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BackgroundThe COVID-19 pandemic has changed the landscape of healthcare service delivery. This review aims to describe telemedicine-delivered substance use disorder (SUD) treatments and services along the cascade of care in the U.S. after the start of the COVID-19 pandemic.MethodsA literature review was conducted on PubMed, Embase, Web of Science, and Cochrane Library (Wiley). English-language articles that describe any healthcare services for patients with SUDs using telemedicine in the U.S. since the onset of the COVID-19 pandemic were identified (N=33). We narratively summarized telemedicine-based service provision along the cascade of SUD care, such as screening/assessment, prescription, monitoring, recovery support, and other services.ResultsSoon after the onset of COVID-19 and mandated restrictions, cadres of healthcare providers from different specialties mobilized to ramp up video- and audio-based services to remotely treat patients with SUDs. Medication prescription (48.5%) and individual counseling (39.4%) were the most frequently reported services delivered via telemedicine. Other steps of SUD care delivered by telemedicine characterized in our review included SUD screening and assessment (30.3%), induction (21.2%), medication management (27.3%), monitoring (27.3%), recovery support (15.2%), and referral (24.2%). Feasibility issues and challenges to implementing telemedicine included patients' lack of access to technology and health insurance coverage, providers' capacity limits and concerns, and clinics' financial and office-space constraints.ConclusionThe COVID-19 pandemic has offered a window of opportunity to advance telemedicine expertise by formalizing clinical guidance and routinizing provider in-service training in virtual SUD treatment. Findings suggest enhanced efforts to reduce disparities in telemedicine-based services.

This study examined mental health service utilization and disparities during the first year of COVID. We analyzed data from all adult respondents with any mental illness in the past year (n = 6967) in the 2020 National Survey on Drug Use and Health to evaluate if mental health service utilization differed by geographic areas, race/ethnicity, and age groups. Only 46% of individuals with any mental illness had received mental health treatment. Compared to non-Hispanic Whites, Asian and Hispanics were less likely to receive outpatient services and prescription medicine. Rural residents received less outpatient treatment compared to large metropolitan residents. No difference was found in telemedicine utilization across area types and race/ethnicity groups. Older individuals were less likely to utilize telemedicine services. Our findings highlighted continued mental health treatment disparities among race/ethnic minorities and other sub-populations during COVID. Targeted strategies are warranted to allow older populations to benefit from telemedicine.

Purpose To examine characteristics associated with disparities in digital access (i.e., access to high-speed Internet via a computer or smartphone) in American rural and urban households given that digital access has a direct impact on access to telemedicine-based services. Methods Using the 2019 American Community Survey, we analyzed the proportions of geographic area, race/ethnicity, and socioeconomic status according to device and high-speed Internet access. Maximum likelihood logit estimators estimated how these factors influenced device and high-speed Internet access. Findings Of 105,312,959 households, 32.29% were without a desktop or laptop computer with high-speed Internet (WDW), 21.51% were without a smartphone with a data plan for wireless Internet (WSW), and 14.02% were without any digital access (WDA). Nonmetropolitan households were significantly more likely to be WDA than metropolitan households (odds ratio [OR] = 1.87; 95% confidence interval [CI]: 1.83-1.91). Relative to non-Hispanic Whites, non-Hispanic Blacks (OR = 1.60; 95% CI: 1.56-1.64), American Indian or Alaska natives (OR = 2.00; 95% CI: 1.82-2.19), or Hispanics (OR = 1.70; 95% CI: 1.66-1.74) were significantly more likely to be WDA. When compared to households with private health insurance coverage, households WDA were significantly more likely to have no insurance (OR = 2.44; 95% CI: 2.36-2.53) or public insurance coverage (OR = 3.78; 95% CI: 3.70-3.86). Households with any digital access reported higher income and more family members living at home. Using the same predictors, similar findings were reported for households WDW or WSW. Conclusions Significant disparities in digital access exist among nonmetropolitan households, racial/ethnic minority households, and lower-income households. The lack of digital access has implications for the accessibility of health care services via telemedicine and thus could exacerbate health disparities.

Background and aims As treatment for opioid use disorder (OUD) expands within general healthcare settings such as primary care, mechanisms to facilitate decision-making processes are increasingly necessary. Decision aids have the capacity to bolster existing resources in diverse treatment settings by increasing knowledge of treatment options and facilitating shared decision making. The aim of this study is to develop and test a patient decision aid for medication treatment for opioid use disorder (PtDA-MOUD) that assists individuals with OUD in making informed decisions about treatment at the time of initial clinical visit. Use of the PtDA-MOUD will be further tested in diverse treatment settings within the California Hub and Spoke System developed under the SAMHSA State Targeted Response to the Opioid Crisis grants. Methods The PtDA-MOUD was iteratively developed with input from a scientific expert panel and both patient and provider focus groups, incorporating International Patient Decision Aid Standards. Thirty-six patients with OUD entering treatment pilot tested the PtDA and completed assessments, and results from clinical records were compared with matched controls who did not receive the PtDA. A clinical profile based on assessment data was created for use within the clinical visit. Results The developed decision aid provides information on MOUD and captures patient characteristics relevant to medication treatment decisions. Feedback indicated that the PtDA-MOUD was feasible to implement and useful. Though the small sample size limited the ability to detect significant differences (p > .05), a greater number of individuals who reviewed the PtDA (37%) were inducted on MOUD than controls (11%) and received MOUD for more days (M = 14.0, SD = 24.7) than controls (M = 8.4; SD = 22.5). Moreover, the difference in means for days receiving MOUD had an approximately medium effect size (r = 0.25). Conclusions Patient perceptions of the decision aid were favorable and it showed promise as a tool in the OUD treatment process. Pilot testing results suggested preliminary positive effects on MOUD initiation. Future phases of this study will further investigate the usefulness of this tool. ClinicalTrials.gov Identifier: NCT03394261

Objectives: Both COVID-19 deaths and opioid overdose deaths continue to increase in the United States. Little is known about the characteristics of counties with high rates of mortality for both. Methods: We analyzed county-level data on COVID-19 mortality from January 1 to May 31, 2020, and on opioid overdose mortality during 2014-2018. The outcome variable, “high-risk county” was a binary indicator of high mortality rates (above 75% quartile) for both COVID-19 and opioid overdose. We conducted geospatial logistic regression models separately for urban and rural counties to identify social determinants of health associated with being a high-risk county. Results: After adjusting for other covariates, the overall mortality rate of COVID-19 is higher in counties with larger population size and a higher proportion of racial/ethnic minorities, although counties with high rates of opioid overdose mortality have lower proportions of racial/ethnic minorities, a higher proportion of females, and are more economically disadvantaged. Significant predictors of rural counties with high mortality rates for both COVID-19 and opioid overdose include higher proportions of Blacks (Adjusted odds ratio [aOR], 1.04; 95%CI, 1.01–1.07), American Indians and Alaska Natives (aOR, 1.07; 95%CI, 1.02–1.13), and two or more races (aOR, 1.34; 95%CI, 1.13–1.60). Additional predictors for high-risk urban counties include population density (aOR, 1.12; 95%CI, 1.04–1.22) and higher unemployment rates during the COVID-19 pandemic (aOR, 1.23; 95%CI, 1.07–1.41). Conclusions: Rural counties with high proportions of racial/ethnic minorities and urban counties with high unemployment rates are at high mortality risk for COVID-19 and opioid overdose.

OBJECTIVE: Co-prescription of opioids and benzodiazepines (BDZ) is associated with adverse outcomes, including greater healthcare utilization and overdose risk. This study aims to examine opioid and BDZ co-prescription, dosing, and mortality among patients with and without opioid use disorder (OUD) in a large healthcare system. METHODS: Using data from the California state Prescription Drug Monitoring Program during 2010–2014 linked with a large healthcare system electronic health record database and mortality records from the Centers for Disease Control National Death Index, this study examined 5,202 patients (1,978 with OUD, 3,224 controls). Multiple logistic regression analyses were conducted to examine relationships between most recent BDZ and opioid prescription, and their interaction with respect to mortality. RESULTS: 10.5% of the sample died on or before December 31, 2014. 17.7% were prescribed BDZ during the final month of observation. Individuals with OUD were prescribed higher average BDZ and opioid doses than those without OUD. After adjusting for covariates, increased prescribed doses of BDZ (odds ratio [OR]=1.34, 95%CI: 1.15–1.55 per 10 mg/day increment) and opioids (OR=1.04, 95%CI: 1.02–1.05 per 10 mg/day increment) were positively associated with mortality. Non-OUD patients who received both BDZ and opioid prescriptions had a higher mortality than those who received only BDZ or opioids (The ratio of odds ratio (ROR) =3.83, 95%CI: 1.78–8.21). CONCLUSIONS: Study findings highlight significant mortality associated with the co-prescription of opioids and BDZ in a general healthcare setting. Further research is needed to elucidate factors associated with mortality among non-OUD patients who are co-prescribed opioids and BDZ.

BACKGROUND AND AIM: There is no gold-standard and considerable heterogeneity in outcome measures used to evaluate treatments for opioid use disorder (OUD) along the opioid treatment cascade. The aim of this study was to develop the US National Institute on Drug Abuse (NIDA) National Drug Abuse Treatment Clinical Trials Network (CTN) opioid use disorder core outcomes set (OUD-COS). DESIGN: Four-round, e-Delphi expert panel consensus study and plenary research group discussion and targeted consultation. SETTING: United States. PARTICIPANTS: A panel of 25 members including clinical practitioners, clinical researchers and administrative staff from the CTN, the network's affiliated clinical and community sites and the NIDA Centre for the CTN. MEASUREMENTS: From a pool of 24 candidate items in four domains (biomedical/disease status; behaviors, symptoms and functioning; opioid treatment cascade; and morbidity and mortality), the panel completed an on-line questionnaire to rank items with defined specification on a 9-point scale for importance, with a standard 70% consensus criterion. FINDINGS: After the fourth round of the questionnaire and subsequent discussion, consensus was reached for five outcomes: two patient-reported (global impression of improvement and incident non-fatal overdose); one clinician-reported (illicit/non-medical drug toxicology); and two from administrative records (duration of treatment and fatal opioid poisoning). CONCLUSIONS: An e-Delphi consensus study has produced the US National Institute on Drug Abuse (NIDA) National Drug Abuse Treatment Clinical Trials Network opioid use disorder core outcomes set (version 1) for opioid use disorder treatment efficacy and effectiveness research.

Background Nationwide efforts seek to address the opioid epidemic by increasing access to medications for opioid use disorder (OUD), particularly with buprenorphine. A poorly understood challenge is that among individuals with OUD who do receive buprenorphine, many do not adhere to the pharmacotherapy long enough to achieve sustained benefits. We aimed to identify factors associated with buprenorphine treatment utilization over time. Methods We used random-intercept modeling to identify factors associated with buprenorphine treatment utilization over 2 years after first follow-up by 789 individuals with OUD who had participated in a multi-site randomized clinical trial of buprenorphine compared to methadone. Key predictors were participants' reports of buprenorphine treatment accessibility and acceptability (assessed at first follow-up) and their interaction effects, controlling for baseline randomization status, sociodemographics, and other covariates. Results Approximately 9.3–11.2% of participants utilized buprenorphine treatment over the 2 years of follow-up. Interaction effects indicated that individuals who perceived buprenorphine to be both accessible and acceptable were most likely to use buprenorphine during follow-up, controlling for other factors. In contrast, individuals who perceived buprenorphine to be unacceptable were least likely to use buprenorphine, regardless the level of perceived access to the medication. Buprenorphine treatment utilization was also negatively associated with Hispanic ethnicity, West coast context, and cumulative months receiving methadone treatment and incarceration during follow-up. Conclusions To engage more individuals with OUD in long-term treatment with buprenorphine, interventions should target buprenorphine treatment acceptability, in addition to increasing buprenorphine access, and tailor efforts to meet the needs of vulnerable populations. Trial registration The START Follow-up Study on ClinicalTrials.gov ( NCT01592461 ).

BACKGROUND: Individuals treated for opioid use disorder (OUD) have high rates of psychiatric disorders potentially diminishing treatment outcomes. We examined long-term treatment experiences and outcomes by type of psychiatric disorder among participants who participated in the Starting Treatment with Agonist Replacement Therapies (START) study and its follow-up study. METHODS: We categorized the 593 participants who completed the Mini-International Neuropsychiatric Interview (MINI) during the START follow-up study into four mutually exclusive groups to indicate current psychiatric diagnosis: 1) bipolar disorder (BPD; n = 51), 2) major depressive disorder (MDD; n = 85), 3) anxiety disorder (AXD; n = 121), and 4) no comorbid mental disorder (NMD; n = 336). We compared participants’ baseline characteristics and treatment outcomes. RESULTS: Groups with mental disorders had worse substance use outcomes and poorer psychosocial functioning than the NMD group. Participants with BPD had significantly more self-reported days using opioids (Mean: 8.6 for BPD vs. 3.4 days for NMD, p < 0.01) and heroin (Mean: 6.4 for BPD vs. 2.0 for MDD, 3.1 days for NMD, p < 0.05) in the 30 days prior to the final interview. Compared to patients without mental disorders, patients with MDD spent more time engaged with OUD pharmacotherapy during the ~16-month period between MINI and final interview (mean: 71.6 % vs. 50.6 %; p < 0.001). CONCLUSIONS: Our results show that treatment outcomes in individuals with OUD vary by psychiatric comorbidity groups, which supports the need for mental health assessment and treatment for psychiatric conditions in the context of pharmacotherapy for patients with OUD.

Telemedicine (TM) enabled by digital health technologies to provide medical services has been considered a key solution to increasing health care access in rural communities. With the immediate need for remote care due to the COVID-19 pandemic, many health care systems have rapidly incorporated digital technologies to support the delivery of remote care options, including medication treatment for individuals with opioid use disorder (OUD). In responding to the opioid crisis and the COVID-19 pandemic, public health officials and scientific communities strongly support and advocate for greater use of TM-based medication treatment for opioid use disorder (MOUD) to improve access to care and have suggested that broad use of TM during the pandemic should be sustained. Nevertheless, research on the implementation and effectiveness of TM-based MOUD has been limited. To address this knowledge gap, the National Drug Abuse Treatment Clinical Trials Network (CTN) funded (via the NIH HEAL Initiative) a study on Rural Expansion of Medication Treatment for Opioid Use Disorder (Rural MOUD; CTN-0102) to investigate the implementation and effectiveness of adding TM-based MOUD to rural primary care for expanding access to MOUD. In preparation for this large-scale, randomized controlled trial incorporating TM in rural primary care, a feasibility study is being conducted to develop and pilot test implementation procedures. In this commentary, we share some of our experiences, which include several challenges, during the initial two-month period of the feasibility study phase. While these challenges could be due, at least in part, to adjusting to the COVID-19 pandemic and new workflows to accommodate the study, they are notable and could have a substantial impact on the larger, planned pragmatic trial and on TM-based MOUD more broadly. Challenges include low rates of identification of risk for OUD from screening, low rates of referral to TM, digital device and internet access issues, workflow and capacity barriers, and insurance coverage. These challenges also highlight the lack of empirical guidance for best TM practice and quality remote care models. With TM expanding rapidly, understanding implementation and demonstrating what TM approaches are effective are critical for ensuring the best care for persons with OUD.

Background A lack of consensus on the optimal outcome measures to assess the efficacy and effectiveness of interventions for the treatment of opioid use disorder (OUD) has hampered the pooling of research data for evidence synthesis and clinical guidelines. A core outcome set (COS) is a minimum set of outcome measures that are recommended for all studies of a particular condition. The National Drug Abuse Treatment Clinical Trials Network (CTN) Core Outcome Set for OUD (COS-OUD) is a development study to identify core constructs, meaningful outcomes, and their optimal measurement for all efficacy and effectiveness studies of OUD treatment and service delivery. Methods/design Overseen by an expert workgroup, a modified, stepwise, e-Delphi methodology will be used to gain consensus among a panel of clinical practitioners and researchers involved in the treatment of OUD, who are members of the CTN. Sequential rounds of anonymous, online questionnaires will be used to identify, rate the importance of, and refine a core outcome set. A consensus threshold will be achieved if at least 70% of the panel rate the measure as critical for inclusion in the COS-OUD. Where consensus is not reached or there are suggestions for new measures, these will be brought forward to a further round of review prior to a consensus meeting. Products from this study will be communicated via peer-reviewed scientific journals and conferences. Discussion This initiative will develop a COS for OUD intervention trials, treatment studies, and service delivery and will support the pooling of research and clinical practice data and efforts to develop measurement-based care within the OUD treatment cascade. Trial registration http://www.comet-initiative.org/Studies/Details/1579

Purpose To examine the prevalence of comorbid chronic pain among patients with opioid use disorder (OUD) and to compare other comorbidities (substance use disorder (SUD), mental health disorders, health/disease conditions) among patients in four categories: no chronic pain (No Pain), OUD prior to pain (OUD First), OUD and pain at the same time (Same Time), or pain condition prior to OUD (Pain First). Methods Using an electronic health record (EHR) database from 2006–2015, the study assessed 5307 adult patients with OUD in a large healthcare system; 35.6% were No Pain, 9.7% were OUD First, 14.9% were Same Time, and 39.8% were Pain First. Results Most OUD patients (64.4%) had chronic pain conditions, and among them 61.8% had chronic pain before their first OUD diagnosis. Other SUDs occurred more frequently among OUD First patients than among other groups in terms of alcohol (33.4% vs. 25.4% for No Pain, 20.7% for Same Time, and 20.3% for Pain First), cocaine (19.0%, vs. 13.8%, 9.4%, 7.1%), and alcohol or drug-induced disorders. OUD First patients also had the highest rates of HIV (4.7%) and hepatitis C virus (HCV; 28.2%) among the four groups. Pain First patients had the highest rates of mental disorder (81.7%), heart disease (72.0%), respiratory disease (68.4%), sleep disorder (41.8%), cancer (23.4%), and diabetes (19.3%). Conclusions The alarming high rates of chronic pain conditions occurring before OUD and the associated severe mental health and physical health conditions require better models of assessment and coordinated care plans to address these complex medical conditions.

Aims This study compared the cause-specific standardized mortality ratios (SMRs) and expected years of life lost (EYLL) among opioid-dependent individuals in the United States and Taiwan. Methods Survival data came from two cohorts followed until 2014: The U.S. data were based on a randomized trial of 1267 opioid-dependent participants enrolled between 2006 and 2009; the Taiwan data were from a study of 983 individuals that began in 2006, when opioid agonist treatment (OAT) was implemented in Taiwan. SMRs were calculated for each national cohort and compared. Kaplan–Meier estimation was performed on the survival data, then lifespans were extrapolated to 70 years (840 months) to estimate life expectancy using a semi-parametric method. EYLLs for both cohorts were estimated by subtracting their life expectancies from the age- and gender-matched referents within the general population of their respective country. Results Compared with age- and gender-matched referents, the SMRs were 3.2 for the U.S. sample and 7.8 for the Taiwan sample; the EYLLs were 7.7 and 16.4 years, respectively. Half of decedents died of unnatural causes in both cohorts; overdose deaths predominated in the U.S. and suicide in Taiwan. Conclusions Our study identified differences by country in EYLL and causes of deaths. These findings suggest that intervention strategies to reduce mortality risk by overdose (particularly in the U.S.) and suicide (particularly in Taiwan) are urgently needed in these countries.

Background and aims Treatment for opioid use disorders (OUD) reduces the risk of mortality and infectious disease transmission; however, opportunities to quantify the potential economic benefits of associated decreases in drug-related crime are scarce. This paper aimed to estimate the costs of crime during and after periods of engagement in publicly funded treatment for OUD to compare total costs of crime during a hypothetical 6-month period following initiation of opioid agonist treatment (OAT) versus detoxification. Design Retrospective, administrative data-based cohort study with comprehensive information on drug treatment and criminal justice systems interactions. Setting Publicly funded drug treatment facilities in California, USA (2006–10). Participants A total of 31 659 individuals admitted for the first time to treatment for OUD, and who were linked with criminal justice and mortality data, were followed during a median 2.3 years. Median age at first treatment admission was 32, 35.8% were women and 37.1% primarily used prescription opioids. Measurements Daily costs of crime (US$2014) were calculated from a societal perspective and were composed of the costs of policing, court, corrections and criminal victimization. We estimated the average marginal effect of treatment engagement in OAT or detoxification adjusting for potential fixed and time-varying confounders, including drug use and criminal justice system involvement prior to treatment initiation. Findings Daily costs of crime during treatment compared with after treatment were $126 lower for OAT [95% confidence interval (CI) = $116, $136] and $144 lower for detoxification (95% CI = $135, $154). Summing the costs of crime during and after treatment over a hypothetical 6-month period using the observed median durations of OAT (161 days) and detoxification (19 days), we estimated that enrolling an individual in OAT as opposed to detoxification would save $17 550 ($16 840, $18 383). Conclusions In publicly funded drug treatment facilities in California, USA, engagement in treatment for opioid use disorders is associated with lower costs of crime in the 6 months following initiation of treatment, and the economic benefits were far greater for individuals receiving time-unlimited treatment.

BACKGROUND: Objective outcomes for measuring the physical health effects of substance use disorder treatment are needed. We compared the responsiveness of CD4, HIV-1 RNA and a biomarker index (VACS Index 2.0) to changes in opioid use among people with HIV (PWH) and uninfected individuals receiving opioid agonist treatment (OAT). METHODS: Electronic health record data were used to identify patients who received ≥90 days of OAT and had ≥1 urine toxicology test in the Veterans Aging Cohort Study. Trajectory models identified patterns of opioid urine toxicology results. We used linear regression adjusted for age and race/ethnicity to determine associations between opioid toxicology groups and biomarker changes from up to one-year pre OAT to 3–15 months after OAT initiation. RESULTS: Among 266 with detectable HIV-1 RNA, 366 with suppressed HIV-1 RNA, and 1183 uninfected patients, we identified five opioid toxicology groups ranging from consistently negative (54%) to consistently positive (9%). Among PWH with detectable HIV-1 RNA, all three biomarkers improved more for those consistently negative compared to those consistently positive (all p≤.05). Among PWH with suppressed HIV-1 RNA, CD4 improved for those consistently negative; and worsened for those in the slow decrease toward negative group (p=.04). Among those uninfected, VACS Index 2.0 did not differ by opioid toxicology groups. CONCLUSIONS: Among patients on OAT, changes in biomarkers are associated with opioid toxicology groups among PWH, but vary by HIV-1 RNA. These findings may be useful for measuring the health effects of OAT.

Studies on the relationships between marijuana use and quality of life have reported mixed findings. Based on a survey of 123 marijuana users conducted in Los Angeles during 2017-2018, we investigated the relationships between marijuana use frequency, severity of marijuana-related problems, and health-related quality of life (HRQoL). Results indicated that (1) marijuana use frequency was positively related to severity of marijuana-related problems; (2) severity of marijuana-related problems was negatively related to mental domain of HRQoL but was not significantly related to physical domain of HRQoL; and (3) marijuana use frequency was positively associated with mental health symptoms and physical health conditions, and both in turn were negatively linked to mental and physical domains of HRQoL, respectively. Reduction of marijuana-related problems and mitigation of mental and physical health problems may improve HRQoL among marijuana users. The study findings may contribute to developing treatment interventions for marijuana use that simultaneously address marijuana-related problems and associated mental and physical issues.

Studies of the long-term course of opioid use disorder (OUD) underscore how the condition is exacerbated by factors such as interactions with the criminal justice system, limited access to medications to treat OUD, chronic unemployment and conditions of poverty, physical/psychological trauma and related mental illness, social isolation, and poor social support. Developments in pharmacotherapies for OUD and innovative means of administration have yielded important advances in effective medication-based treatments, yet social and political structures remain as obstacles in some regions of the United States and other parts of the world affected by OUD. Changes in perceptions about OUD as a chronic brain disease and about the effectiveness of pharmacotherapies for OUD indicate a public health approach may slowly supersede the criminal justice approach to addressing OUD. This chapter provides an overview of OUD problems as they have emerged and as they are societally and clinically addressed, emphasizing the management and treatment of OUD with effective use of available pharmacotherapies and within environments that are supportive of recovery.

This special issue contains 20 papers including 3 Perspectives, 1 Brief Report, 6 Invited Reviews, and 10 Original Articles, which highlight the work by presenters at the second meeting of the biennial Conference Series to Promote Global Health held on April 22-24, 2015 in Hangzhou, Zhejiang, China. These papers focused on the prevalent substance misuse of amphetamine-type-stimulants and opioids, and the increasing prevalence of HIV-infection in Asian countries. The Conference Series is sponsored by the National Institute on Drug Abuse, of the U.S. National Institutes of Health, with the goal of exchanging knowledge and ideas related to, and promoting international collaborative work on, the prevention and treatment of substance use disorders and HIV-infection, in order to promote health in Asian and Pacific Islanders and other populations.

Drug abuse and co-occurring infections are associated with significant morbidity and mortality. Asian countries are particularly vulnerable to the deleterious consequences of these risks/problems, as they have some of the highest rates of these diseases. This review describes drug abuse, HIV, and hepatitis C (HCV) in Asian countries. The most commonly used illicit drugs include opioids, amphetamine-type stimulants (ATS), cannabis, and ketamine. Among people who inject drugs, HIV rates range from 6.3 % in China to 19 % in Malaysia, and HCV ranges from 41 % in India and Taiwan to 74 % in Vietnam. In the face of the HIV epidemics, drug policies in these countries are slowly changing from the traditional punitive approach (e.g., incarcerating drug users or requiring registration as a drug user) to embrace public health approaches, including, for example, community-based treatment options as well as harm reduction approaches to reduce needle sharing and thus HIV transmission. HIV and HCV molecular epidemiology indicates limited geographic diffusion. While the HIV prevalence is declining in all five countries, use of new drugs (e.g., ATS, ketamine) continues to increase, as well as high-risk sexual behaviors associated with drug use-increasing the risk of sexual transmission of HIV, particularly among men who have sex with men. Screening, early intervention, and continued scaling up of therapeutic options (drug treatment and recovery support, ART, long-term HIV and HCV care for drug users) are critical for effective control or continued reduction of drug abuse and co-infections.

Aims To compare long-term outcomes among participants randomized to buprenorphine or methadone. Design, Setting and Participants Follow-up was conducted in 2011–14 of 1080 opioid-dependent participants entering seven opioid treatment programs in the United States between 2006 and 2009 and randomized (within each program) to receive open-label buprenorphine/naloxone or methadone for up to 24 weeks; 795 participants completed in-person interviews (~74% follow-up interview rate) covering on average 4.5 years. Measurements Outcomes were indicated by mortality and opioid use. Covariates included demographics, site, cocaine use and treatment experiences. Findings Mortality was not different between the two randomized conditions, with 23 (3.6%) of 630 participants randomized to buprenorphine having died versus 26 (5.8%) of 450 participants randomized to methadone. Opioid use at follow-up was higher among participants randomized to buprenorphine relative to methadone [42.8 versus 31.7% positive opioid urine specimens, P

Opioid dependence is associated with high levels of morbidity, yet sparse data exists regarding the health-related quality of life (HRQoL) of individuals with opioid dependence, particularly following treatment initiation. To inform cost-effectiveness analyses of treatment modalities, this study investigates short-term changes in HRQoL following enrollment into opioid agonist treatment (OAT), across treatment modalities and patient subgroups.Data was analyzed from the Starting Treatment with Agonist Replacement Therapies (START) and Prescription Opioid Addiction Treatment Studies (POATS) randomized controlled trials. Participants included individuals dependent on prescription opioids (POs) or heroin, receiving limited-term or time-unlimited treatment. PO- or heroin-users in START received buprenorphine/naloxone (BUP/NX) or methadone (MET) over 24 weeks. PO-users in POATS received psychosocial care and short-term (4-week) taper with BUP/NX, with non-responders offered subsequent extended (12-week) stabilization and taper. HRQoL was assessed using the short-form SF-6D while in and out of OAT, with distinction between MMT and BUP/NX in START. Linear mixed effects regression models were fitted to determine the independent effects of OAT on HRQoL and characterize HRQoL trajectories.Treatment had a similar immediate and modest positive association with HRQoL in each patient subgroup. The association of OAT on HRQoL was statistically significant in each model, with effect sizes between 0.039 (heroin-users receiving BUP/NX) and 0.071 (PO-users receiving MET). After initial improvement, HRQoL decreased slightly, or increased at a diminished rate.OAT, whether delivered in time-limited or unlimited form, using BUP/NX or MET, is associated with modest immediate HRQoL improvements, with diminishing benefits thereafter.

Cocaine dependence has been associated with deficits in white matter (WM) integrity. Nevertheless, what happens to WM integrity after long-term abstinence is not fully understood. To bridge this gap, changes in WM integrity were examined with diffusion tensor imaging (DTI) applied to 39 participants: 12 participants who used cocaine in the last year (CURRENT USERS), 20 who were at different stages of cocaine abstinence (ABSTINENCE) [five with 1-5 years of abstinence (ABS1), five with 6-10 years of abstinence (ABS2), and 10 with over 10 years of abstinence (ABS3)], and 7 healthy controls (CONTROLS). The CONTROL group had higher fractional anisotropy (FA) compared to CURRENT USERS in frontal cortex tracts, including the bilateral corpus callosum, bilateral superior longitudinal fasciculus, bilateral inferior fronto-occipital fasciculus, left internal capsule, left middle cingulum, and left ventral and dorsal medial frontal regions. The ABSTINENCE group also had higher FA compared to CURRENT USERS in frontal cortex tracts, such as the bilateral corpus callosum, bilateral superior longitudinal fasciculus, left inferior longitudinal fasciculus, left uncinate fasciculus, left inferior fronto-occipital fasciculus, and the left ventral and dorsal medial frontal regions. Tractography analysis showed (1) deficits in terms of number of fibers and fiber length in these regions, and that (2) while there was some recovery of white matter in dorsolateral regions during abstinence, duration of abstinence was not associated with such recovery. The results identified WM differences among cocaine users, cocaine abstinent participants, and controls. These preliminary findings point to WM tracts that recover, and some that do not, after long-term abstinence from cocaine.

Although numerous studies have shown that child obesity is associated with internalizing symptoms, relatively few studies have examined the role of parenting behaviors on this relationship. Youth meeting obesity status may be at higher risk of psychosocial maladjustment when exposed to more vulnerable parenting contexts. The current study interviewed mothers with a history of substance abuse to assess whether parenting behaviors moderated the relationship between obesity and internalizing symptoms among adolescents ( N = 160; 51% girls; M = 12.76 years). Hierarchical regression analyses identified physical discipline as a moderator; girls meeting obesity status displayed higher levels of internalizing symptoms when exposed to higher versus lower levels of physical discipline. Prevention/intervention efforts targeting mothers with substance abuse histories should aim to not only improve physical and emotional health but also highlight the connections between physical and emotional health and the influence of parenting behaviors on associations.

OBJECTIVE Prescription Drug Monitoring Programs (PDMPs) are intended to help reduce prescription drug misuse and opioid overdose, yet little is known about the longitudinal patterns of opioid prescribing that may be associated with mortality. This study investigated longitudinal opioid prescribing patterns among patients with opioid use disorder (OUD) and without OUD in relation to mortality using PDMP data. METHODS Growth modeling was used to examine opioid prescription data from the California PDMP for a 4-year period before death or a comparable period ending in 2014 for those remaining from a sample of 7728 patients (2576 with OUD, and 5152 matched non-OUD controls) treated in a large healthcare system. RESULTS Compared to controls, individuals with OUD (alive and deceased) had received significantly more opioid prescriptions, greater number of days' supply, and steeper increases of opioid dosages over time. For morphine equivalents (ME, in grams), the interaction of OUD and mortality was significant at both intercept (β = 10.4, SE = 4.4, P

Aims To compare long-term criminal justice outcomes among opioid-dependent individuals randomized to receive buprenorphine or methadone. Design, setting and participants A 5-year follow-up was conducted in 2011-14 of 303 opioid-dependent participants entering three opioid treatment programs in California, USA in 2006-09 and randomized to receive either buprenorphine/naloxone or methadone. Intervention and comparator Participants received buprenorphine/naloxone (BUP; n = 179) or methadone (MET; n = 124) for 24 weeks and then were tapered off their treatment over ≤ 8 weeks or referred for ongoing clinical treatment. Midway through the study, the randomization scheme was switched from 1 : 1 BUP : MET to 2 : 1 because of higher dropout in the BUP arm. Measurements Study outcomes included arrests and self-reported incarceration. Predictors included randomization condition (buprenorphine versus methadone), age, gender, race/ethnicity, use of cocaine, drug injection in the 30 days prior to baseline and study site. Treatment status (buprenorphine, methadone, none) during follow-up was included as a time-varying covariate. Findings There was no significant difference by randomization condition in the proportion arrested (buprenorphine: 55.3%, methadone: 54.0%) or incarcerated (40.9%, 47.3%) during follow-up. Among methadone-randomized individuals, arrest was less likely with methadone treatment (0.50, 0.35-0.72) during follow-up (relative to no treatment) and switching to buprenorphine had a lower likelihood of arrest than those receiving no treatment (0.39, 0.18-0.87). Among buprenorphine-randomized individuals, arrest was less likely with receipt of buprenorphine (0.49, 0.33-0.75) during follow-up and switching to methadone had a similar likelihood of arrest as methadone-randomized individuals receiving no treatment. Likelihood of arrest was also negatively associated with older age (0.98, 0.96-1.00); it was positively associated with Hispanic ethnicity (1.63, 1.04-2.56), cocaine use (2.00, 1.33-3.03), injection drug use (2.19, 1.26-3.83), and study site. Conclusions In a US sample of people treated for opioid use disorder, continued treatment with either buprenorphine or methadone was associated with a reduction in arrests relative to no treatment. Cocaine use, injection drug use, Hispanic ethnicity and younger age were associated with higher likelihood of arrest.

This special issue contains 11 papers, including 3 Invited Reviews, one Brief Report and 6 Original Articles, which highlight the work by selected presenters at the third meeting of the biennial Conference Series to Promote Global Health held on August 15-17, 2017 in Los Angeles University City, California, USA. The Conference Series is sponsored by the National Institute on Drug Abuse, of the U.S. National Institutes of Health. A major goal of the conference is to promote international collaboration that will improve practices in the US and other countries, which is greatly needed to keep the scientific, treatment and service communities around the world abreast of the latest research findings and methods in substance abuse, HIV, and related areas, and to lead future directions in research. The papers in this special issue highlight current reseach in the areas of substance use disorders and HIV-infection, and related treatments to these disorders, as well as advancing the research of precision medicine in substance abuse, HIV, and care. Future research directions and unanswered questions are emphasized in each of these articles. ᅟ Graphical Abstract.

Opioid use disorder (OUD) is a chronic, relapsing condition with severe negative health consequences. Previous studies have reported that 5-year opioid abstinence is a good predictor of reduced likelihoods of relapse, but factors that shape long-term opioid abstinence are poorly understood. The present study is based on data from a prospective study of 699 adults with OUD who had been randomized to either methadone or buprenorphine/naloxone and who were followed for at least 5 years. During the 5 years prior to the participants’ last follow-up interview, 232 (33.2%) had achieved 5-year abstinence from heroin. Of those 232, 145 (20.7% of the total) had remained abstinent from both heroin and other opioids (e.g., hydrocodone, oxycodone, other opioid analgesics, excluding methadone or buprenorphine). Compared to non-abstinent individuals, those in both categories of opioid abstinence had lower problem severity in health and social functioning at the final follow-up. Logistic regression results indicated that cocaine users and injection drug users were less likely to achieve 5-year heroin abstinence, whereas Hispanics (vs. whites) and those treated in clinics on the West Coast (vs. East) were less likely to achieve 5-year abstinence from heroin and other opioids. For both abstinence category groups, abstinence was positively associated with older age at first opioid use, lower impulsivity, longer duration of treatment for OUD, and greater social support. Reducing cocaine use and injection drug use and increasing social support and retention in treatment may help maintain long-term abstinence from opioids among individuals treated with agonist pharmacotherapy.

BACKGROUND: Mobile health (mHealth) technologies have the potential to facilitate self-monitoring and self-management for individuals with substance use disorders (SUD). S-Health is a bilingual smartphone application based on cognitive behavioral principles and is designed to support recovery from drug addiction by trigger recognition so as to allow practice in-the-moment coping to prevent relapse. METHOD: For this pilot randomized controlled study, 75 participants were recruited from methadone maintenance treatment clinics and the social worker consortium in Shanghai, China. Participants in the control group (N=25) received text messages from S-Health (e.g., HIV prevention and other educational materials). Participants in the intervention group (N=50) received both text messages and daily surveys on cravings, affects, triggers, responses to triggers, and social contexts. RESULTS: At the end of the 1-month study trial, 26.2% of the intervention group and 50% of the control group had positive urine test results (p=0.06). Also, the number of days using drug in the past week was significantly lower among participants in the intervention group (Mean= 0.71, SD=1.87) relative to the control group (Mean=2.20, SD=3.06) (p

Background: Mobile health technologies have been found to improve the self-management of chronic diseases. However, there is limited research regarding their feasibility in supporting recovery from substance use disorders (SUDs) in China. Objective: The objective of this study was to examine the feasibility of a mobile phone-based ecological momentary assessment (EMA) app by testing the concordance of drug use assessed by the EMA, urine testing, and a life experience timeline (LET) assessment. Methods: A total of 75 participants dependent on heroin or amphetamine-type stimulant (ATS) in Shanghai were recruited to participate in a 4-week pilot study. Of the participants, 50 (67% [50/75]) were randomly assigned to the experimental group and 25 (33% [25/75]) were assigned to the control group. The experimental group used mobile health (mHealth) based EMA technology to assess their daily drug use in natural environments and received 2 short health messages each day, whereas the control group only received 2 short health messages each day from the app. Urine tests and LET assessments were conducted each week and a post-intervention survey was administered to both groups. The correlations among the EMA, the LET assessment, and the urine test were investigated. Results: The mean age of the participants was 41.6 (SD 8.0) years, and 71% (53/75) were male. During the 4 weeks of observation, 690 daily EMA survey data were recorded, with a response rate of 49.29% (690/1400). With respect to drug use, the percent of agreement between the EMA and the LET was 66.7%, 79.2%, 72.4%, and 85.8%, respectively, for each of the 4 weeks, whereas the percent of agreement between the EMA and the urine test was 51.2%, 65.1%, 61.9%, and 71.5%, respectively. The post-intervention survey indicated that 46% (32/70) of the participants preferred face-to-face interviews rather than the mHealth app. Conclusions: This study demonstrated poor agreement between the EMA data and the LET and found that the acceptance of mHealth among individuals with SUDs in China was not positive. Hence, greater efforts are needed to improve the feasibility of mHealth in China. [JMIR Mhealth Uhealth 2018;6(2):e46]

Aims To assess gender differences in characteristics, mortality rates, and the causes and predictors of death among treated opioid-dependent individuals. Methods Linked vital statistics data were obtained for all individuals first enrolled in publicly funded pharmacological treatment for opioid dependence in California from 2006 to 2010. Standardized mortality ratios (SMR) were calculated by gender. Cox proportional hazards models with time-varying covariates were fitted to determine the effect of gender on the hazard of all-cause mortality, controlling for covariates. Results Over a median 2.6 years (interquartile range: 1.4–3.7), 1.031 deaths were observed, including 2.2% (259/11,564) of women and 3.7% (772/20,758) of men. Women had a greater increased risk of mortality compared to the general population (SMR 5.1 95% CI: 4.5, 5.7) than men (SMR 4.3 95% CI: 4.0, 4.6). The relative risk of death for women compared with men was 1.18 (95% CI: 1.02, 1.36). Women had a lower instantaneous hazard of all-cause mortality than men (HR 0.58, 95% CI 0.50, 0.68), controlling for other factors. Significant interaction effects indicated that among men, mortality risk was decreased by full-time employment and increased by non-daily heroin use (relative to daily use) and medical problems. Concurrent opioid and methamphetamine/cocaine use increased mortality risk among women and decreased it among men. Conclusions Treatment for opioid dependence is likely to reduce mortality risk among men by addressing employment and medical problems, and via interventions to reduce overdose risk after heroin abstinence, and among women by attending to the concurrent use of methamphetamine/cocaine and opioids.

We examined risk factors associated with hepatitis C virus (HCV) infection among opioid-dependent patients enrolled into medication-assisted therapy (buprenorphine or methadone) to determine factors affecting chronic infection. Patients (N = 1039) were randomized as part of a larger, multisite clinical trial sponsored by the National Drug Abuse Treatment Clinical Trials Network assessing liver function. HCV status was first assessed with an antibody screen; if positive, then current infection was determined with an antigen screen testing for detectable virus. Patients were classified as HCV negative, HCV positive but have cleared the virus, or as having chronic HCV. Logistic regression analysis was used to examine demographic and behavioral correlates of the three groups. Thirty-four percent of patients were classified with chronic infection and 14% had evidence of prior infection with apparent clearing of the virus. Chronic infection was associated with recent injection drug use and cocaine use. Chronic HCV infection was also associated with being older and Hispanic. Age, ethnicity, and current drug use increase the likelihood of being chronically infected with HCV. Strategies targeting high risk subgroups can aid in preventing further disease escalation.

Aims To estimate mortality rates among treated opioid-dependent individuals by cause and in relation to the general population, and to estimate the instantaneous effects of opioid detoxification and maintenance treatment (MMT) on the hazard of all-cause and cause-specific mortality. Design Population-based treatment cohort study. Setting Linked mortality data on all individuals first enrolled in publicly funded pharmacological treatment for opioid dependence in California, USA from 2006 to 2010. Participants A total of 32 322 individuals, among whom there were 1031 deaths (3.2%) over a median follow-up of 2.6 years (interquartile range = 1.4-3.7). Measurements The primary outcome was mortality, indicated by time to death, crude mortality rates (CMR) and standardized mortality ratios (SMR). Findings Individuals being treated for opioid dependence had a more than fourfold increase of mortality risk compared with the general population [SMR = 4.5, 95% confidence interval (CI) = 4.2, 4.8]. Mortality risk was higher (1) when individuals were out-of-treatment (SMR = 6.1, 95% CI = 5.7, 6.5) than in-treatment (SMR = 1.8, 95% CI = 1.6, 2.1) and (2) during detoxification (SMR = 2.4, 95% CI = 1.5, 3.8) than during MMT (SMR = 1.8, 95% CI = 1.5, 2.1), especially in the 2 weeks post-treatment entry (SMR = 5.5, 95% CI = 2.7, 9.8 versus SMR = 2.5, 95% CI = 1.7, 4.9). Detoxification and MMT both independently reduced the instantaneous hazard of all-cause and drug-related mortality. MMT preceded by detoxification was associated with lower all-cause and other cause-specific mortality than MMT alone. Conclusions In people with opiate dependence, detoxification and methadone maintenance treatment both independently reduce the instantaneous hazard of all-cause and drug-related mortality. Language: en

AimsThis study examined the longitudinal association between reductions in cannabis use and changes in anxiety, depression, sleep quality, and quality of life.MethodsSecondary analyses were conducted based on data from a cannabis use disorder medication trial in 302 adults (ages 18-50). Changes in symptoms of anxiety and depression, sleep quality, and quality of life were assessed in relation to changes in cannabis use during the 12-week trial of treatment.ResultsBased on the slope of individual cannabis use trajectory, the sample was classified into two groups (Cannabis Use Reduction, n=152 vs. Cannabis Use Increase, n=150) which was included as a binary covariate in subsequent modeling. Controlling for demographics (age, gender, race/ethnicity), treatment condition, and time-varying tobacco and alcohol use, separate latent growth curve models showed a significant association between the Cannabis Use Reduction group and improvement (i.e., lower values in slope) in anxiety (β=-0.09, SE=0.04; p

Cumulative evidence suggests that cocaine use could alter the structure and function of different brain systems. However, the extent to which the altered brain structure and function possibly recover over time after cocaine abstinence remains less clear. The present study examines 39 male military veterans with different stages of cocaine addiction and long-term abstinence (from 1 year up to 30 years) and evaluates plausible changes in brain structure and function of specific brain regions that sub-serve addictions. These include the striatum that is involved in cocaine reward; the lateral prefrontal cortex (especially the dorsolateral PFC) that plays a major role in inhibitory control; the insula, which has been implicated in craving; and the medial orbitofrontal (OFC) and ventromedial prefrontal cortex (VMPFC) shown to play key roles in foresight and decision-making. The results suggest that there are differences in both brain structure (gray matter volume, GMV) and function between cocaine USERS and CONTROLS, with USERS showing plausible relative strengthening in neural systems for processing reward and craving, and relative weakening in neural systems involved in inhibitory control and decision-making. Examination of possible neural changes after abstinence suggests that presumed recovery occurs mostly in neural systems related to reward, craving, and inhibitory control, but to a lesser extent in neural systems related to decision-making. Given the limitations of the data in terms of a small sample size, as well as the lack of certainty about occasional use in the abstinent group, these results may be considered as preliminary. However, they are compelling in that they suggest that male military veterans cocaine USERS are indefinitely at a higher risk compared to CONTROLS for making lapses in judgment and decision-making leading to possible relapse, if reward salience and craving become more intense. Understanding the neurobiology of long-term cocaine abstinence in vulnerable populations and beyond could help devising better therapeutic strategies that prevent relapse.

BACKGROUND Mobile health technologies have been found to improve the self-management of chronic diseases. However, there is limited research regarding their feasibility in supporting recovery from substance use disorders (SUDs) in China. OBJECTIVE The objective of this study was to examine the feasibility of a mobile phone-based ecological momentary assessment (EMA) app by testing the concordance of drug use assessed by the EMA, urine testing, and a life experience timeline (LET) assessment. METHODS A total of 75 participants dependent on heroin or amphetamine-type stimulant (ATS) in Shanghai were recruited to participate in a 4-week pilot study. Of the participants, 50 (67% [50/75]) were randomly assigned to the experimental group and 25 (33% [25/75]) were assigned to the control group. The experimental group used mobile health (mHealth) based EMA technology to assess their daily drug use in natural environments and received 2 short health messages each day, whereas the control group only received 2 short health messages each day from the app. Urine tests and LET assessments were conducted each week and a post-intervention survey was administered to both groups. The correlations among the EMA, the LET assessment, and the urine test were investigated. RESULTS The mean age of the participants was 41.6 (SD 8.0) years, and 71% (53/75) were male. During the 4 weeks of observation, 690 daily EMA survey data were recorded, with a response rate of 49.29% (690/1400). With respect to drug use, the percent of agreement between the EMA and the LET was 66.7%, 79.2%, 72.4%, and 85.8%, respectively, for each of the 4 weeks, whereas the percent of agreement between the EMA and the urine test was 51.2%, 65.1%, 61.9%, and 71.5%, respectively. The post-intervention survey indicated that 46% (32/70) of the participants preferred face-to-face interviews rather than the mHealth app. CONCLUSIONS This study demonstrated poor agreement between the EMA data and the LET and found that the acceptance of mHealth among individuals with SUDs in China was not positive. Hence, greater efforts are needed to improve the feasibility of mHealth in China.

ObjectivesElevated mortality has been observed among individuals with opioid use disorder (OUD) treated in addiction specialty clinics or programs. Information about OUD patients in general healthcare settings is needed in light of the current effort to integrate addiction services into primary healthcare systems. This study examined mortality rates, causes of death, and associated risk factors among patients with OUD in a large general healthcare system.MethodsMortality data were linked with electronic health records of 2576 OUD patients cared for in a large university health system from 2006 to 2014.ResultsThere were 465 deaths confirmed (18.1% of the study participants), corresponding to a crude mortality rate of 48.6 per 1000 person-years and standardized mortality ratio of 10.3 (95% confidence interval [CI] 9.4-11.3). Drug overdose and disorder (19.8%), cardiovascular diseases (17.4%), cancer (16.8%), and infectious diseases (13.5%, including 12% hepatitis C virus [HCV]) were the leading causes of death. HCV (hazard ratio [HR] 1.99, 95% CI 1.62-2.46) and alcohol use disorder (HR 1.27, 95% CI 1.05-1.55) were 2 clinically important indicators of overall mortality risk. Tobacco use disorder (adjusted HR [AHR] 2.58, 95% CI 1.60-4.17) was associated with increased risk of cardiovascular death, HCV infection (AHR 2.55, 95% CI 1.52-4.26) with cancer mortality risk, and HCV (AHR 1.92, 95% CI 1.03-3.60) and alcohol use disorder (AHR 5.44, 95% CI 2.95-10.05) with liver-related mortality risk.ConclusionsPatients with OUD in a general healthcare system demonstrated alarmingly high morbidity and mortality, which challenges healthcare systems to find innovative ways to identify and treat patients with substance use disorder.

This chapter presents statistical methods and issues commonly encountered in the design and analysis of substance abuse research studies. It begins with a general discussion contrasting primary and secondary data analysis, followed by an overview of study design from the perspective of the conduct of primary research, including hypothesis and planned analysis specification, sampling schemes, and power analysis. Next, descriptions of study characteristics are included from the perspective of secondary analysis, paying particular attention to characteristics that need to be considered when determining appropriate analytic methods and interpreting results. Statistical methods reviewed include: various types of regression (linear regression, logistic regression, survival analysis), related topics, such as moderators and mediators, as well as multilevel models (for longitudinal or clustered observations), and latent variable modeling techniques, including structural equation modeling, latent class analysis, latent transition analysis, and growth mixture modeling. Finally, overviews of four major special topics particularly important when using secondary data are provided, which include: multiplicity of hypotheses, combining data and results from multiple studies, missing data, and propensity scores. Where helpful, concepts and methods are illustrated using practical examples.

Background California treats the largest population of opioid dependent individuals in the USA and is among a small group of states that applies regulations for opioid treatment that are more stringent than existing federal regulations. We aim to characterize changes in patient characteristics and treatment utilization over time, and identify determinants of successful completion of detoxification and MMT retention in repeated attempts. Methods State-wide administrative data was obtained from California Outcome Measurement System during the period: January 1st, 1991–March 31st, 2012. Short-term detoxification treatment and long-term maintenance treatment, primarily with methadone, was available to study participants. Mixed effects regression models were used to define determinants of successful completion of the detoxification treatment protocol (as classified by treatment staff) and duration of maintenance treatment. Results The study sample consisted of 237,709 unique individuals and 885,971 treatment episodes; 837% were detoxification treatment episodes in 1994, dropping to 40.5% in 2010. Among individuals accessing only detoxification, the adjusted odds of success declined with each successive attempt (vs. 1st attempt: 2nd: OR: 0.679; 95% CI (0.610, 0.755); 3rd: 0.557 (0.484, 0.641); 4th: 0.526 (0.445, 0.622); 5th: 0.407 (0.334, 0.497); ≥6th: 0.339 (0.288, 0.399). For those ever accessing maintenance treatment, later subsequent attempts were longer in duration, and those with two or more prior attempts at detoxification had marginally longer subsequent maintenance episodes (hazard ratio: 0.97; 95% CI: 0.95, 0.99). Finally, only 10.9% of all detoxification episodes were followed by admission into maintenance treatment within 14 days. Conclusions This study has revealed high rates of detoxification treatment for opioid dependence in California throughout the study period, and decreasing odds of success in repeated attempts at detoxification.