Dataset Information

Diagnostic and prognostic accuracy of Protein C in adult patients with sepsis: protocol for a systematic review and meta-analysis.

ABSTRACT:

Introduction

Sepsis is a dysregulated host response to infection characterised by activation of proinflammatory and procoagulant mechanisms. Protein C (PC)'s activity as an anticoagulant and antiinflammatory molecule makes it an appealing target for sepsis biomarker studies. To date, there has been no systematic review of PC as a sepsis biomarker.

Objectives

To evaluate the diagnostic accuracy and prognostic strength of PC as a biomarker for adult sepsis.

Methods and analysis

Medline, Embase, Cochrane Library, PubMed and Cumulative Index to Nursing and Allied Health Literature (CINAHL) will be searched from inception through 20 January 2021 for prospective observational studies that evaluate the use of PC as a diagnostic or prognostic biomarker for adult sepsis. Title and abstract screening, full-text screening and data extraction will be conducted in duplicate. Risk of bias will be assessed using the Quality Assessment of Diagnostic Accuracy Studies and Quality in Prognostic Studies tools. If sufficient data are available, a meta-analysis will be conducted. The standardised mean difference and 95% CI will be calculated for prognostic and diagnostic studies. If possible, a hierarchical summary receiver operator characteristic curve will be generated to assess overall prognostic and diagnostic biomarker accuracy. I² statistics will be used to assess heterogeneity. Sensitivity analysis will be performed by removing studies with a high risk of bias and re-examining the meta-analysis results.

Ethics and dissemination

Given this is a systematic review and meta-analysis, there is no requirement for ethics approval. Findings will be disseminated through a peer-reviewed publication and social media.

Prospero registration number

CRD42021229786.

SUBMITTER: Catenacci V

PROVIDER: S-EPMC8438940 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundSepsis, the dysregulated host response to infection, triggers abnormal pro-coagulant and pro-inflammatory host responses. Limitations in early disease intervention highlight the need for effective diagnostic and prognostic biomarkers. Protein C's role as an anticoagulant and anti-inflammatory molecule makes it an appealing target for sepsis biomarker studies. This meta-analysis aims to assess the diagnostic and prognostic value of protein C (PC) as a biomarker for adult sepsis.MethodsWe searched MEDLINE, PubMed, EMBASE, CINAHL and Cochrane Library from database inception to September 12, 2021. We included prospective observational studies of (1) adult patients (> 17) with sepsis or suspicion of sepsis that; (2) measured PC levels with 24 h of study admission with; and (3) the goal of examining PC as a diagnostic or prognostic biomarker. Two authors screened articles and conducted risk of bias (RoB) assessment, using the Quality in Prognosis Studies (QUIPS) and the Quality Assessment in Diagnostic Studies-2 (QUADAS-2) tools. If sufficient data were available, meta-analysis was conducted to estimate the standardized mean difference (SMD) between patient populations.ResultsTwelve studies were included, and 8 were synthesized for meta-analysis. Pooled analysis demonstrated moderate certainty of evidence that PC levels were less reduced in sepsis survivors compared to non-survivors (6 studies, 741 patients, SMD = 0.52, 95% CI 0.24-0.81, p = 0.0003, I2 = 55%), and low certainty of evidence that PC levels were less reduced in septic patients without disseminated intravascular coagulation (DIC) compared to those with DIC (3 studies, 644 patients, SMD = 0.97, 95% CI 0.62-1.32, p < 0.00001, I2 = 67%). PC could not be evaluated as a diagnostic tool due to heterogeneous control populations between studies.Conclusion and relevanceOur review demonstrates that PC levels were significantly higher in sepsis survivors compared to non-survivors and patients with sepsis but not disseminated intravascular coagulation (DIC). Our evaluation is limited by high RoB in included studies and poor reporting of the sensitivity and specificity of PC as a sepsis biomarker. Future studies are needed to determine the sensitivity and specificity of PC to identify its clinical significance as a biomarker for early sepsis recognition. Trial Registration PROSPERO registration number: CRD42021229786. The study protocol was published in BMJ Open.

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Project description:IntroductionDisseminated intravascular coagulation (DIC) is a common and serious condition that can lead to poor outcomes in critically ill patients. To make a correct diagnosis and improve the outcome of patients with DIC, several organisations have put forward DIC scoring systems. However, which criteria is the best to use for diagnosing DIC remains a continuing controversy even though many studies have been conducted to validate the diagnostic accuracy of each DIC scoring system.Methods and analysisWe will conduct a systematic review and meta-analysis of the diagnostic accuracy of DIC criteria for the prediction of mortality in critically ill adult patients. The primary objective is to assess the predictive values of the DIC criteria of Japanese Association for Acute Medicine, International Society on Thrombosis and Haemostasis, Japanese Ministry of Health and Welfare, Korean Society on Thrombosis and Hemostasis and Chinese Diagnostic Scoring System for 28-day mortality. We will search electronic bibliographic databases such as MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials. Two reviewers will independently screen titles and abstracts, perform full article reviews and extract study data. We will report study characteristics and assess methodological quality using the Quality of Diagnostic Accuracy Studies-II tool. If pooling is appropriate, we will compute parameter estimates using bivariate random-effects and hierarchical summary receiver operating characteristic models to produce summary receiver operating curves, summary operating points (pooled sensitivity and specificity) and 95% confidence regions around the summary operating points. Clinical and methodological subgroup and sensitivity analyses will be performed to explore heterogeneity.Ethics and disseminationThis systematic review will help physicians diagnose DIC accurately and improve their clinical practice in critically ill settings. Approval from an ethics committee is not required. The findings will be disseminated through publication in a peer-reviewed journal.Prospero registration numberCRD42017079350.