Jimmy Volmink

Beta‐blockers for hypertension

Abstract Background Beta‐blockers refer to a mixed group of drugs with diverse pharmacodynamic and pharmacokinetic properties. They have shown long‐term beneficial effects on mortality and cardiovascular disease (CVD) when used in people with heart failure or acute myocardial infarction. Beta‐blockers were thought to have similar beneficial effects when used as first‐line therapy for hypertension. However, the benefit of beta‐blockers as first‐line therapy for hypertension without compelling indications is controversial. This review is an update of a Cochrane Review initially published in 2007 and updated in 2012. Objectives To assess the effects of beta‐blockers on morbidity and mortality endpoints in adults with hypertension. Search methods The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to June 2016: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 6), MEDLINE (from 1946), Embase (from 1974), and ClinicalTrials.gov. We checked reference lists of relevant reviews, and reference lists of studies potentially eligible for inclusion in this review, and also searched the the World Health Organization International Clinical Trials Registry Platform on 06 July 2015. Selection criteria Randomised controlled trials (RCTs) of at least one year of duration, which assessed the effects of beta‐blockers compared to placebo or other drugs, as first‐line therapy for hypertension, on mortality and morbidity in adults. Data collection and analysis We selected studies and extracted data in duplicate, resolving discrepancies by consensus. We expressed study results as risk ratios (RR) with 95% confidence intervals (CI) and conducted fixed‐effect or random‐effects meta‐analyses, as appropriate. We also used GRADE to assess the certainty of the evidence. GRADE classifies the certainty of evidence as high (if we are confident that the true effect lies close to that of the estimate of effect), moderate (if the true effect is likely to be close to the estimate of effect), low (if the true effect may be substantially different from the estimate of effect), and very low (if we are very uncertain about the estimate of effect). Main results Thirteen RCTs met inclusion criteria. They compared beta‐blockers to placebo (4 RCTs, 23,613 participants), diuretics (5 RCTs, 18,241 participants), calcium‐channel blockers (CCBs: 4 RCTs, 44,825 participants), and renin‐angiotensin system (RAS) inhibitors (3 RCTs, 10,828 participants). These RCTs were conducted between the 1970s and 2000s and most of them had a high risk of bias resulting from limitations in study design, conduct, and data analysis. There were 40,245 participants taking beta‐blockers, three‐quarters of them taking atenolol. We found no outcome trials involving the newer vasodilating beta‐blockers (e.g. nebivolol). There was no difference in all‐cause mortality between beta‐blockers and placebo (RR 0.99, 95% CI 0.88 to 1.11), diuretics or RAS inhibitors, but it was higher for beta‐blockers compared to CCBs (RR 1.07, 95% CI 1.00 to 1.14). The evidence on mortality was of moderate‐certainty for all comparisons. Total CVD was lower for beta‐blockers compared to placebo (RR 0.88, 95% CI 0.79 to 0.97; low‐certainty evidence), a reflection of the decrease in stroke (RR 0.80, 95% CI 0.66 to 0.96; low‐certainty evidence) since there was no difference in coronary heart disease (CHD: RR 0.93, 95% CI 0.81 to 1.07; moderate‐certainty evidence). The effect of beta‐blockers on CVD was worse than that of CCBs (RR 1.18, 95% CI 1.08 to 1.29; moderate‐certainty evidence), but was not different from that of diuretics (moderate‐certainty) or RAS inhibitors (low‐certainty). In addition, there was an increase in stroke in beta‐blockers compared to CCBs (RR 1.24, 95% CI 1.11 to 1.40; moderate‐certainty evidence) and RAS inhibitors (RR 1.30, 95% CI 1.11 to 1.53; moderate‐certainty evidence). However, there was little or no difference in CHD between beta‐blockers and diuretics (low‐certainty evidence), CCBs (moderate‐certainty evidence) or RAS inhibitors (low‐certainty evidence). In the single trial involving participants aged 65 years and older, atenolol was associated with an increased CHD incidence compared to diuretics (RR 1.63, 95% CI 1.15 to 2.32). Participants taking beta‐blockers were more likely to discontinue treatment due to adverse events than participants taking RAS inhibitors (RR 1.41, 95% CI 1.29 to 1.54; moderate‐certainty evidence), but there was little or no difference with placebo, diuretics or CCBs (low‐certainty evidence). Authors conclusions Most outcome RCTs on beta‐blockers as initial therapy for hypertension have high risk of bias. Atenolol was the beta‐blocker most used. Current evidence suggests that initiating treatment of hypertension with beta‐blockers leads to modest CVD reductions and little or no effects on mortality. These beta‐blocker effects are inferior to those of other antihypertensive drugs. Further research should be of high quality and should explore whether there are differences between different subtypes of beta‐blockers or whether beta‐blockers have differential effects on younger and older people.

Nutritional interventions for reducing morbidity and mortality in people with HIV.

BACKGROUNDnAdequate nutrition is important for optimal immune and metabolic function. Dietary support may, therefore, improve clinical outcomes in HIV-infected individuals by reducing the incidence of HIV-associated complications and attenuating progression of HIV disease, improving quality of life and ultimately reducing disease-related mortality.nnnOBJECTIVESnTo evaluate the effectiveness of various macronutrient interventions, given orally, in reducing morbidity and mortality in adults and children living with HIV infection.nnnSEARCH METHODSnWe searched CENTRAL (up to August 2011), MEDLINE (1966 to August 2011), EMBASE (1988 to August 2011), LILACS (up to February 2012), and Gateway (March 2006-February 2010). We also scanned reference lists of articles and contacted authors of relevant studies and other researchers.nnnSELECTION CRITERIAnRandomised controlled trials evaluating the effectiveness of macronutrient interventions compared with no nutritional supplements or placebo in the management of adults and children infected with HIV.nnnDATA COLLECTION AND ANALYSISnThree reviewers independently applied study selection criteria, assessed study quality, and extracted data. Effects were assessed using mean difference and 95% confidence intervals. Homogenous studies were combined wherever it was clinically meaningful to do so and a meta-analysis using the random effects model was conducted.nnnMAIN RESULTSnFourteen trials (including 1725 HIV positive adults and 271 HIV positive children), were included in this review. Neither supplementary food nor daily supplement of Spirulina significantly altered the risk of death compared with no supplement or placebo in malnourished, ART naive adult participants in the two studies which reported on this outcome. A nutritional supplement enhanced with protein did not significantly alter the risk of death compared to standard nutritional care in children with prolonged diarrhoea. Supplementation with macronutrient formulas given to provide protein and/or energy and fortified with micronutrients, in conjunction with nutrition counselling, significantly improved energy intake (3 trials; n=131; MD 393.57 kcal/day; 95% CI: 224.66 to 562.47;p<0.00001) and protein intake (2 trials; n=81; MD 23.5 g/day; 95% CI: 12.68, 34.01; p<0.00001) compared with no nutritional supplementation or nutrition counselling alone in adult participants with weight loss. In general supplementation with specific macronutrients such as amino acids, whey protein concentration or Spirulina did not significantly alter clinical, anthropometric or immunological outcomes compared with placebo in HIV-infected adults and children.nnnAUTHORS CONCLUSIONSnGiven the current evidence base, which is limited to fourteen relatively small trials all evaluating different macronutrient supplements in different populations at different stages of HIV infection and with varying treatment status, no firm conclusions can be drawn about the effects of macronutrient supplementation on morbidity and mortality in people living with HIV. It is, however, promising to see more studies being conducted in low-income countries, and particularly in children, where macronutrient supplementation both pre-antiretroviral treatment and in conjunction with antiretroviral treatment might prove to be beneficial.

Antibiotics for the primary prevention of acute rheumatic fever: a meta-analysis

BackgroundRheumatic fever continues to put a significant burden on the health of low socio-economic populations in low and middle-income countries despite the near disappearance of the disease in the developed world over the past century. Antibiotics have long been thought of as an effective method for preventing the onset of acute rheumatic fever following a Group-A streptococcal (GAS) throat infection; however, their use has not been widely adopted in developing countries for the treatment of sore throats. We have used the tools of systematic review and meta-analysis to quantify the effectiveness of antibiotic treatment for sore throat, with symptoms suggestive of group A streptococcal (GAS) infection, for the primary prevention of acute rheumatic fever.MethodsTrials were identified through a systematic search of titles and abstracts found in the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 4, 2003), MEDLINE (1966–2003), EMBASE (1966–2003), and the reference lists of identified studies. The selection criteria included randomised or quasi-randomised controlled trials comparing the effectiveness of antibiotics versus no antibiotics for the prevention of rheumatic fever in patients presenting with a sore throat, with or without confirmation of GAS infection, and no history of rheumatic fever.ResultsTen trials (n = 7665) were eligible for inclusion in this review. The methodological quality of the studies, in general, was poor. All of the included trials were conducted during the period of 1950 and 1961 and in 8 of the 10 trials the study population consisted of young adult males living on United States military bases. Fixed effects, meta-analysis revealed an overall protective effect for the use of antibiotics against acute rheumatic fever of 70% (RR = 0.32; 95% CI = 0.21–0.48). The absolute risk reduction was 1.67% with an NNT of 53. When meta-analysis was restricted to include only trials evaluating penicillin, a protective effect of 80% was found (Fixed effect RR = 0.20, 95% CI = 0.11–0.36) with an NNT of 60. The marginal cost of preventing one case of rheumatic fever by a single intramuscular injection of penicillin is approximately US

What Are the Effects of Teaching Evidence-Based Health Care (EBHC)? Overview of Systematic Reviews

46 in South Africa.ConclusionAntibiotics appear to be effective in reducing the incidence of acute rheumatic fever following an episode of suspected GAS pharyngitis. This effect may be achieved at relatively low cost if a single intramuscular penicillin injection is administered.

Low Carbohydrate versus Isoenergetic Balanced Diets for Reducing Weight and Cardiovascular Risk: A Systematic Review and Meta-Analysis

Background An evidence-based approach to health care is recognized internationally as a key competency for healthcare practitioners. This overview systematically evaluated and organized evidence from systematic reviews on teaching evidence-based health care (EBHC). Methods/Findings We searched for systematic reviews evaluating interventions for teaching EBHC to health professionals compared to no intervention or different strategies. Outcomes covered EBHC knowledge, skills, attitudes, practices and health outcomes. Comprehensive searches were conducted in April 2013. Two reviewers independently selected eligible reviews, extracted data and evaluated methodological quality. We included 16 systematic reviews, published between 1993 and 2013. There was considerable overlap across reviews. We found that 171 source studies included in the reviews related to 81 separate studies, of which 37 are in more than one review. Studies used various methodologies to evaluate educational interventions of varying content, format and duration in undergraduates, interns, residents and practicing health professionals. The evidence in the reviews showed that multifaceted, clinically integrated interventions, with assessment, led to improvements in knowledge, skills and attitudes. Interventions improved critical appraisal skills and integration of results into decisions, and improved knowledge, skills, attitudes and behaviour amongst practicing health professionals. Considering single interventions, EBHC knowledge and attitude were similar for lecture-based versus online teaching. Journal clubs appeared to increase clinical epidemiology and biostatistics knowledge and reading behavior, but not appraisal skills. EBHC courses improved appraisal skills and knowledge. Amongst practicing health professionals, interactive online courses with guided critical appraisal showed significant increase in knowledge and appraisal skills. A short workshop using problem-based approaches, compared to no intervention, increased knowledge but not appraisal skills. Conclusions EBHC teaching and learning strategies should focus on implementing multifaceted, clinically integrated approaches with assessment. Future rigorous research should evaluate minimum components for multifaceted interventions, assessment of medium to long-term outcomes, and implementation of these interventions.

Clinical characteristics and initial management of patients with tuberculous pericarditis in the HIV era: the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry

Background Some popular weight loss diets restricting carbohydrates (CHO) claim to be more effective, and have additional health benefits in preventing cardiovascular disease compared to balanced weight loss diets. Methods and Findings We compared the effects of low CHO and isoenergetic balanced weight loss diets in overweight and obese adults assessed in randomised controlled trials (minimum follow-up of 12 weeks), and summarised the effects on weight, as well as cardiovascular and diabetes risk. Dietary criteria were derived from existing macronutrient recommendations. We searched Medline, EMBASE and CENTRAL (19 March 2014). Analysis was stratified by outcomes at 3–6 months and 1–2 years, and participants with diabetes were analysed separately. We evaluated dietary adherence and used GRADE to assess the quality of evidence. We calculated mean differences (MD) and performed random-effects meta-analysis. Nineteen trials were included (nu200a=u200a3209); 3 had adequate allocation concealment. In non-diabetic participants, our analysis showed little or no difference in mean weight loss in the two groups at 3–6 months (MD 0.74 kg, 95%CI −1.49 to 0.01 kg; I2u200a=u200a53%; nu200a=u200a1745, 14 trials; moderate quality evidence) and 1–2 years (MD 0.48 kg, 95%CI −1.44 kg to 0.49 kg; I2u200a=u200a12%; nu200a=u200a1025; 7 trials, moderate quality evidence). Furthermore, little or no difference was detected at 3–6 months and 1–2 years for blood pressure, LDL, HDL and total cholesterol, triglycerides and fasting blood glucose (>914 participants). In diabetic participants, findings showed a similar pattern. Conclusions Trials show weight loss in the short-term irrespective of whether the diet is low CHO or balanced. There is probably little or no difference in weight loss and changes in cardiovascular risk factors up to two years of follow-up when overweight and obese adults, with or without type 2 diabetes, are randomised to low CHO diets and isoenergetic balanced weight loss diets.

Patient education and counselling for promoting adherence to treatment for tuberculosis.

BackgroundThe incidence of tuberculous pericarditis has increased in Africa as a result of the human immunodeficiency virus (HIV) epidemic. However, the effect of HIV co-infection on clinical features and prognosis in tuberculous pericarditis is not well characterised. We have used baseline data of the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry to assess the impact of HIV co-infection on clinical presentation, diagnostic evaluation, and treatment of patients with suspected tuberculous pericarditis in sub-Saharan Africa.MethodsConsecutive adult patients in 15 hospitals in three countries in sub-Saharan Africa were recruited on commencement of treatment for tuberculous pericarditis, following informed consent. We recorded demographic, clinical, diagnostic and therapeutic information at baseline, and have used the chi-square test and analysis of variance to assess probabilities of significant differences (in these variables) between groups defined by HIV status.ResultsA total of 185 patients were enrolled from 01 March 2004 to 31 October 2004, 147 (79.5%) of whom had effusive, 28 (15.1%) effusive-constrictive, and 10 (5.4%) constrictive or acute dry pericarditis. Seventy-four (40%) had clinical features of HIV infection. Patients with clinical HIV disease were more likely to present with dyspnoea (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.4 to 7.4, P = 0.005) and electrocardiographic features of myopericarditis (OR 2.8, 95% CI 1.1 to 6.9, P = 0.03). In addition to electrocardiographic features of myopericarditis, a positive HIV serological status was associated with greater cardiomegaly (OR 3.89, 95% CI 1.34 to 11.32, P = 0.01) and haemodynamic instability (OR 9.68, 95% CI 2.09 to 44.80, P = 0.0008). However, stage of pericardial disease at diagnosis and use of diagnostic tests were not related to clinical HIV status. Similar results were obtained for serological HIV status. Most patients were treated on clinical grounds, with microbiological evidence of tuberculosis obtained in only 13 (7.0%) patients. Adjunctive corticosteroids were used in 109 (58.9%) patients, with patients having clinical HIV disease less likely to be put on them (OR 0.37, 95% CI 0.20 to 0.68). Seven patients were on antiretroviral drugs.ConclusionPatients with suspected tuberculous pericarditis and HIV infection in Africa have greater evidence of myopericarditis, dyspnoea, and haemodynamic instability. These findings, if confirmed in other studies, may suggest more intensive management of the cardiac disease is warranted in patients with HIV-associated pericardial disease.

Research synthesis and dissemination as a bridge to knowledge management: the Cochrane Collaboration

BACKGROUNDnNon-adherence to tuberculosis treatment can lead to prolonged periods of infectiousness, relapse, emergence of drug-resistance, and increased morbidity and mortality. In this review, we assess whether patient education or counselling, or both, promotes adherence to tuberculosis treatment.nnnOBJECTIVESnTo evaluate the effects of patient education or counselling, or both, on treatment completion and cure in people requiring treatment for active or latent tuberculosis.nnnSEARCH METHODSnWithout language restriction, we searched for eligible studies in the Cochrane Infectious Diseases Group Specialized Register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and LILACS; checked reference lists of relevant articles; and contacted relevant researchers and organizations up to 24 November 2011.nnnSELECTION CRITERIAnRandomized controlled trials examining the effects of education or counselling, or both, on treatment completion and cure in people with clinical tuberculosis; and treatment completion and clinical tuberculosis in people with latent disease.nnnDATA COLLECTION AND ANALYSISnWe independently screened identified studies for eligibility, assessed methodological quality, and extracted data; with differences resolved by consensus. We expressed study results as risk ratios (RRs) with 95% confidence intervals (CI).nnnMAIN RESULTSnWe found three trials, with a total of 1437 participants, which examined the effects of different educational and counselling interventions on adherence to treatment for latent tuberculosis.All three trials reported the proportion of people who successfully completed treatment for latent tuberculosis. Overall, education or counselling interventions may increase successful treatment completion but the magnitude of benefit is likely to vary depending on the nature of the intervention, and the setting (data not pooled, 923 participants, three trials, low quality evidence).In a four-arm trial in children from Spain, counselling by nurses via telephone increased the proportion of children completing treatment from 65% to 94% (RR 1.44, 95% CI 1.21 to 1.72; 157 participants, one trial), and counselling by nurses through home visits increased completion to 95% (RR 1.46, 95% CI 1.23 to 1.74; 156 participants, one trial). Both of these interventions were superior to counselling by physicians at the tuberculosis clinic (RR 1.20, 95% CI 0.98 to 1.47; 159 participants, one trial).In the USA, a programme of peer counselling for adolescents failed to show an effect on treatment completion rates at six months (RR 1.01, 95% CI 0.90 to 1.13; 394 participants, one trial). In this trial treatment completion was around 75% even in the control group.In the third study, in prisoners from the USA, treatment completion was very low in the control group (12%), and although counselling significantly improved this, completion in the intervention group remained low at 24% (RR 1.94, 95% CI 1.03 to 3.68; 211 participants, one trial).None of these trials aimed to assess the effect of these interventions on the subsequent development of active tuberculosis, and we found no trials that assessed the effects of patient education or counselling on adherence to treatment for active tuberculosis.nnnAUTHORS CONCLUSIONSnEducational or counselling interventions may improve completion of treatment for latent tuberculosis. As would be expected, the magnitude of the benefit is likely to depend on the nature of the intervention, and the reasons for low completion rates in the specific setting.

Validation study of cause of death statistics in Cape Town, South Africa, found poor agreement

In the current information age, research synthesis is a particularly useful tool for keeping track of scientific research and making sense of the large volumes of frequently conflicting data derived from primary studies. The Cochrane Collaboration is a global initiative to help people make well-informed decisions about health care by preparing, maintaining and promoting the accessibility of systematic reviews of the effects of healthcare interventions. In this paper we set the work of the Cochrane Collaboration in historical perspective, explain what a Cochrane review is, and describe initiatives for promoting worldwide dissemination of synthesized information. We also consider emerging evidence of the Cochrane Collaborations impact on health-care practice, policy, research and education. Finally, we highlight the need for increased investment in the preparation and maintenance of Cochrane reviews, particularly those that address health issues that are relevant to people living in low- and middle-income countries.

Incentives and enablers to improve adherence in tuberculosis

OBJECTIVEnThe validity of the underlying cause of death on death notification forms was assessed by comparing it to the underlying cause determined independently from medical records.nnnSTUDY DESIGN AND SETTINGnRetrospective study of 703 deaths in two suburbs of Cape Town, South Africa. Two medical doctors completed a medical review death certificate to validate the registration death certificate for each decedent. Agreement, sensitivity, and positive predictive value were measured for underlying causes of death using the World Health Organization (WHO) mortality tabulation list 1.nnnRESULTSnAgreement was poor, with only 55.3% (95% confidence interval [CI]: 51.7, 59.0) of diagnoses matching at WHO mortality tabulation list 1 level. Validity of reported causes of death was poor for HIV, cardiovascular diseases, and diabetes. With correct reporting, the cause-specific mortality fraction for HIV increased from 11.9% to 18.3% (53.6%; 95% CI: 36.9, 77.6), for ischemic heart disease from 3.3% to 7.3% (121.7%; 95% CI: 53.5, 228.7), and for hypertensive diseases from 3.3% to 5.7% (73.9%; 95% CI: 14.4, 167.8). For diabetes, the mortality fraction decreased from 6.0% to 2.3% (-64.3%; 95% CI: -77.1, -37.8) and for ill-defined deaths from 7.4% to 2.3% (-69.2%; 95% CI: -81.0, -51.6).nnnCONCLUSIONnCurrent cause-specific mortality levels should be cautiously interpreted. Death certification training is required to improve the validity of mortality data.