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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 ( Results Among the Medicare cohorts with uncontrolled hypertension, 16.7% (39/234) of patients from the care coordination clinics were prescribed RPM versus Conclusion Care coordination facilitated RPM enrollment among poorly controlled hypertension patients and may improve hypertension control in primary care among Medicare patients.

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.

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 P P Conclusions: Education and place of birth confer the largest statistical contributions to the racial and ethnic differences in mean CVH score among US adults.

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.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.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.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.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.

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.

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 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.

To evaluate the effectiveness of netarsudil in combination with other ocular hypotensive agents in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).Retrospective cohort study.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.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.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.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 (P0.001). A reduction in IOP was observed in eyes on 1 (2.0 mmHg, P0.001), 2 (1.0 mmHg, P = 0.12), 3 (3.0 mmHg, P0.001), 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.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.

Introduction: Prevalence of pre-pregnancy hypertension (HTN) has increased concurrently with maternal age in the US. We sought to understand the contribution of changes in maternal age vs. age-related HTN prevalence to trends in pre-pregnancy HTN. Methods: We included individuals aged 15-44 years old with a singleton first live birth in 1995-1999 and 2015-2019 from the National Vital Statistics System. We calculated the prevalence of pre-pregnancy HTN per 1,000 live births in 1995-1999 and 2015-2019, overall and in each 5-year age group. Using a Kitagawa analysis, we decomposed change in prevalence into two parts: (1) change in maternal age distribution and (2) change in age-specific prevalence of pre-pregnancy HTN (rate component). Analyses were repeated by self-identified race and ethnicity. Results: From 1995-1999 to 2015-2019, the proportion of first births decreased from 53% to 39% in 15-24 year olds and increased from 47% to 61% in 25-44 year olds. Pre-pregnancy HTN prevalence increased from 6.4 in 1995-1999 to 16.7 in 2015-2019 per 1,000 live births ( TABLE ). Changes in maternal age distribution and age-specific prevalence were associated with 16% and 84% of the increase in pre-pregnancy HTN, respectively. While prevalence differed by race and ethnicity, changes in age-specific prevalence accounted for the majority of changes in pre-pregnancy HTN in each group. Conclusions: Adverse trends in pre-pregnancy HTN were driven primarily by increasing age-specific prevalence overall, and in all race and ethnicity groups. Public health efforts are needed to identify and target the cardiovascular risk factors driving these age-specific trends and improve maternal health.

Hypothesis: We hypothesized that a single regimen of no or limited diuretics post-discharge after pediatric cardiac surgery for patients with two ventricles is not inferior to prolonged diuretics for prevention of readmission for pleural effusion. Material and Methods: 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 to 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 five-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 five days of twice per day furosemide at discharge. Results: 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). Conclusions: 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 small, but statistically significant, increase in readmissions for pericardial effusions after implementation of this study protocol.

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.

Objective:To investigate if food security mediated the impact of a nutrition-sensitive agroecology intervention on women’s depressive symptoms.Design:We used annual longitudinal data (four time points) from a cluster-randomised effectiveness trial of a participatory nutrition-sensitive agroecology intervention, the Singida Nutrition and Agroecology Project. Structural equation modelling estimation of total, natural direct and natural indirect effects was used to investigate food security’s role in the intervention’s impact on women’s risk of probable depression (Center for Epidemiologic Studies Depression Scale > 17) across 3 years.Setting:Rural Singida, Tanzania.Participants:548 food insecure, married, smallholder women farmers with children < 1 year old at baseline.Results:At baseline, one-third of the women in each group had probable depression (Control: 32·0 %, Intervention: 31·9 %, P difference = 0·97). The intervention lowered the odds of probable depression by 43 % (OR = 0·57, 95 % CI: 0·43, 0·70). Differences in food insecurity explained approximately 10 percentage points of the effects of the intervention on odds of probable depression (OR = 0·90, 95 % CI: 0·83, 0·95).Conclusions:This is the first evidence of the strong, positive effect that lowering food insecurity has on reducing women’s depressive symptoms. Nutrition-sensitive agricultural interventions can have broader impacts than previously demonstrated, i.e. improvements in mental health; changes in food security play an important causal role in this pathway. As such, these data suggest participatory nutrition-sensitive agroecology interventions have the potential to be an accessible method of improving women’s well-being in farming communities.

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%, p0.01). 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%, p0.01), 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.

When reporting results from randomized experiments, researchers often choose to present a per-protocol effect in addition to an intention-to-treat effect. However, these per-protocol effects are often described retrospectively, for example, comparing outcomes among individuals who adhered to their assigned treatment strategy throughout the study. This retrospective definition of a per-protocol effect is often confounded and cannot be interpreted causally because it encounters treatment-confounder feedback loops, where past confounders affect future treatment, and current treatment affects future confounders. Per-protocol effects estimated using this method are highly susceptible to the placebo paradox, also called the “healthy adherers” bias, where individuals who adhere to placebo appear to have better survival than those who don’t. This result is generally not due to a benefit of placebo, but rather is most often the result of uncontrolled confounding. Here, we aim to provide an overview to causal inference for survival outcomes with time-varying exposures for static interventions using inverse probability weighting. The basic concepts described here can also apply to other types of exposure strategies, although these may require additional design or analytic considerations. We provide a workshop guide with solutions manual, fully reproducible R, SAS, and Stata code, and a simulated dataset on a GitHub repository for the reader to explore.

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.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.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.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.Period and birth cohort effects have contributed to the rising incidence of gestational diabetes mellitus in the United States from 2011 to 2019.

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.This work aims to describe temporal trends in CMR imaging for pediatric myocarditis and examine associations between CMR use, hospital cost, and outcomes.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.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.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.

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

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.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.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.Year of delivery (period) and birth year (cohort) of pregnant individuals.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.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]).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 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 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 mid-pregnancy glucose and BMI with childhood adiposity. RESEARCH DESIGN AND METHODS Data on mother/offspring pairs (N=4832) 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 sum of skinfolds was associated with child outcomes (adjusted mean difference, 95% CI, p-value) BMI(0.26,0.12-0.39, 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.

INTRODUCTION: Rates of gestational diabetes mellitus (GDM) are increasing in parallel with rates of overweight and obesity. This analysis examines nationwide trends in the population-attributable fraction for GDM 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), 23.0–27.4 kg/m(2)) and obesity (≥30.0 kg/m(2), ≥27.5 kg/m(2)) based on standard and Asian-specific BMI categories, respectively, were quantified. Logistic regression estimated adjusted associations between prepregnancy overweight and obesity and GDM with normal weight (18.0–24.9 kg/m(2), 18.0–22.9 kg/m(2)) as the ref. Annual population-attributable fractions for GDM associated with prepregnancy overweight and obesity were calculated, which account for both prevalence of the risk factor and the associated risk of GDM. RESULTS: Among 11,950,881 included women, mean maternal age was 26.3 years. Population-attributable fractions for GDM associated with overweight were stable (Hispanic: 12.0% to 11.3%, non-Hispanic Asian: 12.1% to 11.6%, p≥0.20) or decreased (non-Hispanic White: 10.8% to 9.4%, non-Hispanic Black: 12.3% to 9.2%, p

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 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 ( 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.

Introduction: Social determinants of health are multi-dimensional and span various interrelated domains. In order to inform community-engaged clinical and policy efforts, we sought to examine the association between a national social vulnerability index (SVI) and age-adjusted mortality rate (AAMR) of CVD. Hypothesis: Higher county-level SVI or greater vulnerability will be associated with higher AAMR of CVD between 1999-2018 in the United States. Methods: In this serial, cross-sectional analysis, we queried CDC WONDER for age-adjusted mortality rates (AAMRs) per 100,000 population for cardiovascular disease (I00-78) at the county-level between 1999-2018. We quantified the association of county-level SVI and CVD AAMR using Spearman correlation coefficients and examined trends in CVD AAMR stratified by median SVI at the county-level. Finally, we performed geospatial county-level analysis stratified by combined median SVI and CVD AAMR (high/high, high/low, low/high, and low/low). Results: We included data from 2766 counties (representing 95% of counties in the US) with median SVI 0.53 (IQR 0.28, 0.76). Overall SVI and the household and socioeconomic subcomponents were strongly correlated with 2018 CVD AAMR (0.47, 0.50, and 0.56, respectively with p Conclusion: County-level social vulnerability is associated with higher CVD mortality. High SVI and CVD AAMR coexist in more than 1 in 3 US counties and have persisted over the past 2 decades. Identifying counties that are disproportionately vulnerable may inform targeted and community-based strategies to equitably improve cardiovascular health across the country.

Introduction: Rural areas face greater challenges in access to cardiovascular care related to lower physician density compared with urban areas. However, whether the association between recent changes in primary care physicians (PCP) and cardiologist density and contemporary CVD mortality differs by county-level urbanization is unknown. Hypothesis: Decreases in county-level physician density per capita between 2011-2017 will be associated with higher CVD mortality in rural compared with urban counties in 2017-18 in the US. Methods: Death certificates from CDC WONDER with CVD (ICD-10 codes I00-09, I11, I13, I20-51) listed as the underlying cause of death between 2017-2018 were queried to calculate age-adjusted mortality rate (AAMR) at the county-level. Changes in county-level PCPs (2011-2017) and cardiologists (2011-2017) per 100,000 population were derived from the Area Health Resources Files. We performed univariable and multivariable linear regression to determine the association between change in physician density and county-level CVD AAMR adjusted for county-level demographic and socioeconomic characteristics and baseline physician density. Results: PCP and cardiologist density was lower in rural counties compared with urban counties (Table). Between 2011 and 2017, PCP density decreased in rural (-2.2 [SD 15.8]) and increased in urban counties (0.8 [9.1]). Conversely, cardiologist density increased in rural (0.1 [1.8]) and decreased in urban counties (-0.1 [2.1]). Increases in PCP density were associated with lower CVD AAMR in both rural and urban counties (p Conclusion: Cardiologist density in rural counties was less than one-third that of urban counties and was not associated with CVD mortality. Increases in PCP density between 2011-17 was significantly associated with lower CVD AAMR in 2017-18 in both rural and urban counties.

Introduction: Cardiovascular disease (CVD) is the leading cause of death in women and early onset of menopause before the age of 40 years has been identified as a risk enhancer for future CVD events. Quantifying the magnitude of risk for premature CVD among women with early menopause may inform and guide the intensity of sex-specific preventive strategies. Methods: We included all women in the Coronary Artery Risk Development in Young Adults (CARDIA) study who attended a follow-up exam after the age of 40 years, had available data on menopausal status, and had not experienced premature CVD before 40 years. We performed multivariable Cox proportional hazards regression to examine the relationship between early onset of menopause defined as Results: Among 2136 women with mean age of 43.0 (SD 3.0), 9.1% reported premature menopause before the age of 40 years (4.5% in white and 13.9% in black women). Over a median follow-up of 14.0 (IQR 11.5, 16.9) years, 81 premature CVD events occurred. Incidence rate (95% CI) of CVD was 6.46 (2.43, 17.22) and 1.41 (0.92, 2.17) per 1,000 per person-years for white women with and without early onset menopause, respectively; 4.94 (2.66, 9.16) and 3.92 (2.94, 5.24) per 1,000 person-years for black women with and without early onset menopause (FIGURE). Conclusions: In a population-based sample, white women with early onset of menopause had a 3-fold higher rate of premature CVD events, independent of perimenopausal risk factor levels. Interventions to intensify CVD prevention in at-risk women are needed following early onset of menopause.

Introduction: Women who experience premature menopause are known to have higher rates of long-term atherosclerotic cardiovascular disease (ASCVD). Specifically, menopause prior to age of 40 years has been identified as a risk enhancer by the 2019 AHA/ACC Primary Prevention guidelines. Coronary artery calcium (CAC) may have clinical utility for refinement of risk stratification in this high-risk group of women for the primary prevention of ASCVD. Methods: We included women from the Coronary Artery Risk Development in Young Adults (CARDIA) study who completed a coronary-gated CT scan at a baseline age of 43-55 years. We excluded women who had a myocardial infarction prior to CAC assessment. Menopausal status was self-reported as before the age of 40 years, at 40 years or older, or pre-menopausal. No significant interaction by race was observed. We performed multinomial logistic regression analysis to examine the association between premature menopause and 3 categories of CAC (0, 1-99, and ≥100 Agatston units). In separate multivariable models, we adjusted for demographic and cardiovascular risk factors at the time of CAC measurement. Results: Of 1786 women, 167 (9.4%) experienced premature menopause, 1175 (65.8%) reached menopause after the age of 40 years, and 444 (24.9%) were pre-menopausal at the time of CT. Presence of any CAC in these 3 groups was 18.0%, 19.6%, and 11.3% for premature menopause, ≥40 menopausal, and the pre-menopausal groups, respectively (FIGURE). Premature menopause was not associated with higher odds of non-zero CAC in unadjusted or adjusted analyses. Conclusions: Premature menopause was not associated with prevalent CAC score in these women in mid-life. Consideration of alternative approaches or biomarkers for risk stratification for ASCVD should be evaluated in this high-risk group.

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, 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.

As of June 2020, the United States (US) has experienced the highest number of deaths related to coronavirus disease 2019 (Covid-19) in the world, but significant geographic heterogeneity exists at the county-level. Therefore, we sought to classify counties in the United States across multiple domains utilizing a socioecological framework and examine the association between these county-level groups and Covid-19 mortality. We harmonized and linked county-level sociodemographic, health, and environmental metrics associated with increased susceptibility for Covid-19 mortality. Latent class analysis defined a county-level susceptibility index (CSI) based on these metrics (n=2701 counties). Next, we used linear regression models to estimate the associations of the CSI and Covid-19 deaths per capita and initial mortality doubling time (as of 6/2/20), adjusted for days since first Covid-19 case. We identified 4 groups classified by the CSI with distinct sociodemographic, health, and environmental profiles and widespread geographic dispersion. Covid-19 deaths per capita were significantly higher in the group consisting of rural, vulnerable counties (55.8 [95% CI 50.3-61.2] deaths per 100,000) compared with the group with diverse, urban counties (32.2 [27.3-37.0]) at similar points in the outbreak (76 days since first case). Our findings can inform equitable resource allocation for Covid-19 to allow targeted public health preparedness and response in vulnerable counties.

Summary: 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. The Bigger Picture: Causal inference is a core task of data science. When data from randomized experiments are not available, data analysts often rely on nonexperimental (observational) data to estimate causal effects. The parametric g-formula is a statistical method to estimate the causal effects of sustained treatment strategies from observational data with time-varying treatments, confounders, and outcomes. Although this methodology was introduced in the 1980s, it has not been widely used due to the lack of open-source software. This article presents the gfoRmula package, an implementation of the parametric g-formula in R. The aim of this software is to facilitate the application of the parametric g-formula to complex, observational data to answer causal questions. Furthermore, this package helps provide a way to compare the performance of the parametric g-formula to other methods in the causal inference literature.

OBJECTIVES: In 2015, depressive disorders led to over 50 million disability-adjusted life years lost globally, with more than 80% occurring in low- and middle-income countries. Depressive disorders are also risk factors of a number of adverse maternal and child health outcomes. To our knowledge, the Singida Nutrition and Agroecology Project (SNAP-Tz), is the first nutrition-sensitive agriculture (NSA) intervention identified to improve women's probable depression (2020). Food security has been posited to play an important role in the relationship between NSA interventions and depression, yet causal factors have not yet been analyzed quantitatively. Therefore, we investigated food security's mediating role on this impact. METHODS: SNAP-Tz is a 30-month participatory agroecological intervention aimed to improve sustainable agriculture, nutrition and gender equity in Singida, Tanzania. Food insecure, married, smallholder female farmers with children

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.