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Biomedical subjects

S J Pocock

Publications and source records attributed to S J Pocock.

At least 91 records · Page 5Linked to original sources

A scoring system to identify men at high risk of a heart attack.

A scoring system for identification of men at high risk of a heart attack within 5 years of screening is presented. The full scoring system includes an electrocardiogram and blood cholesterol measurement and the top fifth of the distribution of this full score yields 59% of the major ischaemic heart disease events occurring in the 5 years after screening. An intermediate scoring system, without an electrocardiogram but retaining blood cholesterol, yields 58% of cases from the top fifth of the score distribution. A basic (GP) score, without electrocardiogram or blood cholesterol measurement, yields 54% of cases and is recommended for use in opportunistic screening in general practice. This high risk strategy would increase public awareness of the size of the problem, help to prevent premature death and provide a useful complement to the population strategies of health education and government policy.

Adult↗

Interim analyses in randomized clinical trials: ramifications and guidelines for practitioners.

Recent developments in group sequential methods have had a great impact on the design and analysis of randomized clinical trials. The consequences for both planned and unplanned interim analyses are discussed using several real trials as illustrations. Guidelines for the conduct of interim analysis are given, including tables of nominal significance levels and required sample sizes for several group sequential plans. Areas in need of further theoretical advance include multiple endpoints, estimation of treatment differences, stratification, and design of multiple-armed trials.

Clinical Trials as Topic↗

The analysis of multiple endpoints in clinical trials.

Treatment comparisons in randomized clinical trials usually involve several endpoints such that conventional significance testing can seriously inflate the overall Type I error rate. One option is to select a single primary endpoint for formal statistical inference, but this is not always feasible. Another approach is to apply Bonferroni correction (i.e., multiply each P-value by the total number of endpoints). Its conservatism for correlated endpoints is examined for multivariate normal data. A third approach is to derive an appropriate global test statistic and this paper explores one such test applicable to any set of asymptotically normal test statistics. Quantitative, binary, and survival endpoints are all considered within this general framework. Two examples are presented and the relative merits of the proposed strategies are discussed.

Asthma↗

Giving up smoking and the risk of heart attacks. A report from The British Regional Heart Study.

In a prospective study of 7735 middle-aged men, both current and ex-cigarette-smokers had a risk of a major IHD event, within an average 6.2 years of screening, more than twice that in men who had never smoked cigarettes; men who had given up smoking more than 20 years ago still had an increased risk. This excess risk among ex-smokers is only to a small extent explained by their higher blood pressure, serum total cholesterol, and body-mass index. An increased prevalence of IHD in men who had recently given up smoking also made a small contribution to excess risk. In both current and former cigarette smokers, the number of years a man had smoked cigarettes ("smoking-years") was the clearest indicator of IHD risk due to cigarettes. The major benefit of giving up smoking may lie in halting the accumulation of smoking years.

Adult↗

Identifying men at high risk of heart attacks: strategy for use in general practice.

A strategy was devised for identifying men at high risk of acute myocardial infarction or sudden ischaemic death. A risk score was devised using cigarette smoking, mean blood pressure, recall of ischaemic heart disease or diabetes mellitus diagnosed by a doctor, history of parental death from "heart trouble," and the presence of angina reported on a questionnaire. The top fifth of the score distribution identified 53% of ischaemic heart disease cases--that is, men who subsequently experienced major ischaemic heart disease over the next five years. The addition of serum total cholesterol concentration and electrocardiographic evidence only slightly improved prediction (to 59%) and would have considerably increased the cost and effort of screening. Using this risk score on an opportunistic basis could be particularly valuable in general practice. Management of this high risk group is regarded as appropriate medical care and is complementary to the population approach to preventing ischaemic heart disease. Such a strategy for reducing the incidence of and mortality from ischaemic heart disease in men at high risk would also increase professional and public awareness of the need for preventive action.

Adult↗

High density lipoprotein cholesterol is not a major risk factor for ischaemic heart disease in British men.

The concentration of high density lipoprotein cholesterol (HDL cholesterol) in serum was measured at initial examination in a large prospective study of men aged 40-59 drawn from general practices in 24 British towns. After an average follow up of 4.2 years 193 cases of major ischaemic heart disease had been registered in 7415 men in whom both HDL cholesterol and total cholesterol values had been measured. The mean HDL cholesterol concentration was lower in the men with ischaemic heart disease ("cases") compared with other men, but the difference became small and non-significant after adjustment for age, body mass index, blood pressure, cigarette smoking, and concentration of non-HDL cholesterol. The higher mean concentration of non-HDL cholesterol in "cases" remained highly significant after adjustment for other factors. Men in the highest fifth of non-HDL cholesterol values had over three times the risk of major ischaemic heart disease compared with men in the lowest fifth. Multivariate analysis showed that non-HDL cholesterol was a more powerful predictor of risk than the HDL to total cholesterol ratio. These British findings were compared with six other prospective studies. All the larger studies showed similar results, suggesting that HDL cholesterol is not a major risk factor in the aetiology of ischaemic heart disease.

Adult↗

Current issues in the design and interpretation of clinical trials.

Though there have been considerable improvements in the use of statistical methods for clinical trials in recent years, there remain major practical difficulties in the design and interpretation of many trials. This paper concentrates on problems relating to randomisation, the overemphasis on significance testing, and the inadequate size of many trials. Each topic is illustrated by examples from recent trials.

Breast Neoplasms↗

Risk factors for ischaemic heart disease: the prospective phase of the British Regional Heart Study.

Risk factors for major ischaemic heart disease (acute myocardial infarction or sudden death) have been investigated in a prospective study of 7735 men aged 40-59 years drawn from general practices in 24 British towns. After a mean follow-up of 4.2 years, there have been 202 cases of major ischaemic heart disease. Univariate estimates of the risk of ischaemic heart disease show that serum total cholesterol, HDL-cholesterol and triglyceride concentrations, systolic and diastolic blood pressures, cigarette smoking, and body mass index are all associated with increased risk of ischaemic heart disease. Evidence of ischaemic heart disease at initial examination is also strongly associated with increased risk of subsequent ischaemic heart disease. All these factors were then considered simultaneously using multiple logistic models. Definite myocardial infarction on electrocardiogram and recall of a doctor diagnosis of ischaemic heart disease remained predictive of subsequent major ischaemic heart disease, after allowance for all other risk factors. Serum total cholesterol, blood pressure, and cigarette smoking each remained as highly significant independent risk factors whereas overweight, above average levels of HDL-cholesterol and serum triglyceride were not predictive of risk after allowance for the above factors. Men with and without pre-existing ischaemic heart disease were examined separately in the same way (using multiple logistic models). The strength of association between the principal risk factors and subsequent major ischaemic heart disease was reduced in the men with pre-existing ischaemic heart disease, only age and serum total cholesterol remaining highly significant. Overall the levels of the major risk factors commonly encountered in British men have a marked effect on the risk of ischaemic heart disease. Modification of these risk factors in the general population constitutes an important national priority.

Adult↗

Biochemical and haematological response to alcohol intake.

In a clinical survey of 7735 middle-aged men, alcohol consumption has been related to 25 biochemical and haematological measurements obtained from a single blood sample. Most measurements showed some association with alcohol consumption, gamma-glutamyl transferase (GGT) being the most strongly associated. Lead, mean corpuscular haemoglobin (MCH), mean corpuscular volume, high-density lipoprotein-cholesterol (HDL-C), urate and aspartate transaminase also showed substantial associations with alcohol intake. Using a discriminant analysis technique, a simple score based on five variables (GGT, HDL-C, urate, MCH and lead) provided the best discrimination between heavy drinkers (e.g. more than three pints of beer daily) and occasional drinkers, but still failed to identify more than half of the heavy drinkers. This combined score may prove a useful measure of an individual's biochemical/haematological response to alcohol consumption for use in epidemiological and clinical studies of alcohol related disorders. The use of such indices should complement but not replace measures of alcohol intake derived from questionnaires.

Adult↗

Blood lead concentration, blood pressure, and renal function.

Blood lead concentrations were related to blood pressure and indicators of renal function in a clinical survey of 7735 middle aged men from 24 British towns. There was no overall evidence that blood lead concentrations were associated with systolic or diastolic blood pressure (r = +0.03 and +0.01, respectively). In the 74 men with a blood lead concentration of 1.8 mumol/l (37.3 micrograms/100 ml) or more there was some suggestion of increased hypertension, but this did not reach significance. Blood lead concentration did not have any relation with serum creatinine concentration. Moderate increases in blood lead concentration were associated with small increases in mean serum urate concentration and small decreases in mean serum urea concentration; these associations were both reduced when alcohol consumption was taken into account. There is no indication that exposure to lead at concentrations commonly encountered in British men is responsible for impaired renal function or increased blood pressure.

Adult↗

Reduction in exposure to lead from drinking water and its effect on blood lead concentrations.

The water supply in Ayr (Scotland, UK) was plumbosolvent and many dwellings in Ayr contained lead pipes. In 1981 treatment of the water supply to reduce its plumbosolvency was initiated. Measurements of water and blood lead concentrations were made before and subsequent to the treatment. Most of the measurements made before and after water treatment began were made on water samples from the same dwellings and blood samples from the same women. Water treatment produced a sharp fall in water lead concentrations and a decrease in the median blood lead concentration from 21 to 13 micrograms/100 ml. Two women had higher than expected blood lead concentrations, both these women had been removing old paint. Women who had lead pipes removed from their dwellings all showed substantial decreases in their blood lead concentrations. The curvilinearity of the relation between blood lead and water lead concentrations is confirmed. Even relatively low (less than 40 micrograms/l) water lead concentrations may make a substantial contribution to blood lead concentrations.

Adult↗

Effects of tap water lead, water hardness, alcohol, and cigarettes on blood lead concentrations.

A survey of middle-aged men in 24 British towns has found pronounced geographical variation in blood lead concentrations. Towns with the highest mean blood lead concentrations have soft water supplies and have the highest water lead concentrations. Individual blood lead can be considerably increased by raised household tap water lead concentrations. Mean blood lead is estimated to be 43% higher for men when the concentration of lead in first-draw domestic tap water is 100 micrograms/l compared with a zero concentration. Individual blood lead is also affected by alcohol consumption and cigarette smoking, such that on average these two life-style habits together contribute an estimated 17% to the blood concentration of lead in middle-aged men. Lead in water should be given greater priority in any national campaign to reduce lead exposure.

Adult↗

Multiple regression in geographical mortality studies, with allowance for spatially correlated errors.

In order to provide clues to the aetiology of a disease, mortality indices for different areas are often related to explanatory variables by using multiple regression. However, mortality in nearby areas may be similar for reasons not attributable to the covariates, so the errors will not be independent. This paper suggests a way of finding a parameterized form for the correlated error structure by examining the residuals from an ordinary least squares regression. Such a model is then fitted by using maximum likelihood. An example based on cardiovascular mortality in British towns is used to illustrate the problem and our solution.

Cardiovascular Diseases↗