The impact of resection method and patient factors on quality of life among stage IA non-small cell lung cancer surgical patients.

BACKGROUND AND OBJECTIVES: Given the increased number of treatment options for stage IA lung cancer patients, there is a growing body of literature that focuses on comparing each option's relative impact on quality of life (QoL). The current study seeks to further understand the differences in these patients' QoL according to surgical approach. METHODS: Screening-diagnosed first primary pathologic stage IA non-small-cell lung cancer surgical patients from the I-ELCAP cohort who answered a baseline and 1-year follow-up QoL questionnaire (SF-12) were included in the analysis. Thoracotomy patients (N = 85) were compared with VATS patients (N = 15) using paired t-tests and analysis of variance tests. RESULTS: Multivariate analyses indicated no differences in QoL change between the two groups from pre- to post-surgery. Physical and emotional role functioning significantly improved among VATS patients and worsened among thoracotomy patients. Among thoracotomy patients, a significant decrease in post-surgical physical QoL was observed only in those who underwent lobectomy (-3.3; 95% CI: -5.1,-1.5), not limited resection. CONCLUSIONS: Although the sample size is small, preliminary findings underscore that changes in overall QoL are similar in VATS and thoracotomy stage IA lung cancer patients. Extension of the resection may be a more relevant factor on QoL post-surgery. J. Surg. Oncol. 2017;115:173-180. © 2016 Wiley Periodicals, Inc.

Are organic foods safer or healthier than conventional alternatives?: a systematic review.

BACKGROUND: The health benefits of organic foods are unclear. PURPOSE: To review evidence comparing the health effects of organic and conventional foods. DATA SOURCES: MEDLINE (January 1966 to May 2011), EMBASE, CAB Direct, Agricola, TOXNET, Cochrane Library (January 1966 to May 2009), and bibliographies of retrieved articles. STUDY SELECTION: English-language reports of comparisons of organically and conventionally grown food or of populations consuming these foods. DATA EXTRACTION: 2 independent investigators extracted data on methods, health outcomes, and nutrient and contaminant levels. DATA SYNTHESIS: 17 studies in humans and 223 studies of nutrient and contaminant levels in foods met inclusion criteria. Only 3 of the human studies examined clinical outcomes, finding no significant differences between populations by food type for allergic outcomes (eczema, wheeze, atopic sensitization) or symptomatic Campylobacter infection. Two studies reported significantly lower urinary pesticide levels among children consuming organic versus conventional diets, but studies of biomarker and nutrient levels in serum, urine, breast milk, and semen in adults did not identify clinically meaningful differences. All estimates of differences in nutrient and contaminant levels in foods were highly heterogeneous except for the estimate for phosphorus; phosphorus levels were significantly higher than in conventional produce, although this difference is not clinically significant. The risk for contamination with detectable pesticide residues was lower among organic than conventional produce (risk difference, 30% [CI, -37% to -23%]), but differences in risk for exceeding maximum allowed limits were small. Escherichia coli contamination risk did not differ between organic and conventional produce. Bacterial contamination of retail chicken and pork was common but unrelated to farming method. However, the risk for isolating bacteria resistant to 3 or more antibiotics was higher in conventional than in organic chicken and pork (risk difference, 33% [CI, 21% to 45%]). LIMITATION: Studies were heterogeneous and limited in number, and publication bias may be present. CONCLUSION: The published literature lacks strong evidence that organic foods are significantly more nutritious than conventional foods. Consumption of organic foods may reduce exposure to pesticide residues and antibiotic-resistant bacteria. PRIMARY FUNDING SOURCE: None.

Lack of significant interactions between clopidogrel and proton pump inhibitor therapy: meta-analysis of existing literature.

BACKGROUND: Published data regarding the effect of concomitant clopidogrel and proton pump inhibitor (PPI) therapy on cardiovascular outcomes have been conflicting. AIM: To perform an updated meta-analysis in order to determine changes in risk differences (RD) between primary and secondary outcome analyses. METHODS: Primary analysis was based on definite vascular outcomes, including all cause mortality, cardiac death, myocardial infarction, and/or stroke. Secondary analysis also incorporated probable cardiac events, which included re-hospitalization for cardiac symptoms or revascularization procedures. RD were combined using a random-effects model. RESULTS: We reviewed 1,204 publications of which 26 studies (16 published articles, 10 abstracts) met inclusion criteria. The meta-analysis of outcomes from the two randomized controlled trials did not show an increased risk (RD 0.0, 95% CI -0.01, 0.01) for adverse outcomes. The meta-analysis of primary outcomes showed a RD of 0.02 (95% CI 0.01, 0.03) for all studies. The meta-analysis for secondary outcomes yielded a RD of 0.02 (95% CI 0.01-0.04) based on 19 published papers and abstracts. When primary and secondary outcomes were combined, the meta-analysis for published papers yielded an overall RD of 0.05 (95% CI 0.03-0.06). CONCLUSIONS: In patients using concomitant clopidogrel and PPI therapy, the risk of adverse cardiac outcomes was 0% based on data from well-controlled randomized trials. Data from retrospective studies and the addition of probable vascular events significantly increased the RD estimates, likely due to lack of adjustment for potential confounders.

Meta-analysis of effect sizes reported at multiple time points: a multivariate approach.

BACKGROUND: Many comparative studies report results at multiple time points. Such data are correlated because they pertain to the same patients, but are typically meta-analyzed as separate quantitative syntheses at each time point, ignoring the correlations between time points. PURPOSE: To develop a meta-analytic approach that estimates treatment effects at successive time points and takes account of the stochastic dependencies of those effects. METHODS: We present both fixed and random effects methods for multivariate meta-analysis of effect sizes reported at multiple time points. We provide formulas for calculating the covariance (and correlations) of the effect sizes at successive time points for four common metrics (log odds ratio, log risk ratio, risk difference, and arcsine difference) based on data reported in the primary studies. We work through an example of a meta-analysis of 17 randomized trials of radiotherapy and chemotherapy versus radiotherapy alone for the postoperative treatment of patients with malignant gliomas, where in each trial survival is assessed at 6, 12, 18, and 24 months post randomization. We also provide software code for the main analyses described in the article. RESULTS: We discuss the estimation of fixed and random effects models and explore five options for the structure of the covariance matrix of the random effects. In the example, we compare separate (univariate) meta-analyses at each of the four time points with joint analyses across all four time points using the proposed methods. Although results of univariate and multivariate analyses are generally similar in the example, there are small differences in the magnitude of the effect sizes and the corresponding standard errors. We also discuss conditional multivariate analyses where one compares treatment effects at later time points given observed data at earlier time points. LIMITATIONS: Simulation and empirical studies are needed to clarify the gains of multivariate analyses compared with separate meta-analyses under a variety of conditions. CONCLUSIONS: Data reported at multiple time points are multivariate in nature and are efficiently analyzed using multivariate methods. The latter are an attractive alternative or complement to performing separate meta-analyses.

Systematic review: benefits and harms of in-hospital use of recombinant factor VIIa for off-label indications.

BACKGROUND: Recombinant factor VIIa (rFVIIa), a hemostatic agent approved for hemophilia, is increasingly used for off-label indications. PURPOSE: To evaluate the benefits and harms of rFVIIa use for 5 off-label, in-hospital indications: intracranial hemorrhage, cardiac surgery, trauma, liver transplantation, and prostatectomy. DATA SOURCES: Ten databases (including PubMed, EMBASE, and the Cochrane Library) queried from inception through December 2010. Articles published in English were analyzed. STUDY SELECTION: Two reviewers independently screened titles and abstracts to identify clinical use of rFVIIa for the selected indications and identified all randomized, controlled trials (RCTs) and observational studies for full-text review. DATA EXTRACTION: Two reviewers independently assessed study characteristics and rated study quality and indication-wide strength of evidence. DATA SYNTHESIS: 16 RCTs, 26 comparative observational studies, and 22 noncomparative observational studies met inclusion criteria. Identified comparators were limited to placebo (RCTs) or usual care (observational studies). For intracranial hemorrhage, mortality was not improved with rFVIIa use across a range of doses. Arterial thromboembolism was increased with medium-dose rFVIIa use (risk difference [RD], 0.03 [95% CI, 0.01 to 0.06]) and high-dose rFVIIa use (RD, 0.06 [CI, 0.01 to 0.11]). For adult cardiac surgery, there was no mortality difference, but there was an increased risk for thromboembolism (RD, 0.05 [CI, 0.01 to 0.10]) with rFVIIa. For body trauma, there were no differences in mortality or thromboembolism, but there was a reduced risk for the acute respiratory distress syndrome (RD, -0.05 [CI, -0.02 to -0.08]). Mortality was higher in observational studies than in RCTs. LIMITATIONS: The amount and strength of evidence were low for most outcomes and indications. Publication bias could not be excluded. CONCLUSION: Limited available evidence for 5 off-label indications suggests no mortality reduction with rFVIIa use. For some indications, it increases thromboembolism.

Systematic review: the effects of growth hormone on athletic performance.

BACKGROUND: Human growth hormone is reportedly used to enhance athletic performance, although its safety and efficacy for this purpose are poorly understood. PURPOSE: To evaluate evidence about the effects of growth hormone on athletic performance in physically fit, young individuals. DATA SOURCES: MEDLINE, EMBASE, SPORTDiscus, and Cochrane Collaboration databases were searched for English-language studies published between January 1966 and October 2007. STUDY SELECTION: Randomized, controlled trials that compared growth hormone treatment with no growth hormone treatment in community-dwelling healthy participants between 13 and 45 years of age. DATA EXTRACTION: 2 authors independently reviewed articles and abstracted data. DATA SYNTHESIS: 44 articles describing 27 study samples met inclusion criteria; 303 participants received growth hormone, representing 13.3 person-years of treatment. Participants were young (mean age, 27 years [SD, 3]), lean (mean body mass index, 24 kg/m2 [SD, 2]), and physically fit (mean maximum oxygen uptake, 51 mL/kg of body weight per minute [SD, 8]). Growth hormone dosage (mean, 36 microg/kg per day [SD, 21]) and treatment duration (mean, 20 days [SD, 18] for studies giving growth hormone for >1 day) varied. Lean body mass increased in growth hormone recipients compared with participants who did not receive growth hormone (increase, 2.1 kg [95% CI, 1.3 to 2.9 kg]), but strength and exercise capacity did not seem to improve. Lactate levels during exercise were statistically significantly higher in 2 of 3 studies that evaluated this outcome. Growth hormone-treated participants more frequently experienced soft tissue edema and fatigue than did those not treated with growth hormone. LIMITATIONS: Few studies evaluated athletic performance. Growth hormone protocols in the studies may not reflect real-world doses and regimens. CONCLUSION: Claims that growth hormone enhances physical performance are not supported by the scientific literature. Although the limited available evidence suggests that growth hormone increases lean body mass, it may not improve strength; in addition, it may worsen exercise capacity and increase adverse events. More research is needed to conclusively determine the effects of growth hormone on athletic performance.

Different evidence summaries have implications for contextualizing findings of meta-analysis of diagnostic tests.

OBJECTIVE: To evaluate diagnostic tests, analysts use meta-analyses to provide inputs to parameters in decision models. Choosing parameter estimands from meta-analyses requires understanding the meta-analytic and decision-making contexts. STUDY DESIGN AND SETTING: We expand on an analysis comparing positron emission tomography (PET), PET with computed tomography (PET/CT), and conventional workup (CW) in women with suspected recurrent breast cancer. We discuss Bayesian meta-analytic summaries (posterior mean over a set of existing studies, posterior estimate in an existing study, posterior predictive mean in a new study) used to estimate diagnostic test parameters (prevalence, sensitivity, specificity) needed to calculate quality-adjusted life years in a decision model contextualizing PET, PET/CT, and CW. RESULTS: The mean and predictive mean give similar estimates, but the latter displays greater uncertainty. Namely, PET/CT outperforms CW on average but may not do better than CW when implemented in future settings. CONCLUSION: Selecting estimands for decision model parameters from meta-analyses requires understanding the relationship between decision settings and meta-analysis studies' settings, specifically whether the former resemble one or all study settings or represents new settings. We provide an algorithm recommending appropriate estimands as input parameters in decision models for diagnostic tests to obtain output parameters consistent with the decision context.

Systematic review: the safety and efficacy of growth hormone in the healthy elderly.

BACKGROUND: Human growth hormone (GH) is widely used as an antiaging therapy, although its use for this purpose has not been approved by the U.S. Food and Drug Administration and its distribution as an antiaging agent is illegal in the United States. PURPOSE: To evaluate the safety and efficacy of GH therapy in the healthy elderly. DATA SOURCES: The authors searched MEDLINE and EMBASE databases for English-language studies published through 21 November 2005 by using such terms as growth hormone and aging. STUDY SELECTION: The authors included randomized, controlled trials that compared GH therapy with no GH therapy or GH and lifestyle interventions (exercise with or without diet) with lifestyle interventions alone. Included trials provided GH for 2 weeks or more to community-dwelling participants with a mean age of 50 years or more and a body mass index of 35 kg/m2 or less. The authors excluded studies that evaluated GH as treatment for a specific illness. DATA EXTRACTION: Two authors independently reviewed articles and abstracted data. DATA SYNTHESIS: 31 articles describing 18 unique study populations met the inclusion criteria. A total of 220 participants who received GH (107 person-years) completed their respective studies. Study participants were elderly (mean age, 69 years [SD, 6]) and overweight (mean body mass index, 28 kg/m2 [SD, 2]). Initial daily GH dose (mean, 14 microg per kg of body weight [SD, 7]) and treatment duration (mean, 27 weeks [SD, 16]) varied. In participants treated with GH compared with those not treated with GH, overall fat mass decreased (change in fat mass, -2.1 kg [95% CI, -2.8 to -1.35] and overall lean body mass increased (change in lean body mass, 2.1 kg [CI, 1.3 to 2.9]) (P < 0.001), and their weight did not change significantly (change in weight, 0.1 kg [CI, -0.7 to 0.8]; P = 0.87). Total cholesterol levels decreased (change in cholesterol, -0.29 mmol/L [-11.21 mg/dL]; P = 0.006), although not significantly after adjustment for body composition changes. Other outcomes, including bone density and other serum lipid levels, did not change. Persons treated with GH were significantly more likely to experience soft tissue edema, arthralgias, carpal tunnel syndrome, and gynecomastia and were somewhat more likely to experience the onset of diabetes mellitus and impaired fasting glucose. LIMITATIONS: Some important outcomes were infrequently or heterogeneously measured and could not be synthesized. Most included studies had small sample sizes. CONCLUSIONS: The literature published on randomized, controlled trials evaluating GH therapy in the healthy elderly is limited but suggests that it is associated with small changes in body composition and increased rates of adverse events. On the basis of this evidence, GH cannot be recommended as an antiaging therapy.

Meta-analysis: accuracy of quantitative ultrasound for identifying patients with osteoporosis.

BACKGROUND: There is increased interest in quantitative ultrasound for osteoporosis screening because it predicts fracture risk, is portable, and is relatively inexpensive. However, there is no consensus regarding its accuracy for identifying patients with osteoporosis. PURPOSE: To determine the sensitivity and specificity of calcaneal quantitative ultrasound for identifying patients who meet the World Health Organization's diagnostic criteria for osteoporosis. Dual-energy x-ray absorptiometry (DXA) was used as the reference standard. DATA SOURCES: MEDLINE (1966 to October 2005), EMBASE (1993 to May 2004), Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (1952 to March 2004), and the Science Citation Index (1945 to April 2004). STUDY SELECTION: English-language articles that evaluated the sensitivity and specificity of calcaneal quantitative ultrasound for identifying adults with DXA T-scores of -2.5 or less at the hip or spine. DATA EXTRACTION: Two authors independently reviewed articles and abstracted data. DATA SYNTHESIS: The authors identified 1908 potentially relevant articles, of which 25 met the inclusion criteria, and calculated the sensitivity and specificity of quantitative ultrasound over a range of thresholds. For the quantitative ultrasound index parameter T-score cutoff threshold of -1, sensitivity was 79% (95% CI, 69% to 86%) and specificity was 58% (CI, 44% to 70%) for identifying individuals with DXA T-scores of -2.5 or less at the hip or spine. For a T-score threshold of 0, sensitivity improved to 93% (CI, 87% to 97%) but specificity decreased to 24% (CI, 10% to 47%). At a pretest probability of 22% (for example, a 65-year-old white woman at average risk), the post-test probability of DXA-determined osteoporosis was 34% (CI, 26% to 41%) after a positive result and 10% (CI, 5% to 12%) after a negative result when using a T-score cutoff threshold of -1. Analysis of other quantitative ultrasound parameters (for example, broadband ultrasound attenuation) revealed similar estimates of accuracy. LIMITATIONS: The relatively small number of included studies limited the authors' ability to evaluate the effects of heterogeneous study characteristics on the diagnostic accuracy of quantitative ultrasound. CONCLUSIONS: The currently available literature suggests that results of calcaneal quantitative ultrasound at commonly used cutoff thresholds do not definitively exclude or confirm DXA-determined osteoporosis. Additional research is needed before use of this test can be recommended in evidence-based screening programs for osteoporosis.

Using pedometers to increase physical activity and improve health: a systematic review.

CONTEXT: Without detailed evidence of their effectiveness, pedometers have recently become popular as a tool for motivating physical activity. OBJECTIVE: To evaluate the association of pedometer use with physical activity and health outcomes among outpatient adults. DATA SOURCES: English-language articles from MEDLINE, EMBASE, Sport Discus, PsychINFO, Cochrane Library, Thompson Scientific (formerly known as Thompson ISI), and ERIC (1966-2007); bibliographies of retrieved articles; and conference proceedings. STUDY SELECTION: Studies were eligible for inclusion if they reported an assessment of pedometer use among adult outpatients, reported a change in steps per day, and included more than 5 participants. DATA EXTRACTION AND DATA SYNTHESIS: Two investigators independently abstracted data about the intervention; participants; number of steps per day; and presence or absence of obesity, diabetes, hypertension, or hyperlipidemia. Data were pooled using random-effects calculations, and meta-regression was performed. RESULTS: Our searches identified 2246 citations; 26 studies with a total of 2767 participants met inclusion criteria (8 randomized controlled trials [RCTs] and 18 observational studies). The participants' mean (SD) age was 49 (9) years and 85% were women. The mean intervention duration was 18 weeks. In the RCTs, pedometer users significantly increased their physical activity by 2491 steps per day more than control participants (95% confidence interval [CI], 1098-3885 steps per day, P < .001). Among the observational studies, pedometer users significantly increased their physical activity by 2183 steps per day over baseline (95% CI, 1571-2796 steps per day, P < .0001). Overall, pedometer users increased their physical activity by 26.9% over baseline. An important predictor of increased physical activity was having a step goal such as 10,000 steps per day (P = .001). When data from all studies were combined, pedometer users significantly decreased their body mass index by 0.38 (95% CI, 0.05-0.72; P = .03). This decrease was associated with older age (P = .001) and having a step goal (P = .04). Intervention participants significantly decreased their systolic blood pressure by 3.8 mm Hg (95% CI, 1.7-5.9 mm Hg, P < .001). This decrease was associated with greater baseline systolic blood pressure (P = .009) and change in steps per day (P = .08). CONCLUSIONS: The results suggest that the use of a pedometer is associated with significant increases in physical activity and significant decreases in body mass index and blood pressure. Whether these changes are durable over the long term is undetermined.

Overlap between treatment and control distributions as an effect size measure in experiments.

The proportion π of treatment group observations that exceed the control group mean has been proposed as an effect size measure for experiments that randomly assign independent units into 2 groups. We give the exact distribution of a simple estimator of π based on the standardized mean difference and use it to study the small sample bias of this estimator. We also give the minimum variance unbiased estimator of π under 2 models, one in which the variance of the mean difference is known and one in which the variance is unknown. We show how to use the relation between the standardized mean difference and the overlap measure to compute confidence intervals for π and show that these results can be used to obtain unbiased estimators, large sample variances, and confidence intervals for 3 related effect size measures based on the overlap. Finally, we show how the effect size π can be used in a meta-analysis.

Impact of surgery for stage IA non-small-cell lung cancer on patient quality of life.

BACKGROUND: There is a paucity of literature comparing quality of life (QoL) before and after surgery in stage IA lung cancer, where surgical resection is the recommended curative treatment. OBJECTIVE: To assess the impact of surgery on physical and mental health-related QoL in patients with stage IA lung cancer treated with surgical resection. METHODS: Participants in the I-ELCAP cohort who were diagnosed with their first primary pathologic stage IA non-small-cell lung cancer, underwent surgery, and provided follow-up information on QoL 1 year later were included in the present analysis (N = 107). QoL information was collected using the SF-12 (12-item Short Form Health Survey), which generates 2 component scores related to mental health and physical health. RESULTS: Statistical analyses indicated that physical health QoL was significantly worsened from before surgery to after surgery, whereas mental health QoL marginally improved from before to after surgery. Physical health QoL worsened for women from baseline to follow-up, but not for men. Only lobectomy (not limited resection) had an impact on QoL from before to after surgery. LIMITATIONS: Results are considered preliminary given the small sample size and multiple comparisons. CONCLUSIONS: The current study findings have implications for lung cancer health care professionals in regard to how they can most effectively present the possible impact of surgery on quality of life to this subset of patients in which disease has not yet significantly progressed.

Outcomes of lung cancers manifesting as nonsolid nodules.

This is a comprehensive review and re-analysis of available literature to assess the outcome of lung cancer presenting as nonsolid nodules (NSNs), a more indolent form of cancer. PubMed and EMBASE were searched for articles reporting on CT-detected lung cancers manifesting as NSNs published in English on or before July 17, 2015. Only studies including clinicopathologic data, lung cancer-specific survival, or overall survival were included. Data extraction was performed by three independent reviewers using prespecified criteria. Twenty-four articles from 5 countries met criteria and they included 704 subjects with 712 lung cancers manifesting as NSNs. Each article reported from 2 to 100 lung cancer cases with a median follow up of 18-51 months. All NSNs were Stage I adenocarcinoma without pathologic nodal involvement upon resection, except for one case in which the NSN progressed to become part-solid nodule after 6 years of follow-up. The five-year lung cancer-specific survival rate was 100%. These findings suggest an indolent course for lung cancers manifesting as NSNs.

Survival after Sublobar Resection for Early-Stage Lung Cancer: Methodological Obstacles in Comparing the Efficacy to Lobectomy.

INTRODUCTION: Surgery is the treatment of choice for early-stage lung cancer (LC). Although lobectomy (L) is the historic standard treatment, the issue of whether long-term outcomes of sublobar resection (SL) are comparable is still under debate. The objective of this study was to perform a review of the literature on 5-year survival rates after SL compared to L for patients with early-stage LC. METHODS: A priori inclusion criteria were as follows: (1) observational studies, (2) L compared to SL for early-stage LC, (3) radiographic staging by computed tomography scan, and (4) 5-year survival reported. A Medline search through January 2015 resulted in 31 studies representing 23 distinct datasets. The absolute difference in 5-year survival was calculated and plotted for each study. RESULTS: L was performed in 4564 patients and SL in 2287 patients. Of 19 studies reporting the reason for SL, 11 indicated that SL was performed because of comorbidities or impaired cardiopulmonary function. Four studies showed no difference in 5-year survival, 13 favored L, and six favored SL. One propensity score study favored L and the other favored SL. Of 20 studies reporting recurrence rate, 11 favored L and nine favored SL. CONCLUSIONS: Studies comparing 5-year survival rates of SL to L are sufficiently heterogeneous to prevent carrying out traditional meta-analysis. SL survival is often similar to L when adjustments are made for age, comorbidities, or impaired cardiopulmonary function. New approaches are needed for the comparison of L to SL.

A Survey of Tables of Probability Distributions.

This article is a survey of the tables of probability distributions published about or after the publication in 1964 of the Handbook of Mathematical Functions, edited by Abramowitz and Stegun.

Cilostazol, clopidogrel or ticlopidine to prevent sub-acute stent thrombosis: a meta-analysis of randomized trials.

BACKGROUND: Sub-acute thrombosis is a serious complication of coronary artery stenting. Clopidogrel plus aspirin is the accepted prophylactic regimen, but has yet to be proven superior to ticlopidine plus aspirin, and a new regimen combining cilostazol and aspirin has been introduced. METHODS: We conducted a meta-analysis of all trials that compared >or=2 oral anti-thrombotic strategies in patients undergoing coronary stent placement to determine which treatment optimally prevents adverse cardiac events in the 30 days following stent insertion. We used meta-regression to compare all strategies to a shared control strategy: ticlopidine plus aspirin. We also compared randomized trials to historically controlled and other non-randomized trials. We conducted sensitivity analysis and subgroup analysis to assess for possible heterogeneity. RESULTS: In comparison to ticlopidine plus aspirin the odds-ratios for cardiac events, with 95% confidence intervals were: aspirin alone, 4.29 (3.09-5.97), coumadin plus aspirin, 2.65 (2.18-3.21), clopidogrel plus aspirin, 1.06 (0.86-1.31), cilostazol plus aspirin, 0.73 (0.47-1.14). Among trials that compared clopidogrel plus aspirin to ticlopidine plus aspirin, historically controlled trials were statistically distinct from randomized trials. The analysis of cilostazol was sensitive to the small size of the included studies. CONCLUSIONS: Neither clopidogrel plus aspirin nor cilostazol plus aspirin can be statistically distinguished from ticlopidine plus aspirin for the prevention of adverse cardiac events in the 30 days after stenting. A randomized trial including cilostazol is warranted.

Bayesian network meta-analysis for unordered categorical outcomes with incomplete data.

We develop a Bayesian multinomial network meta-analysis model for unordered (nominal) categorical outcomes that allows for partially observed data in which exact event counts may not be known for each category. This model properly accounts for correlations of counts in mutually exclusive categories and enables proper comparison and ranking of treatment effects across multiple treatments and multiple outcome categories. We apply the model to analyze 17 trials, each of which compares two of three treatments (high and low dose statins and standard care/control) for three outcomes for which data are complete: cardiovascular death, non-cardiovascular death and no death. We also analyze the cardiovascular death category divided into the three subcategories (coronary heart disease, stroke and other cardiovascular diseases) that are not completely observed. The multinomial and network representations show that high dose statins are effective in reducing the risk of cardiovascular disease.

Risk of cardiovascular disease from antiretroviral therapy for HIV: a systematic review.

BACKGROUND: Recent studies suggest certain antiretroviral therapy (ART) drugs are associated with increases in cardiovascular disease. PURPOSE: We performed a systematic review and meta-analysis to summarize the available evidence, with the goal of elucidating whether specific ART drugs are associated with an increased risk of myocardial infarction (MI). DATA SOURCES: We searched Medline, Web of Science, the Cochrane Library, and abstract archives from the Conference on Retroviruses and Opportunistic Infections and International AIDS Society up to June 2011 to identify published articles and abstracts. STUDY SELECTION: Eligible studies were comparative and included MI, strokes, or other cardiovascular events as outcomes. DATA EXTRACTION: Eligibility screening, data extraction, and quality assessment were performed independently by two investigators. DATA SYNTHESIS: Random effects methods and Fisher's combined probability test were used to summarize evidence. FINDINGS: Twenty-seven studies met inclusion criteria, with 8 contributing to a formal meta-analysis. Findings based on two observational studies indicated an increase in risk of MI for patients recently exposed (usually defined as within last 6 months) to abacavir (RR 1.92, 95% CI 1.51-2.42) and protease inhibitors (PI) (RR 2.13, 95% CI 1.06-4.28). Our analysis also suggested an increased risk associated with each additional year of exposure to indinavir (RR 1.11, 95% CI 1.05-1.17) and lopinavir (RR 1.22, 95% CI 1.01-1.47). Our findings of increased cardiovascular risk from abacavir and PIs were in contrast to four published meta-analyses based on secondary analyses of randomized controlled trials, which found no increased risk from cardiovascular disease. CONCLUSION: Although observational studies implicated specific drugs, the evidence is mixed. Further, meta-analyses of randomized trials did not find increased risk from abacavir and PIs. Our findings that implicate specific ARTs in the observational setting provide sufficient evidence to warrant further investigation of this relationship in studies designed for that purpose.