. We triangulated results with a group of interventional cardiologists and radiologists (interventionalists)., Main Outcomes and Measures: Common themes and factors associated with anticoagulant selection for hospitalized patients with acute PE. Reflexive thematic analysis was used to identify these themes and factors., Results: Of the 46 interviewees (median [IQR] age, 43 [36-50] years; 33 who identified as men [71.7%]), 25 (54.3%) were emergency physicians, 17 (37.0%) were hospitalists, and 4 (8.7%) were interventionalists. Each interview lasted a median (IQR) of 29 (25-32) minutes. Prominent themes associated with anticoagulant selection included agnosticism regarding choice of anticoagulant, the inertia of learned practice, and therapeutic momentum after anticoagulation initiation. Institutional culture and support were factors associated with choice of the dominant anticoagulation strategy. Additionally, factors associated with UFH use were fear of decompensation and misperceptions regarding the pharmacology of anticoagulants and catheter-directed treatments., Conclusions and Relevance: In this qualitative study, physicians across a spectrum of specialties and geographical settings reported common barriers and facilitators to the use of guideline-concordant anticoagulation in patients hospitalized with acute PE, particularly agnosticism regarding choice of anticoagulant, inertia of learned practice, therapeutic momentum after anticoagulation initiation, and institutional culture and support. Future implementation efforts may consider targeting these domains.

Aims: Gestational diabetes mellitus (GDM) poses a significant risk for developing type 2 diabetes mellitus (T2D) and exhibits heterogeneity. However, understanding the link between different types of post-GDM individuals without diabetes and their progression to T2D is crucial to advance personalised medicine approaches., Materials and Methods: We employed a discovery-based unsupervised machine learning clustering method to generate clustering models for analysing metabolomics, clinical, and biochemical datasets. For this analysis, we selected 225 women who later developed T2D during the 12-year follow-up period from the cohort of 1010 women who returned to a non-diabetic state at 6-9 weeks (study baseline) after a GDM pregnancy based on 2-h 75 g research OGTTs. The optimal model was selected by assessing Bayesian Information Criterion values, class separation performance, and the potential for clinically distinguishable clusters, accounting for participant prenatal and early postpartum characteristics., Results: The selected model comprises three clusters: pancreatic beta cell dysfunction (cluster-β: median HOMA-B 161.3 and median HOMA-IR 3.8), insulin-resistance (cluster-IR: median HOMA-B 630.5 and median HOMA-IR 16.8), and a mixed cluster (cluster-mixed: median HOMA-B 307.2 and median HOMA-IR 8.6). These clusters are distinguishable based on postpartum blood test parameters such as glucose tolerance, HOMA indices, and fasting lipid profiles including triglycerides, leptin, HDL-c, and adiponectin, as well as participant age and BMI. Metabolomic analysis identified unique molecular signatures for each cluster. However, the time to T2D onset was not statistically significant among the three clusters (p = 0.22)., Conclusion: This study enhances our understanding of the heterogeneity of early postpartum metabolic profiles that characterise the future onset of T2D diabetes in a diverse cohort of women with GDM, revealing insights into distinct mechanisms and personalised intervention strategies for the prevention of T2D., (© 2025 The Author(s). Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Background: A plant-based diet is associated with better survival among patients with nonmetastatic colorectal cancer (CRC), but its association in metastatic CRC is unknown., Methods: Using an National Cancer Institute-sponsored trial (CALGB/SWOG 80405), we included 1284 patients who completed validated food frequency questionnaires at the initiation of metastatic CRC treatment. We calculated 3 indices: overall plant-based diet index (PDI), which emphasized consumption of all plant foods while reducing animal food intake; healthful plant-based diet index (hPDI), which emphasized consumption of healthful plant foods such as whole grains, fruits, and vegetables; and unhealthful plant-based diet index (uPDI), which emphasized consumption of less healthful plant foods such as fruit juices, refined grains, and sugar-sweetened beverages. We estimated the associations of 3 indices (quintiles) with overall survival (OS) and progression-free survival (PFS) using multivariable Cox proportional hazards regression., Results: We observed 1100 deaths and 1204 progression events (median follow-up = 6.1 years). Compared with the lowest quintile, patients in the highest quintile of PDI had significantly better survival (hazard ratio [HR] for OS = 0.76 [0.62-0.94], Ptrend = .004; PFS = 0.81 [0.66-0.99], Ptrend = .09). Similar findings were observed for hPDI (HR for OS = 0.81 [0.65-1.01], Ptrend = .053; PFS = 0.80 [0.65-0.98], Ptrend = .04), whereas uPDI was not associated with worse survival (HR for OS = 1.16 [0.94-1.43], Ptrend = .21; PFS = 1.12 [0.92-1.36], Ptrend = .42)., Conclusions: Our study suggests that a plant-based diet, especially when rich in healthful plant foods, is associated with better survival among patients with metastatic CRC. The cause of survival benefits warrants further investigation., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Competing Interests: Disclosure: This study was approved as observational and data-only study by the Kaiser Foundation Research Institute’s institutional review board with a waiver of consent because of minimal risk with de-identified data.

Background: Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) remains underused. Acute heart failure (HF) hospitalization represents a critical opportunity for rapid initiation of evidence-based medications. However, data on GDMT use at discharge are mostly derived from national quality improvement registries., Objectives: This study aimed to describe contemporary GDMT use patterns across HF hospitalizations at community-based health systems., Methods: The authors identified HF hospitalizations from 2016 to 2022 in a U.S. database aggregating deidentified electronic health record data from more than 30 health systems. In-hospital and discharge rates of GDMT use were reported for eligible HFrEF patients. Factors associated with inpatient GDMT use and predischarge discontinuation were evaluated with the use of multivariable models., Results: A total of 20,387 HF hospitalizations among 13,729 HFrEF patients were identified. Renin-angiotensin system inhibitors, beta-blockers, and mineralocorticoid receptor antagonists were administered during 70%, 86%, and 37% of eligible hospitalizations, respectively. Angiotensin receptor-neprilysin inhibitors and sodium-glucose cotransporter 2 inhibitors were used in 17% and 8% of eligible hospitalizations, respectively. Discharge GDMT rates were low. Triple/quadruple therapy was administered in 26% of hospitalizations, falling to 14% on discharge. Predischarge GDMT discontinuations were associated with inpatient hypotension, hyperkalemia, and worsening renal function, but 43%-57% had no medical contraindications. In adjusted analyses, use of 3 or more GDMT classes was associated with fewer 90-day all-cause deaths and HF readmissions compared with less comprehensive GDMT., Conclusions: Inpatient GDMT use in a national analysis of HF hospitalizations was lower than reported in quality improvement registries. High discontinuation rates emphasize an unmet need for inpatient and postdischarge strategies to optimize GDMT use., Competing Interests: Funding Support and Author Disclosures Dr Zheng has consulted for Reprieve Cardiovascular. Dr Sandhu has received relevant research support from the National Heart Lung, Blood Institute (1K23HL151672) and the American Heart Association and has consulted for Reprieve Cardiovascular, Lexicon Pharmaceuticals, and Cleerly. Dr Bhatt has received relevant research support through grants to his institution from the National Heart, Lung, and Blood Institute, National Institute on Aging, Centers for Disease Control (CDC), and American College of Cardiology Foundation and has received consulting fees from Sanofi Pasteur and Novo Nordisk. Dr Collins receives research support from the National Institutes of Health, Patient-Centered Outcomes Research Institute, Department of Defense, and Beckman Coulter and consulting fees from Abbott, Redesign Health, and Reprieve Cardiovascular. Dr Flint receives relevant grant funding from Abbott and has consulted for Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson and Johnson, Medtronic, Merck, Novartis, and Pfizer. Dr Fudim receives research support from Reprieve and consults for Lexicon. Dr Greene has received research support from the Duke University Department of Medicine Chair’s Research Award, American Heart Association (number 929502), Amgen, AstraZeneca, Boehinger Ingelheim, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, Pfizer, and Sanofi; has served on advisory boards or as consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Lilly, Bristol Myers Squibb, Corteria, CSL Vifor, Cytokinetics, Lexicon, Merck, Roche Diagnostics, Sanofi, scPharmaceuticals, Tricog Health, and Urovant Pharmaceuticals; and has received speaker fees from Boehringer Ingelheim, Cytokinetics, Lexicon, and Roche Diagnostics. Dr Varshney has received consulting fees from Broadview Ventures. Dr Ambrosy has received relevant research support through grants to his institution from the National Heart, Lung, and Blood Institute (K23HL150159), American Heart Association (2nd Century Early Faculty Independence Award), Permanente Medical Group, Northern California Community Benefits Programs, Garfield Memorial Fund, Abbott Laboratories, Amarin Pharma, Edwards Lifesciences, Esperion Therapeutics, and Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: Hypertension is a major risk factor for dementia, but sustained blood pressure control is difficult to achieve. We evaluated whether inadequately controlled hypertension may contribute to excess dementia risk among people with HIV., Design: A retrospective cohort study., Methods: We studied demographically matched people with and without HIV between July 1, 2013, and December 31, 2021, who were at least 50 years old and had a hypertension diagnosis but no dementia diagnosis. Hypertension control was calculated using a disease management index (DMI), which captured degree and duration above the hypertension treatment goals of SBP less than 140 mmHg and DBP less than 90 mmHg. DMI values ranged from 0 to 100% (perfect control); hypertension was considered 'inadequately controlled' if DMI was less than 80% (i.e., in control for <80% of the time). Annual, time-updated DMI was calculated for SBP and DBP. Associations of SPB and DPB control with incident dementia were evaluated using extended Cox regression models., Results: The study included 3099 hypertensive people with HIV (mean age: 58.3 years, 90.2% men) and 66 016 people without HIV. Each year of inadequate SBP control was associated with greater dementia risk in both people with HIV (adjusted hazard ratio [aHR] = 1.26, 0.92-1.64) and people without HIV (aHR = 1.27 (1.21-1.33); P- interaction = 0.85). Similarly, inadequate DBP control was associated with greater dementia risk in both people with HIV (aHR = 1.43, 0.90-1.95) and people without HIV (aHR = 1.71, 1.50-1.93; P -interaction = 0.57)., Conclusion: Findings suggest the association of inadequate hypertension control with greater dementia risk is similar by HIV status. Stronger associations of DBP control with dementia merit further investigation., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Hazardous drinking is a public health problem affecting approximately 20 % of the U.S. primary care population. Clinical trials have documented the efficacy and effectiveness of Alcohol Screening and Brief Intervention (ASBI), yet widespread implementation remains elusive, and questions remain regarding optimal implementation and sustainment strategies. Kaiser Permanente Northern California (KPNC) implemented systematic ASBI in adult primary care in mid-2013. We used 8 years of electronic health record (EHR) data, combined with surveys which captured primary care provider perceptions organized into PRISM (Practical, Robust Implementation and Sustainability Model) implementation framework domains (Intervention, External Environment, Implementation Infrastructure, and Recipients), to characterize ASBI implementation and sustainment and test how various factors are associated with ASBI rates., Methods: Using EHR data, we calculated yearly screening rates of adults with a primary care visit, and brief intervention (BI) rates among those with a positive hazardous drinking screen, (exceeding the age and sex-specific daily and weekly low-risk NIH guidelines (≤3 per day and ≤ 7 per week for women and older men; ≤4 per day and ≤ 14 per week for men 18-65)), across KPNC, from 2014 to 2021. We collected web-based survey data, informed by the PRISM domains, from primary care providers (n = 796; 35.5 % RR) to assess perceptions on ASBI implementation and sustainability., Results: Between 1/1/2014 and 12/31/21 there were 5,072,270 completed screenings and 624,167 BIs. After adjusting for patient panel characteristics, we found that facilities with higher Implementation Infrastructure domain scores, indicating more robust implementation capacity, had higher screening and BI rates; facilities with higher Intervention domain scores, indicating positive perceptions of SBIRT evidence, and facilities with higher Recipients domain scores, indicating perceived organizational robustness, clinician culture and management support; and greater perceived patient needs and their likely benefit from SBIRT, had higher BI rates., Conclusions: Results provide information on factors which may facilitate successful ASBI implementation and sustainability and could inform future ASBI implementation efforts in healthcare system settings. In particular, efforts toward bolstering an organization's implementation infrastructure capacity, prior to embarking on implementation of a systematic ASBI program, could potentially help pave the way for successful implementation., Competing Interests: Declaration of competing interest The authors have no financial relationships relevant to this article or potential conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Childhood adversity harms neurodevelopment. Literature on late-life brain health is limited, and findings on late-life cognition are mixed., Methods: Pooling data from Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) and Study of Healthy Aging in African Americans (STAR) cohorts, we assessed the impact of childhood adversity (factor score from seven self-reported items) on (a) executive function and verbal memory decline using linear mixed effects models (n = 2447), (b) structural magnetic resonance imaging (MRI) using linear regression (n = 618), and (c) amyloid positron emission tomography (PET) using generalized linear models (n = 331), all adjusting for early-life demographic and socioeconomic confounders., Results: Childhood adversity was not associated with cognition except for a slightly faster decline in verbal memory ( β ̂ $\hat \beta $  = -0.013 SD/year, 95% confidence interval [-0.025, -0.001]). Among neuroimaging outcomes, childhood adversity was associated with only larger temporal lobe volumes ( β ̂ $\hat \beta $  = 0.092 SD [0.012, 0.173])., Discussion: More research evaluating sources of resilience, heterogeneity, and bias is needed to explain inconsistent findings across studies., Highlights: We developed measurement models to capture childhood adversity in a diverse cohort. Childhood adversity was associated with a slightly faster verbal memory decline. We examined childhood adversity's effect on structural MRI and amyloid PET measures. Higher childhood adversity was associated with larger temporal lobe volumes., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: Patients with advanced ALK-positive NSCLC typically have poor response to immunotherapy; the benefit of consolidation durvalumab in patients with unresectable stage III ALK-positive NSCLC remains unclear. Herein, we compare the efficacy and safety of consolidation ALK tyrosine kinase inhibitor (TKI) versus durvalumab or observation after concurrent chemoradiation., Methods: We conducted a retrospective study using a multicenter study of 17 institutions globally. Patients with unresectable stage III ALK-positive NSCLC treated between 2015 and 2022 were included. Patients received ALK TKI, durvalumab, or observation after concurrent chemoradiation. Real-world progression-free survival (rwPFS) and overall survival (OS) were estimated using Kaplan-Meier method. Treatment-related adverse events (trAEs) were classified by Common Terminology Criteria for Adverse Events version 5.0. Outcomes were assessed by multivariable Cox regression analysis., Results: A total of 67 patients were included, of whom 39 (58%) were female. Median age was 57 (interquartile range: 49-67) years. Furthermore, 15 received consolidation ALK TKI, 30 received durvalumab, and 22 underwent observation. Baseline characteristics were similar across the three groups other than differences in race. After adjusting for stage, age, and nodal status, median rwPFS was significantly longer for ALK TKI (rwPFS not reached, 95% confidence interval [CI]: 22.7- not reached) versus durvalumab (11.3 mo, 95% CI: 8.9-18.5, hazard ratio [HR] = 0.12, 95% CI: 0.026-0.5, p-adjusted [p-adj] = 0.006) or observation (7.2 mo, 95% CI: 3.4-10.6, HR = 0.04, 95% CI: 0.009-0.2, p-adj < 0.0001). Durvalumab significantly improved median rwPFS compared with observation (HR = 0.37, 95% CI: 0.19-0.71, p-adj = 0.002). Median OS in the ALK TKI and durvalumab cohorts was significantly improved compared with patients on observation (ALK TKI-observation: p = 0.04; durvalumab-observation: p = 0.03). TrAE of any grade occurred in eight (53%) and 11 (37%) patients treated with ALK TKI and durvalumab, respectively. Grade greater than or equal to three trAEs occurred in 27% (n = 4) of patients treated with ALK TKI and 6.7% of patients treated with durvalumab., Conclusions: Patients with ALK-positive NSCLC experience significantly improved rwPFS when treated with consolidation ALK TKI therapy, surpassing outcomes found with either durvalumab or observation. Although both ALK TKI therapy and durvalumab offer an extension in OS compared with observation alone, it seems that ALK TKI therapy is the superior choice, underscoring its pivotal role in enhancing patient survival., Competing Interests: Disclosure Dr. Nassar receives honoraria from OncLive, TEMPUS, and Korean Society for Medical Oncology and consulting fees from Guidepoint Global and Putnam Associates. Dr. Goldberg receives research funding from AstraZeneca, Boehringer Ingelheim, and Mirati; is an advisory board member for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Amgen, Blueprint Medicine, Sanofi Genzyme, Daiichi Sankyo, Takeda, Janssen, Summit Therapeutics, Merck, Regeneron, and Eli Lilly; and receives honoraria for lectures for Amgen and AstraZeneca. Dr. Naqash receives funding to institution for trials he is PI on Loxo@Lilly, Surface Oncology, ADC Therapeutics, IGM Biosciences, EMD Serono, Aravive, Nikang Therapeutics, Inspirna, Exelexis, Revolution Medicine, Jacobio, Pionyr, Jazz Pharmaceuticals, NGM Biopharmaceuticals, Immunocore, Phanes Therapeutics, Deka, Kymera, IDEAYA, IGM Biosciences, Selexine, and Chipscreen Biosciences; receives consultant editor compensation from JCO Precision Oncology; receives travel compensation from SITC, American Association for Cancer Reasearch, Conquer Cancer Foundation, BinayTara Foundation, Foundation Med, Caris Life Sciences, Sarah Cannon Research Institute, Jazz Pharmaceuticals, ASCO, and ASTRO; serves on the advisory board of Foundation Med and NGM Biosciences; receives current research grant support from Swog Hope Foundation, FDA Broad Agency Award, and OSCTR; and has genomics research agreements from Tempus, Caris, and Foundation One. Dr. Kim receives institutional funding from Loxo@Lilly, AstraZeneca, Boehringer Ingelheim, Genentech, Bristol-Myers Squibb, DynamiCure, Seagen, Genmab, and Nykode Therapeutics. Dr. Reuss reports serving on the advisory board/as consultant of Sanofi/Genzyme, Personalis, Guardant, AstraZeneca, Bristol-Myers Squibb, Arcus, AbbVie, Daiichi Sankyo, Catalym, Seagen, Gilead, Janssen, Novocure, Regeneron, and Summit Therapeutics; receiving research funding (to institution) from Genentech/Roche, Verastem, Nuvalent, and Exelixis; and receiving honoraria from Merck and AstraZeneca. Dr. Cortellini reports receiving grants for consultancies/advisory boards from Merck Sharp & Dohme, Bristol-Myers Squibb, OncoC4, IQVIA, AstraZeneca, Regeneron, Access Infinity, Ardelis Health, Alpha Sight, Guidepoint, and Roche; receiving speaker fees from AstraZeneca, Pierre-Fabre, Merck Sharp & Dohme, and Sanofi/Regeneron; having writing/editorial activity for Bristol-Myers Squibb and Merck Sharp & Dohme; and receiving travel support from Sanofi/Regeneron and Merck Sharp & Dohme. Dr. Marron currently or has previously served on advisory and/or data safety monitoring boards for Rockefeller University, Regeneron, AbbVie, Merck, Bristol-Myers Squibb, Boehringer Ingelheim, Atara, AstraZeneca, Genentech, Celldex, Chimeric, DrenBio, Glenmark, Simcere, Surface, G1 Therapeutics, NGMbio, DBV Technologies, Arcus, Fate, Ono, Larkspur, Avammune, and Astellas; and has received research grants from Regeneron, Genentech, Bristol-Myers Squibb, Merck, and Boehringer Ingelheim. Dr. Fitzgerald receives institutional research funding from Genentech/Roche, PPD, and bioatla and travel funding from IASLC. Dr. Dilling has served on the advisory boards for AstraZeneca and is a member of the NCCN Non–Small Cell Lung Cancer Panel. Dr. Bar is an advisor of AbbVie, Amgen, AstraZeneca, Bayer, Merck Sharp & Dohme, Merck-Serono, Roche, and Takeda; has writing/speaker engagement for Bristol-Myers Squibb, Medison, and Pfizer, and has received research funding from Immunai, OncoHost, Merck Sharp & Dohme, AstraZeneca, Roche, and AbbVie. Dr. Aredo reports receiving consulting fees from AstraZeneca. Dr. Lin has served as a compensated consultant for Genentech, C4 Therapeutics, Blueprint Medicines, Nuvalent, Bayer, Elevation Oncology, Novartis, Mirati Therapeutics, AnHeart Therapeutics, CLaiM Therapeutics, Ellipses, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Yuhan, Merus, Regeneron, Pfizer, and Turning Point Therapeutics; received institutional research funds from Hengrui Therapeutics, Turning Point Therapeutics, Neon Therapeutics, Relay Therapeutics, Bayer, Elevation Oncology, Roche, Linnaeus Therapeutics, Nuvalent, and Novartis; and has received travel support from Pfizer and Merus. Dr. Kwiatkowski receives research funding from AADI and Genentech; and consults for Genentech, AADI, Expertconnect, Guidepoint, Bridgebio, Slingshot Insights, William Blair, MEDACorp, and Radyus Research. Dr. Yu has done consulting for AstraZeneca, Daiichi, Janssen, Amgen, Black Diamond, Blueprint, Cullinan, Takeda, and Taiho. Dr. Feng reports receiving speaker honoraria from AstraZeneca Canada. Dr. Velazquez reports receiving consulting fees from AstraZeneca, Merus, Novocure, and Regeneron., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Objective: This study investigated ICD-10-CM codes for adverse social determinants of health (SDoH) across 12 U.S. health systems by using data from multiple health care encounter types for diverse patients covered by multiple payers., Methods: The authors described documentation of 11 SDoH ICD-10-CM code categories (e.g., educational problems or social environmental problems) between 2016 and 2021; assessed changes over time by using chi-square tests for trend in proportions; compared documentation in 2021 by gender, age, race-ethnicity, and site with chi-square tests; and compared all patients' mental health outcomes in 2021 with those of patients with documented SDoH ICD-10-CM codes by using exact binomial tests and one-proportion z tests., Results: Documentation of any SDoH ICD-10-CM code significantly increased, from 1.7% of patients in 2016 to 2.7% in 2021, as did that for all SDoH categories except educational problems. Documentation was often more prevalent among female patients and those of other or unknown gender than among male patients and among American Indian or Alaska Native, Black or African American, and Hispanic individuals than among those belonging to other race-ethnicity categories. More educational problems were documented for younger patients, and more social environmental problems were documented for older patients. Psychiatric diagnoses and emergency department visits and hospitalizations related to mental health were more common among patients with documented SDoH codes., Conclusions: SDoH ICD-10-CM code documentation was infrequent and differed by population subgroup. Differences may reflect documentation practices or true SDoH prevalence variation. Standardized SDoH documentation methods are needed in health care settings., Competing Interests: The authors report no financial relationships with commercial interests.

Importance: The results of small studies suggest that off-label use of low-dose oral minoxidil (LDOM) may be safe and effective for patients with hair loss, but larger trials and standardized guidelines are lacking., Objective: To create an expert consensus statement for LDOM prescribing for patients with hair loss., Evidence Review: The current literature on the pharmacological properties, adverse effect profile, and use of LDOM for patients with hair loss was reviewed. Topics of interest were identified, and a modified Delphi consensus process was created. A total of 43 hair loss specialist dermatologists from 12 countries participated in a modified Delphi process. Consensus was reached if at least 70% agreed or strongly agreed on a 5-point Likert scale., Findings: Over 4 survey rounds, 180 items in the first round, 121 items in the second round, 16 items in the third round, and 11 items in the fourth round were considered and revised. A total of 76 items achieved consensus including diagnoses for which LDOM may provide direct or supportive benefit, indications for LDOM compared to topical minoxidil, dosing for adults (18 years and older) and adolescents (aged 12 to 17 years), contraindications, precautions, baseline evaluation, monitoring, adjunctive therapy, and specialty consultation. Pediatric use and dosing items for children younger than 12 years, and LDOM titration protocols fell short of consensus., Conclusions and Relevance: This international expert consensus statement regarding the off-label prescribing of LDOM for patients with hair loss can help guide clinical practice until more data emerge. Hair loss experts with experience treating pediatric patients were underrepresented on this expert panel. Future research should investigate best practices for LDOM use in pediatric patients. Other critical topics for further investigation include the comparative efficacy of topical minoxidil vs oral minoxidil, the safety of oral minoxidil for patients with a history of allergic contact dermatitis to topical minoxidil, the long-term safety of LDOM, and the use of other off-label forms of minoxidil, such as compounded formulations of oral minoxidil and sublingual minoxidil. As additional evidence-based data emerge, these recommendations should be updated.

Despite the prevalence and significant concern of COVID-19 in maternal and offspring health, little is known about the impact of COVID-19 during pregnancy on newborn immunity and neurodevelopment. This study aimed to examine 1) the relationship between maternal COVID-19 during pregnancy and newborn immune profiles and investigate the 2) associations between specific newborn immune profiles and the risk of subsequent diagnosis of a neurodevelopmental disorder (NDD) among children with prenatal exposure to COVID-19. Newborn dried bloodspots (NBS) from 545 children born at Kaiser Permanente Northern California between January 2020 and September 2021 (460 [223 males, 237 females] to COVID-19-infected [COVID+] mothers; 85 [45 males, 40 females] to COVID-19-uninfected [COVID-] mothers) were used to profile newborn immune molecules via a 42-plex cytokine/chemokine assay. Among the 460 children born to COVID+ mothers, 73 (47 males, 27 females) were later diagnosed with an NDD. In the first set of analyses examining the association between maternal COVID-19 infection during pregnancy and newborn immune profile, the results adjusted for covariates but uncorrected for multiple comparisons showed that newborns of COVID+ mothers had significantly higher levels of IL-22 (estimate [est.] = 0.16, 95 % Cl 0.01, 0.3, p = 0.04) and GM-CSF (est. = 0.27, 95 % Cl 0.09, 0.46, p = 0.004) compared to newborns of COVID- mothers. These differences were no longer statistically significant after multiple comparison adjustments. In the second analysis exploring the association between newborn profile and later diagnosis of NDD among newborns born to COVID+ mothers, the results adjusted for covariates revealed an association between higher neonatal levels of IL-22 (hazard ratio [HR] = 0.49, 95 % Cl 0.33, 0.75, p = 0.001) and lower risk of a later diagnosis of an NDD, which remained significant after multiple comparison adjustments (p = 0.04). Other neonatal cytokines/chemokines/growth factors such as sCD40L (HR = 0.7, 95 % Cl 0.57, 0.9, p = 0.009), IP-10 (HR = 0.46, 95 % Cl 0.25, 0.83, p = 0.009), MIG (HR = 0.52, 95 % Cl 0.3, 0.9, p = 0.02), FLT-3L (HR = 0.45, 95 % Cl 0.24, 0.83, p = 0.01), PDGF AB/BB (HR = 0.56, 95 % Cl 0.36, 0.99, p = 0.046), VEGF (HR = 0.57, 95 % Cl 0.34, 0.98, p = 0.04), and IL-4 (HR = 0.48, 95 % Cl 0.26, 0.93, p = 0.03) were no longer statistically significant after multiple comparison adjustments. Despite the imbalance between the number of COVID-19 exposed and unexposed newborns in this study cohort, our novel findings enhance our understanding of the potential impact of maternal COVID-19 infection during pregnancy on the developing neonatal immune system. Our findings highlight the role of immune molecules, beyond those considered to be pro-inflammatory, that may be crucial in maternal and newborn immunity against COVID-19 infection during pregnancy. Furthermore, our results suggest that reduced levels of neonatal immune molecules in newborns of COVID + mothers may be linked to an increased risk of a subsequent diagnosis of an NDD., 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. Published by Elsevier Inc.)

Heart failure (HF) poses a major global health challenge with rising prevalence, significant morbidity and mortality, and substantial associated healthcare costs. With aging of the population and an increasing burden of comorbidities, the complex interplay between cardiovascular, kidney, and metabolic risk factors have been thrust into the spotlight and have broadened the traditional focus from HF treatment to an increased emphasis on prevention. In recognition of the evolving HF landscape, the American Heart Association released the PREVENT models which are comprehensive risk assessment tools that estimate 10- and 30-year risk of incident cardiovascular disease and its subtypes, including atherosclerotic cardiovascular disease (ASCVD) and, for the first time, HF. While it is an accurate risk estimation tool and represents a step forward in improving risk stratification for primary prevention of HF, there remain several limitations and unknowns like model performance across disaggregated racial and ethnic groups, the role of traditional ASCVD vs. HF-specific risk factors, HF prediction among those with known ASCVD, and the use of traditional regression techniques in lieu of potentially more powerful machine learning-based modeling approaches. Furthermore, it remains unclear how to optimize risk estimation in clinical care. The emergence of multiple novel pharmacological therapies that prevent incident HF, including sodium-glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 (GLP1) receptor agonists, and nonsteroidal mineralocorticoid receptor antagonists (MRAs), highlights the importance of accurate HF risk prediction. To provide HF prevention with these effective but costly therapies, we must understand the optimal strategy in sequencing and combining these therapies and prioritize patients at highest risk. Such implementation requires both accurate risk stratification and a better understanding of how to communicate risk to patients and providers. This state-of-the-art review aims to provide a comprehensive overview of recent trends in HF prevention, including risk assessment, care management strategies, and emerging and novel treatments., Competing Interests: Declarations. Competing interest: Dr. Greene has received research support from the Duke University Department of Medicine Chair’s Research Award, American Heart Association , Amgen, AstraZeneca, Boehinger Ingelheim, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, Pfizer, and Sanofi; has served on advisory boards or as consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Corcept Therapeutics, Corteria Pharmaceuticals, CSL Vifor, Cytokinetics, Eli Lilly, Lexicon, Merck, Otsuka, Roche Diagnostics, Sanofi, scPharmaceuticals, Tricog Health, and Urovant Pharmaceuticals; and has received speaker fees from AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Lexicon, and Roche Diagnostics. Dr. Sandhu has received research support from National Institutes of Health, American Heart Association , Novartis Pharmaceuticals, and Repreive Cardiovascular and has served as a consultant for Lexicon Pharmaceuticals. Dr. Go has received research support from the National Heart, Lung and Blood Institute and the National Institute of Diabetes, Digestive and Kidney Diseases. Dr. Ambrosy has received relevant research support through grants to his institution from the National Heart, Lung, and Blood Institute (K23HL150159), the American Heart Association (2nd Century Early Faculty Independence Award), The Permanente Medical Group, Northern California Community Benefits Programs, Garfield Memorial Fund, Abbott Laboratories, Amarin Pharma, Inc., Bayer, Cordio Medical, Edwards Lifesciences LLC, Esperion Therapeutics, Inc., Merck, and Novartis. Dr. Stephen J. Greene, Dr. Josephine Harrington, and Dr. Andrew P. Ambrosy are Editorial Board members of Heart Failure Reviews. All other authors report no relevant disclosures., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Alcohol use disorder (AUD) treatment can help improve clinical outcomes among patients with alcohol-associated cirrhosis but is underutilized. Among socioeconomically disadvantaged patients with alcohol-associated cirrhosis, we examined rates of lifetime and past 12-month AUD treatment utilization and associated demographic and clinical characteristics., Methods: Racial/ethnically diverse patients with alcohol-associated cirrhosis who had at least one hepatology clinic visit in the prior 6 months were recruited from three Northern California medical centers serving veterans and safety-net populations. Participants self-reported their AUD treatment utilization, liver disease quality of life (LDQoL), history and current symptoms of anxiety and depression, and problematic drinking as measured by the Alcohol Use Disorders Identification Test (AUDIT). Clinical measures including liver disease severity were captured from medical records., Results: Among 196 participants, the majority were male (88%) with a mean age of 62 years. Two-thirds of participants (67%) reported ever utilizing AUD treatment and 32% reported utilizing AUD treatment in the past 12 months. Compared with those who did not utilize AUD treatment, participants who utilized lifetime or past 12-month AUD treatment were younger, had lower LDQoL scores, and had higher scores on current symptoms of anxiety, depression, and problematic drinking. In multivariable analyses, the odds of ever utilizing pharmacological treatment alone or both behavioral and pharmacological treatment (vs. none) were lower with older age or higher LDQoL, and higher among those with a history of anxiety/depressive disorder. For past 12-month treatment utilization, odds were lower with older age, and higher among those with current clinically significant anxiety/depression or problematic drinking., Conclusions: Patients with alcohol-associated cirrhosis who were younger or had anxiety/depression and problematic drinking were more likely to utilize AUD treatment. To improve AUD treatment utilization, targeted outreach to patients less likely to receive care and the provision of integrated ALD and AUD treatment is warranted., (© 2024 Research Society on Alcohol. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)