{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T18:34:26Z","timestamp":1793298866979,"version":"4.5.0"},"reference-count":20,"publisher":"American Medical Association (AMA)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Four clinical phenotypes of sepsis based on data from electronic health records have been proposed. Although promising, the generalizability of these phenotypes remains uncertain, and multisite validation is needed.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To validate, using the same methods and inclusion criteria, the 4 clinical phenotypes derived from Sepsis Endotyping in Emergency Care (SENECA) data.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This multisite retrospective cohort study uses data on adult patients admitted to the emergency departments in Stockholm, Sweden (January 1, 2011, to September 1, 2023); Oxford, England (February 4, 2014, to June 20, 2021); and Oslo, Norway (January 4, 2019, to October 9, 2023) university hospitals. Included encounters are those with body fluid cultures taken, documented antibiotic administration, and Sequential Organ Failure Assessment scores of 2 or more, all within 6 hours of admission. Data analysis was conducted from November 2, 2023, to September 1, 2025.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n \n Consensus clustering with\n k<\/jats:italic>\n -means was used to derive 4 clinical phenotypes at each site, comparing them with the SENECA-derived phenotypes, as well as with one another.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n There were 30\u202f865 patient encounters in Stockholm (mean [SD] age, 68 [16] years; 18\u202f165 men [59%]), 15\u202f575 in Oxford (mean [SD] age, 71 [18] years; 9067 men [58%]), and 1806 in Oslo (mean [SD] age, 71 [17] years; 1068 men [59%]). There was little consistency between the SENECA clinical phenotypes and each site\u2019s own phenotypes, with a Cohen \u03ba of 0.32 for Stockholm, 0.37 for Oslo, and 0.40 for Oxford; the Adjusted Rand Indices were 0.21 for Stockholm, 0.27 for Oslo, and 0.26 for Oxford. There was also little consistency between the phenotypes derived in Stockholm, Oxford, and Oslo.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This study suggests that the 4 clinical phenotypes of the SENECA data are not generalizable across 3 independent cohorts. This calls for further exploration of possible underlying sepsis subgroups using alternative approaches that mitigate the inherent stochasticity in many unsupervised and semisupervised clustering methods.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.16134","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T15:30:35Z","timestamp":1780327835000},"page":"e2616134","source":"Crossref","is-referenced-by-count":4,"title":["Multicenter Validation of Clinical Sepsis Phenotypes"],"prefix":"10.1001","volume":"9","author":[{"given":"Chang Ho","family":"Yoon","sequence":"first","affiliation":[{"name":"Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom"},{"name":"Big Data Institute, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Sj\u00f6holm","sequence":"additional","affiliation":[{"name":"Department of Medicine Solna, Clinical Epidemiology Unit, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin E.","family":"Wickstr\u00f8m","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Blood Cell Research Group, Oslo University Hospital, Oslo, Norway"},{"name":"Department of Medical Biochemistry, Unilabs Laboratory Medicine, Oslo, Norway"},{"name":"Institute of Clinical Medicine, University of Oslo, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders Skyrud","family":"Danielsen","sequence":"additional","affiliation":[{"name":"Department of Infection Control and Preparedness, Norwegian Institute of Public Health, Oslo, Norway"},{"name":"Department of Microbiology, Oslo University Hospital, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Prebensen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, University of Oslo, Oslo, Norway"},{"name":"Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Karlsson","family":"Valik","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Karolinska Institutet, Solna, Stockholm, Sweden"},{"name":"Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander Rygh","family":"Holten","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, University of Oslo, Oslo, Norway"},{"name":"Department of Acute Medicine, Oslo University Hospital, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik Koldberg","family":"Amundsen","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Blood Cell Research Group, Oslo University Hospital, Oslo, Norway"},{"name":"Department of Life Sciences and Health, Oslo Metropolitan University, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Sarah","family":"Walker","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom"},{"name":"The National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford, Oxford, United Kingdom"},{"name":"National Institute for Health Research, Oxford Biomedical Research Centre, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Eyre","sequence":"additional","affiliation":[{"name":"Big Data Institute, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom"},{"name":"The National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford, Oxford, United Kingdom"},{"name":"National Institute for Health Research, Oxford Biomedical Research Centre, 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