Bone Marrow Stem Cell Treatment for Ischemic Heart Disease in Patients with No Option of Revascularization: A Systematic Review and Meta-Analysis

PMCID: PMC3686792This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Dealing with substantial heterogeneity in Cochrane reviews. Cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Dealing with heterogeneity in meta-analyses is often tricky, and there is only limited advice for authors on what to do. We investigated how authors addressed different degrees of heterogeneity, in particular whether they used a fixed effect model, which assumes that all the included studies are estimating the same true effect, or a random effects model where this is not assumed.</p> <p>Methods</p> <p>We sampled randomly 60 Cochrane reviews from 2008, which presented a result in its first meta-analysis with substantial heterogeneity (I²greater than 50%, i.e. more than 50% of the variation is due to heterogeneity rather than chance). We extracted information on choice of statistical model, how the authors had handled the heterogeneity, and assessed the methodological quality of the reviews in relation to this.</p> <p>Results</p> <p>The distribution of heterogeneity was rather uniform in the whole I²interval, 50-100%. A fixed effect model was used in 33 reviews (55%), but there was no correlation between I²and choice of model (P = 0.79). We considered that 20 reviews (33%), 16 of which had used a fixed effect model, had major problems. The most common problems were: use of a fixed effect model and lack of rationale for choice of that model, lack of comment on even severe heterogeneity and of reservations and explanations of its likely causes. The problematic reviews had significantly fewer included trials than other reviews (4.3 vs. 8.0, P = 0.024). The problems became less pronounced with time, as those reviews that were most recently updated more often used a random effects model.</p> <p>Conclusion</p> <p>One-third of Cochrane reviews with substantial heterogeneity had major problems in relation to their handling of heterogeneity. More attention is needed to this issue, as the problems we identified can be essential for the conclusions of the reviews.</p

Consciousness and the Physical World

The main file in this deposition is a pdf file containing the scanned pages of the Proceedings. Additional files OCR.txt and OCR.pdf (the latter having the same pagination as the book) are included to simplify search, etc. Because of their automated creation using software, the accuracy of the OCR files cannot be guaranteed, though some checking has been carried out. In the scanned version, entering 'go to page n' in a pdf reader will access the pair of pages 2n and 2n+1. Alternatively, go to the contents pages (accessible via 'go to page', entering 'contents' at the prompt) for the numbers to use with 'go to' for specific chapters. © By arrangement with the publishers, the editors (Brian D Josephson and Vilayanur S Ramachandran) are the present copyright holders. They grant permission for the use of the material in this book in accord with the terms of the CC licence below.Edited proceedings of an interdisciplinary symposium on consciousness held at the University of Cambridge in January 1978. The purpose of the Cambridge conference was to encourage distinguished scientists to express their views on the relationship of conscious experience to the physical world.The conference was supported by a grant from Research Corporation of New York

A Microsoft-Excel-based tool for running and critically appraising network meta-analyses--an overview and application of NetMetaXL.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.BACKGROUND: The use of network meta-analysis has increased dramatically in recent years. WinBUGS, a freely available Bayesian software package, has been the most widely used software package to conduct network meta-analyses. However, the learning curve for WinBUGS can be daunting, especially for new users. Furthermore, critical appraisal of network meta-analyses conducted in WinBUGS can be challenging given its limited data manipulation capabilities and the fact that generation of graphical output from network meta-analyses often relies on different software packages than the analyses themselves. METHODS: We developed a freely available Microsoft-Excel-based tool called NetMetaXL, programmed in Visual Basic for Applications, which provides an interface for conducting a Bayesian network meta-analysis using WinBUGS from within Microsoft Excel. . This tool allows the user to easily prepare and enter data, set model assumptions, and run the network meta-analysis, with results being automatically displayed in an Excel spreadsheet. It also contains macros that use NetMetaXL's interface to generate evidence network diagrams, forest plots, league tables of pairwise comparisons, probability plots (rankograms), and inconsistency plots within Microsoft Excel. All figures generated are publication quality, thereby increasing the efficiency of knowledge transfer and manuscript preparation. RESULTS: We demonstrate the application of NetMetaXL using data from a network meta-analysis published previously which compares combined resynchronization and implantable defibrillator therapy in left ventricular dysfunction. We replicate results from the previous publication while demonstrating result summaries generated by the software. CONCLUSIONS: Use of the freely available NetMetaXL successfully demonstrated its ability to make running network meta-analyses more accessible to novice WinBUGS users by allowing analyses to be conducted entirely within Microsoft Excel. NetMetaXL also allows for more efficient and transparent critical appraisal of network meta-analyses, enhanced standardization of reporting, and integration with health economic evaluations which are frequently Excel-based.CC is a recipient of a Vanier Canada Graduate Scholarship from the Canadian Institutes of Health Research (funding reference number—CGV 121171) and is a trainee on the Canadian Institutes of Health Research Drug Safety and Effectiveness Network team grant (funding reference number—116573). BH is funded by a New Investigator award from the Canadian Institutes of Health Research and the Drug Safety and Effectiveness Network. This research was partly supported by funding from CADTH as part of a project to develop Excel-based tools to support the conduct of health technology assessments. This research was also supported by Cornerstone Research Group

Joint synthesis of conditionally related multiple outcomes makes better use of data than separate meta-analyses

Background: When there are structural relationships between outcomes reported in different trials, separate analyses of each outcome do not provide a single coherent analysis, which is required for decision-making. For example, trials of intrapartum anti-bacterial prophylaxis (IAP) to prevent early onset group B streptococcal (EOGBS) disease can report three treatment effects: the effect on bacterial colonisation of the newborn, the effect on EOGBS, and the effect on EOGBS conditional on newborn colonisation. These outcomes are conditionally related, or nested, in a multi-state model. This paper shows how to exploit these structural relationships, providing a single coherent synthesis of all the available data, while checking to ensure that different sources of evidence are consistent. Results: Overall, the use of IAP reduces the risk of EOGBS (RR: 0.03; 95% Credible Interval (CrI): 0.002-0.13). Most of the treatment effect is due to the prevention of colonisation in newborns of colonised mothers (RR: 0.08, 95% CrI: 0.04-0.14). Node-splitting demonstrated that the treatment effect calculated using only direct evidence was consistent with that predicted from the remaining evidence (p=0.15). The findings accorded with previously published separate meta-analyses of the different outcomes, once these are re-analysed correctly accounting for zero cells. Conclusion: Multiple outcomes should be synthesised together where possible, taking account of their structural relationships. This generates an internally coherent analysis, suitable for decision making, in which estimates of each of the treatment effects are based on all available evidence (direct and indirect). Separate meta-analyses of each outcome have none of these properties

Exercise cardiovascular magnetic resonance: feasibility and development of biventricular function and great vessel flow assessment, during continuous exercise accelerated by Compressed SENSE: preliminary results in healthy volunteers

Purpose Exercise cardiovascular magnetic resonance (Ex-CMR) typically requires complex post-processing or transient exercise cessation, decreasing clinical utility. We aimed to demonstrate the feasibility of assessing biventricular volumes and great vessel flow during continuous in-scanner Ex-CMR, using vendor provided Compressed SENSE (C-SENSE) sequences and commercial analysis software (Cvi42). Methods 12 healthy volunteers (8-male, age: 35 ± 9 years) underwent continuous supine cycle ergometer (Lode-BV) Ex-CMR (1.5T Philips, Ingenia). Free-breathing, respiratory navigated C-SENSE short-axis cines and aortic/pulmonary phase contrast magnetic resonance (PCMR) sequences were validated against clinical sequences at rest and used during low and moderate intensity Ex-CMR. Optimal PCMR C-SENSE acceleration, C-SENSE-3 (CS3) vs C-SENSE-6 (CS6), was further investigated by image quality scoring. Intra-and inter-operator reproducibility of biventricular and flow indices was performed. Results All CS3 PCMR image quality scores were superior (p  0.93). During Ex-CMR, biventricular end-diastolic volumes (EDV) remained unchanged, except right-ventricular EDV decreasing at moderate exercise. Biventricular ejection-fractions increased at each stage. Exercise biventricular cine and PCMR stroke volumes correlated very strongly (r ≥ 0.9), demonstrating internal validity. Intra-observer reproducibility was excellent, co-efficient of variance (COV) < 10%. Inter-observer reproducibility was excellent, except for resting right-ventricular, and exercise bi-ventricular end-systolic volumes which were good (COV 10–20%). Conclusion Biventricular function, aortic and pulmonary flow assessment during continuous Ex-CMR using CS3 sequences is feasible, reproducible and analysable using commercially available software

Effect of antiandrogen flutamide on measures of hepatic regeneration in rats

Male rat liver undergoes a process of demasculinization during hepatic regeneration following partial hepatectomy. The possibility that antiandrogens might potentiate this demasculinization process and in so doing augment the hepatic regenerative response was investigated. Adult male Wistar rats were treated with the antiandrogen flutamide (2 mg/rat/day or 5 mg/rat/day subcutaneously) or vehicle for three days prior to and daily after a 70% partial hepatectomy. At various times after hepatectomy, the liver remnants were removed and weighed. Rates of DNA and polyamine synthesis were assessed by measuring thymidine kinase and ornithine decarboxylase activities, respectively. Hepatic estrogen receptor status and the activity of alcohol dehydrogenase, an androgen-sensitive protein, were measured. Prior to surgery, the administration of 5 mg/day flutamide reduced the hepatic cytosolic androgen receptor activity by 98% and hepatic cytosolic estrogen receptor content by 92% compared to that present in vehicle-treated controls. After hepatectomy, however, all differences in sex hormone receptor activity between the treatment groups were abolished. The rate of liver growth after partial hepatectomy in the three groups was identical. Moreover, hepatectomy-induced increases in ornithine decarboxylase activity and thymidine kinase activity were comparable. These data demonstrate that, although flutamide administration initially alters the sex hormone receptor status of the liver, these affects have no effect on the hepatic regenerative response following a partial hepatectomy. © 1989 Plenum Publishing Corporation

A method for assessing robustness of the results of a star-shaped network meta-analysis under the unidentifiable consistency assumption

Background In a star-shaped network, pairwise comparisons link treatments with a reference treatment (often placebo or standard care), but not with each other. Thus, comparisons between non-reference treatments rely on indirect evidence, and are based on the unidentifiable consistency assumption, limiting the reliability of the results. We suggest a method of performing a sensitivity analysis through data imputation to assess the robustness of results with an unknown degree of inconsistency. Methods The method involves imputation of data for randomized controlled trials comparing non-reference treatments, to produce a complete network. The imputed data simulate a situation that would allow mixed treatment comparison, with a statistically acceptable extent of inconsistency. By comparing the agreement between the results obtained from the original star-shaped network meta-analysis and the results after incorporating the imputed data, the robustness of the results of the original star-shaped network meta-analysis can be quantified and assessed. To illustrate this method, we applied it to two real datasets and some simulated datasets. Results Applying the method to the star-shaped network formed by discarding all comparisons between non-reference treatments from a real complete network, 33% of the results from the analysis incorporating imputed data under acceptable inconsistency indicated that the treatment ranking would be different from the ranking obtained from the star-shaped network. Through a simulation study, we demonstrated the sensitivity of the results after data imputation for a star-shaped network with different levels of within- and between-study variability. An extended usability of the method was also demonstrated by another example where some head-to-head comparisons were incorporated. Conclusions Our method will serve as a practical technique to assess the reliability of results from a star-shaped network meta-analysis under the unverifiable consistency assumption.This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI19C1178). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Meta-analyses and Forest plots using a microsoft excel spreadsheet: step-by-step guide focusing on descriptive data analysis

<p>Abstract</p> <p>Background</p> <p>Meta-analyses are necessary to synthesize data obtained from primary research, and in many situations reviews of observational studies are the only available alternative. General purpose statistical packages can meta-analyze data, but usually require external macros or coding. Commercial specialist software is available, but may be expensive and focused in a particular type of primary data. Most available softwares have limitations in dealing with descriptive data, and the graphical display of summary statistics such as incidence and prevalence is unsatisfactory. Analyses can be conducted using Microsoft Excel, but there was no previous guide available.</p> <p>Findings</p> <p>We constructed a step-by-step guide to perform a meta-analysis in a Microsoft Excel spreadsheet, using either fixed-effect or random-effects models. We have also developed a second spreadsheet capable of producing customized forest plots.</p> <p>Conclusions</p> <p>It is possible to conduct a meta-analysis using only Microsoft Excel. More important, to our knowledge this is the first description of a method for producing a statistically adequate but graphically appealing forest plot summarizing descriptive data, using widely available software.</p

A meta-analytic review of stand-alone interventions to improve body image

Objective Numerous stand-alone interventions to improve body image have been developed. The present review used meta-analysis to estimate the effectiveness of such interventions, and to identify the specific change techniques that lead to improvement in body image. Methods The inclusion criteria were that (a) the intervention was stand-alone (i.e., solely focused on improving body image), (b) a control group was used, (c) participants were randomly assigned to conditions, and (d) at least one pretest and one posttest measure of body image was taken. Effect sizes were meta-analysed and moderator analyses were conducted. A taxonomy of 48 change techniques used in interventions targeted at body image was developed; all interventions were coded using this taxonomy. Results The literature search identified 62 tests of interventions (N = 3,846). Interventions produced a small-to-medium improvement in body image (d+ = 0.38), a small-to-medium reduction in beauty ideal internalisation (d+ = -0.37), and a large reduction in social comparison tendencies (d+ = -0.72). However, the effect size for body image was inflated by bias both within and across studies, and was reliable but of small magnitude once corrections for bias were applied. Effect sizes for the other outcomes were no longer reliable once corrections for bias were applied. Several features of the sample, intervention, and methodology moderated intervention effects. Twelve change techniques were associated with improvements in body image, and three techniques were contra-indicated. Conclusions The findings show that interventions engender only small improvements in body image, and underline the need for large-scale, high-quality trials in this area. The review identifies effective techniques that could be deployed in future interventions