Characterizing opioid overdose hotspots for place-based overdose prevention and treatment interventions: A geo-spatial analysis of Rhode Island, USA.

OBJECTIVE: Examine differences in neighborhood characteristics and services between overdose hotspot and non-hotspot neighborhoods and identify neighborhood-level population factors associated with increased overdose incidence. METHODS: We conducted a population-based retrospective analysis of Rhode Island, USA residents who had a fatal or non-fatal overdose from 2016 to 2020 using an environmental scan and data from Rhode Island emergency medical services, State Unintentional Drug Overdose Reporting System, and the American Community Survey. We conducted a spatial scan via SaTScan to identify non-fatal and fatal overdose hotspots and compared the characteristics of hotspot and non-hotspot neighborhoods. We identified associations between census block group-level characteristics using a Besag-York-Mollié model specification with a conditional autoregressive spatial random effect. RESULTS: We identified 7 non-fatal and 3 fatal overdose hotspots in Rhode Island during the study period. Hotspot neighborhoods had higher proportions of Black and Latino/a residents, renter-occupied housing, vacant housing, unemployment, and cost-burdened households. A higher proportion of hotspot neighborhoods had a religious organization, a health center, or a police station. Non-fatal overdose risk increased in a dose responsive manner with increasing proportions of residents living in poverty. There was increased relative risk of non-fatal and fatal overdoses in neighborhoods with crowded housing above the mean (RR 1.19 [95 % CI 1.05, 1.34]; RR 1.21 [95 % CI 1.18, 1.38], respectively). CONCLUSION: Neighborhoods with increased prevalence of housing instability and poverty are at highest risk of overdose. The high availability of social services in overdose hotspots presents an opportunity to work with established organizations to prevent overdose deaths.

Assessment of a naloxone distribution plan in a veteran population who experienced an opioid-related overdose event.

BACKGROUND: The Veteran Health Administration prioritizes the distribution of naloxone to veterans diagnosed with opioid use disorder (OUD) to prevent deaths due to opioid-related overdose. The Overdose Education and Naloxone Distribution (OEND) program was created with tools to supplement efforts in identifying veterans at risk of opioid-related adverse events secondary to OUD or other comorbidities and increase access, education, and distribution of naloxone. Utilizing the OEND tool, Veteran Health Indiana (VHI) employed two different distribution initiatives to increase access to naloxone. OBJECTIVE: The purpose of this study is to assess naloxone distribution efforts at a VA medical center and evaluate outcomes in patients who experienced opioid overdose events before and after the OEND initiatives were implemented. The primary outcome is to assess the distribution of naloxone within the year prior to the documented overdose event before and after the OEND initiatives. Secondary outcomes include assessment of the number of naloxone doses administered during the overdose event, substances involved in the overdose, and distribution of outpatient naloxone prescriptions after the overdose event. METHODS: This study was a retrospective electronic chart review of all patients who experienced an opioid-related overdose event at VHI from March 1, 2019, to March 1, 2022. RESULTS: Of the 59 opioid-overdose events analyzed, the percentage of patients with a naloxone prescription within 12 months prior to an opioid-overdose event was similar between the pre- and post-OEND initiatives. Within 12 months following the overdose event, naloxone was dispensed to nearly 10% more patients in the post-OEND group compared to the pre-OEND group. CONCLUSIONS: The OEND initiatives increased naloxone distribution amongst patients who ultimately experienced an opioid-related overdose. Additional research is needed to assess if these efforts prevented further overdoses.

Racial and ethnic disparities in medication for opioid use disorder access, use, and treatment outcomes in Medicare.

INTRODUCTION: Overdose deaths are increasing disproportionately for minoritized populations in the United States. Disparities in substance use disorder treatment access and use have been a key contributor to this phenomenon. However, little is known about the magnitude of these disparities and the role of social determinants of health (SDOH) and provider characteristics in driving them. Our study measures the association between race and ethnicity and visits with Medication for Opioid Use Disorder (MOUD) providers, MOUD treatment conditional on a provider visit, and opioid overdose following MOUD treatment in Medicare. We also evaluate the role of social determinants of health and provider characteristics in modifying disparities. METHODS: Using a population of 230,198 US Medicare fee-for-service beneficiaries diagnosed with opioid use disorder (OUD), we estimate logistic regression models to quantify the association between belonging to a racial or ethnic group and the probability of visiting a buprenorphine or naltrexone provider, receiving a prescription or medication administration during or after a visit, and experiencing an opioid overdose after treatment with MOUD. Data included Medicare claims data and the Agency for Health Research and Quality Social Determinants of Health Database files between 2013 and 2017. RESULTS: Compared to Non-Hispanic White Medicare beneficiaries, Asian/Pacific Islander, American Indian/Alaska Native, Black, Hispanic, and Other/Unknown Race beneficiaries were between 3.0 and 9.3 percentage points less likely to have a visit with a buprenorphine or naltrexone provider. Conditional on having a buprenorphine or naltrexone provider visit, Asian/Pacific Islander, American Indian/Alaska Native, Black, Hispanic, and Other/Unknown Race were between 2.6 and 8.1 percentage points less likely to receive buprenorphine or naltrexone than white beneficiaries. Controlling for provider characteristics and SDOH increased disparities in visits and MOUD treatment for all groups besides American Indians/Alaska Natives. Conditional on treatment, only Black Medicare beneficiaries were at greater associated risk of overdose than non-Hispanic white beneficiaries, although differences became statistically insignificant after controlling for SDOH and including provider fixed effects. CONCLUSION: Ongoing equity programming and measurement efforts by CMS should include explicit consideration for disparities in access and use of MOUD. This may help ensure greater MOUD utilization by minoritized Medicare beneficiaries and reduce rising disparities in overdose deaths.

Risks of opioid overdose among New York State Medicaid recipients with chronic pain before and during the COVID-19 pandemic.

OBJECTIVE: The COVID-19 pandemic contributed to healthcare disruptions for patients with chronic pain. Following initial disruptions, national policies were enacted to expand access to long-term opioid therapy (LTOT) for chronic pain and opioid use disorder (OUD) treatment services, which may have modified risk of opioid overdose. We examined associations between LTOT and/or OUD with fatal and non-fatal opioid overdoses, and whether the pandemic moderated overdose risk in these groups. METHODS: We analyzed New York State Medicaid claims data (3/1/2019-12/31/20) of patients with chronic pain (N = 236,391). We used generalized estimating equations models to assess associations between LTOT and/or OUD (neither LTOT or OUD [ref], LTOT only, OUD only, and LTOT and OUD) and the pandemic (03/2020-12/2020) with opioid overdose. RESULTS: The pandemic did not significantly (ns) affect opioid overdose among patients with LTOT and/or OUD. While patients with LTOT (vs. no LTOT) had a slight increase in opioid overdose during the pandemic (pre-pandemic: aOR:1.65, 95% CI:1.05, 2.57; pandemic: aOR:2.43, CI:1.75,3.37, ns), patients with OUD had a slightly attenuated odds of overdose during the pandemic (pre-pandemic: aOR:5.65, CI:4.73, 6.75; pandemic: aOR:5.16, CI:4.33, 6.14, ns). Patients with both LTOT and OUD also experienced a slightly reduced odds of opioid overdose during the pandemic (pre-pandemic: aOR:5.82, CI:3.58, 9.44; pandemic: aOR:3.70, CI:2.11, 6.50, ns). CONCLUSIONS: Findings demonstrated no significant effect of the pandemic on opioid overdose among people with chronic pain and LTOT and/or OUD, suggesting pandemic policies expanding access to chronic pain and OUD treatment services may have mitigated the risk of opioid overdose.

Removal of Medicaid Prior Authorization Requirements and Buprenorphine Treatment for Opioid Use Disorder.

Importance: Buprenorphine treatment for opioid use disorder (OUD) is associated with decreased morbidity and mortality. Despite its effectiveness, buprenorphine uptake has been limited relative to the burden of OUD. Prior authorization (PA) policies may present a barrier to treatment, though research is limited, particularly in Medicaid populations. Objective: To assess whether removal of Medicaid PAs for buprenorphine to treat OUD is associated with changes in buprenorphine prescriptions for Medicaid enrollees. Design, Setting, and Participants: This state-level, serial cross-sectional study used quarterly data from 2015 through the first quarter (January-March) of 2019 to compare buprenorphine prescriptions in states that did and did not remove Medicaid PAs. Analyses were conducted between June 10, 2021, and August 15, 2023. The study included 23 states with active Medicaid PAs for buprenorphine in 2015 that required similar PA policies in fee-for-service and managed care plans and had at least 2 quarters of pre- and postperiod buprenorphine prescribing data. Exposures: Removal of Medicaid PA for at least 1 formulation of buprenorphine for OUD. Main Outcomes and Measures: The main outcome was number of quarterly buprenorphine prescriptions per 1000 Medicaid enrollees. Results: Between 2015 and the first quarter of 2019, 6 states in the sample removed Medicaid PAs for at least 1 formulation of buprenorphine and had at least 2 quarters of pre- and postpolicy change data. Seventeen states maintained buprenorphine PAs throughout the study period. At baseline, relative to states that repealed PAs, states that maintained PAs had lower buprenorphine prescribing per 1000 Medicaid enrollees (median, 6.6 [IQR, 2.6-13.9] vs 24.1 [IQR, 8.7-27.5] prescriptions) and lower Medicaid managed care penetration (median, 38.5% [IQR, 0.0%-74.1%] vs 79.5% [IQR, 78.1%-83.5%] of enrollees) but similar opioid overdose rates and X-waivered buprenorphine clinicians per 100 000 population. In fully adjusted difference-in-differences models, removal of Medicaid PAs for buprenorphine was not associated with buprenorphine prescribing (1.4% decrease; 95% CI, -31.2% to 41.4%). For states with below-median baseline buprenorphine prescribing, PA removal was associated with increased buprenorphine prescriptions per 1000 Medicaid enrollees (40.1%; 95% CI, 0.6% to 95.1%), while states with above-median prescribing showed no change (-20.7%; 95% CI, -41.0% to 6.6%). Conclusions and Relevance: In this serial cross-sectional study of Medicaid PA policies for buprenorphine for OUD, removal of PAs was not associated with overall changes in buprenorphine prescribing among Medicaid enrollees. Given the ongoing burden of opioid overdoses, continued multipronged efforts are needed to remove barriers to buprenorphine care and increase availability of this lifesaving treatment.

Mortality, incarceration and cost implications of fentanyl felonization laws: A modeling study.

BACKGROUND: Opioid overdose continues to be a major cause of death in the United States. One effort to control opioid use has been to implement policies that enhance criminalization of opioid possession. Laws to further criminalize possession of fentanyl have been enacted or are under consideration across the country, including at the national level. OBJECTIVE: Estimate the long-term effects on opioid death and incarceration resulting from increasingly strict fentanyl possession laws . DESIGN: We built a Markov simulation model to explore the potential outcomes of a 2022 Colorado law which made possession of >1 g of drug with any amount of fentanyl a Level 4 drug felony (and escalation of the previous law, where >4 g of any drug with any amount of fentanyl in possession was considered a felony). The model simulates a cohort of people with fentanyl possession moving through the criminal justice system, exploring the probability of overdose and incarceration under different scenarios, including various fentanyl possession policies and potential interventions. SETTING: Colorado PARTICIPANTS: A simulated cohort of people in possession of fentanyl. MEASUREMENTS: Number of opioid overdose deaths, people incarcerated, and associated costs over 5 years. RESULTS: When >4 g of a drug containing any amount of fentanyl is considered a felony in Colorado, the model predicts 5460 overdose deaths (95% CrI 410-9260) and 2,740 incarcerations for fentanyl possession (95% CrI: 230-10,500) over 5 years. When the policy changes so that >1 g possession of drug with fentanyl is considered a felony, opioid overdose deaths increase by 19% (95% CRI: 16-38%) and incarcerations for possession increase by 98% (CrI: 85-98%). Diversion programs and MOUD in prison help alleviate some of the increases in death and incarceration, but do not completely offset them. LIMITATIONS: The mathematical model is meant to offer broad assessment of the impact of these policies, not forecast specific and exact numerical outcomes. CONCLUSIONS: Our model shows that lowering thresholds for felony possession of fentanyl containing drugs can lead to more opioid overdose deaths and incarceration.

Healthcare costs and use before and after opioid overdose in Veterans Health Administration patients with opioid use disorder.

AIMS: To compare healthcare costs and use between United States (US) Veterans Health Administration (VHA) patients with opioid use disorder (OUD) who experienced an opioid overdose (OD cohort) and patients with OUD who did not experience an opioid overdose (non-OD cohort). DESIGN: This is a retrospective cohort study of administrative and clinical data. SETTING: The largest integrated national health-care system is the US Veterans Health Administration's healthcare systems. PARTICIPANTS: We included VHA patients diagnosed with OUD from October 1, 2017 through September 30, 2018. We identified the index date of overdose for patients who had an overdose. Our control group, which included patients with OUD who did not have an overdose, was randomly assigned an index date. A total of 66 513 patients with OUD were included for analysis (OD cohort: n = 1413; non-OD cohort: n = 65 100). MEASUREMENTS: Monthly adjusted healthcare-related costs and use in the year before and after the index date. We used generalized estimating equation models to compare patients with an opioid overdose and controls in a difference-in-differences framework. FINDINGS: Compared with the non-OD cohort, an opioid overdose was associated with an increase of $16 890 [95% confidence interval (CI) = $15 611-18 169; P < 0.001] in healthcare costs for an estimated $23.9 million in direct costs to VHA (95% CI = $22.1 million, $25.7 million) within the 30 days following overdose after adjusting for baseline characteristics. Inpatient costs ($13 515; 95% CI = $12 378-14 652; P < 0.001) reflected most of this increase. Inpatient days (+6.15 days; 95% CI, = 5.33-6.97; P < 0.001), inpatient admissions (+1.01 admissions; 95% CI = 0.93-1.10; P < 0.001) and outpatient visits (+1.59 visits; 95% CI = 1.34-1.84; P < 0.001) also increased in the month after opioid overdose. Within the overdose cohort, healthcare costs and use remained higher in the year after overdose compared with pre-overdose trends. CONCLUSIONS: The US Veterans Health Administration patients with opioid use disorder (OUD) who have experienced an opioid overdose have increased healthcare costs and use that remain significantly higher in the month and continuing through the year after overdose than OUD patients who have not experienced an overdose.

Opportunities for pharmacist prescriptive authority of buprenorphine following passage of the Mainstreaming Addiction Treatment (MAT) Act.

In December 2022, Congress passed the Mainstreaming Addiction Treatment Act, which removed the federal legal barrier to pharmacist buprenorphine prescribing. As a result, each state can now decide whether or not to allow pharmacists to prescribe buprenorphine as an additional access point to reduce fatal opioid overdoses. At least 10 states allow pharmacists to prescribe controlled substances under collaborative practice agreements. Two states (California and Idaho) have also created pathways for independent prescribing of buprenorphine by pharmacists. Additional states should seek to enable pharmacists to prescribe buprenorphine to increase access to a proven beneficial treatment and help reduce fatal opioid overdoses.

State- and County-Level Geographic Variation in Opioid Use Disorder, Medication Treatment, and Opioid-Related Overdose Among Medicaid Enrollees.

Importance: The opioid crisis disproportionately affects Medicaid enrollees, yet little systematic evidence exists regarding how prevalence of and health care utilization for opioid use disorder (OUD) vary across geographical areas. Objectives: To characterize state- and county-level variation in claims-based prevalence of OUD and rates of medication treatment for OUD and OUD-related nonfatal overdose among Medicaid enrollees. Design, Setting, and Participants: This cross-sectional study used data from the Transformed Medicaid Statistical Information System Analytic Files from January 1, 2016, to December 31, 2018. Participants were Medicaid enrollees with or without OUD in 46 states; Washington, DC; and Puerto Rico who were aged 18 to 64 years and not dually enrolled in Medicare. The analysis was conducted between September 2022 and April 2023. Exposure: Calendar-year OUD prevalence. Main Outcomes and Measures: The main outcomes were claims-based measures of OUD prevalence and rates of medication treatment for OUD and opioid-related nonfatal overdose. Individual records were aggregated at the state and county level, and variation was assessed within and across states. Results: Of the 76 390 817 Medicaid enrollee-year observations included in our study (mean [SD] enrollee age, 36.5 [1.6] years; 59.0% female), 2 280 272 (3.0%) had a claims-based OUD (mean [SD] age, 38.9 [3.6] years; 51.4% female). Of enrollees with OUD, 41.2% were eligible due to Medicaid expansion, 46.4% had other substance use disorders, 55.8% had mental health conditions, 55.2% had claims indicating some form of OUD medication, and 5.8% had claims indicating an overdose during a calendar year. Claims-based outcomes exhibited substantial variation across states: OUD prevalence ranged from 0.6% in Arkansas and Puerto Rico to 9.7% in Maryland, rates of OUD medication treatment ranged from 17.7% in Kansas to 82.8% in Maine, and rates of overdose ranged from 0.3% in Mississippi to 10.5% in Illinois. Pronounced variation was also found within states (eg, OUD prevalence in Maryland ranged from 2.2% in Prince George's County to 21.6% in Cecil County). Conclusions and Relevance: In this cross-sectional study of Medicaid enrollees from 2016 to 2018, claims-based prevalence of OUD and rates of OUD medication treatment and opioid-related overdose varied substantially across and within states. Further research appears to be needed to identify important factors influencing this variation.

Cost-effectiveness of Increasing Buprenorphine Treatment Initiation, Duration, and Capacity Among Individuals Who Use Opioids.

Importance: Buprenorphine is an effective and cost-effective medication to treat opioid use disorder (OUD), but is not readily available to many people with OUD in the US. The current cost-effectiveness literature does not consider interventions that concurrently increase buprenorphine initiation, duration, and capacity. Objective: To conduct a cost-effectiveness analysis and compare interventions associated with increased buprenorphine treatment initiation, duration, and capacity. Design and Setting: This study modeled the effects of 5 interventions individually and in combination using SOURCE, a recent system dynamics model of prescription opioid and illicit opioid use, treatment, and remission, calibrated to US data from 1999 to 2020. The analysis was run during a 12-year time horizon from 2021 to 2032, with lifetime follow-up. A probabilistic sensitivity analysis on intervention effectiveness and costs was conducted. Analyses were performed from April 2021 through March 2023. Modeled participants included people with opioid misuse and OUD in the US. Interventions: Interventions included emergency department buprenorphine initiation, contingency management, psychotherapy, telehealth, and expansion of hub-and-spoke narcotic treatment programs, individually and in combination. Main Outcomes and Measures: Total national opioid overdose deaths, quality-adjusted life years (QALYs) gained, and costs from the societal and health care perspective. Results: Projections showed that contingency management expansion would avert 3530 opioid overdose deaths over 12 years, more than any other single-intervention strategy. Interventions that increased buprenorphine treatment duration initially were associated with an increased number of opioid overdose deaths in the absence of expanded treatment capacity. With an incremental cost- effectiveness ratio of $19 381 per QALY gained (2021 USD), the strategy that expanded contingency management, hub-and-spoke training, emergency department initiation, and telehealth was the preferred strategy for any willingness-to-pay threshold from $20 000 to $200 000/QALY gained, as it was associated with increased treatment duration and capacity simultaneously. Conclusion and Relevance: This modeling analysis simulated the effects of implementing several intervention strategies across the buprenorphine cascade of care and found that strategies that were concurrently associated with increased buprenorphine treatment initiation, duration, and capacity were cost-effective.

Early buprenorphine-naloxone initiation for opioid use disorder reduces opioid overdose, emergency room visits, and healthcare cost compared to late initiation.

Background: Although the effectiveness of buprenorphine-naloxone (BUP-NX) has been established, real-world evidence on the benefits of early treatment initiation is limited.Objective: To evaluate the association between early BUP-NX initiation and health-related outcomes among insured adults with opioid use disorder (OUD).Methods: We conducted a cross-sectional analysis using the Optum's de-identified Clinformatics® Data Mart Database from 2010 to 2018. Patients who initiated BUP-NX within 30 days of OUD diagnosis were classified as early initiators. Patients who initiated BUP-NX later, but within the one-year follow-up, were defined as late initiators. Outcomes included opioid overdose, opioid overdose-related emergency department (ED) visits, and all-cause healthcare cost during the year after OUD diagnosis. We employed generalized linear models to compare outcomes between early and late initiators, adjusting for baseline covariates and accounting for missing information for covariates using multiple imputation.Results: A total of 8,388 patients with OUD were identified; mean age was 39.9 years; 36% were female; and 67.6% were early initiators. Early initiators had an estimated 42% lower rate of opioid overdose (adjusted rate ratio (aRR) = 0.58; 95% confidence interval (CI): 0.52, 0.64); 51% lower rate of opioid overdose-related ED visits (aRR = 0.49; 95% CI: 0.44, 0.55); and 31% lower total healthcare cost (adjusted cost ratio = 0.69; 95% CI: 0.66, 0.72), compared to late initiators.Conclusion: Compared to late BUP-NX initiation, early initiation was associated with a lower risk of opioid overdose and opioid overdose-related ED visits, and reduced total healthcare cost among insured adult patients with OUD.

Cost-effectiveness of Treatments for Opioid Use Disorder.

Importance: Opioid use disorder (OUD) is a significant cause of morbidity and mortality in the US, yet many individuals with OUD do not receive treatment. Objective: To assess the cost-effectiveness of OUD treatments and association of these treatments with outcomes in the US. Design and Setting: This model-based cost-effectiveness analysis included a US population with OUD. Interventions: Medication-assisted treatment (MAT) with buprenorphine, methadone, or injectable extended-release naltrexone; psychotherapy (beyond standard counseling); overdose education and naloxone distribution (OEND); and contingency management (CM). Main Outcomes and Measures: Fatal and nonfatal overdoses and deaths throughout 5 years, discounted lifetime quality-adjusted life-years (QALYs), and costs. Results: In the base case, in the absence of treatment, 42 717 overdoses (4132 fatal, 38 585 nonfatal) and 12 660 deaths were estimated to occur in a cohort of 100 000 patients over 5 years, and 11.58 discounted lifetime QALYs were estimated to be experienced per person. An estimated reduction in overdoses was associated with MAT with methadone (10.7%), MAT with buprenorphine or naltrexone (22.0%), and when combined with CM and psychotherapy (range, 21.0%-31.4%). Estimated deceased deaths were associated with MAT with methadone (6%), MAT with buprenorphine or naltrexone (13.9%), and when combined with CM, OEND, and psychotherapy (16.9%). MAT yielded discounted gains of 1.02 to 1.07 QALYs per person. Including only health care sector costs, methadone cost $16 000/QALY gained compared with no treatment, followed by methadone with OEND ($22 000/QALY gained), then by buprenorphine with OEND and CM ($42 000/QALY gained), and then by buprenorphine with OEND, CM, and psychotherapy ($250 000/QALY gained). MAT with naltrexone was dominated by other treatment alternatives. When criminal justice costs were included, all forms of MAT (with buprenorphine, methadone, and naltrexone) were associated with cost savings compared with no treatment, yielding savings of $25 000 to $105 000 in lifetime costs per person. The largest cost savings were associated with methadone plus CM. Results were qualitatively unchanged over a wide range of sensitivity analyses. An analysis using demographic and cost data for Veterans Health Administration patients yielded similar findings. Conclusions and Relevance: In this cost-effectiveness analysis, expanded access to MAT, combined with OEND and CM, was associated with cost-saving reductions in morbidity and mortality from OUD. Lack of widespread MAT availability limits access to a cost-saving medical intervention that reduces morbidity and mortality from OUD. Opioid overdoses in the US likely reached a record high in 2020 because of COVID-19 increasing substance use, exacerbating stress and social isolation, and interfering with opioid treatment. It is essential to understand the cost-effectiveness of alternative forms of MAT to treat OUD.

Naloxone's role in the national opioid crisis-past struggles, current efforts, and future opportunities.

Over the past 25 years, naloxone has emerged as a critical lifesaving overdose antidote. Public health advocates and community activists established early methods for naloxone distribution to people who inject drugs, but a legacy of stigmatization and opposition to universal naloxone access continues to limit the drug's full potential to reduce opioid-related mortality. The establishment of naloxone distribution programs under the umbrella of syringe exchange programs faces the same practical, ideological and financial barriers to expansion similar to those faced by syringe exchange programs themselves. The expansion of naloxone from the confines of a few syringe exchange programs to what we see today represents an enormous triumph for the grass-roots activists, service providers, and public health professionals who have fought to guarantee lay access to naloxone. Despite the extensive efforts to expand access to naloxone, naloxone continues to remains a scarce resource in many US localities. Considerable naloxone "deserts" remain and even where there is naloxone access, it does not always reach those at risk. Promising areas for expansion include the development of more robust telehealth methods for naloxone distribution, including subsidized mail delivery programs; lowering barriers to pharmacy access; working with hospitals, ambulances, and law enforcement to expand naloxone "leave behind" programs; providing naloxone co-prescription with medications for opioid use disorder; and working with prisons, shelters, and networks of people who use drugs to increase access to the lifesaving medication. Efforts to ensure over-the-counter and low- or no-cost naloxone are ongoing and stand alongside medication-assisted treatments as efficacious, readily-actionable, and cost-efficient population-level interventions available for combatting opioid-related overdose in the United States.

Systematic review of the emerging literature on the effectiveness of naloxone access laws in the United States.

BACKGROUND AND AIMS: Naloxone access laws (NALs) have been suggested to be an important strategy to reduce opioid-related harm. We describe the evolution of NALs across states and over time and review existing evidence of their overall association with naloxone distribution and opioid overdose as well as the potential effects of specific NAL components. METHODS: Descriptive analysis of temporal variation in US regional adoption of NAL components, accompanied by a systematic search of 13 databases for studies (published between 2005 and 20 December 2019) assessing the effects of NALs on naloxone distribution or opioid-related health outcomes. Eleven studies, all published since 2018, met inclusion criteria. Study time-frames spanned 1999-2017. Opioid-related overdose mortality, emergency department episodes and naloxone distribution were correlated with the presence of a NAL and, where data were available, NAL components. RESULTS: Existing evidence suggests mixed, but generally beneficial, effects for NALs. Nearly all studies show that NALs, particularly those that permit naloxone distribution without patient-specific prescriptions, are associated with increased naloxone access [incidence rate ratios (IRR) range from 1.40, 95% confidence interval (CI) = 1.15-1.66 to 7.75, 95% CI = 1.22-49.35] and increased opioid-related emergency department visits (IRR range from 1.14, 95% CI = 1.07-1.20 to 1.15, 95% CI = 1.02-1.29). Most studies show NALs are associated with reduced overdose mortality, although findings vary depending on the specific NAL components and time-period analyzed (IRR range from 0.66, 95% CI = 0.42-0.90 to 1.27, 95% CI = 1.27-1.27). Few studies account for the variation in opioid environments (i.e. illicit versus prescription) or other policy dimensions that may be correlated with outcomes. CONCLUSIONS: The existing literature on naloxone access laws in the United States supports beneficial effects for increased naloxone distribution, but provides inconclusive evidence for reduced fatal opioid overdose. Mixed findings may reflect variation in the laws' design and implementation, confounding effects of concurrent policy adoption, or differential effectiveness in light of changing opioid environments.

Predictors of enrollment in opioid agonist therapy after opioid overdose or diagnosis with opioid use disorder: A cohort study.

BACKGROUND: Medicaid recipients have a high burden of opioid overdose and opioid use disorder (OUD). Opioid agonist therapies are an effective treatment for OUD, but there is a wide and persisting gap between those who are indicated and those who receive treatment. The objective of this study was to identify the predictors of enrollment in opioid agonist therapy within 6 months of an opioid overdose or OUD diagnosis in a cohort of Medicaid recipients. METHODS: Using multiple linked, state-level databases, we conducted a retrospective cohort study of 17,449 Medicaid recipients in Rhode Island who had an opioid overdose or an OUD diagnosis between July 2013 and June 2018. RESULTS: The majority (58 %) of Medicaid recipients did not enroll in opioid agonist therapy within 6 months. In adjusted models, having one or more prior overdose (adjusted risk ratio [ARR] = 0.33, 95 % CI: 0.28, 0.38), alcohol use disorder (ARR = 0.56, 95 % CI: 0.52, 0.60), or back problems (ARR = 0.58, 95 % CI: 0.55, 0.61) were strong predictors of non-enrollment. Conversely, emergency department (ARR = 1.31, 95 % CI: 1.28-1.34) and primary care provider (ARR = 1.03, 95 % CI: 1.01-1.34) visit frequency above the 75th percentile were associated with timely enrollment in opioid agonist therapy. CONCLUSIONS: Our findings underscore the need to enhance pathways to treatment for OUD through varied nodes of engagement with healthcare systems. Interventions to improve screening for OUD and referrals to opioid agonist therapies should include high-impact settings, such as treatment programs for alcohol and substance use disorders, pain clinics, and outpatient behavioral care settings.

Treatment for opioid use disorder in the Florida medicaid population: Using a cascade of care model to evaluate quality.

Background: A cascade of care (CoC) model may improve understanding of gaps in addiction treatment availability and quality over current single measure methods. Despite increased funding, opioid overdose rates remain high. Therefore, it is critical to understand where the health-care system is failing to provide appropriate care for people with opioid use disorder (OUD) diagnoses, and to assess disparities in receipt of medication for OUD (MOUD).Objective: Using a CoC framework, assess treatment quality and outcomes for OUD in the Florida Medicaid population in 2017/2018 by demographics and primary vs. secondary diagnosis.Methods: Data from Florida Medicaid claims for 2017 and 2018 were used to calculate the number of enrollees who were diagnosed, began MOUD, were retained on medication for a minimum of 180 days, and who died.Results: Only 28% of those diagnosed with OUD began treatment with an FDA approved MOUD (buprenorphine, methadone, or injectable naltrexone). Once on medication, 38% of newly diagnosed enrollees were retained in treatment for180 days. Those who remained on MOUD for 180 days had a hazard ratio of death of 0.226 (95% CI = 0.174 to 0.294) compared to those that did not initiate MOUD, a reduction in mortality from 10% without MOUD to 2% with MOUD.Conclusions: Initiating medication after OUD diagnosis offers the greatest opportunity for intervention to reduce overdose deaths, though efforts to increase retention are also warranted. Analyzing claims data with CoC identifies system functioning for specific populations, and suggests policies and clinical pathways to target for improvement.

Rates and Costs of Dispensing Naloxone to Patients at High Risk for Opioid Overdose in the United States, 2014-2018.

INTRODUCTION: Clinical practice guidelines recommend co-prescribing naloxone to patients at high risk of opioid overdose, but few such patients receive naloxone. High costs of naloxone may contribute to limited dispensing. OBJECTIVE: The aim of this study was to evaluate rates and costs of dispensing naloxone to patients receiving opioid prescriptions and at high risk for opioid overdose. METHODS: Using claims data from a large US commercial insurance company, we conducted a retrospective cohort study of new opioid initiators between January 2014 and December 2018. We identified patients at high risk for overdose defined as a diagnosis of opioid use disorder, prior overdose, an opioid prescription of ≥ 50 mg morphine equivalents/day for ≥ 90 days, and/or concurrent benzodiazepine prescriptions. RESULTS: Among 5,292,098 new opioid initiators, 616,444 (12%) met criteria for high risk of overdose during follow-up, and, of those, 3096 (0.5%) were dispensed naloxone. The average copayment was US$24.83 for naloxone (standard deviation [SD] 67.66) versus US$9.74 for the index opioid (SD 19.75). The average deductible was US$6.18 for naloxone (SD 27.32) versus US$3.74 for the index opioid (SD 25.56), with 94% and 88% having deductibles of US$0 for their naloxone and opioid prescriptions, respectively. The average out-of-pocket cost was US$31.01 for naloxone (SD 73.64) versus US$13.48 for the index opioid (SD 34.95). CONCLUSIONS: Rates of dispensing naloxone to high risk patients were extremely low, and prescription costs varied greatly. Since improving naloxone's affordability may increase access, whether naloxone's high cost is associated with low dispensing rates should be evaluated.

Expanding access to diacetylmorphine and hydromorphone for people who use opioids in Canada.

The increasing incidence of fatal opioid overdose is a public health crisis in Canada. While buprenorphine/naloxone and methadone are the standard first-line of opioid substitution options, limitations, including difficulty achieving long-term retention for some people who use opioids, are well known. For this group, injectable diacetylmorphine or hydromorphone can achieve positive outcomes, including high retention rates, reduced use of unregulated opioids, and reduced criminal activity. In May 2019, Health Canada announced changes to increase the accessibility of diacetylmorphine and hydromorphone, and in September 2019, the CIHR-funded Canadian Research Initiative in Substance Misuse released a national clinical guideline for diacetylmorphine and hydromorphone as additional frontline substitution options. While these developments present opportunities for scale-up, significant financial, structural, and practice barriers continue to impede access. This commentary explores the current state of policy and practice for diacetylmorphine and hydromorphone as opioid substitution options in Canada, outlines the rationale for rapid expansion of access, and highlights clinical and policy changes that must be undertaken or the death toll will continue to rise.

Legal requirements and recommendations to prescribe naloxone.

BACKGROUND: The continued toll of opioid-related overdoses has motivated efforts to expand availability of naloxone to persons at high risk of overdose, with 2016 federal guidance encouraging clinicians to co-prescribe naloxone to patients with increased overdose risk. Some states have pursued analogous or stricter legal requirements that could more heavily influence prescriber behavior. METHODS: We conducted a systematic legal review of state laws that mandate or recommend that healthcare providers prescribe naloxone to patients with indicators for opioid overdose risk. We coded relevant statutes and regulations for: applicable populations, patient criteria, educational requirements, and exemptions. RESULTS: As of September 2019, 17 states had enacted naloxone co-prescribing laws, the earliest of which was implemented by Louisiana in January 2016. If patient overdose risk criteria are met, over half of these states mandate that providers prescribe naloxone (7 states, 41.1 %) or offer a naloxone prescription (2 states, 11.8 %); the remainder encourage prescribers to consider prescribing naloxone (8 states). Most states (58.8 %) define patient overdose risk based on opioid dosages prescribed, although the threshold varies substantially; other common overdose risk criteria include concomitant opioid and benzodiazepine prescriptions and patient history of substance use disorder or mental illness. CONCLUSIONS: A growing minority of states has adopted a naloxone prescribing law, although these policies remain less prevalent than other naloxone access laws. By targeting higher-risk patients during clinical encounters, naloxone prescribing requirements could increase naloxone prescribed, destigmatize naloxone use, and reduce overdose harms. Further investigation into policy effectiveness, unintended consequences, and appropriate parameters is warranted.