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      Integrase inhibitors versus efavirenz combination antiretroviral therapies for TB/HIV coinfection: a meta-analysis of randomized controlled trials

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          Abstract

          Background

          Integrase inhibitors (INIs)-based antiretroviral therapies (ART) are more recommended than efavirenz (EFV)-based ART for people living with HIV/AIDS (PLWHA). Yet, the advantage of integrase inhibitors in treating TB/HIV coinfection is uncertain. Therefore, the objective of this systematic review is to evaluate the effects and safety of INIs- versus EFV-based ART in TB/HIV coinfection, and demonstrate the feasibility of the regimens.

          Methods

          Four electronic databases were systematically searched through September 2020. Fixed-effects models were used to calculate pooled effect size for all outcomes. The primary outcomes were virologic suppression and bacteriology suppression for INIs- versus EFV-based ART. Secondary outcomes included CD4 + cell counts change from baseline, adherence and safety.

          Results

          Three trials (including 672 TB/HIV patients) were eligible. ART combining INIs and EFV had similar effects for all outcomes, with none of the point estimates argued against the INIs-based ART on TB/HIV patients. Compared to EFV-based ART as the reference group, the RR was 0.94 (95% CI 0.85 to 1.05) for virologic suppression, 1.00 (95% CI 0.95 to 1.05) for bacteriology suppression, 0.98 (95% CI 0.95 to 1.01) for adherence. The mean difference in CD4 + cell counts increase between the two groups was 14.23 cells/μl (95% CI 0− 6.40 to 34.86). With regard to safety (adverse events, drug-related adverse events, discontinuation for drugs, grade 3–4 adverse events, IRIS (grade 3–4), and death), INIs-based regimen was broadly similar to EFV-based regimens. The analytical results in all sub-analyses of raltegravir- (RAL) and dolutegravir (DTG) -based ART were valid.

          Conclusion

          This meta-analysis demonstrates similar efficacy and safety of INIs-based ART compared with EFV-based ART. This finding supports INIs-based ART as a first-line treatment in TB/HIV patients. The conclusions presented here still await further validation owing to insufficient data.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12981-021-00348-w.

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          Most cited references48

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          Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range

          Background In systematic reviews and meta-analysis, researchers often pool the results of the sample mean and standard deviation from a set of similar clinical trials. A number of the trials, however, reported the study using the median, the minimum and maximum values, and/or the first and third quartiles. Hence, in order to combine results, one may have to estimate the sample mean and standard deviation for such trials. Methods In this paper, we propose to improve the existing literature in several directions. First, we show that the sample standard deviation estimation in Hozo et al.’s method (BMC Med Res Methodol 5:13, 2005) has some serious limitations and is always less satisfactory in practice. Inspired by this, we propose a new estimation method by incorporating the sample size. Second, we systematically study the sample mean and standard deviation estimation problem under several other interesting settings where the interquartile range is also available for the trials. Results We demonstrate the performance of the proposed methods through simulation studies for the three frequently encountered scenarios, respectively. For the first two scenarios, our method greatly improves existing methods and provides a nearly unbiased estimate of the true sample standard deviation for normal data and a slightly biased estimate for skewed data. For the third scenario, our method still performs very well for both normal data and skewed data. Furthermore, we compare the estimators of the sample mean and standard deviation under all three scenarios and present some suggestions on which scenario is preferred in real-world applications. Conclusions In this paper, we discuss different approximation methods in the estimation of the sample mean and standard deviation and propose some new estimation methods to improve the existing literature. We conclude our work with a summary table (an Excel spread sheet including all formulas) that serves as a comprehensive guidance for performing meta-analysis in different situations. Electronic supplementary material The online version of this article (doi:10.1186/1471-2288-14-135) contains supplementary material, which is available to authorized users.
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            Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation.

            Protocols of systematic reviews and meta-analyses allow for planning and documentation of review methods, act as a guard against arbitrary decision making during review conduct, enable readers to assess for the presence of selective reporting against completed reviews, and, when made publicly available, reduce duplication of efforts and potentially prompt collaboration. Evidence documenting the existence of selective reporting and excessive duplication of reviews on the same or similar topics is accumulating and many calls have been made in support of the documentation and public availability of review protocols. Several efforts have emerged in recent years to rectify these problems, including development of an international register for prospective reviews (PROSPERO) and launch of the first open access journal dedicated to the exclusive publication of systematic review products, including protocols (BioMed Central's Systematic Reviews). Furthering these efforts and building on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines, an international group of experts has created a guideline to improve the transparency, accuracy, completeness, and frequency of documented systematic review and meta-analysis protocols--PRISMA-P (for protocols) 2015. The PRISMA-P checklist contains 17 items considered to be essential and minimum components of a systematic review or meta-analysis protocol.This PRISMA-P 2015 Explanation and Elaboration paper provides readers with a full understanding of and evidence about the necessity of each item as well as a model example from an existing published protocol. This paper should be read together with the PRISMA-P 2015 statement. Systematic review authors and assessors are strongly encouraged to make use of PRISMA-P when drafting and appraising review protocols. © BMJ Publishing Group Ltd 2014.
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              Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range

              The era of big data is coming, and evidence-based medicine is attracting increasing attention to improve decision making in medical practice via integrating evidence from well designed and conducted clinical research. Meta-analysis is a statistical technique widely used in evidence-based medicine for analytically combining the findings from independent clinical trials to provide an overall estimation of a treatment effectiveness. The sample mean and standard deviation are two commonly used statistics in meta-analysis but some trials use the median, the minimum and maximum values, or sometimes the first and third quartiles to report the results. Thus, to pool results in a consistent format, researchers need to transform those information back to the sample mean and standard deviation. In this article, we investigate the optimal estimation of the sample mean for meta-analysis from both theoretical and empirical perspectives. A major drawback in the literature is that the sample size, needless to say its importance, is either ignored or used in a stepwise but somewhat arbitrary manner, e.g. the famous method proposed by Hozo et al. We solve this issue by incorporating the sample size in a smoothly changing weight in the estimators to reach the optimal estimation. Our proposed estimators not only improve the existing ones significantly but also share the same virtue of the simplicity. The real data application indicates that our proposed estimators are capable to serve as "rules of thumb" and will be widely applied in evidence-based medicine.
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                Author and article information

                Contributors
                whmj530@163.com
                qiuchengfeng0721@163.com
                Journal
                AIDS Res Ther
                AIDS Res Ther
                AIDS Research and Therapy
                BioMed Central (London )
                1742-6405
                1 May 2021
                1 May 2021
                2021
                : 18
                : 25
                Affiliations
                [1 ]GRID grid.412017.1, ISNI 0000 0001 0266 8918, Department of Evidence-Based Medicine and Clinical Center, , The First People’s Hospital of Huaihua, University of South China, ; Huaihua, 418000 People’s Republic of China
                [2 ]GRID grid.412017.1, ISNI 0000 0001 0266 8918, Department of Clinical Pharmacy, , The First People’s Hospital of Huaihua, University of South China, ; Huaihua, 418000 People’s Republic of China
                [3 ]GRID grid.412017.1, ISNI 0000 0001 0266 8918, Department of Intensive Care Unit, , The First People’s Hospital of Huaihua, University of South China, ; Huaihua, 418000 People’s Republic of China
                [4 ]GRID grid.412017.1, ISNI 0000 0001 0266 8918, Department of General Practice, , The First People’s Hospital of Huaihua, University of South China, ; Huaihua, 418000 People’s Republic of China
                [5 ]GRID grid.67293.39, Hunan University of Medicine, ; Huaihua, 418000 People’s Republic of China
                Article
                348
                10.1186/s12981-021-00348-w
                8088572
                33933131
                1fdd57ee-fdda-431f-a252-916f6dc14f64
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 23 November 2020
                : 12 April 2021
                Funding
                Funded by: Natural Science Foundation of Hunan Province
                Award ID: 2017JJ3250
                Award ID: 2019JJ40230
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100002767, Hunan Provincial Science and Technology Department;
                Award ID: B2019034
                Award Recipient :
                Funded by: Project of Science and Technology of Health Commission of Hunan Province
                Award ID: B2019035
                Award Recipient :
                Funded by: Bethune Medical Scientific Research Foundation
                Award ID: SCZ049BS
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2021

                Infectious disease & Microbiology
                integrase inhibitors,efavirenz,raltegravir,dolutegravir,tb,hiv patients

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