Translating research into action: an international study of the role of research funders.

BACKGROUND: It is widely accepted that research can lead to improved health outcomes. However, translating research into meaningful impacts in peoples' lives requires actions that stretch well beyond those traditionally associated with knowledge creation. The research reported in this manuscript provides an international review of health research funders' efforts to encourage this process of research uptake, application and scaling, often referred to as knowledge translation. METHODS: We conducted web-site review, document review and key informant interviews to investigate knowledge translation at 26 research funding agencies. The sample comprises the regions of Australia, Europe and North America, and a diverse range of funder types, including biomedical, clinical, multi-health domain, philanthropic, public and private organisations. The data builds on a 2008 study by the authors with the same international sample, which permitted longitudinal trend analysis. RESULTS: Knowledge translation is an objective of growing significance for funders across each region studied. However, there is no clear international consensus or standard on how funders might support knowledge translation. We found that approaches and mechanisms vary across region and funder type. Strategically tailored funding opportunities (grants) are the most prevalent modality of support. The most common funder-driven strategy for knowledge translation within these grants is the linking of researchers to research users. Funders could not to provide empirical evidence to support the majority of the knowledge translation activities they encourage or undertake. CONCLUSIONS: Knowledge translation at a research funder relies on context. Accordingly, we suggest that the diversity of approaches uncovered in our research is fitting. We argue that evaluation of funding agency efforts to promote and/or support knowledge translation should be prioritised and actioned. It is paradoxical that funders' efforts to get evidence into practice are not themselves evidence based.

Prevalence of chronic kidney disease and association with cardiovascular risk factors among teachers in Cape Town, South Africa.

Background: There is a need to determine the feasibility of conducting studies of chronic diseases among large cohorts of African patients. One aim of the South African feasibility study was to determine the prevalence of chronic kidney disease (CKD) and its association with cardiovascular disease (CVD) risk factors among school teachers. Methods: In a cross-sectional survey of 489 teachers we captured data on demographics, CVD risk factors, anthropometry and blood pressure. Serum glucose, creatinine, cholesterol and urine protein/creatinine ratio was measured. Glomerular filtration rate was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the Modification of Diet in Renal Disease study equations. Results: The mean (± standard deviation) age of the participants was 46.3 ± 8.5 years, with 70.3% being female and 74.6% of mixed ethnicity. The crude prevalence of CKD using the CKD-EPI equation was 6.1% while the age-adjusted prevalence was 6.4% (95% confidence interval 3.2-9.7%). CKD was associated with the presence of diabetes and higher diastolic blood pressures. Conclusions: In our study population of relatively young, working individuals CKD was common, clinically silent and associated with cardiovascular risk factors. The long-term complications of CKD are serious and expensive to manage and this, therefore, constitutes an important public health problem for South Africa.

HIV infection is associated with a lower incidence of constriction in presumed tuberculous pericarditis: a prospective observational study.

BACKGROUND: Pericardial constriction is a serious complication of tuberculous pericardial effusion that occurs in up to a quarter of patients despite anti-tuberculosis chemotherapy. The impact of human immunodeficiency virus (HIV) infection on the incidence of constrictive pericarditis following tuberculous pericardial effusion is unknown. METHODS AND RESULTS: We conducted a prospective observational study to determine the association between HIV infection and the incidence of constrictive pericarditis among 185 patients (median age 33 years) with suspected tuberculous pericardial effusion. These patients were recruited consecutively between March and October 2004 on commencement of anti-tuberculosis treatment, from 15 hospitals in Cameroon, Nigeria and South Africa. Surviving patients (N = 119) were assessed for clinical evidence of constrictive pericarditis at 3 and 6 months of follow-up. Clinical features of HIV infection were present in 42 (35.2%) of the 119 patients at enrolment into the study. 66 of the 119 (56.9%) patients consented to HIV testing at enrolment. During the 6 months of follow-up, a clinical diagnosis of constrictive pericarditis was made in 13 of the 119 patients (10.9 %, 95% confidence interval [CI] 5.9-18%). Patients with clinical features of HIV infection appear less likely to develop constriction than those without (4.8% versus 14.3%; P = 0.08). None of the 33 HIV seropositive patients developed constriction, but 8 (24.2%, 95%CI 11.1-42.3%) of the 33 HIV seronegative patients did (P = 0.005). In a multivariate logistic regression model adjusting simultaneously for several baseline characteristics, only clinical signs of HIV infection were significantly associated with a lower risk of constriction (odd ratio 0.14, 95% CI 0.02-0.87, P = 0.035). CONCLUSIONS: These data suggest that HIV infection is associated with a lower incidence of pericardial constriction in patients with presumed tuberculous pericarditis.

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 (40% v. 17%, p=0.001). Independent predictors of death during followup were: (i) a proven non-tuberculosis final diagnosis (hazard ratio (HR) 5.35, 95% confidence interval (CI) 1.76 - 16.25), (ii) the presence of clinical signs of HIV infection (HR 2.28, CI 1.14 - 4.56), (iii) coexistent pulmonary tuberculosis (HR 2.33, CI 1.20 - 4.54), and (iv) older age (HR 1.02, CI 1.01 - 1.05). There was also a trend towards an increase in death rate in patients with haemodynamic instability (HR 1.80, CI 0.90 - 3.58) and a decrease in those who underwent pericardiocentesis (HR 0.34, CI 0.10 - 1.19). CONCLUSION: A presumptive diagnosis of tuberculous pericarditis is associated with a high mortality in sub-Saharan Africa. Attention to rapid aetiological diagnosis of pericardial effusion and treatment of concomitant HIV infection may reduce the high mortality associated with the disease.

Contemporary use of adjunctive corticosteroids in tuberculous pericarditis.

There is controversy concerning the effectiveness of adjunctive corticosteroids in reducing mortality in tuberculous pericarditis. To assess the impact of this controversy on contemporary clinical practice, we studied the use of adjunctive corticosteroid in 185 consecutive patients with suspected pericardial tuberculosis from 15 hospitals in Cameroon, Nigeria, and South Africa. 109 (58.9%) patients received steroids with significant variation in corticosteroid use ranging from 0% to 93.5% per centre (P<0.0001). The presence of clinical features of HIV infection was the independent predictor of the non-use of adjunctive corticosteroids (OR 0.39, 95% CI 0.20-0.75, P=0.005). We have demonstrated marked variation in the use of corticosteroids by practitioners, with nearly half of all patients not receiving this intervention. Taken together with the statistical uncertainty regarding the effectiveness of adjunctive steroids in tuberculous pericarditis, these observations probably reflect a state of genuine uncertainty or clinical equipoise among practitioners who care for patients with tuberculous pericarditis in sub-Saharan Africa. These data provide a justification for the establishment of adequately powered randomised clinical trials to assess the effectiveness of adjunctive corticosteroids in patients with tuberculous pericarditis.

How strong is the evidence for use of beta-blockers as first-line therapy for hypertension? Systematic review and meta-analysis.

OBJECTIVE: To quantify the effect of first-line antihypertensive treatment with beta-blockers on mortality, morbidity and withdrawal rates, compared with the other main classes of antihypertensive agents. METHODS: We identified eligible trials by searching the Cochrane Controlled Trials Register, Medline, Embase, reference lists of previous reviews, and contacting researchers. We extracted data independently in duplicate and conducted meta-analysis by analysing trial participants in groups to which they were randomized, regardless of subsequent treatment actually received. RESULTS: Thirteen trials with 91,561 participants, meeting inclusion criteria, compared beta-blockers to placebo (four trials; n = 23,613), diuretics (five trials; n = 18,241), calcium-channel blockers (CCBs) (four trials; n = 44,825), and renin-angiotensin system (RAS) inhibitors, namely angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (three trials; n = 10,828). Compared to placebo, beta-blockers reduced the risk of stroke (relative risk 0.80; 95% confidence interval 0.66-0.96) with a marginal fall in total cardiovascular events (0.88, 0.79-0.97), but did not affect all-cause mortality (0.99, 0.88-1.11), coronary heart disease (0.93, 0.81-1.07) or cardiovascular mortality (0.93, 0.80-1.09). The effect on stroke was less than that of CCBs (1.24, 1.11-1.40) and RAS inhibitors (1.30, 1.11-1.53), and that on total cardiovascular events less than that of CCBs (1.18, 1.08-1.29). In addition, patients on beta-blockers were more likely to discontinue treatment than those on diuretics (1.80; 1.33-2.42) or RAS inhibitors (1.41; 1.29-1.54). CONCLUSION: Beta-blockers are inferior to CCBs and to RAS inhibitors for reducing several important hard end points. Compared with diuretics, they had similar outcomes, but were less well tolerated. Hence beta-blockers are generally suboptimal first-line antihypertensive drugs.

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: The 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. METHODS: Consecutive 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. RESULTS: A 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. CONCLUSION: Patients 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.

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

BACKGROUND: Rheumatic 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. METHODS: Trials 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. RESULTS: Ten 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 USD 46 in South Africa. CONCLUSION: Antibiotics 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.

Lack of adherence to the national guidelines on the prevention of rheumatic fever.

OBJECTIVES: To explore the extent to which current practices for the secondary prevention of rheumatic fever (RF) in Cape Town adhere to those outlined in the national guidelines on the primary prevention and prophylaxis of RF and rheumatic heart disease (RHD) for health professionals at primary level. METHODS: A combination of qualitative tools was used to evaluate the four priority issues identified in the guidelines as fundamental elements of a comprehensive programme for the secondary prophylaxis of RF/RHD: (i) health education and promotion; (ii) case detection of RF and RHD; (iii) secondary prophylaxis every 3-4 weeks at primary level; and (iv) notification of acute rheumatic fever (ARF). The qualitative tools included parent/child interviews of cases diagnosed with ARF in the Cape metropole area during the period 1999-2003; a physician questionnaire focused on awareness and adherence to the national guidelines; and a review of the records on acute rheumatic fever notification in the Cape metropole area from 1999 to 2003. RESULTS: The evaluation revealed four key findings. First, patient knowledge on the disease was almost non-existent. Despite this lack of knowledge, adherence to secondary prophylactic treatment was good. Second, the physicians most likely to encounter a case of rheumatic fever were least likely to be aware of and to comply with the national guideline. Third, the guidelines do not clearly state how increased detection of ARF will be achieved. Finally, the RF notification system is dysfunctional, with discrepancies in the reporting of cases at hospital, city and provincial levels. CONCLUSIONS: Since the publication of the national guidelines in 1997, little progress has been made towards achieving the implementation of a comprehensive programme for the secondary prevention of RF/RHD.