{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:54:52Z","timestamp":1791266092353,"version":"4.1.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Artif. Intell."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sedation is frequently required in the intensive care unit (ICU), but benzodiazepines may worsen respiratory outcomes in patients with chronic obstructive pulmonary disease (COPD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate whether early midazolam exposure after ICU admission is associated with the short-term risk of acute exacerbation of COPD (AECOPD) among critically ill COPD patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, we emulated a target trial and applied a clone-censor-weight (CCW) approach to address immortal time bias and informative censoring. Exposure was midazolam administration within a grace period after ICU admission (primary: 24\u202fh; sensitivity: 12 and 36\u202fh). The primary outcome was AECOPD, defined as initiation of systemic corticosteroids or antibiotics between 24\u202fh and 7\u202fdays after ICU admission. Outcomes were compared using inverse probability of censoring weights (IPCW).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 3,416 ICU stays, 233 (6.8%) received midazolam within 24\u202fh. After IPCW weighting, AECOPD incidence was 29.8% in the midazolam group versus 23.5% in controls (risk difference +6.3%, 95% CI \u22122.7% to +15.8%; odds ratio 1.38, 95% CI 0.86\u20132.12;\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.158). Findings were directionally consistent across grace periods (12\u202fh OR 1.64; 36\u202fh OR 1.29), but none of the grace-period comparisons reached statistical significance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In the primary 24\u202fh analysis, early midazolam exposure was associated with a numerically higher short-term AECOPD risk. These observational findings cannot establish causality, and the present study did not demonstrate a statistically significant causal effect; nevertheless, in view of existing ICU sedation evidence, continued caution in the use of midazolam in critically ill COPD patients appears prudent.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/frai.2026.1836581","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:21:57Z","timestamp":1791264117000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Early midazolam exposure and short-term risk of acute exacerbation of COPD in critically ill patients: a target trial emulation using the MIMIC-IV database"],"prefix":"10.3389","volume":"9","author":[{"given":"Guoping","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Dongguan Qingxi Hospital","place":["Dongguan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Dongguan Qingxi Hospital","place":["Dongguan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e20230369","DOI":"10.36416\/1806-3756\/e20230369","article-title":"GOLD 2024: a brief overview of key changes","volume":"49","author":"Agusti","year":"2023","journal-title":"J Brasil Pneumol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"4227","DOI":"10.1002\/sim.9507","article-title":"CAPITAL: optimal subgroup identification via constrained policy tree search","volume":"41","author":"Cai","year":"2022","journal-title":"Stat. 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