Long-term Health Outcome of Heroin Addiction: Methadone, Statins and the Risk of Mortality
Date Issued
2016
Date
2016
Author(s)
Liao, Ding-Lieh
Abstract
Background: Heroin addiction is a chronic disease with impact on the patient''s long-term health outcome, including HIV infection and other comorbidities, in addition to psychosocial decompensation. Methadone treatment is the standard maintenance treatment. Optimal treatment of heroin addiction with methadone service and treatment of comorbidity is important in overall health outcome of these patients. Although the survival of Human Immunodeficiency Virus (HIV) improved significantly in the era of highly active anti-retroviral treatment, chronic inflammation may be persistent. Statins may have protective effects against chronic virus infection, and hence may be an important modifiable treatment-related factor in the long-term course of HIV infection patients as well as those comorbid with heroin addiction. By using methadone treatment registry by the Centers for Disease Control and reimbursement database of National Health Insurance (NHI) in Taiwan, we conducted explorations with three specific aims: (1) to estimate the utility of nationwide methadone treatment service; (2) to investigate whether dosage, attendance rate, and overall treatment duration are associated with the reduction of mortality risk in heroin addiction patients; (3) to investigate if there is an association of statin use with mortality risk reduction of HIV patients. Methods: In the first part, we conducted an estimation of utility gained from the nationwide methadone treatment service, based on the parameters obtained from current methadone service in Taiwan. In the second part, we conducted a population-based cohort study from Taiwan''s Methadone Registry maintained by the Centers for Disease Control. A total of 33,603 patients were included as the study cohort, with complete records of methadone treatment from 2006 to 2008. All-cause mortality was tracked by the linage to national mortality registry from the Department of Health. Cox proportional hazard regressions were employed to calculate the hazard ratios (HRs) for the association between the methadone dosing and overall mortality risk. In the third part, we used the National Health Insurance Research Database to analyze the health outcome of HIV infection patients, because of the difficulty in identifying heroin addiction in the NHI Research Database. A total of 5183 HIV-infected patients were included as the study cohort. Each subject was individually tracked from 1997 to 2008 to identify mortality since 1999. Subsequent use of statins was identified. Cox proportional hazard regressions were employed to calculate the hazard ratios (HRs) for the association between use of statins and occurrence of mortality in the HIV-infected cohort. Results: In the first part, range of Incremental Cost-Effectiveness Ratio (ICER) was estimated, with sensitivity analysis of difference in gain of Quality Adjusted Life-Year. As the annual cost for administration of methadone program was about 40,000 NTD, which leads to an incremental cost of 133,300 to 333,300 NTD, or 4,170 to 10,420 USD (1 USD=32 NTD) per QALY, the MMT strategy may be cost-effective. In the second part, the overall crude mortality rate is 134.78/10,000 person-years, and the standardized mortality ratio in reference to age-specific general population is approximately 4.68. In the adjusted model of Cox proportional hazard analysis, older age (adjusted hazard ratio, HR = 2.16, P<0.001) and positive HIV infection status (adjusted HR = 2.14, P<0.001) were associated with higher mortality risk. For treatment-related factors, the higher-dosage group has lower mortality risk than the lower-dosage group (adjusted HR＝0.96, 0.75, and 0.68 to reference group, P = 0.03). In one methadone clinical sample study with total 2201 patients, positive rate of HBV, HCV, HIV, and syphilis were 26.4%, 78.2%, 10.8%, and 6.0%, respectively. In the third part, a total of 5183 newly infected patients with HIV were included, with 28323 person-years of follow-up; 576 deaths and 184 cancer diagnoses were recorded during the follow-up period. Among the 480 statin users, the adjusted hazard ratios of all-cause mortality were 0.42 (0.31-0.56) relative to statin non-users in time-dependent Cox regression analysis. The adjusted hazard ratios in 28-89, 90-180, and more than 180 total DDDs are 0.60 (0.24-1.49), 0.40 (0.12-1.28), and 0.16 (0.07-0.38), in a dose-response pattern following adjustments for confounders. Conclusion: This thesis explores the long-term health outcome of heroin addicted patients. The result from the utility estimation of heroin addicted patients reveals that methadone significantly improved the overall utility of the patients and is quite cost-effective in current methadone clinic service in Taiwan. The result from the exploration of methadone treatment database reveals that higher methadone dosage was associated with lower all-cause mortality, indicating the health benefit of methadone service in terms of mortality as an outcome. The result from the exploration of a local methadone clinic confirms a significant proportion of HCV and HIV infection comorbidity in heroin addicted patients. By using the HIV patients as a surrogate in NHI database, the exploration of statin use in HIV patients reveals an association of lower mortality risk in statin users. Since heroin addiction is a major health problem in addiction psychiatry and public health in addition to social welfare, modifiable factors related to the treatment for these patients are important in designing and providing adequate treatment setting, which is new to Taiwan.
Subjects
addiction
methadone
mortality
statin
prevention
HIV
comorbidity
SDGs
Type
thesis
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