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Background Non-communicable diseases are a rapidly growing cause of mortality and morbidity in Peru, accounting for 73% of total deaths. There is limited research on health system readiness to manage this rising burden. Our study characterized the readiness of healthcare facilities to manage patients with hypertension and/or type 2 diabetes (T2D) across two public healthcare systems in Puno, a largely rural and low-income department in Peru. Methods We adapted the World Health Organization Service Availability and Readiness Assessment to characterize resources and services for hypertension and T2D care. We administered the survey to personnel at healthcare facilities in Puno. Service readiness scores were calculated based on tracer items necessary for hypertension or T2D care. Facilities with ≥ 70% of tracer items were considered ready to manage each disease. Results Between June 2022 and June 2023, we surveyed 85% (414/488) of Puno’s government-run healthcare facilities. Overall, only 28% and 29% were considered ready to manage hypertension and T2D, respectively. Despite larger annual cumulative case volumes at health posts and low-level health centers, lower-level facilities were significantly less likely to be ready to manage hypertension (OR = 0.20, 95% CI 0.11–0.36) or T2D (OR = 0.03, 95% CI 0.01–0.06). Areas of concern included an overreliance on aneroid blood pressure monitors, their infrequent calibration, and limited hemoglobin A1c and urine testing. Additionally, only 66% and 48% of providers self-reported that they could diagnose hypertension and T2D, respectively. There was also low essential medication availability including insulin (7.2%) and fixed-dose combinations (0.5%) and a scarcity of trained healthcare professionals, particularly community health workers at health posts (49.8% had none). Conclusions Healthcare facilities were largely unprepared to manage hypertension and T2D, underscoring the critical need for health system strengthening to address disparities in non-communicable disease management across Puno.

Left ventricular hypertrophy (LVH) is one of the strongest predictors of cardiovascular disease (CVD) and mortality; yet the means to diagnose LVH in resource-constrained settings remain limited. The objectives of this study were to determine LVH prevalence by transthoracic echocardiography (TTE) in a high-risk group, and compare TTE vs. electrocardiography (ECG-LVH) for LVH detection. We analyzed enrollment data from the Haiti cardiovascular disease cohort study on adults (≥ 18 years, n  = 3,005) in Port-au-Prince between 2019 and 2021. All participants underwent questionnaires, vital signs, physical exams, and 12-lead ECGs. TTEs were acquired on those with hypertension or exhibiting CVD symptoms ( n  = 1040, 34.7%). TTE-LVH was defined according to the American Society of Echocardiography guidelines and ECG-LVH by Sokolow-Lyon, Cornell, and Limb-Lead Voltage criteria. The prevalence of TTE-LVH was 39.0% (95% CI 36.6–41.5%) and associated with older age. Only 26% of those with TTE-LVH and elevated blood pressure were on antihypertensives. Prevalence of ECG-LVH ranged from 1.9 to 5.0%, and compared to TTE-LVH had low agreement (κ < 0.20), low sensitivity (< 10%) and high specificity (> 90%). These findings indicate a high prevalence of TTE-LVH among high-risk Haitian adults, and poor detection using ECGs compared to TTEs. For those with TTE-LVH, treatment with antihypertensives may reduce the risk of adverse CVD outcomes.

Background Pregnancy is a crucial period to improve cardiovascular health (CVH) for mothers and their families. The current study emphasizes framework-guided factors that influence the adaptation of an evidence-based intervention (Parents as Teachers and Healthy Eating Active Living Taught at Home [PAT + HEALTH]) to support healthy gestational weight gain and postpartum weight management among pregnant women with obesity and their infants in Nigeria. Methods From May to June 2023, 43 in-depth interviews were conducted with 11 parents, 15 community health extension workers (CHEWs)/health educators, and 17 policymakers/ healthcare supervisors in the Federal Capital Territory, Nigeria. Additionally, nine focus groups were conducted with 75 participants. Interviews were recorded, de-identified, and transcribed. The updated Consolidated Framework for Implementation Research (CFIR 2.0) informed the development of the interview guides and the thematic analysis. Transcripts were double-coded using Dedoose. Results We identified assessing context, tailoring strategies, local attitudes, and sustainability as constructs to consider when adapting and implementing the PAT + HEALTH intervention successfully within the Nigerian primary care context. For example, policymakers and healthcare supervisors emphasized the feasibility of the intervention, including raising community awareness, planning for hard-to-reach areas, and ensuring supportive supervision of CHEWs delivering the intervention. Additional factors included customizing educational content and delivery methods to fit the cultural, socioeconomic, and environmental contexts of Nigerian families. CHEWs highlighted the importance of public education on locally available foods for better nutrition. Potential barriers to the PAT + HEALTH intervention included local attitudes influenced by sociocultural factors, such as food taboos, and structural factors, including limited financial support for the long-term sustainability of some components of the home visiting program. Conclusions Building on these formative activities, the ENHANCE CVH trial will advance dissemination and implementation science by adapting, testing, and evaluating the effectiveness and implementation of the PAT + HEALTH intervention among pregnant women with obesity and their infants in Nigeria in a cluster randomized trial. Trial registration ClinicalTrials.gov/NCT06773299, Registration Date: January 14, 2025.

As global adoption of antiretroviral therapy extends the lifespan of People Living with HIV (PLHIV) through viral suppression, the risk of comorbid conditions such as hypertension has risen, creating a need for effective, scalable interventions to manage comorbidities in PLHIV. The Heart, Lung, and Blood Co-morbiditieS Implementation Models in People Living with HIV (HLB-SIMPLe) Alliance has been funded by the National Heart, Lung, and Blood Institute (NHLBI) and the Fogarty International Center (FIC) since September 2020. The Alliance was created to conduct late-stage implementation research to contextualize, implement, and evaluate evidence-based strategies to integrate the diagnosis, treatment, and control of cardiovascular diseases, particularly hypertension, in PLHIV in low- and middle-income countries (LMICs). The Alliance consists of six individually-funded clinical trial cooperative agreement research projects based in Botswana, Mozambique, Nigeria, South Africa, Uganda, and Zambia; the Research Coordinating Center; and personnel from NIH, NHLBI, and FIC (the Federal Team). The Federal Team works together with the members of the seven cooperative agreements which comprise the alliance. The Federal Team includes program officials, project scientists, grant management officials and clinical trial specialists. This Alliance of research scientists, trainees, and administrators works collaboratively to provide and support venues for ongoing information sharing within and across the clinical trials, training and capacity building in research methods, publications, data harmonization, and community engagement. The goal is to leverage shared learning to achieve collective success, where the resulting science and training are greater with an Alliance structure rather than what would be expected from isolated and unconnected individual research projects. In this manuscript, we describe how the Research Coordinating Center performs the role of providing organizational efficiencies, scientific technical assistance, research capacity building, operational coordination, and leadership to support research and training activities in this multi-project cooperative research Alliance. We outline challenges and opportunities during the initial phases of coordinating research and training in the HLB-SIMPLe Alliance, including those most relevant to dissemination and implementation researchers.

Complex diseases such as hypertension are inherently multifactorial and involve many factors of mild-to-minute effect sizes. A genome-wide association study (GWAS) typically tests hundreds of thousands of single-nucleotide polymorphisms (SNPs), and offers opportunity to evaluate aggregated effects of many genetic variants with effects that are too small to detect individually. The gene-set-enrichment analysis (GSEA) is a pathway-based approach that tests for such aggregated effects of genes that are linked by biological functions. A key step in GSEA is the summary statistic (gene score) used to measure the overall relevance of a gene based on all SNPs tested in the gene. Existing GSEA methods use maximum statistics sensitive to gene size and linkage equilibrium. We propose the approach of variable set enrichment analysis (VSEA) and study new gene score methods that are less dependent on gene size. The new method treats groups of variables (SNPs or other variants) as base units for summarizing gene scores and relies less on gene definition itself. The power of VSEA is analyzed by simulation studies modeling various scenarios of complex multiloci interactions. Results show that the new gene scores generally performed better, some substantially so, than existing GSEA extension to GWAS. The new methods are implemented in an R package and when applied to a real GWAS data set demonstrated its practical utility in a GWAS setting.

Objectives: To reduce respondent burden for future evaluations of the National Heart, Lung, and Blood Institute-supported Programs to Increase Diversity Among Indi­viduals Engaged in Health-Related Research (PRIDE), a mentored-research education program, we sought to shorten the 33-item Ragins and McFarlin Mentor Role Instru­ment (RMMRI), measuring mentor-role ap­praisals, and the 69-item Clinical Research Appraisal Inventory (CRAI), measuring research self-efficacy. Methods: Three nationally recruited, junior-faculty cohorts attended two, annual 2-3 week Summer Institutes (SI-1/SI-2: 2011/2012, 2012/2013, 2013/2014) at one of six PRIDE sites. Mentees completed the RMMRI two months after mentor assign­ment and the CRAI at baseline (pre-SI-1) and 6-month (mid-year) and 12-month (post-SI-2) follow-up. Publications data ob­tained from Scopus in October 2015 were verified with mentees’ curriculum vitae. The RMMRI and CRAI were shortened using an iterative process of principal-components analysis. The shortened measures were ex­amined in association with each other (mul­tiple linear regression) and with increase in publications (repeated-measures analysis of covariance). Results: PRIDE enrolled 152 mentees (70% women; 60% Black, 35% Hispanic/Latino). Cronbach’s alphas for the new 9-item RMMRI, 19-item CRAI, and four CRAI-19 subscales were excellent. Controlling for baseline self-efficacy and cohort, RMMRI-9 scores were independently, positively associated with post-SI-2 scores on the CRAI-19 and three subscales (writing, study design/data analysis, and collaboration/grant preparation). Controlling for cohort, higher RMMRI-9 and post-SI-2 CRAI-19 scores were each associated with greater increase in publications. Conclusions: The RMMRI-9 and CRAI- 19 retained the excellent psychometric properties of the longer measures. Find­ings support use of the shortened mea­sures in future evaluations of PRIDE. Ethn Dis. 2017;27(2):179-188; doi:10.18865/ed.27.2.179.

Basic Translational Research Letter To the Editor Elevated levels of inflammatory mediators have been identified in patients with heart failure (HF) with a reduced ejection fraction (HFrEF) in direct relation to worsening New York Heart Association (NYHA) class [1]. [...]we sought to determine whether DAMPs were elevated in HF patients in relation to NYHA class, as well as assess their diagnostic accuracy for HF. Fig. 1 Damage-associated molecular patterns in heart failure (HF) with reduced ejection fraction (EF). (a-e) Biomarker levels in controls (C) and patients with New York Heart Association class I-IV HF for NT-proBNP (a), high-sensitivity (hs) troponin (b), galectin-3 (c), HMGB1 (d), and calprotectin (e).

Background/Aims: Progressive chronic kidney disease (CKD) is associated with worsening cardiovascular (CV) risk not explained by traditional risk factors. Left ventricular (LV) hypertrophy (LVH) is an important CV risk factor, but its progression has not been documented in early CKD. We explored whether progression of LVH in early CKD would occur despite stable kidney function. Methods: We conducted a post hoc analysis of a 12-month study of lanthanum carbonate in stage 3 CKD, which included longitudinal assessments of CV biomarkers. Primary outcome for the analysis was the change in LV mass (LVM) indexed to height in meters 2.7 (LVM/Ht 2.7 ). Secondary outcomes were changes in blood pressure (BP), pulse-wave velocity, LV systolic/diastolic function, fibroblast growth factor 23 (FGF23), klotho, and estimated glomerular filtration rate (eGFR). Results: Thirty-one of 38 original subjects had sufficient data for analysis. LVM/Ht 2.7 increased (47 ± 13 vs. 53 ± 13 g/m 2.7 , p = 0.006) over 12 months despite stable BP, stable eGFR and normal LV systolic function. Vascular stiffness and LV diastolic dysfunction persisted throughout the study. Klotho levels decreased (748 ± 289 to 536 ± 410 pg/ml, p = 0.03) but were unrelated to changes in LVM/Ht 2.7 . The change in FGF23/klotho ratio was strongly correlated with changes in LVM/Ht 2.7 (r 2 = 0.582, p = 0.03). Conclusion: Subjects with stage 3 CKD exhibited increasing LVM, persistent LV diastolic dysfunction and vascular stiffness despite stable kidney function, BP and LV systolic function. Abnormal FGF23 signaling due to reduced klotho expression may be associated with increasing LVM. These findings deserve further evaluation in a larger population given the adverse prognostic value of these CV biomarkers.

Background/Aims: Cardiovascular disease (CVD) is increased in chronic kidney disease (CKD), and contributed to by the CKD-mineral bone disorder (CKD-MBD). CKD-MBD begins in early CKD and its vascular manifestations begin with vascular stiffness proceeding to increased carotid artery intima-media thickness (cIMT) and vascular calcification (VC). Phosphorus is associated with this progression and is considered a CVD risk factor in CKD. We hypothesized that modifying phosphorus balance with lanthanum carbonate (LaCO 3 ) in early CKD would not produce hypophosphatemia and may affect vascular manifestations of CKD-MBD. Methods: We randomized 38 subjects with normophosphatemic stage 3 CKD to a fixed dose of LaCO 3 or matching placebo without adjusting dietary phosphorus in a 12-month randomized, double-blind, pilot and feasibility study. The primary outcome was the change in serum phosphorus. Secondary outcomes were changes in measures of phosphate homeostasis and vascular stiffness assessed by carotid-femoral pulse wave velocity (PWV), cIMT and VC over 12 months. Results: There were no statistically significant differences between LaCO 3 and placebo with respect to the change in serum phosphorus, urinary phosphorus, tubular reabsorption of phosphorus, PWV, cIMT, or VC. Biomarkers of the early CKD-MBD such as plasma fibroblast growth factor-23, Dickkopf-related protein 1 (DKK1), and sclerostin were increased 2- to 3-fold at baseline, but were not affected by LaCO 3 . Conclusion: Twelve months of LaCO 3 had no effect on serum phosphorus and did not alter phosphate homeostasis, PWV, cIMT, VC, or biomarkers of CKD-MBD.

Background Persistent vascular inflammation has been implicated as an important cause for a higher prevalence of cardiovascular disease (CVD) in HIV-infected adults. In several populations at high risk for CVD, vascular 18 Fluorodeoxyglucose ( 18 FDG) uptake quantified using 3D-positron emission-computed tomography (PET-CT) has been used as a molecular level biomarker for the presence of metabolically active proinflammatory macrophages in rupture-prone early atherosclerotic plaques. We hypothesized that 18 FDG PET-CT imaging would detect arterial inflammation and early atherosclerosis in HIV-infected adults with modest CVD risk. Methods We studied 9 HIV-infected participants with fully suppressed HIV viremia on antiretroviral therapy (8 men, median age 52 yrs, median BMI 29 kg/m 2 , median CD4 count 655 cells/μL, 33% current smokers) and 5 HIV-negative participants (4 men, median age 44 yrs, median BMI 25 kg/m 2 , no current smokers). Mean Framingham Risk Scores were higher for HIV-infected persons (9% vs. 2%, p < 0.01). 18 FDG (370 MBq) was administered intravenously. 3D-PET-CT images were obtained 3.5 hrs later. 18 FDG uptake into both carotid arteries and the aorta was compared between the two groups. Results Right and left carotid 18 FDG uptake was greater ( P  < 0.03) in the HIV group (1.77 ±0.26, 1.33 ±0.09 target to background ratio (TBR)) than the control group (1.05 ± 0.10, 1.03 ± 0.05 TBR). 18 FDG uptake in the aorta was greater in HIV (1.50 ±0.16 TBR) vs control group (1.24 ± 0.05 TBR), but did not reach statistical significance ( P  = 0.18). Conclusions Carotid artery 18 FDG PET-CT imaging detected differences in vascular inflammation and early atherosclerosis between HIV-infected adults with CVD risk factors and healthy HIV-seronegative controls. These findings confirm the utility of this molecular level imaging approach for detecting and quantifying glucose uptake into inflammatory macrophages present in metabolically active, rupture-prone atherosclerotic plaques in HIV infected adults; a population with increased CVD risk.