{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:45:05Z","timestamp":1787013905421,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T00:00:00Z","timestamp":1593993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MRC Biostatistics Unit core\u2010funds"],"award-info":[{"award-number":["MRC Biostatistics Unit core\u2010funds"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>As methadone clients age, their drug\u2010related death (DRD) risks increase, more than doubling at 45+ years for methadone\u2010specific DRDs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using Community Health Index (CHI) numbers, mortality to 31 December 2015 was ascertained for 36 347 methadone\u2010prescription clients in Scotland during 2009\u20132015. Cohort entry, quantity of prescribed methadone and daily dose (actual or recovered by effective, simple rules) were defined by clients' first CHI\u2010identified methadone prescription after 30 June 2009 and used in proportional hazards analysis. As custodian of death records, National Records of Scotland identified non\u2010DRDs from DRDs. Methadone\u2010specific DRD means methadone was implicated but neither heroin nor buprenorphine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The cohort's 192 928 person\u2010years included 1857 non\u2010DRDs and 1323 DRDs (42%), 546 of which were methadone specific. Actual\/recovered daily dose was available for 26 533 (73%) clients who experienced 420 methadone\u2010specific DRDs. Top quintile for daily dose at first CHI\u2010identified methadone prescription was &gt;90 mg. Age 45+ years at cohort\u2010entry (hazard ratio\n                      <jats:italic>vs<\/jats:italic>\n                      25\u201334 years: 3.1, 95% confidence interval: 2.4\u20134.2), top quintile for baseline daily dose of prescribed methadone (\n                      <jats:italic>vs<\/jats:italic>\n                      50\u201370 mg: 1.9, 1.1\u20133.1) and being female (1.3, 1.0\u20131.6) significantly increased clients' risk of methadone\u2010specific DRD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Extra care is needed when methadone daily dose exceeds 90 mg. Females' higher risk for methadone\u2010specific DRD is new and needs validation. Further analyses of prescribed daily dose linked to mortality for large cohorts of methadone clients are needed internationally, together with greater pharmacodynamic and pharmacokinetic understanding of methadone by age and sex. Balancing age\u2010related risks is challenging for prescribers who manage chronic opiate dependency against additional uncertainty about the nature, strength and pharmacological characteristics of drugs from illegal markets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bcp.14432","type":"journal-article","created":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T06:12:05Z","timestamp":1591942325000},"page":"652-673","source":"Crossref","is-referenced-by-count":8,"title":["Scotland's 2009\u20132015 methadone\u2010prescription cohort: Quintiles for daily dose of prescribed methadone and risk of methadone\u2010specific death"],"prefix":"10.1111","volume":"87","author":[{"given":"Lu","family":"Gao","sequence":"first","affiliation":[{"name":"MRC Biostatistics Unit University of Cambridge School of Clinical Medicine  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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