Moving Naloxone Over the Counter Is Necessary but Not Sufficient.

Naloxone is an opioid antagonist that is available in numerous formulations and can be easily administered to avert death from opioid overdose. Amid a historic overdose crisis in the United States, naloxone has a crucial role in stemming the loss of life. However, it remains largely inaccessible to the public. Recently, the U.S. Food and Drug Administration announced the approval of the first over-the-counter formulation of naloxone. Although this historic change provides an important opportunity to increase distribution of naloxone, we must take careful steps during this transition so that it does not paradoxically threaten overall access to this life-saving medication. Specifically, we must ensure that a larger supply of naloxone will meet the newly increased demand at a sustainable price for consumers who are most in need. We must also continue to prioritize comprehensive methods of distribution, such as overdose education and naloxone distribution programs, that serve as important tools to reach the most vulnerable populations. In addition, simultaneous investment in harm-reduction strategies, such as supervised consumption spaces, is critical to ensure that naloxone is available in settings where its life-saving potential can be most fully realized.

Outcomes for Patients Discharged to Involuntary Commitment for Substance Use Disorder Directly from the Hospital.

To evaluate the outcomes of patients discharged to involuntary commitment for substance use disorders directly from the hospital. We performed a retrospective chart review of 22 patients discharged to involuntary commitment for substance use disorder from the hospital between October 2016 and February 2020. We collected demographic data, details about each commitment episode, and healthcare utilization outcomes 1 year following involuntary commitment. Nearly all patients had a primary alcohol use disorder (91%) and had additional medical (82%) and psychiatric comorbidities (71%). One year following involuntary commitment, all patients had relapsed to substance use and had at least one emergency department visit while 78.6% had at least one admission. These findings suggest that patients discharged to involuntary commitment directly from the hospital universally relapsed and experienced significant medical morbidity during the first year following their release. This study adds to a growing literature recognizing the harms of involuntary commitment for substance use disorder.

Liver transplantation in alcohol-associated liver disease: ensuring equity through new processes.

Worsened by the COVID-19 pandemic, alcohol use is one of the leading causes of preventable death in the US, in large part due to alcohol-associated liver disease. Throughout history, liver transplantation for this population has been controversial, and many policies and regulations have existed to limit access to lifesaving transplant for patients who use alcohol. In recent years, the rates of liver transplantation for patients with alcohol-associated liver disease have increased dramatically; however, disparities persist. For instance, many criteria used in evaluation for transplant listing, such as social support and prior knowledge of the harms of alcohol use, are not evidence based and may selectively disadvantage patients with alcohol use disorder. In addition, few transplant providers have adequate training in the treatment of alcohol use disorder, and few transplant centers offer specialized addiction treatment. Finally, current approaches to liver transplantation would benefit from adopting principles of harm reduction, which have demonstrated efficacy in the realm of addiction medicine for years. As we look toward the future, we must emphasize the use of evidence-based measures in selecting patients for listing, ensure access to high-quality addiction care for all patients pretransplant and posttransplant, and adopt harm reduction beliefs to better address relapse when it inevitably occurs. We believe that only by addressing each of these issues will we be able to ensure a more equitable distribution of resources in liver transplantation for all patients.

The Use of a Single Dose of Phenobarbital for Inpatient Management of Benzodiazepine Withdrawal: A Case Report.

INTRODUCTION: The current standard of care for physiological dependence to benzodiazepines requires prolonged outpatient tapers, which present challenges for patients and providers. Novel protocols for accelerated benzodiazepine tapers are needed. We describe a case of successful management of benzodiazepine withdrawal in the inpatient setting using a single, loading dose of phenobarbital with adjunctive valproate therapy. CASE REPORT: A 61-year-old woman with benzodiazepine use disorder using 3 to 4 mg of alprazolam daily presented to an inpatient medically supervised withdrawal unit requesting discontinuation of all benzodiazepines and other recreational substances by the time of discharge. Benzodiazepine withdrawal was treated with a single, loading dose of intravenous phenobarbital in line with an approved protocol for the treatment of alcohol withdrawal, as well as adjunctive valproate therapy. The patient experienced resolution of withdrawal symptoms, had no complications, and ongoing abstinence at 60 days of follow-up. DISCUSSION: A single loading dose of phenobarbital in the inpatient setting is a viable alternative to prolonged outpatient tapers for the management of benzodiazepine withdrawal. Although this strategy requires further optimization, the prospect of a single-dose treatment for benzodiazepine withdrawal creates exciting opportunities for alternative management options and settings. CONCLUSIONS: This case describes the successful management of benzodiazepine withdrawal syndrome using a single loading dose of intravenous phenobarbital derived from an approved protocol for alcohol withdrawal syndrome.

Associations Between Copays, Coverage Limits for Naloxone, and Prescribing in Medicaid.

Aims: To describe naloxone dispensing in Medicaid fee-for-service (FFS) and examine relationships between copays and coverage limits for naloxone and its dispensing rates. Methods: Cross-sectional study using Medicaid FFS State Drug Utilization Data to quantify the use of naloxone in 2018. The primary outcomes of this study were the proportion of naloxone prescriptions relative to all prescriptions and all opioid prescriptions dispensed in each state. We obtained drug benefit design information from the Medicaid Behavioral Health Services Database. The primary analysis examined the influence of copays (yes/no), copay amounts, and coverage limits on medication dispensing using simple linear regression, excluding states with no measurable use or less than 5% Medicaid FFS. Results: We found substantial variability across 50 states and DC in the proportion of prescriptions dispensed for Narcan and generic naloxone. We found a positive relationship between copay and copay amount and dispensing of generic naloxone. However, a sensitivity analysis including the broadest possible cohort of states failed to confirm this relationship. We found no other relationships between copays or coverage limits and dispensing of any naloxone formulation. Conclusions: Substantial variation exists between the rates of naloxone dispensing across the US for Medicaid patients, but we did not find a meaningful relationship between plan design and dispensing. Whether drug benefit designs in Medicaid influence naloxone use requires further evaluation to avoid limiting access to this life-saving medication.

Against Our Instincts: Decriminalization of Buprenorphine.

The rate of overdose deaths has increased dramatically over the past 2 decades. Recently, efforts have been made to expand access to medications for opioid use disorder, such as buprenorphine, by removing X-waiver training requirements. However, relieving such barriers has also raised concern about increasing diversion rates for buprenorphine use, defined as the use of buprenorphine for some purpose or by someone other than it was originally intended. Historically, diversion has been addressed through the criminalization of buprenorphine possession without a prescription. We argue that while buprenorphine diversion is not to be condoned, the benefits of such actions greatly outweigh the harms. Thus, criminalization of diverted buprenorphine represents a dangerous and wasteful response that threatens the progress made through expanded access to this lifesaving medication.

Recognizing and Reducing the Impact of Trauma of Hospitalization: Considerations for Persons Who Use Drugs.

Amidst the ongoing opioid crisis, the number of individuals with substance use disorders being hospitalized for acute medical illnesses has increased. There is now a growing recognition that these events may be psychologically traumatic, leading to the development of acute stress reactions, and post-traumatic stress disorder. Patients who use drugs may be particularly susceptible to being traumatized due to their underlying psychiatric comorbidities, prior trauma histories, inadequate treatment of the underlying substance use disorders, and stigmatization. Interventions such as early identification and screening, trauma-informed care, and specialized addiction services may help to mitigate the risks of trauma amongst this population. More research is needed to better guide hospitals to ensure people who use drugs receive optimal care.

Civil commitment for opioid misuse: do short-term benefits outweigh long-term harms?

In response to a sharp rise in opioid-involved overdose deaths in the USA, states have deployed increasingly aggressive strategies to limit the loss of life, including civil commitment-the forcible detention of individuals whose opioid use presents a clear and convincing danger to themselves or others. While civil commitment often succeeds in providing short-term protection from overdose, emerging evidence suggests that it may be associated with long-term harms, including heightened risk of severe withdrawal, relapse and opioid-involved mortality. To better assess and mitigate these harms, states should collect more robust data on long-term health outcomes, decriminalise proceedings and stays, provide access to medications for opioid use disorder and strengthen post-release coordination of community-based treatment.

A neuroeconomic signature of opioid craving: How fluctuations in craving bias drug-related and nondrug-related value.

How does craving bias decisions to pursue drugs over other valuable, and healthier, alternatives in addiction? To address this question, we measured the in-the-moment economic decisions of people with opioid use disorder as they experienced craving, shortly after receiving their scheduled opioid maintenance medication and ~24 h later. We found that higher cravers had higher drug-related valuation, and that moments of higher craving within-person also led to higher drug-related valuation. When experiencing increased opioid craving, participants were willing to pay more for personalized consumer items and foods more closely related to their drug use, but not for alternative "nondrug-related" but equally desirable options. This selective increase in value with craving was greater when the drug-related options were offered in higher quantities and was separable from the effects of other fluctuating psychological states like negative mood. These findings suggest that craving narrows and focuses economic motivation toward the object of craving by selectively and multiplicatively amplifying perceived value along a "drug relatedness" dimension.

Comparative analysis of assays to measure CAR T-cell-mediated cytotoxicity.

The antitumor efficacy of genetically engineered 'living drugs', including chimeric antigen receptor and T-cell receptor T cells, is influenced by their activation, proliferation, inhibition, and exhaustion. A sensitive and reproducible cytotoxicity assay that collectively reflects these functions is an essential requirement for translation of these cellular therapeutic agents. Here, we compare various in vitro cytotoxicity assays (including chromium release, bioluminescence, impedance, and flow cytometry) with respect to their experimental setup, appropriate uses, advantages, and disadvantages, and measures to overcome their limitations. We also highlight the US Food and Drug Administration (FDA) directives for a potency assay for release of clinical cell therapy products. In addition, we discuss advanced assays of repeated antigen exposure and simultaneous testing of combinations of immune effector cells, immunomodulatory antibodies, and targets with variable antigen expression. This review article should help to equip investigators with the necessary knowledge to select appropriate cytotoxicity assays to test the efficacy of immunotherapeutic agents alone or in combination.