Methadone for opioid use disorder can be dispensed only from US Substance Abuse and Mental Health Services Administration (SAMHSA)-certified opioid treatment programs (OTPs), creating access barriers in rural counties with a shortage of facilities. Canada and Australia allow primary care prescribing and pharmacy dispensing of methadone to expand access. 1 Therefore, we examined drive times to the nearest OTP in urban and rural counties in 5 US states with the highest county rates of opioid-related overdose mortality. 2 In addition, we compared drive times to federally qualified health centers (FQHCs) as potential primary care methadone-prescribing locations and to dialysis centers as treatment locations for a different chronic disease requiring frequent engagement. Methods |The outcome was the minimum drive time in minutes from the county mean center of population to the nearest OTP, FQHC, and dialysis center using the Esri ArcGIS rural drive-time tool (September 2017 version), which simulates automobile movement between 2 points along a national street network based on historical average speeds. 3 From the 2010 US Census, we obtained the coordinates of the county mean center of population for all counties in Indiana, Kentucky, Ohio, Virginia, and West Virginia, excluding counties with geographic changes after the census. We geocoded 2017 OTP, FQHC, and dialysis center street addresses from the SAMHSA OTP Directory

Post-release opioid-related overdose mortality is the leading cause of death among people released from jails or prisons (PRJP). Informed by the proximate determinants framework, this paper presents the Post-Release Opioid-Related Overdose Risk Model. It explores the underlying, intermediate, proximate and biological determinants which contribute to risk of post-release opioid-related overdose mortality. PRJP share the underlying exposure of incarceration and the increased prevalence of several moderators (chronic pain, HIV infection, trauma, race, and suicidality) of the risk of opioid-related overdose. Intermediate determinants following release from the criminal justice system include disruption of social networks, interruptions in medical care, poverty, and stigma which exacerbate underlying, and highly prevalent, substance use and mental health disorders. Subsequent proximate determinants include interruptions in substance use treatment, including access to medications for opioid use disorder, polypharmacy, polydrug use, insufficient naloxone access, and a return to solitary opioid use. This leads to the final biological determinant of reduced respiratory tolerance and finally opioid-related overdose mortality. Mitigating the risk of opioid-related overdose mortality among PRJP will require improved coordination across criminal justice, health, and community organizations to reduce barriers to social services, ensure access to health insurance, and reduce interruptions in care continuity and reduce stigma. Healthcare services and harm reduction strategies, such as safe injection sites, should be tailored to the needs of PRJP. Expanding access to opioid agonist therapy and naloxone around the post-release period could reduce overdose deaths. Programs are also needed to divert individuals with substance use disorder away from the criminal justice system and into treatment and social services, preventing incarceration exposure.

IMPORTANCE Methadone access may be uniquely vulnerable to disruption during COVID-19, and even short delays in access are associated with decreased medication initiation and increased illicit opioid use and overdose death. Relative to Canada, US methadone provision is more restricted and limited to specialized opioid treatment programs. OBJECTIVE To compare timely access to methadone initiation in the US and Canada during COVID-19. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study was conducted from May to June 2020. Participating clinics provided methadone for opioid use disorder in 14 US states and territories and 3 Canadian provinces with the highest opioid overdose death rates. Statistical analysis was performed from July 2020 to January 2021. EXPOSURES Nation and type of health insurance (US Medicaid and US self-pay vs Canadian provincial). MAIN OUTCOMES AND MEASURES Proportion of clinics accepting new patients and days to first appointment. RESULTS Among 268 of 298 US clinics contacted as a patient with Medicaid (90%), 271 of 301 US clinics contacted as a self-pay patient (90%), and 237 of 288 Canadian clinics contacted as a patient with provincial insurance (82%), new patients were accepted for methadone at 231 clinics (86%) during US Medicaid contacts, 230 clinics (85%) during US self-pay contacts, and at 210 clinics (89%)during Canadian contacts. Among clinics not accepting new patients, at least 44% of 27 clinics reported that the COVID-19 pandemic was the reason. The mean wait for first appointment was greater among US Medicaid contacts (3.5 days [95% CI, 2.9-4.2 days]) and US self-pay contacts (4.1 days [95% CI, 3.4-4.8 days]) than Canadian contacts (1.9 days [95% CI, 1.7-2.1 days]) (P < .001).Open-access model (walk-in hours for new patients without an appointment) utilization was reported by 57 Medicaid (30%), 57 self-pay (30%), and 115 Canadian (59%) contacts offering an appointment. CONCLUSIONS AND RELEVANCEIn this cross-sectional study of 2 nations, more than 1 in 10 methadone clinics were not accepting new patients. Canadian clinics offered more timely methadone access than US opioid treatment programs. These results suggest that the methadone access shortage was exacerbated by COVID-19 and that changes to the US opioid treatment program model are needed to improve the timeliness of access. Increased open-access model adoption may increase timely access.

Background: Within the United States, there is a shortage of opioid treatment programs (OTPs), facilities which dispense methadone for opioid use disorder. It is unknown how pharmacy-based methadone dispensing, as available internationally, could affect methadone access. We aimed to

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Polarization of the mitochondrial membrane potential (ΔΨ m ) is critical for normal mitochondrial function and cellular energetics. Mitochondrial dysfunction, manifesting as disrupted ΔΨ m polarization (i.e. depolarization or hyperpolarization), underlies several important and highly prevalent diseases, including a variety of cardiac and neurological disorders. As such, ΔΨ m instability might form a unifying mechanism for a class of metabolic disorders affecting excitable tissues. Here, we measured the spatiotemporal kinetics of ΔΨ m changes across the intact heart using high-resolution optical ΔΨ m imaging and uncovered surprisingly complex spatial patterns and dynamically fluctuating changes in ΔΨ m that developed into actively propagating waves of mitochondrial depolarization during global ischemia. Our data further indicated that the recovery of ΔΨ m upon reperfusion is dictated by the duration of the preceding ischemic insult. Postischemic electrical and functional recovery was dependent on early ΔΨ m recovery but independent of overall cellular injury measured using a standard assay of lactate dehydrogenase release. These findings reveal a novel mechanism by which instabilities in cellular energetic properties that are independent of irreversible cellular injury can scale to the level of the intact organ via an organized process of active conduction involving the multi-cellular network. This highlights the importance of investigating cellular metabolic properties in the context of the intact organ.

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