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Cardiovascular diseases (CVDs) are the most common cause of non-communicable disease mortality in sub-Saharan African (SSA) countries. Gaps in knowledge of CVD conditions and their risk factors are important barriers in effective prevention and treatment. Yet, evidence on the awareness and knowledge level of CVD and associated risk factors among populations of SSA is scarce. This review aimed to synthesize available evidence of the level of knowledge of and perceptions towards CVDs and risk factors in the SSA region. Five databases were searched for publications up to December 2016. Narrative synthesis was conducted for knowledge level of CVDs, knowledge of risk factors and clinical signs, factors influencing knowledge of CVDs and source of health information on CVDs. The review was registered with Prospero (CRD42016049165). Of 2212 titles and abstracts screened, 45 full-text papers were retrieved and reviewed and 20 were included: eighteen quantitative and two qualitative studies. Levels of knowledge and awareness for CVD and risk factors were generally low, coupled with poor perception. Most studies reported less than half of their study participants having good knowledge of CVDs and/or risk factors. Proportion of participants who were unable to identify a single risk factor and clinical symptom for CVDs ranged from 1.8% in a study among hospital staff in Nigeria to a high of 73% in a population-based survey in Uganda and 7% among University staff in Nigeria to 75.1% in a general population in Uganda respectively. High educational attainment and place of residence had a significant influence on the levels of knowledge for CVDs among SSA populations. Low knowledge of CVDs, risk factors and clinical symptoms is strongly associated with the low levels of educational attainment and rural residency in the region. These findings provide useful information for implementers of interventions targeted at the prevention and control of CVDs, and encourages them to incorporate health promotion and awareness campaigns in order to enhance knowledge and awareness of CVDs in the region.

Prediction models for gestational hypertension and preeclampsia have been developed with data and assumptions from developed countries. Their suitability and application for low resource settings have not been tested. This review aimed to identify and assess the methodological quality of prediction models for gestational hypertension and pre-eclampsia with reference to their application in low resource settings. Using combinations of keywords for gestational hypertension, preeclampsia and prediction models seven databases were searched to identify prediction models developed with maternal data obtained before 20 weeks of pregnancy and including at least three predictors (Prospero registration CRD 42017078786). Prediction model characteristics and performance measures were extracted using the CHARMS, STROBE and TRIPOD checklists. The National Institute of Health quality assessment tools for observational cohort and cross-sectional studies were used for study quality appraisal. We retrieved 8,309 articles out of which 40 articles were eligible for review. Seventy-seven percent of all the prediction models combined biomarkers with maternal clinical characteristics. Biomarkers used as predictors in most models were pregnancy associated plasma protein-A (PAPP-A) and placental growth factor (PlGF). Only five studies were conducted in a low-and middle income country. Most of the studies evaluated did not completely follow the CHARMS, TRIPOD and STROBE guidelines in prediction model development and reporting. Adherence to these guidelines will improve prediction modelling studies and subsequent application of prediction models in clinical practice. Prediction models using maternal characteristics, with good discrimination and calibration, should be externally validated for use in low and middle income countries where biomarker assays are not routinely available.

Background In the past two decades, the built environment emerged as a conceptually important determinant of obesity. As a result, an abundance of studies aiming to link environmental characteristics to weight-related outcomes have been published, and multiple reviews have attempted to summarise these studies under different scopes and domains. We set out to summarise the accumulated evidence across domains by conducting a review of systematic reviews on associations between any aspect of the built environment and overweight or obesity. Methods Seven databases were searched for eligible publications from the year 2000 onwards. We included systematic literature reviews, meta-analyses and pooled analyses of observational studies in the form of cross-sectional, case–control, longitudinal cohort, ecological, descriptive, intervention studies and natural experiments. We assessed risk of bias and summarised results structured by built environmental themes such as food environment, physical activity environment, urban–rural disparity, socioeconomic status and air pollution. Results From 1850 initial hits, 32 systematic reviews were included, most of which reported equivocal evidence for associations. For food- and physical activity environments, associations were generally very small or absent, although some characteristics within these domains were consistently associated with weight status such as fast-food exposure, urbanisation, land use mix and urban sprawl. Risks of bias were predominantly high. Conclusions Thus far, while most studies have not been able to confirm the assumed influence of built environments on weight, there is evidence for some obesogenic environmental characteristics. Registration : This umbrella review was registered on PROSPERO under ID CRD42019135857.

Diabetes is largely a self-managed disease; thus, care outcomes are closely linked to self-management behaviours. Structured self-management education (DSME) interventions are, however, largely unavailable in Africa. We sought to characterise DSME interventions in two urban low-resource primary settings; and to explore diabetes self-management knowledge and behaviours, of persons living with diabetes (PLD). A convergent parallel mixed-methods study was conducted between January and February 2021 in Accra, Ghana. The sampling methods used for selecting participants were total enumeration, consecutive sampling, purposive and judgemental sampling. Multivariable regression models were used to study the association between diabetes self-management knowledge and behaviours. We employed inductive content analysis of informants' experiences and context, to complement the quantitative findings. In total, 425 PLD (70.1% (n = 298) females, mean age 58 years (SD 12), with a mean blood glucose of 9.4 mmol/l (SD 6.4)) participated in the quantitative study. Two managers, five professionals, two diabetes experts and 16 PLD participated in in-depth interviews. Finally, 24 PLD were involved in four focus group discussions. The median diabetes self-management knowledge score was 40% ((IQR 20-60). For every one unit increase in diabetes self-management knowledge, there were corresponding increases in the diet (5%;[95% CI: 2%-9%, p<0.05]), exercise (5%; [95% CI:2%-8%, p<0.05]) and glucose monitoring (4%;[95% CI:2%-5%, p<0.05]) domains of the diabetes self-care activities scale respectively. The DSME interventions studied, were unstructured and limited by resources. Financial constraints, conflicting messages, beliefs, and stigma were the themes underpinning self-management behaviour. The DSME interventions studied were under-resourced, and unstructured. Diabetes self-management knowledge though limited, was associated with self-management behaviour. DSME interventions in low resource settings should be culturally tailored and should incorporate sessions on mitigating financial constraints. Future studies should focus on creating structured DSME interventions suited to resource-constrained settings.

Several clinical trials have reported inconsistent findings for the effect of fibrates on cardiovascular risk. We undertook a systematic review and meta-analysis to investigate the effects of fibrates on major clinical outcomes. We systematically searched Medline, Embase, and the Cochrane Library for trials published between 1950 and March, 2010. We included prospective randomised controlled trials assessing the effects of fibrates on cardiovascular outcomes compared with placebo. Summary estimates of relative risk (RR) reductions were calculated with a random effects model. Outcomes analysed were major cardiovascular events, coronary events, stroke, heart failure, coronary revascularisation, all-cause mortality, cardiovascular death, non-vascular death, sudden death, new onset albuminuria, and drug-related adverse events. We identified 18 trials providing data for 45 058 participants, including 2870 major cardiovascular events, 4552 coronary events, and 3880 deaths. Fibrate therapy produced a 10% RR reduction (95% CI 0–18) for major cardiovascular events (p=0·048) and a 13% RR reduction (7–19) for coronary events (p<0·0001), but had no benefit on stroke (−3%, −16 to 9; p=0·69). We noted no effect of fibrate therapy on the risk of all-cause mortality (0%, −8 to 7; p=0·92), cardiovascular mortality (3%, −7 to 12; p=0·59), sudden death (11%, −6 to 26; p=0·19), or non-vascular mortality (−10%, −21 to 0·5; p=0·063). Fibrates reduced the risk of albuminuria progression by 14% (2–25; p=0·028). Serious drug-related adverse events were not significantly increased by fibrates (17 413 participants, 225 events; RR 1·21, 0·91–1·61; p=0·19), although increases in serum creatinine concentrations were common (1·99, 1·46–2·70; p<0·0001). Fibrates can reduce the risk of major cardiovascular events predominantly by prevention of coronary events, and might have a role in individuals at high risk of cardiovascular events and in those with combined dyslipidaemia. National Health and Medical Research Council of Australia.

In a follow-up study of patients with type 2 diabetes, mortality benefits in those originally assigned to antihypertensive therapy were evident at the end of follow-up, but in-trial glucose differences did not result in long-term benefits in mortality or macrovascular events. Post-trial follow-up studies involving patients with diabetes have previously shown long-term beneficial effects of earlier periods of intensive glucose control, but not blood-pressure lowering, on a range of outcomes, including mortality and macrovascular events. 1 – 3 The Epidemiology of Diabetes Interventions and Complications (EDIC) study, an extension of the Diabetes Control and Complications Trial (DCCT) involving young patients with type 1 diabetes and no history of cardiovascular disease, hypertension, or hypercholesterolemia, showed a lower risk of macrovascular events, as well as a sustained benefit with respect to microvascular complications, beyond the period of intensive glucose control. 1 The post-intervention follow-up of the . . .

In the past years many inflammatory markers have been studied in association with clinically manifest cardiovascular disease (CVD) and carotid intima-media thickness (CIMT) in HIV-infected patients, to obtain insights in the increased cardiovascular risk observed in HIV infection. This systematic review provides an oversight of the current knowledge. A search was performed in PubMed, Embase and Cochrane in July 2014, identifying all articles from 1996 onwards addressing the relation between inflammatory markers and CVD or CIMT in HIV-positive adults. Two authors, using predefined criteria, independently conducted the selection of articles, critical appraisal and extraction of the data. Analysis was focused on the immune markers that were most frequently assessed. The review protocol was registered in the PROSPERO database at 11 July 2014 (registration number CRD42014010516). This review was performed according to the PRISMA guideline. Forty articles were selected; eight addressing cardiovascular disease (CVD) and thirty-two addressing CIMT. C-reactive protein (CRP), interleukin-6 (IL-6) and d-dimer were assessed most frequently in relation to the occurrence of CVD; in four out of eight studies. All three markers were positively related to CVD in three out of four studies. Studies addressing CIMT were too heterogeneous with respect to patient populations, inflammatory markers, CIMT measurement protocols and statistical methods to allow for a formal meta-analysis to obtain summary statistics. CRP, IL-6 and soluble vascular cell adhesion molecule (sVCAM-1) were the most studied markers in relation to CIMT. None of the inflammatory markers showed an association with CIMT. This review showed a relation between some inflammatory markers and CVD, however, no consistent relation is observed for CIMT. Statistical approaches that yields effect estimates and standardized CIMT protocols should be chosen. Further research should focus on prospective studies and a selected set of inflammatory markers.

Bempedoic acid, an ATP citrate lyase inhibitor, reduces low-density lipoprotein (LDL) cholesterol levels and is associated with a low incidence of muscle-related adverse events; its effects on cardiovascular outcomes remain uncertain. We conducted a double-blind, randomized, placebo-controlled trial involving patients who were unable or unwilling to take statins owing to unacceptable adverse effects (\"statin-intolerant\" patients) and had, or were at high risk for, cardiovascular disease. The patients were assigned to receive oral bempedoic acid, 180 mg daily, or placebo. The primary end point was a four-component composite of major adverse cardiovascular events, defined as death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization. A total of 13,970 patients underwent randomization; 6992 were assigned to the bempedoic acid group and 6978 to the placebo group. The median duration of follow-up was 40.6 months. The mean LDL cholesterol level at baseline was 139.0 mg per deciliter in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg per deciliter; the observed difference in the percent reductions was 21.1 percentage points in favor of bempedoic acid. The incidence of a primary end-point event was significantly lower with bempedoic acid than with placebo (819 patients [11.7%] vs. 927 [13.3%]; hazard ratio, 0.87; 95% confidence interval [CI], 0.79 to 0.96; P = 0.004), as were the incidences of a composite of death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction (575 [8.2%] vs. 663 [9.5%]; hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P = 0.006); fatal or nonfatal myocardial infarction (261 [3.7%] vs. 334 [4.8%]; hazard ratio, 0.77; 95% CI, 0.66 to 0.91; P = 0.002); and coronary revascularization (435 [6.2%] vs. 529 [7.6%]; hazard ratio, 0.81; 95% CI, 0.72 to 0.92; P = 0.001). Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause. The incidences of gout and cholelithiasis were higher with bempedoic acid than with placebo (3.1% vs. 2.1% and 2.2% vs. 1.2%, respectively), as were the incidences of small increases in serum creatinine, uric acid, and hepatic-enzyme levels. Among statin-intolerant patients, treatment with bempedoic acid was associated with a lower risk of major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization). (Funded by Esperion Therapeutics; CLEAR Outcomes ClinicalTrials.gov number, NCT02993406.).

This is the introductory paper in a series of eight papers. In this series, we integrate the theoretical design options with the practice of conducting pragmatic trials. For most new market-approved treatments, the clinical evidence is insufficient to fully guide physicians and policy makers in choosing the optimal treatment for their patients. Pragmatic trials can fill this gap, by providing evidence on the relative effectiveness of a treatment strategy in routine clinical practice, already in an early phase of development, while maintaining the strength of randomized controlled trials. Selecting the setting, study population, mode of intervention, comparator, and outcome are crucial in designing pragmatic trials. In combination with monitoring and data collection that does not change routine care, this will enable appropriate generalization to the target patient group in clinical practice. To benefit from the full potential of pragmatic trials, there is a need for guidance and tools in designing these studies while ensuring operational feasibility. This paper introduces the concept of pragmatic trial design. The complex interplay between pragmatic design options, feasibility, stakeholder acceptability, validity, precision, and generalizability will be clarified. In this way, balanced design choices can be made in pragmatic trials with an optimal chance of success in practice.

Uptake of antiretroviral treatment (ART) is expanding rapidly in low- and middle-income countries (LMIC). Monitoring of virological suppression is recommended at 6 months of treatment and annually thereafter. In case of confirmed virological failure, a switch to second-line ART is indicated. There is a paucity of data on virological suppression and clinical management of patients experiencing viremia in clinical practice in LMIC. We report a large-scale multicenter assessment of virological suppression over time and management of viremia under programmatic conditions. Linked medical record and laboratory source data from adult patients on first-line ART at 52 South African centers between 1 January 2007 and 1 May 2018 were studied. Virological suppression, switch to second-line ART, death, and loss to follow-up were analyzed. Multistate models and Cox proportional hazard models were used to assess suppression over time and predictors of treatment outcomes. A total of 104,719 patients were included. Patients were predominantly female (67.6%). Median age was 35.7 years (interquartile range [IQR]: 29.9-43.0). In on-treatment analysis, suppression below 1,000 copies/mL was 89.0% at month 12 and 90.4% at month 72. Suppression below 50 copies/mL was 73.1% at month 12 and 77.5% at month 72. Intention-to-treat suppression was 75.0% and 64.3% below 1,000 and 50 copies/mL at month 72, respectively. Viremia occurred in 19.8% (20,766/104,719) of patients during a median follow-up of 152 (IQR: 61-265) weeks. Being male and below 35 years of age and having a CD4 count below 200 cells/μL prior to start of ART were risk factors for viremia. After detection of viremia, confirmatory testing took 29 weeks (IQR: 16-54). Viral resuppression to below 1,000 copies/mL without switch of ART occurred frequently (45.6%; 6,030/13,210) but was associated with renewed viral rebound and switch. Of patients with confirmed failure who remained in care, only 41.5% (1,872/4,510) were switched. The median time to switch was 68 weeks (IQR: 35-127), resulting in 12,325 person-years spent with a viral load above 1,000 copies/mL. Limitations of this study include potential missing data, which is in part addressed by the use of cross-matched laboratory source data, and the possibility of unmeasured confounding. In this study, 90% virological suppression below the threshold of 1,000 copies/mL was observed in on-treatment analysis. However, this target was not met at the 50-copies/mL threshold or in intention-to-treat analysis. Clinical management in response to viremia was profoundly delayed, prolonging the duration of viremia and potential for transmission. Diagnostic tools to establish the cause of viremia are urgently needed to accelerate clinical decision-making.