{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T11:51:29Z","timestamp":1792497089581,"version":"4.5.0"},"reference-count":28,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T00:00:00Z","timestamp":1694131200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>New onset atrial fibrillation (NOAF) is the most common arrhythmia affecting critically ill patients with sepsis. NOAF is associated with increased intensive care unit mortality, increased hospital mortality, development of heart failure and increased risk of permanent atrial fibrillation and thromboembolic events such as stroke. The pathophysiology of NOAF has been outlined, however, a knowledge gap exists regarding the association between abnormalities in coagulation and immune biomarkers, and the risk of developing NOAF in patients with sepsis.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods and analysis<\/jats:title>\n<jats:p>This protocol describes a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guideline (PRISMA-P) and the Meta-Analyses and Systematic Reviews of Observational Studies guideline (MOOSE). We will conduct the literature search in Medline, Scopus and Cochrane Library. We will include studies that report data in adult patients (&gt;18 years) with sepsis that develop NOAF. We will extract data from studies that report at least one coagulation or immune biomarker. Risk of bias will be assessed by using the Newcastle Ottawa Scale (NOS) and Risk of Bias 2 tool (RoB2) for non-randomized and randomized trials respectively. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be utilized in assessing the quality of evidence.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Discussion<\/jats:title>\n<jats:p>This systematic review and meta-analysis will explore the scientific literature regarding the association between coagulation and immune activation in critically ill patients with sepsis, who develop NOAF. The findings will add to the existing knowledge base of NOAF in sepsis, highlight areas of uncertainty and identify future areas of interest to guide and improve management strategies for NOAF.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Trial registration<\/jats:title>\n<jats:p><jats:bold>Registration details.<\/jats:bold> <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.crd.york.ac.uk\/prospero\/display_record.php?ID=CRD42022385225\" xlink:type=\"simple\">CRD42022385225<\/jats:ext-link> (PROSPERO).<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0290963","type":"journal-article","created":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T17:55:53Z","timestamp":1694195753000},"page":"e0290963","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Study protocol: A systematic review and meta-analysis regarding the influence of coagulopathy and immune activation on new onset atrial fibrillation in patients with sepsis"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4139-191X","authenticated-orcid":true,"given":"Michael","family":"Downes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingeborg D.","family":"Welters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1634-3297","authenticated-orcid":true,"given":"Brian W.","family":"Johnston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,9,8]]},"reference":[{"issue":"6","key":"pone.0290963.ref001","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1016\/j.chest.2018.03.040","article-title":"Atrial Fibrillation in the ICU","volume":"154","author":"NA Bosch","year":"2018","journal-title":"Chest"},{"issue":"2","key":"pone.0290963.ref002","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1177\/175114371301400212","article-title":"Atrial Fibrillation in the Intensive Care Setting","volume":"14","author":"A Malik","year":"2013","journal-title":"Journal of the Intensive Care Society"},{"issue":"4","key":"pone.0290963.ref003","doi-asserted-by":"crossref","DOI":"10.3390\/jpm12040547","article-title":"Prevalence of New-Onset Atrial Fibrillation and Associated Outcomes in Patients with Sepsis: A Systematic Review and Meta-Analysis","volume":"12","author":"B Corica","year":"2022","journal-title":"J Pers Med"},{"issue":"1","key":"pone.0290963.ref004","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s40560-015-0085-4","article-title":"Epidemiology, prevention, and treatment of new-onset atrial fibrillation in critically ill: a systematic review.","volume":"3","author":"T Yoshida","year":"2015","journal-title":"J Intensive Care"},{"issue":"3","key":"pone.0290963.ref005","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1097\/01.CCM.0000114579.56430.E0","article-title":"Incidence and risk factors of atrial fibrillation in a surgical intensive care unit","volume":"32","author":"P Seguin","year":"2004","journal-title":"Crit Care Med."},{"issue":"3","key":"pone.0290963.ref006","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.jcrc.2011.10.011","article-title":"Epidemiology and management of atrial fibrillation in medical and noncardiac surgical adult intensive care unit patients","volume":"27","author":"S Kanji","year":"2012","journal-title":"J Crit Care"},{"issue":"2","key":"pone.0290963.ref007","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1164\/rccm.201603-0618OC","article-title":"Incidence, Predictors, and Outcomes of New-Onset Atrial Fibrillation in Critically Ill Patients with Sepsis. A Cohort Study","volume":"195","author":"PM Klein Klouwenberg","year":"2017","journal-title":"Am J Respir Crit Care Med"},{"issue":"7","key":"pone.0290963.ref008","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1007\/s00134-019-05633-x","article-title":"New-onset atrial fibrillation in adult critically ill patients: a scoping review.","volume":"45","author":"M Wetterslev","year":"2019","journal-title":"Intensive Care Medicine"},{"issue":"3","key":"pone.0290963.ref009","doi-asserted-by":"crossref","first-page":"R108","DOI":"10.1186\/cc9057","article-title":"Incidence and prognostic impact of new-onset atrial fibrillation in patients with septic shock: a prospective observational study","volume":"14","author":"R Meierhenrich","year":"2010","journal-title":"Critical Care"},{"issue":"1","key":"pone.0290963.ref010","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1186\/s13054-021-03684-5","article-title":"Treatment strategies for new onset atrial fibrillation in patients treated on an intensive care unit: a systematic scoping review","volume":"25","author":"L Drikite","year":"2021","journal-title":"Critical Care"},{"key":"pone.0290963.ref011","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jcrc.2019.06.015","article-title":"Risk factors for new-onset atrial fibrillation on the general adult ICU: A systematic review","volume":"53","author":"JP Bedford","year":"2019","journal-title":"Journal of Critical Care"},{"key":"pone.0290963.ref012","doi-asserted-by":"crossref","first-page":"103114","DOI":"10.1016\/j.iccn.2021.103114","article-title":"Triggers for new-onset atrial fibrillation in critically ill patients.","volume":"67","author":"JP Bedford","year":"2021","journal-title":"Intensive Crit Care Nurs"},{"issue":"20","key":"pone.0290963.ref013","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1001\/jama.2011.1615","article-title":"Incident Stroke and Mortality Associated With New-Onset Atrial Fibrillation in Patients Hospitalized With Severe Sepsis","volume":"306","author":"AJ Walkey","year":"2011","journal-title":"JAMA"},{"issue":"8","key":"pone.0290963.ref014","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1093\/ehjacc\/zuac080","article-title":"New-onset atrial fibrillation in intensive care: epidemiology and outcomes","volume":"11","author":"JP Bedford","year":"2022","journal-title":"European Heart Journal Acute Cardiovascular Care"},{"issue":"1","key":"pone.0290963.ref015","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s12916-015-0327-2","article-title":"Causes and consequences of coagulation activation in sepsis: an evolutionary medicine perspective.","volume":"13","author":"MML Fiusa","year":"2015","journal-title":"BMC Medicine"},{"issue":"10","key":"pone.0290963.ref016","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.molmed.2011.05.007","article-title":"Inflammatory pathways underlying atrial fibrillation","volume":"17","author":"K Friedrichs","year":"2011","journal-title":"Trends Mol Med"},{"key":"pone.0290963.ref017","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"MJ Page","year":"2021","journal-title":"Bmj"},{"key":"pone.0290963.ref018","doi-asserted-by":"crossref","first-page":"n160","DOI":"10.1136\/bmj.n160","article-title":"PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews","volume":"372","author":"MJ Page","year":"2021","journal-title":"Bmj"},{"issue":"1","key":"pone.0290963.ref019","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2046-4053-4-1","article-title":"Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement.","volume":"4","author":"D Moher","year":"2015","journal-title":"Systematic Reviews"},{"key":"pone.0290963.ref020","doi-asserted-by":"crossref","first-page":"g7647","DOI":"10.1136\/bmj.g7647","article-title":"Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation.","volume":"349","author":"L Shamseer","year":"2015","journal-title":"BMJ: British Medical Journal"},{"issue":"15","key":"pone.0290963.ref021","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1001\/jama.283.15.2008","article-title":"Meta-analysis of observational studies in epidemiology: a proposal for reporting. 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