Cooking with liquefied petroleum gas or biomass and fetal growth outcomes: a multi-country randomised controlled trial.

BACKGROUND: Household air pollution might lead to fetal growth restriction during pregnancy. We aimed to investigate whether a liquefied petroleum gas (LPG) intervention to reduce personal exposures to household air pollution during pregnancy would alter fetal growth. METHODS: The Household Air Pollution Intervention Network (HAPIN) trial was an open-label randomised controlled trial conducted in ten resource-limited settings across Guatemala, India, Peru, and Rwanda. Pregnant women aged 18-34 years (9-19 weeks of gestation) were randomly assigned in a 1:1 ratio to receive an LPG stove, continuous fuel delivery, and behavioural messaging or to continue usual cooking with biomass for 18 months. We conducted ultrasound assessments at baseline, 24-28 weeks of gestation (the first pregnancy visit), and 32-36 weeks of gestation (the second pregnancy visit), to measure fetal size; we monitored 24 h personal exposures to household air pollutants during these visits; and we weighed children at birth. We conducted intention-to-treat analyses to estimate differences in fetal size between the intervention and control group, and exposure-response analyses to identify associations between household air pollutants and fetal size. This trial is registered with ClinicalTrials.gov (NCT02944682). FINDINGS: Between May 7, 2018, and Feb 29, 2020, we randomly assigned 3200 pregnant women (1593 to the intervention group and 1607 to the control group). The mean gestational age was 14·5 (SD 3·0) weeks and mean maternal age was 25·6 (4·5) years. We obtained ultrasound assessments in 3147 (98·3%) women at baseline, 3052 (95·4%) women at the first pregnancy visit, and 2962 (92·6%) at the second pregnancy visit, through to Aug 25, 2020. Intervention adherence was high (the median proportion of days with biomass stove use was 0·0%, IQR 0·0-1·6) and pregnant women in the intervention group had lower mean exposures to particulate matter with a diameter less than 2·5 µm (PM2·5; 35·0 [SD 37·2] µg/m3vs 103·3 [97·9] µg/m3) than did women in the control group. We did not find differences in averaged post-randomisation Z scores for head circumference (0·30 vs 0·39; p=0·04), abdominal circumference (0·38 vs 0·39; p=0·99), femur length (0·44 vs 0·45; p=0·73), and estimated fetal weight or birthweight (-0·13 vs -0·12; p=0·70) between the intervention and control groups. Personal exposures to household air pollutants were not associated with fetal size. INTERPRETATION: Although an LPG cooking intervention successfully reduced personal exposure to air pollution during pregnancy, it did not affect fetal size. Our findings do not support the use of unvented liquefied petroleum gas stoves as a strategy to increase fetal growth in settings were biomass fuels are used predominantly for cooking. FUNDING: US National Institutes of Health and Bill & Melinda Gates Foundation. TRANSLATIONS: For the Kinyarwanda, Spanish and Tamil translations of the abstract see Supplementary Materials section.

A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations.

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to genes involved in neurological, thyroidal, bone metabolism, and hematopoietic pathways. Non-overlap between short sleep (12) and long sleep (10) interactions underscores the plausibility of distinct influences of both sleep duration extremes in cardiovascular health. With several of our loci reflecting specificity towards population background or sex, our discovery sheds light on the importance of embracing granularity when addressing heterogeneity entangled in gene-environment interactions, and in therapeutic design approaches for blood pressure management.

Performance of ASCVD Risk Prediction Models in Individuals With Inflammatory Bowel Disease: A UK Biobank Study.

This study suggests that the current atherosclerotic cardiovascular disease risk prediction models used in clinical practice performed better in the non­inflammatory bowel disease (IBD) cohort compared with IBD, highlighting the need for a more specific risk prediction model tailored to the IBD population.

Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci.

Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes. Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: "Some College" (yes/no, for any education beyond high school) and "Graduated College" (yes/no, for completing a 4-year college degree). Genome-wide significant (p < 5 × 10-8) and suggestive (p < 1 × 10-6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals). Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue. Discussion: Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects.

Lung Ultrasound Protocol and Quality Control of Image Interpretation Using an Adjudication Panel in the Household Air Pollution Intervention Network (HAPIN) Trial.

OBJECTIVE: Lung ultrasound (LUS) is an alternative to chest radiography to confirm a diagnosis of pneumonia. For research and disease surveillance, methods to use LUS to diagnose pneumonia are needed. METHODS: In the Household Air Pollution Intervention Network (HAPIN) trial, LUS was used to confirm a clinical diagnosis of severe pneumonia in infants. We developed a standardized definition of pneumonia, protocols for recruitment and training of sonographers, along with LUS image acquisition and interpretation. We use a blinded panel approach to interpretation with LUS cine-loops randomized to non-scanning sonographers with expert review. DISCUSSION: We obtained 357 lung ultrasound scans: 159, 8 and 190 scans were collected in Guatemala, Peru and Rwanda, respectively. The diagnosis of primary endpoint pneumonia (PEP) required an expert tie breaker in 181 scans (39%). PEP was diagnosed in 141 scans (40%), not diagnosed in 213 (60%), with 3 scans (<1%) deemed uninterpretable. Agreement among the two blinded sonographers and the expert reader in Guatemala, Peru and Rwanda was 65%, 62% and 67%, with a prevalence-and-bias-corrected kappa of 0.30, 0.24 and 0.33, respectively. CONCLUSION: Use of standardized imaging protocols, training and an adjudication panel resulted in high confidence for the diagnosis of pneumonia using LUS.

Baseline associations between household air pollution exposure and blood pressure among pregnant women in the Household Air Pollution Intervention Network (HAPIN) multi-country randomized controlled trial.

Cooking and heating using solid fuels can result in dangerous levels of exposure to household air pollution (HAP). HAPIN is an ongoing randomized controlled trial assessing the impact of a liquified petroleum gas stove and fuel intervention on HAP exposure and health in Guatemala, India, Peru, and Rwanda among households that rely primarily on solid cooking fuels. Given the potential impacts of HAP exposure on cardiovascular outcomes during pregnancy, we seek to characterize the relationship between personal exposures to HAP and blood pressure among pregnant women at baseline (prior to intervention) in the study. We assessed associations between PM2.5 (particulate matter with an aerodynamic diameter ≤2.5 µm), BC (black carbon), and CO (carbon monoxide) exposures and blood pressure at baseline, prior to intervention, among 3195 pregnant women between 9 and 19 weeks of gestation. We measured 24-hour personal exposure to PM2.5/BC/CO and gestational blood pressure. Multivariable linear regression models were used to evaluate associations between personal exposures to three air pollutants and blood pressure parameters. Trial-wide, we found moderate increases in systolic blood pressure (SBP) and decreases in diastolic blood pressure (DBP) as exposure to PM2.5, BC, and CO increased. None of these associations, however, were significant at the 0.05 level. HAP exposure and blood pressure associations were inconsistent in direction and magnitude within each country. We observed effect modification by body mass index (BMI) in India and Peru. Compared to women with normal weights, obese women in India and Peru (but not in Rwanda or Guatemala) had higher SBP per unit increase in log transformed PM2.5 and BC exposures. We did not find a cross-sectional association between HAP exposure and blood pressure in pregnant women; however, HAP may be associated with higher blood pressure in pregnant women who are obese, but this increase was not consistent across settings.

Inflammatory Bowel Disease Is Associated With an Increased Risk of Incident Acute Arterial Events: Analysis of the United Kingdom Biobank.

BACKGROUND & AIMS: Population-based studies have suggested an increased risk of acute arterial events (AAEs) in patients with inflammatory bowel disease (IBD). We aimed to assess the risk of incident AAEs and premature AAEs, adjusted for diet, physical activity, and inflammation biomarkers, in participants with IBD in the UK Biobank (UKB) METHODS: UKB participants with IBD and without prevalent AAEs at enrollment were matched to random non-IBD controls. A Cox regression model, adjusting for baseline cardiovascular and IBD risk factors, diet, physical activity, and high-sensitivity C-reactive protein, estimated adjusted hazard ratios (aHRs) for association between IBD and AAEs or premature AAEs (age, <55 years for men and <65 years for women). Predictors of AAEs within the IBD cohort were identified in a Cox model adjusting for disease severity (IBD-related hospitalizations or surgeries). RESULTS: Among 455,950 UKB participants, 5094 with IBD were matched to 20,376 non-IBD controls. After a median follow-up period of 12.4 years, participants with IBD had a higher incident rate of AAE (924.1 vs 730.9 per 100,000 person years; P < .001), risk of all AAEs (aHR, 1.19; 95% CI, 1.08-1.31; P < .001), and premature AAEs (aHR, 1.38; 95% CI, 1.11-1.72; P = .001). High-sensitivity C-reactive protein levels (highest quartile: aHR, 1.53; 95% CI, 1.15-2.03) and disease severity (aHR, 5.40; 95% CI, 4.03-7.22) were independent predictors of AAE in IBD. CONCLUSIONS: In a prospective cohort, there was an increased risk of incident AAEs and premature AAEs in IBD participants. Beyond traditional AAE risk factors, quantifiable indices of IBD disease activity and severity were independent predictors of AAEs.

A prospective cohort study of the impact of outpatient Intensive Cardiac Rehabilitation on depression and cardiac self-efficacy.

Study objective: To evaluate whether an Intensive Cardiac Rehabilitation (ICR) program improves depression and cardiac self-efficacy among patients with a qualifying cardiac diagnosis. Design: Prospective, longitudinal cohort design. Setting: Single-center, tertiary referral, outpatient cardiac rehabilitation center. Participants: Patients with a qualifying diagnosis for ICR. Interventions: Outpatient ICR. Main outcome measures: Mental health, as assessed using the Patient Health Questionnaire-9 (PHQ-9) and cardiac self-efficacy using the Cardiac Self-Efficacy (CSE) scale. Results: Of the 268 patients included (median age 69 y, 73% men), 70% had no depressive symptoms at baseline (PHQ-9 score <5). PHQ-9 scores improved in the overall sample (p < 0.0001), with greater improvements among patients with mild depressive symptoms at baseline (-4 points, p < 0.001) and those with moderate to severe depressive symptoms at baseline (-5.5 points, p < 0.001). Cardiac self-efficacy improved overall, and the two subsections of the cardiac self-efficacy questionnaire titled, "maintain function" and "control symptoms" improved (all p < 0.001). Conclusions: Participation in an outpatient ICR program is associated with fewer depressive symptoms and greater cardiac self-efficacy among patients with CVD who qualify for ICR. The improvement in depression was greatest for those with moderate to severe depressive symptoms.

Whole genome sequence analysis of blood lipid levels in >66,000 individuals.

Blood lipids are heritable modifiable causal factors for coronary artery disease. Despite well-described monogenic and polygenic bases of dyslipidemia, limitations remain in discovery of lipid-associated alleles using whole genome sequencing (WGS), partly due to limited sample sizes, ancestral diversity, and interpretation of clinical significance. Among 66,329 ancestrally diverse (56% non-European) participants, we associate 428M variants from deep-coverage WGS with lipid levels; ~400M variants were not assessed in prior lipids genetic analyses. We find multiple lipid-related genes strongly associated with blood lipids through analysis of common and rare coding variants. We discover several associated rare non-coding variants, largely at Mendelian lipid genes. Notably, we observe rare LDLR intronic variants associated with markedly increased LDL-C, similar to rare LDLR exonic variants. In conclusion, we conducted a systematic whole genome scan for blood lipids expanding the alleles linked to lipids for multiple ancestries and characterize a clinically-relevant rare non-coding variant model for lipids.

A randomized feasibility trial of the Midlife Black Women's Stress and Wellness intervention (B-SWELL); a community participatory intervention to increase adoption of Life's Simple 7 healthy lifestyle behaviors.

BACKGROUND: Black women have a disproportionately higher incidence of cardiovascular disease-related mortality than other groups, yet they are less likely to receive culturally proficient education and competent preventive care. PURPOSE: The purpose of this study was to determine feasibility of the Midlife Black Women's Stress and Wellness intervention (B-SWELL); a culturally adapted, 8-week group intervention leveraging stress reduction and goal setting to increase awareness and adoption of Life's Simple 7 (LS7) healthy lifestyle behaviors. METHODS: A randomized feasibility trial was conducted. Participants (N = 48, mean age = 55 years) were randomized to the B-SWELL or a group wellness (WE) intervention that lacked stress reduction and goal setting instruction. We hypothesized that B-SWELL participants would achieve a lower perceived stress, greater self-efficacy, improved LS7 scores, fewer symptoms (depression and unhealthy days), and greater perceived general health compared to WE participants. Survey data were collected at three timepoints: baseline, 8 weeks, and 12 weeks. RESULTS: Both B-SWELL and WE groups had low attrition and navigated the online platform well. Further, both groups experienced lower perceived stress, improved LS7 scores, reduced depressive symptoms, and greater perceived general health from baseline to 8 weeks. Based on data trends, participants in the B-SWELL had more improvement in perceived stress, self-efficacy, and mental and physical unhealthy days compared to WE participants. CONCLUSION: The B-SWELL is a feasible intervention for midlife Black women. Positive data trends were found for both B-SWELL and WE groups. Based on observations from the feasibility study, a larger outcomes-based study is planned.

Midlife Black women have a greater chance of dying from heart disease compared to other groups. However, Black women are less likely to receive the education and health care needed to affect this difference. The purpose of this study was to compare a new program, the Midlife Black Women's Stress and Wellness intervention (B-SWELL) to a wellness program (WE). The B-SWELL program uses education, stress reduction, and goal setting to improve healthy lifestyle behaviors in midlife Black women. The WE program provided health education in a group setting but did not offer information about stress or goal setting. We enrolled 48 midlife Black women ages 40­64 years old into the study. The women were randomly assigned to either the B-SWELL or WE program. We proposed that women in the B-SWELL program would have lower stress, improved healthy lifestyle scores, less depression, and fewer symptoms compared to women in the WE program. Both groups experienced lower stress, improved healthy lifestyle scores, and less depression. Women in the B-SWELL had greater improvement in stress and symptoms. In conclusion, the B-SWELL program is practical for midlife Black women. A larger study is planned.

Benefits of the First Pritikin Outpatient Intensive Cardiac Rehabilitation Program.

PURPOSE: Intensive cardiac rehabilitation (ICR) is a comprehensive, medically supervised exercise treatment program covered by Medicare for patients with approved cardiac diagnoses. The aim of this study was to determine the benefits of the first Pritikin outpatient ICR program. METHODS: This retrospective analysis included patients referred to ICR or traditional cardiac rehabilitation (CR) during the first 7 yr (2013-2019) at the first facility to implement Pritikin ICR. Intensive cardiac rehabilitation is composed of 36 education sessions on nutrition, exercise, and a healthy mindset, in addition to 36 monitored exercise sessions that comprise traditional CR. Assessments included anthropometrics (weight, body mass index, and waist circumference), dietary patterns, physical function (6-min walk test, [6MWT] Short Physical Performance Battery [SPPB: balance, 4-m walk, chair rise], handgrip strength), and health-related quality of life (Dartmouth COOP, 36-item Short Form Survey). Baseline and follow-up measures were compared within and between groups. RESULTS: A total of 1963 patients enrolled (1507 ICR, 456 CR, 66.1 ± 11.4 yr, 68% male, 82% overweight or obese); 1141 completed the program (58%). The ICR patients completed 22 exercise and 18 education sessions in 9.6 wk; CR patients completed 19 exercise sessions in 10.3 wk. ICR resulted in improvements ( P < .001 pre vs post) in all anthropometric measures, dietary patterns, 6MWT distance, all SPPB components, grip strength, and health-related quality of life. The improvements in anthropometrics and dietary patterns were greater in ICR than in CR. CONCLUSIONS: The Pritikin outpatient ICR program promoted improvements in several cardiovascular health indices. Critical next steps are to assess long-term health outcomes after ICR, including cardiac events and mortality.

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed.

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value <5×10-9) in 36 loci associated with telomere length, including 20 newly associated loci (13 were replicated in external datasets). There was little evidence of effect size heterogeneity across populations. Fine-mapping at OBFC1 indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes.

High rates of undiagnosed and uncontrolled hypertension upon a screening campaign in rural Rwanda: a cross-sectional study.

BACKGROUND: Hypertension remains the major risk factor for cardiovascular diseases (CVDs) worldwide with a prevalence and mortality in low- and middle-income countries (LMICs) among the highest. The early detection of hypertension risk factors is a crucial pillar for CVD prevention. DESIGN AND METHOD: This cross-sectional study included 4284 subjects, mean age 46 ± 16SD, 56.4% females and mean BMI 26.6 ± 3.7 SD. Data were collected through a screening campaign in rural area of Kirehe District, Eastern of Rwanda, with the objective to characterize and examine the prevalence of elevated blood pressure (BP) and other CVD risk factors. An adapted tool from the World Health Organization STEPwise Approach was used for data collection. Elevated BP was defined as ≥ 140/90 mm/Hg and elevated blood glucose as blood glucose ≥ 100 mg/dL after a 6-h fast. RESULTS: Of the sampled population, 21.2% (n = 910) had an elevated BP at screening; BP was elevated among individuals not previously known to have HTN in 18.7% (n = 752). Among individuals with a prior diagnosis of HTN, 62.2% (n = 158 of 254) BP was uncontrolled. Age, weight, smoking, alcohol history and waist circumference were associated with BP in both univariate analyses and multivariate analysis. CONCLUSION: High rates of elevated BP identified through a health screening campaign in this Rwandan district were surprising given the rural characteristics of the district and relatively low population age. These data highlight the need to implement an adequate strategy for the prevention, diagnosis, and control of HTN that includes rural areas of Rwanda as part of a multicomponent strategy for CVD prevention.

Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits.

Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from 5 ancestry groups. In the combined meta-analyses of Stages 1 and 2, we identified 59 loci (p value <5e-8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response (PLCL2), synaptic function and neurotransmission (LIN7A, PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5, CHODL). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations.

Resistance exercise training with protein supplementation improves skeletal muscle strength and improves quality of life in late adolescents and young adults with Barth syndrome: A pilot study.

BACKGROUND: Muscle weakness and exercise intolerance contribute to reduced quality of life (QOL) in Barth syndrome (BTHS). Our group previously found that 12 weeks of resistance exercise training (RET) improved muscle strength, however, did not increase muscle (lean) mass or QOL in n = 3 young adults with BTHS. The overall objective of this pilot study was to examine the safety and effectiveness of RET plus daily protein supplementation (RET + protein) on muscle strength, skeletal muscle mass, exercise tolerance, cardiac function, and QOL in late adolescents/young adults with BTHS. METHODS: Participants with BTHS (n = 5, age 27 ± 7) performed 12 weeks of supervised RET (60 minutes per session, three sessions/week) and consumed 42 g/day of whey protein. Muscle strength, muscle mass, exercise capacity, cardiac function, and health-related QOL were assessed pre-post intervention. RESULTS: RET + protein was safe, increased muscle strength and quality of life, and tended to increase lean mass. CONCLUSIONS: RET + protein appears safe, increases muscle strength and quality of life and tends to increase lean mass. Larger studies are needed to confirm these findings and to fully determine the effects of RET + protein in individuals with BTHS.

Development of a Health Information Technology Tool for Behavior Change to Address Obesity and Prevent Chronic Disease Among Adolescents: Designing for Dissemination and Sustainment Using the ORBIT Model.

Health information technology (HIT) has not been broadly adopted for use in outpatient healthcare settings to effectively address obesity in youth, especially among disadvantaged populations that face greater barriers to good health. A well-designed HIT tool can deliver behavior change recommendations and provide community resources to address this gap, and the Obesity-Related Behavioral Intervention Trials (ORBIT) model can guide its development and refinement. This article reports the application of the ORBIT model to (1) describe the characteristics and design of a novel HIT tool (the PREVENT tool) using behavioral theory, (2) illustrate the use of stakeholder-centered "designing for dissemination and sustainability" principles, and (3) discuss the practical implications and directions for future research. Two types of stakeholder engagement (customer discovery and user testing) were conducted with end users (outpatient healthcare teams). Customer discovery interviews (n = 20) informed PREVENT tool components and intervention targets by identifying (1) what healthcare teams (e.g., physicians, dietitians) identified as their most important "jobs to be done" in helping adolescents who are overweight/obese adopt healthy behaviors, (2) their most critical "pains" and "gains" related to overweight/obesity treatment, and (3) how they define success compared to competing alternatives. Interviews revealed the need for a tool to help healthcare teams efficiently deliver tailored, evidence-based behavior change recommendations, motivate patients, and follow-up with patients within the constraints of clinic schedules and workflows. The PREVENT tool was developed to meet these needs. It facilitates prevention discussions, delivers tailored, evidence-based recommendations for physical activity and food intake, includes an interactive map of community resources to support behavior change, and automates patient follow-up. Based on Self-Determination Theory, the PREVENT tool engages the patient to encourage competence and autonomy to motivate behavior change. The use of this intentional, user-centered design process should increase the likelihood of the intended outcomes (e.g., behavior change, weight stabilization/loss) and ultimately increase uptake, implementation success, and long-term results. After initial tool development, user-testing interviews (n = 13) were conducted using a think-aloud protocol that provided insight into users' (i.e., healthcare teams) cognitive processes, attitudes, and challenges when using the tool. Overall, the PREVENT tool was perceived to be useful, well-organized, and visually appealing.

Exploring contextual factors influencing the implementation of evidence-based care for hypertension in Rwanda: a cross-sectional study using the COACH questionnaire.

IMPORTANCE: Hypertension is the largest contributor to the Global Burden of Disease. In Rwanda, as in most low-income and middle-income countries, an increasing prevalence of hypertension and its associated morbidity and mortality is causing major healthcare and economic impact. Understanding healthcare systems context in hypertension care is necessary. OBJECTIVE: To study the hypertension healthcare context as perceived by healthcare providers using the Context Assessment for Community Health (COACH) tool. DESIGN: A cross-sectional cohort responded to the COACH questionnaire and a survey about hypertension training. SETTING: Three tertiary care hospitals in Rwanda. PARTICIPANTS: Healthcare professionals (n=223). PRIMARY OUTCOMES AND MEASURES: The COACH tool consists of 49 items with eight subscales: resources, community engagement, commitment to work, informal payment, leadership, work culture, monitoring services for action (5-point Likert Scale) and sources of knowledge (on a 0-1 scale). Four questions surveyed training on hypertension. RESULTS: Responders (n=223, 75% women; 56% aged 20-35 years) included nurses (n=142, 64%, midwives (n=42, 19%), primary care physicians (n=28, 13%) and physician specialists (n=11, 5%)). The subscales commitment to work, leadership, work culture and informal payment scored between 4.7 and 4.1 and the community engagement, monitoring services for action and organizational resources scored between 3.1 and 3.5. Sources of knowledge had a mean score of 0.6±0.3. While 73% reported having attended a didactic hypertension seminar in the past year, only 28% had received long-term training and 51% had <3-year experience working with hypertension care delivery. The majority (99%) indicated a need for additional training in hypertension care. CONCLUSIONS: There is a need for increased and continuous training in Rwanda. Healthcare responders stated a commitment to work and reported supportive leadership, while acknowledging limited resources and no monitoring systems. The COACH tool provides contextual guidance to develop training strategies prior to the implementation of a sustainable hypertension care programme.

Population sequencing data reveal a compendium of mutational processes in the human germ line.

Biological mechanisms underlying human germline mutations remain largely unknown. We statistically decompose variation in the rate and spectra of mutations along the genome using volume-regularized nonnegative matrix factorization. The analysis of a sequencing dataset (TOPMed) reveals nine processes that explain the variation in mutation properties between loci. We provide a biological interpretation for seven of these processes. We associate one process with bulky DNA lesions that are resolved asymmetrically with respect to transcription and replication. Two processes track direction of replication fork and replication timing, respectively. We identify a mutagenic effect of active demethylation primarily acting in regulatory regions and a mutagenic effect of long interspersed nuclear elements. We localize a mutagenic process specific to oocytes from population sequencing data. This process appears transcriptionally asymmetric.