Effect of trimethoprim/sulfamethoxazole prophylaxis on outcome of childhood lymphocytic leukemia. A Pediatric Oncology Group Study

The Pediatric Oncology Group (POG) undertook a prospective randomized trial using a single chemotherapy regimen with or without trimethoprim/sulfamethoxazole (TS). In a previous acute lymphocytic leukemia (ALL) study of initial therapy, investigators were free to use TS prophylaxis or not. Analysis of those data seemed to favor TS for duration of continuous complete remission. In the study reported here, of 126 randomized patients with ALL, 63 received TS. There was no effect of TS on disease-free survival after 3 years follow-up. Overall severe toxicity did not differ. However, granulocytopenia was somewhat more severe in the TS group. Hepatic toxicity, measured by enzyme elevation approached significance in the TS group versus controls. Some institutions declined randomization and treated with or without TS as a routine. Outcome and toxicities did not differ from randomized patients. There was no statistically significant effect on severe, life-threatening or fatal infection between the randomized TS versus control groups. Children not receiving TS developed varicella more often, a disease for which one would not expect TS to show a preventative effect. Pneumocystis pneumonias were not reported. The authors conclude that TS prophylaxis did not increase the continuous complete remission rate in children with ALL or decrease the incidence of infection. Toxicity is somewhat higher on TS.     

Empirical vs natural weighting in random effects meta‐analysis

This article brings into serious question the validity of empirically based weighting in random effects meta‐analysis. These methods treat sample sizes as non‐random, whereas they need to be part of the random effects analysis. It will be demonstrated that empirical weighting risks substantial bias. Two alternate methods are proposed. The first estimates the arithmetic mean of the population of study effect sizes per the classical model for random effects meta‐analysis. We show that anything other than an unweighted mean of study effect sizes will risk serious bias for this targeted parameter. The second method estimates a patient level effect size, something quite different from the first. To prevent inconsistent estimation for this population parameter, the study effect sizes must be weighted in proportion to their total sample sizes for the trial. The two approaches will be presented for a meta‐analysis of a nasal decongestant, while at the same time will produce counter‐intuitive results for the DerSimonian–Laird approach, the most popular empirically based weighted method. It is concluded that all past publications based on empirically weighted random effects meta‐analysis should be revisited to see if the qualitative conclusions hold up under the methods proposed herein. It is also recommended that empirically based weighted random effects meta‐analysis not be used in the future, unless strong cautions about the assumptions underlying these analyses are stated, and at a minimum, some form of secondary analysis based on the principles set forth in this article be provided to supplement the primary analysis. Copyright © 2009 John Wiley & Sons, Ltd.     

Disputable and unsolved aspects of mass screening

A critical review of some aspects of follow-up examinations and regular check-ups is provided. A criterion of medical and economic advisability of these examinations is suggested which would permit one to substantiate their regional variations and increase their effectiveness.