Lancet
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Randomized Controlled Trial Clinical Trial
Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)
Drug therapy for hypercholesterolaemia has remained controversial mainly because of insufficient clinical trial evidence for improved survival. The present trial was designed to evaluate the effect of cholesterol lowering with simvastatin on mortality and morbidity in patients with coronary heart disease (CHD). 4444 patients with angina pectoris or previous myocardial infarction and serum cholesterol 5.5-8.0 mmol/L on a lipid-lowering diet were randomised to double-blind treatment with simvastatin or placebo. Over the 5.4 years median follow-up period, simvastatin produced mean changes in total cholesterol, low-density-lipoprotein cholesterol, and high-density-lipoprotein cholesterol of -25%, -35%, and +8%, respectively, with few adverse effects. 256 patients (12%) in the placebo group died, compared with 182 (8%) in the simvastatin group. ⋯ This risk was also significantly reduced in subgroups consisting of women and patients of both sexes aged 60 or more. Other benefits of treatment included a 37% reduction (p < 0.00001) in the risk of undergoing myocardial revascularisation procedures. This study shows that long-term treatment with simvastatin is safe and improves survival in CHD patients.
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Schizophrenia has been linked with childhood psychological abnormalities since it was first described, but studies of associations have not used population samples and so may be subject to bias. We have studied associations between adult-onset schizophrenia and childhood sociodemographic, neurodevelopmental, cognitive, and behavioural factors within a cohort of 5362 people born in the week March 3-9, 1946. Childhood data were gathered prospectively and case ascertainment was independent of routine follow-up of this cohort. 30 cases of schizophrenia arose between ages 16 and 43 years (cumulative risk 0.63% [95% CI 0.41-0.86%]). ⋯ A health visitor's rating of the mother as having below average mothering skills and understanding of her child at age 4 years was a predictor of schizophrenia in that child (odds ratio 5.8 [0.8-31.8], p = 0.02). Differences between children destined to develop schizophrenia as adults and the general population were found across a range of developmental domains. As with some other adult illnesses, the origins of schizophrenia may be found in early life.