Paula A Rochon1,2,3, Andrea Gruneir1,4,5, Sudeep S Gill4,6, Wei Wu1, Lynn Zhu1, Nathan Herrmann7, Chaim M Bell2,3,4,8, Peter C Austin3,4, Nathan M Stall2, Lisa McCarthy1,9, Vasily Giannakeas1,4, Amanda Alberga4, Dallas P Seitz4,10, Sharon-Lise Normand11,12, Jerry H Gurwitz13, Susan E Bronskill1,3,4. 1. Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada. 2. Department of Medicine, University of Toronto, Toronto, Ontario, Canada. 3. Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada. 4. Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada. 5. Department of Family Medicine, University of Alberta, Edmonton, Alberta, Canada. 6. Department of Medicine, Queen's University, Kingston, Ontario, Canada. 7. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. 8. Sinai Health System, Toronto, Ontario, Canada. 9. Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada. 10. Division of Geriatric Psychiatry, Department of Psychiatry, Queen's University, Kingston, Ontario, Canada. 11. Department of Health Care Policy, School of Medicine, Harvard University, Boston, Massachusetts. 12. Department of Biostatistics, T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts. 13. Division of Geriatric Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.
Abstract
OBJECTIVES: To examine dose-related prescribing and short-term serious events associated with initiation of cholinesterase inhibitor (ChEI) therapy. DESIGN: Retrospective, population-based cohort study. SETTING: Ontario, Canada. PARTICIPANTS: Women (n=47,829) and men (n=32,503) aged 66 and older who initiated a ChEI between April 1, 2010, and June 30, 2016. MEASUREMENTS: All-cause serious events (emergency department (ED) visits, inpatient hospitalizations, death) within 30 days of ChEI initiation. Multivariable Cox proportional hazards models were used to estimate adjusted rates of serious events. RESULTS: Overall, 4.8% of older adults were dispensed a lower-than-recommended ChEI starting dose, 87.9% a recommended dose, and 7.3% a higher-than-recommended starting dose. Eight thousand six hundred seventy-one (10.8%) individuals experienced a serious event within 30 days of initiating therapy, primarily ED visits (8,540, 10.6%). Relative to those initiated on a recommended starting dose, those initiated on a higher dose had a significantly increased rate of serious events (women adjusted hazard ratio (aHR) 1.50, 95% confidence interval (CI) =1.38-1.63; men aHR 1.31, 95% CI=1.19-1.45). Similar patterns were found for ED visits and inpatient hospitalizations but not death. The relative effect of higher-than-recommended starting dose dispensed vs. recommended starting dose dispensed was greater in women than it was in men: the number needed to harm was 22 (95% confidence interval (CI)=18-29) for women and 36 (95% CI= 26-61) for men. CONCLUSION: Serious events immediately after initiation of ChEIs were associated with starting ChEI dose. This association was stronger in women.
OBJECTIVES: To examine dose-related prescribing and short-term serious events associated with initiation of cholinesterase inhibitor (ChEI) therapy. DESIGN: Retrospective, population-based cohort study. SETTING: Ontario, Canada. PARTICIPANTS: Women (n=47,829) and men (n=32,503) aged 66 and older who initiated a ChEI between April 1, 2010, and June 30, 2016. MEASUREMENTS: All-cause serious events (emergency department (ED) visits, inpatient hospitalizations, death) within 30 days of ChEI initiation. Multivariable Cox proportional hazards models were used to estimate adjusted rates of serious events. RESULTS: Overall, 4.8% of older adults were dispensed a lower-than-recommended ChEI starting dose, 87.9% a recommended dose, and 7.3% a higher-than-recommended starting dose. Eight thousand six hundred seventy-one (10.8%) individuals experienced a serious event within 30 days of initiating therapy, primarily ED visits (8,540, 10.6%). Relative to those initiated on a recommended starting dose, those initiated on a higher dose had a significantly increased rate of serious events (women adjusted hazard ratio (aHR) 1.50, 95% confidence interval (CI) =1.38-1.63; men aHR 1.31, 95% CI=1.19-1.45). Similar patterns were found for ED visits and inpatient hospitalizations but not death. The relative effect of higher-than-recommended starting dose dispensed vs. recommended starting dose dispensed was greater in women than it was in men: the number needed to harm was 22 (95% confidence interval (CI)=18-29) for women and 36 (95% CI= 26-61) for men. CONCLUSION: Serious events immediately after initiation of ChEIs were associated with starting ChEI dose. This association was stronger in women.
Authors: Joshua D Niznik; Xinhua Zhao; Meiqi He; Sherrie L Aspinall; Joseph T Hanlon; Laura C Hanson; David Nace; Joshua M Thorpe; Carolyn T Thorpe Journal: J Am Geriatr Soc Date: 2019-11-26 Impact factor: 5.562
Authors: Lynn Zhu; Paula A Rochon; Andrea Gruneir; Wei Wu; Vasily Giannakeas; Peter C Austin; Nathan M Stall; Lisa McCarthy; Amanda Alberga; Nathan Herrmann; Sudeep S Gill; Susan E Bronskill Journal: Drugs Aging Date: 2019-09 Impact factor: 3.923
Authors: Prajakta P Masurkar; Satabdi Chatterjee; Jeffrey T Sherer; Hua Chen; Michael L Johnson; Rajender R Aparasu Journal: Drugs Aging Date: 2022-06-06 Impact factor: 4.271
Authors: Paula A Rochon; Andrea Gruneir; Chaim M Bell; Rachel Savage; Sudeep S Gill; Wei Wu; Vasily Giannakeas; Nathan M Stall; Dallas P Seitz; Sharon-Lise Normand; Lynn Zhu; Nathan Herrmann; Lisa McCarthy; Colin Faulkner; Jerry H Gurwitz; Peter C Austin; Susan E Bronskill Journal: PLoS One Date: 2018-10-22 Impact factor: 3.240