Safety and Efficacy of Direct Oral Anticoagulants vs Warfarin in Patients With Obesity and Venous Thromboembolism: A Retrospective Analysis.

BACKGROUND: Current venous thromboembolism guidelines recommend using direct oral anticoagulants (DOACs) over warfarin regardless of obesity status; however, evidence remains limited for the safety and efficacy of DOAC use in patients with obesity. This retrospective analysis sought to demonstrate the safety and efficacy of DOACs compared with warfarin in a diverse population of patients with obesity in light of current prescribing practices. METHODS: A retrospective cohort study was conducted at a large academic health system between July 2014 and September 2019. Adults with an admission diagnosis of deep vein thrombosis (DVT) or pulmonary embolism, with weight greater than 120 kg or a body mass index greater than 40, and who were discharged on an oral anticoagulant were included. Outcomes included occurrence of a thromboembolic event (DVT, pulmonary embolism, or ischemic stroke), bleeding event requiring hospitalization, and all-cause mortality within 12 months following index admission. RESULTS: Out of 787 patients included, 520 were in the DOAC group and 267 were in the warfarin group. Within 12 months of index hospitalization, thromboembolic events occurred in 4.23% of patients in the DOAC group vs 7.12% of patients in the warfarin group (hazard ratio, 0.6 [95% CI, 0.32-1.1]; P = .082). Bleeding events requiring hospitalization occurred in 8.85% of DOAC patients vs 10.1% of warfarin patients (hazard ratio, 0.93 [95% CI, 0.57-1.5]; P = .82). A DVT occurred in 1.7% and 4.9% of patients in the DOAC and warfarin groups, respectively (hazard ratio, 0.35 [95% CI, 0.15-0.84]; P = .046). CONCLUSION: No significant differences could be determined between DOACs and warfarin for cumulative thromboembolic or bleeding events, pulmonary embolism, ischemic stroke, or all-cause mortality. The risk of DVT was lower with apixaban and rivaroxaban. Regardless of patient weight or body mass index, physicians prescribed DOACs more commonly than warfarin.

Early postpartum blood pressure screening is associated with increased detection of cardiovascular risk factors in women with hypertensive disorders of pregnancy.

BACKGROUND: Hypertensive disorders of pregnancy (HDP), including gestational hypertension, preeclampsia, and eclampsia, are risk factors for cardiovascular (CV) disease. Guidelines recommend that women with HDP be screened for the development of hypertension (HTN) within 6-12 months postpartum. However, the extent to which this early blood pressure (BP) screening is being performed and the impact on detection of CV risk factors is unknown. METHODS: Women with HDP and without pre-existing hypertension (HTN) who had at least 6 months of clinical follow-up were categorized by postpartum BP screening status: early BP screen (6-12 months after delivery) or late BP screen (≥12 months after delivery). Multivariable logistic regression identified factors associated with early screening. Multivariable Cox proportional hazards modeling examined the association between early screening and detection of incident CV risk factors: HTN, prediabetes, diabetes mellitus type 2, or hyperlipidemia. RESULTS: Among 4194 women with HDP, 1172 (28%) received early BP screening. Older age, pre-existing hyperlipidemia, diabetes, sickle cell disease, hypothyroidism, gestational diabetes, and delivery during or after 2014 were independently associated with early BP screening, whereas Hispanic ethnicity was associated with late BP screening. Early BP screening was most commonly performed at a primary care visit. After a median follow-up of 3.7 years, 1012 (24%) women had at least 1 new risk factor detected. Even after adjustment for baseline risk, women receiving early BP screening had a significantly higher rate of incident CV risk factor detection than women receiving late BP screening (56% vs 28%; adj. HR 2.70, 95%CI: 2.33-3.23, P < .001). CONCLUSIONS: Early postpartum BP screening was performed in a minority of women with HDP, but was associated with greater detection of CV risk factors. More intensive postpartum CV screening and targeted interventions are needed to optimize CV health in this high-risk population of women with HDP.

Antihypertensive medication use during pregnancy in a real-world cohort of patients diagnosed with a hypertensive disorder of pregnancy.

Hypertensive disorders of pregnancy (HDP) are rising in prevalence and associated with adverse maternal and infant health outcomes. Current guidelines recommend labetalol, nifedipine, and methyldopa as acceptable first-line agents to treat HDP in outpatient settings. However, the current practice regarding antihypertensive medication usage and selection remain unclear. A retrospective, observational cohort study was conducted in 1,641 patients with a physician diagnosis of HDP who delivered at two academic medical centers in North Carolina from 2014 to 2017. Use of any antihypertensive medication, and the agent selected, at any encounter during pregnancy or on the delivery date was collected from the electronic health record. Proportions were compared across HDP diagnosis (eclampsia/severe preeclampsia, chronic hypertension with superimposed preeclampsia, preeclampsia, gestational hypertension) by Chi-square tests and multivariable logistic regression. Antihypertensive medications were used in 1,276 (77.8%) patients overall. Among treated patients, labetalol (74.9%) was the most frequently used medication followed by nifedipine (29.6%) and hydralazine (20.5%). Methyldopa was used infrequently (4.4%). HDP type was the strongest factor associated with use of an antihypertensive agent. Relative to gestational hypertension, antihypertensive use was significantly more likely [odds ratio (95% CI)] in patients with severe preeclampsia [5.94 (3.85-9.16)], chronic hypertension with superimposed preeclampsia [4.99 (3.46-7.19)], and preeclampsia [2.13 (1.61-2.82)]. In a real-world setting, antihypertensive medication use among HDP patients was common, labetalol, nifedipine, and hydralazine were the most commonly selected agents, and increasing HDP severity was associated with a higher likelihood of antihypertensive use. Future studies comparing medication effectiveness in pregnant patients with distinct HDP diagnoses are needed.

Neuropsychological Correlates of Adherence in Youth with Behaviorally Acquired HIV.

Youth living with behaviorally acquired HIV (YLWH) are at-risk for both neuropsychological disorders and antiretroviral therapy (ART) non-adherence; little is known about their interrelationship over time in YLWH. Neuropsychological and psychiatric functioning, substance use, and self-report of 7-day/week and weekend ART adherence were assessed at baseline and Weeks 24, 48, 96 and 144 of a longitudinal study evaluating the impact of early (CD4>350) versus standard of care (CD4≤350) treatment initiation on neuropsychological functioning in 111 treatment-naïve YLWH age 18-24 years at entry. Bayesian multi-level models for adherence (≥ 90% vs. <90%) were fit using random intercepts for repeated measures. Adjusted odds ratios (OR [95% credible interval]) for higher versus lower baseline Motor function for visit adherence were 0.58 (0.25, 1.16), 0.5 (0.15, 1.38), 0.52 (0.16, 1.52), and 0.94 (0.3, 2.8) at Weeks 24, 48, 96, and 144, respectively. Week 24 adherence was associated with higher adjusted odds of Motor function at Week 48 (week: 0.27, -0.05-0.59; weekend: 0.28, -0.07-0.62). Week 96 Complex Executive functioning was associated with higher adjusted odds of adherence at Week 144, OR = 4.26 (1.50, 14.33). Higher Motor functioning emerged most consistently associated with lower odds of adherence in YLWH. Complex Executive functioning was associated with adherence only at end of study, suggesting potential contribution in adherence over the long-term.

Implementation of a Family Support Grant to Subsidize Caregiving Needs and Support Attendance at American Society for Nutrition's Annual Professional Scientific Conference.

Attendance at professional society meetings facilitates networking, collaboration, and success in academic/scientific fields. Insufficient funds, support, or resources for caregiving can inhibit attendance for parents/caretakers, who may become professionally disadvantaged by not attending professional society conferences. The American Society for Nutrition (ASN) offered a family support grant for caregiving needs during the annual conference (maximum: $750); however, the perceived impact of caregiving funds on attendance outcomes is unknown. The objective of this study was to assess the need of family support for attendance to the ASN annual conference among applicants and to assess recipients' experience and usage of funds. Applicants completed a pre-conference survey assessing requested funds, out-of-pocket caregiving expenses to attend the meeting, the influence of receiving the grant on attendance, and additional factors. Recipients completed a post-conference survey assessing use of the funds and impact of the grant on attending/participating. Grant applications (n = 110) were majority women, aged 26-45 y, married, at the trainee or assistant professor level, from diverse racial/ethnic backgrounds, and with parenting noted as the primary responsibility. Thirty-seven percent of applicants were currently lactating or expressing milk. The average amount requested was $650 US dollars, and >60% of respondents indicated plans to use funds to bring a family member/friend to the conference. Seventy-seven percent of respondents indicated that receiving the grant would influence their attendance. The post-conference survey (n = 25) indicated that recipients felt that receiving the grant was helpful in attending the conference (92%), specifically attending scientific sessions (96%) and poster sessions (80%). Recipients indicated the grant helped them network with attendees (88%), visit the exhibitor hall (72%), and participate in career development activities (64%). The ASN family support grant aided attendance and supported recipients' participation in conference activities, particularly early-career women who are parents, with the goal of supporting diversity and inclusivity in scientific/academic fields. This trial was registered at www.clinicaltrials.gov as NCT03432585.

Rapid report on estimating incidence from cross-sectional data.

PURPOSE: In prospective cohort studies, incidence is typically estimated by the ratio of the observed number of events to person-time at risk. This crude estimator is consistent for the true population incidence rate (IR) under mild assumptions. Here we consider a different setting where only cross-sectional data are available, that is, at a single time point, participants are evaluated to identify whether they have previously had the event of interest. METHODS: Unlike the prospective cohort data setting, for cross-sectional data, the crude IR estimator is biased. Instead, the maximum likelihood estimator (MLE) may be used. Although the MLE does not have a simple closed form, it is consistent and easy to compute using statistical software. To compare the bias of the MLE and the crude estimator, a simulation was conducted. RESULTS: The crude estimator underestimated the true incidence, whereas the MLE was approximately unbiased. In general, bias of the crude estimator tended to be roughly one to two orders of magnitude larger (in absolute value) than the MLE. CONCLUSIONS: Under cross-sectional data with exact event times unknown, the MLE of the IR is straightforward to calculate, more accurate than the crude IR estimator, and consistent provided the hazard is constant.

Environmental modifiers of RTS,S/AS01 malaria vaccine efficacy in Lilongwe, Malawi.

BACKGROUND: RTS,S/AS01 is the first vaccine against malaria to undergo pilot implementation, beginning in 2019 and vaccinating 360,000 children per year in Malawi, Ghana, and Kenya. The four-dose vaccine is given as a primary three-dose series with a fourth dose given approximately 18 months later. The efficacy of RTS,S/AS01 was variable among the 11 sites participating in the 2009-2014 phase III trial (MALARIA-055, NCT00866619), possibly due to differences in transmission intensity. However, a within-site examination of environmental factors related to transmission intensity and their impact on vaccine efficacy has yet to be conducted. METHODS: We implemented the phase III RTS,S/AS01 trial at the Malawi site, which enrolled 1578 infants (6-12 weeks) and children (5-17 months) living in the Lilongwe District in Central Malawi and followed them for 3 years between 2009 and 2014. A global positioning system survey and an ecological questionnaire were conducted to collect participant household locations and characteristics, while additional data on background malaria prevalence were obtained from a concurrent Malaria Transmission Intensity (MTI) survey. Negative binomial regression models were used to assess whether the efficacy of the vaccine varied by estimated background malaria prevalence, household roof type, or amount of nearby vegetation. RESULTS: Vaccine efficacy did not significantly vary by estimated malaria prevalence or by roof type. However, increased vegetation cover was associated with an increase in the efficacy of the three-dose primary RTS,S/AS01 series in the 18 months before the fourth dose and a decrease in the efficacy of the primary vaccine series in the second 18 months following, if the fourth dose was not given. Vegetation cover did not alter the efficacy of the fourth dose in a statistically or practically significant manner. CONCLUSIONS: Vegetation coverage in this study site might be a proxy for nearness to rivers or branching, shallow wetlands called "dambos" which could serve as breeding sites for mosquitoes. We observed statistically significant modification of the efficacy of RTS,S/AS01 by forest cover, suggesting that initial vaccine efficacy and the importance of the fourth dose varies based on ecological context. TRIAL REGISTRATION: Efficacy of GSK Biologicals' Candidate Malaria Vaccine (257049) Against Malaria Disease Caused by P. falciparum Infection in Infants and Children in Africa. NCT00866619 prospectively registered 20 March 2009.

The association of employment status with ideal cardiovascular health factors and behaviors among Hispanic/Latino adults: Findings from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

BACKGROUND: The American Heart Association's 2020 Impact Goals propose to improve cardiovascular health (CVH) and reduce deaths from cardiovascular diseases and stroke in the US. Targeted health promotion efforts in workplaces and communities are needed to achieve these population-level changes. The present study examined the sex-specific cross-sectional associations between employment status and ideal CVH among Hispanics/Latinos, and whether these associations were modified by age (i.e., younger adults [aged 18-44] compared to middle-aged and older adults [aged 45-74]). METHODS: This study included 4,797 males and 7,043 females (aged 18-74) from the Hispanic Community Health Study / Study of Latinos. Employment status was categorized as employed full-time (FT), employed part-time (PT), employed (FT or PT) and homemakers, homemakers only, and unemployed. CVH metrics, operationalized as 'ideal' versus 'less than ideal,' included health factors (i.e., blood pressure, cholesterol, and fasting glucose) and health behaviors (i.e., body mass index, smoking, physical activity [PA], and diet). A total CVH score was derived based on the seven CVH metrics, and dichotomized as ideal vs. less than ideal (score of 11-14 vs. 0-10). Survey-based generalized linear regression models with Gaussian binomial distribution were used to estimate adjusted prevalence differences (APDs) and their 95% confidence intervals (CIs) for the associations between employment status (with employed FT as referent) and ideal CVH (total score and each metric), adjusting for socio-demographic characteristics. Effect modification by age was examined. RESULTS: Among males, compared to their employed FT counterparts, those who were employed PT had a higher prevalence of ideal CVH score (APD = 6.8, 95% CI = 1.7, 11.8), ideal BMI (APD = 8.5, 95% CI = 3.0, 14.0), and ideal PA (APD = 4.8, 95% CI = 0.9, 8.7). Age modified the associations of employment type with ideal CVH score and ideal BMI, i.e., younger males who were employed PT had a higher prevalence of ideal CVH score and ideal BMI. Among females, employment status was not associated with ideal CVH score. Compared to females employed FT, females who were homemakers had a lower prevalence of ideal (non-) smoking (APD = -4.7, 95% CI = -8.5, -1.0) and ideal PA (APD = -7.9, 95% CI = -12.7, -3.0), and females who were unemployed had a lower prevalence of ideal PA (APD = -10.4, 95% CI = -16.7, -4.1). Age modified the associations of employment type with ideal fasting glucose and ideal PA, i.e., middle-aged and older females who were homemakers or unemployed had a lower prevalence of ideal fasting glucose and ideal PA. CONCLUSIONS: Hispanic/Latino males who were employed PT had the most favorable CVH profiles but these associations were mostly driven by better CVH (total score and metrics) among younger males. Hispanic/Latino females who were homemakers or unemployed had lower rates of ideal CVH metrics.

Free and Bioavailable 25-Hydroxyvitamin D Concentrations are Associated With Disease Activity in Pediatric Patients With Newly Diagnosed Treatment Naïve Ulcerative Colitis.

Background: Vitamin D regulates intestinal epithelial and immune functions, and vitamin D receptor deficiency increases the severity of murine colitis. Bioavailable 25-hydroxyvitamin D (25(OH)D) is available to target tissues and may be a driver of immune function. The aim is to evaluate the relationship of bioavailable 25(OH)D to the clinical expression of treatment naive pediatric ulcerative colitis (UC). Methods: The PROTECT (Predicting Response to Standardized Pediatric Colitis Therapy) study enrolled children ≤17 years newly diagnosed with UC. Free and total 25(OH)D were directly measured and 25(OH)D fractions were compared with disease activity measures. Results: Data were available on 388 subjects, mean age 12.7 years, 49% female, 84% with extensive/pancolitis. The median (IQR) total 25(OH)D concentration was 28.5 (23.9, 34.8) ng/mL, and 57% of subjects demonstrated insufficient vitamin D status (25(OH)D < 30 ng/mL). We found no evidence of association between total 25(OH)D and disease activity. Regression models adjusted for age, sex, race, and ethnicity demonstrated that an increase from 25th to 75th percentile for bioavailable and free 25(OH)D were associated with a mean (95th CI) decrease in the Pediatric Ulcerative Colitis Activity Index (PUCAI) of -8.7 (-13.7, -3.6) and -3.1 (-5.0, -1.2), respectively. No associations were detected between 25(OH)D fractions and fecal calprotectin or Mayo endoscopy score. Conclusions: Vitamin D insufficiency is highly prevalent in children with newly diagnosed UC. We found associations of free and bioavailable, but not total 25(OH)D, with PUCAI. Bioavailable vitamin D may contribute to UC pathophysiology and clinical activity.

Evaluating different criteria for defining a complete ambulatory blood pressure monitoring recording: data from the Jackson Heart Study.

OBJECTIVE: We determined differences in the prevalence of blood pressure (BP) phenotypes and the association of these phenotypes with left ventricular hypertrophy (LVH) for individuals who fulfilled and did not fulfill various criteria used for defining a complete ambulatory blood pressure monitoring (ABPM) recording. METHODS: We analyzed data for 1141 participants from the Jackson Heart Study. Criteria evaluated included having greater than or equal to 80% of planned readings with more than or equal to one reading per hour (Spanish ABPM Registry criteria), more than or equal to 70% of planned readings with a minimum of 20 daytime and seven nighttime readings (2013 European Society of Hypertension criteria), greater than or equal to 14 daytime and greater than or equal to seven nighttime readings (2003 European Society of Hypertension criteria), more than or equal to 10 daytime and more than or equal to 5 nighttime readings (International Database of Ambulatory Blood Pressure in Relation to Cardiovascular Outcome criteria), and greater than or equal to 14 daytime readings (UK National Institute of Health and Clinical Excellence criteria). RESULTS: Between 45.0% (Spanish ABPM Registry) and 91.8% (UK National Institute of Health and Clinical Excellence) of the participants fulfilled the different criteria for a complete ABPM recording. Across the various criteria evaluated, 55.5-57.8% of participants had nocturnal hypertension and 62.8-66.8% had nondipping systolic BP. Among participants with clinic-measured systolic/diastolic BP of more than or equal to 140/90 mmHg, 22.9-26.5% had white-coat hypertension. The prevalence of daytime, 24-h, sustained, and masked hypertension differed by up to 2% for participants fulfilling each criterion. The association of BP phenotypes with LVH was similar for participants who fulfilled versus those who did not fulfill different criteria (each P>0.05). CONCLUSION: Irrespective of the criteria used for defining a complete ABPM recording, the prevalence of BP phenotypes and their association with LVH were similar.

Fine Particulate Matter (PM2.5) and the Risk of Stroke in the REGARDS Cohort.

BACKGROUND: Ambient particulate matter has been shown to be associated with declining human health, although the association between fine particulate matter (PM2.5) and stroke is uncertain. METHODS: We utilized satellite-derived measures of PM2.5 to examine the association between exposure and stroke in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. We used a time-stratified case-crossover design, with exposure lags of 1 day, 2 days, and 3 days. We examined all strokes, as well as ischemic and hemorrhagic strokes separately. RESULTS: Among 30,239 participants in the REGARDS study, 746 incident events were observed: 72 hemorrhagic, 617 ischemic, and 57 of unknown type. Participants exposed to higher levels of PM2.5 more often resided in urban areas compared to rural, and in the southeastern United States. After adjustment for temperature and relative humidity, no association was observed between PM2.5 exposure and stroke, regardless of the lag (1-day lag OR = .99, 95% CI: .83-1.19; 2-day lag OR = .95, 95% CI: .80-1.14; 3-day lag OR = .95, 95% CI = .79-1.13). Similar results were observed for the stroke subtypes. CONCLUSIONS: In this large cohort of African-Americans and whites, no association was observed between PM2.5 and stroke. The ability to examine this association with a large number of outcomes and by stroke subtype helps fill a gap in the literature examining the association between PM2.5 and stroke.