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BackgroundThe second Multicenter Medication Reconciliation Quality Improvement Study demonstrated a marked reduction in medication discrepancies per patient. The aim of the current analysis was to determine the association of patient exposure to each system-level intervention and receipt of each patient-level intervention on these results.MethodsThis study was conducted at 17 North American Hospitals, the study period was 18 months per site, and sites typically adopted interventions after 2–5 months of preintervention data collection. We conducted an on-treatment analysis (ie, an evaluation of outcomes based on patient exposure) of system-level interventions, both at the category level and at the individual component level, based on monthly surveys of implementation site leads at each site (response rate 65%). We then conducted a similar analysis of patient-level interventions, as determined by study pharmacist review of documented activities in the medical record. We analysed the association of each intervention on the adjusted number of medication discrepancies per patient in admission and discharge orders, based on a random sample of up to 22 patients per month per site, using mixed-effects Poisson regression with hospital site as a random effect. We then used a generalised linear mixed-effects model (GLMM) decision tree to determine which patient-level interventions explained the most variance in discrepancy rates.ResultsAmong 4947 patients, patient exposure to seven of the eight system-level component categories was associated with modest but significant reductions in discrepancy rates (adjusted rate ratios (ARR) 0.75–0.97), as were 15 of the 17 individual system-level intervention components, including hiring, reallocating and training personnel to take a best possible medication history (BPMH) and training personnel to perform discharge medication reconciliation and patient counselling. Receipt of five of seven patient-level interventions was independently associated with large reductions in discrepancy rates, including receipt of a BPMH in the emergency department (ED) by a trained clinician (ARR 0.40, 95% CI 0.37 to 0.43), admission medication reconciliation by a trained clinician (ARR 0.57, 95% CI 0.50 to 0.64) and discharge medication reconciliation by a trained clinician (ARR 0.64, 95% CI 0.57 to 0.73). In GLMM decision tree analyses, patients who received both a BPMH in the ED and discharge medication reconciliation by a trained clinician experienced the lowest discrepancy rates (0.08 per medication per patient).Conclusion and relevancePatient-level interventions most associated with reductions in discrepancies were receipt of a BPMH of admitted patients in the ED and admission and discharge medication reconciliation by a trained clinician. System-level interventions were associated with modest reduction in discrepancies for the average patient but are likely important to support patient-level interventions and may reach more patients. These findings can be used to help hospitals and health systems prioritise interventions to improve medication safety during care transitions.