Community partner perspectives on the implementation of a novel safer supply program in Canada: a qualitative study of the MySafe Project.

BACKGROUND: The adulteration of the illicit drug supply with fentanyl and its analogues is driving the ongoing overdose crisis in North America. While various harm reduction interventions address overdose-related risks, there is growing interest in safer supply programs, including the MySafe Project which utilizes a biometric dispensing machine that provides pharmaceutical opioid alternatives to the toxic drug supply. However, the experiences and perspectives of professional community partners on program implementation remain unexplored. This study aims to examine professional community partner perspectives on the feasibility, as well as barriers and facilitators to the implementation of the MySafe program. METHODS: Semi-structured qualitative interviews were conducted with 17 professional community partners involved in program implementation across four pilot locations in Canada. Thematic analysis of interviews focused on perspectives on safer supply, barriers and facilitators faced during program implementation, and recommendations to inform future scale-up of low-barrier safer supply models across Canada. RESULTS: Participants identified a variety of barriers, including the dependence on clinician buy-in, coupled with regulatory and logistical constraints. In addition, some participants perceived hydromorphone to be an inadequate substitute to the increasingly toxic street opioid supply. Lastly, technical difficulties were described as barriers to service uptake and delivery. Conversely, having political and community buy-in, availability of wrap-around services, and collaborative communication from the MySafe team served as facilitators to program implementation. Though community partners preferred establishing MySafe machines into existing community organizations, they also discussed benefits of housing-based MySafe programs. The potential role of this program in mid-sized to rural cities was also emphasized. CONCLUSIONS: To address the overdose crisis, there is an urgent need to implement and evaluate novel solutions that address supply drivers of crisis. Community partner-informed research plays an integral role in ensuring program acceptability and proper implementation. Our findings identify current gaps and facilitators underlying the efficacy of one such model, together with future directions for improvement. Participant recommendations included a diversification of medications offered and types of locations for MySafe programs, a streamlined national approach to prescribing guidelines coupled with more robust training for healthcare professionals, and an emphasis on service delivery within an integrated services model. Our findings underscore a potential gap between the goals of healthcare providers in ensuring comprehensive care and the necessity for low-barrier models such as MySafe that can function both within and outside of integrated service models.

Acceptability of a Fentanyl Vaccine to Prevent Opioid Overdose and Need for Personalized Decision-Making.

BACKGROUND: The opioid epidemic worsened during the coronavirus disease 2019 (COVID-19) pandemic. Synthetic opioids (primarily fentanyl) comprise the most common drugs involved in overdose (OD) death. A vaccine that blocks fentanyl from reaching the brain to prevent OD is under development, and insight is needed into its acceptability. METHODS: Using a semi-structured interview guide, persons with opioid use disorder (OUD), family, professionals, and the public were interviewed about attitudes and concerns regarding a fentanyl vaccine. Reactions to fictional clinical vignettes of persons at risk of OUD because of pain and/or substance use histories were collected, analyzed, and quantified for favorability. Interviews were transcribed, coded, and analyzed thematically. RESULTS: Among N = 64 participants, (70.3% female, average age 32.4 years), attitudes were favorable toward a fentanyl vaccine, with preference for lifelong durability (76% of n = 55 asked). Perceived benefits centered on the potential for a life-saving intervention, suffering averted, healthcare dollars saved, and the utility of a passive harm reduction strategy. Concerns centered on uncertainty regarding vaccine safety, questions about efficacy, worry about implications for future pain management, stigma, and need for supportive counseling and guidance to personalize decision making. Reactions to vignettes revealed complex attitudes toward fentanyl vaccination when considering recipient age, health history, and future risks for addiction and pain. CONCLUSIONS: Positive responses to a fentanyl vaccine were found along with appreciation for the complexity of a vaccine strategy to prevent OD in the setting of pain and uncertain durability. Further research is needed to elucidate operational, ethical, and communications strategies to advance the model.

Definitive urine drug test findings in patients prescribed opioids for pain from a large national database.

OBJECTIVE: Clinicians and policymakers have been wrestling with the appropriateness and safety of opioid therapy during the opioid crisis. Policy and clinical decisions have often been made without much current data on trends in drug use in patients with pain. Thus, we evaluated definitive urine drug test (UDT) results in patients being treated for pain to see if those taking their prescribed opioids were less likely to be positive for the primary illicit drugs currently driving overdose deaths: cocaine, heroin, fentanyl, and methamphetamine. DESIGN, SETTING, AND PATIENTS: A cross-sectional study of UDT results from January 1, 2015 to September 30, 2021, from 600,000 patient specimens submitted for testing by pain management specialists. INTERVENTIONS: UDT by liquid chromatography-tandem mass spectrometry as ordered by the treating clinician. MAIN OUTCOME MEASURES: Presence of other substances stratified by whether a patient's prescribed opioid was found. RESULTS: The presence of cocaine, heroin, fentanyl, and methamphetamine for the total population was low (<5 percent). Of the 347,092 patients prescribed opioids, 76 percent (n = 264,961) were positive on UDT for their prescribed opioid ("consistent"). Compared to patients without their prescribed opioid present ("inconsistent"), patients consistent with therapy were 54 percent (incidence rate ratio (IRR) 1.54, 95 percent confidence interval (CI) 1.47-1.59) less likely to be positive for cocaine, 47 percent [IRR 1.47, 95 percent CI 1.34-1.57] less likely to be positive for heroin, and 35 percent [IRR 1.35, 95 percent CI 1.24-1.45] less likely to be positive for methamphetamine, p < 0.001. Differences between the groups for fentanyl were not significant. CONCLUSIONS: Overall positivity rates for cocaine, heroin, fentanyl, and methamphetamine were low. Patients with prescribed opioid present were less likely to be positive for cocaine, heroin, or methamphetamine. Patterns of substance use within this pain management population should be used to inform ongoing policy decisions.

The impact of the COVID-19 pandemic on access to supervised consumption programs.

BACKGROUND: Supervised consumption sites (SCS) and overdose prevention sites (OPS) have been increasingly implemented in response to the ongoing overdose epidemic in Canada. Although there has been a dramatic increase in overdose deaths since the start of the SARS-CoV 2 (COVID-19) pandemic, little is known about how SCS access may have been affected by this pandemic. Therefore, we sought to characterize potential changes in access to SCS during the COVID-19 pandemic among people who use drugs (PWUD) in Vancouver, Canada. METHODS: Between June and December 2020, data were collected through the Vancouver Injection Drug Users Study (VIDUS) and the AIDS Care Cohort to Evaluate Exposure to Survival Services (ACCESS), two cohort studies involving people who use drugs. Multivariable logistic regression was used to examine individual, social and structural factors associated with self-reported reduced frequency of SCS/OPS use since COVID-19. RESULTS: Among 428 participants, 223 (54.7%) self-identified as male. Among all individuals surveyed, 63 (14.8%) reported a decreased frequency of use of SCS/OPS since COVID-19. However, 281 (66%) reported that they "did not want to" access SCS in the last 6 months. In multivariable analyses, younger age, self-reported fentanyl contamination of drugs used and reduced ease of access to SCS/OPS since COVID-19 were positively associated with a decreased frequency of use of SCS/OPS since COVID-19 (all p < 0.05). CONCLUSIONS: Approximately 15% of PWUD who accessed SCS/OPS reported reduced use of these programs during the COVID-19 pandemic, including those at heightened risk of overdose due to fentanyl exposure. Given the ongoing overdose epidemic, efforts must be made to remove barriers to SCS access throughout public health crises.

Predictors of opioid overdose during the COVID-19 pandemic: The role of relapse, treatment access and nonprescribed buprenorphine/naloxone.

INTRODUCTION: Emerging data indicate a disproportionate increase in overdose deaths since the onset of COVID-19. Speculation about causes for the increase center on rising drug use, illicit drug supply changes, and reduced treatment access. Possible overdose mitigation factors include reduced federal MOUD prescribing restrictions, naloxone distribution programs, and increased use of telehealth. Similarly, nonprescribed buprenorphine (NPB) use, increasingly described as a harm reduction strategy in the absence of treatment, may have moderated overdose risk. This study explored factors associated with pandemic-related overdose in people who use opioids (PWUO) in New Jersey. METHODS: We surveyed 342 PWUO from March to May 2021. Approximately 50 % of our sample was treated at some time since the COVID-19 emergency declaration in March 2020. The risk and protective factors associated with overdose were identified using Pearson's chi square test and ANOVA and tested in a series of multivariable logistic regression models for the full sample and the subsample of PWUO treated during the pandemic. RESULTS: Forty-eight percent of respondents increased their drug use during the pandemic, including 32 % who relapsed after previous abstinence. Fifteen percent overdosed at least once since March 2020. In the full sample, overdose was associated with Hispanic ethnicity (AOR = 3.51; 95 % CI = 1.22-10.11), pre-pandemic overdose (AOR = 6.75; 95 % CI = 3.03-15.02), lack/loss of medical insurance (AOR = 3.02; 95 % CI = 1.01-9.02), relapse (AOR = 2.94; 95 % CI = 1.36-6.36), and nonprescribed use of buprenorphine/naloxone (AOR = 3.16; 95 % CI = 1.49-6.70). The study found similar trends in the treatment sample, with the exceptions that heroin/fentanyl use also predicted overdose (AOR = 3.43; 95 % CI = 1.20-9.78) and the association of overdose with nonprescribed buprenorphine/naloxone was stronger (AOR = 4.91; 95 % CI = 2.01-12.03). Potential mitigating factors, such as take-home methadone and telehealth, were not significant. CONCLUSIONS: Relapse during the pandemic was widespread and a significant contributor to overdose. Lack/loss of medical insurance further exacerbated the risk. Despite the growing literature reporting "therapeutic" use of NPB, people using nonprescribed buprenorphine/naloxone in the current study experienced up to five times the risk of overdose as nonusers. This finding suggests that, despite therapeutic intent, PWUO may be using NPB in ways that are ineffectual for addiction management, especially in the context of changing buprenorphine induction protocols in the context of fentanyl.

Trends and correlated outcomes in population-level prescription opioid and transdermal fentanyl use in Israel.

BACKGROUND: In the last twenty years, there was a documented increase in prescription opioid procurement in Israel. However, there is still little evidence of the association between opioid procurement rates, health service utilisation in secondary care, and enrollment rates to substance use disorder treatment programmes. In this study, we show trends in the reports of opioid-related hospitalisations, emergency department visits, enrollment to community-based outpatient treatment for Prescription Opioid Use Disorder and opioid-related mortality rates. Additionally, we examine potential correlations between these health service utilisation rates and prescription opioid procurement rates at the population level, with a focus on transdermal fentanyl. METHODS: A longitudinal study at the population level. We used seven-year data on indicators of opioid-related morbidity, prescription opioid procurement data for 2015-2021, and six-year opioid-related mortality data for 2015-2020. We measure the correlation between procurement rates of prescription opioids in Oral Morphine Equivalent per capita, and aggregated rates obtained from hospital administrative data for hospitalisations, emergency department visits, and patient enrolment in specialised prescription opioid use disorder outpatient treatment in the community setting. RESULTS: Between 2015 and 2021, procurement rates in primary care per capita for all prescription opioids increased by 85%, while rates of transdermal fentanyl procurement increased by 162%. We found a significant positive correlation at the population level, between annual opioid procurement rates, and rates per population of opioid-related visits to emergency departments (r = 0.96, p value < 0.01, [CI 0.74-0.99]), as well as a positive correlation with the rates per population of patient enrolment in specialised prescription opioid use disorder outpatient treatment (r = 0.93, p value = 0.02, [CI 0.58-0.99]). Opioid-related mortality peaked in 2019 at 0.31 deaths per 100,000 but decreased to 0.20 deaths per 100,000 in 2020. CONCLUSION: Data shows that all-opioid and transdermal fentanyl procurement has increased yearly between 2015 and 2021. This increase is positively correlated with a growing demand for community-based Prescription Opioid Use Disorder outpatient treatment. Efforts to reduce opioid-related morbidity may require effective approaches toward appropriate prescribing, monitoring, and further increasing access to prescription opioid outpatient treatment.

Long-term wastewater-based surveillance and impacts of the COVID-19 pandemic on drug use trends in a U.S. Northeast rural town.

Herein we discuss the findings of a two-year wastewater-based drug use surveillance from September 2018 to August 2020 and present objective evidence on the impacts of the COVID-19 pandemic on drug use in a rural community. 24-h composite wastewater samples were collected twice each month from a university town in Northeastern United States and were analyzed for ten priority opioids and stimulants: morphine, codeine, hydrocodone, methadone, fentanyl cocaine, methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxy-N-ethylamphetamine (MDEA). All target drugs were detected at 100 % frequency in wastewater samples. On a mass basis, the average estimated per capita drug consumption were highest for cocaine, morphine, and amphetamine, and lowest for MDMA, MDEA, and hydrocodone. Furthermore, the estimated per capita consumption of fentanyl was higher than previous reports from rural and university settings in the U.S. Generally, drug consumption was higher during the spring semesters, with year-on-year semester increases also noted over the 2-y study period. Except for methadone and cocaine, the estimated average per capita consumption of drugs increased over the pandemic period, with the highest increase noted for MDMA (286 % increase compared to baseline, p = 0.016). Estimated average consumption of methadone and cocaine decreased slightly by 6 % and 7 %, respectively. These results demonstrate the utility and strength of wastewater-based approaches in capturing long-term and evolving trends in drug use within communities. Our study findings reflect the regionwide problem with opioid-related overdoses and increasing stimulant prescription rates. Our findings also provide objective data and insights for health policymakers on the effects of the pandemic period on community drug use in a rural U.S. town.

Responding to a surge in overdose deaths: perspectives from US syringe services programs.

BACKGROUND: US overdose deaths have reached a record high. Syringe services programs (SSPs) play a critical role in addressing this crisis by providing multiple services to people who use drugs (PWUD) that help prevent overdose death. This study examined the perspectives of leadership and staff from a geographically diverse sample of US SSPs on factors contributing to the overdose surge, their organization's response, and ongoing barriers to preventing overdose death. METHODS: From 2/11/2021 to 4/23/2021, we conducted semi-structured interviews with leadership and staff from 27 SSPs sampled from the North American Syringe Exchange Network directory. Interviews were transcribed and qualitatively analyzed using a Rapid Assessment Process. RESULTS: Respondents reported that increased intentional and unintentional fentanyl use (both alone and combined with other substances) was a major driver of the overdose surge. They also described how the COVID-19 pandemic increased solitary drug use and led to abrupt increases in use due to life disruptions and worsened mental health among PWUD. In response to this surge, SSPs have increased naloxone distribution, including providing more doses per person and expanding distribution to people using non-opioid drugs. They are also adapting overdose prevention education to increase awareness of fentanyl risks, including for people using non-opioid drugs. Some are distributing fentanyl test strips, though a few respondents expressed doubts about strips' effectiveness in reducing overdose harms. Some SSPs are expanding education and naloxone training/distribution in the broader community, beyond PWUD and their friends/family. Respondents described several ongoing barriers to preventing overdose death, including not reaching certain groups at risk of overdose (PWUD who do not inject, PWUD experiencing homelessness, and PWUD of color), an inconsistent naloxone supply and lack of access to intranasal naloxone in particular, inadequate funding, underestimates of overdoses, legal/policy barriers, and community stigma. CONCLUSIONS: SSPs remain essential in preventing overdose deaths amid record numbers likely driven by increased fentanyl use and COVID-19-related impacts. These findings can inform efforts to support SSPs in this work. In the face of ongoing barriers, support for SSPs-including increased resources, political support, and community partnership-is urgently needed to address the worsening overdose crisis.

The North American opioid epidemic: opportunities and challenges for clinical laboratories.

Since 1999, the opioid epidemic in North America has resulted in over 1 million deaths, and it continues to escalate despite numerous efforts in various arenas to combat the upward trend. Clinical laboratories provide drug testing to support practices such as emergency medicine, substance use disorder treatment, and pain management; increasingly, these laboratories are collaborating in novel partnerships including drug-checking services (DCS) and multidisciplinary treatment teams. This review examines drug testing related to management of licit and illicit opioid use, new technologies and test strategies employed by clinical laboratories, barriers hindering laboratory response to the opioid epidemic, and areas for improvement and standardization within drug testing. Literature search terms included combinations of "opioid," "opiate," "fentanyl," "laboratory," "epidemic," "crisis," "mass spectrometry," "immunoassay," "drug screen," "drug test," "guidelines," plus review of PubMed "similar articles" and references within publications. While immunoassay (IA) and point-of-care (POC) test options for synthetic opioids are increasingly available, mass spectrometry (MS) platforms offer the greatest flexibility and sensitivity for detecting novel, potent opioids. Previously reserved as a second-tier application in most drug test algorithms, MS assays are gaining a larger role in initial screening for specific patients and DCS. However, there are substantial differences among laboratories in terms of updating test menus, algorithms, and technologies to meet changing clinical needs. While some clinical laboratories lack the resources and expertise to implement MS, many are also slow to adopt available IA and POC tests for newer opioids such as fentanyl. MS-based testing also presents challenges, including gaps in available guidance for assay validation and ongoing performance assessment that contribute to a dramatic lack of standardization among laboratories. We identify opportunities for improvement in laboratory operations, reporting, and interpretation of drug test results, including laboratorian and provider education and laboratory-focused guidelines. We also highlight the need for collaboration with providers, assay and instrument manufacturers, and national organizations to increase the effectiveness of clinical laboratory and provider efforts in preventing morbidity and mortality associated with opioid use and misuse.

Stability of Drugs Stored in Helicopters for Use by Emergency Medical Services: A Prospective Observational Study.

STUDY OBJECTIVE: Drugs stored in rescue helicopters may be subject to extreme environmental conditions. The aim of this study was to measure whether drugs stored under the real-life conditions of a Swiss helicopter emergency medical service (HEMS) would retain their potency over the course of 1 year. METHODS: A prospective, longitudinal study measuring the temperature exposure and concentration of drugs stored on 2 rescue helicopters in Switzerland over 1 year. The study drugs included epinephrine, norepinephrine, amiodarone, midazolam, fentanyl, naloxone, rocuronium, etomidate, and ketamine. Temperatures were measured inside the medication storage bags and the crew cabins at 10-minute intervals. Drug stability was measured on a monthly basis over the course of 12 months using high-performance liquid chromatography. The medications were considered stable at a minimum remaining drug concentration of 90% of the label claim. RESULTS: Temperatures ranged from -1.2 °C to 38.1 °C (29.84 °F to 100.58 °F) inside the drug storage bags. Of all the temperature measurements inside the drug storage bags, 37% lay outside the recommended storage conditions. All drugs maintained a concentration above 90% of the label claim. The observation periods for rocuronium and etomidate were shortened to 7 months because of a supply shortage of reference samples. CONCLUSION: Drugs stored under the real-life conditions of Swiss HEMS are subjected to temperatures outside the manufacturer's approved storage requirements. Despite this, all drugs stored under these conditions remained stable throughout our study. Real-life stability testing could be a way to extend drug exchange intervals.

Comparing maternal substance use and perinatal outcomes before and during the COVID-19 pandemic.

OBJECTIVE: To examine the effect of the COVID-19 pandemic on maternal substance abuse and neonatal outcomes. STUDY DESIGN: Cross-sectional observational study of neonates admitted to the NICU and born to mothers with evidence of substance abuse pre-pandemic compared to during the COVID-19 pandemic. RESULT: We noted a significant increase in fentanyl (12% vs. 0.6%, p < 0.001) and tobacco use (64% vs. 33%, p < 0.001) during the pandemic compared to pre-pandemic, including an increase in fentanyl use among mothers enrolled in opioid maintenance therapy (OMT) during the pandemic (32.3% vs. 1.5%, p < 0.001). There was a significant increase in preterm births (58% vs. 48%, p = 0.022) and lower birth weight (2315 ± 815 vs. 2455 ± 861 g, p = 0.049) during pandemic. CONCLUSION: There was a significant increase in maternal fentanyl use during the pandemic, even with OMT enrollment, with an increase in preterm births and lower birth weights among infants born to mothers with substance use.

Characteristics and correlates of fentanyl preferences among people with opioid use disorder.

OBJECTIVES: Fentanyl has come to dominate the U.S. illicit opioid supply. We aimed to characterize and examine correlates of preferences for fentanyl vs. other opioids among individuals starting OUD treatment. METHODS: We interviewed 250 adults initiating buprenorphine treatment with positive fentanyl toxicology at intake. We characterized opioid preferences and examined bivariate associations between opioid preference (preference for heroin, fentanyl, heroin-fentanyl mix, or other opioid) and sociodemographic characteristics, psychosocial factors, and substance use behaviors. We then used multinomial logistic regression to examine factors independently associated with fentanyl preferences. RESULTS: Over half (52.0 %) of participants preferred fentanyl (21.2 % fentanyl alone, 30.8 % heroin-fentanyl mix). In bivariate comparisons, participants who preferred fentanyl were a higher acuity group with respect to risks and problems in general. In the multinomial logistic regression, people who preferred fentanyl, either alone or mixed with heroin, used non-prescribed buprenorphine less in the 30 days preceding treatment entry compared to people who preferred heroin or other opioids (RRRalone= 0.88 [0.78, 0.99]; P = 0.037 and RRRmixed= 0.91 [0.84, 0.99]; P = 0.046). People who preferred fentanyl alone were also younger (RRR= 0.93 [0.90, 0.97]; P < 0.001) and more likely to have severe mental illness (RRR= 2.5 [1.1, 5.6]; P = 0.027) than people who prefer heroin or other opioids. CONCLUSIONS: Many people with OUD report preferring fentanyl. People who express preference for fentanyl differ substantively from those with other opioid preferences, and may be at elevated risk for poor health outcomes. Understanding preferences surrounding fentanyl could inform treatment and harm reduction interventions.

I Don't Believe a Person Has to Die When Trying to Get High: Overdose Prevention and Response Strategies in Rural Illinois.

BACKGROUND: Overdose is a leading cause of morbidity and mortality among people who inject drugs. Illicitly manufactured fentanyl is now a major driver of opioid overdose deaths. METHODS: Semi-structured interviews were conducted with 23 participants (19 persons who inject drugs and 4 service providers) from rural southern Illinois. Data were analyzed using constant comparison and theoretical sampling methods. RESULTS: Participants were concerned about the growing presence of fentanyl in both opioids and stimulants, and many disclosed overdose experiences. Strategies participants reported using to lower overdose risk included purchasing drugs from trusted sellers and modifying drug use practices by partially injecting and/or changing the route of transmission. Approximately half of persons who inject drugs sampled had heard of fentanyl test strips, however fentanyl test strip use was low. To reverse overdoses, participants reported using cold water baths. Use of naloxone to reverse overdose was low. Barriers to naloxone access and use included fear of arrest and opioid withdrawal. CONCLUSIONS: People who inject drugs understood fentanyl to be a potential contaminant in their drug supply and actively engaged in harm reduction techniques to try to prevent overdose. Interventions to increase harm reduction education and information about and access to fentanyl test strips and naloxone would be beneficial.

Pharmacological Profiling of Antifentanyl Monoclonal Antibodies in Combination with Naloxone in Pre- and Postexposure Models of Fentanyl Toxicity.

The incidence of fatal drug overdoses in the United States is an alarming public health threat that has been exacerbated by the COVID-19 pandemic, resulting in over 100,000 deaths between April 2020 and April 2021. A significant portion of this is attributable to widespread access to fentanyl and other synthetic opioids, alone or in combination with heroin or psychostimulants, such as cocaine or methamphetamine. Monoclonal antibodies (mAb) offer prophylactic and therapeutic interventions against opioid overdose by binding opioids in serum, reducing distribution of drug to the brain and other organs. Here, we investigated the efficacy of a leading antifentanyl mAb, clone HY6-F9, in reversal and prevention of fentanyl-induced toxicity compared with the opioid receptor antagonist naloxone (NLX) in rats. In postexposure models, rats were challenged with fentanyl, followed by HY6-F9, NLX, or both. HY6-F9 reversed fentanyl-induced antinociception, respiratory depression, and bradycardia, and rats retained protection against additional challenges for at least 1 week. Although intravenous NLX reversed fentanyl-induced respiratory depression more rapidly than mAb alone, kinetics of reversal by intravenous mAb were similar to subcutaneous NLX. Coadministration of mAb and NLX provided greater protection than individual treatments against high doses of fentanyl. Prophylactic administration of mAb reduced the ED50 of NLX approximately twofold against 2.25 mg/kg of fentanyl. Finally, mAb sequestered fentanyl and its metabolite norfentanyl in serum and reduced brain concentrations of fentanyl. These results support the translation of mAb as medical interventions alone or in combination with NLX to prevent and reverse fentanyl-related overdose. SIGNIFICANCE STATEMENT: Fentanyl-related overdoses have increased dramatically in the US and worldwide. Currently, approved pharmacotherapies for treatment of opioid use disorder and reversal of overdose are not sufficient to curb the incidence of opioid-related deaths. Additionally, fentanyl and its potent analogs present a potential risk from use in deliberate poisoning or chemical attacks. This study demonstrates the use of monoclonal antibodies as a countermeasure to fentanyl-induced toxicity in pre- and postexposure scenarios, supporting their use in combination with the opioid antagonist naloxone.

Fatal fentanyl-associated cerebellitis in a young man.

A 22-year-old man was brought in by EMS for coma and respiratory failure. The initial diagnosis was an opioid overdose but the patient did not respond to naloxone. A head CT revealed findings consistent with cerebellitis. The patient developed obstructive hydrocephalus and herniation. Despite neurosurgical and ICU care, the patient did not recover. Cerebellitis is a seldom-discussed complication of opioid use which may become more common as the opioid and fentanyl epidemic evolves.

Increased solitary drug use during COVID-19: An unintended consequence of social distancing.

BACKGROUND: During the COVID-19 pandemic, overdose rates substantially increased in the United States. One possible contributor to this phenomenon may be solitary drug use resulting from social distancing efforts to prevent COVID-19 transmission. METHODS: We surveyed 458 people who use drugs (PWUD) who were recruited from harm reduction and drug treatment providers located in nine states and the District of Columbia. We assessed if solitary drug use had increased since the start of COVID-19. Associations between increased solitary drug use and sociodemographic characteristics, drug use characteristics, and COVID-19 prevention behaviors were examined using multiple logistic regression. RESULTS: Half the sample identified as men (52.7%), White (49.7%), and single (49.3%). The average age was 43.2 (SD:11.8) years. Two-thirds (66.8%) recently injected drugs. 44% reported increased solitary drug use since COVID-19. Significant correlates of increased solitary drug use included being single (adjusted Odds Ratio [aOR]=1.99, 95% Confidence Interval [CI]: 1.33, 2.98), increasing drug use (aOR=2.74, 95% CI: 1.72, 4.37), using more in private locations (aOR=1.91, 95% CI: 1.34, 2.72), and social distancing behaviors (aOR=1.31, 95% CI: 1.11, 1.54). Experiencing homelessness (aOR=0.45, 95% CI: 0.31, 0.65) and identifying as a sexual minority (aOR=0.53, 95% CI: 0.31, 0.93) were associated with being less likely to increase solitary drug use. CONCLUSIONS: Solitary drug use increased during the COVID-19 pandemic. Increases in solitary drug use, in the context of a drug market increasingly permeated by fentanyl, indicates an urgent need for comprehensive harm reduction interventions to reduce overdose mortality.

The United Kingdom's first unsanctioned overdose prevention site; A proof-of-concept evaluation.

BACKGROUND: The United Kingdom (UK) is currently experiencing a public health crisis of drug-related deaths. The government has rejected recommendations to open overdose prevention services, under the Misuse of Drugs Act 1971. To report on the operation and use of an unsanctioned overdose prevention service which operated in Glasgow city centre from September 2020 to May 2021. METHODS: Description of the service, with analysis of data collected on its use. RESULTS: The service operated for nine months without permission or funding from official sources. We report on the 894 injections supervised and recorded, and nine successful interventions with overdose events (seven opioid/two cocaine). Powder cocaine injection predominated either alone (60.6%) or with heroin (22.1%). Injection was mostly in the groin (68.0%) or arm (16.8%). More injections were recorded by males (70.1%). Around 65% of injection events featured an individual who was on a buprenorphine/methadone prescription. CONCLUSION: It is feasible for an overdose prevention service to operate successfully in the UK without being shut down by the police or with negative consequences for the community. Future sites in the UK must tailor to the substances used by their potential clients, international trends (e.g. for fentanyl use) did not apply here. There is an urgent need and demand for these services in the UK to reduce harm, prevent and intervene during overdose, and provide vital psychosocial support for health and wellbeing in a highly marginalised population.

A Case of Phenibut Directed Detoxification Leading to Toxicity During the COVID-19 Pandemic.

BACKGROUND: Phenibut is a non-Food and Drug Administration-approved gamma-aminobutyric acid analog marketed in the United States as an anxiolytic, cognitive enhancer, and alcohol withdrawal treatment through online supplement vendors. In this case report, we describe a woman's self-directed detoxification with phenibut used to manage withdrawal symptoms from fentanyl and benzodiazepines in March 2020 during the height of the COVID-19 pandemic. CASE: A 38-year-old woman with severe opioid, benzodiazepine, gabapentin, stimulant use disorders developed altered mental status after oral phenibut ingestion intended to help self-manage opioid and benzodiazepine withdrawal. She chose self-directed detoxification as she feared COVID-19 exposure in detoxification facilities. Her altered mental status drove her to jump out a third-story window causing multiple spinal fractures. After a long hospitalization, she self-directed her discharge home due to concerns about COVID-19. Her premature discharge disrupted opioid and benzodiazepine use disorder treatment plans. CONCLUSION: This case highlights the risks of phenibut use for selfdirected detoxification. With COVID-19 related changes in the drug supply, people may be more likely to use online pharmaceuticals, therefore, substance use assessments should inquire about the online acquisition of new psychoactive drugs. Public health messaging regarding the risks of infectious disease transmission in addiction care settings is needed to guide addiction treatment choices among people who use substances.

An Interprofessional Approach to Mobilizing Patients With COVID-19 Receiving Extracorporeal Membrane Oxygenation.

OBJECTIVE: To assess survival outcomes with the intervention of an interprofessional mobilization program for patients with COVID-19 who were receiving venovenous extracorporeal membrane oxygenation (VV-ECMO). DESIGN: Preintervention and postintervention retrospective cohort study. METHODS: Survival outcomes of nonmobilized, adult patients (n = 16) with COVID-19 who were receiving VV-ECMO (May 2020 through December 2020) were compared with those of 26 patients who received a mobility care plan (January 2021 through November 2021). In the preintervention group, full sedation and paralysis were used. In the postintervention group, an early mobilization strategy involving interprofessional collaboration was introduced. RESULTS: The postintervention group had improved survival (73.1% vs 43.8%; P < .04); fewer days of receiving paralytics, fentanyl, and midazolam (P < .01 for all); but more days of dexmedetomidine, morphine, and ketamine administration (P < .01 for all). Concomitantly, more patients in the postintervention cohort received oral or transdermal analgesics, oral anxiolytics, and oral antipsychotics (P < .01 for all), and also required more VV-ECMO cannula adjustments (P = .03). CONCLUSION: Early mobilization of patients with COVID-19 who were receiving VV-ECMO improved survival rates but led to more cannula adjustments.