Descriptive study: the novel "full spectrum people-with-opioid-use-disorder care model".

BACKGROUND: People with Opioid Use Disorder (PWOUD) represent an underserved and marginalized population for whom treatment gaps exist. Low-barrier programs like mobile care units and street outreach programs have yielded increased access to buprenorphine and social services, however, OUD pertinent co-occurring behavioral health and medical conditions are frequently left unaddressed. A novel, tailored, comprehensive care delivery model may reduce disparities and improve access to care across a range of pathologies in this historically difficult to reach population and enhance efforts to provide universal treatment access in a harm reduction setting. METHODS: Descriptive data were collected and analyzed regarding patient demographics, retention in treatment and services rendered at a new, wrap-around, low-barrier buprenorphine clinic established at an existing harm reduction site in New Mexico between August 1, 2020, and August 31, 2021. RESULTS: 203 people used any service at the newly implemented program, 137 of whom specifically obtained medical and/or behavioral health care services including prescriptions for buprenorphine at least once from the physician onsite. Thirty-seven unique medical and psychiatric conditions were treated, representing a total of 565 separate encounters. The most common service utilized was buprenorphine treatment for opioid use disorder (81%), followed by treatment for post-traumatic stress disorder (62%), anxiety (44.5%) and depression (40.9%). Retention in buprenorphine treatment was 31.2% at 6 months. CONCLUSIONS: An innovative, multidisciplinary, buprenorphine-centric care model, which targets a wide range of OUD pertinent pathologies while employing a harm reduction approach, can enhance utilization of these services among an underserved PWOUD population in a manner which moves our health system toward universal OUD treatment access thereby potentially reducing overdose and existing disparities.

Association of MOUD ECHO Participation on Expansion of Buprenorphine Prescribing in Rural Primary Care.

BACKGROUND: Lack of access to buprenorphine to treat Opioid Use Disorder is profound in rural areas where over half of small and remote rural counties have no buprenorphine prescriber. To increase prescribing, an online, Medication of Opioid Use Disorder (MOUD) Extensions for Community Healthcare Outcomes (ECHO) was developed that addressed known barriers to the startup and expansion of treatment. The objective of the present study was to determine the relationship between participating in MOUD ECHO sessions and prescribing of buprenorphine for OUD in rural primary care. METHODS: Using non-random, rolling-recruitment from Feb 2018 to October of 2021, all rural primary care clinics in New Mexico were contacted via phone call and fax to recruit providers (Physicians, Nurse Practitioners, and Physician Assistants) who had no or limited buprenorphine experience to enroll in this study. Participation in the MOUD ECHO was tracked across the 12 week series. Start-up and expansion of buprenorphine treatment was measured every 3 months for up to 2 years using 5 implementation benchmarks spanning training completion, obtaining licensure, prescribing and adding patients. Using a dose-response intention to treat type analysis, associations between number of sessions and benchmark achievement were analyzed using logistic regression. RESULTS: Eighty providers were enrolled, mostly female (66%) white (82%), non-Hispanic (82%), and mostly nurse practitioners (51%) or MDs (38%). Achievement of prescribing benchmarks at 6 months was significantly increased by attendance at MOUD ECHO sessions including obtaining training and licensure Odds Ratio (OR = 1.24; P = .001); starting to prescribe (OR = 1.31; P = .004), and adding patients (OR = 1.14; P = .025). CONCLUSIONS: This study provides compelling evidence that MOUD ECHO participation may significantly increase the number of providers implementing this treatment and adding patients onto their panels. The dose-response approach helps address current gaps in ECHO research that call for more rigorous examination of the ECHO model's impact on provider practice improvements.

Evaluation and guide for embedding opioid use disorder education in health professions' curricula.

BACKGROUND: Morbidity and mortality from Opioid Use Disorder is a health crisis in the United States. During the COVID-19 pandemic, there was a devastating increase of 38.4% in overdose deaths from the 12-month period leading up to June 2019 compared with the 12-month period leading up to May 2020, primarily driven by synthetic opioids. Buprenorphine is an effective medication for opioid use disorder but uptake is slow due in part to lack of provider knowledge, confidence, and negative attitudes/stigma toward patients with OUD. Addressing these barriers in academic training is a promising approach to building workforce able to effectively treat opioid use disorder. METHODS: Our university developed a training for pre-licensure physicians, physician assistants and psychiatric nurse practitioners that included the DATA Waiver training and a shadowing experience. Expected outcomes included improved knowledge, skills and attitudes about persons with OUD and buprenorphine treatment, plans to provide this treatment post-graduation, for pre-licensure learners to have completed all requirements to prescribe buprenorphine post-graduation, and for the training to be embedded into school's curricula. RESULTS: Results were positive overall including improved knowledge and attitudes toward persons with OUD, better understanding of the benefits of this treatment for patients, increased confidence and motivation to provide this treatment post-graduation. The training is now embedded in each program's graduation requirements. CONCLUSION: Developing a didactic and experiential training on buprenorphine treatment for opioid use disorder and embedding it into medical, physician assistant, and psychiatric nurse practitioner licensure programs can help prepare future providers to treat opioid use disorder in a range of settings. Key to replicating this program in other university settings is to engage faculty members who actively provide treatment to persons with OUD to ensure shadowing opportunities and serve as role models for learners.

Feasibility and acceptability of an online ECHO intervention to expand access to medications for treatment of opioid use disorder, psychosocial treatments and supports.

Background: Buprenorphine combined with psychosocial support is the standard of care for treatment of opioid use disorder (OUD) in office-based primary care settings. However, uptake of this treatment has been slow due to a number of addressable barriers including providers' lack of training, staffing concerns, stigma and the need for ongoing support and consultation. This study examined acceptability and feasibility of an online Extensions for Community Healthcare Outcomes (ECHO) model intervention developed to support rural primary care clinics to expand treatment and is part of a larger study tracking the impact of participation in this ECHO on expansion of MOUD in rural primary care. Methods: We developed a comprehensive, 12-week online education and mentorship intervention using ECHO aimed at supporting the entire primary care clinic to start or expand treatment using MOUD, psychosocial treatments and recovery supports. We tracked participation and collected feedback using qualitative interviews and post-session questionnaires. Results: Sixty-seven primary care staff across 27 rural clinics in New Mexico participated in the study including 32 prescribers and 35 clinic support staff. Average participation was 4/12 sessions. Post-session questionnaires showed positive feedback, including that 95% or more respondents agreed or strongly agreed that the sessions were relevant and improved their confidence. Qualitative interview themes included strong endorsement of the ECHO curriculum. Clinical duties were the most common barrier to attending sessions. Conclusions: Engagement of 27 clinics, the range of staff and providers who participated, and positive feedback gathered through survey and qualitative interviews provide evidence of feasibility and acceptability of MOUD ECHO to support expansion of this treatment. However, barriers to participation present an important threat to feasibility. Understanding feasibility and acceptability is an important component of research on the impact of ECHO to expand MOUD treatment.

How Hands-On Pain Skills Intensive Trainings Complement ECHO Pain and Opioid Management Programs: A Program Evaluation with the Indian Health Service.

OBJECTIVE: To evaluate the impact of Pain Skills Intensive trainings (PSIs) as a complement to the Indian Health Service (IHS) and the Chronic Pain and Opioid Management TeleECHO Program (ECHO Pain) collaboration. DESIGN: On-site PSIs conducted over two to three days were added to complement ECHO Pain at various IHS areas to enhance pain skills proficiency among primary care teams and to expand the reach of ECHO collaboration to ECHO nonparticipants. SETTING: This evaluation focuses on two PSI trainings offered to IHS clinicians in Albuquerque, New Mexico, and Spokane, Washington, in 2017. METHODS: The mixed-methods design comprises CME surveys and focus groups at the end of training and 12 to 18 months later. Quality of training and perceived competence were evaluated. RESULTS: Thirty-eight participants attended the two PSI workshops. All provided CME survey results, and 28 consented to use of their postsession focus group results. Nine clinicians participated in the virtual follow-up focus groups. IHS clinicians rated the PSIs highly, noting their hands-on and interdisciplinary nature. They reported above-average confidence in their skills. Follow-up focus groups indicated they were pursuing expanded options for their patients, consulting other clinicians, serving as pain consultants to their peers, and changing prescribing practices clinic-wide. However, rurality significantly limits access to ancillary and complementary services for many. Clinicians reported the need for additional training in integrating behavioral health into their practice. CONCLUSIONS: Hands-on pain skills and information on medication-assisted treatment (MAT) are critical to the successful treatment of chronic pain and opioid use disorder. The PSIs provide clinicians with critical competencies in assessment and screening, pain management, and communication skills, complementing required IHS training and telementoring from ECHO Pain.

Methamphetamine Abuse Trends in Psychiatric Emergency Services: A Retrospective Analysis Using Big Data.

OBJECTIVE: This exploratory retrospective study assessed demographic and hospital utilization characteristics of patients presenting with methamphetamine use to an urban psychiatric emergency service in New Mexico. METHODS: De-identified data from patients presenting to PES from 2011 to 2015 were extracted from our health system. Descriptive statistics were used to characterize the study population. We employed bivariate analyses to assess the relationship between methamphetamine use and patient demographics. RESULTS: Methamphetamine use increased faster than any other drug tested during the study's time period. Compared to non-methamphetamine patients, methamphetamine use was associated with a shorter PES stay when the patient was in the PES more than 12 h. CONCLUSIONS: Patients with methamphetamine use are increasingly seeking emergency psychiatric evaluations. Methamphetamine use may impact certain racial, ethnic, and socioeconomic classes disproportionately. Further health service delivery studies are needed to develop clear, evidence-based interventions and policy recommendations to address the methamphetamine crisis in the United States.

Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Extended-release naltrexone (XR-NTX), an opioid antagonist, and sublingual buprenorphine-naloxone (BUP-NX), a partial opioid agonist, are pharmacologically and conceptually distinct interventions to prevent opioid relapse. We aimed to estimate the difference in opioid relapse-free survival between XR-NTX and BUP-NX. METHODS: We initiated this 24 week, open-label, randomised controlled, comparative effectiveness trial at eight US community-based inpatient services and followed up participants as outpatients. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder, and had used non-prescribed opioids in the past 30 days. We stratified participants by treatment site and opioid use severity and used a web-based permuted block design with random equally weighted block sizes of four and six for randomisation (1:1) to receive XR-NTX or BUP-NX. XR-NTX was monthly intramuscular injections (Vivitrol; Alkermes) and BUP-NX was daily self-administered buprenorphine-naloxone sublingual film (Suboxone; Indivior). The primary outcome was opioid relapse-free survival during 24 weeks of outpatient treatment. Relapse was 4 consecutive weeks of any non-study opioid use by urine toxicology or self-report, or 7 consecutive days of self-reported use. This trial is registered with ClinicalTrials.gov, NCT02032433. FINDINGS: Between Jan 30, 2014, and May 25, 2016, we randomly assigned 570 participants to receive XR-NTX (n=283) or BUP-NX (n=287). The last follow-up visit was Jan 31, 2017. As expected, XR-NTX had a substantial induction hurdle: fewer participants successfully initiated XR-NTX (204 [72%] of 283) than BUP-NX (270 [94%] of 287; p<0·0001). Among all participants who were randomly assigned (intention-to-treat population, n=570) 24 week relapse events were greater for XR-NTX (185 [65%] of 283) than for BUP-NX (163 [57%] of 287; hazard ratio [HR] 1·36, 95% CI 1·10-1·68), most or all of this difference accounted for by early relapse in nearly all (70 [89%] of 79) XR-NTX induction failures. Among participants successfully inducted (per-protocol population, n=474), 24 week relapse events were similar across study groups (p=0·44). Opioid-negative urine samples (p<0·0001) and opioid-abstinent days (p<0·0001) favoured BUP-NX compared with XR-NTX among the intention-to-treat population, but were similar across study groups among the per-protocol population. Self-reported opioid craving was initially less with XR-NTX than with BUP-NX (p=0·0012), then converged by week 24 (p=0·20). With the exception of mild-to-moderate XR-NTX injection site reactions, treatment-emergent adverse events including overdose did not differ between treatment groups. Five fatal overdoses occurred (two in the XR-NTX group and three in the BUP-NX group). INTERPRETATION: In this population it is more difficult to initiate patients to XR-NTX than BUP-NX, and this negatively affected overall relapse. However, once initiated, both medications were equally safe and effective. Future work should focus on facilitating induction to XR-NTX and on improving treatment retention for both medications. FUNDING: NIDA Clinical Trials Network.

Evaluation of American Indian Health Service Training in Pain Management and Opioid Substance Use Disorder.

We examined the benefits of a collaboration between the Indian Health Service and an academic medical center to address the high rates of unintentional drug overdose in American Indians/Alaska Natives. In January 2015, the Indian Health Service became the first federal agency to mandate training in pain and opioid substance use disorder for all prescribing clinicians. More than 1300 Indian Health Service clinicians were trained in 7 possible 5-hour courses specific to pain and addiction. We noted positive changes in pre- and postcourse knowledge, self-efficacy, and attitudes as well as thematic responses showing the trainings to be comprehensive, interactive, and convenient.

Coadministration of disulfiram and lorazepam in the treatment of alcohol dependence and co-occurring anxiety disorder: an open-label pilot study.

BACKGROUND: Anxiety is common among persons with alcohol use disorder during early abstinence from alcohol. Although benzodiazepines are effective for short-term treatment of anxiety, they are rarely used beyond acute detoxification due to concerns about misuse or interactions with alcohol. OBJECTIVES: We conducted an open-label trial to explore the effects of coadministering lorazepam and disulfiram to alcohol-dependent patients with anxiety disorder symptoms. The rationale for this model is to minimize the risks of the benzodiazepine, while also potentially enhancing adherence to disulfiram. METHODS: Forty-one participants with DSM-IV alcohol dependence who also met syndromal criteria for anxiety disorder with or without co-occurring major depressive syndrome initiated treatment with lorazepam (starting dose 0.5 mg three times daily) and disulfiram (starting dose 500 mg three times weekly). Participants received 16 weeks of monitored pharmacotherapy with manualized medical management. RESULTS: Adherence to treatment decreased steadily with time (85.4% at 4 weeks, 36.6% at 16 weeks). Participants showed significant increases in percent abstinent days during treatment and at 24 weeks follow-up. Large reductions in anxiety, depression, and craving were observed during treatment, and improvement remained significant at 24 weeks. Duration of adherence with disulfiram strongly predicted abstinence at 16 weeks. There was no evidence of misuse of lorazepam or dose escalation during the study. CONCLUSION: Lorazepam can be safely used for short-term treatment of anxiety in combination with disulfiram treatment of alcohol use disorder. However, it is not clear that making lorazepam dispensing contingent on adherence to disulfiram enhances retention in disulfiram treatment.

Call for evidence-based psychedelic integration.

The use of psychedelics for various purposes was common in different civilizations throughout human history and has been explored scientifically for more than a century. Although the applications of psychedelics show promise in the treatment of various psychiatric and neurological indications, as well as in facilitation of well-being and personal growth, several psychedelic-related risks and challenges have also been identified. Psychedelic integration (PI) refers to various practices that serve to either minimize harms or maximize benefits associated with psychedelic use. PI is also recognized as a substantial part of psychedelic-assisted therapy (PAT), following preparation to and facilitation of the psychedelic experience. In the context of clinical/psychotherapeutic practice, several PI models/methods have already been proposed. However, while a number of these models/methods are theory-driven, or have a history of clinical application, each lack any empirical support and thus cannot be described as evidence based. This is to the disadvantage to countless people who had and who will have their psychedelic experiences in various contexts, as the prevalence of using psychedelics increased in recent years and is expected to grow further. Therefore, consistent with general recommendations for developing and implementing evidence-based mental health practices, this article calls for scientific efforts to the development, examination, and evaluation of psychedelic integration models/methods. This article also briefly summarizes the current literature on psychedelic integration, provides a list of exemplary avenues that research on psychedelic integration might take, as well as anticipates and discusses the limitations and challenges of PI-focused research. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

In It for the Long Haul: Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2.

The COVID-19 pandemic has caused immeasurable clinical, economic, and societal challenges for the world since early 2020. Intense focus has been placed on determining evidence-based acute management of patients infected with the SARS-CoV-2 virus, as well as accelerating vaccination efforts for those eligible to receive it. As patients recover from infection, many are left with long-term symptoms, known as "Long COVID" or "Post-Acute Sequelae of COVID19," that challenges the ability to fully recover, return to baseline health status, and regain quality of life. As the most accessible healthcare professional, pharmacists can assist with the management of long COVID as a member of the multidisciplinary team. Pharmacists' medication acumen is beneficial to the management of long COVID symptomatology as more research comes to the forefront of this deadly disease.

Take-home Naloxone at Opioid Treatment Programs: A Lifesaver.

Opioid-related overdose deaths have increased almost 30% in the US since the COVID-19 pandemic began. Tragically, many of these deaths could be prevented with widespread availability of naloxone. One innocuous harm-reduction strategy would be the federal government mandating the provision of take-home naloxone and brief overdose education to patients at opioid treatment programs. Take-home naloxone, for instance, may be used by a friend or a family member to save the life of the patient receiving treatment for opioid use disorder. Importantly, many studies demonstrate that patients receiving take-home naloxone at an opioid treatment program will use the naloxone to reverse an overdose of someone in their social network. Other successful indications for mandated take-home naloxone include: federal inmates leaving incarceration if they have an opioid substance use disorder diagnosis and federal police officers on active duty. This editorial describes the various organizations, medical societies, and governmental agencies who may consider making robust actionable recommendations regarding naloxone for persons with opioid use disorder. The authors strongly recommend that professional organizations include take-home naloxone as a best practice for any patient who may be at an elevated risk for an opioid overdose.

Psychedelic Therapies at the Crossroads of Trauma and Substance Use: Historical Perspectives and Future Directions, Taking a Lead From New Mexico.

Post-traumatic stress disorder (PTSD), a common condition with potentially devastating individual, family, and societal consequences, is highly associated with substance use disorders (SUDs). The association between PTSD and SUD is complex and may involve adverse childhood experiences (ACEs), historical and multi-generational traumas, and social determinants of health as well as cultural and spiritual contexts. Current psychosocial and pharmacological treatments for PTSD are only modestly effective, and there is a need for more research on therapeutic interventions for co-occurring PTSD and SUD, including whether to provide integrated or sequential treatments. There is a current resurgence of interest in psychedelics as potential treatment augmentation for PTSD and SUDs with an appreciation of the risks in this target population. This paper reviews the historical perspective of psychedelic research and practices, as well as the intersection of historical trauma, ACEs, PTSD, and SUDs through the lens of New Mexico. New Mexico is a state with high populations of Indigenous and Hispanic peoples as well as high rates of trauma, PTSD, and SUDs. Researchers in New Mexico have been leaders in psychedelic research. Future directions for psychedelic researchers to consider are discussed, including the importance of community-based participatory approaches that are more inclusive and respectful of Indigenous and other minority communities.

Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial.

Importance: Although classic psychedelic medications have shown promise in the treatment of alcohol use disorder (AUD), the efficacy of psilocybin remains unknown. Objective: To evaluate whether 2 administrations of high-dose psilocybin improve the percentage of heavy drinking days in patients with AUD undergoing psychotherapy relative to outcomes observed with active placebo medication and psychotherapy. Design, Setting, and Participants: In this double-blind randomized clinical trial, participants were offered 12 weeks of manualized psychotherapy and were randomly assigned to receive psilocybin vs diphenhydramine during 2 day-long medication sessions at weeks 4 and 8. Outcomes were assessed over the 32-week double-blind period following the first dose of study medication. The study was conducted at 2 academic centers in the US. Participants were recruited from the community between March 12, 2014, and March 19, 2020. Adults aged 25 to 65 years with a DSM-IV diagnosis of alcohol dependence and at least 4 heavy drinking days during the 30 days prior to screening were included. Exclusion criteria included major psychiatric and drug use disorders, hallucinogen use, medical conditions that contraindicated the study medications, use of exclusionary medications, and current treatment for AUD. Interventions: Study medications were psilocybin, 25 mg/70 kg, vs diphenhydramine, 50 mg (first session), and psilocybin, 25-40 mg/70 kg, vs diphenhydramine, 50-100 mg (second session). Psychotherapy included motivational enhancement therapy and cognitive behavioral therapy. Main Outcomes and Measures: The primary outcome was percentage of heavy drinking days, assessed using a timeline followback interview, contrasted between groups over the 32-week period following the first administration of study medication using multivariate repeated-measures analysis of variance. Results: A total of 95 participants (mean [SD] age, 46 [12] years; 42 [44.2%] female) were randomized (49 to psilocybin and 46 to diphenhydramine). One participant (1.1%) was American Indian/Alaska Native, 3 (3.2%) were Asian, 4 (4.2%) were Black, 14 (14.7%) were Hispanic, and 75 (78.9%) were non-Hispanic White. Of the 95 randomized participants, 93 received at least 1 dose of study medication and were included in the primary outcome analysis. Percentage of heavy drinking days during the 32-week double-blind period was 9.7% for the psilocybin group and 23.6% for the diphenhydramine group, a mean difference of 13.9%; (95% CI, 3.0-24.7; F1,86 = 6.43; P = .01). Mean daily alcohol consumption (number of standard drinks per day) was also lower in the psilocybin group. There were no serious adverse events among participants who received psilocybin. Conclusions and Relevance: Psilocybin administered in combination with psychotherapy produced robust decreases in percentage of heavy drinking days over and above those produced by active placebo and psychotherapy. These results provide support for further study of psilocybin-assisted treatment for AUD. Trial Registration: ClinicalTrials.gov Identifier: NCT02061293.

Use of a Benchmark Tracking Assessment to Support Expansion of Buprenorphine for Treatment of Opioid Use Disorder in Primary Care.

INTRODUCTION: Barriers to the expansion of opioid use disorder (OUD) treatment in primary care using buprenorphine are well documented. Providers require support along a continuum. A systematic tracking framework to enhance provider progress along this continuum is lacking. METHODS: We developed a benchmark tracking assessment (BTA) as part of data collection in a 5-year study to examine the impact of provider participation in an online intervention to support expansion of buprenorphine treatment for OUD in rural primary care. Providers were contacted via phone every 3 months for up to 2 years to track their advancement along the 5 identified key benchmarks and were offered support for any barriers encountered. RESULTS: Forty-one providers enrolled in the study. Almost half (49%) did not experience a barrier that prevented them from accomplishing their next benchmark. Of the remaining 51% of providers, the majority (75%) experienced barriers early in the training and licensure phases, with most citing lack of time as the main reason. CONCLUSION: The BTA offers a feasible approach to identifying challenges along the training to prescription continuum and facilitated targeted support to address barriers. This framework has the potential, with locally contextual adaptations, to guide medication-assisted treatment implementation and training efforts.

Association of Take-Home Naloxone and Opioid Overdose Reversals Performed by Patients in an Opioid Treatment Program.

Importance: The US opioid crisis was deemed a public health emergency in 2017. More than 130 individuals in the US die daily as a result of unintentional opioid overdose deaths. Objective: To measure use of take-home naloxone for overdose reversals performed by study participants with opioid use disorder receiving treatment at an opioid treatment program. Design, Setting, and Participants: In a year-long cohort study, between April 4, 2016, and May 16, 2017, 395 study participants enrolled at the University of New Mexico Addiction and Substance Abuse Opioid Treatment Program, an outpatient clinic treating substance use disorders. Inclusion criteria included all patients enrolled at University of New Mexico Addiction and Substance Abuse Opioid Treatment Program during the study enrollment period; positive history of opioid use disorder treated with methadone, buprenorphine, or naltrexone; and age 18 years or older. Exclusion criteria included allergy to naloxone and age younger than 18 years. The study closed 1 year after enrollment, on May 17, 2018. Data analysis was performed from May 2018 to July 2019. Exposure: Two doses of take-home naloxone combined with opioid overdose education were provided to study participants. Main Outcomes and Measures: The primary outcome was to measure the association of take-home naloxone with overdose reversals performed by patients with opioid use disorder enrolled in an opioid treatment program. Results: We enrolled 395 study participants (270 female [68.4%]; mean [SD] age, 35.4 [12.6] years; 260 [65.8%] with Hispanic white race/ethnicity) in the 1-year prospective trial. Sixty-eight female participants (25.2% of all female participants) were pregnant at the time of enrollment. Seventy-three of the 395 study participants (18.0%) performed 114 overdose reversals in the community. All community reversals were heroin related. Most study participants (86.8%) stated that the person on whom they performed an overdose reversal was a friend, relative, acquaintance, or significant other. In the year before enrollment, only 18 study participants (4.5%) had been prescribed naloxone. Conclusions and Relevance: Take-home naloxone as part of overdose education and naloxone distribution provided to patients in an opioid treatment program may be associated with a strategic targeted harm reduction response for reversing opioid overdose-related deaths. Policy makers may consider regulations to mandate overdose education and naloxone distribution in opioid treatment programs.

Antidotes for reversal of direct oral anticoagulants.

The main advantage of the direct oral anticoagulants over vitamin K antagonists is reduced rates of major bleeding, especially intracranial hemorrhage. While use of different clotting factor supplements have been used in patients with direct oral anticoagulant induced major bleeding or when there is need for urgent surgery, the lack of preclinical and clinical data are concerning. Idarucizumab is a specific antibody developed with a 350-fold greater affinity for dabigatran than its pharmacologic target thrombin. Andexanet is a modified factor Xa molecule that binds the direct and indirect Xa inhibitors without being enzymatically active. Ciraparantag, has potential to reverse the anticoagulant activity of multiple agents. The pharmacology, preclinical, and clinical data that have developed these specific antidotes are reviewed in this manuscript.

Next-Generation Compound Delivery Platforms to Support Miniaturized Biology.

Recent advancements in science and engineering are revolutionizing our understanding of an individual's disease, and with this knowledge we are gaining an increasingly sophisticated understanding of how discovery can be transformed to deliver personalized medicines. To reach this future state, we must reengineer our approach to enable the use of more relevant human cellular models earlier in the drug discovery process. Stem cells and primary human cells represent more disease-relevant models than immortalized cell lines; however, due to both availability and cost, their use is limited in lead generation activities. Miniaturization of cellular assays below microtiter plate volumes will enable the use of more relevant cells in screening, but this would require a change in how test molecules are introduced to the biology. With these shifting paradigms, Discovery Supply teams at GlaxoSmithKline (GSK) are modernizing our sample handling approaches. Various emerging technologies such as microarrays, nanowells, and microfluidic devices could bring fundamental changes in conventional sample handling support as we transition from microtiter plates to well-less platforms. The discussion here is exploratory in nature and reviews ongoing proof-of-concept experiments. Our ultimate goal is to industrialize the sample management platforms to support future miniaturized biological assay systems.

Engagement With Project ECHO to Increase Medication-Assisted Treatment in Rural Primary Care.

OBJECTIVE: The purpose of this study was to understand the barriers and facilitators that affect engagement with Project ECHO (Extension for Community Healthcare Outcomes) to implement medication-assisted treatment (MAT) in primary care settings. METHODS: A 12-session weekly curriculum was delivered to participating primary care providers and clinic staff (N=24 participants from 13 clinics). Participants completed attendance logs and a qualitative interview in order to identify factors that influence engagement in the ECHO sessions and the potential integration of MAT. RESULTS: Primary care providers and staff valued the ECHO sessions, but overall attendance was low and variable. Participants generally valued the didactic and interactive nature of the sessions but identified system-level constraints that limited engagement. Major barriers to participation included competing demands in patient care and the low degree of endorsement by clinic leadership. CONCLUSIONS: This brief report identifies key systematic challenges that may directly limit primary care providers' engagement in telementoring models such as Project ECHO.

Very late stent thrombosis after dual antiplatelet therapy discontinuation in a patient with a history of acute stent thrombosis.

OBJECTIVE: To describe a case of very late stent thrombosis after dual antiplatelet discontinuation in a patient with a previous history of stent thrombosis. CASE SUMMARY: A 62-year-old man with a history of coronary artery disease, multiple acute coronary syndromes requiring percutaneous coronary interventions with multiple stent placements, and acute stent thrombosis resulting in ST segment elevation myocardial infarction presented to the hospital with chest pain. The chest pain was not relieved by 4 sublingual nitroglycerin tablets. Five days prior to his presentation, the patient had been instructed to discontinue both aspirin and clopidogrel in preparation for a left ankle fusion procedure. He was taken to the cardiac catheterization laboratory where he was found to have thrombosis in a sirolimus-eluting stent placed more than 3 years ago. Thrombectomy and balloon angioplasty were performed, and the patient completed his hospital course without complications. DISCUSSION: Stent thrombosis associated with drug-eluting stents is a complicated pathophysiologic phenomenon with multiple patient-, procedure-, and device-related factors. Application of these risk factors to quantify the risk of stent thrombosis as they apply to a single patient is unknown. Discontinuation of recommended dual antiplatelet therapy with aspirin plus a thienopyridine has been identified as a major risk factor for stent thrombosis, but the optimal duration of dual antiplatelet therapy remains unknown. Current recommendations suggest extending dual antiplatelet therapy beyond one year in patients with low bleeding risk. CONCLUSIONS: Given the overall data at this time and the severity of stent thrombosis, it seems prudent to continue dual antiplatelet therapy with aspirin indefinitely plus a thienopyridine for at least one year, with continuation beyond one year on a case-by-case basis depending on the risks of in-stent thrombosis and bleeding. In patients with a low risk of bleeding, indefinite continuation of dual antiplatelet therapy may be reasonable.