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Group testing, introduced by Dorfman (1943), has been used to reduce costs when estimating the prevalence of a binary characteristic based on a screening test of [Formula: see text] groups that include [Formula: see text] independent individuals in total. If the unknown prevalence is low and the screening test suffers from misclassification, it is also possible to obtain more precise prevalence estimates than those obtained from testing all [Formula: see text] samples separately (Tu et al., 1994). In some applications, the individual binary response corresponds to whether an underlying time-to-event variable [Formula: see text] is less than an observed screening time [Formula: see text], a data structure known as current status data. Given sufficient variation in the observed [Formula: see text] values, it is possible to estimate the distribution function [Formula: see text] of [Formula: see text] nonparametrically, at least at some points in its support, using the pool-adjacent-violators algorithm (Ayer et al., 1955). Here, we consider nonparametric estimation of [Formula: see text] based on group-tested current status data for groups of size [Formula: see text] where the group tests positive if and only if any individual's unobserved [Formula: see text] is less than the corresponding observed [Formula: see text]. We investigate the performance of the group-based estimator as compared to the individual test nonparametric maximum likelihood estimator, and show that the former can be more precise in the presence of misclassification for low values of [Formula: see text]. Potential applications include testing for the presence of various diseases in pooled samples where interest focuses on the age-at-incidence distribution rather than overall prevalence. We apply this estimator to the age-at-incidence curve for hepatitis C infection in a sample of U.S. women who gave birth to a child in 2014, where group assignment is done at random and based on maternal age. We discuss connections to other work in the literature, as well as potential extensions.

Background: Preventive screenings in children encourage maintenance of optimal cardiovascular health, but gaps may exist between recommendations and clinical practice. We evaluated adherence to pediatric guidelines for universal age-based and risk-based screening for body mass index, blood pressure, lipids, and blood glucose., Methods and Results: We used 2010 to 2018 ambulatory visit data from children aged 2 to 12 years within CAPRICORN (Chicago Area Patient-Centered Outcomes Research Network), an electronic health record network in Chicago. This study included 87 549 children who attended 197 559 well-child encounters. Across all encounters, children were 51.5% male and mean (SD) age 6.4 (3.3) years. For each child who attended a well-child visit and met age and/or risk-based criteria, receipt of body mass index, blood pressure, lipids, and/or hemoglobin A1c or fasting blood glucose measurements were assessed. We used generalized estimating equations to calculate proportion adherence for each metric overall and stratified by age, sex, race and ethnicity, and insurance status. Universal age-based screening prevalence (95% CI) per 100 eligible visits was 77.1 (76.8-77.3) for body mass index, 33.4 (33.1-33.7) for blood pressure, and 9.6 (9.3-9.9) for lipids. Risk-based screening prevalence (95% CI) per 100 eligible visits was 13.9 (12.2-15.9) for blood pressure, 6.9 (6.4-7.5) for lipids, and 13.3 (12.6-14.1) for blood glucose., Conclusions: Early screening of cardiovascular health risk factors could lead to earlier interventions, which could alter cardiovascular health trajectories across the lifetime. Low-to-moderate levels of adherence to universal age-based and risk-based cardiovascular health screening highlight the gap between recommendations and clinical practice, emphasizing the need to understand and address barriers to screening in pediatric populations.

Background: Clinical guidelines recommend medications from four drug classes, collectively referred to as quadruple therapy, to improve outcomes for patients with heart failure with reduced ejection fraction (HFrEF). Wide gaps in uptake of these therapies persist across a range of settings. In this qualitative study, we identified determinants (i.e., barriers and facilitators of quadruple therapy intensification, defined as prescribing a new class or increasing the dose of a currently prescribed medication., Methods: We conducted interviews with physicians, nurse practitioners, physician assistants, and pharmacists working in primary care or cardiology settings in an integrated health system or Federally Qualified Health Centers (FQHCs). We report results with a conceptual model integrating two frameworks: 1) the Theory of Planned Behavior (TPB), which explains how personal attitudes, perception of others' attitudes, and perceived behavioral control influence intentions and behaviors; and 2) The Consolidated Framework for Implementation Research (CFIR) 2.0 to understand how multi-level factors influence attitudes toward and intention to use quadruple therapy., Results: Thirty-one clinicians, including thirteen eighteen (58%) primary care and (42%) cardiology clinicians, participated in the interviews. Eight (26%) participants were from FQHCs. A common facilitator in both settings was the belief in the importance of quadruple therapy. Common barriers included challenges presented by patient frailty, clinical inertia, and time constraints. In FQHCs, primary care comfort and ownership enhanced the intensification of quadruple therapy while limited access to and communication with cardiology specialists presented a barrier. Results are presented using a combined TPB-CFIR framework to help illustrate the potential impact of contextual factors on individual-level behaviors., Conclusions: Determinants of quadruple therapy intensification vary by clinician specialty and care setting. Future research should explore implementation strategies that address these determinants by specialty and setting to promote health equity.

Background: Referral of patients with heart failure (HF) who are at high mortality risk for specialist evaluation is recommended. Yet, most tools for identifying such patients are difficult to implement in electronic health record (EHR) systems., Objective: To assess the performance and ease of implementation of Machine learning Assessment of RisK and EaRly mortality in Heart Failure (MARKER-HF), a machine-learning model that uses structured data that is readily available in the EHR, and compare it with two commonly used risk scores: the Seattle Heart Failure Model (SHFM) and Meta-Analysis Global Group in Chronic (MAGGIC) Heart Failure Risk Score., Design: Retrospective, cohort study., Participants: Data from 6764 adults with HF were abstracted from EHRs at a large integrated health system from 1/1/10 to 12/31/19., Main Measures: One-year survival from time of first cardiology or primary care visit was estimated using MARKER-HF, SHFM, and MAGGIC. Discrimination was measured by the area under the receiver operating curve (AUC). Calibration was assessed graphically., Key Results: Compared to MARKER-HF, both SHFM and MAGGIC required a considerably larger amount of data engineering and imputation to generate risk score estimates. MARKER-HF, SHFM, and MAGGIC exhibited similar discriminations with AUCs of 0.70 (0.69-0.73), 0.71 (0.69-0.72), and 0.71 (95% CI 0.70-0.73), respectively. All three scores showed good calibration across the full risk spectrum., Conclusions: These findings suggest that MARKER-HF, which uses readily available clinical and lab measurements in the EHR and required less imputation and data engineering than SHFM and MAGGIC, is an easier tool to identify high-risk patients in ambulatory clinics who could benefit from referral to a HF specialist., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Objective: To evaluate the relationship between changes in Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) enrollment during pregnancy from 2016 to 2019 and rates of adverse pregnancy outcomes in U.S. counties in 2019., Methods: We conducted a serial, cross-sectional ecologic study at the county level using National Center for Health Statistics natality data from 2016 to 2019 of nulliparous individuals eligible for WIC. The exposure was the change in county-level WIC enrollment from 2016 to 2019 (increase [more than 0%] vs no change or decrease [0% or less]). Outcomes were adverse pregnancy outcomes assessed in 2019 and included maternal outcomes (ie, gestational diabetes mellitus [GDM], hypertensive disorders of pregnancy, cesarean delivery, intensive care unit [ICU] admission, and transfusion) and neonatal outcomes (ie, large for gestational age [LGA], small for gestational age [SGA], preterm birth, and neonatal intensive care unit [NICU] admission)., Results: Among 1,945,914 deliveries from 3,120 U.S. counties, the age-standardized rate of WIC enrollment decreased from 73.1 (95% CI, 73.0-73.2) per 100 live births in 2016 to 66.1 (95% CI, 66.0-66.2) per 100 live births in 2019, for a mean annual percent change decrease of 3.2% (95% CI, -3.7% to -2.9%) per year. Compared with individuals in counties in which WIC enrollment decreased or did not change, individuals living in counties in which WIC enrollment increased had lower rates of maternal adverse pregnancy outcomes, including GDM (adjusted odds ratio [aOR] 0.71, 95% CI, 0.57-0.89), ICU admission (aOR 0.47, 95% CI, 0.34-0.65), and transfusion (aOR 0.68, 95% CI, 0.53-0.88), and neonatal adverse pregnancy outcomes, including preterm birth (aOR 0.71, 95% CI, 0.56-0.90) and NICU admission (aOR 0.77, 95% CI, 0.60-0.97), but not cesarean delivery, hypertensive disorders of pregnancy, or LGA or SGA birth., Conclusion: Increasing WIC enrollment during pregnancy at the county level was associated with a lower risk of adverse pregnancy outcomes. In an era when WIC enrollment has decreased and food and nutrition insecurity has increased, efforts are needed to increase WIC enrollment among eligible individuals in pregnancy., Competing Interests: Financial Disclosure Lucia C. Petito reported that money was paid to her institution from Omron Healthcare Co., Ltd. The other 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.)

Introduction: This study aimed to determine the association between changes in age distribution and maternal mortality rates (MMR) in a subset of the United States between 2014 and 2021., Methods: A serial cross-sectional analysis of birthing individuals aged 15-44 years from 2014 to 2021 was performed. States that had not adopted the pregnancy checkbox as of 2014 were excluded from the primary analysis. A significant inflection point in MMR was identified in 2019 with the Joinpoint Regression Program, so all analyses were stratified: 2014-2019 and 2019-2021. The Kitagawa decomposition was applied to quantify the contribution from (1) changes in age distribution and (2) changes in age-specific MMR (ASMR) to total MMR. Data analysis occurred between 2022 and 2023., Results: From 2014 to 2021, the mean (standard deviation) age of birthing individuals changed from 28.3 (5.8) to 29.4 (5.7) years. The MMR (95% CI) increased significantly from 16.5 (15.8-18.5) to 18.9 (17.4-20.5) per 100,000 live births from 2014 to 2019 with acceleration in MMR to 31.8 (30.0-33.8) by 2021. The change in maternal age distribution contributed to 36% of the total change in the MMR from 2014 to 2019 and 4% from 2019 to 2021. Age-specific MMR components increased significantly for those aged 25-29 years and 30-34 years from 2014 to 2019. All 5-year age strata except the 15-19 year old group saw increases in age-specific MMR from 2019 to 2021., Conclusions: MMR increased significantly from 2014 to 2021 with rapid increase after 2019. However, older age of birthing individuals explained only a minority of the increased MMR in both periods. The greatest contribution to MMR arose from increases in age-specific MMR., (Copyright © 2024 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Emulation of the "target trial" (TT), a hypothetical pragmatic randomized controlled trial (RCT), using observational data can be used to mitigate issues commonly encountered in comparative effectiveness research (CER) when randomized trials are not logistically, ethically, or financially feasible. However, cardiovascular (CV) health research has been slow to adopt TT emulation. Here, we demonstrate the design and analysis of a TT emulation using electronic health records to study the comparative effectiveness of the addition of a disease-modifying anti-rheumatic drug (DMARD) to a regimen of methotrexate on CV events among rheumatoid arthritis (RA) patients., Methods: We used data from an electronic medical records-based cohort of RA patients from Northwestern Medicine to emulate the TT. Follow-up began 3 months after initial prescription of MTX (2000-2020) and included all available follow-up through June 30, 2020. Weighted pooled logistic regression was used to estimate differences in CVD risk and survival. Cloning was used to handle immortal time bias and weights to improve baseline and time-varying covariate imbalance., Results: We identified 659 eligible people with RA with average follow-up of 46 months and 31 MACE events. The month 24 adjusted risk difference for MACE comparing initiation vs non-initiation of a DMARD was -1.47% (95% confidence interval [CI]: -4.74, 1.95%), and the marginal hazard ratio (HR) was 0.72 (95% CI: 0.71, 1.23). In analyses subject to immortal time bias, the HR was 0.62 (95% CI: 0.29-1.44)., Conclusion: In this sample, we did not observe evidence of differences in risk of MACE, a finding that is compatible with previously published meta-analyses of RCTs. Thoughtful application of the TT framework provides opportunities to conduct CER in observational data. Benchmarking results of observational analyses to previously published RCTs can lend credibility to interpretation., Competing Interests: ASR was supported by the American Heart Association Predoctoral Fellowship (825793) for unrelated research. LCP receives funds for unrelated research from Omron Healthcare Co., Ltd. Other authors have no other conflicts to declare. The mentioned organizations had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials, (Copyright: © 2024 Rivera et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Effective strategies are needed to curtail overuse that may lead to harm., Objective: To evaluate the effects of clinician decision support redirecting attention to harms and engaging social and reputational concerns on overuse in older primary care patients., Design: 18-month, single-blind, pragmatic, cluster randomized trial, constrained randomization. (ClinicalTrials.gov: NCT04289753)., Setting: 60 primary care internal medicine, family medicine and geriatrics practices within a health system from 1 September 2020 to 28 February 2022., Participants: 371 primary care clinicians and their older adult patients from participating practices., Intervention: Behavioral science-informed, point-of-care, clinical decision support tools plus brief case-based education addressing the 3 primary clinical outcomes (187 clinicians from 30 clinics) were compared with brief case-based education alone (187 clinicians from 30 clinics). Decision support was designed to increase salience of potential harms, convey social norms, and promote accountability., Measurements: Prostate-specific antigen (PSA) testing in men aged 76 years and older without previous prostate cancer, urine testing for nonspecific reasons in women aged 65 years and older, and overtreatment of diabetes with hypoglycemic agents in patients aged 75 years and older and hemoglobin A 1c (HbA 1c ) less than 7%., Results: At randomization, mean clinic annual PSA testing, unspecified urine testing, and diabetes overtreatment rates were 24.9, 23.9, and 16.8 per 100 patients, respectively. After 18 months of intervention, the intervention group had lower adjusted difference-in-differences in annual rates of PSA testing (-8.7 [95% CI, -10.2 to -7.1]), unspecified urine testing (-5.5 [CI, -7.0 to -3.6]), and diabetes overtreatment (-1.4 [CI, -2.9 to -0.03]) compared with education only. Safety measures did not show increased emergency care related to urinary tract infections or hyperglycemia. An HbA 1c greater than 9.0% was more common with the intervention among previously overtreated diabetes patients (adjusted difference-in-differences, 0.47 per 100 patients [95% CI, 0.04 to 1.20])., Limitation: A single health system limits generalizability; electronic health data limit ability to differentiate between overtesting and underdocumentation., Conclusion: Decision support designed to increase clinicians' attention to possible harms, social norms, and reputational concerns reduced unspecified testing compared with offering traditional case-based education alone. Small decreases in diabetes overtreatment may also result in higher rates of uncontrolled diabetes., Primary Funding Source: National Institute on Aging., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-2183.

Introduction: Clinical cardiovascular health is a construct that includes 4 health factors-systolic and diastolic blood pressure, fasting glucose, total cholesterol, and body mass index-which together provide an evidence-based, more holistic view of cardiovascular health risk in adults than each component separately. Currently, no pediatric version of this construct exists. This study sought to develop sex-specific charts of clinical cardiovascular health for age to describe current patterns of clinical cardiovascular health throughout childhood., Methods: Data were used from children and adolescents aged 8-19 years in six pooled childhood cohorts (19,261 participants, collected between 1972 and 2010) to create reference standards for fasting glucose and total cholesterol. Using the models for glucose and cholesterol as well as previously published reference standards for body mass index and blood pressure, clinical cardiovascular health charts were developed. All models were estimated using sex-specific random-effects linear regression, and modeling was performed during 2020-2022., Results: Models were created to generate charts with smoothed means, percentiles, and standard deviations of clinical cardiovascular health for each year of childhood. For example, a 10-year-old girl with a body mass index of 16 kg/m 2 (30th percentile), blood pressure of 100/60 mm Hg (46th/50th), glucose of 80 mg/dL (31st), and total cholesterol of 160 mg/dL (46th) (lower implies better) would have a clinical cardiovascular health percentile of 62 (higher implies better)., Conclusions: Clinical cardiovascular health charts based on pediatric data offer a standardized approach to express clinical cardiovascular health as an age- and sex-standardized percentile for clinicians to assess cardiovascular health in childhood to consider preventive approaches at early ages and proactively optimize lifetime trajectories of cardiovascular health., (Copyright © 2023 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

It is increasingly clear that longitudinal risk factor levels and trajectories are related to risk for atherosclerotic cardiovascular disease (ASCVD) above and beyond single measures. Currently used in clinical care, the Pooled Cohort Equations (PCE) are based on regression methods that predict ASCVD risk based on cross-sectional risk factor levels. Deep learning (DL) models have been developed to incorporate longitudinal data for risk prediction but its benefit for ASCVD risk prediction relative to the traditional Pooled Cohort Equations (PCE) remain unknown. Our study included 15,565 participants from four cardiovascular disease cohorts free of baseline ASCVD who were followed for adjudicated ASCVD. Ten-year ASCVD risk was calculated in the training set using our benchmark, the PCE, and a longitudinal DL model, Dynamic-DeepHit. Predictors included those incorporated in the PCE: sex, race, age, total cholesterol, high density lipid cholesterol, systolic and diastolic blood pressure, diabetes, hypertension treatment and smoking. The discrimination and calibration performance of the two models were evaluated in an overall hold-out testing dataset. Of the 15,565 participants in our dataset, 2170 (13.9%) developed ASCVD. The performance of the longitudinal DL model that incorporated 8 years of longitudinal risk factor data improved upon that of the PCE [AUROC: 0.815 (CI 0.782-0.844) vs 0.792 (CI 0.760-0.825)] and the net reclassification index was 0.385. The brier score for the DL model was 0.0514 compared with 0.0542 in the PCE. Incorporating longitudinal risk factors in ASCVD risk prediction using DL can improve model discrimination and calibration., (© 2024. The Author(s).)

Background: Social and psychosocial determinants are associated with cardiovascular health (CVH)., Objectives: To quantify the contributions of social and psychosocial factors to racial/ethnic differences in CVH., Methods: In the Multi-Ethnic Study of Atherosclerosis and Mediators of Atherosclerosis in South Asians Living in America cohorts, Kitagawa-Blinder-Oaxaca decomposition quantified the contributions of social and psychosocial factors to differences in mean CVH score (range 0-14) in Black, Chinese, Hispanic, or South Asian compared with White participants., Results: Among 7,978 adults (mean age 61 [SD 10] years, 52 % female), there were 1,892 Black (mean CVH score for decomposition analysis 7.96 [SD 2.1]), 804 Chinese (CVH 9.69 [1.8]), 1,496 Hispanic (CVH 8.00 [2.1]), 1,164 South Asian (CVH 9.16 [2.0]), and 2,622 White (CVH 8.91 [2.1]) participants. The factors that were associated with the largest magnitude of explained differences in mean CVH score were income for Black participants (if mean income in Black participants were equal to White participants, Black participants' mean CVH score would be 0.14 [SE 0.05] points higher); place of birth for Chinese participants (if proportion of US-born and foreign-born individuals among Chinese adults were equivalent to White participants, Chinese participants' mean CVH score would be 0.22 [0.10] points lower); and education for Hispanic and South Asian participants (if educational attainment were equivalent to White participants, Hispanic and South Asian participants' mean CVH score would be 0.55 [0.11] points higher and 0.37 [0.11] points lower, respectively)., Conclusions: In these multiethnic US cohorts, social and psychosocial factors were associated with racial/ethnic differences in CVH., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nilay S. Shah reports financial support was provided by National Heart Lung and Blood Institute. Alka M. Kanaya reports financial support was provided by National Heart Lung and Blood Institute. Alka M. Kanaya reports financial support was provided by National Center for Advancing Translational Sciences. 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., (© 2024 The Authors. Published by Elsevier B.V.)

Objective: To compare trends in pregestational (DM) and gestational diabetes (GDM) in pregnancy in rural and urban areas in the USA, because pregnant women living in rural areas face unique challenges that contribute to rural-urban disparities in adverse pregnancy outcomes., Design: Serial, cross-sectional analysis., Setting: US National Center for Health Statistics (NCHS) Natality Files from 2011 to 2019., Population: A total of 12 401 888 singleton live births to nulliparous women aged 15-44 years., Methods: We calculated the frequency (95% confidence interval [CI]) per 1000 live births, the mean annual percentage change (APC), and unadjusted and age-adjusted rate ratios (aRR) of DM and GDM in rural compared with urban maternal residence (reference) per the NCHS Urban-Rural Classification Scheme overall, and by delivery year, reported race and ethnicity, and US region (effect measure modification)., Main Outcome Measures: The outcomes (modelled separately) were diagnoses of DM and GDM., Results: From 2011 to 2019, there were increases in both the frequency (per 1000 live births; mean APC, 95% CI per year) of DM and GDM in rural areas (DM: 7.6 to 10.4 per 1000 live births; APC 2.8%, 95% CI 2.2%-3.4%; and GDM: 41.4 to 58.7 per 1000 live births; APC 3.1%, 95% CI 2.6%-3.6%) and urban areas (DM: 6.1 to 8.4 per 1000 live births; APC 3.3%, 95% CI 2.2%-4.4%; and GDM: 40.8 to 61.2 per 1000 live births; APC 3.9%, 95% CI 3.3%-4.6%). Individuals living in rural areas were at higher risk of DM (aRR 1.48, 95% CI 1.45%-1.51%) and GDM versus those in urban areas (aRR 1.17, 95% CI 1.16%-1.18%). The increased risk was similar each year for DM (interaction p = 0.8), but widened over time for GDM (interaction p < 0.01). The rural-urban disparity for DM was wider for individuals who identified as Hispanic race/ethnicity and in the South and West (interaction p < 0.01 for all); and for GDM the rural-urban disparity was generally wider for similar factors (i.e. Hispanic race/ethnicity, and in the South; interaction p < 0.05 for all)., Conclusions: The frequency of DM and GDM increased in both rural and urban areas of the USA from 2011 to 2019 among nulliparous pregnant women. Significant rural-urban disparities existed for DM and GDM, and increased over time for GDM. These rural-urban disparities were generally worse among those of Hispanic race/ethnicity and in women who lived in the South. These findings have implications for delivering equitable diabetes care in pregnancy in rural US communities., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Remote patient monitoring (RPM) for hypertension enables automatic transmission of blood pressure (BP) and pulse into the electronic health record (EHR), but its effectiveness in primary care is unknown. This pragmatic matched cohort study using EHR data compared BP outcomes between individuals prescribed RPM and temporally-matched controls from six primary care practices. We retrospectively created a cohort of 288 Medicare-enrolled patients prescribed BP RPM (cases) and 1152 propensity score-matched controls (1:4). Matching was based on age, sex, systolic blood pressure (SBP), marital status, and other characteristics. Outcomes at 3, 6, 9 and 12 months were: controlling high BP (most recent BP < 140/90 mm Hg), antihypertensive medication intensification, and most recent SBP assessed using: all measurements, and office measurements only. At baseline, RPM-prescribed patients and controls had similar ages and systolic BP. BP control diverged at 3 months (RPM: 72.2%, control: 51%, p < 0.001). This difference persisted but decreased over follow-up. After 12 months, the RPM-prescribed cohort had greater BP control (RPM: 71.5%, control: 58.1%, p < 0.001) and lower SBP (132.3 versus 136.5 mm Hg, p = 0.003) using all measurements, but they did not differ using only office measurements (12 month BP control: 60.8% versus 58.1%, p = 0.44; SBP: 135.9 versus 136.5 mm Hg, p = 0.91). At 12 months, the most recent BP measurements were more current for RPM-prescribed patients (median [IQR] 8 [0-109] versus 134 [56-239] days). Net increases in antihypertensive medications by 12 months were similar. Implementation of RPM in primary care could inform hypertension management strategies and increase hypertension control. Registration: ClinicalTrials.gov identifier: NCT05562921., (© 2023. The Author(s).)

Background: Obesity is a well-established risk factor for both adverse pregnancy outcomes (APOs) and cardiovascular disease (CVD). However, it is not known whether APOs are mediators or markers of the obesity-CVD relationship. This study examined the association between body mass index, APOs, and postpartum CVD risk factors., Methods: The sample included adults from the nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be) Heart Health Study who were enrolled in their first trimester (6 weeks-13 weeks 6 days gestation) from 8 United States sites. Participants had a follow-up visit at 3.7 years postpartum. APOs, which included hypertensive disorders of pregnancy, preterm birth, small-for-gestational-age birth, and gestational diabetes, were centrally adjudicated. Mediation analyses estimated the association between early pregnancy body mass index and postpartum CVD risk factors (hypertension, hyperlipidemia, and diabetes) and the proportion mediated by each APO adjusted for demographics and baseline health behaviors, psychosocial stressors, and CVD risk factor levels., Results: Among 4216 participants enrolled, mean±SD maternal age was 27±6 years. Early pregnancy prevalence of overweight was 25%, and obesity was 22%. Hypertensive disorders of pregnancy occurred in 15%, preterm birth in 8%, small-for-gestational-age birth in 11%, and gestational diabetes in 4%. Early pregnancy obesity, compared with normal body mass index, was associated with significantly higher incidence of postpartum hypertension (adjusted odds ratio, 1.14 [95% CI, 1.10-1.18]), hyperlipidemia (1.11 [95% CI, 1.08-1.14]), and diabetes (1.03 [95% CI, 1.01-1.04]) even after adjustment for baseline CVD risk factor levels. APOs were associated with higher incidence of postpartum hypertension (1.97 [95% CI, 1.61-2.40]) and hyperlipidemia (1.31 [95% CI, 1.03-1.67]). Hypertensive disorders of pregnancy mediated a small proportion of the association between obesity and incident hypertension (13% [11%-15%]) and did not mediate associations with incident hyperlipidemia or diabetes. There was no significant mediation by preterm birth or small-for-gestational-age birth., Conclusions: There was heterogeneity across APO subtypes in their association with postpartum CVD risk factors and mediation of the association between early pregnancy obesity and postpartum CVD risk factors. However, only a small or nonsignificant proportion of the association between obesity and CVD risk factors was mediated by any of the APOs, suggesting APOs are a marker of prepregnancy CVD risk and not a predominant cause of postpartum CVD risk., Competing Interests: Disclosures The views expressed in this article are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the US Department of Health and Human Services. The authors report no conflicts.

Introduction: The 2017 American College of Cardiology/American Heart Association blood pressure guideline redefined hypertension and lowered the blood pressure treatment target. Empirical data on the guideline's impact are needed., Methods: Data were analyzed from Atherosclerosis Risk in Communities study participants who attended baseline pre-guideline (2016-2017) and post-guideline (2018-2019) visits with baseline systolic blood pressure between 120 and 159 mmHg. Participants were grouped according to baseline systolic blood pressure by change in classification under the new guideline as follows: not reclassified (120-129 mmHg), reclassified to Stage 1 hypertension (130-139 mmHg), and reclassified to Stage 2 hypertension (140-159 mmHg). Means and 95% CIs for systolic blood pressure changes between baseline and follow-up, changes in antihypertensive use, and percentages that achieved the post-guideline recommendation (systolic blood pressure <130 mmHg) were calculated. Analyses were performed in 2021-2022., Results: Among 2,193 community-dwelling Atherosclerosis Risk in Communities participants aged 71-95 years at baseline, systolic blood pressure changes between baseline and follow-up visits differed among participants not reclassified (+4.1 mmHg, 95% CI=3.0, 5.3 mmHg), reclassified to Stage 1 hypertension (-1.1 mmHg, 95% CI= -2.2, 0.1 mmHg), and reclassified to Stage 2 hypertension (-5.7 mmHg, 95% CI= -6.8, -4.7 mmHg). Antihypertensive use changed from 77.3% to 78.4% (p=0.25) among participants reclassified to Stage 1 hypertension and from 78.3% to 81.4% (p<0.01) among participants reclassified to Stage 2 hypertension. At follow-up, 41.8% of the Stage 1 and 22.4% of the Stage 2 hypertension groups reached the systolic blood pressure <130 mmHg goal., Conclusions: There were small decreases in systolic blood pressure and increases in antihypertensive therapy among older adults reclassified to Stage 2 hypertension but not among those reclassified to Stage 1 hypertension by the 2017 American College of Cardiology/American Heart Association guideline., (Copyright © 2023 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: Many children have non-ideal cardiovascular health (CVH), but little is known about the course of CVH in early childhood. We identified CVH trajectories in children and assess the generalizability of these trajectories in an external sample., Methods: We used data spanning 2010-2018 from children aged 2-12 years within the Chicago Area Patient-Centered Outcomes Research Network-an electronic health record network. Four clinical systems comprised the derivation sample and a fifth the validation sample. Body mass index, blood pressure, cholesterol, and blood glucose were categorized as ideal, intermediate, and poor using clinical measurements, laboratory readings, and International Classification of Diseases diagnosis codes and summed for an overall CVH score. Group-based trajectory modeling was used to create CVH score trajectories which were assessed for classification accuracy in the validation sample., Results: Using data from 122,363 children (47% female, 47% non-Hispanic White) three trajectories were identified: 59.5% maintained high levels of clinical CVH, 23.4% had high levels of CVH that declined, and 17.1% had intermediate levels of CVH that further declined with age. A similar classification emerged when the trajectories were fitted in the validation sample., Conclusions: Stratification of CVH was present by age 2, implicating the need for early life and preconception prevention strategies., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Norrina Allen reports financial support was provided by American Heart Association., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We present methods for causally interpretable meta-analyses that combine information from multiple randomized trials to draw causal inferences for a target population of substantive interest. We consider identifiability conditions, derive implications of the conditions for the law of the observed data, and obtain identification results for transporting causal inferences from a collection of independent randomized trials to a new target population in which experimental data may not be available. We propose an estimator for the potential outcome mean in the target population under each treatment studied in the trials. The estimator uses covariate, treatment, and outcome data from the collection of trials, but only covariate data from the target population sample. We show that it is doubly robust in the sense that it is consistent and asymptotically normal when at least one of the models it relies on is correctly specified. We study the finite sample properties of the estimator in simulation studies and demonstrate its implementation using data from a multicenter randomized trial., (© 2022 The International Biometric Society.)

Background: Out-of-office blood pressure (BP) measurements contribute valuable information for guiding clinical management of hypertension. Measurements from home devices can be directly transmitted to patients' electronic health record for use in remote monitoring programs., Objective: This study aimed to compare in primary care practice care coordinator-assisted implementation of remote patient monitoring (RPM) for hypertension to RPM implementation alone and to usual care., Methods: This was a pragmatic observational cohort study. Patients aged 65 to 85 years with Medicare insurance from two populations were included: those with uncontrolled hypertension and a general hypertension group seeing primary care physicians (PCPs) within one health system. Exposures were clinic-level availability of RPM plus care coordination, RPM alone, or usual care. At two clinics (13 PCPs), nurse care coordinators with PCP approval offered RPM to patients with uncontrolled office BP and assisted with initiation. At two clinics (39 PCPs), RPM was at PCPs' discretion. Twenty clinics continued usual care. Main measures were controlling high BP (<140/90 mm Hg), last office systolic blood pressure (SBP), and proportion with antihypertensive medication intensification., Results: Among the Medicare cohorts with uncontrolled hypertension, 16.7% (39/234) of patients from the care coordination clinics were prescribed RPM versus <1% (4/600) at noncare coordination sites. RPM-enrolled care coordination group patients had higher baseline SBP than the noncare coordination group (148.8 vs. 140.0 mm Hg). After 6 months, in the uncontrolled hypertension cohorts the prevalences of controlling high BP were 32.5% (RPM with care coordination), 30.7 % (RPM alone), and 27.1% (usual care); multivariable adjusted odds ratios (95% confidence interval) were 1.63 (1.12-2.39; p  = 0.011) and 1.29 (0.98-1.69; p  = 0.068) compared with usual care, respectively., Conclusion: Care coordination facilitated RPM enrollment among poorly controlled hypertension patients and may improve hypertension control in primary care among Medicare patients., Competing Interests: The Northwestern University and the Northwestern Medicine investigators (L.C.P., L.A., Y.P., J.Y.L., S.D.P., J.C., T.C., K.P.) reported receiving grant funding from Omron Healthcare Co. Ltd during the conduct of the study. S.D.P. reported receiving an honorarium for speaking from Omron Healthcare Co. Ltd. J.L. reported receiving salary and reimbursement for travel from Omron Healthcare Co. Ltd. H.S. reported receiving salary and reimbursement for travel from Omron Healthcare Co. Ltd. An employee from Downshift Consulting (C.J.D.) participated and provided input into study meetings and revision of the manuscript. No other disclosures were reported. S.D.P. reported other from Omron Healthcare Co. Ltd, during the conduct of the study; personal fees and other from Omron Healthcare Co. Ltd, personal fees from RAND Corporation, personal fees from the National Committee for Quality Assurance, outside the submitted work; and S.D.P. has served as Chair of the Cardiovascular Measurement Advisory Panel for the National Committee for Quality Assurance., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Objective: Electronic health record (EHR) data are a valuable resource for population health research but lack critical information such as relationships between individuals. Emergency contacts in EHRs can be used to link family members, creating a population that is more representative of a community than traditional family cohorts., Materials and Methods: We revised a published algorithm: relationship inference from the electronic health record (RIFTEHR). Our version, Pythonic RIFTEHR (P-RIFTEHR), identifies a patient's emergency contacts, matches them to existing patients (when available) using network graphs, checks for conflicts, and infers new relationships. P-RIFTEHR was run on December 15, 2021 in the Northwestern Medicine Electronic Data Warehouse (NMEDW) on approximately 2.95 million individuals and was validated using the existing link between children born at NM hospitals and their mothers. As proof-of-concept, we modeled the association between parent and child obesity using logistic regression., Results: The P-RIFTEHR algorithm matched 1 157 454 individuals in 448 278 families. The median family size was 2, the largest was 32 persons, and 247 families spanned 4 generations or more. Validation of the mother-child pairs resulted in 95.1% sensitivity. Children were 2 times more likely to be obese if a parent is obese (OR: 2.30; 95% CI, 2.23-2.37)., Conclusion: P-RIFTEHR can identify familiar relationships in a large, diverse population in an integrated health system. Estimates of parent-child inheritability of obesity using family structures identified by the algorithm were consistent with previously published estimates from traditional cohort studies., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

A prospective, one-armed, safety non-inferiority trial with historical controls was performed at a single-center, quaternary, children's hospital. Inclusion criteria were children aged 3 months-18 years after pediatric cardiac surgery resulting in a two-ventricle repair between 7/2020 and 7/2021. Eligible patients were compared with patients from a 5-year historical period (selected using a database search). The intervention was that "regular risk" patients received no diuretics and pre-specified "high risk" patients received 5 days of twice per day furosemide at discharge. 61 Subjects received the intervention. None were readmitted for pleural effusions, though 1 subject was treated for a symptomatic pleural effusion with outpatient furosemide. The study was halted after an interim analysis demonstrated that 4 subjects were readmitted with pericardial effusion during the study period versus 2 during the historical control (2.9% versus 0.2%, P = 0.003). We found no evidence that limited post-discharge diuretics results in an increase in readmissions for pleural effusions. This conclusion is limited as not enough subjects were enrolled to definitively show that this strategy is not inferior to the historical practice. There was a statistically significant increase in readmissions for pericardial effusions after implementation of this study protocol which can lead to serious complications and requires further study before conclusions can be drawn regarding optimal diuretic regimens., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: Statin use prior to hospitalization for Coronavirus Disease 2019 (COVID-19) is hypothesized to improve inpatient outcomes including mortality, but prior findings from large observational studies have been inconsistent, due in part to confounding. Recent advances in statistics, including incorporation of machine learning techniques into augmented inverse probability weighting with targeted maximum likelihood estimation, address baseline covariate imbalance while maximizing statistical efficiency., Objective: To estimate the association of antecedent statin use with progression to severe inpatient outcomes among patients admitted for COVD-19., Design, Setting and Participants: We retrospectively analyzed electronic health records (EHR) from individuals ≥ 40-years-old who were admitted between March 2020 and September 2022 for ≥ 24 h and tested positive for SARS-CoV-2 infection in the 30 days before to 7 days after admission., Exposure: Antecedent statin use-statin prescription ≥ 30 days prior to COVID-19 admission., Main Outcome: Composite end point of in-hospital death, intubation, and intensive care unit (ICU) admission., Results: Of 15,524 eligible COVID-19 patients, 4412 (20%) were antecedent statin users. Compared with non-users, statin users were older (72.9 (SD: 12.6) versus 65.6 (SD: 14.5) years) and more likely to be male (54% vs. 51%), White (76% vs. 71%), and have ≥ 1 medical comorbidity (99% vs. 86%). Unadjusted analysis demonstrated that a lower proportion of antecedent users experienced the composite outcome (14.8% vs 19.3%), ICU admission (13.9% vs 18.3%), intubation (5.1% vs 8.3%) and inpatient deaths (4.4% vs 5.2%) compared with non-users. Risk differences adjusted for labs and demographics were estimated using augmented inverse probability weighting with targeted maximum likelihood estimation using Super Learner. Statin users still had lower rates of the composite outcome (adjusted risk difference: - 3.4%; 95% CI: - 4.6% to - 2.1%), ICU admissions (- 3.3%; - 4.5% to - 2.1%), and intubation (- 1.9%; - 2.8% to - 1.0%) but comparable inpatient deaths (0.6%; - 1.3% to 0.1%)., Conclusions and Relevance: After controlling for confounding using doubly robust methods, antecedent statin use was associated with minimally lower risk of severe COVID-19-related outcomes, ICU admission and intubation, however, we were not able to corroborate a statin-associated mortality benefit., (© 2023. The Author(s).)

Background: Mindfulness-based interventions have been shown to improve psychological outcomes including stress, anxiety, and depression in general population studies. However, effectiveness has not been sufficiently examined in racially and ethnically diverse community-based settings. We will evaluate the effectiveness and implementation of a mindfulness-based intervention on depressive symptoms among predominantly Black women at a Federally Qualified Health Center in a metropolitan city., Methods: In this 2-armed, stratified, individually randomized group-treated controlled trial, 274 English-speaking participants with depressive symptoms ages 18-65 years old will be randomly assigned to (1) eight weekly, 90-min group sessions of a mindfulness-based intervention (M-Body), or (2) enhanced usual care. Exclusion criteria include suicidal ideation in 30 days prior to enrollment and regular (>4x/week) meditation practice. Study metrics will be assessed at baseline and 2, 4, and 6 months after baseline, through clinical interviews, self-report surveys, and stress biomarker data including blood pressure, heart rate, and stress related biomarkers. The primary study outcome is depressive symptom score after 6 months., Discussion: If M-Body is found to be an effective intervention for adults with depressive symptoms, this accessible, scalable treatment will widely increase access to mental health treatment in underserved, racial/ethnic minority communities., Trial Registration: ClinicalTrials.gov NCT03620721. Registered on 8 August 2018., (© 2023. The Author(s).)

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP1-RAs) reduce cardiovascular events and mortality in patients with type 2 diabetes mellitus (T2DM). We sought to describe trends in prescribing for SGLT2is and GLP1-RAs in diverse care settings, including (1) the outpatient clinics of a midwestern integrated health system and (2) small- and medium-sized community-based primary care practices and health centers in 3 midwestern states. We included adults with T2DM and ≥1 outpatient clinic visit. The outcomes of interest were annual active prescription rates for SGLT2is and GLP1-RAs (separately). In the integrated health system, 22,672 patients met the case definition of T2DM. From 2013 to 2019, the overall prescription rate for SGLT2is increased from 1% to 15% (absolute difference [AD] 14%, 95% confidence interval [CI] 13% to 15%, p <0.01). The GLP1-RA prescription rate was stable at 10% (AD 0%, 95% CI -1% to 1%, p = 0.9). In community-based primary care practices, 43,340 patients met the case definition of T2DM. From 2013 to 2017, the SGLT2i prescription rate increased from 3% to 7% (AD 4%, 95% CI 3% to 6%, p <0.01), whereas the GLP1-RA prescription rate was stable at 2% to 3% (AD 1%, 95% CI -1 to 1%, p = 0.40). In a fully adjusted regression model, non-Hispanic Black patients had lower odds of SGLT2i or GLP1-RA prescription (odds ratio 0.56, 95% CI 0.34 to 0.89, p = 0.016). In conclusion, the increase in prescription rates was greater for SGLT2is than for GLP1-RAs in patients with T2DM in a large integrated medical center and community primary care practices. Overall, prescription rates for eligible patients were low, and racial disparities were observed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Since 2019, the Centers for Medicare and Medicaid Services covers remote physiologic monitoring (RPM) for blood pressure (BP) per hypertension diagnosis and treatment guidelines. Here, we integrated Omron VitalSight RPM into the health system's electronic health record to transmit BP and pulse without manual entry, assessed feasibility, and used pragmatic prospective matched cohort studies to assess initial effects in (1) uncontrolled (last two office BP ≥140/90 mmHg) and (2) general (diagnosed hypertension or last office BP ≥140/90 mmHg) hypertension patient populations., Materials and Methods: Seventeen clinicians at two internal medicine practices were oriented. Eligible patients were aged 65-85 years had Medicare insurance with ≥1 office visit in the previous year. We prospectively identified matched controls (age, sex, BP, and number of office visits in previous year) from other primary care practices within the health system and estimated the association between RPM availability (clinic-level) and patient BP outcomes after 6 months. ClinicalTrials.gov: NCT04604925., Results: Feasibility. Uptake was low at pilot clinics: 10 physicians prescribed RPM to 118 patients during the 6-month pilot. This included 7% (14/207) of the prespecified uncontrolled hypertension cohort and 3.3% (78/2356) of the general hypertension cohort. Surveyed clinicians ( n  = 4) reported changing their patients' medical treatment in response to RPM BPs, although they recommended having a dedicated RN or LPN to review BP readings. Effectiveness. At 6 months, BP control was greater at pilot practices than among matched controls (uncontrolled: 31.4% vs 22.8%; P  = .007; general: 64.0% vs 59.7%; P  < .001). Systolic BP at last office visit did not differ (mean [SD] 146.0 [15.7] vs 147.1 [15.6]; P  = .48) in the uncontrolled population, and was lower in the general population (131.8 [15.7] vs 132.8 [15.9]; P  = .04).The frequency of antihypertensive medication changes was similar in both groups (uncontrolled P  = .986; general P  = .218)., Discussion and Conclusions: Uptake notwithstanding, RPM may have improved BP control. A potential mechanism is increased physician awareness of and attention to uncontrolled hypertension. Barriers to RPM use among physicians require further study., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Background: Social and psychosocial factors are associated with cardiovascular health (CVH). Our objective was to examine the contributions of individual-level social and psychosocial factors to racial and ethnic differences in population CVH in the NHANES (National Health and Nutrition Examination Surveys) 2011 to 2018, to inform strategies to mitigate CVH inequities., Methods: In NHANES participants ages ≥20 years, Kitagawa-Blinder-Oaxaca decomposition estimated the statistical contribution of individual-level factors (education, income, food security, marital status, health insurance, place of birth, depression) to racial and ethnic differences in population mean CVH score (range, 0-14, accounting for diet, smoking, physical activity, body mass index, blood pressure, cholesterol, blood glucose) among Hispanic, non-Hispanic Asian, or non-Hispanic Black adults compared with non-Hispanic White adults., Results: Among 16 172 participants (representing 255 million US adults), 24% were Hispanic, 12% non-Hispanic Asian, 23% non-Hispanic Black, and 41% non-Hispanic White. Among men, mean (SE) CVH score was 7.45 (2.3) in Hispanic, 8.71 (2.2) in non-Hispanic Asian, 7.48 (2.4) in non-Hispanic Black, and 7.58 (2.3) in non-Hispanic White adults. In Kitagawa-Blinder-Oaxaca decomposition, education explained the largest component of CVH differences among men (if distribution of education were similar to non-Hispanic White participants, CVH score would be 0.36 [0.04] points higher in Hispanic, 0.24 [0.04] points lower in non-Hispanic Asian, and 0.23 [0.03] points higher in non-Hispanic Black participants; P <0.05). Among women, mean (SE) CVH score was 8.03 (2.4) in Hispanic, 9.34 (2.1) in non-Hispanic Asian, 7.43 (2.3) in non-Hispanic Black, and 8.00 (2.5) in non-Hispanic White adults. Education explained the largest component of CVH difference in non-Hispanic Black women (if distribution of education were similar to non-Hispanic White participants, CVH score would be 0.17 [0.03] points higher in non-Hispanic Black participants; P <0.05). Place of birth (born in the United States versus born outside the United States) explained the largest component of CVH difference in Hispanic and non-Hispanic Asian women (if distribution of place of birth were similar to non-Hispanic White participants, CVH score would be 0.36 [0.07] points lower and 0.49 [0.16] points lower, respectively; P <0.05)., Conclusions: Education and place of birth confer the largest statistical contributions to the racial and ethnic differences in mean CVH score among US adults.

Background: The rate of gestational diabetes mellitus has increased over the past decade. An age, period, and cohort epidemiologic analysis can be used to understand how and why disease trends have changed over time., Objective: This study aimed to estimate the associations of age (at delivery), period (delivery year), and cohort (birth year) of the pregnant individual with trends in the incidence of gestational diabetes mellitus in the United States., Study Design: We conducted an age, period, and cohort analysis of nulliparous pregnant adults aged 18 to 44 years with singleton live births from the National Vital Statistics System from 2011 to 2019. Generalized linear mixed models were used to calculate the adjusted rate ratios for the incidence of gestational diabetes mellitus for each 3-year maternal age span, period, and cohort group compared with the reference group for each. We repeated the analyses with stratification according to self-reported racial and ethnic group (non-Hispanic Asian-Pacific Islander, non-Hispanic Black, Hispanic, and non-Hispanic White) because of differences in the incidence of and risk factors for gestational diabetes mellitus by race and ethnicity., Results: Among 11,897,766 pregnant individuals, 5.2% had gestational diabetes mellitus. The incidence of gestational diabetes mellitus was higher with increasing 3-year maternal age span, among those in the more recent delivery period, and among the younger birth cohort. For example, individuals aged 42 to 44 years at delivery had a 5-fold higher risk for gestational diabetes mellitus than those aged 18 to 20 years (adjusted rate ratio, 5.57; 95% confidence interval, 5.43-5.72) after adjusting for cohort and period. Individuals who delivered between 2017 and 2019 were at higher risk for gestational diabetes mellitus than those who delivered between 2011 and 2013 (adjusted rate ratio, 1.24; 95% confidence interval, 1.23-1.25) after adjusting for age and cohort. Individuals born between 1999 and 2001 had a 3-fold higher risk for gestational diabetes mellitus than those born between 1969 and 1971 (adjusted rate ratio, 3.12; 95% confidence interval, 2.87-3.39) after adjusting for age and period. Similar age, period, and cohort effects were observed for the assessed racial and ethnic groups, with the greatest period effects observed among Asian and Pacific Islander individuals., Conclusion: Period and birth cohort effects have contributed to the rising incidence of gestational diabetes mellitus in the United States from 2011 to 2019., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Pediatric cardiac extracorporeal membrane oxygenation (ECMO) patients have high mortality rates. The purpose of our study was to develop and validate the Pediatric Survival After Veno-arterial ECMO (Pedi-SAVE) score for predicting survival at hospital discharge after pediatric cardiac veno-arterial (VA) ECMO. We used data for pediatric cardiac VA-ECMO patients from the Extracorporeal Life Support Organization registry (1/1/2001-12/31/2015). Development and validation cohorts were created using 2:1 random sampling. Predictors of survival to develop pre- and postcannulation models were selected using multivariable logistic regression and random forest models. ß-coefficients were standardized to create the Pedi-SAVE score. Of 10,091 pediatric cardiac VA-ECMO patients, 4,996 (50%) survived to hospital discharge. Pre- and postcannulation Pedi-SAVE scores predicted that the lowest risk patients have a 65% and 74% chance of survival at hospital discharge, respectively, compared to 33% and 22% in the highest risk patients. In the validation cohort, pre- and postcannulation Pedi-SAVE scores had c-statistics of 0.64 and 0.71, respectively. Precannulation factors associated with survival included: nonsingle ventricle congenital heart disease, older age, white race, lower STAT mortality category, higher pH, not requiring acid-buffer administration, <2 cardiac procedures, and indication for VA-ECMO other than failure to wean from cardiopulmonary bypass. Postcannulation, additional factors associated with survival included: lower ECMO pump flows at 24 hours and lack of complications. The Pedi-SAVE score is a novel validated tool to predict survival at hospital discharge for pediatric cardiac VA-ECMO patients, and is an important advancement in risk adjustment and benchmarking for this population., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2022.)

Purpose: We hypothesized that a pain management prescribing tool embedded in the electronic health record system of a multihospital health care system would decrease prescription opioids for postoperative pain by hand, orthopedic, plastic, and spine surgeons., Methods: A prescribing tool for postoperative pain was designed for hand, orthopedic, plastic, and spine surgeons and implemented into electronic discharge order sets in a 10-hospital health care system. Stakeholders were educated on tool use in person and/or by email on 2 occasions. A dashboard was created to monitor opioid pill quantities and morphine milligram equivalents (MMEs) prescribed. Overall compliance with the suggested opioid amounts was assessed for 20 months after tool implementation. A subgroup of 6 hand surgeons, one of whom was instrumental in designing the tool, were evaluated for MMEs prescribed, opioid refills, patient emergency room visits, and patient readmissions within 30 days after discharge. Comparisons in this subgroup were made from 12 months before to 15 months after tool implementation., Results: The mean system-wide compliance with the suggested opioid pill quantities and MMEs prescribed in all 4 specialties improved by less than 5%. In the subgroup of hand surgeons, 5 of whom championed tool use, prescribed MMEs decreased by 10% during each of the 4 quarters before launching the tool and contracted an additional 26% in the first quarter after tool implementation. Opioid refills held steady at 5%, and there were no emergency room visits or readmissions within 30 days after discharge in this patient subgroup., Conclusions: The prescribing tool had a negligible impact on system-wide compliance with suggested prescription opioid pill quantities and MMEs. In a small group of surgeons who championed the use of the tool, there was a significant and sustained decline in MMEs prescribed without adversely impacting patient refills, emergency room visits, or readmissions., Clinical Relevance: An electronic prescribing tool to assist surgeons in lowering opioid prescription pill quantities and MMEs may have a negligible impact on prescribing behavior in a multihospital health care system., (Copyright © 2022. Published by Elsevier Inc.)

Importance: Hypertensive disorders of pregnancy are leading causes of morbidity and mortality among pregnant individuals as well as newborns, with increasing incidence during the past decade. Understanding the individual associations of advancing age of pregnant individuals at delivery, more recent delivery year (period), and more recent birth year of pregnant individuals (cohort) with adverse trends in hypertensive disorders of pregnancy could help guide public health efforts to improve the health of pregnant individuals., Objective: To clarify the independent associations of delivery year and birth year of pregnant individuals, independent of age of pregnant individuals, with incident rates of hypertensive disorders of pregnancy., Design, Setting, and Participants: This serial cross-sectional study of 38 141 561 nulliparous individuals aged 15 to 44 years with a singleton, live birth used 1995-2019 natality data from the National Vital Statistics System., Exposures: Year of delivery (period) and birth year (cohort) of pregnant individuals., Main Outcomes and Measures: Rates of incident hypertensive disorders of pregnancy, defined as gestational hypertension, preeclampsia, or eclampsia, recorded on birth certificates. Generalized linear mixed models were used to calculate adjusted rate ratios (aRRs) comparing the incidence of hypertensive disorders of pregnancy in each delivery period (adjusted for age and cohort) and birth cohort (adjusted for age and period) with the baseline group as the reference for each. Analyses were additionally stratified by the self-reported racial and ethnic group of pregnant individuals., Results: Of 38 141 561 individuals, 20.2% were Hispanic, 0.8% were non-Hispanic American Indian or Alaska Native, 6.5% were non-Hispanic Asian or Pacific Islander, 13.9% were non-Hispanic Black, and 57.8% were non-Hispanic White. Among pregnant individuals who delivered in 2015 to 2019 compared with 1995 to 1999, the aRR for the incidence of hypertensive disorders of pregnancy was 1.59 (95% CI, 1.57-1.62), adjusted for age and cohort. Among pregnant individuals born in 1996 to 2004 compared with 1951 to 1959, the aRR for the incidence of hypertensive disorders of pregnancy was 2.61 (95% CI, 2.41-2.84), adjusted for age and period. The incidence was higher among self-identified non-Hispanic Black individuals in each birth cohort, with similar relative changes for period (aRR, 1.76 [95% CI, 1.70-1.81]) and cohort (aRR, 3.26 [95% CI, 2.72-3.91]) compared with non-Hispanic White individuals (period: aRR, 1.60 [95% CI, 1.57-1.63]; cohort: aRR, 2.53 [95% CI, 2.26-2.83])., Conclusions and Relevance: This cross-sectional study suggests that more recent birth cohorts of pregnant individuals have experienced a doubling of rates of hypertensive disorders of pregnancy, even after adjustment for age and delivery period. Substantial racial and ethnic disparities persisted across generations.

Background: Racial differences in cardiovascular disease (CVD) are likely related to differences in clinical and social factors. The relative contributions of these factors to Black-White differences in premature CVD have not been investigated., Methods: In Black and White adults aged 18 to 30 years at baseline in the CARDIA study (Coronary Artery Risk Development in Young Adults), the associations of clinical, lifestyle, depression, socioeconomic, and neighborhood factors across young adulthood with racial differences in incident premature CVD were evaluated in sex-stratified, multivariable-adjusted Cox proportional hazards models using multiply imputed data assuming missing at random. Percent reduction in the β estimate (log-hazard ratio [HR]) for race quantified the contribution of each factor group to racial differences in incident CVD., Results: Among 2785 Black and 2327 White participants followed for a median 33.9 years (25th-75th percentile, 33.7-34.0), Black (versus White) adults had a higher risk of incident premature CVD (Black women: HR, 2.44 [95% CI, 1.71-3.49], Black men: HR, 1.59 [1.20-2.10] adjusted for age and center). Racial differences were not statistically significant after full adjustment (Black women: HR, 0.91 [0.55-1.52], Black men: HR 1.02 [0.70-1.49]). In women, the largest magnitude percent reduction in the β estimate for race occurred with adjustment for clinical (87%), neighborhood (32%), and socioeconomic (23%) factors. In men, the largest magnitude percent reduction in the β estimate for race occurred with an adjustment for clinical (64%), socioeconomic (50%), and lifestyle (34%) factors., Conclusions: In CARDIA, the significantly higher risk for premature CVD in Black versus White adults was statistically explained by adjustment for antecedent multilevel factors. The largest contributions to racial differences were from clinical and neighborhood factors in women, and clinical and socioeconomic factors in men.

Background: Cardiac magnetic resonance (CMR) provides tissue characterization and structural and functional data. CMR has high sensitivity and specificity for myocarditis in adults and children. The relationship between pediatric CMR use, cost, and clinical outcome has not been studied., Objectives: This work aims to describe temporal trends in CMR imaging for pediatric myocarditis and examine associations between CMR use, hospital cost, and outcomes., Methods: A retrospective cohort study of all inpatients <21 years of age with a diagnosis of myocarditis reported to the Pediatric Health Information System (2004-2019) was performed. Trends in CMR use were examined. A propensity-matched subcohort using center and patient level variables was used to assess whether outcomes differed by CMR use., Results: A total of 4,195 children with myocarditis from 47 hospitals were identified. The median age was 11.5 years (IQR: 1.5-16.0 years) and 2,617 (62%) were male. CMR was used in 23% and mortality occurred in 6%. CMR use during hospitalization increased from 2% in 2004 to 37% in 2019 (odds ratio [OR]: 1.19 [95% CI: 1.17-1.21]). After propensity score matching, CMR use was associated with higher median cost (+$5,340 [95% CI: +$1,739 to +$9,936]) and similar median length of stay (0 days [95% CI: -1 to +1 days]). Using quantile regression, CMR was associated with lower 90th percentile cost (-$77,200 [95% CI: -$127,373 to -$31,339]). More children receiving CMR were discharged alive in the first 30 days after admission (OR: 1.89 days [95% CI: 1.28-2.29]). Within the propensity matched cohort, <10 of 790 CMR recipients died compared to 42 of 790 in the non-CMR group., Conclusions: CMR use in children with myocarditis has increased over the past 15 years. CMR use is associated with higher cost of hospitalization and similar length of stay for most children but lower cost among the sickest children. CMR use in specific patients may improve clinical outcomes at a lower cost., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Geographic heterogeneity in COVID-19 outcomes in the United States is well-documented and has been linked with factors at the county level, including sociodemographic and health factors. Whether an integrated measure of place-based risk can classify counties at high risk for COVID-19 outcomes is not known., Methods: We conducted an ecological nationwide analysis of 2,701 US counties from 1/21/20 to 2/17/21. County-level characteristics across multiple domains, including demographic, socioeconomic, healthcare access, physical environment, and health factor prevalence were harmonized and linked from a variety of sources. We performed latent class analysis to identify distinct groups of counties based on multiple sociodemographic, health, and environmental domains and examined the association with COVID-19 cases and deaths per 100,000 population., Results: Analysis of 25.9 million COVID-19 cases and 481,238 COVID-19 deaths revealed large between-county differences with widespread geographic dispersion, with the gap in cumulative cases and death rates between counties in the 90 th and 10 th percentile of 6,581 and 291 per 100,000, respectively. Counties from rural areas tended to cluster together compared with urban areas and were further stratified by social determinants of health factors that reflected high and low social vulnerability. Highest rates of cumulative COVID-19 cases (9,557 [2,520]) and deaths (210 [97]) per 100,000 occurred in the cluster comprised of rural disadvantaged counties., Conclusions: County-level COVID-19 cases and deaths had substantial disparities with heterogeneous geographic spread across the US. The approach to county-level risk characterization used in this study has the potential to provide novel insights into communicable disease patterns and disparities at the local level., (© 2022. The Author(s).)

Background: Overtesting and treatment of older patients is common and may lead to harms. The Choosing Wisely campaign has provided recommendations to reduce overtesting and overtreatment of older adults. Behavioral economics-informed interventions embedded within the electronic health record (EHR) have been shown to reduce overuse in several areas. Our objective is to conduct a parallel arm, pragmatic cluster-randomized trial to evaluate the effectiveness of behavioral-economics-informed clinical decision support (CDS) interventions previously piloted in primary care clinics and designed to reduce overtesting and overtreatment in older adults., Methods/design: This trial has two parallel arms: clinician education alone vs. clinician education plus behavioral-economics-informed CDS. There are three co-primary outcomes for this trial: (1) prostate-specific antigen (PSA) screening in older men, (2) urine testing for non-specific reasons in older women, and (3) overtreatment of diabetes in older adults. All eligible primary care clinics from a large regional health system were randomized using a modified constrained randomization process and their attributed clinicians were included. Clinicians were recruited to complete a survey and educational module. We randomized 60 primary care clinics with 374 primary care clinicians and achieved adequate balance between the study arms for prespecified constrained variables. Baseline annual overuse rates for the three co-primary outcomes were 25%, 23%, and 17% for the PSA, urine, and diabetes measures, respectively., Discussion: This trial is evaluating behavioral-economics-informed EHR-embedded interventions to reduce overuse of specific tests and treatments for older adults. The study will evaluate the effectiveness and safety of these interventions., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: The rates of gestational diabetes mellitus are increasing in parallel with the rates of overweight and obesity. This analysis examines nationwide trends in the population-attributable fraction for gestational diabetes mellitus associated with prepregnancy overweight and obesity., Methods: A serial, cross-sectional study was performed using U.S. population-based birth data files maintained by the National Center for Health Statistics between 2011 and 2019. Live singleton births to nulliparous women aged 15-44 years were included, and all analyses were stratified by race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, non-Hispanic Asian). Prevalences of prepregnancy overweight (25.0-29.9 kg/m 2 and 23.0-27.4 kg/m 2 ) and obesity (≥30.0 kg/m 2 and ≥27.5 kg/m 2 ) based on standard and Asian-specific BMI categories, respectively, were quantified. Logistic regression estimated the adjusted associations between prepregnancy overweight and obesity and gestational diabetes mellitus, with normal weight (18.0-24.9 kg/m 2 and 18.0-22.9 kg/m 2 ) as the ref. Annual population-attributable fractions for gestational diabetes mellitus associated with prepregnancy overweight and obesity were calculated, which account for both the prevalence of the risk factor and the associated risk of gestational diabetes mellitus., Results: Among 11,950,881 included women, the mean maternal age was 26.3 years. From 2011 to 2019, the population-attributable fractions for gestational diabetes mellitus associated with overweight were stable (Hispanic: 12.0%-11.3%, non-Hispanic Asian: 12.1%-11.6%, p≥0.20) or decreased (non-Hispanic White: 10.8%-9.4%, non-Hispanic Black: 12.3%-9.2%, p<0.002); the population-attributable fractions for gestational diabetes mellitus associated with obesity were stable (non-Hispanic Black: 36.3%-37.9%, p=0.11) or increased (non-Hispanic White: 30.9%-33.3%, Hispanic: 27.2%-33.3%, non-Hispanic Asian 12.2%-15.4%, p<0.001)., Conclusions: The population-attributable fractions for gestational diabetes mellitus associated with obesity largely increased in the past decade, underscoring the importance of optimizing weight before pregnancy., (Copyright © 2021 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the effectiveness of netarsudil in combination with other ocular hypotensive agents in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT)., Design: Retrospective cohort study., Participants: All patients with OAG or OHT with netarsudil added to a regimen of at least 1 other ocular hypotensive agent between March 2018 and March 2019., Methods: Subjects with at least 2 baseline intraocular pressure (IOP) measurements on the same medication regimen before initiation of netarsudil were included. Subjects were excluded if they experienced other changes in their ocular hypotensive medication regimen., Main Outcome Measures: Change in IOP after initiation of netarsudil was assessed using linear mixed-effect models. Kaplan-Meier survival analysis was used to evaluate the time to discontinuation of netarsudil for any reason., Results: Netarsudil was prescribed for 191 eyes of 138 patients. All of these subjects were included in the analysis of adverse effects. Twelve subjects discontinued netarsudil before the first follow-up visit because of adverse effects, leaving 175 eyes of 126 patients with at least 1 follow-up visit while using netarsudil included in the effectiveness analysis. The mean baseline IOP ± standard deviation was 17.1 ± 5.2 mmHg on a median of 2 ocular hypotensive medications. Including all observations on the same medication regimen after the addition of netarsudil, the mean IOP was 15.0 ± 4.5 mmHg, with a mean reduction of 2.2 mmHg (P < 0.001). A reduction in IOP was observed in eyes on 1 (2.0 mmHg, P < 0.001), 2 (1.0 mmHg, P = 0.12), 3 (3.0 mmHg, P < 0.001), and 4 (2.9 mmHg, P = 0.002) medications at baseline. A sustained ≥ 20% IOP reduction was observed in 16.2% of 123 eyes with at least 2 observations on treatment with netarsudil. Of the 138 subjects who were treated with netarsudil, 26.8% discontinued it because of adverse effects. The median time to discontinuation of netarsudil for any reason was 88 days., Conclusions: This study demonstrates a modest reduction in IOP is achievable with netarsudil in patients with OAG or OHT who are taking as many as 4 ocular hypotensive medications. The incidence of discontinuation due to adverse effects or inadequate efficacy was high., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background Cardiovascular disease mortality related to heart failure (HF) is rising in the United States. It is unknown whether trends in HF mortality are consistent across geographic areas and are associated with state-level variation in cardiovascular health (CVH). The goal of the present study was to assess regional and state-level trends in cardiovascular disease mortality related to HF and their association with variation in state-level CVH. Methods and Results Age-adjusted mortality rates (AAMR) per 100 000 attributable to HF were ascertained using the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research from 1999 to 2017. CVH at the state-level was quantified using the Behavioral Risk Factor Surveillance System. Linear regression was used to assess temporal trends in HF AAMR were examined by census region and state and to examine the association between state-level CVH and HF AAMR. AAMR attributable to HF declined from 1999 to 2011 and increased between 2011 and 2017 across all census regions. Annual increases after 2011 were greatest in the Midwest (β=1.14 [95% CI, 0.75, 1.53]) and South (β=0.96 [0.66, 1.26]). States in the South and Midwest consistently had the highest HF AAMR in all time periods, with Mississippi having the highest AAMR (109.6 [104.5, 114.6] in 2017). Within race‒sex groups, consistent geographic patterns were observed. The variability in HF AAMR was associated with state-level CVH ( P <0.001). Conclusions Wide geographic variation exists in HF mortality, with the highest rates and greatest recent increases observed in the South and Midwest. Higher levels of poor CVH in these states suggest the potential for interventions to promote CVH and reduce the burden of HF.

Objective: Excessive childhood adiposity is a risk factor for adverse metabolic health. The objective was to investigate associations of newborn body composition and cord C-peptide with childhood anthropometrics and explore whether these newborn measures mediate associations of maternal midpregnancy glucose and BMI with childhood adiposity., Research Design and Methods: Data on mother/offspring pairs ( N = 4,832) from the epidemiological Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and HAPO Follow-up Study (HAPO FUS) were analyzed. Linear regression was used to study associations between newborn and childhood anthropometrics. Structural equation modeling was used to explore newborn anthropometric measures as potential mediators of the associations of maternal BMI and glucose during pregnancy with childhood anthropometric outcomes., Results: In models including maternal glucose and BMI adjustments, newborn adiposity as measured by the sum of skinfolds was associated with child outcomes (adjusted mean difference, 95% CI, P value) BMI (0.26, 0.12-0.39, <0.001), BMI z -score (0.072, 0.033-0.11, <0.001), fat mass (kg) (0.51, 0.26-0.76, <0.001), percentage of body fat (0.61, 0.27-0.95, <0.001), and sum of skinfolds (mm) (1.14, 0.43-1.86, 0.0017). Structural equation models demonstrated significant mediation by newborn sum of skinfolds and cord C-peptide of maternal BMI effects on childhood BMI (proportion of total effect 2.5% and 1%, respectively), fat mass (3.1%, 1.2%), percentage of body fat (3.6%, 1.8%), and sum of skinfolds (2.9%, 1.8%), and significant mediation by newborn sum of skinfolds and cord C-peptide of maternal glucose effects on child fat mass (proportion of total association 22.0% and 21.0%, respectively), percentage of body fat (15.0%, 18.0%), and sum of skinfolds (15.0%, 20.0%)., Conclusions: Newborn adiposity is independently associated with childhood adiposity and, along with fetal hyperinsulinemia, mediates, in part, associations of maternal glucose and BMI with childhood adiposity., (© 2021 by the American Diabetes Association.)

Background: Adults in rural counties in the United States (US) experience higher rates broadly of cardiovascular disease (CVD) compared with adults in urban counties. Mortality rates specifically due to heart failure (HF) have increased since 2011, but estimates of heterogeneity at the county-level in HF-related mortality have not been produced. The objectives of this study were 1) to quantify nationwide trends by rural-urban designation and 2) examine county-level factors associated with rural-urban differences in HF-related mortality rates., Methods and Findings: We queried CDC WONDER to identify HF deaths between 2011-2018 defined as CVD (I00-78) as the underlying cause of death and HF (I50) as a contributing cause of death. First, we calculated national age-adjusted mortality rates (AAMR) and examined trends stratified by rural-urban status (defined using 2013 NCHS Urban-Rural Classification Scheme), age (35-64 and 65-84 years), and race-sex subgroups per year. Second, we combined all deaths from 2011-2018 and estimated incidence rate ratios (IRR) in HF-related mortality for rural versus urban counties using multivariable negative binomial regression models with adjustment for demographic and socioeconomic characteristics, risk factor prevalence, and physician density. Between 2011-2018, 162,314 and 580,305 HF-related deaths occurred in rural and urban counties, respectively. AAMRs were consistently higher for residents in rural compared with urban counties (73.2 [95% CI: 72.2-74.2] vs. 57.2 [56.8-57.6] in 2018, respectively). The highest AAMR was observed in rural Black men (131.1 [123.3-138.9] in 2018) with greatest increases in HF-related mortality in those 35-64 years (+6.1%/year). The rural-urban IRR persisted among both younger (1.10 [1.04-1.16]) and older adults (1.04 [1.02-1.07]) after adjustment for county-level factors. Main limitations included lack of individual-level data and county dropout due to low event rates (<20)., Conclusions: Differences in county-level factors may account for a significant amount of the observed variation in HF-related mortality between rural and urban counties. Efforts to reduce the rural-urban disparity in HF-related mortality rates will likely require diverse public health and clinical interventions targeting the underlying causes of this disparity., Competing Interests: The authors have declared that no competing interests exist.

Epidemiological studies have highlighted the disparate impact of coronavirus disease 2019 (COVID-19) on racial and ethnic minority and socioeconomically disadvantaged populations, but data at the neighborhood-level is sparse. The objective of this study was to investigate the disparate impact of COVID-19 on disadvantaged neighborhoods and racial/ethnic minorities in Chicago, Illinois. Using data from the Cook County Medical Examiner, we conducted a neighborhood-level analysis of COVID-19 decedents in Chicago and quantified age-standardized years of potential life lost (YPLL) due to COVID-19 among demographic subgroups and neighborhoods with geospatial clustering of high and low rates of COVID-19 mortality. We show that age-standardized YPLL was markedly higher among the non-Hispanic (NH) Black (559 years per 100,000 population) and the Hispanic (811) compared with NH white decedents (312). We demonstrate that geomapping using residential address data at the individual-level identifies hot-spots of COVID-19 mortality in neighborhoods on the Northeast, West, and South areas of Chicago that reflect a legacy of residential segregation and persistence of inequality in education, income, and access to healthcare. Our results may contribute to ongoing public health and community-engaged efforts to prevent the spread of infection and mitigate the disproportionate loss of life among these communities due to COVID-19 as well as highlight the urgent need to broadly target neighborhood disadvantage as a cause of pervasive racial inequalities in life and health., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background Given the increasing prevalence of diabetes mellitus (DM) in the United States, estimating the effects of population-level increases in obesity on incident DM has substantial implications for public health policy. Therefore, we determined the population attributable fraction, which accounts for the prevalence and excess risk of DM associated with obesity. Methods and Results We included non-Hispanic White, non-Hispanic Black, and Mexican American participants without DM at baseline from MESA (Multi-Ethnic Study of Atherosclerosis) with available data on body mass index and key covariates from 2000 to 2017 to calculate unadjusted and adjusted (age, study site, physical activity, diet, income, and education level) hazard ratios (HR) for obesity-attributable DM. We calculated national age-adjusted prevalence estimates for obesity using data from NHANES (National Health and Nutrition Examination Survey) in 4 pooled cycles (2001-2016) among adults with similar characteristics to MESA participants. Last, we calculated unadjusted and adjusted population attributable fractions from the race/ethnic and sex-specific HR and prevalence estimates. Of 4200 MESA participants, the median age was 61 years, 46.8% were men, 53.9% were non-Hispanic White, 32.9% were non-Hispanic Black, and 13.3% were Mexican. Among MESA participants, incident DM occurred in 11.6% over a median follow-up of 9.2 years. The adjusted HR for obesity-related DM was 2.7 (95% CI, 2.2-3.3). Adjusted population attributable fractions were 0.35 (95% CI, 0.29-0.40) in 2001 to 2004 and 0.41 (95% CI, 0.36-0.46) in 2013 to 2016, and greatest among non-Hispanic White women. Conclusions The contribution of obesity towards DM in the population remains substantial and varies significantly by race/ethnicity and sex, highlighting the need for tailored public health interventions to reduce obesity. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NC00005487, NCT00005154.

Background: Coronavirus disease 2019 (COVID-19) data from race/ethnic subgroups remain limited, potentially masking subgroup-level heterogeneity. We evaluated differences in outcomes in Asian American/Pacific Islander (AAPI) and Hispanic/Latino subgroups compared with non-Hispanic White patients hospitalized with COVID-19., Methods: In the American Heart Association COVID-19 registry including 105 US hospitals, mortality and major adverse cardiovascular events in adults age ≥18 years hospitalized with COVID-19 between March-November 2020 were evaluated. Race/ethnicity groups included AAPI overall and subgroups (Chinese, Asian Indian, Vietnamese, and Pacific Islander), Hispanic/Latino overall and subgroups (Mexican, Puerto Rican), compared with non-Hispanic White (NHW)., Results: Among 13,511 patients, 7% were identified as AAPI (of whom 17% were identified as Chinese, 9% Asian Indian, 8% Pacific Islander, and 7% Vietnamese); 35% as Hispanic (of whom 15% were identified as Mexican and 1% Puerto Rican); and 59% as NHW. Mean [SD] age at hospitalization was lower in Asian Indian (60.4 [17.4] years), Pacific Islander (49.4 [16.7] years), and Mexican patients (57.4 [16.9] years), compared with NHW patients (66.9 [17.3] years, p<0.01). Mean age at death was lower in Mexican (67.7 [15.5] years) compared with NHW patients (75.5 [13.5] years, p<0.01). No differences in odds of mortality or MACE in AAPI or Hispanic patients relative to NHW patients were observed after adjustment for age., Conclusions: Pacific Islander, Asian Indian, and Mexican patients hospitalized with COVID-19 in the AHA registry were significantly younger than NHW patients. COVID-19 infection leading to hospitalization may disproportionately burden some younger AAPI and Hispanic subgroups in the US., (© 2021 The Author(s).)

Importance: Despite recent advances in therapies for heart failure (HF), deaths from HF are increasing, with persistent disparities between Black and White adults. Recent national trends in the prevalence of HF need to be clarified to appropriately allocate resources and develop effective preventive interventions., Objectives: To examine the prevalence of ambulatory HF overall and by race/ethnicity and age and the temporal changes in HF prevalence between 2001 and 2016., Design, Setting, and Participants: This cross-sectional study of nationally representative data collected biennially through the National Health and Nutrition Examination Survey (NHANES) from January 1, 2001, to December 31, 2016, assessed nonpregnant adults 35 years and older who self-identified as non-Hispanic Black, non-Hispanic White, or Mexican American. Data analysis was performed from November 16, 2019, to April 12, 2020., Exposures: Survey period, race/ethnicity, and age group., Main Outcomes and Measures: Age-standardized prevalence was calculated within 4-year survey periods (2001-2004, 2005-2008, 2009-2012, and 2013-2016) based on self-report of ambulatory HF overall and by race/ethnicity and age group (35-64 and ≥65 years). Weighted multivariable logistic regression was used to examine trends in ambulatory HF prevalence over time by race/ethnicity and age group., Results: A total of 26 097 participants (mean [SD] age, 55.9 [10.7] years; 13 192 [52%] female; 6519 [12%] non-Hispanic Black; and 4906 [7%] Mexican American) were studied. Overall age-standardized prevalence (per 100 000 population) of ambulatory HF was 3184 (95% CI, 2641-3728) from 2001 to 2005 and 3045 (95% CI, 2651-3438) from 2013 to 2016. The prevalence of ambulatory HF was highest among non-Hispanic Black adults: from 2013 to 2016, HF prevalence (per 100 000 population) was 5017 (95% CI, 3755-6279) among non-Hispanic Black adults, 2746 (95% CI, 2313-3179) among non-Hispanic White adults, and 2508 (95% CI, 1154-3862) among Mexican American adults. Differences between White and Black adults in HF prevalence were also present in younger and middle-aged adults (eg, 35-64 years of age in 2013-2016: 3864 [95% CI, 2369-5359] for non-Hispanic Black adults vs 1297 [95% CI, 878-1716] for non-Hispanic White adults)., Conclusions and Relevance: This study found that a high burden of ambulatory HF persisted between 2001 and 2016 in the US. Disparities were most prominent by age group. Alongside prevention and aggressive management of risk factors, targeted efforts aimed at mitigating racial disparities are needed.

Researchers are often interested in estimating the causal effects of sustained treatment strategies, i.e., of (hypothetical) interventions involving time-varying treatments. When using observational data, estimating those effects requires adjustment for confounding. However, conventional regression methods cannot appropriately adjust for confounding in the presence of treatment-confounder feedback. In contrast, estimators derived from Robins's g-formula may correctly adjust for confounding even if treatment-confounder feedback exists. The package gfoRmula implements in R one such estimator: the parametric g-formula. This estimator can be used to estimate the effects of binary or continuous time-varying treatments as well as contrasts defined by static or dynamic, deterministic, or random interventions, as well as interventions that depend on the natural value of treatment. The package accommodates survival outcomes as well as binary or continuous outcomes measured at the end of follow-up. This paper describes the gfoRmula package, along with motivating background, features, and examples., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

We take steps toward causally interpretable meta-analysis by describing methods for transporting causal inferences from a collection of randomized trials to a new target population, one trial at a time and pooling all trials. We discuss identifiability conditions for average treatment effects in the target population and provide identification results. We show that the assumptions that allow inferences to be transported from all trials in the collection to the same target population have implications for the law underlying the observed data. We propose average treatment effect estimators that rely on different working models and provide code for their implementation in statistical software. We discuss how to use the data to examine whether transported inferences are homogeneous across the collection of trials, sketch approaches for sensitivity analysis to violations of the identifiability conditions, and describe extensions to address nonadherence in the trials. Last, we illustrate the proposed methods using data from the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial.

Importance: The Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database may provide insights into the comparative effectiveness of oncological treatments for elderly individuals who are underrepresented in clinical trials., Objective: To evaluate the suitability of SEER-Medicare data for assessing the effectiveness of adding a drug to an existing treatment regimen on the overall survival of elderly patients with cancer., Design, Setting, and Participants: This comparative effectiveness study analyzed SEER-Medicare data from 9549 individuals who received a new diagnosis of stage II colorectal cancer (2008-2012) and 940 patients who received a new diagnosis of advanced pancreatic adenocarcinoma (2007-2012), with follow-up to December 31, 2013 (SEER-Medicare data released in 2015). Two (hypothetical) target trials were designed and emulated based on 2 existing randomized clinical trials: (1) adjuvant fluorouracil after curative surgery for individuals with stage II colorectal cancer and (2) erlotinib added to gemcitabine for individuals with advanced pancreatic adenocarcinoma. Data were analyzed January 2018 to March 2019., Exposures: The following treatment strategies were compared: (1) fluorouracil initiation vs no initiation within 3 months of tumor resection and (2) erlotinib initiation vs no initiation within 12 weeks of gemcitabine initiation., Main Outcomes and Measures: All-cause mortality within 60 months of baseline for the fluorouracil trial and within 72 weeks for the erlotinib trial., Results: Compared with 3293 individuals in the existing fluorouracil trial, 9549 eligible individuals included in the present analyses were more likely to have colon cancer (8565 [90%] vs 2291 [71%]) and were older (median [interquartile range], 79 [73-84] vs 63 [56-68] years). The 5-year risk difference for initiation vs noninitiation of fluorouracil after surgery was -3.8% (95% CI, -14.8% to 12.6%), and the mortality hazard ratio (HR) was 0.95 (95% CI, 0.85-1.04). Compared with 569 individuals in the existing erlotinib trial, 940 eligible patients included in the present analysis were older (median [range], 74 [66-93] vs 64 [36-92] years) and more likely to be male (547 [58%] vs 298 [52%]). The 1-year risk difference for initiation vs noninitiation of erlotinib was 4.7% (95% CI, -9.4% to 18.0%), and the corresponding mortality HR was 1.04 (95% CI, 0.86-1.42). In naive analyses, the mortality HR estimate was 1.14 (95% CI, 0.95-1.36) for the fluorouracil emulation and 0.68 (95% CI, 0.54-0.87) for the erlotinib emulation., Conclusions and Relevance: The present estimates were similar to those from randomized clinical trials that studied adding the same cancer drugs to existing regimens. The published HR was 1.02 (95% CI, 0.70-1.48) in the fluorouracil trial for individuals aged 70 or older and 0.96 (95% CI, 0.74-1.24) in the erlotinib trial for individuals aged 65 years or older. The SEER-Medicare database may be adequate for studying the real-world effectiveness of adding a drug to treatment regimens used for elderly individuals with cancer.