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Biomedical subjects

M D Edwardes

Publications and source records attributed to M D Edwardes.

11 recordsLinked to original sources
PubMed2001

Meta-analysis comparing newer antipsychotic drugs for the treatment of schizophrenia: evaluating the indirect approach.

BACKGROUND: Meta-analysis is a useful method to assess the efficacy of newer antipsychotic drugs compared with older drugs or placebo. However, few trials directly compare novel drugs to each other. OBJECTIVE: The purpose of this study was to evaluate the method of indirect meta-analysis by applying it to data on olanzapine versus haloperidol and risperidone versus haloperidol to enable a comparison between olanzapine and risperidone. METHODS: Published randomized controlled trials (RCTs) of risperidone, olanzapine, and/or haloperidol were identified through literature searches (1983 to 1999) of the MEDLINE, Current Contents, and HealthSTAR databases and reviewed. Data for the Brief Psychiatric Rating Scale (BPRS) total score, the Positive and Negative Syndrome Scale (PANSS) negative subscale, the percentage of patients using anticholinergic drugs, and the percentage of patients dropping out due to lack of efficacy, side effects, or any cause were extracted and combined using the indirect method. These findings were compared with those from a direct comparative study of olanzapine and risperidone. RESULTS: The literature search yielded 8 RCTs comparing risperidone to haloperidol and 3 comparing olanzapine to haloperidol. Only 1 trial directly comparing olanzapine and risperidone was found. In this trial, the change in BPRS total and PANSS negative subscale scores tended to be higher with olanzapine by 1.80 and 1.10, respectively, but these differences were not statistically significant. Indirect meta-analysis yielded similar results. Changes in both BPRS total scores and PANSS negative subscale scores tended to be higher with olanzapine by 0.37 and 0.54, respectively, and again, the differences were not statistically significant. In the indirect meta-analysis, the rate of anticholinergic drug use was 19.5% greater among patients treated with risperidone than among patients treated with olanzapine (P < 0.05). In the direct comparative RCT, the rate was 13.1% higher among patients treated with risperidone (P < 0.05). The dropout rates were similar for patients treated with risperidone and those treated with olanzapine in both analyses. CONCLUSION: An indirect meta-analysis of studies comparing olanzapine with haloperidol and risperidone with haloperidol yielded conclusions similar to those found in a direct comparative RCT of olanzapine and risperidone.

Antipsychotic Agents↗
PubMed2001

Clinical, biological, and histologic parameters as predictors of relapse in ulcerative colitis.

BACKGROUND & AIMS: Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease. We aimed to assess whether clinical, biological, and histologic parameters in quiescent UC predict time to clinical relapse. METHODS: Seventy-four patients with clinically and endoscopically determined inactive UC were followed up for 1 year or for a shorter period if they had a relapse. Serum erythrocyte sedimentation rate; C-reactive protein, interleukin (IL)-1beta, IL-6, and IL-15 values; anti-neutrophil cytoplasmic antibody titers; and rectal biopsy specimens were obtained at baseline, at 6 and 12 months, and/or at relapse. Multivariate survival analysis was performed to determine independent predictors of clinical relapse. RESULTS: Twenty-seven patients relapsed (19/42 women; 8/32 men). Multivariate Cox regression analysis retained younger age (P = 0.003; hazard ratio, 0.4 per decade), greater number of prior relapses in women (P < 0.001; hazard ratio, 1.6 per prior relapse), and basal plasmacytosis (P = 0.003; hazard ratio, 4.5) on rectal biopsy specimens as predictors of shorter time to clinical relapse. Kaplan-Meier survival curves showed the 20-30-year-old age group and women with more than 5 prior relapses to be groups with shorter times to relapse. CONCLUSIONS: Younger age, multiple previous relapses (for women), and basal plasmacytosis on rectal biopsy specimens were independent predictors of earlier relapse. These findings may help identify patients with inactive UC who will require optimal maintenance medical therapy.

Adult↗
PubMed2001

Prognostic markers in resectable non-small cell lung cancer: a multivariate analysis.

OBJECTIVE: To identify the prognostic significance of certain clinical, cellular and immunologic markers in resectable non-small cell lung cancer (NSCLC). DESIGN: A cohort of patients with resectable NSCLC was prospectively followed up for 8 years (100% follow-up). SETTING: A university hospital in a large Canadian city. PATIENTS: One hundred and thirteen consecutive patients who underwent surgical resection of primary NSCLC. MAIN OUTCOME MEASURES: Presence of peritumoral B lymphocytes (identified with antibody to CD20) and T lymphocytes (antibody to CD43), along with tumour markers (carcinoembryonic antigen [CEA], keratin, cytokeratin, S-100 protein, vimentin, chromogranin) and other factors such as age, sex, cell type, American Joint Committee on Cancer (AJCC) stage, histologic grade, DNA ploidy and S-phase fraction were correlated with survival. RESULTS: The mean age of patients in the study was 66.0 years; 60% were male. Histologic types of the tumours were: adenocarcinoma 57 (50.4%), squamous cell 47 (41.6%), adenosquamous 6 (5.3%) and large cell 3 (2.6%). AJCC stages were: I 66 (58.4%), II 20 (17.7%) and III 27 (23.9%). Histologic grades were: I (well differentiated) 31 (27.4%), II 50 (44.2%), III 29 (25.7%) and IV 3 (2.6%). Survival was 85% at 1 year (95% confidence interval [CI] 76%-90%), 44% at 5 years (95% CI 34%-53%) and 34% at 10 years (95% CI 22%-46%). Multivariate analyses using the Cox proportional hazards model for survival confirmed AJCC stage (p < 0.001) in all histologic subtypes to be the strongest factor of independent prognostic significance. It also revealed the presence of CD20-stained B lymphocytes (p = 0.04) in the peritumoral region of all tumours to be a positive prognostic factor. This relation was especially strong for nonsquamous cell carcinomas (p < 0.001). For squamous cell carcinomas, the immunohistochemical presence of CEA was of marginally negative prognostic value (p = 0.04). DNA ploidy and a high S-phase fraction showed no evidence of prognostic value for stage I tumours, but for stages II and III tumours there was strong evidence of prognostic value (p < 0.001 jointly). The evidence for DNA ploidy was especially strong in stages II and III squamous cell tumours (p = 0.008), and for a high S-phase fraction was strongest in stages II and III nonsquamous cell tumours (p = 0.002). CONCLUSIONS: AJCC stage remains the most important prognostic indicator from a variety of clinical variables and tumour markers in postoperative patients with resectable NSCLC. For nonsquamous cell lung carcinomas, the presence of peritumoral B lymphocytes was strongly associated with improved survival, suggesting an important role for humoral mediated immunity.

Adult↗
PubMed2000

The generalization of the odds ratio, risk ratio and risk difference to r x k tables.

Familiar measures of association for 2 x 2 tables are the odds ratio, the risk ratio and the risk difference. Analagous measures of outcome-exposure association are desirable when there are several degrees of severity of both exposure and disease outcome. One such measure (alpha), which we label the general odds ratio (OR(G)), was proposed by Agresti. Convenient methods are given for calculation of both standard error and 95 per cent confidence intervals for OR(G). Other approaches to generalizing the odds ratio entail fitting statistical models which might not fit the data, and cannot handle some zero frequencies. We propose a generalization of the risk ratio (RR(G)) following the statistical approaches of Agresti, Goodman and Kruskal. A method of calculating the standard error and 95 per cent confidence interval for RR(G) is provided. A known statistic, Somers' d, fulfils the characteristics necessary for a generalized risk difference (RD(G)). These measures have straightforward interpretations, are easily computed, are at least as precise as other methods and do not require fitting statistical models to the data. We also examine the pooling of such measures as in, for example, meta-analysis.

Anti-Ulcer Agents↗
PubMed2000

GEE analysis of negatively correlated binary responses: a caution.

The method of generalized estimating equations has become almost standard for analysing longitudinal and other correlated response data. However, we have found that if binary responses have less than binomial variation over clusters, and are modelled using exchangeable correlations, prevailing software implementations may give unreliable results. Bounding the negative correlation away from its theoretical minimum may not always be a satisfactory solution. In such instances, using the independence working correlation structure and robust SEs is a more trustworthy alternative.

Binomial Distribution↗
PubMed1999

A physician-centred intervention to shorten hospital stay: a pilot study.

BACKGROUND: Studies of length of stay (LOS) in hospital usually focus on physician-independent factors. In this study, the authors identified physician-dependent factors and tested an intervention aimed at them to determine its effect on LOS. METHODS: A prospective comparison of LOS on 2 general medical wards in a tertiary care teaching hospital before and after the intervention. The pre-intervention (control) period and the intervention period were each 4 weeks. The intervention consisted of a checklist for planning management and discharge. RESULTS: Overall, the mean LOS was shorter during the intervention period than during the control period, but the difference was not statistically significant (12.0 and 14.4 days respectively, p = 0.13). The difference was significant on ward A (11.0 v. 14.7 days respectively, p = 0.02) but not on ward B (13.0 and 14.0 days respectively, p = 0.90). INTERPRETATION: An intervention at the level of the admitting physician may help to shorten LOS on a general medical ward.

Case Management↗
PubMed1998

External comparisons from nested case-control designs.

The nested case-control design, used to sample within cohorts, is usually employed for internal comparisons. We propose to use this design for external comparisons. We present two probability-weighted estimators of the expected number of cases under a given exposure, based on external rates, for two versions of the nested case-control design. These estimators are used, along with their variance estimators, to form confidence intervals for standardized mortality ratios. The estimators are practically unbiased, whereas the naive estimator that treats the nested case-control sample as a random sample of the cohort is clearly biased. An estimator from the alternative Cox model-based approach is found to be substantially biased when applied in this context. Comparing the proposed estimators for nested case-control designs to a corresponding estimator for the case-cohort design, we found that the correlation between follow-up time and exposure time (that is, the amount of time under the exposure effect) has an impact on which type of design is more efficient for external comparisons. A small correlation favors the case-cohort design and a large correlation the nested case-control design. We examine empirical properties of these estimators through computer simulations, using a cohort study of the incidence of second cancer in 2,189 patients with Hodgkin's disease.

Bias↗
PubMed1997

Adjusted odds ratios for case-control studies with missing confounder data in controls.

Nonexperimental studies using computerized databases often give rise to missing or partially available information on confounders. A frequent situation occurs when data on exposure are available for all subjects of a case-control study, but data on confounders are available only for the cases but not for the controls. In that situation, the fact of confounding can be verified by assessing the association between exposure and a confounder in the cases, but the data are insufficient to produce an adjusted estimate of the relative risk if confounding is found to be present. We propose simple conditions under which an adjusted estimate of the relative risk can be obtained when data on a confounder are available only for the cases, and we derive formulae for the estimator and its confidence limits. The method requires an external estimate of the confounder prevalence or, additionally, of the confounder-exposure odds ratio. We illustrate the technique with data from a nested case-control study of the risk of acute cardiac death associated with the use of bronchodilator drugs within a cohort of 12,301 asthmatics, with smoking as the confounder of interest.

Asthma↗
PubMed1995

A confidence interval for Pr(X < Y) - Pr(X > Y) estimated from simple cluster samples.

Distribution-free confidence intervals based on Somers' d (a simple function of the Mann-Whitney U statistic) are developed for Pr(X < Y) - Pr(X > Y), where X and Y are the ranks of any two observations from two independent populations. The approach accommodates a complex sampling design, and explicit formulas are given for simple cluster sampling. The method also accommodates simple progressive left- and right-censoring. The accuracy of the interval is shown to improve when the tanh-1 transform is used. A bootstrap solution was tried and did not perform as well as the proposed solution.

Analysis of Variance↗