Mortality risk and causes of death among people who use opioids in a take-home naloxone cohort

Background: People who use opioids (PWUO) have an excess mortality from a range of causes. The cumulative effect of behavioral, social, and health risk factors complicates the interpretation of the effects of suitable interventions. This study explores mortality causes among a cohort of PWUO in the take-home naloxone (THN) program. Methods: This was a prospective cohort study of PWUO who received THN between 2015 and 2023. Participant data was linked with death registry data. Crude mortality rates and standardized mortality ratios (SMRs) were calculated for all causes, internal causes, and accidental opioid overdoses (AOOs). In addition to age and gender, risk factors like main route of administration, polydrug use, self -experienced overdoses, and using while alone were fitted in a Cox Regression model to explore factors associated with mortality. Results: The 2194 participants had a considerably higher mortality ratio for all causes investigated when compared to the general population (SMR=10.9, 95 % CI = 9.3,12.6). AOOs were the most prevalent cause of death (49 %). Those who reported frequent opioid use while alone had an elevated risk of dying of 2.6 (95 % CI = 1.1,6.4) compared to those who never used while alone. Conclusions: Frequent opioid use while alone was associated with elevated mortality risk, supporting the importance of overdose prevention education with naloxone distribution, and additional efforts to improve environmental and social areas for safer drug -use practices among PWUO. The variety of mortality causes found in this study illustrates the need for multifaceted and targeted interventions for people at risk of overdosing.