| Summary: | 博士 === 國立成功大學 === 公共衛生研究所 === 107 === Opioid use disorder contributes to a heavy burden of disease globally, including excessive early mortality and poor quality of life. The Taiwan Center for Disease Control (CDC) permitted MET as an agonist treatment for heroin users in response to human immunodeficiency virus (HIV) epidemic since 2006 and the effectiveness of opioid agonist treatment (OAT) should be comprehensively evaluated. This dissertation first estimated the life expectancy (LE) and expected years of life lost (EYLL) in a cohort of heroin users stratified by OAT for comparison. A total of 1283 heroin users recruited in the beginning of OAT implementation (2006) were linked to the National Mortality Registry until 2012 with stratification by OAT. Kaplan-Meier estimation for survival was performed, and it was extrapolated to lifetime to obtain the LE using a semi-parametric method. We further estimated the EYLL for both cohorts by subtracting their life expectancies from the age-, sex-, and calendar year-matched referents simulated from vital statistics. Cause-specific standardized mortality ratios (SMRs) for the OAT and non-OAT groups showed 7.5 and 10.2 compared with the general population, indicating good representativeness for our sample. In contrast, SMR of suicide mortality elevated 16.2- and 3.1-fold in OAT and non-OAT group, respectively. Moreover, OAT saves 7.8 EYLL more than non-OAT after accounting for lead time bias.
Then I applied the novel extrapolation method to compare the treated opioid users between U.S. and Taiwan. Survival data came from two cohorts followed until 2014: The U.S. data are based on a randomized trial of 1,267 opioid-dependent participants enrolled between 2006 and 2009; the Taiwan data are from the OAT group (N=983) that began in 2006, when OAT was implemented in Taiwan. The EYLLs, estimated by subtracting their life expectancies from the age- and gender-matched referents simulated from the vital statistics of their respective country, were 7.7 and 16.4 years for the U.S. and Taiwan/OAT cohort, respectively. However, a striking difference in suicide mortality existed between these two groups, with a suicide mortality rate of 25 percent for the Taiwan cohort versus 1 percent for the U.S. cohort. The combination of comorbidities and the stigma associated with heroin use could lead to psychological distress (depression) and, eventually suicide. The high rate of suicide morality along with the low rates of psychiatric medication among opioid users in Taiwan raises the concern of stigma issue. Thereafter, we attempted to determine the effects of stigma (assessed by the Self-Stigma Scale-Short (SSS-S)) and psychological distress (assessed by the Chinese Health Questionnaire-12 (CHQ-12)) on QOL (as assessed by the brief version of the World Health Organization Quality of Life instrument (WHOQOL-BREF)) and to explore possible mediation effects between psychological distress and stigma in a consecutive sample of 268 heroin users. The CHQ-12 score was predictive of the scores for the four domains and almost all facets of the WHOQOL-BREF except the item, “Dependence on medical aids.” Nonetheless, the SSS-S score predicted three of the four facets of the social QOL after adjustment of the CHQ-12 score. Psychological distress completely mediated the association between self-stigma and the physical, psychological, and environmental domains, and partially mediated association between self-stigma and social QOL (two-tailed Sobel test: p=0.02 for each domain).
Finally, we quantified the quality-adjusted life years (QALY) saved by OAT versus non-OAT from the loss of quality-adjusted life expectancy (QALE) in heroin users. A total of 1283 heroin users stratified by OAT were linked to the National Mortality Registry for 8 years (2006-2014) to obtain survival functions, which were extrapolated to lifetime by applying a rolling extrapolation algorithm of logit transformed survival ratio between the sub-cohorts and age-, sex-, and calendar year-matched referents simulated from vital statistics of Taiwan. On those with a valid state of OAT or non-OAT plus newly recruited consecutive patients, we performed measurement of EQ-5D on 349 participants during 2015-2017 for utility values, while QOL of referents were abstracted from the 2009 National Health Interview Survey. The QALE was calculated by summing the product of the mean QOL function and survival function throughout life. The QALE difference between the cohort and corresponding referents was the loss-of-QALE. QOL of the OAT group was significantly better than that of the non-OAT group in every domain of the EQ-5D, which was quantified to be 0.23 in utility value after controlling for other potential confounding variables. The estimated QALE and loss-of-QALE were 17.8 and 18.2 QALY for OAT subjects, respectively, while those of the non-OAT group were 9.2 and 27.9 QALY. Receiving OAT could save 9.7 QALYs for heroin users compared with non-OAT after accounting for QOL differences along time.
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