{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:58:06Z","timestamp":1787018286255,"version":"build-2736575974"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1065571"],"award-info":[{"award-number":["1065571"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1065571"],"award-info":[{"award-number":["1065571"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Regular, low-dose, sustained-release morphine is frequently prescribed for persistent breathlessness in chronic obstructive pulmonary disease (COPD). However, effects on daytime sleepiness, perceived sleep quality, and daytime function have not been rigorously investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We sought to determine the effects of regular, low-dose, sustained-release morphine on sleep parameters in COPD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted prespecified secondary analyses of validated sleep questionnaire data from a randomized trial of daily, low-dose, sustained-release morphine versus placebo over 4\u2009weeks commencing at 8 or 16\u2009mg\/d with blinded up-titration over 2\u2009weeks to a maximum of 32\u2009mg\/d. Primary outcomes for these analyses were Week-1 Epworth Sleepiness Scale (ESS) and Karolinska Sleepiness Scale (KSS) scores on morphine versus placebo. Secondary outcomes included Leeds Sleep Evaluation Questionnaire scores (end of Weeks 1 and 4), KSS and ESS scores beyond Week 1, and associations between breathlessness, morphine, and questionnaire scores.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>One hundred fifty-six people were randomized. Week-1 sleepiness scores were not different on morphine versus placebo (\u0394ESS [95% confidence interval] versus placebo: 8-mg group, \u22120.59 [\u22121.99, 0.81], P\u2009=\u20090.41; 16-mg group, \u22120.72 [\u22122.33, 0.9], P\u2009=\u20090.38; \u0394KSS vs. placebo, 8-mg group: 0.11 [\u22120.7, 0.9], P\u2009=\u20090.78; 16-mg group, \u22120.41 [\u22121.31, 0.49], P\u2009=\u20090.37). This neutral effect persisted at later time points. In addition, participants who reported reduced breathlessness with morphine at 4\u2009weeks also showed improvement in LSEQ domain scores including perceived sleep quality and daytime function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Regular, low-dose morphine does not worsen sleepiness when used for breathlessness in COPD. Individual improvements in breathlessness with morphine may be related to improvements in sleep.<\/jats:p>\n                    <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT 02720822).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202310-1780oc","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T09:51:42Z","timestamp":1710323502000},"page":"1113-1122","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":7,"title":["Low-Dose Morphine Does Not Cause Sleepiness in Chronic Obstructive Pulmonary Disease: A Secondary Analysis of a Randomized Clinical Trial"],"prefix":"10.1093","volume":"210","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1979-8975","authenticated-orcid":false,"given":"Thomas J.","family":"Altree","sequence":"first","affiliation":[{"name":"Flinders Health and Medical Research Institute\u2013Adelaide Institute for Sleep Health, Flinders University, Bedford Park, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6661-9971","authenticated-orcid":false,"given":"Barbara","family":"Toson","sequence":"additional","affiliation":[{"name":"Flinders Health and Medical Research Institute\u2013Adelaide Institute for Sleep Health, Flinders University, Bedford Park, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3302-5995","authenticated-orcid":false,"given":"Kelly A.","family":"Loffler","sequence":"additional","affiliation":[{"name":"Flinders Health and Medical Research Institute\u2013Adelaide Institute for Sleep Health, Flinders University, Bedford Park, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7227-5113","authenticated-orcid":false,"given":"Magnus","family":"Ekstr\u00f6m","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Clinical Sciences, Respiratory Medicine, Allergology and Palliative Medicine, Lund University, Lund, Sweden"},{"name":"Faculty of Health, Improving Palliative, Aged and Chronic Care through Clinical Research and Translation (IMPACCT), University of Technology Sydney, Ultimo, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1988-1250","authenticated-orcid":false,"given":"David C.","family":"Currow","sequence":"additional","affiliation":[{"name":"Faculty of Health, Improving Palliative, Aged and Chronic Care through Clinical Research and Translation (IMPACCT), University of Technology Sydney, Ultimo, New South Wales, Australia"},{"name":"Faculty of 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