The motives and methods of methamphetamine and 'heroin' co-use in West Virginia.

BACKGROUND: Opioid and methamphetamine co-use is increasing across the USA with overdoses involving these drugs also rising. West Virginia (WV) has led the US in opioid overdose death rates since at least 2013 and rising co-use of methamphetamine with opioids has played a greater role in deaths over the last 5 years. METHODS: This study used rapid ethnography to examine methods and motivations behind opioids and methamphetamine co-use from the viewpoint of their consumers. Participants (n = 30) were people who injected heroin/fentanyl also using methamphetamine who participated in semi-structured interviews. RESULTS: We found multiple methods of co-using opioids and methamphetamine, whether alternately or simultaneously and in varying order. Most prioritized opioids, with motives for using methamphetamine forming three thematic categories: 'intrinsic use', encompassing both inherent pleasure of combined use greater than using both drugs separately or for self-medication of particular conditions; 'opioid assisting use' in which methamphetamine helped people manage their existing heroin/fentanyl use; and 'reluctant or indifferent use' for social participation, reflecting methamphetamine's low cost and easy availability. CONCLUSIONS: Methamphetamine serves multiple functions among people using opioids in WV. Beliefs persist that methamphetamine can play a role in preventing and reversing opioid overdose, including some arguments for sequential use being protective of overdose. 'Reluctant' uptake attests to methamphetamine's social use and the influence of supply. The impact on overdose risk of the many varied co-use patterns needs further investigation.

Longitudinal Opioid Surveillance Project Involving Toxicologic Analysis of Postmortem Specimens from 9 Counties in Michigan Suggests the Discovery of New High-Intensity Drug Trafficking Areas.

ABSTRACT: Acetyl fentanyl (AF) is a Schedule I fentanyl analog that has been increasingly seen in heroin and fentanyl polydrug toxicity overdoses in Michigan (MI). Drug users are often unaware of the presence of AF in their drugs because it is often sold mixed into or disguised as heroin. High levels of AF in heroin drug products can cause increased incidence of overdose. This article describes data from a longitudinal opioid surveillance program and details 102 decedents in MI who were found to have evidence of heroin in their postmortem blood. A large portion of these decedents were also found to have evidence of fentanyl and AF. Our data further show significant overlap in incidence rates of AF and heroin-related overdose deaths in several MI counties, suggesting that AF is becoming enmeshed in heroin trafficking. Furthermore, we report unprecedented high incidence rates of AF and heroin-related overdose deaths in Calhoun county, and we propose that it is a high-intensity drug trafficking area. Highways US-131 and US-31 are likely used to transport these drugs. More study is needed into the drug trafficking trends in MI to ascertain drug sources and monitor the ever developing and dangerous polydrug heroin combinations.

Forensic pathological study of methadone-related deaths in the Genoa (Italy) district: A six-year study.

Methadone is a synthetic opioid, a pure agonist of the µ receptor. It is used for opioid maintenance therapy in heroin addiction. In recent years, Italian studies of incidence and prevalence have indicated an increase in the illegal sales of methadone and, consequently, an increase in deaths due to acute methadone intoxication as well. The present review is a prospective-observational study regarding epidemiological and toxicological analyses of methadone-related deaths recorded in the district of Genoa (Italy) from 2013 to 2018. The study includes a list of twenty-six people that have died from methadone toxicity: twenty-two males and four females. The concentration of methadone in the blood samples ranged from 181 to 4058.53 ng/mL, with an average of 964.29 ng/mL. Six subjects tested positive for methadone alone; twenty cases, however, presented drugs or substances in different concentrations in the blood samples. Illegal sales and consumption of methadone have a negative impact on the self-administration therapy of opioid addiction, inducing patients to increase their dosage or sell methadone in order to purchase illegal drugs. As shown in our study, this behaviour is associated with an increase in methadone-related deaths. Accordingly, careful monitoring of dosage administrated to patients is required in order to render the system safer.

Suicide mortality risk in a cohort of individuals treated for alcohol, heroin or cocaine abuse: Results of a follow-up study.

Cohort study. This follow-up study (from 1975 to 2016) was aimed to estimate the mortality risk for suicide in a cohort of patients presenting to a public treatment centre for addiction (SERD) with Alcohol Use Disorder (AUD), Heroin Use Disorder - HUD or Cocaine Use Disorder (CUD), also relating to their access to a Mental Heath Service. Crude Mortality Rates for suicide were higher for patients with AUDs, for men and subjects 45-64 years old. Hanging was the main cause of suicide death. We highlight an increase in mortality in the period 2009-2012, which coincides with the economic recession, and in the year of first contact with a SERD. The Standardized Mortality Ratios (SMRs) were 4.9, higher among females than males. From the multivariate analysis, a higher risk for patients that were separated or divorced was observed. The results of our study provide some guidance on the features of subjects at greatest risk of death from suicide, which may be useful in reducing and preventing suicide and gaining a better clinical management of patients with SUDs.

Nonmedical Use of Prescription Opioids, Heroin Use, Injection Drug Use, and Overdose Mortality in U.S. Adolescents.

OBJECTIVE: We assessed overdose mortality by opioid types involved as well as interrelationships between nonmedical use of prescription opioids (NUPO) and heroin and injection drug use (IDU) among adolescents. METHOD: We examined 2010 and 2016 overdose data by drug type for decedents in the United States ages 15-19 years from the Multiple Cause of Death Files. We also analyzed data from the 2017 National Youth Risk Behavior Survey, a nationally representative survey of high school students. We assessed lifetime NUPO and calculated heroin use and IDU by frequency of lifetime NUPO. Adjusted prevalence ratios (aPRs) were generated, and linear contrast analysis determined dose-response relationships between frequency of lifetime NUPO and the two outcomes. RESULTS: The percentage of deaths involving prescription opioids that also involved illicit opioids such as heroin or fentanyl was 5.5% in 2010 and 25.0% in 2016. We observed a positive dose-response relationship with frequency of lifetime NUPO; aPRs were highest for 20 or more times of NUPO and heroin use (aPR = 49.49, 95% CI [33.39, 73.34]) and IDU (aPR = 44.37, 95% CI [23.16, 84.99]). However, aPRs for heroin and IDU were high even among those reporting just one or two occasions of NUPO (aPRs = 9.25, 95% CI [5.90, 14.49] and 6.63, 95% CI [3.99, 11.02], respectively). CONCLUSIONS: Adolescent prescription opioid overdose deaths now frequently involve illicit opioids. Heroin use and IDU are higher among students reporting even a few instances of NUPO, indicating that students with any NUPO are an important risk group. Clinical, community, and school-based efforts can address NUPO, noting these associations.

Relationship between opiates and asthma in the determination of death.

Several studies have shown an association between asthma and opiate abuse. This retrospective study aims to analyse the demographic, toxicological, and seasonal differences in asthmatic and non-asthmatic subjects who died of opiates. In addition, the relationship between toxicological levels of opiates and histologic grade of lung inflammation is examined. Deaths from 2013 to 2018 involving opiates as the primary cause of death in Cook County, Illinois (USA) were reviewed. Twenty-six cases of opiate deaths of individuals with a history of asthma and lung histology slides available were identified. In comparison, 40 cases of deaths due to opiates only were analysed. A check-list system for the evaluation of the grade of microscopic inflammation in asthma was developed. We found statistically significant differences between the asthmatics and the non-asthmatics regarding demography (age and race) and toxicology (6-MAM presence). In particular, the "opiate and asthma group" was mainly composed of African-American subjects, in contrast with the "opiate group", consisting mostly of Caucasian. The mean age was significantly higher in the "opiate and asthma group" compared with the "opiate group". A greater presence of 6-MAM was detected in the "opiate group" compared with the "opiate and asthma group". While we expected to find that low opiate levels would lead to deaths in asthmatics and, in particular, that lower opiate concentrations would cause deaths in subjects with higher grades of histologic inflammation, our study suggests that the quantity of drug and the level of inflammation are not statistically significant in the determination of death. We, therefore, recommend histologic examination of the lungs to evaluate for asthma, particularly in suspected low-level opiate-related deaths, to help further clarify any relationship between asthma and opiate use.

Vascular Injuries in Intravenous Drug Addicts-A Single-Center Experience.

BACKGROUND: Infected false aneurysms (IFA) caused by intravenous drug abuse are uncommon but challenging lesions. The best approach for the surgical management of this condition is still unknown. The aim is to present a single-center 14-year experience in the IFA treatment in intravenous drug abusers, thus providing additional data regarding the treatment options and outcome in these patients. METHODS: A retrospective analysis of 32 consecutive patients with vascular injuries secondary to intravenous drug abuse, during the period from January 2004 to April 2018, was performed. Data of interest were extracted from patients' medical history records, anesthesia charts, and database implemented in daily practice, or were obtained by personal contact. The diagnosis was set based on history, physical examination and/or color Doppler sonography, multidetector computed tomographic angiography, and digital subtraction angiography. The outcome included graft patency, limb amputation, and mortality. RESULTS: During study period, 32 heroin abusers, predominantly males (81%), were surgically treated due to vascular injuries, with mean age of 35.2 years. The vast majority of patients have had an injury of the lower extremity blood vessels (84.3%) and the common femoral artery was the most common site of injury (59.4%). Three-quarters of patients underwent resection of the false aneurysm and ligation of the artery without reconstruction of the blood vessel. In 7 cases (21.9%), arterial reconstruction was performed with overall failure rate of 42.86%. The overall mortality rate was 6.25% and the rate of extremity salvage was 96.7%. CONCLUSIONS: The best treatment option is yet to be found, but based on the results of the present study, ligation of affected artery without revascularization seems to be an efficient, safe, and optimal treatment method, with minor risk of the extremity loss.

Postmortem Liver and Kidney Tissue Concentrations of Heroin Biomarkers and Their Metabolites in Heroin-Related Fatalities*†.

A method was developed and validated for analyzing 6-monoacetylmorphine, morphine, 6-acetylcodeine, and codeine in routine postmortem liver and kidney specimens using liquid chromatography-tandem mass spectrometry. Samples were prepared with a Stomacher instrument followed by solid-phase extraction. All calibration curves [0.5-1000 ng/g] were linear with coefficients of determination greater than 0.99 and limits of quantification of 1.0 ng/g. Within-run precision ranged between 2.0% and 8.0%, between-run precision ranged between 1.0% and 9.0%, and accuracy ranged between -5.0% and +3.0%. Matrix effects ranged from -18% to +9%. After matrix effects were excluded, analytical recoveries ranged from 76% to 94%. The distributions of 6-monoacetylmorphine, morphine, 6-acetylcodeine, and codeine were investigated in 31 postmortem cases in which heroin was the primary cause of death. In the current study, the median free morphine ratios were calculated for liver to blood and kidney to blood, which were 2.2 and 4.0, respectively. The current report highlights the importance of testing multiple specimens, including liver and kidney, in heroin-related deaths, especially if no blood samples are available. Furthermore, this work presents new information regarding the distribution of heroin metabolites in liver and kidney.

Mortality Risk among Heroin Users Accessing Treatment: Natives and Non-Natives Patients Results of a Longitudinal Study.

The aim of this study was to examine mortality risk and causes of death for natives and non-natives in a cohort of heroin population of treated in Northern Italy. Crude Mortality Rates (CMRs) were 12.78 per 1,000 Person Years (PY), Standardized Mortality Rate (SMR) was 9.93. Mortality has been decreasing over time, was higher for patients who accessed the treatment services before 2001 and has been increasing with age. CMRs and SMRs were higher among natives, while non-natives were distinguished by higher CMRs and SMRs for suicide. The natives were at greater risk of death than non-natives both injecting and non-injecting, but the mortality risk was not statistically significant in the different periods of first admission. Among non-native patients, older on average, there was a lower proportion of injecting, and a higher quota of people unemployed than among Italian natives. We highlight differences between the various areas of origin concerning consumption patterns and risk of death. The results of the study highlight a particular sub-population of heroin users, the non-natives, who as compared with the Italians, have less invasive consumption styles, reach the health services later but benefit from fewer medical controls.

Postmortem Fluid Concentrations of Heroin Biomarkers and Their Metabolites.

Only limited data exist concerning the utility of complementary specimens in heroin-related deaths. As such, this report employed a validated LC-MS-MS method to quantify 6-monoacetylmorphine (6-MAM), 6-acetylcodeine (6-AC), and their metabolites morphine and codeine in blood with (BN) and without preservative (B) and the additional unpreserved specimens of vitreous humor, urine, stomach contents, and bile from 20 postmortem cases in which heroin was the primary cause of death. The median concentration of 6-MAM in BN was 0.011 mg/L, B was 0.008 mg/L, urine was 0.186 mg/L, vitreous humor was 0.022 mg/L, stomach contents was 0.147 mg/L, and bile was 0.012 mg/L. Only one case was found to be positive for 6-AC in B (case 6, 0.002 mg/L), and the median concentration of 6-AC was 0.002 mg/L in BN, 0.012 mg/L in urine, 0.003 mg/L in vitreous humor, 0.057 mg/L in stomach contents, and 0.004 mg/L in bile. These findings present new information on the distribution of these analytes in complementary matrices and support their inclusion for accurately determining the role of heroin in opioid-related deaths.

Prescription drug monitoring programs operational characteristics and fatal heroin poisoning.

BACKGROUND: Prescription drug monitoring programs (PDMP), by reducing access to prescribed opioids (POs), may contribute to a policy environment in which some people with opioid dependence are at increased risk for transitioning from POs to heroin/other illegal opioids. This study examines how PDMP adoption and changes in the characteristics of PDMPs over time contribute to changes in fatal heroin poisoning in counties within states from 2002 to 2016. METHODS: Latent transition analysis to classify PDMPs into latent classes (Cooperative, Proactive, and Weak) for each state and year, across three intervals (1999-2004, 2005-2009, 2010-2016). We examined the association between probability of PDMP latent class membership and the rate of county-level heroin poisoning death. RESULTS: After adjustment for potential county-level confounders and co-occurring policy changes, adoption of a PDMP was significantly associated with increased heroin poisoning rates (22% increase by third year post-adoption). Findings varied by PDMP type. From 2010-2016, states with Cooperative PDMPs (those more likely to share data with other states, to require more frequent reporting, and include more drug schedules) had 19% higher heroin poisoning rates than states with Weak PDMPs (adjusted rate ratio [ARR] = 1.19; 95% CI = 1.14, 1.25). States with Proactive PDMPs (those more likely to report outlying prescribing and dispensing and provide broader access to law enforcement) had 6% lower heroin poisoning rates than states with No/Weak PDMPs (ARR = 0.94; 95% CI = 0.90, 0.98). CONCLUSION: There is a consistent, positive association between state PDMP adoption and heroin poisoning mortality. However, this varies by PDMP type, with Proactive PDMPs associated with a small reduction in heroin poisoning deaths. This raises questions about the potential for PDMPs to support efforts to decrease heroin overdose risk, particularly by using proactive alerts to identify patients in need of treatment for opioid use disorder. Future research on mechanisms explaining the reduction in heroin poisonings after enactment of Proactive PDMPs is merited.

Causes of hospital admission and mortality among 6683 people who use heroin: A cohort study comparing relative and absolute risks.

BACKGROUND: Mortality in high-risk groups such as people who use illicit drugs is often expressed in relative terms such as standardised ratios. These measures are highest for diseases that are rare in the general population, such as hepatitis C, and may understate the importance of common long-term conditions. POPULATION: 6683 people in community-based treatment for heroin dependence between 2006 and 2017 in London, England, linked to national hospital and mortality databases with 55,683 years of follow-up. METHOD: Age- and sex-specific mortality and hospital admission rates in the general population of London were used to calculate the number of expected events. We compared standardised ratios (relative risk) to excess deaths and admissions (absolute risk) across ICD-10 chapters and subcategories. RESULTS: Drug-related diseases had the highest relative risks, with a standardised mortality ratio (SMR) of 48 (95% CI 42-54) and standardised admission ratio (SAR) of 293 (95% CI 282-304). By contrast, other diseases had an SMR of 4.4 (95% CI 4.0-4.9) and an SAR of 3.15 (95% CI 3.11-3.19). However, the majority of the 621 excess deaths (95% CI 569-676) were not drug-related (361; 58%). The largest groups were liver disease (75 excess deaths) and COPD (45). Similarly, 80% (11,790) of the 14,668 excess admissions (95% CI 14,382-14,957) were not drug-related. The largest groups were skin infections (1073 excess admissions), alcohol (1060), COPD (812) and head injury (612). CONCLUSIONS: Although relative risks of drug-related diseases are very high, most excess morbidity and mortality in this cohort was caused by common long-term conditions.

The impact of drug court participation on mortality: 15-year outcomes from a randomized controlled trial.

AIM: To test the effects of drug court participation on long-term mortality risk. METHODS: During 1997-98, 235 individuals charged with a non-violent offense were randomly assigned to Baltimore City Drug Treatment Court (BCDTC) or traditional adjudication. Heroin was the predominant substance of choice among the sample. Participant mortality was observed for 15 years following randomization. RESULTS: Over 20% of participants died during the study, at an average age of 46.6 years, and 64.4% of deaths were substance-use related. Survival analyses estimated that neither mortality from any cause nor from substance use-related causes significantly differed between BCDTC and traditional adjudication. CONCLUSIONS: Frequent and premature death among the sample indicates that this is a high-risk population in need of effective substance use treatment. Roughly half of drug treatment courts are now estimated to offer medication assisted treatment (MAT), which is currently the most effective treatment for opioid use disorders. In this study of BCDTC implemented over 15 years ago, only 7% of participants received MAT, which may explain the lack of program impact on mortality. Historical barriers to providing MAT in drug court settings include access, concerns about diversion, negative attitudes, blanket prohibitions, and stigma. Drug treatment courts should implement best practice standards for substance use treatment and overdose prevention, including increased access to MAT and naloxone, and training to reduce stigmatizing language and practice.

Access to Office-Based Buprenorphine Treatment in Areas With High Rates of Opioid-Related Mortality: An Audit Study.

Background: Improving access to treatment for opioid use disorder is a national priority, but little is known about the barriers encountered by patients seeking buprenorphine-naloxone ("buprenorphine") treatment. Objective: To assess real-world access to buprenorphine treatment for uninsured or Medicaid-covered patients reporting current heroin use. Design: Audit survey ("secret shopper" study). Setting: 6 U.S. jurisdictions with a high burden of opioid-related mortality (Massachusetts, Maryland, New Hampshire, West Virginia, Ohio, and the District of Columbia). Participants: From July to November 2018, callers contacted 546 publicly listed buprenorphine prescribers twice, posing as uninsured or Medicaid-covered patients seeking buprenorphine treatment. Measurements: Rates of new appointments offered, whether buprenorphine prescription was possible at the first visit, and wait times. Results: Among 1092 contacts with 546 clinicians, schedulers were reached for 849 calls (78% response rate). Clinicians offered new appointments to 54% of Medicaid contacts and 62% of uninsured-self-pay contacts, whereas 27% of Medicaid and 41% of uninsured-self-pay contacts were offered an appointment with the possibility of buprenorphine prescription at the first visit. The median wait time to the first appointment was 6 days (interquartile range [IQR], 2 to 10 days) for Medicaid contacts and 5 days (IQR, 1 to 9 days) for uninsured-self-pay contacts. These wait times were similar regardless of clinician type or payer status. The median wait time from first contact to possible buprenorphine induction was 8 days (IQR, 4 to 15 days) for Medicaid and 7 days (IQR, 3 to 14 days) for uninsured-self-pay contacts. Limitation: The survey sample included only publicly listed buprenorphine prescribers. Conclusion: Many buprenorphine prescribers did not offer new appointments or rapid buprenorphine access to callers reporting active heroin use, particularly those with Medicaid coverage. Nevertheless, wait times were not long, implying that opportunities may exist to increase access by using the existing prescriber workforce. Primary Funding Source: National Institute on Drug Abuse.

Misuse and Mortality Related to Gabapentin and Pregabalin are Being Under-Estimated: A Two-Year Post-Mortem Population Study.

Due to the rise in their misuse and associated mortality, the UK government is reclassifying gabapentin (GBP) and pregabalin (PGL) to Class C controlled drugs from April 2019. However, it is impossible to gauge the extent of their use with current post-mortem toxicological screening, where GBP and PGL are only screened for if they are mentioned in the case documents. This study determines the prevalence of GBP and PGL, the potential extent of their under-reporting and poly-drug use in a post-mortem population. Between 1 January 2016 and 31 December 2017, 3,750 deceased from Coroners' cases in London and South East England underwent a routine drugs screen and a specific screen for GBP and PGL. The prevalence of both drugs was determined in the cohort and the subcategories of heroin users and non-heroin-users. The prevalence of both drugs was compared to tramadol (Class C drug). Case documents were reviewed to investigate the under-reporting of GBP and PGL and poly-drug use. Of 3,750 samples analyzed, 118 (3.1%) were positive for GBP, 229 (6.1%) for PGL and 120 (3.2%) were positive for tramadol. If routine analysis without additional screening of GBP and PGL had been performed in this cohort, GBP would have been under-reported by 57.6% (P < 0.0001) and PGL by 53.7% (P < 0.0001) in deaths. The most common drug group observed with GBP and PGL was non-heroin-related opioids at 60.2% and 64.6%, respectively. In total 354 deceased (9.4%) were heroin users. GBP was positive in 23 (6.5%) of these cases and PGL was positive in 69 (19.5%). The prevalence of PGL in heroin users (19.5%) was 4.1 times greater than in non-heroin users (4.7%) (P < 0.0001). GBP and PGL are being significantly under reported in fatalities. Both drugs are extensively used with opioids. The prevalence of PGL in heroin users is highly significant.

Drug overdose deaths at work, 2011-2016.

Drug overdose fatalities have risen sharply and the impact on US workplaces has not been described. This paper describes US workplace overdose deaths between 2011 and 2016. Drug overdose deaths were identified from the Census of Fatal Occupational Injuries and fatality rates calculated using denominators from the Current Population Survey. Fatality rates were compared among demographic groups and industries. Negative binomial regression was used to analyse trends. Between 2011 and 2016, 760 workplace drug overdoses occurred for a fatality rate of 0.9 per 1 000 000 full-time equivalents (FTEs). Workplace overdose fatality rates significantly increased 24% annually. Workplace overdose fatality rates were highest in transportation and mining industries (3.0 and 2.6 per 1 000 000 FTEs, respectively). One-third of workplace overdose fatalities occurred in workplaces with fewer than 10 employees. Heroin was the single most frequent drug documented in workplace overdose deaths (17%). Workplace overdose deaths were low, but increased considerably over the six-year period. Workplaces are impacted by the national opioid overdose epidemic.

Challenges with take-home naloxone in reducing heroin mortality: a review of fatal heroin overdose cases in Victoria, Australia.

AIM: Take-home naloxone (THN) programs have been implemented in order to reduce the number of heroin-overdose deaths. Because of recent legislative changes in Australia, there is a provision for a greater distribution of naloxone in the community, however, the potential impact of these changes for reduced heroin mortality remains unclear. The aim of this study was to examine the characteristics of the entire cohort of fatal heroin overdose cases and assess whether there was an opportunity for bystander intervention had naloxone been available at the location and time of each of the fatal overdose events to potentially avert the fatal outcome in these cases. METHODS: The circumstances related to the fatal overdose event for the cohort of heroin-overdose deaths in the state of Victoria, Australia between 1 January 2012 and 31 December 2013 were investigated. Coronial data were investigated for all cases and data linkage was performed to additionally investigate the Emergency Medical Services information about the circumstances of the fatal heroin overdose event for each of the decedents. RESULTS AND DISCUSSION: There were 235 fatal heroin overdose cases identified over the study period. Data revealed that the majority of fatal heroin overdose cases occurred at a private residence (n = 186, 79%) and where the decedent was also alone at the time of the fatal overdose event (n = 192, 83%). There were only 38 cases (17%) where the decedent was with someone else or there was a witness to the overdose event, and in half of these cases the witness was significantly impaired, incapacitated or asleep at the time of the fatal heroin overdose. There were 19 fatal heroin overdose cases (8%) identified where there was the potential for appropriate and timely intervention by a bystander or witness. CONCLUSION: This study demonstrated that THN introduction alone could have led to a very modest reduction in the number of fatal heroin overdose cases over the study period. A lack of supervision or a witness to provide meaningful and timely intervention was evident in most of the fatal heroin overdose cases.

Mortality rate in patients on methadone treatment and infected with the human immunodeficiency virus and/or the hepatitis C virus. / Mortalidad entre los pacientes en tratamiento con metadona e infectados con el virus de la inmunodeficiencia humana y/o hepatitis C.

Letter to the editor.

Carta al editor.

Variation Overtime among Patients of the Six Methadone Maintenance Treatment Clinics in Thai Nguyen from 2011 to 2015.

BACKGROUND: Methadone Maintenance Treatment (MMT) program's success depends on the likelihood of reducing drop-out rate and keeping patients remaining in the program. There have been neither comprehensive studies about variation among patients who have been experiencing MMT for long period nor prediction of MMT period in which the risk of drop-out would be the highest in Thai Nguyen, a northern mountainous province where the MMT was established in 2011. OBJECTIVES: To analyze variation of the MMT population through indicators of drop-out and death, re-enrolment, and retention rate in the six Thai Nguyen MMT clinics. METHODS: A retrospective study by reviewing daily treatment notebooks of the six MMT clinics in Thai Nguyen to identify events of drop-out, death, reenrolment among 2,567 patients registered from 12 May 2011 to 6 September 2015. RESULTS: Cumulative hazard of drop-out over period from the first to the fourth year of MMT treatment has an increasing trend at 0.15; 0.31; 0.46; and 0.61, respectively. The cumulative probability of re-enrolment among 740 patients who have already quit the MMT program and then returned slightly increased from 0.07 to 0.16 between the first years and the fourth year in which the highest returning rate occurred within the first 2 years after drop-out. The cumulative retention rate decreased annually and stayed at 71.7% after 4 years of running the MMT. CONCLUSIONS: MMT patients and their families should be informed and consulted about the highest risk period of drop-out and also about period when drop-out patients are most likely to reenter the MMT. Counseling adherence for patients should be conducted not only at the beginning but also during the ongoing MMT and play an extremely important role in reducing drop-out of the program while special counseling should also be reenforced for the re-enrolment patients of MMT.

Modeling Health Benefits and Harms of Public Policy Responses to the US Opioid Epidemic.

OBJECTIVES: To estimate health outcomes of policies to mitigate the opioid epidemic. METHODS: We used dynamic compartmental modeling of US adults, in various pain, opioid use, and opioid addiction health states, to project addiction-related deaths, life years, and quality-adjusted life years from 2016 to 2025 for 11 policy responses to the opioid epidemic. RESULTS: Over 5 years, increasing naloxone availability, promoting needle exchange, expanding medication-assisted addiction treatment, and increasing psychosocial treatment increased life years and quality-adjusted life years and reduced deaths. Other policies reduced opioid prescription supply and related deaths but led some addicted prescription users to switch to heroin use, which increased heroin-related deaths. Over a longer horizon, some such policies may avert enough new addiction to outweigh the harms. No single policy is likely to substantially reduce deaths over 5 to 10 years. CONCLUSIONS: Policies focused on services for addicted people improve population health without harming any groups. Policies that reduce the prescription opioid supply may increase heroin use and reduce quality of life in the short term, but in the long term could generate positive health benefits. A portfolio of interventions will be needed for eventual mitigation.