Carina D'Aiuto: Department of Community Health Sciences, Faculty of Medicine and Health Sciences, University of Sherbrooke, 150 Place Charles-Le Moyne, Longueuil, QC, J4K 0A8, Canada. ORCID
Carlotta Lunghi: Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. ORCID
Line Gu��nette: Population Health and Optimal Health Practices Research Unit, CHU de Qu��bec Research Center, Qu��bec City, QC, Canada. ORCID
Djamal Berbiche: Department of Community Health Sciences, Faculty of Medicine and Health Sciences, University of Sherbrooke, 150 Place Charles-Le Moyne, Longueuil, QC, J4K 0A8, Canada. ORCID
Karine Bertrand: Department of Community Health Sciences, Faculty of Medicine and Health Sciences, University of Sherbrooke, 150 Place Charles-Le Moyne, Longueuil, QC, J4K 0A8, Canada. ORCID
Helen-Maria Vasiliadis: Department of Community Health Sciences, Faculty of Medicine and Health Sciences, University of Sherbrooke, 150 Place Charles-Le Moyne, Longueuil, QC, J4K 0A8, Canada. Helen-maria.vasiliadis@usherbrooke.ca. ORCID
INTRODUCTION AND OBJECTIVE: As the population ages, understanding the potential risks associated with inappropriate medication use becomes increasingly important. Given the lack of studies in this area, our objective was to study the risk of mortality associated with potentially inappropriate medication use involving opioids in community-dwelling older adults. METHODS: Data came from a longitudinal study on older adults aged ������65 years recruited in primary care clinics between 2011 and 2013 with an average follow-up of 4.25 years. Older adults were excluded if they used an opioid or had a malignant tumor diagnosis in the year before the study survey. A nested case-control within a cohort of older adults with at least one opioid claim during follow-up was used to evaluate the risk of all-cause mortality. Four controls per case were matched on follow-up time using risk-set sampling, i.e., while still at risk of death when their matched case died. The risk of mortality was estimated using conditional logistic regression analyses. Exposure to potentially inappropriate medication use involving opioids, defined using the Beers 2019 criteria, was assessed from provincial drug claims data in the 0-90 days before death. RESULTS: In a cohort of 472 community-dwelling older adults with an incident episode of opioid use, there were 40 cases matched to 160 controls. Exposure to inappropriate medication use involving opioids in the 90 days before death was associated with an increased risk of mortality (odds ratio 6.81, 95% confidence interval 1.69-27.47), after adjusting for potential confounders. CONCLUSIONS: Exposure to inappropriate medication use involving opioids in the 90 days before death is associated with an increased risk of mortality in older adults. These findings can be used to encourage safer pain management strategies in older adults.
References
Organisation for Economic Co-operation and Development (OECD). Urgent action needed to address growing opioid crisis. 2019. https://www.oecd.org/canada/urgent-action-needed-to-address-growing-opioid-crisis.htm . Accessed 5 Mar 2020.
Canadian Centre on Substance Use and Addiction (CCSA). Canadian Drug Summary: Opioids. 2022. https://www.ccsa.ca/opioids-canadian-drug-summary . Accessed 28 Nov 2022.
American Geriatrics Society. American Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67(4):674���94. https://doi.org/10.1111/jgs.15767 .
[DOI: 10.1111/jgs.15767]
Canadian Institute for Health Information (CIHI). Hospitalizations and Emergency Department Visits Due to Opioid Poisoning in Canada. 2016. https://secure.cihi.ca/free_products/Opioid%20Poisoning%20Report%20%20EN.pdf . Accessed 27 July 2022.
D'Aiuto C, Lunghi C, Gu��nette L, Berbiche D, Bertrand K, Vasiliadis HM. Health care system costs related to potentially inappropriate medication use involving opioids in older adults in Canada. BMC Health Serv Res. 2023;23(1):1295. https://doi.org/10.1186/s12913-023-10303-2 .
Corsonello A, Pedone C, Antonelli IR. Age-related pharmacokinetic and pharmacodynamic changes and related risk of adverse drug reactions. Curr Med Chem. 2010;17(6):571���84. https://doi.org/10.2174/092986710790416326 .
[DOI: 10.2174/092986710790416326]
Kwan D, Farrell B. Polypharmacy: optimizing medication use in elderly patients. Can Geriatr Soc J CME. 2014;4(1):7.
McLean AJ, Le Couteur DG. Aging biology and geriatric clinical pharmacology. Pharmacol Rev. 2004;56(2):163���84. https://doi.org/10.1124/pr.56.2.4 .
[DOI: 10.1124/pr.56.2.4]
Government of Canada, Statistics Canada. Older adults and population aging statistics. Statcan. 2019. https://www.statcan.gc.ca/en/subjects-start/older_adults_and_population_aging . Accessed 24 Jan 2022.
Ray WA, Chung CP, Murray KT, Malow BA, Daugherty JR, Stein CM. Mortality and concurrent use of opioids and hypnotics in older patients: a retrospective cohort study. PLoS Med. 2021;18(7): e1003709. https://doi.org/10.1371/journal.pmed.1003709 .
[DOI: 10.1371/journal.pmed.1003709]
Rose AJ, McBain R, Schuler MS, et al. Effect of age on opioid prescribing, overdose, and mortality in Massachusetts, 2011 to 2015. J Am Geriatr Soc. 2019;67(1):128���32. https://doi.org/10.1111/jgs.15659 .
[DOI: 10.1111/jgs.15659]
Sharma V, Simpson SH, Samanani S, Jess E, Eurich DT. Concurrent use of opioids and benzodiazepines/Z-drugs in Alberta, Canada and the risk of hospitalisation and death: a case cross-over study. BMJ Open. 2020;10(11): e038692. https://doi.org/10.1136/bmjopen-2020-038692 .
[DOI: 10.1136/bmjopen-2020-038692]
Chin MH, Wang LC, Jin L, et al. Appropriateness of medication selection for older persons in an urban academic emergency department. Acad Emerg Med. 1999;6(12):1232���42. https://doi.org/10.1111/j.1553-2712.1999.tb00139.x .
[DOI: 10.1111/j.1553-2712.1999.tb00139.x]
Perri M III, Menon AM, Deshpande AD, et al. Adverse outcomes associated with inappropriate drug use in nursing homes. Ann Pharmacother. 2005;39(3):405���11. https://doi.org/10.1345/aph.1E230 .
[DOI: 10.1345/aph.1E230]
Tamblyn R, Lavoie G, Petrella L, Monette J. The use of prescription claims databases in pharmacoepidemiological research: the accuracy and comprehensiveness of the prescription claims database in Qu��bec. J Clin Epidemiol. 1995;48(8):999���1009. https://doi.org/10.1016/0895-4356(94)00234-h .
[DOI: 10.1016/0895-4356(94)00234-h]
Government of Canada. MED-��CHO���S14 Report���interregional mobility, hospital days by region, treatment and residence. 2023. https://open.canada.ca/data/en/dataset/f8b8190b-c63d-41ca-bbc3-8f494092c4bc . Accessed 22 Feb 2024.
Pr��ville M, Mechakra-Tahiri SD, Vasiliadis HM, et al. Family violence among older adult patients consulting in primary care clinics: results from the ESA (Enqu��te sur la sant�� des a��n��s) Services study on mental health and aging. Can J Psychiatry. 2014;59(8):426���33. https://doi.org/10.1177/070674371405900805 .
[DOI: 10.1177/070674371405900805]
Ray WA. Evaluating medication effects outside of clinical trials: new-user designs. Am J Epidemiol. 2003;158(9):915���20. https://doi.org/10.1093/aje/kwg231 .
[DOI: 10.1093/aje/kwg231]
Essebag V, Platt RW, Abrahamowicz M, Pilote L. Comparison of nested case-control and survival analysis methodologies for analysis of time-dependent exposure. BMC Med Res Methodol. 2005;5(1):5. https://doi.org/10.1186/1471-2288-5-5 .
[DOI: 10.1186/1471-2288-5-5]
Csizmadi I, Collet JP. Bias and confounding in pharmacoepidemiology. In: Strom BL, Kimmel SE, editors. Textbook of pharmacoepidemiology. 2nd ed. Wiley; 2013. p. 261���75. https://doi.org/10.1002/9781118707999.ch16 .
D���Arcy M, St��rmer T, Lund JL. The importance and implications of comparator selection in pharmacoepidemiologic research. Curr Epidemiol Rep. 2018;5(3):272���83. https://doi.org/10.1007/s40471-018-0155-y .
[DOI: 10.1007/s40471-018-0155-y]
Suissa S. Immortal time bias in observational studies of drug effects. Pharmacoepidemiol Drug Saf. 2007;16(3):241���9. https://doi.org/10.1002/pds.1357 .
[DOI: 10.1002/pds.1357]
Suissa S. Immortal time bias in pharmacoepidemiology. Am J Epidemiol. 2008;167(4):492���9. https://doi.org/10.1093/aje/kwm324 .
[DOI: 10.1093/aje/kwm324]
D���Aiuto C, Lunghi C, Gu��nette L, et al. Factors associated with potentially inappropriate opioid use in community-living older adults consulting in primary care. Int J Geriatr Psychiatry. 2022;37(8):1���12. https://doi.org/10.1002/gps.5780 .
[DOI: 10.1002/gps.5780]
Zullo AR, Danko KJ, Moyo P, et al. Prevention, diagnosis, and management of opioids, opioid misuse, and opioid use disorder in older adults. Agency for Healthcare Research and Quality (AHRQ); 2020. https://doi.org/10.23970/AHRQEPCTB37 .
Gontijo Guerra S, Berbiche D, Vasiliadis HM. Measuring multimorbidity in older adults: comparing different data sources. BMC Geriatr. 2019;19(1):166. https://doi.org/10.1186/s12877-019-1173-4 .
[DOI: 10.1186/s12877-019-1173-4]
American Psychiatric Association APA. Diagnostic and statistical manual of mental disorders (DSM). 5th ed. American Psychiatric Publishing; 2013.
Bice T, Boxerman S. A quantitative measure of continuity of care. Med Care. 1977;15(4):347���9. https://doi.org/10.1097/00005650-197704000-00010 .
[DOI: 10.1097/00005650-197704000-00010]
Cyr MC, Martens AC, Berbiche D, Perreault S, Blais L. Continuity of care in the ambulatory treatment of adolescents with asthma. J Adolesc Health. 2006;39(6):926.e11-926.e17. https://doi.org/10.1016/j.jadohealth.2006.06.013 .
[DOI: 10.1016/j.jadohealth.2006.06.013]
Mason M, Cates CJ, Smith I. Effects of opioid, hypnotic and sedating medications on sleep-disordered breathing in adults with obstructive sleep apnoea. Cochrane Database Syst Rev. 2015;(7):CD011090. https://doi.org/10.1002/14651858.CD011090.pub2 .
McCance-Katz EF, Sullivan LE, Nallani S. Drug interactions of clinical importance among the opioids, methadone and buprenorphine, and other frequently prescribed medications: a review: drug interactions with methadone and buprenorphine. Am J Addict. 2010;19(1):4���16. https://doi.org/10.1111/j.1521-0391.2009.00005.x .
[DOI: 10.1111/j.1521-0391.2009.00005.x]
World Health Organization (WHO). Medication without harm. World Health Organization (WHO). 2017. https://apps.who.int/iris/handle/10665/255263 . Accessed 6 Dec 2022.
Renoux C, Dell���Aniello S, Brenner B, Suissa S. Bias from depletion of susceptibles: the example of hormone replacement therapy and the risk of venous thromboembolism. Pharmacoepidemiol Drug Saf. 2017;26(5):554���60. https://doi.org/10.1002/pds.4197 .
[DOI: 10.1002/pds.4197]
Suissa S. Immeasurable time bias in observational studies of drug effects on mortality. Am J Epidemiol. 2008;168(3):329���35. https://doi.org/10.1093/aje/kwn135 .
[DOI: 10.1093/aje/kwn135]
