Systematic review and meta-analysis: rapid diagnostic tests versus placental histology, microscopy and PCR for malaria in pregnant women

Background

To prepare field sites for malaria vaccine trials, it is important to determine baseline antibody and T cell responses to candidate malaria vaccine antigens. Assessing T cell responses is especially challenging, given genetic restriction, low responses observed in endemic areas, their variability over time, potential suppression by parasitaemia and the intrinsic variability of the assays.

Methods

In Part A of this study, antibody titres were measured in adults from urban and rural communities in Ghana to recombinant Plasmodium falciparum CSP, SSP2/TRAP, LSA1, EXP1, MSP1, MSP3 and EBA175 by ELISA, and to sporozoites and infected erythrocytes by IFA. Positive ELISA responses were determined using two methods. T cell responses to defined CD8 or CD4 T cell epitopes from CSP, SSP2/TRAP, LSA1 and EXP1 were measured by ex vivo IFN-γ ELISpot assays using HLA-matched Class I- and DR-restricted synthetic peptides. In Part B, the reproducibility of the ELISpot assay to CSP and AMA1 was measured by repeating assays of individual samples using peptide pools and low, medium or high stringency criteria for defining positive responses, and by comparing samples collected two weeks apart.

Results

In Part A, positive antibody responses varied widely from 17%-100%, according to the antigen and statistical method, with blood stage antigens showing more frequent and higher magnitude responses. ELISA titres were higher in rural subjects, while IFA titres and the frequencies and magnitudes of ex vivo ELISpot activities were similar in both communities. DR-restricted peptides showed stronger responses than Class I-restricted peptides. In Part B, the most stringent statistical criteria gave the fewest, and the least stringent the most positive responses, with reproducibility slightly higher using the least stringent method when assays were repeated. Results varied significantly between the two-week time-points for many participants.

Conclusions

All participants were positive for at least one malaria protein by ELISA, with results dependent on the criteria for positivity. Likewise, ELISpot responses varied among participants, but were relatively reproducible by the three methods tested, especially the least stringent, when assays were repeated. However, results often differed between samples taken two weeks apart, indicating significant biological variability over short intervals.     

Systematic reviews and meta-analyses on treatment of asthma: critical evaluation

ObjectiveTo evaluate the clinical, methodological, and reporting aspects of systematic reviews and meta-analyses on the treatment of asthma and to compare those published by the Cochrane Collaboration with those published in paper based journals.DesignAnalysis of studies identified from Medline, CINAHL, HealthSTAR, EMBASE, Cochrane Library, personal collections, and reference lists.StudiesArticles describing a systematic review or a meta-analysis of the treatment of asthma that were published as a full report, in any language or format, in a peer reviewed journal or the Cochrane Library.Results50 systematic reviews and meta-analyses were included. More than half were published in the past two years. Twelve reviews were published in the Cochrane Library and 38 were published in 22 peer reviewed journals. Forced expiratory volume in one second was the most frequently used outcome, but few reviews evaluated the effect of treatment on costs or patient preferences. Forty reviews were judged to have serious or extensive flaws. All six reviews associated with industry were in this group. Seven of the 10 most rigorous reviews were published in the Cochrane Library.ConclusionsMost reviews published in peer reviewed journals or funded by industry have serious methodological flaws that limit their value to guide decisions. Cochrane reviews are more rigorous and better reported than those published in peer reviewed journals.     

Systematic reviews: a primer for plastic surgery research

Clinicians rely on review articles to keep current with the rapid accumulation of medical and surgical literature. Traditional expert reviews, however, often suffer from inherent personal biases and may not reflect a true synthesis of the existing literature on a particular subject. Systematic reviews are structured, scientific articles that address the shortcomings of traditional reviews by adhering to strict, reproducible methods and recommended guidelines. The methods are designed to eliminate possible sources of bias, ensure as complete a review of the existing literature as possible, and present the results in a way that is useful for its intended audience. Systematic reviews may at times include a quantitative synthesis of the available data in the form of a meta-analysis. Meta-analysis is a statistical tool for combining the numerical results of separate studies to obtain a summary outcome with increased precision due to the larger, combined number of patients. Meta-analyses may be particularly helpful when individual study results are conflicting and the existing literature is inconclusive. The validity of meta-analysis, however, is highly dependent on the quality of data available in the literature. In its strictest form, meta-analysis is used to combine data from only randomized controlled clinical trials. Because randomized controlled clinical trials are infrequently performed in plastic surgery research, this article will focus on systematic reviews to provide the readers with a useful guide in performing this field of study.