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Biomedical subjects

S G Thompson

Publications and source records attributed to S G Thompson.

At least 19 recordsLinked to original sources
PubMed1992

The Lancet's statistical review process: areas for improvement by authors.

The Lancet now incorporates statistical review of submitted papers which remain candidates for publication after conventional review. We summarise here criticisms noted by the statistical reviewers for 191 such papers received between November, 1990, and June, 1991. Only 54% of papers were deemed acceptable or acceptable after revision; the others were either recommended for rejection (14%) or for more substantial revision and re-review (32%). Descriptions of methods and of results were found inadequate in about half of the papers; about one-quarter of papers had inadequate abstracts and conclusions. Major errors of inference were made in 48 papers and went hand in hand with major criticisms of analysis or design in those papers. The natural focus of statistical review is whether conclusions drawn are justified by study design and statistical analysis. In this, there is room for improvement by authors.

Bias↗
PubMed1992

Model-based screening by risk with application to Down's syndrome.

Screening for a disorder may be carried out by assessing the risk that an individual is affected given the values of variables whose distributions alter when the disorder is present. An optimal screening policy is obtained by identifying those individuals whose risk is greater than some cut-off value. This paper summarizes the way in which risk is derived from the likelihood ratio of being affected by the disorder, and compares three different methods of estimating the likelihood ratio, namely direct estimation, logistic regression and distribution modelling. For continuous variables that have a multivariate normal distribution, screening by risk is equivalent to the use of quadratic discrimination. The paper shows how estimates of the risk and associated detection and false positive rates can be derived for a screening policy which uses specified risk cut-offs. Screening by risk has the counter-intuitive property that as the separation in the distribution of screening variables between affected and unaffected individuals increases, the detection and false positive rates may both increase. The approach is explored using data on antenatal screening for Down's syndrome. The method of choice is model-based; the model is described and tested for goodness of fit. Complications arising from outliers and non-normality must be overcome before an appropriate assessment of risk can be made. The concept of shrinkage is used to estimate the detection of false positive rates that may be expected in a new data set.

Confidence Intervals↗
PubMed1992

The relationship between hemostatic tests and cardiovascular risk factors in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities (ECAT) Angina Pectoris Group.

Baseline data are presented of the ECAT Angina Pectoris Study. Both plasminogen activator inhibitor and fibrinogen were positively associated with a number of cardiovascular risk factors such as smoking, body mass index, and also with the presence of coronary stenosis. Results indicate a role of the hemostatic system in the progress of coronary arteriosclerosis.

Angina Pectoris↗
PubMed1992

Factors affecting the precision of warfarin treatment.

AIM: To determine what factors influence the precision of anticoagulant control using warfarin by examining the computerised records of 2207 patients. METHODS: Records from seven district general hospitals were combined and analysed. The precision of anticoagulant control was taken as the absolute deviation of International Normalised Ratio (INR) from target at the most recent determination. This quantity was examined using univariate and multiple regression analyses. RESULTS: Deviation of INR from target was continuously distributed, almost symmetrically about a mean of zero. The patients' age and sex had little bearing on control. Patients with a high target INR were more likely to be undertreated, and patients taking higher doses of warfarin were more likely to be overtreated. Previous over- or undertreatment were strongly related to poorer current control. The control of treatment varied substantially among the seven hospitals. One possible cause of this variation was the dose adjustment coefficient: the greater the dose adjustment for a given deviation from target INR, the better was the control achieved. CONCLUSION: Several groups of patients were identified whose control was less satisfactory and in whom anticoagulant treatment needs particular scrutiny: these include patients with a record of previous over- or undertreatment, but not elderly patients in general. The variation in control among hospitals is a source of concern that merits further attention to achieve better uniformity of anticoagulant treatment.

Age Factors↗
PubMed1992

Factors affecting the maintenance dose of warfarin.

AIM: To identify the possible factors determining the dose of warfarin prescribed in patients receiving anticoagulant treatment. METHODS: The computerised records of 2305 patients maintained on the drug in seven hospitals were amalgamated and classified into one of seven diagnostic groups. The associations with the dose of warfarin prescribed were investigated by univariate and multiple regression analysis. Differences between hospitals were studied with regard to the coagulometric method and the thromboplastin preparation used. RESULTS: The geometric mean dose of warfarin was 4.57 mg and 5% of patients were prescribed 10 mg or greater. There was a noticeable decrease in dose with increasing age, which averaged about 6 mg for patients aged 30 but 3.5 mg for those aged 80. Men required slightly more warfarin than women. Patients with heart disease or atrial fibrillation required lower doses of warfarin, while higher doses were required by patients with deep vein thrombosis. Significant differences in mean warfarin dose among the seven hospitals were evident. These differences could not be explained entirely by the use of different coagulometric methods or thromboplastins. CONCLUSIONS: Clinicians should be aware that older patients need reduced doses of warfarin. The considerable differences in doses of warfarin among hospitals indicates that further efforts to improve uniformity are required.

Adult↗
PubMed1991

Can meta-analyses be trusted?

The enthusiasm for meta-analyses (or overviews) expressed by their proponents is not always shared by the broader medical community. To encourage constructive debate, we adopt a critical perspective on the conduct and interpretation of meta-analysis. We focus particularly on some of the statistical issues, especially heterogeneity between studies, and also on the extrapolation of meta-analysis findings to clinical practice. We conclude that meta-analysis is not an exact statistical science that provides definitive simple answers to complex clinical problems. It is more appropriately viewed as a valuable objective descriptive technique, which often furnishes clear qualitative conclusions about broad treatment policies, but whose quantitative results have to be interpreted cautiously.

Bias↗
PubMed1991

The impact of sequential quality assessment exercises on laboratory performance: the multicentre ECAT Angina Pectoris Study. Report from the European Concerted Action on Thrombosis and Disabilities (ECAT).

As an adjunct to a European multicentre prospective study, five quality assessment (QA) exercises, spanning a period of 2.5 years, were undertaken. In these, fifteen laboratories from eight countries each performed ten haemostatic factor assays. The design of the QA exercises allowed the between-duplicate, between-day and between-laboratory coefficients of variation (CVs) to be calculated. The between-duplicate CV decreased by a factor of one quarter, and the between-day CV by a factor of one third, over the five exercises. The activated partial thromboplastin time (APTT) assay consistently showed the lowest CVs, while there was notable improvement in the between-day CVs for von Willebrand factor related antigen (vWF R:Ag) and factor VIII clotting activity (VIII:C). However, the between-laboratory CV, assessing extent of agreement between the different laboratories, did not apparently improve over the five exercises. Thus, while QA exercises may be very useful in improving the performance of haemostatic assays according to criteria which an individual laboratory can assess, improving agreement on haemostatic assay results between laboratories may be more difficult to achieve.

Angina Pectoris↗
PubMed1991

Low serum cholesterol and the risk of cancer: an analysis of the published prospective studies.

Data were analyzed from 33 prospective studies to assess the evidence for a long-term association of low serum cholesterol with cancer. In subjects with cancer diagnosed within two years of the cholesterol measurement or causing death within five years (n = 4,661), the level of serum cholesterol was on average lower than in controls by 0.18 (SE = 0.02) mmol/l in men and 0.11 (SE = 0.04) mmol/l in women; this effect can be attributed to preclinical cancer. For cancers presenting after these intervals (n = 22,030), the average differences were smaller but statistically significant (0.04 [SE = 0.01] mmol/1 [P less than 0.001) in men, and 0.03 [SE = 0.01] mmol/1 [P = 0.005] in women), equivalent to about a 15 percent increase in cancer incidence in the lowest cholesterol quintile. This cannot be attributed entirely to preclinical cancer. In men, there was significant (P = 0.01) heterogeneity between studies as to the extent of a long-term association. The heterogeneity could be substantially explained by socioeconomic status, the association being pronounced in studies of manual workers but absent in studies of professional men. The overall long-term association was attributable mainly to lung cancer in men, and partly to hemopoietic cancers (representing prolongation of survival by treatment). Colon cancer and other cancers unrelated to smoking showed no long-term association with low cholesterol. The data collectively do not justify concern that lowering serum cholesterol to reduce ischemic heart-disease risk might cause cancer. The long-term association with lung cancer is probably caused by smoking and we propose a mechanism.

Cholesterol↗
PubMed1990

How should urinary cotinine concentrations be adjusted for urinary creatinine concentration?

The correlation between cotinine concentrations in a single specimen of urine and in serum collected on the same occasion from 279 male smokers was 0.83. This was significantly increased, to 0.91, by adjusting the urinary cotinine levels for urinary creatinine concentration to take account of variations in urinary dilution between people. The adjustment used was based on the observed regression relationship between urinary cotinine and urinary creatinine concentrations. Expressing urinary cotinine values as a ratio to urinary creatinine, which has been used as a method of adjustment by others, did not improve the correlation between serum and urinary cotinine levels. The method of adjusting urinary cotinine for urinary creatinine is, therefore, important. The principle of such adjustment should apply not only to cotinine but also to other urinary biochemical measurements.

Adult↗
PubMed1990

Prognostic scores for detecting a high risk group: estimating the sensitivity when applied to new data.

The sensitivity of a prognostic scoring system will tend to be exaggerated if the scoring system is both derived and validated on the same data. This paper provides, by analogy to regression with error in an explanatory variable, an intuitive basis for the methodological results of Copas which seek to estimate the degree of such exaggeration. There was good agreement between Copas' results and those achieved in a series of cross-validation exercises where logistic regression models predicting the risk of ischaemic heart disease were derived using data from the prospective British Regional Heart Study. When truly important variables were included, the exaggeration of the sensitivity increased as the number of cases of disease available decreased. It is concluded that Copas' method, which is easy to implement in practice, may be helpful in realistically anticipating the extent of such exaggeration, and that it can be usefully employed before pursuing a scoring system on newly collected data.

Adult↗
PubMed1990

The variability of serum cholesterol measurements: implications for screening and monitoring.

The reliability of screening for high serum total cholesterol is adversely affected by the variability of cholesterol levels over time. This problem is investigated using data on repeated cholesterol measurements for 14,600 men and women in the MRC Mild Hypertension Trial. For measurements 1 year apart, the within-person coefficient of variation (CV) is 7%, which is substantial compared with the between-person CV of 15%. In a screening programme, this within-person variability may lead to the misclassification of individuals and inappropriate intervention. For example, 28% of middle-aged British men with a single cholesterol measurement above 6.9 mmol/l have a long-term average cholesterol below that value even without intervention. Using averages of several cholesterol measurements reduces, but does not eliminate, these problems. Furthermore, monitoring the effect of interventions in individuals by sequential cholesterol measurement may be unhelpful or even misleading. These problems cast serious doubt on the value of general population screening for high cholesterol levels.

Adult↗
PubMed1990

Relation of urinary cotinine concentrations to cigarette smoking and to exposure to other people's smoke.

The relation of urinary cotinine measurements to tobacco consumption in smokers and to exposure to other people's smoke in non-smokers was studied in 49 smokers and 184 reported non-smokers attending a health screening centre. The median urinary cotinine concentration was 1623 ng/ml in the smokers and 6.1 ng/ml in the non-smokers. In smokers the average urinary cotinine concentration increased with reported habitual cigarette consumption; in non-smokers it increased with the reported total seven day duration of exposure to other people's tobacco smoke. Cotinine concentrations were approximately three times higher in non-smokers living with a spouse or partner who was a smoker than in those living with a non-smoker; their reported duration of exposure to tobacco smoke was also three times higher. Non-smoking subjects who were exposed to any tobacco smoke and who lived with a smoker reported 70% of their exposure to be at home (56% for men and 86% for women); the men reported more exposure at work than non-smoking men who lived with a non-smoker. This study confirms the relation of urinary cotinine to stated tobacco smoke exposure in both smokers and non-smokers and further validates the use of information on the smoking habits of the spouse or partner as a measure of tobacco smoke exposure in epidemiological studies of non-smokers.

Adult↗
PubMed1989

The measurement of haemostatic factors in 16 European laboratories: quality assessment for the Multicentre ECAT Angina Pectoris Study. Report from the European Concerted Action on Thrombosis and Disabilities (ECAT).

As part of a European multicentre prospective study involving the measurement of a number of haemostatic factors, a quality assessment (QA) scheme was organized. This paper describes the preparation, design and results of the first QA exercise, involving 16 European laboratories and 10 haemostatic assays. The design allowed the investigation, for each assay, of the variability between duplicates and the variability between days within each centre, and of the agreement between centres. A graphical presentation of each centre's performance in comparison to that of others was adopted, which preserved the confidentiality of each centre's results. The factor VIII clotting activity assay (VIII:C) and the rocket immuno-electrophoresis assays of von Willebrand factor related antigen (vWF R:Ag), antithrombin III, protein C and histidine-rich glycoprotein showed the highest between-duplicate and between-day coefficients of variation (CVs), whereas the clotting assays of activated partial thromboplastin time and fibrinogen had the lowest CVs. CVs for the enzymatic assays using synthetic substrates of antithrombin III, plasminogen and alpha-2-antiplasmin were between these extremes. The between-centre CVs were high for both the VIII:C and vWF R:Ag assays. The QA exercise showed that, in multicentre studies involving the measurement of haemostatic factors, it is feasible to undertake analysis locally at each centre.

Angina Pectoris↗
PubMed1989

Serum cholesterol and subsequent risk of cancer: results from the BUPA study.

In the BUPA study, a prospective study of 22,000 men attending a screening centre in London, the mean serum cholesterol level of the 267 men who developed cancer was 6.66 mmol l-1, not significantly different from the mean level of 6.72 mmol l-1 among the 525 unaffected controls matched for age, smoking history and the calendar quarter of their attendance at the screening centre. There was, however, a significant difference in serum cholesterol levels among men who were diagnosed as having cancer less than 2 years after the date of blood collection (6.49 mmol l-1 for the 116 cancer subjects and 6.78 mmol l-1 for the 224 controls (P = 0.02)) but not in men who developed cancer 2-11 years after blood collection (6.79 mmol l-1 for the 151 cancer subjects and 6.68 mmol l-1 for the 301 controls). The observation that the association between low serum cholesterol and cancer was confined to men in whom a diagnosis of cancer was made within 2 years after the date of blood collection suggests that the low serum cholesterol is a metabolic consequence rather than a precursor of the cancer. Our results, which are consistent with the majority of other published studies, indicate that a low serum cholesterol is not a cause of cancer.

Adult↗
PubMed1989

Risk factors for stroke and myocardial infarction in women in the United Kingdom as assessed in general practice: a case-control study.

Data available in the United Kingdom through the Medical Research Council's General Practice Research Framework were recorded in a study of 603 women aged 45-69 with confirmed diagnoses of stroke or myocardial infarction, each matched by age with two controls. Current cigarette smoking and a family history of myocardial infarction were both strongly associated with the risk of stroke and myocardial infarction, with relative risks of 2.47 (95% confidence interval 1.89 to 3.23) and 1.93 (95% confidence interval 1.52 to 2.44) respectively. The relative risks associated with past smoking decreased according to the length of time since stopping smoking. A family history of stroke was not significantly related to the risk of stroke or myocardial infarction. Single women had a lower risk of stroke and myocardial infarction than married women (relative risk 0.49), but parity, past use of oral contraceptives, and menopausal state were not significantly related to the risk of stroke and myocardial infarction in this study. Other characteristics that were identified as risk factors either for subsequent stroke or for myocardial infarction included not only hypertension, diabetes, and past histories of stroke and myocardial infarction, but also past histories of gynaecological cancer and of venous thrombosis. The association with venous thrombosis may indicate the importance of the haemostatic system in a common pathogenesis of venous thrombosis and myocardial infarction.

Aged↗
PubMed1989

The use of hormonal replacement therapy and the risk of stroke and myocardial infarction in women.

STUDY OBJECTIVE: To determine whether there is an association between the use of hormonal replacement therapy (HRT) and the risk of stroke and myocardial infarction (MI). DESIGN: A case-control study of women with stroke or MI was undertaken. SETTING: The cases were notified from 83 general practices to the coordinating centre at Northwick Park Hospital, where the diagnoses were independently confirmed. SUBJECTS: The cases, 603 white women aged 45-69, were each matched to two controls for age and general practitioner. Of the controls, 79% were the first eligible, 15% the second eligible and 6% were obtained at the third or more attempt. MEASUREMENTS AND MAIN RESULTS: A research nurse completed a questionnaire for each case and both controls, which included information obtained from the medical notes on the prescriptions of HRT. An independent quality control check on the selection of controls and on the abstraction of information from the medical notes was made. More than one HRT prescription had been given to 109 cases (18%) and 174 controls (14%), showing a weak association between the risk of stroke and MI and the past use of HRT (relative risk [RR] 1.36, 95% confidence interval [CI] 1.01-1.81). There was a stronger association with preparations contained progestogen alone (RR 1.90, 95% CI 1.11-3.25). On average, HRT had been used 9 years before recruitment to the study and for 15 months. However, the observed gradients of risk according to the duration of HRT use and time since HRT use do not support a causal interpretation. Also, the estimated relative risks were reduced when allowance was made for other cardiovascular risk factors. CONCLUSIONS: There is no evidence that the use of HRT as recently prescribed in the UK constitutes a major cardiovascular risk or benefit.

Aged↗