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S J Pocock

Publications and source records attributed to S J Pocock.

At least 73 records · Page 4Linked to original sources
PubMed1989

Concentrations of high density lipoprotein cholesterol, triglycerides, and total cholesterol in ischaemic heart disease.

OBJECTIVE: To assess the roles of serum concentrations of total cholesterol, high density lipoprotein cholesterol, and triglycerides in predicting major ischaemic heart disease. DESIGN: Men recruited for the British regional heart study followed up for a mean of 7.5 years. SETTING: General practices in 24 British towns. PATIENTS: 7735 Middle aged men. END POINT: Predictive value of serum concentrations of lipids. MEASUREMENTS AND MAIN RESULTS: At initial screening serum concentrations of total cholesterol, high density lipoprotein cholesterol, and triglycerides were determined from non-fasting blood samples. Altogether 443 major ischaemic heart disease events (fatal and non-fatal) occurred during the study. Men in the highest fifth of the distribution of total cholesterol concentration (greater than or equal to 7.2 mmol/l) had 3.5 times the risk of ischaemic heart disease than did men in the lowest fifth (less than 5.5 mmol/l) after adjustment for high density lipoprotein cholesterol concentration and other risk factors. Men in the lowest fifth of high density lipoprotein cholesterol concentration (less than 0.93 mmol/l) had 2.0 times the risk of men in the highest fifth (greater than or equal to 1.33 mmol/l) after adjustment for total cholesterol concentration and other risk factors. Men in the highest fifth of triglyceride concentration (greater than or equal to 2.8 mmol/l) had only 1.3 times the risk of those in the lowest fifth (less than 1.08 mmol/l) after adjustment for total cholesterol concentration and other risk factors; additional adjustment for high density lipoprotein cholesterol concentration made the association with ischaemic heart disease disappear. CONCLUSIONS: Serum concentration of total cholesterol is the most important single blood lipid risk factor for ischaemic heart disease in men. High density lipoprotein cholesterol concentration is less important, and triglyceride concentrations do not have predictive importance once other risk factors have been taken into account.

Adult↗
PubMed1989

Practical problems in interim analyses, with particular regard to estimation.

This article considers some of the practical problems inherent in interim analyses and stopping rules for randomized clinical trials. Topics covered include group sequential designs, trials with unplanned interim analyses, estimation problems in clinical trials with planned interim analyses, and the balance between individual and collective ethics. Particular attention is paid to the fact that clinical trials that stop early are prone to exaggerate the magnitude of treatment effect. Accordingly, a Bayesian "shrinkage" method of analysis is proposed to help quantify the extent to which surprisingly large point and interval estimates of treatment difference in clinical trials that stop early should be moderated.

Bayes Theorem↗
PubMed1989

Sample size requirements for prospective studies, with examples for coronary heart disease.

Methods of determining the required number of disease cases for estimation of relative odds in prospective studies are evaluated, with examples from coronary heart disease. Data from a British prospective study of coronary heart disease are used in simulation exercises to assess the reliability of estimation formulae for both continuous and categorical risk factors. For continuous risk factors, a univariate formula based on estimation of the standardized relative odds (Whittemore A. S. JAMA 1981; 76: 27-32 [1]), gives reliable estimation of the required number of disease cases, provided the risk factor has a near normal distribution. An extension of the formula to adjustment for other risk factors, was less satisfactory, perhaps because of departures from multivariate normality. For categorical risk factors, an adaption of a univariate method for case control studies (Smith PG, Day NE. Int J Epidemiol 1984; 13: 356-365 [2]), gives reliable estimates of the number of cases required. However, this depends on approximate prior knowledge of the relative odds. In general, prospective studies of coronary heart disease risk factors should aim for at least 400 cases to enable sufficient accuracy of estimation.

Adult↗
PubMed1989

Diurnal variations in serum biochemical and haematological measurements.

Twenty five biochemical and haematological measurements were determined on nonfasting blood and serum samples collected between 9 am and 7 pm from a representative group of 7685 British middle-aged men. Most measurements showed significant diurnal variations, but only for bilirubin, phosphate, and triglyceride did time of day account for more than 5% of the between subject variance. Serum bilirubin concentrations showed a pronounced downward trend in the afternoon, the mean value after 6 pm being 30% lower than the mean value in the morning. Mean serum triglyceride and phosphate concentrations increased steadily through the day. Mean concentrations of potassium, haemoglobin, and haematocrit and red cell count were higher in the morning, while urea and creatinine concentrations and white cell count had higher means in the afternoon. Glucose showed a pattern consistent with short term response to meals. The effects of these diurnal trends on routine use of biochemical tests needs careful consideration, and a greater understanding of their biological mechanisms is required.

Adult↗
PubMed1988

Stopping rules and estimation problems in clinical trials.

Stopping rules in clinical trials can lead to bias in point estimation of the magnitude of treatment difference. A simulation exercise, based on estimation of the risk ratio in a typical post-myocardial infarction trial, examines the nature of this exaggeration of treatment effect under various group sequential plans and also under continuous naive monitoring for statistical significance. For a fixed treatment effect the median bias in group sequential design is small, but it is greatest for effects that the trial has reasonable power to detect. Bias is evidently greater in trials that stop early and is dramatic under naive monitoring for significance. Group sequential plans lead to a multimodal sampling distribution of treatment effect, which poses problems for incorporating their estimates into meta-analyses. By simulating a population of trials with treatment effects modelled by an underlying distribution of true risk ratios, a Bayesian method is proposed for assessing the plausible range of true treatment effect for any trial based on interim results. This approach is particularly useful for producing shrinkage of the unexpectedly large and imprecise observed treatment effects that arise in clinical trials that stop early. Its implications for trial design are discussed.

Bayes Theorem↗
PubMed1988

Prediction of men at high risk of heart attack and its relevance to pilots.

In this paper we have extrapolated from data on the general population of middle-aged men and made suggestions for risk prediction and prevention policy in aircrew. As suggested previously, it would be helpful in future if data on the risk of heart attack in pilots could be generated from a central recording system covering both current pilots and those who retire for whatever reason. Indefinite follow-up information on ischaemic events would also be particularly helpful.

Adult↗
PubMed1988

Parental death from heart disease and the risk of heart attack.

In the British Regional Heart Study, 7735 men aged 40-59 years were asked at initial screening whether their father or mother was alive or dead and to what cause any death had been attributed. They were followed up for the occurrence of major ischaemic heart disease events. At screening the men reported that 23% of the fathers and 43% of the mothers were alive and that 19% of the fathers and 11% of the mothers had died of heart trouble. In a sample of parental deaths, the death certificate was obtained and it was found that a son's report of a parental death from 'heart trouble' was a reliable indication that death had been certified to ischaemic heart disease. However, about half of the parental deaths certified as ischaemic heart disease were not reported as 'heart trouble' by their sons. A major ischaemic heart disease event was experienced by 336 men over an average follow-up of 6.2 years. Men who said their father had died from 'heart trouble' were at twice the risk of a major ischaemic heart disease event compared with men whose fathers were still alive and 1.5 times the risk of men who reported their father to be dead from another or unknown cause, even after accounting for age, systolic blood pressure, serum total cholesterol, cigarette smoking and serum HDL-cholesterol. For men with mother dead from heart trouble, the corresponding figures were 1.3 and 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

The role of risk factors in heart attacks occurring in men with pre-existing ischaemic heart disease.

The importance of three risk factors--serum total cholesterol, systolic blood pressure, and cigarette smoking--on the risk of new major ischaemic heart disease events in men who already have evidence of ischaemic heart disease was assessed. Data from the initial examination in a large prospective study of cardiovascular disease in middle aged men (the British Regional Heart Study) were used to separate 7710 men into three groups on the basis of a resting electrocardiogram, a standardised chest pain questionnaire, and recall of a doctor's diagnosis of angina or of a previous heart attack: (group 1) no evidence of ischaemic heart disease (75%), (group 2) evidence of ischaemic heart disease short of a definite myocardial infarction (20%), (group 3) definite myocardial infarction (6%). In the average follow up period of 7.5 years, 443 men suffered a new major event caused by ischaemic heart disease (fatal or non-fatal myocardial infarction or sudden cardiac death). Age standardised event rates were determined for each of the three groups for varying levels of the established risk factors. Cigarette smoking is strongly associated with the event rate in group 1 but in men with existing heart disease, especially group 3, differences in risk between the smoking categories were smaller. The strong relation between systolic blood pressure and event rate persisted in groups 1 and 2 but not in group 3. The positive association between serum concentration of total cholesterol and the event rate was strongest in group 1 and weaker in groups 2 and 3, though it remained highly significant. These observations, taken together with the results of previous prospective studies and intervention trials, suggest that the important association between serum total cholesterol and the risk of heart attack persists in men with pre-existing ischaemic heart disease, including myocardial infarction. Therefore, in these men the reduction of serum total cholesterol concentration may be at least as important as it is in men without evidence of ischaemic heart disease.

Adult↗
PubMed1988

Blood cadmium concentrations in the general population of British middle-aged men.

Blood cadmium concentrations were determined for 6919 men aged 40-59 randomly selected from general practice registers in 24 British towns. The mean and median blood cadmium were 1.9 and 1.4 micrograms/1 respectively and the distribution was highly skewed. The mean levels in non-smokers was 1.0 micrograms/l and current smokers showed a marked gradient with the daily amount smoked, with a mean of 3.9 micrograms/l in men smoking 40 or more cigarettes per day. Whereas 95% of men who never smoked had blood cadmium less than 2.0 micrograms/l, 80% of men smoking 20 or more cigarettes a day exceeded this figure. 1% of the men had blood cadmium concentrations greater than or equal to 7 micrograms/l virtually all of whom currently smoked cigarettes. Blood cadmium levels in ex-smokers were much lower than in current smokers even for those who had stopped within the past year. However, the mean levels in ex-smokers remained higher than the 'never smoked' for several years after stopping. There was little evidence that age, social class, or alcohol consumption were associated with blood cadmium levels after allowance for cigarette smoking. There is substantial geographic variation in mean blood cadmium for middle-aged men which could not be completely accounted for by smoking differences. Towns in the south and east of England all had mean levels under 2.0 micrograms/l whereas the majority of towns in other parts of Britain had mean levels greater than 2.0 micrograms/l. Possible reasons for this geographic pattern (e.g. geochemistry, industrial exposure, dietary differences) need further exploration.

Adult↗
PubMed1988

The relationship between blood lead, blood pressure, stroke, and heart attacks in middle-aged British men.

The relationship between blood lead concentration and blood pressure is examined in a survey of 7371 men aged 40 to 59 from 24 British towns. After allowance for relevant confounding variables, including town of residence and alcohol consumption, there exists a very weak but statistically significant positive association between blood lead and both systolic and diastolic blood pressure. These cross-sectional data indicate that an estimated mean increase of 1.45 mm Hg in systolic blood pressure occurs for every doubling of blood lead concentration with a 95% confidence interval of 0.47 to 2.43 mm Hg. After 6 years of follow-up, 316 of these men had major ischemic heart disease, and 66 had a stroke. After allowance for the confounding effects of cigarette smoking and town of residence there is no evidence that blood lead is a risk factor for these cardiovascular events. However, as the blood lead-blood pressure association is so weak, it is unlikely that any consequent association between lead and cardiovascular disease could be demonstrated from prospective epidemiological studies. An overview of data from this and other large epidemiological surveys provides reasonably consistent evidence on lead and blood pressure. While NHANES II data on 2254 U.S. men indicate a slightly stronger association between blood lead and systolic blood pressure, data from two Welsh studies on over 2000 men did not show a statistically significant association. However, the overlapping confidence limits for all these studies suggest that there may be a weak positive statistical association whereby systolic blood pressure is increased by about 1 mm Hg for every doubling of blood lead concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Blood pressure and hypertension in middle-aged British men.

Blood pressure measurements in 7735 middle-aged men from general practices in 24 towns in England, Wales and Scotland provide information on the prevalence of hypertension and its management in Great Britain. Despite a substantial correlation (r = 0.70) between systolic and diastolic blood pressures, individuals can show considerable discrepancies between these two measurements; they are not interchangeable. This observation has important implications for the choice of criteria used to define hypertension. However defined, the prevalence of hypertension increases markedly with age, increasing body mass index and with heavy alcohol consumption. It is not related to smoking and only to a small extent to social class. Diastolic hypertension (greater than or equal to 90 mmHg) was present in 26% and systolic hypertension (greater than or equal to 160 mmHg) in 22% of these men. In both systolic and diastolic hypertension, only one quarter of affected men could recall having been diagnosed as hypertensive by a doctor, and only one third of these were on regular antihypertensive treatment. There is a threefold variation in the prevalence of measured hypertension in the 24 towns with a trend towards higher rates in Northern England and Scotland. No relationship was seen between the prevalence rates of measured hypertension in the towns and the rates of doctor diagnosis of hypertension. Cardiovascular mortality rates in the towns were correlated with the measured prevalence rates for systolic and diastolic hypertension (r = 0.70 and r = 0.57, respectively). The geographic variations in blood pressure and hypertension in Great Britain provide a major opportunity for research into the causes of 'essential' hypertension.

Adult↗
PubMed1987

State of the art in comparative cancer clinical trials.

In order to investigate the current state of the art in clinical cancer research, a survey of comparative cancer clinical trials was conducted using a MEDLINE literature search of the 6-month interval from July to December of 1985. Data were obtained primarily from the published abstracts. The major observations from the study are as follows. First, trials in cancer research are published in an extraordinarily wide range of journals covering most of the major medical specialties in addition to the many cancer specialty journals. Second, randomization is now used quite extensively. It is the predominant method of control in chemotherapy trials and in trials reported in cancer journals. However, its use is much less common in other specialties, especially surgery, so efforts to popularize randomization in these specialties would be beneficial. Third, sample sizes are highly variable, and the median sample size (96 patients) is too small to reliably detect and evaluate moderate treatment advances. Finally, our survey reveals that published trials show an inordinately large proportion of breakthroughs in treatment compared with the generally accepted view that only slow progress is being made in developing effective cancer treatments. Our view is that this result reflects the strong tendency to publish only studies with positive results. This hypothesis is supported by the fact that in nonrandom trials there tend to be more positive conclusions and an absence of a strong association between conclusions and sample size.

Clinical Trials as Topic↗
PubMed1987

Statistical problems in the reporting of clinical trials. A survey of three medical journals.

Reports of clinical trials often contain a wealth of data comparing treatments. This can lead to problems in interpretation, particularly when significance testing is used extensively. We examined 45 reports of comparative trials published in the British Medical Journal, the Lancet, or the New England Journal of Medicine to illustrate these statistical problems. The issues we considered included the analysis of multiple end points, the analysis of repeated measurements over time, subgroup analyses, trials of multiple treatments, and the overall number of significance tests in a trial report. Interpretation of large amounts of data is complicated by the common failure to specify in advance the intended size of a trial or statistical stopping rules for interim analyses. In addition, summaries or abstracts of trials tend to emphasize the more statistically significant end points. Overall, the reporting of clinical trials appears to be biased toward an exaggeration of treatment differences. Trials should have a clearer predefined policy for data analysis and reporting. In particular, a limited number of primary treatment comparisons should be specified in advance. The overuse of arbitrary significance levels (for example, P less than 0.05) is detrimental to good scientific reporting, and more emphasis should be given to the magnitude of treatment differences and to estimation methods such as confidence intervals.

Clinical Trials as Topic↗
PubMed1987

Social class differences in ischaemic heart disease in British men.

To examine why ischaemic heart disease (IHD) mortality rates in Britain are higher in manual than in non-manual workers 7735 middle-aged men in the British Regional Heart Study were followed up for 6 years, during which time 336 men experienced a major IHD event (fatal or non-fatal myocardial infarction or sudden cardiac death). The prevalence rates of IHD at screening, were higher in manual workers. Also, the attack rate of major IHD events during follow-up was 44% higher in manual workers. Marked differences in cigarette smoking contributed substantially to the increased risk of IHD in manual workers, who also had higher levels of blood pressure, were more obese, and took much less physical activity in leisure time. Adjustment for differences in these risk factors narrowed the gap between manual and non-manual workers in attack rates of IHD. Since the risk of IHD in Great Britain is high in all social classes, there would seem to be little justification for any overall policy for prevention of IHD to focus on social class. However, anti-smoking strategies might well take into account the social class differences described.

Adult↗
PubMed1987

Alcohol and ischaemic heart disease in middle aged British men.

The relation between alcohol intake and ischaemic heart disease was examined in a large scale prospective study of middle aged men drawn from general practices in 24 British towns. After an average follow up of 6.2 years 335 of the 7729 men had experienced a myocardial infarction (fatal or non-fatal) or sudden cardiac death. No significant relation was found between reported alcohol intake and the incidence of such events. Though the group of light daily drinkers had the lowest incidence of ischaemic heart disease events, it also contained the lowest proportion of current smokers, had the lowest mean blood pressure, had the lowest mean body mass index, and contained the lowest proportion of manual workers. These characteristics are more likely to account for the apparent protective effect of alcohol against ischaemic heart disease than a direct effect of alcohol. Compared with the effects of established risk factors alcohol seems to be quite unimportant in the development of ischaemic heart disease.

Adult↗
PubMed1987

Lead exposure and children's intellectual performance.

The Institute of Child Health/Southampton study is the largest cross-sectional survey of lead exposure and children's intelligence. 402 six year olds in London with tooth lead concentration in three pre-defined ranges were selected for neuropsychological testing. This paper presents new findings on the relationship between child IQ and tooth lead levels which build on previous findings in four respects: Rather than simply classifying children into high, medium and low lead groups the actual concentrations of lead in each child's tooth have been used to provide a more powerful assessment of the association between IQ and body lead burden. The influence of parental and social factors on child IQ is explored in detail in order to see if any residual lead-IQ association exists after allowance for such confounders. The methods of multiple regression, including an 'optimal' statistical policy, are more fully described. The possibility of interactions between lead and confounders is explored. Findings are that parental IQ is the most important influence on child IQ, though several other factors (eg: family size, social class and quality of marital relationships) were also significantly related. There was no overall evidence that tooth lead concentrations were related to child IQ once these other factors were taken into account. However, a significant interaction between tooth lead and sex of child indicates that the lead-IQ association appears much more pronounced in boys. This unexpected finding needs cautious interpretation and further exploration in other studies.

Child↗