{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T05:49:19Z","timestamp":1783144159313,"version":"3.54.6"},"reference-count":67,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,1,15]],"date-time":"2020-01-15T00:00:00Z","timestamp":1579046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction"],"published-print":{"date-parts":[[2020,6]]},"abstract":"Abstract<\/jats:title>Aim<\/jats:title>To understand the potential harmful effects of dose escalation among patients with chronic, non\u2010cancer pain (CNCP) on chronic opioid therapy.<\/jats:p><\/jats:sec>Design<\/jats:title>Retrospective cohort study.<\/jats:p><\/jats:sec>Setting<\/jats:title>United States Veterans Healthcare Administration.<\/jats:p><\/jats:sec>Participants<\/jats:title>Veterans with CNCP and on chronic opioid therapy were identified using data from fiscal years 2008\u201315. The Veteran sample was approximately 90% male and 70% white.<\/jats:p><\/jats:sec>Measurements<\/jats:title>Dose escalators [increase of\u00a0>\u00a020% average morphine milligram equivalent (MME) daily dose] were compared with dose maintainers (change of \u00b120% average MME daily dose). A composite measure of subsequent substance use disorders (SUDs: opioid, non\u2010opioid and alcohol use disorders) and opioid\u2010related adverse outcomes (AOs: accidents resulting in wounds\/injuries, opioid\u2010related and alcohol and non\u2010opioid medication\u2010related accidents and overdoses, self\u2010inflicted injuries) as well as the individual SUDs and AOs was examined. The primary analyses were conducted among a 1\u00a0:\u00a01 matched sample of escalators and maintainers matched on propensity score and index date. Propensity scores were generated using demographic characteristics, medical comorbidities, medication and health\u2010care utilization characteristics. Subgroup analyses were conducted by quartile of the propensity score. Sensitivity analyses were conducted using adjusted logistic regression, logistic regression using stabilized inverse probability of treatment weighting (SIPTW) and instrumental variable (IV) models using geographic variation in opioid dose escalation as the IV.<\/jats:p><\/jats:sec>Findings<\/jats:title>There were 32\u2009420 maintainers and 20\u2009767 escalators resulting in 19\u2009358 (93.2%) matched pairs. Composite AOs [odds ratio (OR)\u00a0=\u00a01.31, 95% confidence interval (CI)\u00a0= 1.23, 1.40], composite SUDs (OR\u00a0=\u00a01.31, 95% CI\u00a0=\u00a01.22, 1.41) and individual SUD and AO subtypes were higher among dose escalators, except for opioid\u2010related accidents and overdoses and violence\u2010related injuries. Subgroup analyses within the propensity score quartiles found similar results. Sensitivity analyses with the adjusted and SIPTW logistic regressions found similar results to the primary analyses for all outcomes except for opioid\u2010related accidents and overdoses, which were found to be significantly higher among escalators. Sensitivity analyses with IV models provided mixed results with SUDs and the individual types of AOs.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Escalating the opioid dose for those with chronic, non\u2010cancer pain is associated with increased risks of substance use disorder and opioid\u2010related adverse outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/add.14940","type":"journal-article","created":{"date-parts":[[2020,1,15]],"date-time":"2020-01-15T16:50:12Z","timestamp":1579107012000},"page":"1098-1112","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Impact of opioid dose escalation on the development of substance use disorders, accidents, self\u2010inflicted injuries, opioid overdoses and alcohol and non\u2010opioid drug\u2010related overdoses: a retrospective cohort study"],"prefix":"10.1111","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7776-6157","authenticated-orcid":false,"given":"Corey J.","family":"Hayes","sequence":"first","affiliation":[{"name":"Division of Health Services Research, College of Medicine University of Arkansas for Medical Sciences Little Rock AR USA"},{"name":"Center for Mental Healthcare and Outcomes Research, Central AR Veterans Healthcare System Little Rock AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin E.","family":"Krebs","sequence":"additional","affiliation":[{"name":"Center for Care Delivery and Outcomes Research, Minneapolis VA Healthcare System Minneapolis MN USA"},{"name":"Department of Medicine University of Minnesota Medical School Minneapolis MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Hudson","sequence":"additional","affiliation":[{"name":"Division of Health Services Research, College of Medicine University of Arkansas for Medical Sciences Little Rock AR USA"},{"name":"Center for Mental Healthcare and Outcomes Research, Central AR Veterans Healthcare System Little Rock AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Brown","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Safety, Department of Pharmaceutical Outcomes and Policy College of Pharmacy, University of Florida Gainsville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghui","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Evaluation and Policy, College of Pharmacy University of Arkansas for Medical Sciences Little Rock AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8402-3098","authenticated-orcid":false,"given":"Bradley C.","family":"Martin","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Evaluation and Policy, College of Pharmacy University of Arkansas for Medical Sciences Little Rock AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2019.01.003"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.8-6-567"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.0899"},{"key":"e_1_2_8_5_1","first-page":"129","article-title":"Age, gender, and earlier opioid requirement associations with the rate of dose escalation in long\u2010term opioid therapy","author":"Han H","year":"2013","journal-title":"J Opioid Manag"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0134550"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01335.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.5055\/jom.2017.0373"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/pme.12634"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S199243"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0134550"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2019.01.061"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/ADM.0000000000000458"},{"key":"e_1_2_8_14_1","unstructured":"About VHA\u2014Veterans Health Administration[internet] [cited 2018 Aug 24]. 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