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Biomedical subjects

S G Thompson

Publications and source records attributed to S G Thompson.

At least 91 records · Page 5Linked to original sources
PubMed1993

Age at last full-term pregnancy and risk of breast cancer.

Age at first full-term pregnancy (FTP) has long been thought to be the major reproductive risk factor in breast cancer but a Norwegian study suggested that age at last FTP might be more important. In Norway "high parity" means 4 or more deliveries. Does this finding hold in an area with a much broader distribution of parity? Data from a case-control study done in 1980-82 in Fortaleza and Recife, two cities in Brazil's impoverished north-east, have been used to explore further the influence of age at last FTP. The cases were 509 women with histologically diagnosed breast cancer who were matched with hospital controls for age and area of residence. The analysis was based on case-control pairs interviewed by the same person. High breast cancer risk was associated with low parity; after adjustment for parity, breast cancer risk was related both to late age at first FTP (odds ratio [OR] 1.21 for each 5 year increase, p = 0.008) and to late age at last FTP (OR 1.24, p = 0.0007). However, multivariate analysis revealed that the effect of age at last FTP dominated that of age at first FTP: once age at last FTP was taken into account the effect of age at first FTP was no longer significant (OR 1.08, p = 0.38) while the association with parity became more striking. These results challenge the view that age at first FTP is the principal reproductive variable related to breast cancer risk. Moreover, they suggest that high parity is protective independent of ages at first and last FTP. Given recent worldwide reductions in fertility rates, breast cancer incidence may be expected to increase. Balancing that may be the willingness of some women to complete their families by, say, age 35 if they were to be told that this might reduce their risk of breast cancer.

Adult↗
PubMed1993

Relation of fibrinogen to presence and severity of coronary artery disease is independent of other coexisting heart disease. The ECAT Angina Pectoris Study Group.

Six hundred fifty seven patients with angina pectoris underwent coronary angiography after measurement of plasma fibrinogen levels. Coronary artery disease (CAD) was angiographically confirmed in 75% of the patients. Other cardiac disease, either alone or in combination with CAD, was diagnosed in 8% and 11% of cases, respectively; 17% of the patients had no evidence of overt heart disease. Fibrinogen concentrations showed a graded increase according to the severity of coronary stenosis (p = 0.02) but were not significantly associated with any other cardiac heart disease. However, patients with valvular heart diseases had on average a 5.9% elevation of fibrinogen levels as compared to patients without proven cardiac disease (p = 0.08), similar to the observed 6.9% increase for CAD (p = 0.005). On average, patients with cardiomyopathies or pulmonary hypertension had only a 1.6% or 1.2% increase, respectively. The increase in fibrinogen levels associated with CAD was similar in patients with and without coexisting heart diseases. The results demonstrate a significant positive relation of fibrinogen to the presence and severity of CAD irrespective of a possible confounding influence from other cardiac diseases. The results therefore lend support to the hypothesis of a pathogenetic role for fibrinogen as a cardiovascular risk factor.

Coronary Angiography↗
PubMed1993

Involvement of the hemostatic system in the insulin resistance syndrome. A study of 1500 patients with angina pectoris. The ECAT Angina Pectoris Study Group.

Hyperinsulinemia, a major indicator of insulin resistance, may exert its influence on the risk of coronary artery disease partially through disturbances of the hemostatic system. The relations of fasting insulin concentrations with the degree of coronary atherosclerosis, other coronary risk factors (including some markers of the insulin resistance syndrome such as body mass index and triglyceride), markers of inflammation, and hemostatic factors were investigated in 1484 patients with angina pectoris. Mean insulin levels were higher in patients with one or more coronary vessel stenoses than in those without (9.9 microU/mL compared with 9.0 microU/mL, P < .0001). However, the association the presence of vessel stenoses was stronger in patients with a previous myocardial infarction than in those without. Insulin increased markedly (P < .0001) and independently of other risk factors with age body mass index, triglyceride concentration, and markers of inflammation, such as white blood cell count and C-reactive protein. The strongest relations between insulin and hemostatic factors were observed with fibrinolytic variables, particularly plasminogen activator inhibitor-1 (PAI-1) levels (r = .44, P < .0001). This relation decreased somewhat (r = .29) after simultaneous adjustment for markers of the insulin resistance syndrome, mainly body mass index and triglycerides, but not after adjustment for markers of inflammation. Therefore, we propose that increased PAI-1 levels, which are essentially related to the classic metabolic aspect of the insulin resistance syndrome, have to be included in this syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Controversies in meta-analysis: the case of the trials of serum cholesterol reduction.

There has recently been disagreement in the literature on the results and interpretation of meta-analyses of the trials of serum cholesterol reduction, both in terms of the quantification of the effect on ischaemic heart disease and as regards the evidence of any adverse effect on other causes of death. This paper describes statistical aspects of a recent meta-analysis of these trials, and draws some more general conclusions about the methods used in meta-analysis. Tests of an overall null hypothesis are shown to have a basis clearly distinct from the more extensive assumptions needed to provide an overall estimate of effect. The fixed effect approach to estimation relies on the implausible assumption of homogeneity of treatment effects across the trials, and is therefore likely to yield confidence intervals which are too narrow and conclusions which are too dogmatic. However the conventional random effects method relies on its own set of unrealistic assumptions, and cannot be regarded as a robust solution to the problem of statistical heterogeneity. The random effects method is more usefully regarded as a type of sensitivity analysis in which the weights allocated to each study in estimating the overall effect are modified. However, rather than using a statistical model for the 'unexplained' heterogeneity, greater insight and scientific understanding of the results of a set of trials may be obtained by a careful exploration of potential sources of heterogeneity. In the context of the cholesterol trials, the heterogeneity according to the extent and duration of cholesterol reduction are of prime concern and are investigated using logistic regression. It is concluded that the long-term benefits of serum cholesterol reduction on the risk of heart disease have been seriously underestimated in some previous meta-analyses, while the evidence for adverse effects on other causes of death have been misleadingly exaggerated.

Cholesterol↗
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↗