{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T10:11:18Z","timestamp":1791886278435,"version":"4.3.4"},"reference-count":66,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["agsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J American Geriatrics Society"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Disturbances in sleep\u2013wake homeostasis (Process S) and circadian rhythm (Process C) are common precipitants of delirium, especially among older hospitalized adults. We conducted a systematic review and meta\u2010analysis to test whether four sleep\u2010modulation agents\u2014melatonin, ramelteon, suvorexant, and lemborexant\u2014lower delirium incidence or shorten its duration in hospitalized patients, with stratified analyses by drug class, age, and surgical status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We systematically searched PubMed, Embase, and CENTRAL through March 2025. We included randomized controlled trials (RCTs) and observational studies assessing delirium prevention with melatonin, ramelteon, suvorexant, and lemborexant in hospitalized adults (\u2265\u200918\u2009years), compared to placebo or standard care. Data synthesis was performed separately for RCTs and observational studies using random\u2010effects models. Meta\u2010regression was used to explore effect modifiers. Risk of bias was assessed using RoB2\/ROBINS\u2010I tools. Certainty of evidence was graded using the GRADE assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thirty\u2010seven studies (27 RCTs, 10 observational) comprising 7845 patients were included. Among RCTs, melatonin (RR 0.94; 95% CI 0.72\u20131.22) and ramelteon (RR 0.63; 95% CI 0.39\u20131.03) showed no significant effect on delirium incidence, whereas orexin receptor antagonists were associated with a lower risk (RR 0.55; 95% CI 0.35\u20130.87). Evidence for a class difference was inconsistent across analytic approaches: a subgroup heterogeneity test suggested differential effects (interaction\u2010\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.09), but the meta\u2010regression found no between\u2010class difference (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.14). No other specific test for subgroup differences was statistically significant in RCTs. Meta\u2010regression confirmed patient setting as a significant modifier in observational studies, but not in RCTs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Sleep\u2013wake pharmacotherapies may reduce incident delirium in hospitalized adults. In randomized trials, melatonin and ramelteon did not significantly reduce delirium incidence, whereas dual orexin receptor antagonists showed a possible benefit, but the meta\u2010regression did not demonstrate a reliable between\u2010class difference, and the evidence remains limited. Adequately powered randomized trials across inpatient settings are needed to clarify any true differences and define clinical relevance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jgs.70305","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T08:25:22Z","timestamp":1768551922000},"page":"1439-1449","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pharmacologic Modulation of Circadian Rhythms for Delirium Prevention: An Age\u2010Stratified Systematic Review and Meta\u2010Analysis"],"prefix":"10.1111","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0061-7492","authenticated-orcid":false,"given":"Helen Michaela","family":"de Oliveira","sequence":"first","affiliation":[{"name":"Department of Medicine Federal University of Mato Grosso  Sinop Mato Grosso Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariano","family":"Gallo Ruelas","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Nutricional (IIN)  Lima Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tariq","family":"Parker","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Massachusetts General Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilo Andr\u00e9 Viana","family":"Diaz","sequence":"additional","affiliation":[{"name":"Department of Medicine Federal University of Tri\u00e2ngulo Mineiro  Uberaba Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme","family":"Oliveira de Paula","sequence":"additional","affiliation":[{"name":"Department of Medicine Federal University of Mato Grosso  Sinop Mato Grosso Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda Valeriano","family":"Zamora","sequence":"additional","affiliation":[{"name":"Department of Medicine Federal University of Minas Gerais  Belo Horizonte Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo Ramon","family":"Fruett da Costa","sequence":"additional","affiliation":[{"name":"Department of Functional Neurosurgery Sinedor Clinic  Sinop Mato Grosso Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100041\u20101733791"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010022\u201000698\u20107"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2020.06.063"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100044\u20101791666"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26617"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12871\u2010023\u201002163\u20104"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.14789\/jmj.JMJ21\u20100035\u2010R"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaclp.2025.05.003"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000006737"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755\u20105949.2008.00066.x"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010pharmtox\u2010010510\u2010100528"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2013.00230"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010015\u20100419\u20105"},{"issue":"2","key":"e_1_2_12_15_1","first-page":"225","article-title":"Intravenous Dexmedetomidine Prolongs Bupivacaine Spinal Analgesia","volume":"20","author":"Al\u2010Mustafa M. 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