Adam J Rose1,2, Dana Bernson3, Kenneth Kwan Ho Chui4, Thomas Land3, Alexander Y Walley5,3, Marc R LaRochelle5, Bradley D Stein6,7, Thomas J Stopka4,8. 1. RAND Corporation, Boston, MA, USA. arose@rand.org. 2. Section of General Internal Medicine, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA. arose@rand.org. 3. Massachusetts Department of Public Health, Boston, MA, USA. 4. Tufts University School of Medicine, Boston, MA, USA. 5. Section of General Internal Medicine, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA. 6. RAND Corporation, Pittsburgh, PA, USA. 7. University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. 8. Tufts Clinical and Translational Sciences Institute, Boston, MA, USA.
Abstract
BACKGROUND: Potentially inappropriate prescribing (PIP) may contribute to opioid overdose. OBJECTIVE: To examine the association between PIP and adverse events. DESIGN: Cohort study. PARTICIPANTS: Three million seventy-eight thousand thirty-four individuals age ≥ 18, without disseminated cancer, who received prescription opioids between 2011 and 2015. MAIN MEASURES: We defined PIP as (a) morphine equivalent dose ≥ 100 mg/day in ≥ 3 months; (b) overlapping opioid and benzodiazepine prescriptions in ≥ 3 months; (c) ≥ 4 opioid prescribers in any quarter; (d) ≥ 4 opioid-dispensing pharmacies in any quarter; (e) cash purchase of prescription opioids on ≥ 3 occasions; and (f) receipt of opioids in 3 consecutive months without a documented pain diagnosis. We used Cox proportional hazards models to identify PIP practices associated with non-fatal opioid overdose, fatal opioid overdose, and all-cause mortality, controlling for covariates. KEY RESULTS: All six types of PIP were associated with higher adjusted hazard for all-cause mortality, four of six with non-fatal overdose, and five of six with fatal overdose. Lacking a documented pain diagnosis was associated with non-fatal overdose (adjusted hazard ratio [AHR] 2.21, 95% confidence interval [CI] 2.02-2.41), as was high-dose opioids (AHR 1.68, 95% CI 1.59-1.76). Co-prescription of benzodiazepines was associated with fatal overdose (AHR 4.23, 95% CI 3.85-4.65). High-dose opioids were associated with all-cause mortality (AHR 2.18, 95% CI 2.14-2.23), as was lacking a documented pain diagnosis (AHR 2.05, 95% CI 2.01-2.09). Compared to those who received opioids without PIP, the hazard for fatal opioid overdose with one, two, three, and ≥ four PIP subtypes were 4.24, 7.05, 10.28, and 12.99 (test of linear trend, p < 0.001). CONCLUSIONS: PIP was associated with higher hazard for all-cause mortality, fatal overdose, and non-fatal overdose. Our study implies the possibility of creating a risk score incorporating multiple PIP subtypes, which could be displayed to prescribers in real time.
BACKGROUND: Potentially inappropriate prescribing (PIP) may contribute to opioid overdose. OBJECTIVE: To examine the association between PIP and adverse events. DESIGN: Cohort study. PARTICIPANTS: Three million seventy-eight thousand thirty-four individuals age ≥ 18, without disseminated cancer, who received prescription opioids between 2011 and 2015. MAIN MEASURES: We defined PIP as (a) morphine equivalent dose ≥ 100 mg/day in ≥ 3 months; (b) overlapping opioid and benzodiazepine prescriptions in ≥ 3 months; (c) ≥ 4 opioid prescribers in any quarter; (d) ≥ 4 opioid-dispensing pharmacies in any quarter; (e) cash purchase of prescription opioids on ≥ 3 occasions; and (f) receipt of opioids in 3 consecutive months without a documented pain diagnosis. We used Cox proportional hazards models to identify PIP practices associated with non-fatal opioid overdose, fatal opioid overdose, and all-cause mortality, controlling for covariates. KEY RESULTS: All six types of PIP were associated with higher adjusted hazard for all-cause mortality, four of six with non-fatal overdose, and five of six with fatal overdose. Lacking a documented pain diagnosis was associated with non-fatal overdose (adjusted hazard ratio [AHR] 2.21, 95% confidence interval [CI] 2.02-2.41), as was high-dose opioids (AHR 1.68, 95% CI 1.59-1.76). Co-prescription of benzodiazepines was associated with fatal overdose (AHR 4.23, 95% CI 3.85-4.65). High-dose opioids were associated with all-cause mortality (AHR 2.18, 95% CI 2.14-2.23), as was lacking a documented pain diagnosis (AHR 2.05, 95% CI 2.01-2.09). Compared to those who received opioids without PIP, the hazard for fatal opioid overdose with one, two, three, and ≥ four PIP subtypes were 4.24, 7.05, 10.28, and 12.99 (test of linear trend, p < 0.001). CONCLUSIONS:PIP was associated with higher hazard for all-cause mortality, fatal overdose, and non-fatal overdose. Our study implies the possibility of creating a risk score incorporating multiple PIP subtypes, which could be displayed to prescribers in real time.
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