{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T16:34:20Z","timestamp":1793378060168,"version":"4.5.0"},"reference-count":32,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2019,12,18]],"date-time":"2019-12-18T00:00:00Z","timestamp":1576627200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Hosp Pharm"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:p>\n                    Introduction: Concurrent opioid and benzodiazepine use (\u201cdouble-threat\u201d) and double-threat and muscle relaxant use (\u201ctriple-threat\u201d) are postulated to increase morbidity versus opioids alone. Study objectives were to measure association between double- and triple-threat exposure and hospitalizations in a validated, nationally representative database of the United States. Methods: A retrospective cohort study was conducted using the 2013 and 2014 Medical Expenditure Panel Survey (MEPS) longitudinal dataset and affiliated Prescribed Medicines Files. Association between 2013 and 2014 double- and triple-threat exposures and outcome of hospitalizations compared to nonusers, opioid users, and all combinations were assessed via logistic regression. The cohort surveyed in MEPS has been weighted to be reflective of the actual US population in the years 2013 and 2014. Logistic regression applying the subject-level MEPS survey weights was performed to measure association via odds ratios (ORs) of medication exposures with the outcome of all-cause hospitalization. Study subjects were categorized into exposure groups as nonusers (nonuse of opioids, benzodiazepines, or muscle relaxants), opioid users, benzodiazepine users, muscle relaxant users, \u201cdouble-threat\u201d users, and \u201ctriple-threat\u201d users. Analyses were conducted using RStudio\n                    <jats:sup>\u00ae<\/jats:sup>\n                    1.1.5 (Boston, MA) with \u03b1 level = 0.05 for all comparisons. Results: Opioids, benzodiazepines, and muscle relaxants were used in 11.9% (38.4 million), 4.2% (13.5 million), and 3.4% (10.9 million) lives of the United States in 2013, respectively. Double-threat prevalence rose from 1.6% to 1.9% from 2013 to 2014. Triple-threat prevalence remained unchanged at 0.53%. Compared to nonusers, triple-threat patients increased hospitalization probability with ORs of 8.52 (95% confidence interval [CI]: 8.50-8.55) in 2013, 5.06 (95% CI: 5.04-5.08) in 2014, and 4.61 (95% CI: 4.59-4.63) in the 2013-2014 longitudinal analysis. Compared to nonusers, double-threat patients increased hospitalization probability with ORs of 5.71 (95% CI: 5.69-5.72) in 2013, 11.47 (95% CI: 11.44-11.49) in 2014, and 5.59 (95% CI: 5.57-5.60) in the longitudinal analysis. Conclusion: Concurrent opioid and benzodiazepine use and opioid, benzodiazepine, and muscle relaxant use were associated with increased hospitalization likelihood. Amplified efforts in surveillance, prescribing, monitoring, and deprescribing for concurrent opioid, benzodiazepine, and muscle relaxant use are needed to reduce this public health concern.\n                  <\/jats:p>","DOI":"10.1177\/0018578719894702","type":"journal-article","created":{"date-parts":[[2019,12,18]],"date-time":"2019-12-18T04:55:08Z","timestamp":1576644908000},"page":"286-291","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":11,"title":["Hospitalization and Combined Use of Opioids, Benzodiazepines, and Muscle Relaxants in the United States"],"prefix":"10.1177","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2543-5305","authenticated-orcid":false,"given":"Jonathan H.","family":"Watanabe","sequence":"first","affiliation":[{"name":"University of California San Diego, La Jolla, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jincheng","family":"Yang","sequence":"additional","affiliation":[{"name":"University of California San Diego, La Jolla, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,12,18]]},"reference":[{"key":"bibr1-0018578719894702","unstructured":"CDC Injury Center. Understanding the epidemic. Drug overdose. https:\/\/www.cdc.gov\/drugoverdose\/epidemic\/index.html. Published July 24, 2019. Accessed October 8, 2019."},{"key":"bibr2-0018578719894702","unstructured":"National Institute on Drug Abuse. Overdose death rates. https:\/\/www.drugabuse.gov\/related-topics\/trends-statistics\/overdose-death-rates. Published January 29, 2019. Accessed September 12, 2019."},{"key":"bibr3-0018578719894702","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm655051e1"},{"key":"bibr4-0018578719894702","unstructured":"Centers for Disease Control and Prevention (CDC). U.S. drug overdose deaths continue to rise; increase fueled by synthetic opioids. CDC Online Newsroom. https:\/\/www.cdc.gov\/media\/releases\/2018\/p0329-drug-overdose-deaths.html. Published September 24, 2018. Accessed April 16, 2019."},{"key":"bibr5-0018578719894702","unstructured":"The White House. Council of economic advisers report: the underestimated cost of the opioid crisis. https:\/\/www.whitehouse.gov\/briefings-statements\/cea-report-underestimated-cost-opioid-crisis\/. Published November 20, 2017. Accessed April 17, 2019."},{"key":"bibr6-0018578719894702","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4637.2011.01075.x"},{"key":"bibr7-0018578719894702","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.j760"},{"key":"bibr8-0018578719894702","doi-asserted-by":"publisher","DOI":"10.1002\/pds.3776"},{"key":"bibr9-0018578719894702","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704459"},{"key":"bibr10-0018578719894702","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.151142"},{"key":"bibr11-0018578719894702","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.12655"},{"key":"bibr12-0018578719894702","unstructured":"L.A. Care Health Plan. Point-of-sale safety alerts. http:\/\/www.lacare.org\/tl\/node\/29188. Published February 21, 2019. Accessed April 17, 2019."},{"key":"bibr13-0018578719894702","unstructured":"Medical Expenditure Panel Survey Home. https:\/\/meps.ahrq.gov\/mepsweb\/. Accessed September 17, 2019."},{"issue":"4","key":"bibr14-0018578719894702","first-page":"373","volume":"33","author":"Cohen JW","year":"1996","journal-title":"Inquiry"},{"issue":"7","key":"bibr15-0018578719894702","first-page":"III5","volume":"41","author":"Cohen SB.","year":"2003","journal-title":"Med Care"},{"key":"bibr16-0018578719894702","unstructured":"World Health Organization. 3. Defined Daily Dose (DDD). http:\/\/www.who.int\/medicines\/regulation\/medicines-safety\/toolkit_ddd\/en\/. Accessed October 8, 2019."},{"key":"bibr17-0018578719894702","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.2016.303061"},{"key":"bibr18-0018578719894702","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2012.07.007"},{"key":"bibr19-0018578719894702","doi-asserted-by":"publisher","DOI":"10.1097\/AAP.0000000000000022"},{"key":"bibr20-0018578719894702","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13776"},{"key":"bibr21-0018578719894702","doi-asserted-by":"publisher","DOI":"10.3928\/02793695-20180521-03"},{"key":"bibr22-0018578719894702","unstructured":"US Food & Drug Administration (FDA). New Safety Measures Announced for Opioid Analgesics, Prescription Opioid Cough Products, and Benzodiazepines. http:\/\/www.fda.gov\/drugs\/information-drug-class\/new-safety-measures-announced-opioid-analgesics-prescription-opioid-cough-products-and. Published 2019. Accessed September 20, 2019."},{"key":"bibr23-0018578719894702","unstructured":"CMS. 2019 Medicare advantage and Part D rate announcement and call letter. https:\/\/www.cms.gov\/newsroom\/fact-sheets\/2019-medicare-advantage-and-part-d-rate-announcement-and-call-letter. Published 2018. Accessed September 20, 2019."},{"key":"bibr24-0018578719894702","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.rr6501e1"},{"key":"bibr25-0018578719894702","doi-asserted-by":"publisher","DOI":"10.7812\/TPP\/16-169"},{"key":"bibr26-0018578719894702","doi-asserted-by":"publisher","DOI":"10.1331\/JAPhA.2013.13040"},{"key":"bibr27-0018578719894702","unstructured":"2016-2017 prescription drug monitoring program annual report. http:\/\/www.floridahealth.gov\/statistics-and-data\/e-forcse\/funding\/2017pdmpannualreport.pdf. Published 2017. Accessed September 19, 2019."},{"key":"bibr28-0018578719894702","unstructured":"State of Illinois opioid action plan. http:\/\/dph.illinois.gov\/sites\/default\/files\/publications\/Illinois-Opioid-Action-Plan-Sept-6-2017-FINAL.pdf. Published 2017. Accessed September 19, 2019."},{"key":"bibr29-0018578719894702","unstructured":"Model Prescription Monitoring Program (PMP) Act. https:\/\/namsdl.org\/wp-content\/uploads\/Model-Prescription-Monitoring-Program-PMP-Act.pdf. Published 2015. Accessed September 18, 2019."},{"key":"bibr30-0018578719894702","unstructured":"CMCS Informational Bulletin. https:\/\/www.medicaid.gov\/federal-policy-guidance\/downloads\/cib-02-02-16.pdf. Accessed September 19, 2019."},{"key":"bibr31-0018578719894702","doi-asserted-by":"publisher","DOI":"10.1097\/MLR.0000000000000861"},{"key":"bibr32-0018578719894702","unstructured":"Pharmacy Healthcare Solutions. PQA opioid core measure set. http:\/\/phsirx.com\/blog\/pqa-opioid-core-measure-set. 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