| アブストラクト | BACKGROUND: Acetylcholinesterase inhibitors (AChEIs), are commonly prescribed for dementia and can cause adverse drug events that may lead to new prescriptions, known as prescription cascades. We aimed to identify potential AChEI-induced prescription cascades using high-throughput sequence symmetry analysis (SSA). METHODS: Patients aged >/=18 years with 365 days of prior observation initiating AChEIs (donepezil, rivastigmine, or galantamine) were identified from the Clinical Practice Research Datalink GOLD (2002-2022). We screened 510 drug classes and 1213 individual ingredients initiated within +/-180 days of AChEI initiation (365 days in sensitivity analyses). Crude and adjusted sequence ratios (ASRs) were calculated, and positive signals were reviewed for clinical plausibility. RESULTS: We identified 66 155 AChEI initiators (median age 81 years [IQR 76-85]; 62.8% female). Among ATC classes and individual ingredients, 51 and 46 signals were positive with 28 (55%) and 22 (48%) classified as potential prescription cascades after review. Gastrointestinal drugs showed positive signals including antipropulsives (ASR 1.50 [99% CI 1.28-1.75]), loperamide (ASR 1.52 [1.30-1.77]) and cyclizine (ASR 2.10 [1.72-2.59]). Positive signals were also observed nervous system drugs such as benzodiazepine derivatives (ASR 1.83 [1.55-2.16]) and respiratory drugs including corticosteroids (ASR 1.66 [1.33-2.08]) and glucocorticoids (ASR 1.54 [1.30-1.83]). Most positive signals remained in sensitivity analysis. CONCLUSIONS: These findings suggest potential AChEI-related prescription cascades consistent with gastrointestinal, neuropsychiatric, dermatological and respiratory adverse effects. While findings require further validation, this study demonstrates the utility of high-throughput signal detection to support pharmacovigilance in high-risk populations. |
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| 投稿者 | Newby, Danielle; Bobba, Sai Sumedha; Raventos, Berta; Rowlands, Elin J; Chen, Xihang; Molina-Porcel, Laura; Reyes, Carlen; Duarte-Salles, Talita; Delmestri, Antonella; Man, Wai Yi; Burn, Edward; Catala Sabate, Marti; Pratt, Nicole; Jodicke, Annika M; Prieto-Alhambra, Daniel |
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| 組織名 | Health Data Sciences (HDS), Translational Sciences, Botnar Research Centre,;University of Oxford, Oxford, UK.;Health System, University of Alabama at Birmingham Birmingham, Alabama 35294,;USA.;IDIAP Jordi Gol, Fundacio Institut Universitari per a la recerca a l'Atencio;Primaria de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain.;Erasmus MC Universitair Medisch Centrum Rotterdam, Department of Medical;Informatics, Erasmus University Medical Center, Rotterdam, ZH, The Netherlands.;Biobanc de l'Hospital Clinic IDIBAPS, Neurological Tissue Bank of the;Biobanc-Hospital Clinic-Fundacio de Recerca Clinic Barcelona-Institut;d'Investigacions Biomediques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Spain.;IDIBAPS-Alzheimer's disease and other cognitive disorders unit, Neurology;Service, Hospital Clinic, Barcelona, Spain.;Sardenya Primary Health Care Center, Equip d'Atencio Primaria Barcelona Sardenya;research unit- Sant Pau Research Institute (EAP Sarden), Barcelona, Spain.;Department of Medical Informatics, Erasmus Medical Center, Rotterdam,;Zuid-Holland, The Netherlands.;NHMRC Medicines Intelligence Centre, NHMRC Medicines Intelligence Centre of;Research Excellence, Adelaide, South Australia, Australia.;Quality Use of Medicines and Pharmacy Research Centre, Clinical and Health;Sciences, University of South Australia, Adelaide, South Australia, Australia. |
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