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      A meta-analysis of efficacy and safety of doripenem for treating bacterial infections

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          Abstract

          Objective

          The aim of this article is to compare the efficacy and safety of doripenem for bacterial infections.

          Methods

          We included six randomized clinical trials identified from PubMed and Embase up to July 31, 2014. The included trials compared efficacy and safety of doripenem for complicated intra-abdominal infections, complicated urinary tract infection, nosocomial pneumonia, and acute biliary tract infection. The meta-analysis was carried on by the statistical software of Review Manager, version 5.2.

          Results

          Compared with empirical antimicrobial agents on overall treatment efficacy, doripenem was associated with similar clinical and microbiological treatment success rates (for the clinical evaluable population, odds ratio [OR] = 1.26, 95% confidence interval [CI] 0.93–1.69, p = 0.13; for clinical modified intent-to-treatment population, OR = 0.88, 95% CI 0.55–1.41, p = 0.60; for microbiology evaluable population, OR = 1.16, 95% CI 0.90–1.50, p = 0.26; for microbiological modified intent-to-treatment (m-mITT), OR = 0.98, 95% CI 0.81–1.20, p = 0.87). We compared incidence of adverse events and all-cause mortality to analyze treatment safety. The outcomes suggested that doripenem was similar to comparators in terms of incidence of adverse events and all-cause mortality on modified intent-to-treatment population (for incidence of AEs, OR = 1.10, 95% CI 0.90–1.35, p = 0.33; for all-cause mortality, OR = 1.08, 95% CI 0.77–1.51, p = 0.67). In nosocomial pneumonia and ventilator-associated pneumonia treatment, doripenem was not inferior to other antibacterial agents in terms of efficacy and safety.

          Conclusion

          From this meta-analysis, we can conclude that doripenem is as valuable and well-tolerated than empirical antimicrobial agents for complicated intra-abdominal infections, complicated urinary tract infection, acute biliary tract infection and nosocomial pneumonia treatment.

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          Most cited references22

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          Measuring inconsistency in meta-analyses.

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            Assessing the quality of reports of randomized clinical trials: is blinding necessary?

            It has been suggested that the quality of clinical trials should be assessed by blinded raters to limit the risk of introducing bias into meta-analyses and systematic reviews, and into the peer-review process. There is very little evidence in the literature to substantiate this. This study describes the development of an instrument to assess the quality of reports of randomized clinical trials (RCTs) in pain research and its use to determine the effect of rater blinding on the assessments of quality. A multidisciplinary panel of six judges produced an initial version of the instrument. Fourteen raters from three different backgrounds assessed the quality of 36 research reports in pain research, selected from three different samples. Seven were allocated randomly to perform the assessments under blind conditions. The final version of the instrument included three items. These items were scored consistently by all the raters regardless of background and could discriminate between reports from the different samples. Blind assessments produced significantly lower and more consistent scores than open assessments. The implications of this finding for systematic reviews, meta-analytic research and the peer-review process are discussed.
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              Pathway and network-based analysis of genome-wide association studies in multiple sclerosis

              Genome-wide association studies (GWAS) testing several hundred thousand SNPs have been performed in multiple sclerosis (MS) and other complex diseases. Typically, the number of markers in which the evidence for association exceeds the genome-wide significance threshold is very small, and markers that do not exceed this threshold are generally neglected. Classical statistical analysis of these datasets in MS revealed genes with known immunological functions. However, many of the markers showing modest association may represent false negatives. We hypothesize that certain combinations of genes flagged by these markers can be identified if they belong to a common biological pathway. Here we conduct a pathway-oriented analysis of two GWAS in MS that takes into account all SNPs with nominal evidence of association (P < 0.05). Gene-wise P-values were superimposed on a human protein interaction network and searches were conducted to identify sub-networks containing a higher proportion of genes associated with MS than expected by chance. These sub-networks, and others generated at random as a control, were categorized for membership of biological pathways. GWAS from eight other diseases were analyzed to assess the specificity of the pathways identified. In the MS datasets, we identified sub-networks of genes from several immunological pathways including cell adhesion, communication and signaling. Remarkably, neural pathways, namely axon-guidance and synaptic potentiation, were also over-represented in MS. In addition to the immunological pathways previously identified, we report here for the first time the potential involvement of neural pathways in MS susceptibility.
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                Author and article information

                Contributors
                Journal
                Braz J Infect Dis
                Braz J Infect Dis
                The Brazilian Journal of Infectious Diseases
                Elsevier
                1413-8670
                1678-4391
                27 January 2015
                Mar-Apr 2015
                27 January 2015
                : 19
                : 2
                : 156-162
                Affiliations
                [a ]Department of Pharmacy, The First Hospital of Jilin University, Changchun 130021, PR China
                [b ]Department of Technical Center, Jilin Entry Exit Inspection and Quarantine Bureau, Changchun 130062, PR China
                Author notes
                [* ] Corresponding author at: Xinmin Street 71#, Changchun City, PR China. 350740439@ 123456qq.com
                Article
                S1413-8670(15)00022-7
                10.1016/j.bjid.2014.10.010
                9425342
                25636188
                dc8094b7-1cdc-40ee-a8fe-0ececc6e13d4
                © 2015 Elsevier Editora Ltda. All rights reserved.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 19 August 2014
                : 29 October 2014
                Categories
                Original Article

                doripenem,meta-analysis,efficacy,safety,infection
                doripenem, meta-analysis, efficacy, safety, infection

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