n observations are taken from a mixture of K normal subpopulations, where the value of K is known. It is assumed that these n observations are given as N frequencies from equally spaced intervals. Initial guesses of the K means, K variances, and K -1 proportions are made using the maximum likelihood estimates for a single truncated normal population as derived by Hald. Then an approximation to the likelihood function of the entire sample is used, and attempts to maximize this yield two iteration formulas. In practice, the method of steepest descent always converged, although the rate was not always fast. Special cases of equal variances and variances proportional to the square of the mean are also considered.

Epoetin treatment offers an attractive but costly alternative to red blood cell transfusion for managing anemia associated with cancer therapy. The goal of this review is to facilitate more efficient use of epoetin by 1) quantifying the effects of epoetin on the likelihood of transfusion and on quality of life in patients with cancer treatment-related anemia and 2) evaluating whether outcomes are superior when epoetin treatment is initiated at higher hemoglobin thresholds. Two independent reviewers followed a prospective protocol for identifying studies. Outcomes data were combined with the use of a random-effects meta-analysis model. Double-blind, randomized, controlled trials that minimized patient exclusions were defined as higher quality for sensitivity analysis; randomized but unblinded trials and trials with excessive exclusions were included in the meta-analysis but were defined as lower quality. Twenty-two trials (n = 1927) met inclusion criteria, and 12 (n = 1390) could be combined for estimation of odds of transfusion. Epoetin decreased the percentage of patients transfused by 9%-45% in adults with mean baseline hemoglobin concentrations of 10 g/dL or less (seven trials; n = 1080), by 7%-47% in those with hemoglobin concentrations greater than 10 g/dL but less than 12 g/dL (seven trials; n = 431), and by 7%-39% in those with hemoglobin concentrations of 12 g/dL or higher (five trials; n = 308). In sensitivity analysis, the combined odds ratio for transfusion in epoetin-treated patients as compared with controls was 0.45 (95% confidence interval [CI] = 0.33 to 0.62) in higher quality studies and 0.14 (95% CI = 0.06 to 0.31) in lower quality studies. The number of patients needed to treat to prevent one transfusion is 4.4 for all studies, 5.2 for higher quality studies, and 2.6 for lower quality studies. Only studies with mean baseline hemoglobin concentrations of 10 g/dL or less reported statistically significant effects of epoetin treatment on quality of life; quality-of-life data were insufficient for meta-analysis. No studies addressed epoetin's effects on anemia-related symptoms. We conclude that epoetin reduces the odds of transfusion for cancer patients undergoing therapy. Evidence is insufficient to determine whether initiating epoetin earlier spares more patients from transfusion or results in better quality of life than waiting until hemoglobin concentrations decline to nearly 10 g/dL.

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The synthesis of qualitative and quantitative research findings is increasingly promoted, but many of the conceptual and methodological issues it raises have yet to be fully understood and resolved. In this article, we describe how we handled issues encountered in efforts to synthesize the findings in forty-two reports of studies of antiretroviral adherence in HIV-positive women in the course of an ongoing study to develop methods to synthesize qualitative and quantitative research findings in common domains of health-related research. Working with these reports underscored the importance of looking past method claims and ideals and directly at the findings themselves, differentiating between aggregative syntheses in which findings are assimilated and interpretive syntheses in which they are configured, and understanding the judgments involved in designating relationships between findings as confirmatory, divergent, or complementary.

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Background: Discordant results have been reported on the effects of concomitant use of proton pump inhibitors (PPIs) and dual antiplatelet therapy (DAPT) for cardiovascular outcomes. We conducted a systematic review comparing the effectiveness and safety of concomitant use of PPIs and DAPT in the postdischarge treatment of unstable angina/non-ST segment elevation myocardial infarction (UA/NSTEMI) patients. Methods and Results: We searched for clinical studies in MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews, from 1995–2012. Reviewers screened and extracted data, assessed applicability and quality, and graded the strength of evidence. We performed meta-analyses of direct comparisons when outcomes and follow-up periods were comparable. Thirty-five studies were eligible. Five (4 RCTs, 1 observational) assessed the effect of omeprazole when added to DAPT; the other 30 (observational) assessed the effect of PPIs as a class compared with no PPIs. Random-effects meta-analyses of the studies assessing PPIs as a class consistently reported higher event rates in patients receiving PPIs for various clinical outcomes at 1 year (composite ischemic endpoints, all-cause mortality, nonfatal MI, stroke, revascularization, and stent thrombosis). However, the results from RCTs evaluating omeprazole compared with placebo showed no difference in ischemic outcomes, despite a reduction in upper gastrointestinal bleeding with omeprazole. Conclusions: Large, well-conducted observational studies of PPIs and RCTs of omeprazole seem to provide conflicting results for the effect of PPIs on cardiovascular outcomes when coadministered with DAPT. Prospective trials that directly compare pharmacodynamic parameters and clinical events among specific PPI agents in UA/NSTEMI patients treated with DAPT are warranted.

Knee pain has a lifetime prevalence of up to 45% and as many as 31% of individuals with knee pain will consult a general practitioner. 5 Roughly 5% of these individuals will undergo a tibial meniscectomy, 5 and many more will undergo partial meniscectomy or meniscus repair. Surgery of the meniscus is a common orthopedic procedure, constituting 10% to 20% of surgeries performed in some practices. 37 Primary practitioners must make a STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES:To identify, analyze, and synthesize the literature to determine which physical examination tests, if any, accurately diagnose a torn tibial meniscus. BACKGROUND:Knee pain has a lifetime prevalence of up to 45%, and as many as 31% of individuals with knee pain will consult a general practitioner. Roughly 5% of these individuals will undergo a tibial meniscectomy and many more will undergo partial meniscectomy or meniscus repair. Determining which of these individuals is appropriate for surgical consult depends on clinical examination findings. METHODS AND MEASURES:We searched MEDLINE, CINAHL, and SPORTDiscus from1966 to August 2006 and extracted all English-and German-language studies that reported the diagnostic accuracy of individual physical examination tests for a torn meniscus. We retrieved data regarding true positives, false positives, true negatives, and false negatives to create 2-by-2 tables for each article and test. Like tests were then subjected to meta-analysis and subanalysis. Cochran Q test and the I2 statistic were used to examine for the presence of heterogeneity and the extent of the effect of heterogeneity, respectively. A qualitative analysis was also performed using the QUADAS tool. RESULTS:Eighteen studies qualified for the final analyses. Three physical examination tests (McMurray's, Apley's, and joint line tenderness) were examined in more than 7 studies and had enough data to consider meta-analysis. However, study results were heterogeneous. Pooled sensitivity and specificity were 70% and 71% for McMurray's, 60% and 70% for Apley's, and 63% and 77% for joint line tenderness. Large between-study differences could not be explained by prevalence, study quality, or how well an index test was described. CONCLUSIONS:No single physical examination test appears to accurately diagnose a torn tibial meniscus and the value of history plus physical examination is unknown. Differences between studies in diagnostic performance remain unexplained, presumably due to local differences in the way the tests are defined, performed, and interpreted. We recommend a more standardized approach to performing and interpreting these tests and the development of a clinical prediction rule to aid clinicians in the diagnosis of a torn tibial meniscus.

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