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Study objective: Persons with substance use disorders frequently utilize emergency department (ED) services, creating an opportunity for intervention and referral to addiction treatment and harm-reduction services. However, EDs may not have the appropriate tools to distinguish which patients are at greatest risk for negative outcomes. We link hospital ED and medical examiner mortality databases in one state to identify individual-level risk factors associated with overdose death among ED patients with substance-related encounters. Methods: This retrospective cohort study linked Maryland statewide ED hospital claims records for adults with nonfatal overdose or substance use disorder encounters in 2014 to 2015 with medical examiner mortality records in 2015 to 2016. Logistic regression was used to identify factors in hospital records associated with risk of opioid overdose death. Predicted probabilities for overdose death were calculated for hypothetical patients with different combinations of overdose and substance use diagnostic histories. Results: A total of 139,252 patients had substance-related ED encounters in 2014 to 2015. Of these patients, 963 later experienced an opioid overdose death, indicating a case fatality rate of 69.2 per 10,000 patients, 6 times higher than that of patients who used the ED for any cause. Factors most strongly associated with death included having both an opioid and another substance use disorder (adjusted odds ratio 2.88; 95% confidence interval 2.04 to 4.07), having greater than or equal to 3 previous nonfatal overdoses (adjusted odds ratio 2.89; 95% confidence interval 1.54 to 5.43), and having a previous nonfatal overdose involving heroin (adjusted odds ratio 2.24; 95% confidence interval 1.64 to 3.05). Conclusion: These results highlight important differences in overdose risk among patients receiving care in EDs for substance-related conditions. The findings demonstrate the potential utility of incorporating routine data from patient records to assess risk of future negative outcomes and identify primary targets for initiation and linkage to lifesaving care.

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