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Biomedical subjects

M D Hughes

Publications and source records attributed to M D Hughes.

62 records · Page 4Linked to original sources
PubMed1989

Significant bacteriuria has prognostic significance in primary biliary cirrhosis.

Significant bacteriuria in women has been found to be associated with increased mortality in community-based studies. We have previously reported a high prevalence of significant bacteriuria with a high recurrence rate in females with primary biliary cirrhosis (PBC), particularly those with late stage disease on liver biopsy. During a 5-year period we prospectively screened for significant bacteriuria in 187 women with primary biliary cirrhosis, (median follow-up of 47 months, range 1-83). Significant bacteriuria was found in 30 (17%) in their first urine (index bacteriuria), 90 (48%) died and 15 (8%) had liver transplants. Cox's proportional hazard models showed that age, serum bilirubin, ascites and cirrhosis were independent prognostic variables. Index bacteriuria added significantly to this model (P = 0.069) being independent from other variables, with an increased relative hazard for death of 1.65 (65% increase in risk of death) compared to non-bacteriuric patients. This effect was due mainly to non-cirrhotic patients with significant bacteriuria as shown by using multiplicative variables for histological stage and significant bacteriuria. An index of recurrent bacteriuria was significantly increased in patients with index bacteriuria (P less than 0.001) and in those who died or underwent transplantation (P less than 0.001). In this study, significant bacteriuria defined a specific sub-group of PBC patients with an increased risk of death.

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

Fetal omphalocele: prenatal US detection of concurrent anomalies and other predictors of outcome.

Forty-six consecutive fetuses with an identified omphalocele were examined with prenatal ultrasound (US) to determine the accuracy of detecting concurrent malformations and to evaluate other possible indicators of fetal outcome. In 43 fetuses with adequate follow-up, 29 (67%) had additional malformations, including 23 with major malformations and six with minor malformations. Thirty-six fetuses (78%) died at termination of pregnancy (n = 23) or spontaneously (n = 13). With the exclusion of pregnancy terminations, fetal mortality was strongly associated with the presence of concurrent malformations, (P less than .001). In 10 surviving fetuses, only three had concurrent malformations, and all were minor. Fetal mortality was also found to be statistically associated with anomalies detected at US (P = .01) and abnormal amniotic fluid volume but was not associated with fetal ascites (P = .64) or omphalocele size (P = .65). Chromosome abnormalities correlated with the absence of liver in the omphalocele sac (P less than .001) and with abnormal amniotic fluid volume (P = .02). Prenatal US can help predict the outcome in fetuses with an omphalocele.

Abnormalities, Multiple↗
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↗
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

Immune donors can protect marrow-transplant recipients from severe cytomegalovirus infections.

To study the importance of transferred immunity against cytomegalovirus (CMV) in allogeneic, HLA-matched, T-cell-depleted bone-marrow transplantation, the incidence, severity, and outcome of CMV infections were studied in 40 CMV-seropositive recipients in relation to the donors' immunity against CMV. There was no significant difference in the incidence of CMV infections between recipients of seropositive (n = 27) and seronegative (n = 13) marrow. However, the incidence of CMV pneumonitis (8/13 compared with 4/27; p less than 0.001) and the mortality attributable to CMV infection (6/13 compared with 1/27, p less than 0.01) were significantly greater in the group with seronegative donors than in those with seropositive donors. Multivariate regression analysis showed that recipients of seronegative marrow had a fifteen-fold greater risk of CMV pneumonitis and a fifty-fold increase in risk of a fatal CMV infection than recipients of seropositive marrow. Thus, after T-cell depletion CMV-seropositive marrow protects seropositive recipients against severe CMV infections; whenever possible, therefore, such recipients should be given marrow from seropositive donors. Ultimately, active immunisation of CMV-seronegative donors might help to protect seropositive recipients of T-cell-depleted marrow transplants against severe CMV infections.

Adult↗