Literature Collection

Physicians who want to prescribe buprenorphine to treat opioid use disorder require a waiver established by the Drug Addiction Treatment Act (DATA) of 2000, often through completion of an eight-hour training course. This is an issue for a number of reasons, including that opioid overdose deaths continue to rise nationally. However, on October 24, 2018, the SUPPORT (Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment) for Patients and Communities Act was signed into law. This bill allows any physician who graduates in good standing from an allopathic or osteopathic medical school in the United States that incorporates necessary material around opioid misuse in their standard curriculum, without need for any additional training, to prescribe buprenorphine. This perspective piece describes why this is an important first step and what more needs to be done within medical education to combat the opioid epidemic.

BACKGROUND: Methadone is a synthetic mu-opioid receptor agonist that is used in the management of pain, neonatal abstinence withdrawal syndrome, and opioid dependence. Overdose can cause miosis, respiratory depression, and central nervous system depression. Rarely, hypoglycemia has been reported. We present the case of an 11-month-old male who developed hypoketotic, hyperinsulinemic, hypoglycemia after an acute, unintentional methadone exposure. CASE DETAILS: The patient was a previously healthy 11-month-old male who presented in respiratory failure. He was intubated and transferred to a large tertiary care center where his physical exam was notable for miosis. His labs were notable for a blood glucose of 17 mg/dL, an elevated insulin level, and suppressed serum beta-hydroxybutyrate. The patient was given a dextrose bolus with improvement in blood glucose. Administration of IV naloxone improved his miosis and mental status. A quantitative methadone level was sent upon arrival and was 123 ng/mL. Testing for ethanol, salicylates, sulfonylureas, and metabolic causes of hypoglycemia was negative. A fasting study showed euglycemia with suppression of insulin and appropriate ketosis. Case discussion: We present the case of an 11-month-old male who developed hypoketotic, hyperinsulinemic, hypoglycemia after an acute, unintentional methadone exposure. Alternative explanations for hypoketotic hypoglycemia were rule out. Methadone-induced hypoglycemia has been reported in cancer patients receiving methadone for pain, but a mechanism has not been identified. Based on this case, we believe that the patient's hypoglycemia was the result of methadone-induced insulin secretion. CONCLUSIONS: This case proposes that hyperinsulinism is the mechanism responsible for methadone-associated hypoglycemia. Methadone exposure should be included in the differential diagnosis of new onset hypoglycemia.

Aims: This study concerns the perspectives of Indigenous persons who use injection drugs (IPWIDs) and key stakeholders across multiple sectors regarding healthcare service and treatment accessibility in the United States.Methods: Sixty in-depth interviews were undertaken with selected participants (30 people who use injection drugs and 30 stakeholders) across three non-urban locations in the United States. An inductive analytic approach was used to explore perspectives regarding healthcare accessibility gaps.Results: IPWIDs described injecting stimulants, opioids, and diverted medications for opioid use disorder, as well as having unstable access to sterile syringes. Often, the most accessible treatment for IPWID substance use was engagement with punitive aspects of the criminal justice system. While local health and social services were described as providing limited or inadequate services for IPWIDs, human capital deficiencies in those agencies and institutions often reinforced barriers to accessibility for IPWIDs, further aggravating the epidemics of Hepatitis C Virus infection and overdose risk in Indigenous communities. Conclusions: Decolonizing approaches to IPWID-centered services are urgently needed to reduce disparities in transmission of infectious diseases and other health consequences of injection drug use among American Indian people. Potential pathways forward include moving away from punitive treatment of IPWIDs by the criminal justice system and toward local, tribally-centered, culturally appropriate treatment models. We identify an urgent need to provide reliable and local access to sterile injection equipment and opioid substitution treatment on or near reservations.

BACKGROUND: Opioid overdose deaths involving synthetic opioids, particularly illicitly manufactured fentanyl, remain a substantial public health concern in North America. Responses to overdose events (e.g., administration of naloxone and rescue breathing) are effective at reducing mortality; however, more interventions are needed to prevent overdoses involving illicitly manufactured fentanyl. This study protocol aims to evaluate the effectiveness of a behavior change intervention that incorporates individual counseling, practical training in fentanyl test strip use, and distribution of fentanyl test strips for take-home use among people who use drugs. METHODS: Residents of Rhode Island aged 18-65 years who report recent substance use (including prescription pills obtained from the street; heroin, powder cocaine, crack cocaine, methamphetamine; or any drug by injection) (n = 500) will be recruited through advertisements and targeted street-based outreach into a two-arm randomized clinical trial with 12 months of post-randomization follow-up. Eligible participants will be randomized (1:1) to receive either the RAPIDS intervention (i.e., fentanyl-specific overdose education, behavior change motivational interviewing (MI) sessions focused on using fentanyl test strips to reduce overdose risk, fentanyl test strip training, and distribution of fentanyl test strips for personal use) or standard overdose education as control. Participants will attend MI booster sessions (intervention) or attention-matched control sessions at 1, 2, and 3 months post-randomization. All participants will be offered naloxone at enrolment. The primary outcome is a composite measure of self-reported overdose in the previous month at 6- and/or 12-month follow-up visit. Secondary outcome measures include administratively linked data regarding fatal (post-mortem investigation) and non-fatal (hospitalization or emergency medical service utilization) overdoses. DISCUSSION: If the RAPIDS intervention is found to be effective, its brief MI and fentanyl test strip training components could be easily incorporated into existing community-based overdose prevention programming to help reduce the rates of fentanyl-related opioid overdose. TRIAL REGISTRATION: ClinicalTrials.gov NCT04372238 . Registered on 01 May 2020.

BACKGROUND: Hospitalized patients with opioid use disorder (OUD) are rarely started on buprenorphine or methadone maintenance despite evidence that these medications reduce all-cause mortality, overdoses, and hospital readmissions. OBJECTIVE: To assess whether clinician education and a team of residents and hospitalist attendings waivered to prescribe buprenorphine increased the rate of starting patients with OUD on buprenorphine maintenance. DESIGN, SETTING, AND PARTICIPANTS: Quality improvement study conducted at a large, urban, academic hospital in Maryland involving hospitalized patients with OUD on internal medicine resident services. INTERVENTION: We developed a protocol for initiating buprenorphine maintenance, presented an educational conference, and started the resident-led Buprenorphine Bridge Team of residents and attendings waivered to prescribe buprenorphine to bridge patients from discharge to follow-up. MEASUREMENTS: The percent of eligible inpatients with OUD initiated on buprenorphine maintenance, 24 weeks before and after the intervention; engagement in treatment after discharge; and resident knowledge and comfort with buprenorphine. RESULTS: The rate of starting buprenorphine maintenance increased from 10% (30 of 305 eligible patients) to 24% (64 of 270 eligible patients) after the intervention, with interrupted time series analysis showing a significant increase in rate (14.4%; 95% CI, 3.6%-25.3%; P = .02). Engagement in treatment after discharge was unchanged (40%-46% engaged 30 days after discharge). Of 156 internal medicine residents, 89 (57%) completed the baseline survey and 66 (42%) completed the follow-up survey. Responses demonstrated improved resident knowledge and comfort with buprenorphine. CONCLUSION: Internal medicine resident teams were more likely to start patients on buprenorphine maintenance after clinician education and implementation of a Buprenorphine Bridge Team.

BACKGROUND: Naloxone co-prescription is recommended for patients on long-term opioids for pain, yet there are few data on the practice. OBJECTIVE: To explore naloxone co-prescribing acceptability among primary care providers for patients on long-term opioids. DESIGN: We surveyed providers at six safety-net primary care clinics in San Francisco that had initiated naloxone co-prescribing. Providers were encouraged to offer naloxone to patients on long-term opioids or otherwise at risk of witnessing or experiencing an overdose. Surveys were administered electronically 4 to 11 months after co-prescribing began. KEY RESULTS: One hundred eleven providers (69 %) responded to the survey, among whom 41.4 % were residents; 40.5 % practiced internal medicine and 55.0 % practiced family medicine. Most (79.3 %) prescribed naloxone, to a mean of 7.7 patients; 99.1 % were likely to prescribe naloxone in the future. Providers reported they were likely to prescribe naloxone to most patients, including those on low doses, defined as /=65 years old (83.9 %), with no overdose history (80.7 %), and with no substance use disorder (73.6 %). Most providers felt that prescribing naloxone did not affect their opioid prescribing, 22.5 % felt that they might prescribe fewer opioids, and 3.6 % felt that they might prescribe more. Concerns about providing naloxone were largely administrative, relating to time and pharmacy or payer logistics. Internists (incidence rate ratio [IRR] = 0.49, 95 % CI = 0.26-0.93, p = 0.029), those licensed for 5-20 years (IRR = 2.10, 95 % CI = 1.35-3.25, p = 0.001), and those with more patients prescribed long-term opioids (IRR = 1.10, 95 % CI = 1.05-1.14, p <0.001) were independently more likely to prescribe a greater number of naloxone compared to participants without these exposures. CONCLUSIONS: Naloxone co-prescription is considered acceptable among primary care providers. Barriers such as time and dispensing logistics may be alleviated by novel naloxone formulations intended for laypersons recently approved by the U.S. Food and Drug Administration.

IMPORTANCE: With increasing rates of opioid use disorder (OUD) and overdose deaths in the US, increased access to medications for OUD (MOUD) is paramount. Rigorous effectiveness evaluations of large-scale implementation initiatives using quasi-experimental designs are needed to inform expansion efforts. OBJECTIVE: To evaluate a US Department of Veterans Affairs (VA) initiative to increase MOUD use in nonaddiction clinics. DESIGN, SETTING, AND PARTICIPANTS: This quality improvement initiative used interrupted time series design to compare trends in MOUD receipt. Primary care, pain, and mental health clinics in the VA health care system (n = 35) located at 18 intervention facilities and nonintervention comparison clinics (n = 35) were matched on preimplementation MOUD prescribing trends, clinic size, and facility complexity. The cohort of patients with OUD who received care in intervention or comparison clinics in the year after September 1, 2018, were evaluated. The preimplementation period extended from September 1, 2017, through August 31, 2018, and the postimplementation period from September 1, 2018, through August 31, 2019. EXPOSURES: The multifaceted implementation intervention included education, external facilitation, and quarterly reports. MAIN OUTCOMES AND MEASURES: The main outcomes were the proportion of patients receiving MOUD and the number of patients per clinician prescribing MOUD. Segmented logistic regression evaluated monthly proportions of MOUD receipt 1 year before and after initiative launch, adjusting for demographic and clinical covariates. Poisson regression models examined yearly changes in clinician prescribing over the same time frame. RESULTS: Overall, 7488 patients were seen in intervention clinics (mean [SD] age, 53.3 [14.2] years; 6858 [91.6%] male; 1476 [19.7%] Black, 417 [5.6%] Hispanic; 5162 [68.9%] White; 239 [3.2%] other race [including American Indian or Alaska Native, Asian, Native Hawaiian or other Pacific Islander, and multiple races]; and 194 [2.6%] unknown) and 7558 in comparison clinics (mean [SD] age, 53.4 [14.0] years; 6943 [91.9%] male; 1463 [19.4%] Black; 405 [5.4%] Hispanic; 5196 [68.9%] White; 244 [3.2%] other race; 250 [3.3%] unknown). During the preimplementation year, the proportion of patients receiving MOUD in intervention clinics increased monthly by 5.0% (adjusted odds ratio [AOR], 1.05; 95% CI, 1.03-1.07). Accounting for this preimplementation trend, the proportion of patients receiving MOUD increased monthly by an additional 2.3% (AOR, 1.02; 95% CI, 1.00-1.04) during the implementation year. Comparison clinics increased by 2.6% monthly before implementation (AOR, 1.03; 95% CI, 1.01-1.04), with no changes detected after implementation. Although preimplementation-year trends in monthly MOUD receipt were similar in intervention and comparison clinics, greater increases were seen in intervention clinics after implementation (AOR, 1.04; 95% CI, 1.01-1.08). Patients treated with MOUD per clinician in intervention clinics saw greater increases from before to after implementation compared with comparison clinics (incidence rate ratio, 1.50; 95% CI, 1.28-1.77). CONCLUSIONS AND RELEVANCE: A multifaceted implementation initiative in nonaddiction clinics was associated with increased MOUD prescribing. Findings suggest that engagement of clinicians in general clinical settings may increase MOUD access.

BACKGROUND: Opioid use disorder (OUD) among women delivering at a hospital has increased 400% from 1999-2014 in the United States. From the years 2007 to 2016, opioid-related mortality during pregnancy increased over 200%, and drug-overdose deaths made up nearly 10% of all pregnancy-associated mortality in 2016 in the US. Disproportionately higher rates of neonatal opioid withdrawal syndrome (NOWS) have been reported in rural areas of the country, suggesting that perinatal OUD is a pressing issue among these communities. There is an urgent need for comprehensive, evidence-based treatment services for pregnant women experiencing OUD. The purpose of this article is to describe a study protocol aimed at developing and evaluating a perinatal OUD curriculum, enhancing evidence-based perinatal OUD treatment in a rural setting, and evaluating the implementation of such collaborative care for perinatal OUD. METHODS: This two-year study employed a one group, repeated measures, hybrid type-1 effectiveness-implementation design. This study delivered interventions at 2 levels, both targeting improvement of care for pregnant women with OUD. The first area of focus was at the community healthcare provider-level, which aimed to evaluate the acceptability and feasibility of perinatal OUD education across time and to improve provider education by increasing knowledge specific to: MOUD provision; screening, brief intervention, and referral to treatment (SBIRT) utilization; and NOWS treatment. The second area of intervention focus was at the patient-level, which assessed the preliminary effect of perinatal OUD provider education in promoting illicit opioid abstinence and treatment engagement among pregnant women with OUD. We adopted constructs from the Consolidated Framework for Implementation Research (CFIR) to assess contextual factors that may influence implementation, and the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) model to comprehensively evaluate implementation outcomes. DISCUSSION: This article presents the protocol of an implementation study that is employing the CFIR and RE-AIM frameworks to implement and evaluate a perinatal OUD education and service coordination program in two rural counties. This protocol could serve as a model for clinicians and researchers seeking to implement improvements in perinatal care for women with OUD in other rural communities. Trial registration NCT04448015 clinicaltrials.gov.

Opioid use disorders (OUDs) have long been a global problem, but the prevalence rates have increased over 20 years to epidemic proportions in the US, with concomitant increases in morbidity and all-cause mortality, but especially opioid overdose. These increases are in part attributable to a several-fold expansion in the prescription of opioid pain medications over the same time period. Opioid detoxification and psychosocial treatments alone have each not yielded sufficient efficacy for OUD, but mu-opioid receptor agonist, partial agonist, and antagonist medications have demonstrated the greatest overall benefit in OUD treatment. Buprenorphine, a mu-opioid receptor partial agonist, has been used successfully on an international basis for several decades in sublingual tablet and film preparations for the treatment of OUD, but the nature of formulation, which is typically self-administered, renders it susceptible to nonadherence, diversion, and accidental exposure. This article reviews the clinical trial data for novel buprenorphine delivery systems in the form of subcutaneous depot injections, transdermal patches, and subdermal implants for the treatment of OUD and discusses both the clinical efficacy of longer-acting formulations through increasing consistent medication exposure and their potential utility in reducing diversion. These new delivery systems also offer new dosing opportunities for buprenorphine and strategies for dosing intervals in the treatment of OUD.

INTRODUCTION: Take-Home Naloxone programs have been introduced across North America in response to rising opioid overdose deaths. There is currently limited real-world data on bystander naloxone administration, overdose outcomes, and evidence related to adverse events following bystander naloxone administration. METHODS: The research team used descriptive statistics from Take-Home Naloxone administration forms. We explored reported demographic variables and adverse events among people who received by-stander administered naloxone in a suspected opioid overdose event between August 31, 2012 and December 31, 2018 in British Columbia. We examined and contextualized differences across years given policy, program and drug toxicity changes. We used multivariate logistic regression to examine whether an association exists between number of ampoules of naloxone administered and the odds that the recipient will experience withdrawal symptoms. RESULTS: A large majority (98.1%) of individuals who were administered naloxone survived their overdose and 69.2% had no or only mild withdrawal symptoms. Receiving three (Adjusted Odds Ratio (AOR) 1.64 (95% Confidence Interval (CI): 1.08-2.48)) or four or more (AOR 2.19 (95% CI: 1.32-3.62)) ampoules of naloxone was significantly associated with odds of moderate or severe withdrawal compared to receiving one ampoule of naloxone. CONCLUSIONS: This study provides evidence from thousands of bystander reversed opioid overdoses using Take-Home Naloxone kits in British Columbia, and suggests bystander-administered naloxone is safe and effective for opioid overdose reversal. Data suggests an emphasis on titration during bystander naloxone training in situations where the person experiencing overdose can be adequately ventilated may help avoid severe withdrawal symptoms. We identified a decreasing trend in the likelihood of moderate or severe withdrawal over the study period.