Burden of depressive symptoms and non-alcohol substance abuse; and their association with alcohol use and partner violence: a cross-sectional study in four sub-Saharan Africa countries.

In sub-Saharan Africa, there are limited data on burden of non-alcohol substance abuse (NAS) and depressive symptoms (DS), yet potential risk factors such as alcohol and intimate partner violence (IPV) are common and NAS abuse may be the rise. The aim of this study was to measure the burden of DS and NAS abuse, and determine whether alcohol use and IPV are associated with DS and/or NAS abuse. We conducted a cross-sectional study at five sites in four countries: Nigeria (nurses), South Africa (teachers), Tanzania (teachers) and two sites in Uganda (rural and peri-urban residents). Participants were selected by simple random sampling from a sampling frame at each of the study sites. We used a standardized tool to collect data on demographics, alcohol use and NAS use, IPV and DS and calculated prevalence ratios (PR). We enrolled 1415 respondents and of these 34.6% were male. DS occurred among 383 (32.3%) and NAS use among 52 (4.3%). In the multivariable analysis, being female (PR  =  1.49, p  =  0.008), NAS abuse (PR  =  2.06, p  =  0.02) and IPV (PR  =  2.93, p < 0.001) were significantly associated with DS. Older age [odds ratio (OR) = 0.31, p < 0.001)], female (OR = 0.48, p  =  0.036) were protective of NAS but current smokers (OR = 2.98, p < 0.001) and those reporting IPV (OR  =  2.16, p  =  0.024) were more likely to use NAS. Longitudinal studies should be done to establish temporal relationships with these risk factors to provide basis for interventions.

When is a randomised controlled trial health equity relevant? Development and validation of a conceptual framework.

BACKGROUND: Randomised controlled trials can provide evidence relevant to assessing the equity impact of an intervention, but such information is often poorly reported. We describe a conceptual framework to identify health equity-relevant randomised trials with the aim of improving the design and reporting of such trials. METHODS: An interdisciplinary and international research team engaged in an iterative consensus building process to develop and refine the conceptual framework via face-to-face meetings, teleconferences and email correspondence, including findings from a validation exercise whereby two independent reviewers used the emerging framework to classify a sample of randomised trials. RESULTS: A randomised trial can usefully be classified as 'health equity relevant' if it assesses the effects of an intervention on the health or its determinants of either individuals or a population who experience ill health due to disadvantage defined across one or more social determinants of health. Health equity-relevant randomised trials can either exclusively focus on a single population or collect data potentially useful for assessing differential effects of the intervention across multiple populations experiencing different levels or types of social disadvantage. Trials that are not classified as 'health equity relevant' may nevertheless provide information that is indirectly relevant to assessing equity impact, including information about individual level variation unrelated to social disadvantage and potentially useful in secondary modelling studies. CONCLUSION: The conceptual framework may be used to design and report randomised trials. The framework could also be used for other study designs to contribute to the evidence base for improved health equity.

Risk of cardiovascular disease among teachers in Cape Town: Findings of the South African PaCT pilot study.

BACKGROUND: The accelerating epidemic of cardiovascular disease (CVD) and other non-communicable diseases (NCDs) highlights the need to establish long-term cohort studies in Africa. OBJECTIVE: The Partnership for Cohort Research and Training (PaCT) seeks to study NCDs in South Africa (SA), Uganda, Tanzania and Nigeria on a long-term basis. Pilot studies at each site have tested feasibility. The SA site additionally studied the prevalence of CVD risk factors and categorised participants' 10-year predicted risk of a cardiovascular event. METHODS: We enrolled teachers from 111 public schools in the Metro South Education District in Cape Town, SA, between January 2011 and May 2012. Participants completed a self-administered questionnaire and biological measurements, and chose post or email for 6-month follow-up. RESULTS: The participation of schools was permitted by 53.2% of principals, and 489 of 1 779 teachers agreed to participate. Of teachers willing to participate in the follow-up, 52% were retained, three-quarters by post and a quarter by email. Their mean age was 46.3 years and 70.3% were female. The prevalence of CVD risk factors was high and featured hypertension (48.5%), hypercholesterolaemia (20.5%), smoking (18.0%), diabetes (10.1%) and chronic kidney disease (10.4%), while 84.7% were overweight or obese. Of the participants, 18.7% were at high risk of a heart attack or stroke within 10 years. CONCLUSION: Establishing a cohort study among teachers has challenges but also opportunities for addressing CVD, which will soon impose a substantial burden on Cape Town's education system.

South African medical schools: Current state of selection criteria and medical students' demographic profile.

BACKGROUND: Selection of medical students at South African (SA) medical schools must promote equitable and fair access to students from all population groups, while ensuring optimal student throughput and success, and training future healthcare practitioners who will fulfil the needs of the local society. In keeping with international practices, a variety of academic and non-academic measures are used to select applicants for medical training programmes in SA medical schools. OBJECTIVES: To provide an overview of the selection procedures used by all eight medical schools in SA, and the student demographics (race and gender) at these medical schools, and to determine to what extent collective practices are achieving the goals of student diversity and inclusivity. METHODS: A retrospective, quantitative, descriptive study design was used. All eight medical schools in SA provided information regarding selection criteria, selection procedures, and student demographics (race and gender). Descriptive analysis of data was done by calculating frequencies and percentages of the variables measured. RESULTS: Medical schools in SA make use of academic and non-academic criteria in their selection processes. The latter include indices of socioeconomic disadvantage. Most undergraduate medical students in SA are black (38.7%), followed by white (33.0%), coloured (13.4%) and Indian/Asian (13.6%). The majority of students are female (62.2%). The number of black students is still proportionately lower than in the general population, while other groups are overrepresented. CONCLUSION: Selection policies for undergraduate medical programmes aimed at redress should be continued and further refined, along with the provision of support to ensure student success.

Cohort studies around the world: methodologies, research questions and integration to address the emerging global epidemic of chronic diseases.

With ageing populations, increased economic prosperity and the ensuing lifestyle changes, there has been a dramatic increase in the burden of chronic non-communicable diseases in countries of the developing world. The distribution of risk factors for chronic diseases among populations in developing countries has traditionally been very different from that in their Western counterparts, thus resulting in considerable variation in disease distribution in these settings. However, with the increase in globalization along with rapid advancements in technology, many developing countries are now faced with the challenge of a dual disease burden, battling existing communicable infectious diseases as well as the emerging epidemic of non-communicable chronic diseases. This paper highlights the need for multiple cohort studies on chronic diseases around the world, and explores some of the challenges in establishing and maintaining these studies in resource-constrained settings.

Educational factors that influence the urban-rural distribution of health professionals in South Africa: a case-control study.

SETTING: The influence of undergraduate and postgraduate training on health professionals' career choices in favour of rural and underserved communities has not been clearly demonstrated in resource-constrained settings. OBJECTIVES: This study aimed to evaluate the influence of educational factors on the choice of rural or urban sites of practice of health professionals in South Africa. METHODS: Responses to a questionnaire on undergraduate and postgraduate educational experiences by 174 medical practitioners in rural public practice were compared with those from 142 urban public hospital doctors. Outcomes measured included specific undergraduate and postgraduate educational experiences, and non-educational factors such as family and community influences that were likely to affect the choice of the site of practice. RESULTS: Compared with urban doctors, rural respondents were significantly less experienced, more likely to be black, and felt significantly more accountable to the community that they served. They were more than twice as likely as the urban group to have been exposed to rural situations during their undergraduate training, and were also five times more likely than urban respondents to state that exposure to rural practice as an undergraduate had influenced their choice of where they practise. Urban respondents were significantly more attracted to working where they do by professional development and postgraduate education opportunities and family factors than the rural group. CONCLUSIONS: Evidence is provided that rural exposure influences the choice of practice site by health professionals in a developing country context, but the precise curricular elements that have the most effect deserve further research.

Does South Africa need a national clinical trials support unit?

BACKGROUND: No national South African institution provides a coherent suite of support, available skills and training for clinicians wishing to conduct randomised controlled trials (RCTs) in the public sector. We report on a study to assess the need for establishing a national South African Clinical Trials Support Unit. OBJECTIVES: To determine the need for additional training and support for conduct of RCTs within South African institutions; identify challenges facing institutions conducting RCTs; and provide recommendations for enhancing trial conduct within South African public institutions. DESIGN: Key informant interviews of senior decision-makers at institutions with a stake in the South African public sector clinical trials research environment. RESULTS: Trial conduct in South Africa faces many challenges, including lack of dedicated funding, the burden on clinical load, and lengthy approval processes. Strengths include the high burden of disease and the prevalence of treatment-naïve patients. Participants expressed a significant need for a national initiative to support and enhance the conduct of public sector RCTs. Research methods training and statistical support were viewed as key. There was a broad range of views regarding the structure and focus of such an initiative, but there was agreement that the national government should provide specific funding for this purpose. CONCLUSIONS: Stakeholders generally support the establishment of a national clinical trials support initiative. Consideration must be given to the sustainability of such an initiative, in terms of funding, staffing, expected research outputs and permanence of location.

Incidence of acute rheumatic fever in the world: a systematic review of population-based studies.

BACKGROUND: There is no systematic overview of prospective studies of incidence of acute rheumatic fever (ARF) in the world. AIM: To summarise all population-based studies of the incidence of ARF world wide. METHOD: A systematic review of prospective population-based studies of the overall mean and annual specific incidence of the first episode of ARF was carried out. RESULTS: A systematic literature search identified 10 eligible studies from 10 countries on all continents, except Africa. The overall mean incidence rate of first attack of ARF was 5-51/100,000 population (mean 19/100,000; 95% CI 9 to 30/100,000). A low incidence rate of 10/100,000) was documented in Eastern Europe, Middle East (highest), Asia and Australasia. Studies with longitudinal data displayed a falling incidence rate over time. CONCLUSION: Despite an apparent fall in incidence over time, ARF incidence rates remain relatively high in non-Western countries. No information is available for Africa.

Mortality in Patients Treated for Tuberculous Pericarditis in Sub-Saharan Africa

Objective: To determine the mortality rate and its predictors in patients with a presumptive diagnosis of tuberculous pericarditis in sub-Saharan Africa. Design: Between 1 March 2004 and 31 October 2004; we enrolled 185 consecutive patients with presumed tuberculous pericarditis from 15 referral hospitals in Cameroon; Nigeria; and South Africa; and observed them during the 6-month course of antituberculosis treatment for the major outcome of mortality. This was an observational study; with the diagnosis and management of each patient left at the discretion of the attending physician. Using Cox regression; we have assessed the effect of clinical and therapeutic characteristics (recorded at baseline) on mortality during follow-up. Results: We obtained the vital status of 174 (94) patients (median age 33; range 14-87 years). The overall mortality rate was 26. Mortality was higher in patients who had clinical features of HIV infection than in those who did not (40versus 17; P=0.001). Independent predictors of death during follow-up were: (1) a proven non-tuberculosis final diagnosis (hazard ratio [HR] 5.35; 95confidence interval 1.76 to 16.25); (2) the presence of clinical signs of HIV infection (HR 2.28; 1.14-4.56); (3) co-existent pulmonary tuberculosis (HR 2.33; 1.20-4.54); and (4) older age (HR 1.02; 1.01-1.05). There was also a trend towards an increase in death rate in patients with haemodynamic instability (HR 1.80; 0.90-3.58) and a decrease in those who underwent pericardiocentesis (HR 0.34; 0.10-1.19). Conclusion : A presumptive diagnosis of tuberculous pericarditis is associated with a high mortality in sub-Saharan Africans. Attention to rapid aetiological diagnosis of pericardial effusion and treatment of concomitant HIV infection may reduce the high mortality associated with the disease

Corticosteroids for tuberculous pleurisy.

BACKGROUND: Corticosteroids used in addition to antituberculous therapy have been reported to benefit people with tuberculous pleurisy. However, research findings are inconsistent, raising doubt as to whether such treatment is worthwhile. Concern also exists regarding the potential adverse effects of corticosteroids, especially in HIV-positive people. OBJECTIVES: To evaluate the effects of adding corticosteroids to drug regimens for tuberculous pleural effusion. SEARCH STRATEGY: In May 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007, Issue 2), MEDLINE, EMBASE, LILACS, Current Controlled Trials, and reference lists of articles. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing any corticosteroid with no treatment, placebo, or other active treatment (both groups should receive the same antituberculous drug regimen) in people diagnosed with tuberculous pleurisy. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial methodological quality and extracted data. Data were analysed using relative risks (RR) and weighted mean difference (WMD) with 95% confidence intervals (CI). The fixed-effect model was applied in the absence of statistically significant heterogeneity. MAIN RESULTS: Six trials with 633 participants met the inclusion criteria; one trial included only HIV-positive people. Compared to control, corticosteroid use was associated with less residual pleural fluid at four weeks (RR 0.76, 95% CI 0.62 to 0.94; 394 participants, 3 trials) and reduced pleural thickening (RR 0.69, 95% CI 0.51 to 0.94; 309 participants, 4 trials). We found no evidence of an effect of corticosteroids on death from any cause (194 participants, 1 trial), respiratory function (191 participants, 2 trials), residual pleural fluid at eight weeks (399 participants, 4 trials), or pleural adhesions (123 participants, 2 trials). Although discontinuation of treatment due to adverse events was more frequent in participants receiving corticosteroids than placebo (RR 2.80, 95% CI 1.12 to 6.98; 586 participants, 6 trials), the effects were generally mild. The risk of Kaposi sarcoma may be increased in HIV-positive people receiving corticosteroids (RR 13.00, 95% CI 0.74 to 227.63; 194 participants, 1 trial). AUTHORS' CONCLUSIONS: There are insufficient data to support evidence-based recommendations regarding the use of adjunctive corticosteroids in people with tuberculous pleurisy. Randomized controlled trials that are sufficiently powered to evaluate the effects of corticosteroids on both morbidity and mortality are needed. The effects of corticosteroids on HIV-related complications, such as Kaposi sarcoma, should be assessed in people co-infected with HIV.

Directly observed therapy for treating tuberculosis.

BACKGROUND: For tuberculosis treatment, policies have been introduced to encourage adherence to treatment regimens. One such policy is directly observed therapy (DOT), which involves people directly observing patients taking their antituberculous drugs. OBJECTIVES: To compare DOT with self administration of treatment or different DOT options for people requiring treatment for clinically active tuberculosis or prevention of active disease. SEARCH STRATEGY: In May 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007, Issue 2), MEDLINE, EMBASE, LILACS, and mRCT. We also checked article reference lists and contacted relevant researchers and organizations. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing a health worker, family member, or community volunteer routinely observing people taking antituberculous drugs compared with routine self administration of treatment at home. We include people requiring treatment for clinically active tuberculosis or medication for preventing active disease. DATA COLLECTION AND ANALYSIS: Both authors independently assessed trial methodological quality and extracted data. Data were analysed using relative risks (RR) with 95% confidence intervals (CI) and the fixed-effect model when there was no statistically significant heterogeneity (chi square P > 0.1). Trials of drug users were analysed separately. MAIN RESULTS: Eleven trials with 5609 participants met the inclusion criteria. No statistically significant difference was detected between DOT and self administration in terms of cure (RR 1.02, 95% CI 0.86 to 1.21, random-effects model; 1603 participants, 4 trials), with similar results for cure plus completion of treatment. When stratified by location, DOT provided at home compared with DOT provided at clinic suggests a possible small advantage with home-based DOT for cure (RR 1.10, 95% CI 1.02 to 1.18; 1365 participants, 3 trials). There was no significant difference detected in clinical outcomes between DOT at a clinic versus by a family member or community health worker (2 trials), or for DOT provided by a family member versus a community health worker (1326 participants, 1 trial). Two small trials of tuberculosis prophylaxis in intravenous drugs users found no statistically significant difference between DOT and self administration (199 participants, 1 trial) or a choice of location for DOT for completion of treatment (108 participants, 1 trial). AUTHORS' CONCLUSIONS: The results of randomized controlled trials conducted in low-, middle-, and high-income countries provide no assurance that DOT compared with self administration of treatment has any quantitatively important effect on cure or treatment completion in people receiving treatment for tuberculosis.

WITHDRAWN: Steroids for treating tuberculous meningitis.

BACKGROUND: Even though corticosteroids have been used alongside antituberculosis drugs for tuberculous meningitis (TBM) since the 1950s their role remains controversial. Some believe corticosteroids improve outcome while others point to the lack of supportive evidence. In patients who are immunocompromised because of HIV infection the risks and benefits of steroids are unknown. OBJECTIVES: To assess the effects of steroids on death and disability in patients with TBM. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group specialized trials register (February 2005), The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to February 2005), EMBASE (1980 to February 2005), and LILACS (February 2005). SELECTION CRITERIA: Randomised controlled trials of steroids in people on TB treatment for TBM. DATA COLLECTION AND ANALYSIS: Two independent reviewers applied study selection criteria, assessed methodological quality and extracted data. MAIN RESULTS: Six trials of 595 patients met the inclusion criteria. No study described allocation concealment. Steroids were associated with fewer deaths (relative risk [RR] 0.79; 95% confidence interval [CI] 0.65 to 0.97) and a reduced incidence of death and severe residual disability (RR 0.58, 95% CI 0.38 to 0.88). Subgroup analysis suggests an effect on mortality in children (RR 0.77, 95% CI 0.62 to 0.96) but the results in a smaller number of adults are inconclusive (RR 0.96, 95% CI 0.50 to 1.84). There is little evidence that the severity of disease influences the effects of steroids on mortality. AUTHORS' CONCLUSIONS: Adjunctive steroids might be of benefit in patients with TBM. However, existing studies are small, and poor allocation concealment and publication bias may account for the positive results found in this review. No data are available on the use of steroids in HIV positive persons. Future placebo-controlled studies should include patients with HIV infection and should be large enough to assess both mortality and disability.

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

BACKGROUND: Adequate nutrition promotes and maintains optimal immune 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, thereby improving quality of life and ultimately reducing disease-related mortality. OBJECTIVES: To evaluate the effectiveness of various macronutrient interventions, such as a balanced diet or high protein, high carbohydrate, or high fat diets given orally, in reducing morbidity and mortality in adults and children living with HIV infection. SEARCH STRATEGY: We searched CENTRAL (up to March 2006), MEDLINE (1966 to March 2006), EMBASE (1988 to March 2006), LILACS (up to March 2006), and AIDSearch (up to March 2006). We also scanned reference lists of articles and contacted authors of relevant studies and other researchers. SELECTION CRITERIA: Randomised 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. DATA COLLECTION AND ANALYSIS: Three reviewers independently applied study selection criteria, assessed study quality, and extracted data. Effects were assessed using weighted mean difference and 95% confidence intervals. Meta-analysis employed a fixed-effect model, except when the chi-square test for heterogeneity was significant (p<0.1). MAIN RESULTS: Eight trials (with a total of 486 participants), met the criteria for inclusion in our review. None of the studies reported on mortality, morbidity, or disease progression. Overall, macronutrient supplementation (with or without nutritional counselling) significantly improved energy intake (5 trials; n=254; WMD 367 kcal.day-1; 95% CI: 217 to 516) and protein intake (3 trials; n=128; WMD 17 g.day-1; 95% CI: 8 to 26) compared with no nutritional supplementation or placebo. There was no evidence of an effect on body weight (8 trials; n=423; WMD 0.24 kg; 95% CI: -0.6 to 1.1), fat mass (6 trials; n=305; WMD -0.73 kg; 95% CI: -1.83 to 0.37), fat-free mass (5 trials; n=311; WMD 0 kg; 95% CI: -2.3 to 2.4) or CD4 count (6 trials; n=271; WMD 0.23 cells.mm-3; 95% CI: -40.2 to 40.6). AUTHORS' CONCLUSIONS: Given the current evidence base, which is limited to a few small trials in high-income countries, no firm conclusions can be drawn about the effects of macronutrient supplementation on morbidity and mortality in people living with HIV.

WITHDRAWN: Interventions for promoting adherence to tuberculosis management.

BACKGROUND: Up to half the people with tuberculosis do not complete their treatment. Strategies to improve adherence to diagnostic and treatment regimens are therefore important. OBJECTIVES: To assess the effects of various interventions aimed at promoting adherence to anti-tuberculosis treatment and completion of TB diagnostic protocols. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, the Cochrane Infectious Diseases Group trials register, Medline, Embase, Lilacs and reference lists of articles. We contacted experts in the field. SELECTION CRITERIA: Randomised and quasi-randomised trials of interventions to promote adherence with curative or preventive chemotherapy and diagnostic protocols for tuberculosis. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Fourteen trials were included. Reminder cards sent to defaulters, a combination package of a monetary incentive and health education and more supervision of clinic staff increased the number of people completing their tuberculosis treatment. Intensive counselling/education did not help in one study. Direct observation showed better clinical outcomes in one study, and no difference in another. Return to the clinic for reading of a tuberculin skin test was enhanced by monetary incentives, assistance by lay health workers, contracts and telephone prompts but not by health education. AUTHORS' CONCLUSIONS: We have found evidence of benefit for a number of specific interventions to improve adherence to anti-tuberculous therapy and completion of diagnostic protocols. These should be implemented by health care providers where appropriate to local circumstances. Future studies in low income countries are a priority and should measure adherence and clinical outcomes. This review summarises trials up to 2000. It is being replaced by a series of reviews on particular intervention strategies. The details are in the 'Published notes' section.

Beta-blockers for hypertension.

BACKGROUND: Two recent systematic reviews found first-line beta-blockers to be less effective in reducing the incidence of stroke and the combined endpoint of stroke, myocardial infarction, and death compared to all other antihypertensive drugs taken together. However, beta-blockers might be better or worse than a specific class of drugs for a particular outcome measure so that comparing beta-blockers with all other classes taken together could be misleading. In addition, these systematic reviews did not assess the tolerability of beta-blockers relative to other antihypertensive medications. We thus undertook this review to re-assess the place of beta-blockade as first-line therapy for hypertension relative to each of the other major classes of antihypertensive drugs. OBJECTIVES: To quantify the effectiveness and safety of beta-blockers on morbidity and mortality endpoints in adults with hypertension. SEARCH STRATEGY: We searched eligible studies up to June 2006 in the Cochrane Controlled Trials Register, Medline, Embase, and reference lists of previous reviews, and by contacting hypertension experts. SELECTION CRITERIA: We selected randomised controlled trials which assessed the effectiveness of beta-blockers compared to placebo, no therapy or other drug classes, as monotherapy or first-line therapy for hypertension, on mortality and morbidity endpoints in men and non-pregnant women aged 18 years or older. DATA COLLECTION AND ANALYSIS: At least two authors independently applied study selection criteria, assessed study quality, and extracted data; with differences resolved by consensus. We expressed study results as relative risks (RR) with 95% confidence intervals (CI) and conducted quantitative analyses with trial participants in groups to which they were randomly allocated, regardless of which or how much treatment they actually received. In the absence of significant heterogeneity between studies (p>0.1), we performed meta-analysis using a fixed effects method. Otherwise, we used the random effects method and investigated the cause of heterogeneity by stratified analysis. In addition, we used the Higgins statistic (I(2)) to quantify the amount of between-study variability in effect attributable to true heterogeneity rather than chance. MAIN RESULTS: Thirteen randomised controlled trials (N=91,561 participants), which met our inclusion criteria, compared beta-blockers to placebo or no treatment (4 trials with 23,613 participants), diuretics (5 trials with 18,241 participants), calcium-channel blockers (CCBs: 4 trials with 44,825 participants), and renin-angiotensin system (RAS) inhibitors (3 trials with 10,828 participants). The risk of all-cause mortality was not different between first-line beta-blockers and placebo (RR 0.99, 95%CI 0.88 to 1.11, I(2)=0%), diuretics or RAS inhibitors, but was higher for beta-blockers compared to CCBs (RR 1.07, 95%CI 1.00 to 1.14, I(2)=2.2%; ARI=0.5%, NNH=200). The risk of total cardiovascular disease (CVD) was lower for first-line beta-blockers compared to placebo (RR 0.88, 95%CI 0.79 to 0.97, I(2)=21.4%, ARR=0.7%, NNT=140). This is primarily a reflection of the significant decrease in stroke (RR 0.80, 95%CI 0.66 to 0.96; I(2)=0%; ARR=0.5%, NNT=200); coronary heart disease (CHD) risk was not significantly different between beta-blockers and placebo. The effect of beta-blockers on CVD was significantly worse than that of CCBs (RR 1.18, 95%CI 1.08 to 1.29, I(2)=0%; ARI=1.3%, NNH=80), but was not significantly different from that of diuretics or RAS inhibitors. Increased total CVD was due to an increase in stroke compared to CCBs (RR 1.24, 95%CI 1.11 to 1.40, I(2)=0%; ARI=0.6%, NNH=180). There was also an increase in stroke with beta-blockers as compared to RAS inhibitors (RR 1.30, 95%CI 1.11 to 1.53, I(2)=29.1%; ARI=1.5%, NNH=65). CHD was not significantly different between beta-blockers and diuretics or CCBs or RAS inhibitors. In addition, patients on beta-blockers were more likely to discontinue treatment due to side effects than those on diuretics (RR 1.86, 95%CI 1.39 to 2.50, I(2)=78.2%, ARI=6.4% NNH=16) and RAS inhibitors (RR 1.41, 95%CI 1.29 to 1.54, I(2)=12.1%; ARI=5.5%, NNH=18), but there was no significant difference with CCBs. AUTHORS' CONCLUSIONS: The available evidence does not support the use of beta-blockers as first-line drugs in the treatment of hypertension. This conclusion is based on the relatively weak effect of beta-blockers to reduce stroke and the absence of an effect on coronary heart disease when compared to placebo or no treatment. More importantly, it is based on the trend towards worse outcomes in comparison with calcium-channel blockers, renin-angiotensin system inhibitors, and thiazide diuretics. Most of the evidence for these conclusions comes from trials where atenolol was the beta-blocker used (75% of beta-blocker participants in this review). However, it is not known at present whether beta-blockers have differential effects on younger and elderly patients or whether there are differences between the different sub-types of beta-blockers.

Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection.

BACKGROUND: Antiretroviral drugs (ARV) reduce viral replication and can reduce mother-to-child transmission of HIV either by lowing plasma viral load in pregnant women or through post-exposure prophylaxis in their newborns. In rich countries, highly active antiretroviral therapy (HAART) has reduced the vertical transmission rates to around 1-2%, but HAART is not yet widely available in low and middle income countries. In these countries, various simpler and less costly antiretroviral regimens have been offered to pregnant women or to their newborn babies, or to both. OBJECTIVES: To determine whether, and to what extent, antiretroviral regimens aimed at decreasing the risk of mother-to-child transmission of HIV infection achieve a clinically useful decrease in transmission risk, and what effect these interventions have on maternal and infant mortality and morbidity. SEARCH STRATEGY: We sought to identify all relevant studies regardless of language or publication status by searching the Cochrane HIV/AIDS Review Group Trials Register, The Cochrane Library, Medline, EMBASE and AIDSearch and relevant conference abstracts. We also contacted research organizations and experts in the field for unpublished and ongoing studies. The original review search strategy was updated in 2006. SELECTION CRITERIA: Randomised controlled trials of any antiretroviral regimen aimed at decreasing the risk of mother-to-child transmission of HIV infection compared with placebo or no treatment. DATA COLLECTION AND ANALYSIS: Two authors independently selected relevant studies, extracted data and assessed trial quality. For the primary outcomes, we used survival analysis to estimate the probability of infants being infected with HIV (the observed proportion) at various specific time-points and calculated efficacy at a specific time as the relative reduction in the proportion infected. Efficacy, at a specific time, is defined as the preventive fraction in the exposed group compared to the reference group, which is the relative reduction in the proportion infected: 1-(Re/Rf). For those studies where efficacy and hence confidence intervals were not calculated, we calculated the approximate confidence intervals for the efficacy using recommended methods. For analysis of results that are not based on survival analyses we present the relative risk for each trial outcome based on the number randomised. No meta-analysis was conducted as no trial assessed the identical drug regimens. MAIN RESULTS: Eighteen trials including 14,398 participants conducted in 16 countries were eligible for inclusion in the review. The first trial began in April 1991 and assessed zidovudine (ZDV) versus placebo and since then, the type, dosage and duration of drugs to be compared has been modified in each subsequent trial. Antiretrovirals versus placebo In breastfeeding populations, three trials found that:ZDV given to mothers from 36 to 38 weeks gestation, during labour and for 7 days after delivery significantly reduced HIV infection at 4-8 weeks (Efficacy 32.00%; 95% CI 0.64 to 63.36), 3 to 4 months (Efficacy 34.00%; 95% CI 6.56 to 61.44), 6 months (Efficacy 35.00%; 95% CI 9.52 to 60.48), 12 months (Efficacy 34.00%; 95% CI 8.52 to 59.48) and 18 months (Efficacy 30.00%; 95% CI 2.56 to 57.44).ZDV given to mothers from 36 weeks gestation and during labour significantly reduced HIV infection at 4 to 8 weeks (Efficacy 44.00%; 95% CI 8.72 to 79.28) and 3 to 4 months (Efficacy 37.00%; 95% CI 3.68 to 70.32) but not at birth.ZDV plus lamivudine (3TC) given to mothers from 36 weeks gestation, during labour and for 7 days after delivery and to babies for the first 7 days of life (PETRA 'regimen A') significantly reduced HIV infection (Efficacy 63.00%; 95% CI 41.44 to 84.56) and a combined endpoint of HIV infection or death (Efficacy 61.00%; 95% CI 41.40 to 80.60) at 4 to 8 weeks but these effects were not sustained at 18 months.ZDV plus 3TC given to mothers from the start of labour until 7 days after delivery and to babies for the first 7 days of life (PETRA 'regimen B') significantly reduced HIV infection (Efficacy 42.00%; 95% CI 12.60 to 71.40) and HIV infection or death at 4 to 8 weeks (Efficacy 36.00%; 95% CI 8.56 to 63.44) but the effects were not sustained at 18 months.ZDV plus 3TC given to mothers during labour only (PETRA 'regimen C') with no treatment to babies did not reduce the risk of HIV infection at either 4 to 8 weeks or 18 months. In non-breastfeeding populations, three trials found that:ZDV given to mothers from 14 to 34 weeks gestation and during labour and to babies for the first 6 weeks of life significantly reduced HIV infection in babies at 18 months (Efficacy 66.00%; 95% CI 34.64 to 97.36).ZDV given to mothers from 36 weeks gestation and during labour with no treatment to babies ('Thai-CDC regimen') significantly reduced HIV infection at 4 to 8 weeks (Efficacy 50.00%; 95% CI 12.76 to 87.24) but not at birthZDV given to mothers from 38 weeks gestation and during labour with no treatment to babies did not influence HIV transmission at 6 months. Longer versus shorter regimens using the same antiretrovirals One trial in a breastfeeding population found that:ZDV given to mothers during labour and to their babies for the first 3 days of life compared with ZDV given to mothers from 36 weeks and during labour (similar to 'Thai-CDC') resulted in HIV infection rates that were not significantly different at birth, 4-8 weeks, 3 to 4 months, 6 months and 12 months. Three trials in non-breastfeeding populations found that:ZDV given to mothers from 28 weeks gestation during labour and to infants for the first 3 days after birth compared with ZDV given to mothers from 35 weeks gestation through labour and to infants from birth to 6 weeks significantly reduced HIV infection rate at 6 months (Efficacy 45.00%; 95% CI 1.88 to 88.12) but compared with the same regimen ZDV given to mothers from 28 weeks gestation through labour and to infants from birth to 6 weeks did not result in a statistically significant difference in HIV infection at 6 months. ZDV given to mothers from 35 weeks gestation during labour and to infants for the first 3 days after birth was considered ineffective for reducing transmission rates and this regimen was discontinued.An antenatal/intrapartum course of ZDV used for a median of 76 days compared with an antenatal/intrapartum ZDV regimen used for a median 28 days with no treatment to babies in either group did not result in HIV infection rates that were significantly different at birth and at 3 to 4 months. In a programme where mothers were routinely receiving ZDV in the third trimester of pregnancy and babies were receiving one week of ZDV therapy, a single dose of nevirapine (NVP) given to mothers in labour and to their babies soon after birth compared with a single dose of NVP given to mothers only resulted in HIV infection rates that were not significantly different at birth and 6 months. However the reduction in risk of HIV infection or death at 6 months was marginally significant (Efficacy 45.00%; 95% CI -4.00 to 94.00). Antiretroviral regimens using different drugs and durations of treatment In breastfeeding populations, three trials found that:A single dose of NVP given to mothers at the onset of labour plus a single dose of NVP given to their babies immediately after birth ('HIVNET 012 regimen') compared with ZDV given to mothers during labour and to their babies for a week after birth resulted in lower HIV infection rates at 4-8 weeks (Efficacy 41.00%; 95% CI 11.60 to 70.40), 3-4 months (Efficacy 39.00%; 95% CI 11.56 to 66.44), 12 months (Efficacy 36.00%; 95% CI 8.56 to 63.44) and 18 months (Efficacy 39.00%; 95% CI 13.52 to 64.48). In addition, the NVP regimen significantly reduced the risk of HIV infection or death at 4-8 weeks (Efficacy 42.00%; 95% CI 14.56 to 69.44), 3 to 4 months (Efficacy 40.00%; 95% CI 14.52 to 65.48), 12 months (Efficacy 32.00%; 95% CI 8.48 to 55.52) and 18 months (Efficacy 33.00%; 95% CI 9.48 to 56.52). The 'HIVNET 012 regimen' plus ZDV given to babies for 1 week after birth compared with the 'HIVNET 012 regimen' alone did not result in a statistically significant difference in HIV infection at 4 to 8 weeks.A single dose of NVP given to babies immediately after birth plus ZDV given to babies for 1 week after birth compared with a single dose of NVP given to babies only significantly reduced the HIV infection rate at 4 to 8 weeks (Efficacy 37.00%; 95% CI 3.68 to 70.32). Five trials in non-breastfeeding populations found that:In a population in which mothers were receiving 'standard' ARV for HIV infection a single dose of NVP given to mothers in labour plus a single dose of NVP given to babies immediately after birth ('HIVNET 012 regimen') compared with placebo did not result in a statistically significant difference in HIV infection rates at birth and at 4 to 8 weeks. The 'Thai CDC regimen' compared with the 'HIVNET 012 regimen' did not result in a significant difference in HIV infection at 4 to 8 weeks.A single dose of NVP given to babies immediately after birth compared to ZDV given to babies for the first 6 weeks of life did not result in a significant difference in HIV infection rates at 4-8 weeks and 3 to 4 months.ZDV plus 3TC given to mothers in labour and for a week after delivery and to their infants for a week after birth (similar to 'PETRA regimen B') compared with NVP given to mothers in labour and immediately after delivery plus a single dose of NVP to their babies immediately after birth (similar to 'HIVNET 012 regimen') did not result in a significant difference in the HIV infection rate at 4 to 8 weeks. (ABSTRACT TRUNCATED)