A primary goal of meta-analysis is to improve the estimation of treatment effects by pooling results of similar studies. This article explains how the most widely used method for pooling ...heterogeneous studies--the Der Simonian-Laird (DL) estimator--can produce biased estimates with falsely high precision. A classic example is presented to show that use of the DL estimator can lead to erroneous conclusions. Particular problems with the DL estimator are discussed, and several alternative methods for summarizing heterogeneous evidence are presented. The authors support replacing universal use of the DL estimator with analyses based on a critical synthesis that recognizes the uncertainty in the evidence,focuses on describing and explaining the probable sources of variation in the evidence, and uses random-effects estimates that provide more accurate confidence limits than the DL estimator.
The concise yet authoritative presentation of key techniques for basic mixtures experiments Inspired by the author's bestselling advanced book on the topic, A Primer on Experiments with Mixtures ...provides an introductory presentation of the key principles behind experimenting with mixtures. Outlining useful techniques through an applied approach with examples from real research situations, the book supplies a comprehensive discussion of how to design and set up basic mixture experiments, then analyze the data and draw inferences from results. Drawing from his extensive experience teaching the topic at various levels, the author presents the mixture experiments in an easy-to-follow manner that is void of unnecessary formulas and theory. Succinct presentations explore key methods and techniques for carrying out basic mixture experiments, including: * Designs and models for exploring the entire simplex factor space, with coverage of simplex-lattice and simplex-centroid designs, canonical polynomials, the plotting of individual residuals, and axial designs * Multiple constraints on the component proportions in the form of lower and/or upper bounds, introducing L-Pseudocomponents, multicomponent constraints, and multiple lattice designs for major and minor component classifications * Techniques for analyzing mixture data such as model reduction and screening components, as well as additional topics such as measuring the leverage of certain design points * Models containing ratios of the components, Cox's mixture polynomials, and the fitting of a slack variable model * A review of least squares and the analysis of variance for fitting data Each chapter concludes with a summary and appendices with details on the technical aspects of the material. Throughout the book, exercise sets with selected answers allow readers to test their comprehension of the material, and References and Recommended Reading sections outline further resources for study of the presented topics. A Primer on Experiments with Mixtures is an excellent book for one-semester courses on mixture designs and can also serve as a supplement for design of experiments courses at the upper-undergraduate and graduate levels. It is also a suitable reference for practitioners and researchers who have an interest in experiments with mixtures and would like to learn more about the related mixture designs and models.
The importance of clinical risk factors for postoperative pulmonary complications and the value of preoperative testing to stratify risk are the subject of debate.
To systematically review the ...literature on preoperative pulmonary risk stratification before noncardiothoracic surgery.
MEDLINE search from 1 January 1980 through 30 June 2005 and hand search of the bibliographies of retrieved articles.
English-language studies that reported the effect of patient- and procedure-related risk factors and laboratory predictors on postoperative pulmonary complication rates after noncardiothoracic surgery and that met predefined inclusion criteria.
The authors used standardized abstraction instruments to extract data on study characteristics, hierarchy of research design, study quality, risk factors, and laboratory predictors.
The authors determined random-effects pooled estimate odds ratios and, when appropriate, trim-and-fill estimates for patient- and procedure-related risk factors from studies that used multivariable analyses. They assigned summary strength of evidence scores for each factor. Good evidence supports patient-related risk factors for postoperative pulmonary complications, including advanced age, American Society of Anesthesiologists class 2 or higher, functional dependence, chronic obstructive pulmonary disease, and congestive heart failure. Good evidence supports procedure-related risk factors for postoperative pulmonary complications, including aortic aneurysm repair, nonresective thoracic surgery, abdominal surgery, neurosurgery, emergency surgery, general anesthesia, head and neck surgery, vascular surgery, and prolonged surgery. Among laboratory predictors, good evidence exists only for serum albumin level less than 30 g/L. Insufficient evidence supports preoperative spirometry as a tool to stratify risk.
For certain risk factors and laboratory predictors, the literature provides only unadjusted estimates of risk. Prescreening, variable selection algorithms, and publication bias limited reporting of risk factors among studies using multivariable analysis.
Selected clinical and laboratory factors allow risk stratification for postoperative pulmonary complications after noncardiothoracic surgery.
Purpose We sought to determine the efficacy of genetically distinct bacillus Calmette-Guérin strains in preventing disease recurrence in patients with nonmuscle invasive bladder cancer. Materials and ...Methods We conducted a systematic review and network meta-analysis of trials evaluating bacillus Calmette-Guérin strains against all possible comparators (different bacillus Calmette-Guérin strains, chemotherapy and nonbacillus Calmette-Guérin biological therapies) with intravesical chemotherapy as the common comparator. MEDLINE® ( http://www.ncbi.nlm.nih.gov/pubmed ) served as the primary data source, with the search from inception to October 2016 for clinical trials involving patients with nonmuscle invasive bladder cancer receiving bacillus Calmette-Guérin. Primary outcome measure was bladder cancer recurrence, defined as recurrent bladder tumor of any grade or stage. Random effect network meta-analysis provided estimates for outcomes and is presented as odds ratios. Results Across all possible comparators (65 trials, 12,246 patients, 9 strains) there were 2,177 recurrences in 5,642 treated patients (38.6%) and 2,316 recurrences in 5,441 comparators (42.6%). With chemotherapy as the common comparator (28 trials, 5,757 patients, 5 strains) Tokyo 127 (OR 0.39, 95% CI 0.16–0.93), Pasteur (OR 0.49, 95% CI 0.28–0.86) and TICE® (OR 0.61, 95% CI 0.40–0.93) strains were significantly better than chemotherapy at preventing recurrence. No bacillus Calmette-Guérin strain demonstrated significant superiority when compared to any other strain at preventing recurrence in our network meta-analysis. Conclusions Bacillus Calmette-Guérin strains exhibited significant differences in efficacy compared to chemotherapy. However, no definitive conclusions could be reached regarding strain superiority, and head-to-head trials are greatly needed to further understand the importance of strain selection in determining bacillus Calmette-Guérin efficacy.
Postoperative pulmonary complications are as frequent and clinically important as cardiac complications in terms of morbidity, mortality, and length of stay. However, there has been much less ...research and no previous systematic reviews of the evidence of interventions to prevent pulmonary complications.
To systematically review the literature on interventions to prevent postoperative pulmonary complications after noncardiothoracic surgery.
MEDLINE English-language literature search, 1 January 1980 through 30 June 2005, plus bibliographies of retrieved publications.
Randomized, controlled trials (RCTs); systematic reviews; or meta-analyses that met predefined inclusion criteria.
Using standardized forms, the authors abstracted data on study methods, quality, intervention and control groups, patient characteristics, surgery, postoperative pulmonary complications, and adverse events.
The authors qualitatively synthesized, without meta-analysis, evidence from eligible studies. Good evidence (2 systematic reviews, 5 additional RCTs) indicates that lung expansion interventions (for example, incentive spirometry, deep breathing exercises, and continuous positive airway pressure) reduce pulmonary risk. Fair evidence suggests that selective, rather than routine, use of nasogastric tubes after abdominal surgery (2 meta-analyses) and short-acting rather than long-acting intraoperative neuromuscular blocking agents (1 RCT) reduce risk. The evidence is conflicting or insufficient for preoperative smoking cessation (1 RCT), epidural anesthesia (2 meta-analyses), epidural analgesia (6 RCTs, 1 meta-analysis), and laparoscopic (vs. open) operations (1 systematic review, 1 meta-analysis, 2 additional RCTs), although laparoscopic operations reduce pain and pulmonary compromise as measured by spirometry. While malnutrition is associated with increased pulmonary risk, routine total enteral or parenteral nutrition does not reduce risk (1 meta-analysis, 3 additional RCTs). Enteral formulations designed to improve immune status (immunonutrition) may prevent postoperative pneumonia (1 meta-analysis, 1 additional RCT).
The overall quality of the literature was fair: Ten of 20 RCTs and 6 of 11 systematic reviews were good quality.
Few interventions have been shown to clearly or possibly reduce postoperative pulmonary complications.
Physiological and pathological processes in spermatozoa involve the production of reactive oxygen species (ROS), but the identity of the ROS-producing enzyme system(s) remains a matter of ...speculation. We provide the first evidence that NOX5 NADPH oxidase is expressed and functions in human spermatozoa. Immunofluorescence microscopy detected NOX5 protein in both the flagella/neck region and the acrosome. Functionally, spermatozoa exposed to calcium ionophore, phorbol ester, or H(2)O(2) exhibited superoxide anion production, which was blocked by addition of superoxide dismutase, a Ca(2+) chelator, or inhibitors of either flavoprotein oxidases (diphenylene iododonium) or NOX enzymes (GKT136901). Consistent with our previous overexpression studies, we found that H(2)O(2)-induced superoxide production by primary sperm cells was mediated by the non-receptor tyrosine kinase c-Abl. Moreover, the H(V)1 proton channel, which was recently implicated in spermatozoa motility, was required for optimal superoxide production by spermatozoa. Immunoprecipitation experiments suggested an interaction among NOX5, c-Abl, and H(V)1. H(2)O(2) treatment increased the proportion of motile sperm in a NOX5-dependent manner. Statistical analyses showed a pH-dependent correlation between superoxide production and enhanced sperm motility. Collectively, our findings show that NOX5 is a major source of ROS in human spermatozoa and indicate a role for NOX5-dependent ROS generation in human spermatozoa motility.
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