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BMJ Open Is Committed to Open Peer Review. As Part of This Commitment We Make the Peer Review History of Every Article We Publish Publicly Available BMJ Open: first published as 10.1136/bmjopen-2019-030858 on 6 September 2019. Downloaded from BMJ Open is committed to open peer review. As part of this commitment we make the peer review history of every article we publish publicly available. When an article is published we post the peer reviewers’ comments and the authors’ responses online. We also post the versions of the paper that were used during peer review. These are the versions that the peer review comments apply to. The versions of the paper that follow are the versions that were submitted during the peer review process. They are not the versions of record or the final published versions. They should not be cited or distributed as the published version of this manuscript. BMJ Open is an open access journal and the full, final, typeset and author-corrected version of record of the manuscript is available on our site with no access controls, subscription charges or pay-per-view fees (http://bmjopen.bmj.com). If you have any questions on BMJ Open’s open peer review process please email [email protected] http://bmjopen.bmj.com/ on September 26, 2021 by guest. Protected copyright. BMJ Open BMJ Open: first published as 10.1136/bmjopen-2019-030858 on 6 September 2019. Downloaded from Characterization of Concurrent Use of Prescription Opioids and Benzodiazepine/Z Drugs In Alberta: A Population- Based Study ForJournal: peerBMJ Open review only Manuscript ID bmjopen-2019-030858 Article Type: Research Date Submitted by the 04-Apr-2019 Author: Complete List of Authors: Sharma, Vishal; University of Alberta, School of Public Health Weir, Daniala; Mcgill Clinical and Health Informatics, Samanani, Salim; Okaki Health Intelligence, Simpson, Scot H.; University of Alberta, Pharmacy and Pharmaceutical Sciences Gilani, Fizza; The College of Physicians & Surgeons of Alberta Jess, Ed; The College of Physicians & Surgeons of Alberta, Eurich, Dean; University of Alberta, School of Public Health opioids, benzodiazepines, benzodiazepine receptor agonists, concurrent Keywords: use, PUBLIC HEALTH, concurrent prescribing http://bmjopen.bmj.com/ on September 26, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 1 of 27 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2019-030858 on 6 September 2019. Downloaded from 1 2 3 Characterization of Concurrent Use of Prescription Opioids and Benzodiazepine/Z Drugs In Alberta: A 4 Population-Based Study 5 6 7 8 Author list 9 10 Vishal Sharma (0000-0001-7907-1183), Daniala L Weir (0000-0001-7044-2443), Salim Samanani (0000-0001- 11 6751-4805), Scot Simpson (0000-0002-9880-2129), Fizza Gilani (0000-0002-1708-7451), Ed Jess, Dean Eurich 12 (0000-0003-2197-0463) 13 14 Address for each author 15 16 2-040 Li Ka Shing CenterFor for Health peer Research Innovation,review School of only Public Health, University of Alberta, 17 Edmonton, Alberta, Canada, T6G 2E1 Vishal Sharma BPharm MSc Candidate, Clinical and Health 18 Informatics Research Group, Department of Epidemiology, Biostatistics and Occupational Health, McGill 19 University, Montreal, Quebec, Canada Daniala L Weir PhD Candidate, OKAKI Health intelligence, Calgary, 20 21 Alberta, Canada Salim Samanani CEO and Medical Director OKAKI, Faculty of Pharmacy and 22 Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada, T6G 2E1 Scot Simpson 23 professor, The College of Physicians & Surgeons of Alberta, Edmonton, Alberta, Canada, T5J 0N3 Fizza 24 Gilani Program Manager Prescribing & Analytics, The College of Physicians & Surgeons of Alberta, 25 Edmonton, Alberta, Canada, T5J 0N3 Ed Jess Director of Prescribing & Analytics, 2-040 Li Ka Shing Center 26 27 for Health Research Innovation, School of Public Health, University of Alberta, Edmonton, Alberta, 28 Canada, T6G 2E1 Dean Eurich professor 29 30 Corresponding Author: 31 32 Dean Eurich, 2-040 Li Ka Shing Center for Health Research Innovation, University of Alberta, Edmonton, 33 Alberta, Canada, T6G 2E1; Phone 780-492-6333; fax 780-492-7455; email: [email protected] http://bmjopen.bmj.com/ 34 35 36 37 38 39 40 41 on September 26, 2021 by guest. Protected copyright. 42 ACKNOWLEDGEMENT – This study is based in part on data provided by Alberta Health and was 43 commissioned by the College of Physicians & Surgeons of Alberta (CPSA). The interpretation and 44 conclusions contained herein are those of the researchers and do not necessarily represent the views of the 45 Government of Alberta or CPSA. Neither the Government of Alberta nor Alberta Health expresses any 46 47 opinion in relation to this study. 48 49 50 51 52 53 54 55 56 57 58 1 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 2 of 27 BMJ Open: first published as 10.1136/bmjopen-2019-030858 on 6 September 2019. Downloaded from 1 2 3 Contributors: VS DE SS and DLW were involved in the conception and design of the study. VS and DE 4 analyzed the data. VS and DE drafted the article. EJ SS FG DLW and SS revised the article. All authors 5 6 gave final approval of the version to be published. The corresponding author attests that all listed 7 authors meet authorship criteria and that no others meeting the criteria have been omitted. DE is the 8 guarantor. 9 10 Funding: This study received no funding. 11 12 Copyright/license for publication: The Corresponding Author has the right to grant on behalf of all 13 authors and does grant on behalf of all authors, a worldwide licence to the Publishers and its licensees in 14 perpetuity, in all forms, formats and media (whether known now or created in the future), to i) publish, 15 reproduce, distribute, display and store the Contribution, ii) translate the Contribution into other 16 For peer review only 17 languages, create adaptations, reprints, include within collections and create summaries, extracts 18 and/or, abstracts of the Contribution, iii) create any other derivative work(s) based on the Contribution, 19 iv) to exploit all subsidiary rights in the Contribution, v) the inclusion of electronic links from the 20 Contribution to third party material where-ever it may be located; and, vi) licence any third party to do 21 22 any or all of the above. 23 24 Competing Interest: All authors have completed the ICMJE uniform disclosure form at 25 www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted 26 27 work; Salim Samanani has received research grants from the College of Physicians & Surgeons 28 29 of Alberta; no other relationships or activities that could appear to have influenced the submitted 30 31 work. 32 33 Ethical approval: This study was approved by the health ethics research board at the University of http://bmjopen.bmj.com/ 34 Alberta (#Pro00083807). 35 36 Data Sharing: The data used in this study is not available for external analysis. However, administrative 37 health data can be accessed from AH by following defined research protocols and confidentiality 38 agreements. 39 40 Transparency: The lead author (the manuscript's guarantor) affirms that the manuscript is an honest, 41 accurate, and transparent account of the study being reported; that no important aspects of the study on September 26, 2021 by guest. Protected copyright. 42 have been omitted; and that any discrepancies from the study as originally planned (and, if relevant, 43 44 registered) have been explained. 45 46 Summary Box: 47 Section 1: What is already known on this topic 48 49 Prescribed opioids are a major contributor to the opioid crisis and a substantial number of opioid related 50 deaths also involve benzodiazepines. 51 52 Numerous health authorities and medical associations warn against concurrent prescribing of opioids 53 54 and benzodiazepines. 55 56 57 58 2 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 3 of 27 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2019-030858 on 6 September 2019. Downloaded from 1 2 3 Although it is known that women, the elderly and chronic opioid users have a higher prevalence of 4 concurrent use, characterization of concurrent use of benzodiazepines within the opioid using 5 6 population has not been adequately carried out using potential markers of inappropriate use. 7 8 Section 2: What this study adds 9 The prevalence of concurrent use of opioids and benzodiazepines is alarmingly high especially among 10 11 chronic and high dose opioid users, high users of the health care system, opioid dependency treatment 12 patients, and the elderly. 13 14 The warnings against concurrent use of opioids and benzodiazepines from health authorities and 15 medical associations need to be further emphasized through education and policies. 16 For peer review only 17 More health care resources must be allocated towards treatment programs for substance abuse 18 disorders, chronic pain and mental health. 19 20 21 22 Word Count: 2909 23 24 25 26 27 28 29 30 31 32 33 http://bmjopen.bmj.com/ 34 35 36 37 38 39 40 41 on September 26, 2021 by guest. Protected copyright. 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 3 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 4 of 27 BMJ Open: first published as 10.1136/bmjopen-2019-030858 on 6 September 2019. Downloaded from 1 2 3 Abstract 4 5 6 Objective: The objective of this study is to characterize concurrent use of benzodiazepines among 7 8 prescription opioid users in Alberta in 2017. 9 10 11 Design: A population based retrospective study. 12 13 14 Setting: Alberta, Canada in the year 2017.
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