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Biomedical subjects

R Peto

Publications and source records attributed to R Peto.

At least 145 records · Page 8Linked to original sources

Blood pressure, stroke, and coronary heart disease. Part 2, Short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context.

There are 14 unconfounded randomised trials of antihypertensive drugs (chiefly diuretics or beta-blockers): total 37,000 individuals, mean treatment duration 5 years, mean diastolic blood pressure (DBP) difference 5-6 mm Hg. In prospective observational studies, a long-term difference of 5-6 mm Hg in usual DBP is associated with about 35-40% less stroke and 20-25% less coronary heart disease (CHD). For those dying in the trials, the DBP difference had persisted only 2-3 years, yet an overview showed that vascular mortality was significantly reduced (2p less than 0.0002); non-vascular mortality appeared unchanged. Stroke was reduced by 42% SD 6 (95% confidence interval 35-50%; 289 vs 484 events, 2p less than 0.0001), suggesting that virtually all the epidemiologically expected stroke reduction appears rapidly. CHD was reduced by 14% SD 5 (95% CI 4-22%; 671 vs 771 events, 2p less than 0.01), suggesting that just over half the epidemiologically expected CHD reduction appears rapidly. Although this significant CHD reduction could well be worthwhile, its size remains indefinite for most circumstances (though beta-blockers after myocardial infarction are of substantial benefit). At present, therefore, a sufficiently high risk of stroke (perhaps because of age, blood pressure, or, in particular, history of cerebrovascular disease) may be the clearest indication for antihypertensive treatment.

Antihypertensive Agents↗

Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias.

The associations of diastolic blood pressure (DBP) with stroke and with coronary heart disease (CHD) were investigated in nine major prospective observational studies: total 420,000 individuals, 843 strokes, and 4856 CHD events, 6-25 (mean 10) years of follow-up. The combined results demonstrate positive, continuous, and apparently independent associations, with no significant heterogeneity of effect among different studies. Within the range of DBP studied (about 70-110 mm Hg), there was no evidence of any "threshold" below which lower levels of DBP were not associated with lower risks of stroke and of CHD. Previous analyses have described the uncorrected associations of DBP measured just at "baseline" with subsequent disease rates. But, because of the diluting effects of random fluctuations in DBP, these substantially underestimate the true associations of the usual DBP (ie, an individual's long-term average DBP) with disease. After correction for this "regression dilution" bias, prolonged differences in usual DBP of 5, 7.5, and 10 mm Hg were respectively associated with at least 34%, 46%, and 56% less stroke and at least 21%, 29%, and 37% less CHD. These associations are about 60% greater than in previous uncorrected analyses. (This regression dilution bias is quite general, so analogous corrections to the relations of cholesterol to CHD or of various other risk factors to CHD or to other diseases would likewise increase their estimated strengths.) The DBP results suggest that for the large majority of individuals, whether conventionally "hypertensive" or "normotensive", a lower blood pressure should eventually confer a lower risk of vascular disease.

Adult↗

Liver transplantation for acute hepatic failure?

In the absence of definitive medical treatment for severe fulminant hepatic failure, liver transplantation may be appropriate in selected patients. However, uniform and easily applicable criteria for diagnosis of severity and analysis of results are needed to prevent unnecessary transplantation and to ensure that patients who may benefit are appropriately treated. Previous regimens for treatment of fulminant hepatic failure were often advocated, on the basis of data from historical controls, for several years until controlled trials failed to show any benefit. To obtain reliable information more rapidly than achieved before, a controlled trial between specialist liver transplant units is needed to establish the role of emergency hepatic transplantation in patients with fulminant hepatic failure.

Acute Disease↗

Serum vitamin A and subsequent risk of cancer: cancer incidence follow-up of the Finnish Mobile Clinic Health Examination Survey.

From 1968 to 1977, the association between the level of vitamin A in serum and the subsequent incidence of cancer was examined in a longitudinal study of 36,265 persons initially aged 15-99 years in 25 population groups in Finland. During a mean follow-up of 8 years, 766 cancers were diagnosed. Serum retinol, retinol-binding protein, and beta-carotene levels were measured from frozen serum samples (stored at -20 degrees C) drawn from these persons before the start of follow-up and from 1,419 controls matched for sex, age, and place of residence who did not develop cancer during follow-up. The mean level of serum retinol among the cancer cases was 645 micrograms/liter for men and 587 micrograms/liter for women. The corresponding levels in the controls were 3.3% and 2.8% higher. There was an inverse gradient between serum retinol level and the occurrence of cancer among men. This association was, however, mainly concentrated in the first 2 years of follow-up. The mean level of serum beta-carotene was 72.3 micrograms/liter among male cases and 119.5 micrograms/liter among female cases. The corresponding levels of the controls were 14.0% and 5.5% higher. The differences were particularly clear with regard to lung cancer. These findings suggest that the association between retinol and cancer may be due to preclinical cancer and that there may be an association between beta-carotene and cancer.

Adolescent↗

Effects of prophylactic lidocaine in suspected acute myocardial infarction. An overview of results from the randomized, controlled trials.

The effects of prophylactic lidocaine hydrochloride on early ventricular fibrillation and death in patients with suspected acute myocardial infarction were investigated in an overview of 14 randomized trials. During follow-up intervals of one to four hours in the trials of intramuscular lidocaine infusion (6961 patients) and 24 to 48 hours in the trials of intravenous lidocaine injection (2194 patients), a total of 103 cases of ventricular fibrillation and 137 deaths were recorded. Overall, allocation to lidocaine was associated with a reduction in the odds of ventricular fibrillation of about one third, with a 95% confidence interval that ranged from a 3% to a 56% reduction. There was no evidence of any beneficial effect on early mortality; indeed, the odds of early death were about one third greater among patients allocated lidocaine, though this difference was not statistically significant (95% confidence interval, 2% reduction to 95% increase). Because of the small numbers of reported events, the short follow-up periods, and the unavailability of data for some specific causes of death, even an overview of all the trial results does not provide good evidence as to whether prophylactic lidocaine is likely to be helpful or harmful. To answer this question reliably, future trials will need to involve large numbers of patients and prolonged follow-up.

Clinical Trials as Topic↗

Effect of intravenous nitrates on mortality in acute myocardial infarction: an overview of the randomised trials.

About 2000 patients have been randomised in ten trials of intravenous nitroglycerin or nitroprusside in acute myocardial infarction. Taken separately, the individual trials have all been too small to provide a reliable estimate of the effects of treatment on mortality, but collectively they provide strong evidence of benefit. In total there have been 136 nitrate and 193 control deaths, and an appropriate overview of the separate trial results indicated a "typical" reduction of 35% (SD 10) in the odds of death (2p less than 0.001, with 95% confidence limits of about one-sixth to one-half). Both nitroglycerin and nitroprusside reduced mortality, the reduction being non-significantly greater with nitroglycerin than with nitroprusside. The greatest reduction in mortality occurred during the first week or so of follow-up, with a non-significant further reduction after this early period. This suggests that the early benefit is not rapidly lost.

Clinical Trials as Topic↗

Randomised trial of prophylactic daily aspirin in British male doctors.

A six year randomised trial was conducted among 5139 apparently healthy male doctors to see whether 500 mg aspirin daily would reduce the incidence of and mortality from stroke, myocardial infarction, or other vascular conditions. Though total mortality was 10% lower in the treated than control group, this difference was not statistically significant and chiefly involved diseases other than stroke or myocardial infarction. Likewise, there was no significant difference in the incidence of non-fatal myocardial infarction or stroke--indeed, disabling strokes were somewhat commoner among those allocated aspirin. The lower confidence limit for the effect of aspirin on non-fatal stroke or myocardial infarction, however, was a substantial 25% reduction. Migraine and certain types of musculoskeletal pain were reported significantly less often in the treated than control group, but as the control group was not given a placebo the relevance of these findings was difficult to assess. There was no apparent reduction in the incidence of cataract in the treated group. The lack of any apparent reduction in disabling stroke or vascular death contrasts with the established value of antiplatelet treatment after occlusive vascular disease.

Aspirin↗