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To date, randomized controlled trials have failed to demonstrate a benefit of these therapies and heterogeneity of treatment effect is suspected. In this study, we aimed at assessing the heterogeneity of treatment effect of thiamine (B1) and the combination of B1 plus ascorbic acid (AA\u2009+\u2009B1) in critically ill patients with sepsis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We conducted a bi-centric retrospective cohort study. All adult patients admitted to the ICU with sepsis or septic shock between January 2012 and August 2022 were included. Patient clusters were identified using latent variable analysis based on demographics and physiological variables obtained within 24\u00a0h of admission. Within each cluster and using inverse probability weighted Cox models, we compared in-hospital mortality between patients who received standard treatment (control), standard treatment plus B1 (B1 group), and standard treatment plus a combination of thiamine and ascorbic acid (AA\u2009+\u2009B1 group).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>A total of 3465 septic patients were included, 2183, 1054 and 228 in the standard, B1 and AA\u2009+\u2009B1 groups respectively. Five clusters of patients were identified in an unsupervised manner. The \u201cCluster Severe\u201d included the most severely ill patients, the \u201cCluster Resp\u201d patients presented with predominantly respiratory failure, the \u201cCluster Old\u201d included elderly patients with multiple comorbidities, the \u201cCluster Fit\u201d patients were young, healthy with low severity indices and \u201cCluster Liver\u201d included patients with predominant liver failure. B1 treatment was associated with different outcomes across the five clusters. It was associated with a lower in-hospital mortality in the \u201cCluster Severe\u201d and \u201cCluster Resp\u201d. On the other hand, the combination of thiamine and ascorbic acid was not associated with reduced mortality in any cluster but an increased mortality in\u201dCluster Old\u201d.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>These results reinforce the lack of efficacy of the combination of AA\u2009+\u2009B1 reported in recent trials and even raise concerns about potential harm in older patients with comorbidities. On the contrary, we reported improved ICU survival associated with B1 supplementation in the most severe patients and those with predominant respiratory failure, supporting the need for further trials in this specific population.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13054-024-05188-4","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T11:57:11Z","timestamp":1732881431000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Differential effects of thiamine and ascorbic acid in clusters of septic patients identified by latent variable analysis"],"prefix":"10.1186","volume":"28","author":[{"given":"David","family":"Legouis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Monard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimad","family":"Ourahmoune","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Sgardello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Quintard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Criton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Sangla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,29]]},"reference":[{"issue":"8","key":"5188_CR1","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1001\/jama.2016.0287","volume":"315","author":"M Singer","year":"2016","unstructured":"Singer M, Deutschman CS, Seymour CW, et al. 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