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S G Thompson

Publications and source records attributed to S G Thompson.

At least 55 records · Page 3Linked to original sources
PubMed2000

Changes in negative symptoms and the risk of tardive dyskinesia: a longitudinal study. UK700 Group.

OBJECTIVE: To examine whether the development of tardive dyskinesia (TD) is accompanied by a parallel process of worsening negative symptoms in a longitudinal study. METHOD: A sample of 708 psychotic patients were followed over a period of 2 years, using the Abnormal Involuntary Movement Scale and the Scale for the Assessment of Negative Symptoms (SANS). RESULTS: Of 361 individuals with no prior evidence of dyskinesia, 46 (13%) developed TD by year 2. Independent of the effects of male sex (odds ratio (OR)=2.18, 95% confidence interval: 1.00-4.74), age (OR per quartile group = 1.39, 95% CI: 1.01-1.90), duration of exposure to antipsychotic medication (OR = 2.35 per 8 months, 95% CI: 1.17-4.72) and average SANS score (OR per quartile group = 1.38, 95% CI: 0.99-1.93), worsening of negative symptoms over the 2 previous years was associated with TD onset (OR per quartile group = 1.46, 95% CI: 1.07-2.00). CONCLUSION: The development of TD is linked, independent of the effect of antipsychotics and older age, to an illness-related pathological process, characterized by worsening negative symptoms.

Adolescent↗
PubMed1999

Explaining heterogeneity in meta-analysis: a comparison of methods.

Exploring the possible reasons for heterogeneity between studies is an important aspect of conducting a meta-analysis. This paper compares a number of methods which can be used to investigate whether a particular covariate, with a value defined for each study in the meta-analysis, explains any heterogeneity. The main example is from a meta-analysis of randomized trials of serum cholesterol reduction, in which the log-odds ratio for coronary events is related to the average extent of cholesterol reduction achieved in each trial. Different forms of weighted normal errors regression and random effects logistic regression are compared. These analyses quantify the extent to which heterogeneity is explained, as well as the effect of cholesterol reduction on the risk of coronary events. In a second example, the relationship between treatment effect estimates and their precision is examined, in order to assess the evidence for publication bias. We conclude that methods which allow for an additive component of residual heterogeneity should be used. In weighted regression, a restricted maximum likelihood estimator is appropriate, although a number of other estimators are also available. Methods which use the original form of the data explicitly, for example the binomial model for observed proportions rather than assuming normality of the log-odds ratios, are now computationally feasible. Although such methods are preferable in principle, they often give similar results in practice.

Bayes Theorem↗
PubMed1999

Analysing repeated measurements data: a practical comparison of methods.

A variety of methods are available for analysing repeated measurements data where the outcome is continuous. However, there is little information on how established methods, such as summary statistics and repeated measures analysis of variance (RMAOV), compare in practice with methods that have become available to applied statisticians more recently, such as marginal models (based on generalized estimating equation methodology) and multilevel models (that is, hierarchical random effects models). The aim of this paper is to exemplify the use of these methods, and directly compare their results by application to a clinical trial data set. The focus is on practical aspects rather than technical issues. The data considered were taken from a clinical trial of treatments for asthma in 240 children, in which a baseline and four post-randomization measurements of outcomes were taken. The simplicity of the method of summary statistics using the post-randomization mean of observations provided a useful initial analysis. However, fixed time effects or treatment-time interactions cannot be included in such an analysis, and choice of appropriate weighting when there is substantial missing data is problematic. RMAOV, marginal models and multilevel models generally provided similar estimates and standard errors for the treatment effects, although in one example with a relatively complex variance structure the marginal model produced less efficient estimates. Two advantages of multilevel models are that they provide direct estimates of variance components which are often of interest in their own right, and that they can be naturally extended to handle multivariate outcomes.

Adolescent↗
PubMed1999

The Vein Graft Surveillance Trial: rationale, design and methods. VGST participants.

OBJECTIVES: to compare the amputation rates, quality of life and health care costs in patients receiving duplex ultrasound scanning against clinical surveillance following femoropopliteal and femorocrural vein bypass. DESIGN: multi-centre, prospective, randomised controlled trial. METHODS: 1200 patients with a patent vein graft at 30 days postoperatively will be randomised to either clinical or duplex follow-up. All patients are seen in an out-patient clinic at 6 weeks, then 3, 6, 9, 12 and 18 months postoperatively. At each appointment patients are examined clinically; palpable pulses in the graft and crural vessels, presenting symptoms and their ankle-branchial pressure indices (ABPIs) measured. In the duplex group only, the results of the scan are monitored. The incidence of radiological and/or surgical interventions throughout the follow-up period are also noted. Quality of life is measured using the SF-36 and EuroQol questionnaires at the 6 and 18 month appointments. Hospital stays and resource use are documented for health economic analysis. RESULTS: the primary endpoint of this study is amputation or death from vascular causes; however, graft patency rates will also be compared between the groups. Quality of life and health economic data will be used to determine if there is any benefit in either arm in these outcomes between follow-up strategies. CONCLUSIONS: this large, randomised-controlled trial will hopefully provide direct evidence on the benefit of duplex surveillance for vein grafts in terms of limb salvage, quality of life of the patients and cost-benefit to the purchaser.

Anastomosis, Surgical↗
PubMed1999

Incidence and aetiology of heart failure; a population-based study.

AIMS: To determine the incidence and aetiology of heart failure in the general population. METHODS AND RESULTS: New cases of heart failure were identified from a population of 151 000 served by 82 general practitioners in Hillingdon, West London through surveillance of acute hospital admissions and through a rapid access clinic to which general practitioners referred all new cases of suspected heart failure. On the basis of clinical assessment, electrocardiography, chest radiography and transthoracic echocardiography, a panel of three cardiologists decided that 220 patients met the case definition of new heart failure over a 20 month period (crude incidence rate of 1.3 cases per 1000 population per year for those aged 25 years or over). The incidence rate increased from 0.02 cases per 1000 population per year in those aged 25-34 years to 11.6 in those aged 85 years and over. The incidence was higher in males than females (age-adjusted incidence ratio 1.75 [95% confidence interval 1.34-2.29, P<0.0001]). The median age at presentation was 76 years. The primary aetiologies were coronary heart disease (36%), unknown (34%), hypertension (14%), valve disease (7%), atrial fibrillation alone (5%), and other (5%). CONCLUSIONS: Within the general population, new cases of heart failure largely occur in the elderly, and the incidence is higher in men than women. The single most common aetiology is coronary heart disease, but in a third of cases the aetiology cannot be determined on the basis of non-invasive investigation alone. To be relevant to clinical practice, future clinical trials in heart failure should not exclude the elderly.

Adult↗
PubMed1999

Tardive dyskinesia in psychosis: are women really more at risk? UK700 Group.

It is commonly held that women are more at risk of developing tardive dyskinesia (TD). However, recent evidence suggests that this may only be the case in samples of older patients, men being more at risk in the younger age groups. Abnormal movements were measured with the Abnormal Involuntary Movement Scale (AIMS) in a sample of 706 chronic psychotic patients aged not older than 65 years (median age 36 years). Female gender was associated with a lower risk of TD (OR, 0.5; 95% CI, 0.3-0.7). The effect of gender was independent of other risk factors such as older age, severity of negative symptoms and exposure to antipsychotic medication in the previous 2 years. There was no evidence that the effect of these risk factors differed between the sexes. In samples of relatively young patients with chronic psychotic illness, who typically represent the majority of patients in community programmes for the severely mentally ill, men are more at risk of TD than women.

Adult↗
PubMed1999

Prediction of deep vein thrombosis after elective hip replacement surgery by preoperative clinical and haemostatic variables: the ECAT DVT Study. European Concerted Action on Thrombosis.

The European Concerted Action on Thrombosis (ECAT) DVT Study was a collaborative study of preoperative haemostatic tests in prediction of DVT (diagnosed by routine bilateral venography) after elective hip replacement. 480 patients were recruited in 11 centres across Europe. Clinical risk factors were assessed, and stored citrated plasma aliquots were centrally assayed for 29 haemostatic factors according to the ECAT methodology. 120 (32%) of 375 evaluable patients had DVT, and 41 (11%) had proximal DVT. Among clinical variables, DVT was significantly associated with increased age, obesity, and possibly non-use of stockings. Of the 29 haemostatic factors, mean preoperative levels were significantly higher in patients with subsequent DVT (on univariate analyses) for factor VIII activity, prothrombin fragment F1+2, thrombin-antithrombin complexes, and fibrin D-dimer; and significantly lower for APTT and APC sensitivity ratio. Factor V Leiden was also associated with DVT. Most of these variables were also associated with age, while D-dimer was higher in patients with varicose veins. On multivariate analyses including clinical variables, only a shorter APTT (locally but not centrally performed) and APC resistance showed a statistically significant association with DVT. We conclude that (a) DVT is common after elective hip replacement despite prophylaxis; (b) the study provides some evidence that DVT is associated with a preoperative hypercoaguable state; and (c) preoperative haemostatic tests do not add significantly to prediction of DVT from clinical variables, with the possible exception of APC resistance.

Aged↗
PubMed1998

The analysis of complex patterns of longitudinal binary response: an example of transient dysphagia following radiotherapy.

In many clinical trials, treatment is given in phases and the prevalence of symptoms is recorded longitudinally. As a result, complex non-linear response patterns may be observed as the prevalence of symptoms changes as a consequence of treatment. In such cases, although profiles of the marginal response over time give an informative description of the data, they do not allow a formal treatment comparison or adjustment for covariates of interest. Here we analyse previously reported data on transient dysphagia in patients with non-small-cell lung cancer treated with radiotherapy. We use a generalized estimating equation approach for repeated measurement binary response to give robust standard errors taking account of the dependence of observations taken on the same subject, alongside a natural cubic spline to represent the complex shape of the marginal response. This provides a reasonable model for the marginal response and allows unbiased estimation of an apparent treatment difference. The effect of different choices for the working correlation matrix is discussed, as is the modelling of treatment group differences that vary over time. We conclude that these models provide a powerful tool for the analysis of such data that can now be applied using generally accessible software.

Carcinoma, Non-Small-Cell Lung↗
PubMed1998

Analysis and interpretation of cost data in randomised controlled trials: review of published studies.

OBJECTIVE: To review critically the statistical methods used for health economic evaluations in randomised controlled trials where an estimate of cost is available for each patient in the study. DESIGN: Survey of published randomised trials including an economic evaluation with cost values suitable for statistical analysis; 45 such trials published in 1995 were identified from Medline. MAIN OUTCOME MEASURES: The use of statistical methods for cost data was assessed in terms of the descriptive statistics reported, use of statistical inference, and whether the reported conclusions were justified. RESULTS: Although all 45 trials reviewed apparently had cost data for each patient, only 9 (20%) reported adequate measures of variability for these data and only 25 (56%) gave results of statistical tests or a measure of precision for the comparison of costs between the randomised groups. Only 16 (36%) of the articles gave conclusions which were justified on the basis of results presented in the paper. No paper reported sample size calculations for costs. CONCLUSIONS: The analysis and interpretation of cost data from published trials reveal a lack of statistical awareness. Strong and potentially misleading conclusions about the relative costs of alternative therapies have often been reported in the absence of supporting statistical evidence. Improvements in the analysis and reporting of health economic assessments are urgently required. Health economic guidelines need to be revised to incorporate more detailed statistical advice.

Cost-Benefit Analysis↗
PubMed1998

Detecting and describing heterogeneity in meta-analysis.

The investigation of heterogeneity is a crucial part of any meta-analysis. While it has been stated that the test for heterogeneity has low power, this has not been well quantified. Moreover the assumptions of normality implicit in the standard methods of meta-analysis are often not scrutinized in practice. Here we simulate how the power of the test for heterogeneity depends on the number of studies included, the total information (that is total weight or inverse variance) available and the distribution of weights among the different studies. We show that the power increases with the total information available rather than simply the number of studies, and that it is substantially lowered if, as is quite common in practice, one study comprises a large proportion of the total information. We also describe normal plots that are useful in assessing whether the data conform to a fixed effect or random effects model, together with appropriate tests, and give an application to the analysis of a multi-centre trial of blood pressure reduction. We conclude that the test of heterogeneity should not be the sole determinant of model choice in meta-analysis, and inspection of relevant normal plots, as well as clinical insight, may be more relevant to both the investigation and modelling of heterogeneity.

Adult↗
PubMed1997

Investigating underlying risk as a source of heterogeneity in meta-analysis.

In a meta-analysis of clinical trials, an important issue is whether the treatment benefit varies according to the underlying risk of the patients in the different trials. The usual naive analyses employed to investigate this question use either the observed risk of events in the control groups, or the average risk in the control and treatment groups, as a measure of underlying risk. These analyses are flawed and can produce seriously misleading results. We show how their biases depend on three components of variability, the within-trial and between-trial variances of the control group risks, and the between-trial variance of the treatment effects. We propose a Bayesian solution to the problem which can be carried out using the BUGS implementation of Gibbs sampling. The analysis is illustrated for a meta-analysis of bleeding and mortality data in trials of sclerotherapy for patients with cirrhosis, and the results contrasted with those from the naive approaches. Comparisons with other methods recently proposed for this problem are also made. We conclude that the Bayesian solution presented in this paper is not only more appropriate than other proposed methods, but is also sufficiently easy to implement that it can be used by applied researchers undertaking meta-analyses.

Bayes Theorem↗
PubMed1997

Value of natriuretic peptides in assessment of patients with possible new heart failure in primary care.

BACKGROUND: The reliability of a clinical diagnosis of heart failure in primary care is poor. Concentrations of natriuretic peptides are high in heart failure. This population-based study examined the predictive value of natriuretic peptides in patients with a new primary-care diagnosis of heart failure. METHODS: Concentrations of plasma atrial (ANP and N-terminal ANP) and B-type (BNP) natriuretic peptides were measured by radioimmunoassay in 122 consecutive patients referred to a rapid-access heart-failure clinic with a new primary-care diagnosis of heart failure. On the basis of clinical assessment, chest radiography, and transthoracic echocardiography, a panel of three cardiologists decided that 35 (29%) patients met the case definition for new heart failure. ANP and NT-ANP results were available for 117 patients (34 with heart failure) and BNP results for 106 (29 with heart failure). FINDINGS: Geometric mean concentrations of natriuretic peptides were much higher in patients with heart failure than in those with other diagnoses (29.2 vs 12.4 pmol/L for ANP; 63.9 vs 13.9 pmol/L for BNP; 1187 vs 410.6 pmol/L for NT-ANP; all p < 0.001). At cut-off values chosen to give negative predictive values for heart failure of 98% (ANP > or = 18.1 pmol/L, NT-ANP > or = 537.6 pmol/L, BNP > or = 22.2 pmol/L), the sensitivity, specificity, and positive predictive value for ANP were 97%, 72%, and 55%; for NT-ANP 97%, 66%, and 54%; and for BNP 97%, 84%, and 70%. Addition of ANP or NT-ANP concentration or both did not improve the predictive power of a logistic regression model containing BNP concentration alone. INTERPRETATION: In patients with symptoms suspected by a general practitioner to be due to heart failure, plasma BNP concentration seems to be a useful indicator of which patients are likely to have heart failure and require further clinical assessment.

Adult↗
PubMed1997

The design and analysis of paired cluster randomized trials: an application of meta-analysis techniques.

The statistical issues in clinical trials where clusters, communities or groups rather than individuals are randomized are often not fully appreciated. In this paper we discuss the design and analysis of trials in which pairs of clusters are randomized in the context of one recent trial, the British Family Heart Study. Both sample size calculations and the analysis strategy need to take account of the between-cluster component of variance. The analysis can be considered as a random effects meta-analysis across cluster pairs, and can usefully be presented as such. Techniques developed in the context of meta-analysis can then be used in the analysis, for example using a profile likelihood method to derive a confidence interval for the overall treatment effect which takes into account the variability in the estimate of the between-cluster variance. The methods presented here are contrasted with previously published methods for cluster randomized trials.

Adult↗
PubMed1997

Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group.

BACKGROUND: Inflammation is an important feature of atherosclerotic lesions, and increased production of the acute-phase reactant. C-reactive protein (CRF), is associated with a poor prognosis in severe unstable angina. We have investigated the existence and possible significance of the acute-phase responses of CRP and another sensitive reactant, serum amyloid A protein (SAA), in patients with unstable or stable angina. METHODS: We used new ultrasensitive immunoassays to measure CRP and SAA concentrations in plasma from 2121 outpatients with angina (1030 unstable, 743 stable, the rest atypical) enrolled in the European Concerted Action on Thrombosis and Disabilities (ECAT) Angina Pectoris Study. All patients underwent coronary angiography and extensive clinical and laboratory assessment at study entry, and were then followed up for 2 years. All suspected coronary events during follow-up were reviewed by an independent endpoint committee. FINDINGS: 75 individuals (41 with unstable, 29 with stable, and 5 with atypical angina) had a coronary event during follow-up. Concentrations of CRP at study entry were associated with coronary events in patients with stable or unstable angina: there was about a two-fold increase in the risk of a coronary event in patients whose CRP concentration was in the fifth quintile (> 3.6 mg/L), compared with the first four quintiles. A third of the events occurred among patients who had a CRP concentration of more than 3.6 mg/L. CRP concentrations were positively correlated with age, smoking, body-mass index, triglycerides, extent of coronary stenosis, history of myocardial infarction, and lower ejection fraction. By contrast, concentrations of SAA were not associated with risk of a coronary event. INTERPRETATION: We found that raised circulating concentrations of CRP are predictors of coronary events in patients with stable or unstable angina. The modest acute-phase responses of CRP were probably not the result of myocardial necrosis. Whatever the underlying mechanisms, the sensitive measurement of CRP as a prognostic marker may be useful in the management of coronary heart disease.

Angina Pectoris↗
PubMed1996

Multi-level models for repeated measurement data: application to quality of life data in clinical trials.

Quality of life data present considerable statistical challenges because of their longitudinal and multidimensional nature, and also because the available data are often very unbalanced through missing values. Here we exemplify the potential of multi-level models, that is, hierarchical random coefficient models, for such data. The discussion is developed in the context of analysing the quality of life data from a trial of palliative treatment in non-small-cell lung cancer. Not only do multi-level models provide a flexible modelling framework for the investigation of the underlying behaviour of response, for example, giving simple estimates of treatment effects, but they also permit a description of the differences between subjects and allow the analysis of multi-dimensional outcomes. The assumptions of Normality, homogeneity, and independence of the within- and between-subject variance components can be investigated and the models can be extended to provide explicit modelling of variance heterogeneity. It is concluded that multi-level models, for which software is now available, provide a natural and powerful approach to the analysis of longitudinal data in general, and multi-dimensional quality of life data in particular.

Carcinoma, Non-Small-Cell Lung↗