Biomedical subjects

Jonathan J Deeks

Publications and source records attributed to Jonathan J Deeks.

23 records · Page 2Linked to original sources

PubMed2002

Efficacy, tolerability, and upper gastrointestinal safety of celecoxib for treatment of osteoarthritis and rheumatoid arthritis: systematic review of randomised controlled trials.

OBJECTIVE: To determine the efficacy, gastrointestinal safety, and tolerability of celecoxib (a cyclo-oxygenase 2 (COX 2) inhibitor) used in the treatment of osteoarthritis and rheumatoid arthritis. DESIGN: Systematic review of randomised trials that compared at least 12 weeks' celecoxib treatment with another non-steroidal anti-inflammatory drug (NSAID) or placebo and reported efficacy, tolerability, or safety. Trials identified from manufacturer and by searching electronic databases and evaluated according to predefined inclusion and quality criteria. Data combined through meta-analysis. PARTICIPANTS: 15 187 patients with osteoarthritis or rheumatoid arthritis. MAIN OUTCOME MEASURES EFFICACY: Western Ontario and McMaster universities osteoarthritis index; American College of Rheumatology responder index and joint scores for rheumatoid arthritis. Tolerability: withdrawal rates for adverse effects. Gastrointestinal safety: incidence of ulcers, bleeds, perforations, and obstructions. RESULTS: Nine randomised controlled trials were included. Celecoxib and NSAIDS were equally effective for all efficacy outcomes. Compared with those taking other NSAIDs, in patients taking celecoxib the rate of withdrawals due to adverse gastrointestinal events was 46% lower (95% confidence interval 29% to 58%; NNT 35 at three months), the incidence of ulcers detectable by endoscopy was 71% lower (59% to 79%; NNT 6 at three months), and the incidence of symptoms of ulcers, perforations, bleeds, and obstructions was 39% lower (4% to 61%; NNT 208 at six months). Subgroup analysis of patients taking aspirin showed that the incidence of ulcers detected by endoscopy was reduced by 51% (14% to 72%) in those given celecoxib compared with other NSAIDs. The reduction was greater (73%, 52% to 84%) in those not taking aspirin. CONCLUSION: Celecoxib is as effective as other NSAIDs for relief of symptoms of osteoarthritis and rheumatoid arthritis and has significantly improved gastrointestinal safety and tolerability.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2002

Issues in the selection of a summary statistic for meta-analysis of clinical trials with binary outcomes.

Meta-analysis of binary data involves the computation of a weighted average of summary statistics calculated for each trial. The selection of the appropriate summary statistic is a subject of debate due to conflicts in the relative importance of mathematical properties and the ability to intuitively interpret results. This paper explores the process of identifying a summary statistic most likely to be consistent across trials when there is variation in control group event rates. Four summary statistics are considered: odds ratios (OR); risk differences (RD) and risk ratios of beneficial (RR(B)); and harmful outcomes (RR(H)). Each summary statistic corresponds to a different pattern of predicted absolute benefit of treatment with variation in baseline risk, the greatest difference in patterns of prediction being between RR(B) and RR(H). Selection of a summary statistic solely based on identification of the best-fitting model by comparing tests of heterogeneity is problematic, principally due to low numbers of trials. It is proposed that choice of a summary statistic should be guided by both empirical evidence and clinically informed debate as to which model is likely to be closest to the expected pattern of treatment benefit across baseline risks. Empirical investigations comparing the four summary statistics on a sample of 551 systematic reviews provide evidence that the RR and OR models are on average more consistent than RD, there being no difference on average between RR and OR. From a second sample of 114 meta-analyses evidence indicates that for interventions aimed at preventing an undesirable event, greatest absolute benefits are observed in trials with the highest baseline event rates, corresponding to the model of constant RR(H). The appropriate selection for a particular meta-analysis may depend on understanding reasons for variation in control group event rates; in some situations uncertainty about the choice of summary statistic will remain.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2002

Meta-analysis, Simpson's paradox, and the number needed to treat.

BACKGROUND: There is debate concerning methods for calculating numbers needed to treat (NNT) from results of systematic reviews. METHODS: We investigate the susceptibility to bias for alternative methods for calculating NNTs through illustrative examples and mathematical theory. RESULTS: Two competing methods have been recommended: one method involves calculating the NNT from meta-analytical estimates, the other by treating the data as if it all arose from a single trial. The 'treat-as-one-trial' method was found to be susceptible to bias when there were imbalances between groups within one or more trials in the meta-analysis (Simpson's paradox). Calculation of NNTs from meta-analytical estimates is not prone to the same bias. The method of calculating the NNT from a meta-analysis depends on the treatment effect used. When relative measures of treatment effect are used the estimates of NNTs can be tailored to the level of baseline risk. CONCLUSIONS: The treat-as-one-trial method of calculating numbers needed to treat should not be used as it is prone to bias. Analysts should always report the method they use to compute estimates to enable readers to judge whether it is appropriate.

Bias↗

PubMed2002

Accuracy of history, wheezing, and forced expiratory time in the diagnosis of chronic obstructive pulmonary disease.

OBJECTIVE: To determine the accuracy of the history and selected elements of the physical examination in the diagnosis of chronic obstructive pulmonary disease (COPD). DESIGN: Independent blind comparison of the standard clinical examination (evaluating the accuracy of history, wheezing, and forced expiratory time [FET]) with spirometry. The gold standard for diagnosis of COPD was a forced expiratory volume at 1 second (FEV1) below the fifth percentile (adjusted for patient height and age). SETTING: Seven sites in 6 countries, including investigators from primary care and secondary care settings. PARTICIPANTS: One hundred sixty-one consecutive patients with varying severity of disease (known COPD, suspected COPD, or no COPD) participated in the study. MAIN RESULTS: One hundred sixty-one patients (mean age 65 years, 39% female, 41% with known COPD, 27% with suspected COPD, and 32% normal) were recruited. Mean (+/-SD) FEV1 and forced vital capacity were 1,720 (+/-830) mL and 2,520 (+/-970) mL. The likelihood ratios (LR) for the tested elements of the clinical examination (and their P values on chi2 testing) were: self-reported history of COPD, 5.6 (P <.001); FET greater than 9 seconds, 6.7 (P < 0.01); smoked longer than 40 pack years, 3.3 (P =.001); wheezing, 4.0 (P <.001); male gender, 1.6 (P <.001); and age over 65 years, 1.6 (P =.025). The accuracy of these elements was not appreciably different when reference standards other than FEV1 below the 5th percentile were applied. Only 3 elements of the clinical examination were significantly associated with the diagnosis of COPD on multivariate analysis: self-reported history of COPD (adjusted LR 4.4), wheezing (adjusted LR 2.9), and FET greater than 9 seconds (adjusted LR 4.6). Area under the receiver operating characteristic curve for the model incorporating these 3 factors was 0.86. CONCLUSIONS: Less emphasis should be placed on the presence of isolated symptoms or signs in the diagnosis of COPD. While numerous elements of the clinical examination are associated with the diagnosis of COPD, only 3 are significant on multivariate analysis. Patients having all 3 of these findings have an LR of 33 (ruling in COPD); those with none have an LR of 0.18 (ruling out COPD).

Female↗

PubMedDate not supplied

Effect of BCG vaccination on risk of Mycobacterium tuberculosis infection in children with household tuberculosis contact: a prospective community-based study.

BACKGROUND: Little is known about factors that affect the risk of acquiring infection in children exposed to Mycobacterium tuberculosis. The effect of BCG vaccination has been difficult to ascertain because the tuberculin skin test (TST), until recently the only method for detecting M tuberculosis infection, does not reliably distinguish between tuberculosis infection and BCG vaccination. METHODS: We investigated risk factors for tuberculosis infection in 979 child household contacts of 414 adult index patients with sputum smear-positive pulmonary tuberculosis in Istanbul, Turkey. Children were aged up to 16 years (median 7, IQR 3-11) and 770 of 979 (79%) had a BCG scar. A T-cell-based enzyme-linked immunospot assay (ELISpot), which is not confounded by BCG vaccination, and TST were used to assess infection. Independent risk factors for infection were identified through multivariate analysis. FINDINGS: Amount of tuberculosis exposure within the household and age (a marker of tuberculosis exposure outside the household) were strongly associated with likelihood of infection as measured by both TST and ELISpot. ELISpot also identified absence of BCG scar as an independent risk factor for infection in tuberculosis-exposed children; BCG-vaccinated children had an odds ratio of 0.60 (95% CI 0.43-0.83, p=0.003) for tuberculosis infection, compared with unvaccinated children. INTERPRETATION: Contrary to the prevailing theory that BCG vaccination protects only against tuberculosis disease, our results suggest that the vaccine also protects against tuberculosis infection. This finding has important implications for our understanding of the biology of tuberculosis infection and development of improved tuberculosis vaccines.

Adolescent↗