{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:11:23Z","timestamp":1784592683573,"version":"3.55.0"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":46,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JJ Mason & HS Williams Memorial Fund"},{"name":"The Julia Lowy Foundation"},{"name":"Harry Triguboff Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Delirium affects up to 25% of hospitalised older patients; however, there are no effective pharmacological treatments. Accumulating evidence of brain insulin resistance and altered cerebral glucose metabolism during delirium present a promising therapeutic target.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To assess the safety and efficacy of intranasal insulin in the treatment of delirium.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Single-centre, randomised, double-blind, placebo-controlled trial.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>Two geriatric medicine wards in a tertiary hospital.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>100 patients aged over 64\u00a0years presenting to hospital and admitted under geriatric medicine with delirium.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Interventions<\/jats:title>\n                  <jats:p>Participants were randomised in a 1:1 ratio to receive 20\u00a0IU of long-acting insulin or placebo intranasally twice daily until delirium resolution, hospital discharge or intervention futility defined by prespecified criteria.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main outcome<\/jats:title>\n                  <jats:p>The primary outcome was delirium duration, assessed daily using the Confusion Assessment Method. Secondary outcomes included acute length of stay (LOS), delirium severity, antipsychotic use, hospital complications and mortality.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The intention-to-treat analysis included 97 participants [intranasal insulin n\u00a0=\u200948, control n\u00a0=\u200949; mean (SD) age, 87.6 (7.0) years; 63% female]. Baseline characteristics were similar between groups. Median delirium duration [days (IQR)] was 4.8 [2.9, 9.2] for intranasal insulin and 6.8 [4.0, 9.8] for the control (HR 0.7, 95% CI 0.43\u20131.15; P\u00a0=\u2009.16). Median acute LOS (days) was 7.9 [4.6, 14.5] for intranasal insulin and 12.9 [6.9, 16.8] for the control (HR 0.56, 0.35\u20130.89; P\u00a0=\u2009.014). No significant differences were observed in other secondary outcomes. Intranasal insulin demonstrated favourable tolerability. Overall, 86% of the participants were compliant with the intervention (\u226580% of doses). Prespecified subgroup analysis revealed an age-related response, with participants aged \u226488\u00a0years showing shorter delirium duration with intranasal insulin [n\u00a0=\u200946; intranasal insulin: median 3.9 (IQR 2.9, 6.9) days vs control: 7.0 (4.7, 9.7); HR 0.34, 0.16\u20130.74; P\u00a0=\u2009.006], whereas no difference was observed in participants aged &amp;gt;88\u00a0years [n\u00a0=\u200951; intranasal insulin 5.4 (2.9, 11.1) vs control 4.9 (2.6, 12.9); HR 0.87, 0.39\u20131.94; P\u00a0=\u2009.73].<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion and relevance<\/jats:title>\n                  <jats:p>This is the first study of intranasal insulin for delirium treatment. The reduced LOS combined with the observed age-related effects warrants further investigation into the clinical potential of intranasal insulin in managing delirium in older patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration<\/jats:title>\n                  <jats:p>ACTRN 12618000318280.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ageing\/afaf276","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T17:31:50Z","timestamp":1760549510000},"source":"Crossref","is-referenced-by-count":8,"title":["Long-acting intranasal insulin for the treatment of delirium\u2014a randomised clinical trial"],"prefix":"10.1093","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9215-0844","authenticated-orcid":false,"given":"Anita","family":"Nitchingham","sequence":"first","affiliation":[{"name":"Randwick Clinical Campus, University of New South Wales , Randwick, NSW ,","place":["Australia"]},{"name":"Department of Geriatric Medicine, Prince of Wales Hospital and Community Health Services , Randwick, NSW ,","place":["Australia"]},{"name":"Falls, Balance and Injury Research Centre, Neuroscience Research Australia , Randwick, NSW ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2908-9507","authenticated-orcid":false,"given":"Jacqueline C T","family":"Close","sequence":"additional","affiliation":[{"name":"Randwick Clinical Campus, University of New South Wales , Randwick, NSW ,","place":["Australia"]},{"name":"Department of Geriatric Medicine, Prince of Wales Hospital and Community Health Services , Randwick, NSW ,","place":["Australia"]},{"name":"Falls, Balance and Injury Research Centre, Neuroscience Research Australia , Randwick, NSW ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6260-8001","authenticated-orcid":false,"given":"Lara Ann","family":"Harvey","sequence":"additional","affiliation":[{"name":"Falls, Balance and Injury Research Centre, Neuroscience Research Australia , Randwick, NSW ,","place":["Australia"]},{"name":"School of Public Health and Community Medicine, University of New South Wales , Sydney, NSW ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morag E","family":"Taylor","sequence":"additional","affiliation":[{"name":"Falls, Balance and Injury Research Centre, Neuroscience Research Australia , Randwick, NSW ,","place":["Australia"]},{"name":"School of Health Sciences, University of New South Wales , Sydney, NSW ,","place":["Australia"]},{"name":"Ageing Futures Institute, University of New South Wales , Sydney, NSW 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