Objective To assess whether the association of serum homocysteine concentration with ischaemic heart disease, deep vein thrombosis and pulmonary embolism, and stroke is causal and, if so, to quantify the effect of homocysteine reduction in preventing them. Design Meta-analyses of the above three diseases using (a) 72 studies in which the prevalence of a mutation in the MTHFR gene (which increases homocysteine) was determined in cases (n=16 849) and controls, and (b) 20 prospective studies (3820 participants) of serum homocysteine and disease risk. Main outcome measures Odds ratios of the three diseases for a 5 mol/l increase in serum homocysteine concentration.

Objective To determine the average reduction in blood pressure, prevalence of adverse effects, and reduction in risk of stroke and ischaemic heart disease events produced by the five main categories of blood pressure lowering drugs according to dose, singly and in combination. Design Meta-analysis of 354 randomised double blind placebo controlled trials of thiazides, blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, and calcium channel blockers in fixed dose. Subjects 40 000 treated patients and 16 000 patients given placebo. Main outcome measures Placebo adjusted reductions in systolic and diastolic blood pressure and prevalence of adverse effects, according to dose expressed as a multiple of the standard (recommended) doses of the drugs. Results All five categories of drug produced similar reductions in blood pressure. The average reduction was 9.1 mm Hg systolic and 5.5 mm Hg diastolic at standard dose and 7.1 mm Hg systolic and 4.4 mm Hg diastolic (20% lower) at half standard dose. The drugs reduced blood pressure from all pretreatment levels, more so from higher levels; for a 10 mm Hg higher blood pressure the reduction was 1.0 mm Hg systolic and 1.1 mm Hg diastolic greater. The blood pressure lowering effects of different categories of drugs were additive. Symptoms attributable to thiazides, blockers, and calcium channel blockers were strongly dose related; symptoms caused by ACE inhibitors (mainly cough) were not dose related. Angiotensin II receptor antagonists caused no excess of symptoms. The prevalence of symptoms with two drugs in combination was less than additive. Adverse metabolic effects (such as changes in cholesterol or potassium) were negligible at half standard dose. Conclusions Combination low dose drug treatment increases efficacy and reduces adverse effects. From the average blood pressure in people who have strokes (150/90 mm Hg) three drugs at half standard dose are estimated to lower blood pressure by 20 mm Hg systolic and 11 mm Hg diastolic and thereby reduce the risk of stroke by 63% and ischaemic heart disease events by 46% at age 60-69.

Objectives: To estimate the risk of ischaemic heart disease caused by exposure to environmental tobacco smoke and to explain why the associated excess risk is almost half that of smoking 20 cigarettes per day when the exposure is only about 1% that of smoking.

An Anglicized version of the SF-36, a recently developed generic health status measure, was tested among people aged 65 years and over in hospital outpatient and general practice settings as both a self-completed and interview-administered instrument. The SF-36 was quick to complete, with 84% completed in 10 minutes or less (median time 8 minutes), while the distribution of scores provided further evidence of its sensitivity and validity. As an interview-administered instrument the SF-36 was acceptable among all age groups, although 32% of outpatients and 10% of general-practice patients, consisting predominantly of people aged 75 years and over with poor physical or mental health scores, felt unable to self-complete the questionnaire. In addition, 26% of respondents missed out at least one of the 36 statements, with missing items being significantly related to older age and self-completion. Missing responses were mainly concentrated on a small number of questions whose emphasis on work or vigorous activities meant that they were frequently regarded as not applicable by elderly people. Suggested modifications to these questions for elderly respondents are given. With these changes the SF-36 is regarded as suitable for use as a self-completed questionnaire among the younger age group of elderly people, although some assistance may often be required by people aged 75 years and over and especially those with poor physical or mental health.

ObjectiveTo determine the trajectory of cognitive test scores from infancy to adulthood in individuals born extremely preterm compared with term-born individuals.DesignA prospective, population-based cohort study.Setting276 maternity units in the UK and Ireland.Patients315 surviving infants born less than 26 completed weeks of gestation recruited at birth in 1995 and 160 term-born classroom controls recruited at age 6.Main outcome measuresBayley Scales of Infant Development-Second Edition (age 2.5); Kaufman Assessment Battery for Children (ages 6/11); Wechsler Abbreviated Scale of Intelligence-Second Edition (age 19).ResultsThe mean cognitive scores of extremely preterm individuals over the period were on average 25.2 points below their term-born peers (95% CI −27.8 to −22.6) and remained significantly lower at every assessment. Cognitive trajectories in term-born boys and girls did not differ significantly, but the scores of extremely preterm boys were on average 8.8 points below those of extremely preterm girls (95% CI −13.6 to −4.0). Higher maternal education elevated scores in both groups by 3.2 points (95% CI 0.8 to 5.7). Within the extremely preterm group, moderate/severe neonatal brain injury (mean difference: −10.9, 95% CI −15.5 to −6.3) and gestational age less than 25 weeks (mean difference: −4.4, 95% CI −8.4 to −0.4) also had an adverse impact on cognitive function.ConclusionsThere is no evidence that impaired cognitive function in extremely preterm individuals materially recovers or deteriorates from infancy through to 19 years. Cognitive test scores in infancy and early childhood reflect early adult outcomes.