Economic Evaluations of Establishing Opioid Overdose Prevention Centers in 12 North American Cities: A Systematic Review.

OBJECTIVES: Overdose prevention centers (OPCs) provide a safe place where people can consume preobtained drugs under supervision so that a life-saving medical response can be provided quickly in the event of an overdose. OPCs are programs that are established in Canada and have recently become legally sanctioned in only a few United States jurisdictions. METHODS: We conducted a systematic review that summarizes and identifies gaps of economic evidence on establishing OPCs in North America to guide future expansion of OPCs. RESULTS: We included 16 final studies that were evaluated with the Consolidated Health Economic Evaluation Reporting Standards and Drummond checklists. Eight studies reported cost-effectiveness results (eg, cost per overdose avoided or cost per quality-adjusted life-year), with 6 also including cost-benefit; 5 reported only cost-benefit results, and 3 cost offsets. Health outcomes primarily included overdose mortality outcomes or HIV/hepatitis C virus infections averted. Most studies used mathematical modeling and projected OPC outcomes using the experience of a single facility in Vancouver, BC. CONCLUSIONS: OPCs were found to be cost-saving or to have favorable cost-effectiveness or cost-benefit ratios across all studies. Future studies should incorporate the experience of OPCs established in various settings and use a greater diversity of modeling designs.

The association between naloxone claims and proportion of independent vs. chain pharmacies: A longitudinal analysis of naloxone claims in the US.

BACKGROUND: Expanding access to naloxone through pharmacies is an important policy goal. Our objective was to characterize national county-level naloxone dispensing of chain versus independent pharmacies. METHODS: The primary exposure in our longitudinal analysis was the proportion of chain pharmacies in a county, identified through the US Department of Homeland Security 2010 Infrastructure Foundation-Level Data. We defined counties as having "higher proportion" of chain pharmacies if at least 50% of pharmacies were large national chains. The primary outcome was quarter-year (2016Q1-2019Q2) rate of pharmacy naloxone claims per 100,000 persons from Symphony Health at the county-level. We compared the naloxone dispensing rate between county types using two-sample t-tests. We estimated the association between county-level chain pharmacy proportion and rate of naloxone claims using a linear model with year-quarter fixed effects. RESULTS: Nearly one third of counties (n=946) were higher proportion. Higher proportion counties had a significantly higher rate of naloxone claims across the study period, in 4 of 6 urban-rural classifications, and in counties with and without naloxone access laws. The linear model confirmed that higher proportion counties had a significantly higher rate of naloxone claims, adjusting for urban/rural designation, income, population characteristics, opioid mortality rate, co-prescribing laws and naloxone access laws. CONCLUSION: In this national study, we found an association between naloxone dispensing rates and the county-level proportion of chain (versus independent) pharmacies. Incentivizing naloxone dispensing through educational, regulatory, or legal efforts may improve naloxone availability and dispensing rates - particularly in counties with proportionately high numbers of independent pharmacies.

Linkage Case Management and Posthospitalization Outcomes in People With HIV: The Daraja Randomized Clinical Trial.

Importance: Despite the widespread availability of antiretroviral therapy (ART), people with HIV still experience high mortality after hospital admission. Objective: To determine whether a linkage case management intervention (named "Daraja" ["bridge" in Kiswahili]) that was designed to address barriers to HIV care engagement could improve posthospital outcomes. Design, Setting, and Participants: Single-blind, individually randomized clinical trial to evaluate the effectiveness of the Daraja intervention. The study was conducted in 20 hospitals in Northwestern Tanzania. Five hundred people with HIV who were either not treated (ART-naive) or had discontinued ART and were hospitalized for any reason were enrolled between March 2019 and February 2022. Participants were randomly assigned 1:1 to receive either the Daraja intervention or enhanced standard care and were followed up for 12 months through March 2023. Intervention: The Daraja intervention group (n = 250) received up to 5 sessions conducted by a social worker at the hospital, in the home, and in the HIV clinic over a 3-month period. The enhanced standard care group (n = 250) received predischarge HIV counseling and assistance in scheduling an HIV clinic appointment. Main Outcomes and Measures: The primary outcome was all-cause mortality at 12 months after enrollment. Secondary outcomes related to HIV clinic attendance, ART use, and viral load suppression were extracted from HIV medical records. Antiretroviral therapy adherence was self-reported and pharmacy records confirmed perfect adherence. Results: The mean age was 37 (SD, 12) years, 76.8% were female, 35.0% had CD4 cell counts of less than 100/µL, and 80.4% were ART-naive. Intervention fidelity and uptake were high. A total of 85 participants (17.0%) died (43 in the intervention group; 42 in the enhanced standard care group); mortality did not differ by trial group (17.2% with intervention vs 16.8% with standard care; hazard ratio [HR], 1.01; 95% CI, 0.66-1.55; P = .96). The intervention, compared with enhanced standard care, reduced time to HIV clinic linkage (HR, 1.50; 95% CI, 1.24-1.82; P < .001) and ART initiation (HR, 1.56; 95% CI, 1.28-1.89; P < .001). Intervention participants also achieved higher rates of HIV clinic retention (87.4% vs 76.3%; P = .005), ART adherence (81.1% vs 67.6%; P = .002), and HIV viral load suppression (78.6% vs 67.1%; P = .01) at 12 months. The mean cost of the Daraja intervention was about US $22 per participant including startup costs. Conclusions and Relevance: Among hospitalized people with HIV, a linkage case management intervention did not reduce 12-month mortality outcomes. These findings may help inform decisions about the potential role of linkage case management among hospitalized people with HIV. Trial Registration: ClinicalTrials.gov Identifier: NCT03858998.

Protocol for an economic evaluation of scalable strategies to improve mental health among perinatal women: non-specialist care delivered via telemedicine vs. specialist care delivered in-person.

BACKGROUND: Perinatal depression affects an estimated 1 in 5 women in North America during the perinatal period, with annualized lifetime costs estimated at $20.6 billion CAD in Canada and over $45.9 billion USD in the US. Access to psychological treatments remains limited for most perinatal women suffering from depression and anxiety. Some barriers to effective care can be addressed through task-sharing to non-specialist providers and through telemedicine platforms. The cost-effectiveness of these strategies compared to traditional specialist and in-person models remains unknown. This protocol describes an economic evaluation of non-specialist providers and telemedicine, in comparison to specialist providers and in-person sessions within the ongoing Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT) trial. METHODS: The economic evaluation will be undertaken alongside the SUMMIT trial. SUMMIT is a pragmatic, randomized, non-inferiority trial across five North American study sites (N = 1,226) of the comparable effectiveness of two types of providers (specialist vs. non-specialist) and delivery modes (telemedicine vs. in-person) of a behavioural activation treatment for perinatal depressive and anxiety symptoms. The primary economic evaluation will be a cost-utility analysis. The outcome will be the incremental cost-effectiveness ratio, which will be expressed as the additional cost required to achieve an additional quality-adjusted life-year, as assessed by the EuroQol 5-Dimension 5-Level instrument. A secondary cost-effectiveness analysis will use participants' depressive symptom scores. A micro-costing analysis will be conducted to estimate the resources/costs required to implement and sustain the interventions; healthcare resource utilization will be captured via self-report. Data will be pooled and analysed using uniform price and utility weights to determine cost-utility across all trial sites. Secondary country-specific cost-utility and cost-effectiveness analyses will also be completed. Sensitivity analyses will be conducted, and cost-effectiveness acceptability-curves will be generated, in all instances. DISCUSSION: Results of this study are expected to inform key decisions related to dissemination and scale up of evidence-based psychological interventions in Canada, the US, and possibly worldwide. There is potential impact on real-world practice by informing decision makers of the long-term savings to the larger healthcare setting in services to support perinatal women with common mental health conditions.

Racial/ethnic differences in receipt of naloxone distributed by opioid overdose prevention programs in New York City.

INTRODUCTION: We evaluated racial/ethnic differences in the receipt of naloxone distributed by opioid overdose prevention programs (OOPPs) in New York City (NYC). METHODS: We used naloxone recipient racial/ethnic data collected by OOPPs from April 2018 to March 2019. We aggregated quarterly neighborhood-specific rates of naloxone receipt and other covariates to 42 NYC neighborhoods. We used a multilevel negative binomial regression model to assess the relationship between neighborhood-specific naloxone receipt rates and race/ethnicity. Race/ethnicity was stratified into four mutually exclusive groups: Latino, non-Latino Black, non-Latino White, and non-Latino Other. We also conducted racial/ethnic-specific geospatial analyses to assess whether there was within-group geographic variation in naloxone receipt rates for each racial/ethnic group. RESULTS: Non-Latino Black residents had the highest median quarterly naloxone receipt rate of 41.8 per 100,000 residents, followed by Latino residents (22.0 per 100,000), non-Latino White (13.6 per 100,000) and non-Latino Other residents (13.3 per 100,000). In our multivariable analysis, compared with non-Latino White residents, non-Latino Black residents had a significantly higher receipt rate, and non-Latino Other residents had a significantly lower receipt rate. In the geospatial analyses, both Latino and non-Latino Black residents had the most within-group geographic variation in naloxone receipt rates compared to non-Latino White and Other residents. CONCLUSIONS: This study found significant racial/ethnic differences in naloxone receipt from NYC OOPPs. We observed substantial variation in naloxone receipt for non-Latino Black and Latino residents across neighborhoods, indicating relatively poorer access in some neighborhoods and opportunities for new approaches to address geographic and structural barriers in these locations.

Econometric Issues in Prospective Economic Evaluations Alongside Clinical Trials: Combining the Nonparametric Bootstrap With Methods That Address Missing Data.

Prospective economic evaluations conducted alongside clinical trials have become an increasingly popular approach in evaluating the cost-effectiveness of a public health initiative or treatment intervention. These types of economic studies provide improved internal validity and accuracy of cost and effectiveness estimates of health interventions and, compared with simulation or decision-analytic models, have the advantage of jointly observing health and economics outcomes of trial participants. However, missing data due to incomplete response or patient attrition, and sampling uncertainty are common concerns in econometric analysis of clinical trials. Missing data are a particular problem for comparative effectiveness trials of substance use disorder interventions. Multiple imputation and inverse probability weighting are 2 widely recommended methods to address missing data bias, and the nonparametric bootstrap is recommended to address uncertainty in predicted mean cost and effectiveness between trial interventions. Although these methods have been studied extensively by themselves, little is known about how to appropriately combine them and about the potential pitfalls and advantages of different approaches. We provide a review of statistical methods used in 29 economic evaluations of substance use disorder intervention identified from 4 published systematic reviews and a targeted search of the literature. We evaluate how each study addressed missing data bias, whether the recommended nonparametric bootstrap was used, how these 2 methods were combined, and conclude with recommendations for future research.

Baseline representativeness of patients in clinics enrolled in the PRimary care Opioid Use Disorders treatment (PROUD) trial: comparison of trial and non-trial clinics in the same health systems.

BACKGROUND: Pragmatic primary care trials aim to test interventions in "real world" health care settings, but clinics willing and able to participate in trials may not be representative of typical clinics. This analysis compared patients in participating and non-participating clinics from the same health systems at baseline in the PRimary care Opioid Use Disorders treatment (PROUD) trial. METHODS: This observational analysis relied on secondary electronic health record and administrative claims data in 5 of 6 health systems in the PROUD trial. The sample included patients 16-90 years at an eligible primary care visit in the 3 years before randomization. Each system contributed 2 randomized PROUD trial clinics and 4 similarly sized non-trial clinics. We summarized patient characteristics in trial and non-trial clinics in the 2 years before randomization ("baseline"). Using mixed-effect regression models, we compared trial and non-trial clinics on a baseline measure of the primary trial outcome (clinic-level patient-years of opioid use disorder (OUD) treatment, scaled per 10,000 primary care patients seen) and a baseline measure of the secondary trial outcome (patient-level days of acute care utilization among patients with OUD). RESULTS: Patients were generally similar between the 10 trial clinics (n = 248,436) and 20 non-trial clinics (n = 341,130), although trial clinics' patients were slightly younger, more likely to be Hispanic/Latinx, less likely to be white, more likely to have Medicaid/subsidized insurance, and lived in less wealthy neighborhoods. Baseline outcomes did not differ between trial and non-trial clinics: trial clinics had 1.0 more patient-year of OUD treatment per 10,000 patients (95% CI: - 2.9, 5.0) and a 4% higher rate of days of acute care utilization than non-trial clinics (rate ratio: 1.04; 95% CI: 0.76, 1.42). CONCLUSIONS: trial clinics and non-trial clinics were similar regarding most measured patient characteristics, and no differences were observed in baseline measures of trial primary and secondary outcomes. These findings suggest trial clinics were representative of comparably sized clinics within the same health systems. Although results do not reflect generalizability more broadly, this study illustrates an approach to assess representativeness of clinics in future pragmatic primary care trials.

Experimental diffuse brain injury and a model of Alzheimer's disease exhibit disease-specific changes in sleep and incongruous peripheral inflammation.

Elderly populations (≥65 years old) have the highest risk of developing Alzheimer's disease (AD) and/or obtaining a traumatic brain injury (TBI). Using translational mouse models, we investigated sleep disturbances and inflammation associated with normal aging, TBI and aging, and AD. We hypothesized that aging results in marked changes in sleep compared with adult mice, and that TBI and aging would result in sleep and inflammation levels similar to AD mice. We used female 16-month-old wild-type (WT Aged) and 3xTg-AD mice, as well as a 2-month-old reference group (WT Adult), to evaluate sleep changes. WT Aged mice received diffuse TBI by midline fluid percussion, and blood was collected from both WT Aged (pre- and post-TBI) and 3xTg-AD mice to evaluate inflammation. Cognitive behavior was tested, and tissue was collected for histology. Bayesian generalized additive and mixed-effects models were used for analyses. Both normal aging and AD led to increases in sleep compared with adult mice. WT Aged mice with TBI slept substantially more, with fragmented shorter bouts, than they did pre-TBI and compared with AD mice. However, differences between WT Aged and 3xTg-AD mice in immune cell populations and plasma cytokine levels were incongruous, cognitive deficits were similar, and cumulative sleep was not predictive of inflammation or behavior for either group. Our results suggest that in similarly aged individuals, TBI immediately induces more profound sleep alterations than in AD, although both diseases likely include cognitive impairments. Unique pathological sleep pathways may exist in elderly individuals who incur TBI compared with similarly aged individuals who have AD, which may warrant disease-specific treatments in clinical settings.

Diesel and Crude Oil Biodegradation by Cold-Adapted Microbial Communities in the Labrador Sea.

Oil spills in the subarctic marine environment off the coast of Labrador, Canada, are increasingly likely due to potential oil production and increases in ship traffic in the region. To understand the microbiome response and how nutrient biostimulation promotes biodegradation of oil spills in this cold marine setting, marine sediment microcosms amended with diesel or crude oil were incubated at in situ temperature (4°C) for several weeks. Sequencing of 16S rRNA genes following these spill simulations revealed decreased microbial diversity and enrichment of putative hydrocarbonoclastic bacteria that differed depending on the petroleum product. Metagenomic sequencing revealed that the genus Paraperlucidibaca harbors previously unrecognized capabilities for alkane biodegradation, which were also observed in Cycloclasticus. Genomic and amplicon sequencing together suggest that Oleispira and Thalassolituus degraded alkanes from diesel, while Zhongshania and the novel PGZG01 lineage contributed to crude oil alkane biodegradation. Greater losses in PAHs from crude oil than from diesel were consistent with Marinobacter, Pseudomonas_D, and Amphritea genomes exhibiting aromatic hydrocarbon biodegradation potential. Biostimulation with nitrogen and phosphorus (4.67 mM NH4Cl and 1.47 mM KH2PO4) was effective at enhancing n-alkane and PAH degradation following low-concentration (0.1% [vol/vol]) diesel and crude oil amendments, while at higher concentrations (1% [vol/vol]) only n-alkanes in diesel were consumed, suggesting toxicity induced by compounds in unrefined crude oil. Biostimulation allowed for a more rapid shift in the microbial community in response to petroleum amendments, more than doubling the rates of CO2 increase during the first few weeks of incubation. IMPORTANCE Increases in transportation of diesel and crude oil in the Labrador Sea will pose a significant threat to remote benthic and shoreline environments, where coastal communities and wildlife are particularly vulnerable to oil spill contaminants. Whereas marine microbiology has not been incorporated into environmental assessments in the Labrador Sea, there is a growing demand for microbial biodiversity evaluations given the pronounced impact of climate change in this region. Benthic microbial communities are important to consider given that a fraction of spilled oil typically sinks such that its biodegradation occurs at the seafloor, where novel taxa with previously unrecognized potential to degrade hydrocarbons were discovered in this work. Understanding how cold-adapted microbiomes catalyze hydrocarbon degradation at low in situ temperature is crucial in the Labrador Sea, which remains relatively cold throughout the year.

Economic Evaluations of Pharmacologic Treatment for Opioid Use Disorder: A Systematic Literature Review.

OBJECTIVE: The crisis of opioid use puts a strain on resources in the United States and worldwide. There are 3 US Food and Drug Administration-approved medications for treatment of opioid use disorder: methadone, buprenorphine, and injectable extended-release naltrexone (XR-NTX). The comparative effectiveness and cost vary considerably among these 3 medications. Economic evaluations provide evidence that help stakeholders efficiently allocate scarce resources. Our objective was to summarize recent health economic evidence of pharmacologic treatment of opioid use disorder interventions. METHODS: We searched PubMed for peer-reviewed studies in English from August 2015 through December 2019 as an update to a 2015 review. We used the Drummond checklist to evaluate and categorize economic evaluation study quality. We summarized results by economic evaluation methodology and pharmacologic treatment modality. RESULTS: We identified 105 articles as potentially relevant and included 21 (4 cost-offset studies and 17 cost-effectiveness/cost-benefit studies). We found strengthened evidence on buprenorphine and methadone, indicating that these treatments are economically advantageous compared with no pharmacotherapy, but found limited evidence on XR-NTX. Only half of the cost-effectiveness studies used a generic preference-based measure of effectiveness, limiting broad comparison across diseases/disorders. The disease/disorder-specific cost-effectiveness measures vary widely, suggesting a lack of consensus on the value of substance use disorder treatment. CONCLUSION: We found studies that provide new evidence supporting the cost-effectiveness of buprenorphine compared with no pharmacotherapy. We found a lack of evidence supporting superior economic value for buprenorphine versus methadone, suggesting that both are attractive alternatives. Further economic research is needed on XR-NTX, as well as other emerging pharmacotherapies, treatment modalities, and dosage forms.

Narrativity and Referential Activity Predict Episodic Memory Strength in Autobiographical Memories.

Narrativity has been proposed as an indicator of episodic memory strength when people discuss their past (Nelson and Horowitz in Discourse Processes 31:307-324, 2001. https://doi.org/10.1207/S15326950dp31-3_5 ). Referential Activity, the extent to which words convey a speaker's experience of being present in the event being described, has been independently hypothesized to indicate episodic memory strength (Maskit in J Psycholinguist Res, 2021. https://doi.org/10.1007/s10936-021-09761-8 ). These hypotheses are tested using a linguistic measure of narrativity and a computerized measure of referential activity to predict previous independent ratings of episodic memory strength that used the Levine et al. (Psychol Aging 17(4):677-689, 2002. https://doi.org/10.1037//0882-7974.17.4.677 ) measure of internal details in retold personal memories provided by Schacter (Addis et al. in Psychol Sci 19(1):33-41, 2008. https://doi.org/10.1111/j.1467-9280.2008.02043.x ). Raters scored narrativity on four brief near and far past memories elicited from 32 subjects, using Nelson's narrative temporal sequence method based on Labov's (J Narrat Life Hist 7(1-4):395-415, 1997. https://doi.org/10.1075/jnlh.7.49som ) analysis of spoken narratives of personal experience; computerized weighted scores of referential activity (WRAD) were obtained on these same 128 memories. Data analysis showed that narrative temporal sequences predict internal details and WRAD predict internal details. Adding WRAD to narrative temporal sequences improved the prediction of internal details.

Cost-effectiveness of Hepatitis C Virus Treatment Models for People Who Inject Drugs in Opioid Agonist Treatment Programs.

BACKGROUND: Many people who inject drugs in the United States have chronic hepatitis C virus (HCV). On-site treatment in opiate agonist treatment (OAT) programs addresses HCV treatment barriers, but few evidence-based models exist. METHODS: We evaluated the cost-effectiveness of HCV treatment models for OAT patients using data from a randomized trial conducted in Bronx, New York. We used a decision analytic model to compare self-administered individual treatment (SIT), group treatment (GT), directly observed therapy (DOT), and no intervention for a simulated cohort with the same demographic characteristics of trial participants. We projected long-term outcomes using an established model of HCV disease progression and treatment (hepatitis C cost-effectiveness model: HEP-CE). Incremental cost-effectiveness ratios (ICERs) are reported in 2016 US$/quality-adjusted life years (QALY), discounted 3% annually, from the healthcare sector and societal perspectives. RESULTS: For those assigned to SIT, we projected 89% would ever achieve a sustained viral response (SVR), with 7.21 QALYs and a $245 500 lifetime cost, compared to 22% achieving SVR, with 5.49 QALYs and a $161 300 lifetime cost, with no intervention. GT was more efficient than SIT, resulting in 0.33 additional QALYs and a $14 100 lower lifetime cost per person, with an ICER of $34 300/QALY, compared to no intervention. DOT was slightly more effective and costly than GT, with an ICER > $100 000/QALY, compared to GT. In probabilistic sensitivity analyses, GT and DOT were preferred in 91% of simulations at a threshold of <$100 000/QALY; conclusions were similar from the societal perspective. CONCLUSIONS: All models were associated with high rates of achieving SVR, compared to standard care. GT and DOT treatment models should be considered as cost-effective alternatives to SIT.

Acute peripheral inflammation and post-traumatic sleep differ between sexes after experimental diffuse brain injury.

Identifying differential responses between sexes following traumatic brain injury (TBI) can elucidate the mechanisms behind disease pathology. Peripheral and central inflammation in the pathophysiology of TBI can increase sleep in male rodents, but this remains untested in females. We hypothesized that diffuse TBI would increase inflammation and sleep in males more so than in females. Diffuse TBI was induced in C57BL/6J mice and serial blood samples were collected (baseline, 1, 5, 7 days post-injury [DPI]) to quantify peripheral immune cell populations and sleep regulatory cytokines. Brains and spleens were harvested at 7DPI to quantify central and peripheral immune cells, respectively. Mixed-effects regression models were used for data analysis. Female TBI mice had 77%-124% higher IL-6 levels than male TBI mice at 1 and 5DPI, whereas IL-1ß and TNF-α levels were similar between sexes at all timepoints. Despite baseline sex differences in blood-measured Ly6Chigh monocytes (females had 40% more than males), TBI reduced monocytes by 67% in TBI mice at 1DPI. Male TBI mice had 31%-33% more blood-measured and 31% more spleen-measured Ly6G+ neutrophils than female TBI mice at 1 and 5DPI, and 7DPI, respectively. Compared with sham, TBI increased sleep in both sexes during the first light and dark cycles. Male TBI mice slept 11%-17% more than female TBI mice, depending on the cycle. Thus, sex and TBI interactions may alter the peripheral inflammation profile and sleep patterns, which might explain discrepancies in disease progression based on sex.

Cost-Effectiveness of Buprenorphine-Naloxone Versus Extended-Release Naltrexone to Prevent Opioid Relapse.

Background: Not enough evidence exists to compare buprenorphine-naloxone with extended-release naltrexone for treating opioid use disorder. Objective: To evaluate the cost-effectiveness of buprenorphine-naloxone versus extended-release naltrexone. Design: Cost-effectiveness analysis alongside a previously reported randomized clinical trial of 570 adults in 8 U.S. inpatient or residential treatment programs. Data Sources: Study instruments. Target Population: Adults with opioid use disorder. Time Horizon: 24-week intervention with an additional 12 weeks of observation. Perspective: Health care sector and societal. Interventions: Buprenorphine-naloxone and extended-release naltrexone. Outcome Measures: Incremental costs combined with incremental quality-adjusted life-years (QALYs) and incremental time abstinent from opioids. Results of Base-Case Analysis: Use of the health care sector perspective and a willingness-to-pay threshold of $100 000 per QALY showed buprenorphine-naloxone to be preferable to extended-release naltrexone in 97% of bootstrap replications at 24 weeks and in 85% at 36 weeks. Similar results were obtained with incremental time abstinent from opioids as an outcome and with use of the societal perspective. Results of Sensitivity Analysis: The base-case results were sensitive to the cost of the 2 treatments and the success of randomized treatment initiation. Limitation: Relatively short follow-up for a chronic condition, substantial missing data, no information on patient out-of-pocket and social service costs. Conclusion: Buprenorphine-naloxone is preferred to extended-release naltrexone as first-line treatment when both options are clinically appropriate and patients require detoxification before initiating extended-release naltrexone. Primary Funding Source: National Institute on Drug Abuse, National Institutes of Health.

Extended-Release Naltrexone to Prevent Opioid Relapse in Criminal Justice Offenders.

BACKGROUND: Extended-release naltrexone, a sustained-release monthly injectable formulation of the full mu-opioid receptor antagonist, is effective for the prevention of relapse to opioid dependence. Data supporting its effectiveness in U.S. criminal justice populations are limited. METHODS: In this five-site, open-label, randomized trial, we compared a 24-week course of extended-release naltrexone (Vivitrol) with usual treatment, consisting of brief counseling and referrals for community treatment programs, for the prevention of opioid relapse among adult criminal justice offenders (i.e., persons involved in the U.S. criminal justice system) who had a history of opioid dependence and a preference for opioid-free rather than opioid maintenance treatments and who were abstinent from opioids at the time of randomization. The primary outcome was the time to an opioid-relapse event, which was defined as 10 or more days of opioid use in a 28-day period as assessed by self-report or by testing of urine samples obtained every 2 weeks; a positive or missing sample was computed as 5 days of opioid use. Post-treatment follow-up occurred at weeks 27, 52, and 78. RESULTS: A total of 153 participants were assigned to extended-release naltrexone and 155 to usual treatment. During the 24-week treatment phase, participants assigned to extended-release naltrexone had a longer median time to relapse than did those assigned to usual treatment (10.5 vs. 5.0 weeks, P<0.001; hazard ratio, 0.49; 95% confidence interval [CI], 0.36 to 0.68), a lower rate of relapse (43% vs. 64% of participants, P<0.001; odds ratio, 0.43; 95% CI, 0.28 to 0.65), and a higher rate of opioid-negative urine samples (74% vs. 56%, P<0.001; odds ratio, 2.30; 95% CI, 1.48 to 3.54). At week 78 (approximately 1 year after the end of the treatment phase), rates of opioid-negative urine samples were equal (46% in each group, P=0.91). The rates of other prespecified secondary outcome measures--self-reported cocaine, alcohol, and intravenous drug use, unsafe sex, and reincarceration--were not significantly lower with extended-release naltrexone than with usual treatment. Over the total 78 weeks observed, there were no overdose events in the extended-release naltrexone group and seven in the usual-treatment group (P=0.02). CONCLUSIONS: In this trial involving criminal justice offenders, extended-release naltrexone was associated with a rate of opioid relapse that was lower than that with usual treatment. Opioid-use prevention effects waned after treatment discontinuation. (Funded by the National Institute on Drug Abuse; ClinicalTrials.gov number, NCT00781898.).

The "Real" Number of Washington State Adolescents Using Marijuana, and Why: A Misclassification Analysis.

BACKGROUND: Although causality is difficult to establish, the regular use of marijuana has been associated with many adverse physiological and sociological consequences. There is considerable concern regarding marijuana use among adolescents, as the likelihood of adverse consequences increases significantly for this age group. The most comprehensive data for identifying risk factors for adolescent marijuana use is typically self-report, which may be over- or under-reported for a variety of reasons, including stigmatization, peer-pressure, or fear of being discovered. OBJECTIVES: To identify the prevalence of adolescent marijuana use in Washington State, and the associated risk and protective factors, while controlling for and estimating the extent of misreporting, and its determinants. METHOD: Data came from the 2014 Washington State Healthy Youth Survey. We accounted for missingness using chained multivariate imputation equations, resulting in 33,320 complete observations. Our model was estimated using a maximum likelihood multiple regression designed to control for systematic misclassification in binary dependent variables. RESULTS: Approximately 12% of Washington adolescents claimed to have used marijuana in the past 30 days. Our estimates indicate this figure is likely closer to 18%. Determinants of use included use of other substances, gender, age, and measures of deviant social influences, personality/attitude, school and family bonds, bullying, and acquisition ease. Determinants of misreporting included use of other substances, gender, parental education, and family bonds. CONCLUSIONS: Failing to control for misreporting considerably underestimates the prevalence of marijuana use among adolescents. Our model allows us to better identify at-risk adolescents and inform focused prevention efforts.

Decreases in smoking during treatment for methamphetamine-use disorders: preliminary evidence.

Despite high rates of smoking (70-90%) and the severely negative impact of smoking on physical and mental health, only 12% of individuals receiving stimulant-use disorder treatment also receive smoking-cessation treatment. The aim of this investigation was to examine the effect of a contingency management (CM) intervention targeting methamphetamine (MA) use on cigarette smoking. Sixty-one adults with MA-use disorders who were smokers were assigned to CM or standard psychosocial treatment. Rates of smoking-negative breath samples (carbon monoxide <3 ppm) were compared between the two groups while controlling for baseline carbon monoxide level, marijuana use, MA use, and time. This subgroup of mostly male (59%) participants included 44 participants in the CM group and 17 participants in the standard psychosocial treatment. Tobacco smoking participants who received CM targeting MA use were 140% (odds ratio: 2.395; 95% confidence interval: 1.073-5.346) more likely to submit a smoking-negative breath sample relative to standard psychosocial treatment during the treatment period, holding constant several other prespecified covariates. This study provides evidence that a behavioral treatment for MA use results in reductions in cigarette smoking in adults with MA-use disorder.

Physician Time Burden Associated with Querying Prescription Drug Monitoring Programs.

Objective: Prescription drug monitoring programs (PDMPs) enable prescribers to review patient prescription histories, and their use is mandatory in many states. We estimated the cost of physicians retrieving PDMP patient reports compared with a model where a delegate (i.e., administrative staff) retrieves reports. Methods: We performed a cost analysis with a one-year time horizon, from the perspective of physicians' employers. We obtained specialty-specific estimates of controlled substance prescribing frequency from the National Ambulatory Medical Care Survey, 2012-2014. We defined three PDMP usage cases based on the frequency of queries: comprehensive (before every Schedule II-IV controlled substance prescription), selective (before new Schedule II-IV prescriptions and every six months for continuing medications), and minimal (before new Schedule II or III prescriptions and annually for continuing medications). Results: The delegate model was less costly for all specialties in the comprehensive usage case and most specialties in the selective usage case, and it was similar to physician model costs in the minimal usage case. Estimated annual costs of the physician model to a large health care system (1,000 full-time equivalent physicians) were $1.6 million for comprehensive usage, $1.1 million for selective usage, and $645,313 for minimal usage. The delegate model was less costly in the comprehensive (savings of $907,283) and selective usage cases (savings of $156,216). Conclusions: Relying on delegates vs physicians to retrieve reports is less costly in most cases. Automation and integration of PDMP data into electronic health records may reduce costs further. Physicians, health care systems, and states should collaborate to streamline access to PDMPs.

An Economic Evaluation of Coordinated Specialty Care (CSC) Services for First-Episode Psychosis in the U.S. Public Sector.

BACKGROUND: Schizophrenia spectrum disorders exert a large and disproportionate economic impact. Early intervention services may be able to alleviate the burden of schizophrenia spectrum disorders on diagnosed individuals, caregivers, and society at large. Economic analyses of observational studies have supported investments in specialized team-based care for early psychosis; however, questions remain regarding the economic viability of first-episode services in the fragmented U.S. healthcare system. The clinic for Specialized Treatment Early in Psychosis (STEP) was established in 2006, to explicitly model a nationally-relevant U.S. public-sector early intervention service. The purpose of this study was to conduct an economic evaluation of STEP, a Coordinated Specialty Care service (CSC) based in a U.S. State-funded community mental health center, relative to usual treatment (UT). METHODS: Eligible patients were within 5 years of psychosis onset and had no more than 12 weeks of lifetime antipsychotic exposure. Participants were randomized to STEP or UT. The annual per-patient cost of the STEP intervention per se was estimated assuming a steady-state caseload of 30 patients. A cost-offset analysis was conducted to estimate the net value of STEP from a third-party payer perspective. Participant healthcare service utilization was evaluated at 6 months and over the entire 12 months post randomization. Generalized linear model multivariable regressions were used to estimate the effect of STEP on healthcare costs over time, and generate predicted mean costs, which were combined with the per-patient cost of STEP. RESULTS: The annual per-patient cost of STEP was $1,984. STEP participants were significantly less likely to have any inpatient or ED visits; among individuals who did use such services in a given period, the associated costs were significantly lower for STEP participants at month 12. We did not observe a similar effect with regard to other healthcare services. The predicted average total costs were lower for STEP than UT, indicating a net benefit for STEP of $1,029 at month 6 and $2,991 at month 12; however, the differences were not statistically significant. CONCLUSIONS: Our findings are promising with regard to the value of STEP to third-party payers.

Implementation of a nationwide health economic consultation service to assist substance use researchers: Lessons learned.

BACKGROUND: Health economic evaluation findings assist stakeholders in improving the quality, availability, scalability, and sustainability of evidence-based services, and in maximizing the efficiency of service delivery. The Center for Health Economics of Treatment Interventions for Substance Use Disorders, HCV, and HIV (CHERISH) is a NIDA-funded multi-institutional center of excellence whose mission is to develop and disseminate health-economic research on healthcare utilization, health outcomes, and health-related behaviors that informs substance use disorder treatment policy, and HCV and HIV care of people who use substances. METHODS: We designed a consultation service that is free to researchers whose work aligns with CHERISH's mission. The service includes up to six hours of consulting time. After prospective consultees submit their request online, they receive a screening call from the consultation service director, who connects them with a consultant with relevant expertise. Consultees and consultants complete web-based evaluations following the consultation; consultees also complete a six-month follow-up. We report on the status of the service from its inception in July 2015 through June 2017. RESULTS: We have received 28 consultation requests (54% Early Stage Investigators, 57% MD or equivalent, 28% PhD, 61% women) on projects typically related to planning a study or grant application (93%); 71% were HIV/AIDS-related. Leading topics included cost-effectiveness (43%), statistical-analysis/econometrics (36%), cost (32%), cost-benefit (21%), and quality-of-life (18%). All consultees were satisfied with their overall experience, and felt that consultation expectations and objectives were clearly defined and the consultant's expertise was matched appropriately with their needs. Results were similar for consultants, who spent a median of 3 hours on consultations. CONCLUSIONS: There is a need for health-economic methodological guidance among substance use, HCV, and HIV researchers. Lessons learned pertain to the feasibility of service provision, the need to implement systems to measure and improve service value, and strategies for service promotion.