Julia Critchley

Efficacy and safety of intermittent preventive treatment with sulfadoxine-pyrimethamine for malaria in African infants: a pooled analysis of six randomised, placebo-controlled trials

BACKGROUND Intermittent preventive treatment (IPT) is a promising strategy for malaria control in infants. We undertook a pooled analysis of the safety and efficacy of IPT in infants (IPTi) with sulfadoxine-pyrimethamine in Africa. METHODS We pooled data from six double-blind, randomised, placebo-controlled trials (undertaken one each in Tanzania, Mozambique, and Gabon, and three in Ghana) that assessed the efficacy of IPTi with sulfadoxine-pyrimethamine. In all trials, IPTi or placebo was given to infants at the time of routine vaccinations delivered by WHOs Expanded Program on Immunization. Data from the trials for incidence of clinical malaria, risk of anaemia (packed-cell volume <25% or haemoglobin <80 g/L), and incidence of hospital admissions and adverse events in infants up to 12 months of age were reanalysed by use of standard outcome definitions and time periods. Analysis was by modified intention to treat, including all infants who received at least one dose of IPTi or placebo. FINDINGS The six trials provided data for 7930 infants (IPTi, n=3958; placebo, n=3972). IPTi had a protective efficacy of 30.3% (95% CI 19.8-39.4, p<0.0001) against clinical malaria, 21.3% (8.2-32.5, p=0.002) against the risk of anaemia, 38.1% (12.5-56.2, p=0.007) against hospital admissions associated with malaria parasitaemia, and 22.9% (10.0-34.0, p=0.001) against all-cause hospital admissions. There were 56 deaths in the IPTi group compared with 53 in the placebo group (rate ratio 1.05, 95% CI 0.72-1.54, p=0.79). One death, judged as possibly related to IPTi because it occurred 19 days after a treatment dose, was subsequently attributed to probable sepsis. Four of 676 non-fatal hospital admissions in the IPTi group were deemed related to study treatment compared with five of 860 in the placebo group. None of three serious dermatological adverse events in the IPTi group were judged related to study treatment compared with one of 13 in the placebo group. INTERPRETATION IPTi with sulfadoxine-pyrimethamine was safe and efficacious across a range of malaria transmission settings, suggesting that this intervention is a useful contribution to malaria control. FUNDING Bill & Melinda Gates Foundation.

Mortality reductions in patients receiving exercise-based cardiac rehabilitation: how much can be attributed to cardiovascular risk factor improvements?

Background It is unclear how much of the reduction in cardiac mortality in coronary heart disease (CHD) patients with exercise training is the result of direct effects on the heart and coronary vasculature, or to indirect effects, via primary risk factors. Objective The aim of this article was to quantify the cardiac mortality benefits of exercise-based rehabilitation attributable to risk factor reductions versus the direct effects on the heart and vasculature. Methods The IMPACT coronary heart disease model was used to examine the reduction in cardiac mortality attributable to changes in risk factors from a meta-analysis of cardiac rehabilitation randomized, controlled trials. Patients were receiving rehabilitation following an acute myocardial infarction, angina pectoris or revascularization. Outcomes considered were primary risk factors (total cholesterol, systolic blood pressure and smoking behaviour) and cardiac mortality. Results Nineteen exercise-only cardiac rehabilitation trials (including 2984 patients) were identified. Across these trials, exercise training reduced pooled cardiac mortality by 28% (relative risk, 0.72, 95% confidence interval 0.55–0.95), with 30 fewer deaths than in the control group. Applying the CHD model, approximately 17 (58%) of these 30 fewer deaths were attributable to reductions in major cardiovascular risk factors: 7.1 deaths (minimum estimate 6.2, maximum estimate 9.5) attributable to an 18% reduction in smoking prevalence; 5.9 deaths (minimum −0.6, maximum 12.6) to a 0.11 mmol/l reduction in cholesterol, and 4.4 deaths (−1.0 minimum, 6.7 maximum) to a 2.0 mmHg reduction in systolic blood pressure. Conclusions Approximately half of the 28% reduction in cardiac mortality achieved with exercise-based cardiac rehabilitation may be attributed to reductions in major risk factors, particularly smoking. Eur J Cardiovasc Prev Rehabil 13:369–374

Evaluating health research capacity building: An evidence-based tool.

Bates and colleagues describe the development of a tool to assess capacity-building programs in health research, which they used in Kumasi, Ghana.

Analysing the large decline in coronary heart disease mortality in the Icelandic population aged 25-74 between the years 1981 and 2006.

Background Coronary heart disease (CHD) mortality rates have been decreasing in Iceland since the 1980s. We examined how much of the decrease between 1981 and 2006 could be attributed to medical and surgical treatments and how much to changes in cardiovascular risk factors. Methodology The previously validated IMPACT CHD mortality model was applied to the Icelandic population. The data sources were official statistics, national quality registers, published trials and meta-analyses, clinical audits and a series of national population surveys. Principal Findings Between 1981 and 2006, CHD mortality rates in Iceland decreased by 80% in men and women aged 25 to 74 years, which resulted in 295 fewer deaths in 2006 than if the 1981 rates had persisted. Incidence of myocardial infarction (MI) decreased by 66% and resulted in some 500 fewer incident MI cases per year, which is a major determinant of possible deaths from MI. Based on the IMPACT model approximately 73% (lower and upper bound estimates: 54%–93%) of the mortality decrease was attributable to risk factor reductions: cholesterol 32%; smoking 22%; systolic blood pressure 22%, and physical inactivity 5% with adverse trends for diabetes (−5%), and obesity (−4%). Approximately 25% (lower and upper bound estimates: 8%–40%) of the mortality decrease was attributable to treatments in individuals: secondary prevention 8%; heart failure treatments 6%; acute coronary syndrome treatments 5%; revascularisation 3%; hypertension treatments 2%, and statins 0.5%. Conclusions Almost three quarters of the large CHD mortality decrease in Iceland between 1981 and 2006 was attributable to reductions in major cardiovascular risk factors in the population. These findings emphasize the value of a comprehensive prevention strategy that promotes tobacco control and a healthier diet to reduce incidence of MI and highlights the potential importance of effective, evidence based medical treatments.

Is smokeless tobacco a risk factor for coronary heart disease? A systematic review of epidemiological studies

Background There is on-going debate about the wisdom of substituting smokeless tobacco products for cigarette smoking as a ‘harm reduction’ strategy. It is generally believed that health risks associated with smokeless tobacco use (ST) are lower than those with cigarette smoking. However, the population attributable risk of smoking is higher for cardiovascular diseases than for any cancers, and few studies or reviews have considered the cardiovascular outcomes of ST use. A systematic review was therefore carried out to highlight the gaps in the evidence base. Methods Electronic databases were searched, supplemented by screening reference lists, smoking-related websites, and contacting experts. Analytical observational studies of ST use (cohorts, case-control, cross-sectional studies) were included if they reported on cardiovascular disease (CVD) outcomes, or risk factors. Data extraction covered control of confounding, selection of cases and controls, sample size, clear definitions and measurements of the health outcome and ST use. One or two independent reviewers carried out selection, extraction and quality assessments. Results A narrative review was carried out. Very few studies were identified; only three from Sweden consider CVD outcomes and these are discrepant. There may be a modest association between use of Swedish snuff (snus) and cardiovascular disease (e.g., relative risk = 1.4, 95% confidence interval 1.2–1.6) in one prospective cohort study. Several other studies have considered associations between ST use and intermediate outcomes (CVD risk factors). Conclusions There may be an association between ST use and cardiovascular disease. However, further rigorous studies with adequate sample sizes are required. Eur J Cardiovasc Prevention Rehab 11:101–112

Outcomes of pregnancies in women with pre-existing type 1 or type 2 diabetes, in an ethnically mixed population.

Objective  To compare the outcomes of pregnancies in women with pre‐existing, type 1 and type 2, diabetes and to examine the influence of ethnicity on these outcomes.

Albendazole for the control and elimination of lymphatic filariasis: systematic review.

Objectives  The Global Programme to Eliminate Lymphatic Filariasis recommends albendazole in combination with other antifilarial drugs. This systematic review examines albendazole in treatment and control of lymphatic filariasis.

Explaining the decline in coronary heart disease mortality in the Czech Republic between 1985 and 2007

Background Coronary heart disease (CHD) mortality has declined substantially in the Czech Republic over the last two decades. Design The purpose of this study was to determine what proportion of this CHD mortality decline could be associated with temporal trends in major CHD risk factors and what proportion with advances in medical and surgical treatments. Methods The validated IMPACT mortality model was used to combine and analyse data on uptake and effectiveness of CHD management and risk factor trends in the Czech Republic in adults aged 25–74 years between 1985 and 2007. The main sources were official statistics, national quality of care registries, published trials and meta-analyses, and the Czech MONICA and Czech post-MONICA studies. Results Between 1985 and 2007, age-adjusted CHD mortality rates in the Czech Republic decreased by 66.2% in men and 65.4% in women in the age group 25–74 years, representing 12,080 fewer CHD deaths in 2007. Changes in CHD risk factors explained approximately 52% of the total mortality decrease, and improvements in medical treatments approximately 43%. Increases in body mass index and in diabetes prevalence had a negative impact, increasing CHD mortality by approximately 1% and 5%, respectively. Conclusions More than half of the very substantial fall in CHD mortality in the Czech Republic between 1985 and 2007 was attributable to reduction in major cardiovascular risk factors. Improvement in treatments accounted for approximately 43% of the total mortality decrease. These findings emphasize the value of primary prevention and evidence-based medical treatment.

Benzodiazepine prescribing behaviour and attitudes: a survey among general practitioners practicing in northern Thailand.

BackgroundOver-prescribing of benzodiazepines appears common in many countries, a better understanding of prescribing practices and attitudes may help develop strategies to reduce prescribing. This study aimed to evaluate benzodiazepine prescribing behaviour and attitudes in general practitioners practising in Chiang Mai and Lampoon, Thailand.MethodsQuestionnaire survey of general practitioners in community hospitals, to estimate: i) use of benzodiazepines for anxiety/insomnia, panic disorder, depression, essential hypertension, and uncomplicated low back pain and ii) views on the optimal duration of benzodiazepine use.ResultsFifty-five of 100 general practitioners returned the completed questionnaires. They reported use of benzodiazepines for anxiety/insomnia (n = 51, 93%), panic disorder (n = 43, 78%), depression (n = 26, 43%), essential hypertension (n = 15, 27 %) and uncomplicated low back pain (n = 10, 18%). Twenty-eight general practitioners would prescribe benzodiazepines for non-psychiatric conditions, 17 for use as muscle relaxants. Seventy-five per cent, 62% and 29% of the general practitioners agreed or totally agreed with the use of benzodiazepines for insomnia, anxiety and depression, respectively. Practitioners agreed that prescribing should be less than one week (80%); or from 1 week to 1 month (47%); or 1 to 4 months (16%); or 4 to 6 months (5%) or more than 6 months (2%). Twenty-five general practitioners (45%) accepted that they used benzodiazepines excessively in the past year.ConclusionA considerable proportion of general practitioners in Chiang Mai and Lampoon, Thailand inappropriately use benzodiazepines for physical illnesses, especially essential hypertension and uncomplicated low back pain. However, almost half of them thought that they overused benzodiazepines. General practitioners lack of time, knowledge and skills should be taken into account in improving prescribing behaviour and attitudes.

Urine dipstick as a screening test for urinary tract infection

Abstract Background: Febrile illnesses are common among children in Ghana and are often diagnosed as malaria, thus overlooking urinary tract infection (UTI) as a possible cause of fever. Aims: To determine the prevalence of UTI among febrile children <5 years and to estimate the sensitivity, specificity and positive and negative predictive values of urine dipstick as a screening test. Methods: From March to July 2004, children aged 3–60 months attending an outpatient clinic at Komfo Anokye Teaching Hospital, Kumasi were systematically screened for UTI using Combi 10 dipstick (CyBow TM). All dipstick-positive and a sample of dipstick-negative urines underwent microscopy and culture (i.e. gold standard) from clean-catch or catheterised urine. Results: Of 1393 children (median age 20 months), 112 (8%) had a positive dipstick and 29 of these (25.9%) had UTIs; 118/1278 (9.2%) children with a negative dipstick had urine cultured, one of whom (0.8%) had a UTI. The prevalence of UTIs was 2.1% (30/1393) and was higher among females (RR 3.99, 95% CI 1.76–9.04). 70% of UTIs were in children <2 years of age (p=0.08). The sensitivity, specificity and positive and negative predictive values of dipstick were 96.7%, 58.8%, 26.1% and 99.2%, respectively. Use of dipstick as a screening test for UTI was comparable to microscopic analysis for pyuria. 90% of all UTIs were clinically misdiagnosed (70% as malaria). Escherichia coli was the predominant isolate (60%). Co-trimoxazole and ampicillin, commonly used to treat uncomplicated UTIs at first level in Ghana, showed 0% and 8.3% in-vitro sensitivities, respectively. Ciprofloxacin and cefuroxime (widely used at regional/tertiary level) showed good sensitivities, 99.0% and 86.2%, respectively. Conclusions: Urine dipstick should be promoted as a screening test for UTI. First-line use of cotrimoxazole and ampicillin for UTI should be reviewed.