OBJECTIVE: It is unknown whether opioid misuse act as a risk factor for serious adverse events in Korea. In this study, we aimed to examine whether opioid misuse was associated with death or overdose.
METHODS: A retrospective cohort study was conducted using nationally representative data, the N...
OBJECTIVE: It is unknown whether opioid misuse act as a risk factor for serious adverse events in Korea. In this study, we aimed to examine whether opioid misuse was associated with death or overdose.
METHODS: A retrospective cohort study was conducted using nationally representative data, the National Health Insurance Service-National Sample Cohort 2.0 database, that covered approximately one million patients from January 1, 2002, to December 31, 2015. The chronic opioid users aged 18 years or more were included, who have continuously prescribed opioids greater than or equal to 90 days between January 1, 2007, and December 30, 2015, and no greater than the 31-day gap. The exposure assessment window of opioid misuse was set for 90 days after or on the first date of chronic opioid use episode. The last date of the first exposure assessment window was defined as the index date. We excluded patients with cancer diagnoses between January 1, 2002, and December 31, 2015 except for non-melanoma skin cancer. Patients with a history of death and overdose events the year before the index date were also excluded. Chronic opioid users with misuse were matched one to one using propensity score and greedy matching algorithm. Patients with misuse were matched to patients with no misuse based on two variables of misuse measures: overlapping prescriptions and number of prescribers. First, we defined overlapping prescriptions as greater than or equal to 25% of opioid prescriptions overlapped with other opioid prescriptions for the same active components or same therapeutic class. Second, patients visiting four or more prescribers in 90 days were considered as one indicator of opioid misuse. The association between the risk of death and opioid misuse was estimated by using the extended Cox hazards model in the matched cohort with hazard ratios and 95% confidence interval. The relationship between the risk of overdose and opioid misuse was also estimated in the same way. The proportional hazard assumption was checked by log-minus log plots. We conducted sensitivity analyses to assess the impact of using only each measure and using both two measures to define misuse.
RESULTS: Among 41,905 patients with chronic opioid users, 25,138 patients were finally included after the exclusion process. Opioid misuse defined as using either overlapping prescriptions for the same active component or visiting four or more prescribers was associated with higher risk of death (Hazard Ratio [HR] 1.75, 95% Confidence Interval [CI] 1.46-2.10) and overdose (HR 1.81, CI 1.25-2.60). When opioid misuse defined using only overlapping prescriptions for the same active component, opioid misuse was also significantly associated with the increased risk of death (HR 2.05, CI 1.69-2.48) and overdose (HR 1.79, CI 1.19-2.70). Similarly, when opioid misuse defined using overlapping prescriptions for the same therapeutic class, opioid misuse was associated with the increased risk of death (HR 1.88, CI 1.58-2.24) and overdose (HR 1.82, CI 1.27-2.62). When we defined opioid misuse using both overlapping prescriptions for the same active component and visiting four or more prescribers for 90 days, the highest risk of death was observed in patients with misuse compared with patients with no misuse (HR 2.78, CI 1.17-6.61). Opioid misuse defined using visiting four or more prescribers in 90 days was not significantly associated with the risk of death (HR 1.49, CI 0.90-2.48) and overdose (HR 1.38, CI 0.54-3.52).
CONCLUSIONS: This is the first study to examine the association between opioid misuse and its harmful effects in Korea. We identified that opioid misuse was significantly associated with the increased risk of death or overdose. Although there is a possibility that unmeasured confounders might be remained, our findings can lead to positive development in opioid prescribing policies and inform the preventive approaches to manage opioid misuse and its harmful effects. Further research is needed to identify patients at-risk associated with opioid misuse.
OBJECTIVE: It is unknown whether opioid misuse act as a risk factor for serious adverse events in Korea. In this study, we aimed to examine whether opioid misuse was associated with death or overdose.
METHODS: A retrospective cohort study was conducted using nationally representative data, the National Health Insurance Service-National Sample Cohort 2.0 database, that covered approximately one million patients from January 1, 2002, to December 31, 2015. The chronic opioid users aged 18 years or more were included, who have continuously prescribed opioids greater than or equal to 90 days between January 1, 2007, and December 30, 2015, and no greater than the 31-day gap. The exposure assessment window of opioid misuse was set for 90 days after or on the first date of chronic opioid use episode. The last date of the first exposure assessment window was defined as the index date. We excluded patients with cancer diagnoses between January 1, 2002, and December 31, 2015 except for non-melanoma skin cancer. Patients with a history of death and overdose events the year before the index date were also excluded. Chronic opioid users with misuse were matched one to one using propensity score and greedy matching algorithm. Patients with misuse were matched to patients with no misuse based on two variables of misuse measures: overlapping prescriptions and number of prescribers. First, we defined overlapping prescriptions as greater than or equal to 25% of opioid prescriptions overlapped with other opioid prescriptions for the same active components or same therapeutic class. Second, patients visiting four or more prescribers in 90 days were considered as one indicator of opioid misuse. The association between the risk of death and opioid misuse was estimated by using the extended Cox hazards model in the matched cohort with hazard ratios and 95% confidence interval. The relationship between the risk of overdose and opioid misuse was also estimated in the same way. The proportional hazard assumption was checked by log-minus log plots. We conducted sensitivity analyses to assess the impact of using only each measure and using both two measures to define misuse.
RESULTS: Among 41,905 patients with chronic opioid users, 25,138 patients were finally included after the exclusion process. Opioid misuse defined as using either overlapping prescriptions for the same active component or visiting four or more prescribers was associated with higher risk of death (Hazard Ratio [HR] 1.75, 95% Confidence Interval [CI] 1.46-2.10) and overdose (HR 1.81, CI 1.25-2.60). When opioid misuse defined using only overlapping prescriptions for the same active component, opioid misuse was also significantly associated with the increased risk of death (HR 2.05, CI 1.69-2.48) and overdose (HR 1.79, CI 1.19-2.70). Similarly, when opioid misuse defined using overlapping prescriptions for the same therapeutic class, opioid misuse was associated with the increased risk of death (HR 1.88, CI 1.58-2.24) and overdose (HR 1.82, CI 1.27-2.62). When we defined opioid misuse using both overlapping prescriptions for the same active component and visiting four or more prescribers for 90 days, the highest risk of death was observed in patients with misuse compared with patients with no misuse (HR 2.78, CI 1.17-6.61). Opioid misuse defined using visiting four or more prescribers in 90 days was not significantly associated with the risk of death (HR 1.49, CI 0.90-2.48) and overdose (HR 1.38, CI 0.54-3.52).
CONCLUSIONS: This is the first study to examine the association between opioid misuse and its harmful effects in Korea. We identified that opioid misuse was significantly associated with the increased risk of death or overdose. Although there is a possibility that unmeasured confounders might be remained, our findings can lead to positive development in opioid prescribing policies and inform the preventive approaches to manage opioid misuse and its harmful effects. Further research is needed to identify patients at-risk associated with opioid misuse.
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