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      Significance of serum procalcitonin as biomarker for detection of bacterial peritonitis: a systematic review and meta-analysis

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          Abstract

          Background

          Bacterial peritonitis is serious disease and remains a diagnostic challenge for clinicians. Many studies have highlighted the potential usefulness of procalcitonin (PCT) for identification of bacterial peritonitis, however, the overall diagnostic value of PCT remains unclear. Therefore, we performed a meta-analysis to assess the accuracy of PCT for detection of bacterial peritonitis.

          Methods

          We performed a systematic searched in MEDLINE, EMBASE, SCOPUS, China Biology Medicine Database (CBM), China National Knowledge Infrastructure Database (CNKI) and Cochrane databases for trials that evaluated the diagnostic role of PCT for bacterial peritonitis. Sensitivity, specificity and other measures of accuracy of PCT were pooled using bivariate random effects models.

          Results

          Eighteen studies involving 1827 patients were included in the present meta-analysis. The pooled sensitivity and specificity of serum PCT for the diagnosis bacterial peritonitis were 0.83 (95% CI: 0.76–0.89) and 0.92 (95% CI: 0.87–0.96), respectively. The positive likelihood ratio was 11.06 (95% CI: 6.31–19.38), negative likelihood ratio was 0.18 (95% CI: 0.12–0.27) and diagnostic odds ratio (DOR) was 61.52 (95% CI: 27.58–137.21). The area under the receiver operating characteristic curve (AUROC) was 0.94. Use of a common PCT cut-off value could improve the DOR to 75.32 and the AUROC to 0.95. Analysis of the seven studies that measured serum C-reactive protein (CRP) indicated that PCT was more accurate than CRP for the diagnosis of bacterial peritonitis.

          Conclusions

          Our results indicate that PCT determination is a relatively sensitive and specific test for the diagnosis of bacterial peritonitis. However, with regard to methodological limitations and significant heterogeneity, medical decisions should be based on both clinical findings and PCT test results.

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          Most cited references48

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          Optimal cut-point and its corresponding Youden Index to discriminate individuals using pooled blood samples.

          Costs can hamper the evaluation of the effectiveness of new biomarkers. Analysis of smaller numbers of pooled specimens has been shown to be a useful cost-cutting technique. The Youden index (J), a function of sensitivity (q) and specificity (p), is a commonly used measure of overall diagnostic effectiveness. More importantly, J is the maximum vertical distance or difference between the ROC curve and the diagonal or chance line; it occurs at the cut-point that optimizes the biomarker's differentiating ability when equal weight is given to sensitivity and specificity. Using the additive property of the gamma and normal distributions, we present a method to estimate the Youden index and the optimal cut-point, and extend its applications to pooled samples. We study the effect of pooling when only a fixed number of individuals are available for testing, and pooling is carried out to save on the number of assays. We measure loss of information by the change in root mean squared error of the estimates of the optimal cut-point and the Youden index, and we study the extent of this loss via a simulation study. In conclusion, pooling can result in a substantial cost reduction while preserving the effectiveness of estimators, especially when the pool size is not very large.
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            Advanced methods in meta-analysis: multivariate approach and meta-regression.

            This tutorial on advanced statistical methods for meta-analysis can be seen as a sequel to the recent Tutorial in Biostatistics on meta-analysis by Normand, which focused on elementary methods. Within the framework of the general linear mixed model using approximate likelihood, we discuss methods to analyse univariate as well as bivariate treatment effects in meta-analyses as well as meta-regression methods. Several extensions of the models are discussed, like exact likelihood, non-normal mixtures and multiple endpoints. We end with a discussion about the use of Bayesian methods in meta-analysis. All methods are illustrated by a meta-analysis concerning the efficacy of BCG vaccine against tuberculosis. All analyses that use approximate likelihood can be carried out by standard software. We demonstrate how the models can be fitted using SAS Proc Mixed. Copyright 2002 John Wiley & Sons, Ltd.
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              Physiology and genetics of procalcitonin.

              Procalcitonin (PCT), a protein of 116 amino-acids with molecular weight of 13 kDa, was discovered 25 years ago as a prohormone of calcitonin produced by C-cells of the thyroid gland and intracellularly cleaved by proteolytic enzymes into the active hormone. Circulating levels of PCT in healthy subjects are below detection limit. Since 1993 when its elevated level was found in patients with bacterial infection, PCT became an important protein in the detection and differential diagnostics of inflammatory states. The production of PCT during inflammation is linked with a bacterial endotoxin and with inflammatory cytokines (TNF, IL-6). PCT detectable in the plasma during inflammation is not produced in C-cells of the thyroid. The probable site of PCT production during inflammation are the neuroendocrine cells in the lungs or intestine. There is no evidence of plasma PCT binding to cellular receptors of calcitonin, and the role of PCT in calcium and phosphate metabolism during sepsis is still not clear. Other hypothetical roles of PCT (cytokine network regulation, PCT as an endogenous non-steroid antiinflammatory drug) are being considered.
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                Author and article information

                Contributors
                ysk_1234@163.com
                xiaolirenal@163.com
                zhaohaoxiangya@163.com
                xuxiaoxuan1234@163.com
                panaisong5566@163.com
                liufy195202@163.com
                zndxsunlin11@163.com
                Journal
                BMC Infect Dis
                BMC Infect. Dis
                BMC Infectious Diseases
                BioMed Central (London )
                1471-2334
                22 August 2014
                22 August 2014
                2014
                : 14
                : 1
                : 452
                Affiliations
                [ ]Department of Nephrology, The Second Xiangya Hospital, Kidney Institute of Central South University, Changsha, Hunan 410011 China
                [ ]Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province 410013 China
                Article
                3758
                10.1186/1471-2334-14-452
                4155125
                25145785
                51de11be-3189-4db2-93dd-e755585a2601
                © Yang et al.; licensee BioMed Central Ltd. 2014

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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.

                History
                : 24 December 2013
                : 13 August 2014
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2014

                Infectious disease & Microbiology
                procalcitonin,diagnosis,peritonitis,meta-analysis
                Infectious disease & Microbiology
                procalcitonin, diagnosis, peritonitis, meta-analysis

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