{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T13:09:48Z","timestamp":1754485788174,"version":"3.40.5"},"reference-count":20,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T00:00:00Z","timestamp":1712188800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF17OC0028608"],"award-info":[{"award-number":["NNF17OC0028608"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008269","name":"L\u00e6ge Sofus Carl Emil Friis og Hustru Olga Doris Friis' Legat","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005111","name":"Rigshospitalet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005111","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009907","name":"Grosserer Jakob Ehrenreich og Hustru Grete Ehrenreichs Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009907","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Anaesthesiol Scand"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Variation in usual practice in fluid trials assessing lower versus higher volumes may affect overall comparisons. To address this, we will evaluate the effects of heterogeneity in treatment intensity in the Conservative versus Liberal Approach to Fluid Therapy of Septic Shock in Intensive Care trial. This will reflect the effects of differences in site\u2010specific intensities of standard fluid treatment due to local practice preferences while considering participant characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We will assess the effects of heterogeneity in treatment intensity across one primary (all\u2010cause mortality) and three secondary outcomes (serious adverse events or reactions, days alive without life support and days alive out of hospital) after 90\u2009days. We will classify sites based on the site\u2010specific intensity of standard fluid treatment, defined as the mean differences in observed versus predicted intravenous fluid volumes in the first 24\u2009h in the standard\u2010fluid group while accounting for differences in participant characteristics. Predictions will be made using a machine learning model including 22 baseline predictors using the extreme gradient boosting algorithm. Subsequently, sites will be grouped into fluid treatment intensity subgroups containing at least 100 participants each. Subgroups differences will be assessed using hierarchical Bayesian regression models with weakly informative priors. We will present the full posterior distributions of relative (risk ratios and ratios of means) and absolute differences (risk differences and mean differences) in each subgroup.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This study will provide data on the effects of heterogeneity in treatment intensity while accounting for patient characteristics in critically ill adult patients with septic shock.<\/jats:p><\/jats:sec><jats:sec><jats:title>Registrations<\/jats:title><jats:p>The European Clinical Trials Database (EudraCT): 2018\u2010000404\u201042, ClinicalTrials. gov: NCT03668236.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aas.14423","type":"journal-article","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T05:39:26Z","timestamp":1712295566000},"page":"975-982","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of <scp>IV<\/scp> fluid restriction according to site\u2010specific intensity of standard fluid treatment\u2014protocol"],"prefix":"10.1111","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0442-0032","authenticated-orcid":false,"given":"Praleene","family":"Sivapalan","sequence":"first","affiliation":[{"name":"Department of Intensive Care Copenhagen University Hospital\u2014Rigshospitalet  Copenhagen Denmark"},{"name":"Collaboration for Research in Intensive Care (CRIC)  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1023-0371","authenticated-orcid":false,"given":"Benjamin Skov","family":"Kaas\u2010Hansen","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Copenhagen University Hospital\u2014Rigshospitalet  Copenhagen Denmark"},{"name":"Collaboration for Research in Intensive Care (CRIC)  Copenhagen Denmark"},{"name":"Department of Public Health, Section of Biostatistics University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1840-1596","authenticated-orcid":false,"given":"Tine Sylvest","family":"Meyhoff","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Copenhagen University Hospital\u2014Rigshospitalet  Copenhagen Denmark"},{"name":"Collaboration for Research in Intensive Care (CRIC)  Copenhagen Denmark"},{"name":"Department of Anaesthesia and Intensive Care Lilleb\u00e6lt Hospital  Kolding Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3847-3247","authenticated-orcid":false,"given":"Peter Buhl","family":"Hjortrup","sequence":"additional","affiliation":[{"name":"Collaboration for Research in Intensive Care (CRIC)  Copenhagen Denmark"},{"name":"Department of Cardiothoracic Anaesthesia and Intensive Care, The Heart Center Copenhagen University Hospital\u2014Rigshospitalet  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6536-0504","authenticated-orcid":false,"given":"Maj\u2010Brit N.","family":"Kj\u00e6r","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Copenhagen University Hospital\u2014Rigshospitalet  Copenhagen Denmark"},{"name":"Collaboration for Research in Intensive Care (CRIC)  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6157-5359","authenticated-orcid":false,"given":"Jon Henrik","family":"Laake","sequence":"additional","affiliation":[{"name":"Collaboration for Research in Intensive Care (CRIC)  Copenhagen Denmark"},{"name":"Department of Anaesthesiology and Intensive Care Medicine, Division of Emergencies and Critical Care Oslo University Hospital  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0444-8553","authenticated-orcid":false,"given":"Maria","family":"Cronhjort","sequence":"additional","affiliation":[{"name":"Collaboration for Research in Intensive Care (CRIC)  Copenhagen Denmark"},{"name":"Department of Clinical Sciences Danderyd Hospital, Karolinska Institutet  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2195-0473","authenticated-orcid":false,"given":"Stephan M.","family":"Jakob","sequence":"additional","affiliation":[{"name":"Collaboration for Research in Intensive Care (CRIC)  Copenhagen Denmark"},{"name":"University of Bern  Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4376-6538","authenticated-orcid":false,"given":"Maurizio","family":"Cecconi","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Department Humanitas University  Pieve Emanuele Italy"},{"name":"Department of Anaesthesia and Intensive Care IRCCS\u2010Humanitas Research Hospital  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7977-9410","authenticated-orcid":false,"given":"Marek","family":"Nalos","sequence":"additional","affiliation":[{"name":"Collaboration for Research in Intensive Care (CRIC)  Copenhagen Denmark"},{"name":"Department of Anaesthesiology, Perioperative and Intensive Care Medicine, Masaryk Hospital J.E. Purkinje University  Usti nad Labem Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9500-9080","authenticated-orcid":false,"given":"Marlies","family":"Ostermann","sequence":"additional","affiliation":[{"name":"Collaboration for Research in Intensive Care (CRIC)  Copenhagen Denmark"},{"name":"Department of Intensive Care Guy's and St Thomas' Hospital  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1816-5255","authenticated-orcid":false,"given":"Manu L. N. G.","family":"Malbrain","sequence":"additional","affiliation":[{"name":"Collaboration for Research in Intensive Care (CRIC)  Copenhagen Denmark"},{"name":"First Department of Anaesthesiology and Intensive Therapy Medical University of Lublin  Lublin Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6378-9673","authenticated-orcid":false,"given":"Morten Hylander","family":"M\u00f8ller","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Copenhagen University Hospital\u2014Rigshospitalet  Copenhagen Denmark"},{"name":"Collaboration for Research in Intensive Care (CRIC)  Copenhagen Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Science University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4668-0123","authenticated-orcid":false,"given":"Anders","family":"Perner","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Copenhagen University Hospital\u2014Rigshospitalet  Copenhagen Denmark"},{"name":"Collaboration for Research in Intensive Care (CRIC)  Copenhagen Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Science University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5799-7655","authenticated-orcid":false,"given":"Anders","family":"Granholm","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Copenhagen University Hospital\u2014Rigshospitalet  Copenhagen Denmark"},{"name":"Collaboration for Research in Intensive Care (CRIC)  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2023.04.036"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmc2210366"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/aas.13434"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1701380"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/aas.14345"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2021.09.010"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134\u2010019\u201005903\u20108"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040296"},{"key":"e_1_2_11_10_1","unstructured":"TRIPOD Group.TRIPOD checklist: prediction model development.2015:22."},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134\u2010023\u201007114\u20108"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc11454"},{"key":"e_1_2_11_13_1","doi-asserted-by":"crossref","unstructured":"ChenT GuestrinC.XGBoost: a scalable tree boosting system.2016;785\u2010794. doi:10.1145\/2939672.2939785","DOI":"10.1145\/2939672.2939785"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1214\/aos\/1013203450"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.inffus.2021.11.011"},{"key":"e_1_2_11_16_1","unstructured":"JonesDR SchonlauM WilliamJ.Efficient global optimization of expensive black\u2010box functions.1998;13:455\u2010492."},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-77244-8"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v080.i01"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/1740774510396933"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134\u2010021\u201006573\u20101"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134\u2010023\u201007024\u20109"}],"container-title":["Acta Anaesthesiologica Scandinavica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aas.14423","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T02:13:30Z","timestamp":1721960010000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/aas.14423"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,4]]},"references-count":20,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1111\/aas.14423"],"URL":"https:\/\/doi.org\/10.1111\/aas.14423","archive":["Portico"],"relation":{},"ISSN":["0001-5172","1399-6576"],"issn-type":[{"type":"print","value":"0001-5172"},{"type":"electronic","value":"1399-6576"}],"subject":[],"published":{"date-parts":[[2024,4,4]]},"assertion":[{"value":"2024-03-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}