High-dose naloxone formulations are not as essential as we thought.

Naloxone is an effective FDA-approved opioid antagonist for reversing opioid overdoses. Naloxone is available to the public and can be administered through intramuscular (IM), intravenous (IV), and intranasal spray (IN) routes. Our literature review investigates the adequacy of two doses of standard IM or IN naloxone in reversing fentanyl overdoses compared to newer high-dose naloxone formulations. Moreover, our initiative incorporates the experiences of people who use drugs, enabling a more practical and contextually-grounded analysis. The evidence indicates that the vast majority of fentanyl overdoses can be successfully reversed using two standard IM or IN dosages. Exceptions include cases of carfentanil overdose, which necessitates ≥ 3 doses for reversal. Multiple studies documented the risk of precipitated withdrawal using ≥ 2 doses of naloxone, notably including the possibility of recurring overdose symptoms after resuscitation, contingent upon the half-life of the specific opioid involved. We recommend distributing multiple doses of standard IM or IN naloxone to bystanders and educating individuals on the adequacy of two doses in reversing fentanyl overdoses. Individuals should continue administration until the recipient is revived, ensuring appropriate intervals between each dose along with rescue breaths, and calling emergency medical services if the individual is unresponsive after two doses. We do not recommend high-dose naloxone formulations as a substitute for four doses of IM or IN naloxone due to the higher cost, risk of precipitated withdrawal, and limited evidence compared to standard doses. Future research must take into consideration lived and living experience, scientific evidence, conflicts of interest, and the bodily autonomy of people who use drugs.

Acceptability of Event-Driven and Long-Acting HIV Pre-Exposure Prophylaxis Formulations Among Transgender Women Engaged in Street-Based Sex Work in Baltimore, Maryland.

We assessed acceptability of nonoral HIV pre-exposure prophylaxis (PrEP) formulations among transgender women (TW) engaged in street-based sex work in Baltimore, Maryland. In a K-means cluster analysis, TW (N=36) were partitioned into groups characterized by high interest in long-acting injectable PrEP only (Injectable Enthusiasts, 36%), high interest in injectables and subdermal implants (Long-Acting Acceptors, 36%), and low interest across PrEP formulations (Non-Acceptors, 28%). TW's interest in novel PrEP agents varied widely across formulations (range: 22-66%) and clustered around numerous relational, occupational, and structural factors, highlighting the importance of availing multiple PrEP formulations for this impacted population.

Association between willingness to use an overdose prevention center and probation or parole status among people who use drugs in Rhode Island.

BACKGROUND: Overdose prevention centers (OPCs) are being implemented in the United States as a strategy to reduce drug-related mortality and morbidity. Previous studies have suggested that people who use drugs (PWUD) with a history of criminal legal system (CLS) involvement (e.g. current probation/parole) are at greater risk of overdose but may also encounter significant barriers to OPC use. The objective of this study was to explore the association between willingness to use an OPC and probation/parole status in a sample of PWUD in Rhode Island. METHODS: This study utilized data from the Rhode Island Prescription and Illicit Drug Study, which enrolled adult PWUD from August 2020 to February 2023. We used Pearson's chi-square and Wilcoxon rank-sum tests to assess bivariate associations between willingness to use an OPC and probation/parole status (current/previous/never), as well as other sociodemographic and behavioral characteristics. In multivariable Poisson analyses, we examined the association between willingness to use an OPC and probation/parole status, adjusting for key sociodemographic and behavioral characteristics. RESULTS: Among 482 study participants, 67% were male, 56% identified as white, 20% identified as Hispanic/Latine, and the median age was 43 (IQR 35-53). Nearly a quarter (24%) had never been on probation/parole, 44% were not currently on probation/parole but had a lifetime history of probation and parole, and 32% were currently on probation/parole. Most participants (71%) reported willingness to use an OPC, and in both bivariate and multivariable analyses, willingness to use an OPC did not vary by probation/parole status. Crack cocaine use and lifetime non-fatal overdose were associated with greater willingness to use an OPC (all p < 0.05). CONCLUSIONS: These data demonstrate high willingness to use OPC among PWUD in Rhode Island regardless of CLS-involvement. As OPCs begin to be implemented in Rhode Island, it will be imperative to engage people with CLS-involvement and to ensure access to the OPC and protection against re-incarceration due to potential barriers, such as police surveillance of OPCs.

"Make yourself un-NIMBY-able": stakeholder perspectives on strategies to mobilize public and political support for overdose prevention centers in the United States of America.

BACKGROUND: Overdose prevention centers (OPCs), also known as supervised injection facilities and safe consumption sites, are evidenced-based interventions for preventing overdose deaths and drug-related morbidities. The pathways to legalizing OPCs in the USA have confronted multiple social, political, and legal obstacles. We conducted a multi-site, qualitative study to explore heterogeneities in these pathways in four jurisdictions, as well as to understand stakeholder perspectives on valuable strategies for galvanizing political and public support for OPCs. METHODS: From July 2022 to February 2023, we conducted 17 semi-structured, in-depth interviews with OPC policymakers, service providers, advocates, and researchers from California, New York City, Philadelphia, and Rhode Island, where efforts have been undertaken to authorize OPCs. Using inductive thematic analysis, we identified and compared contextually relevant, salient approaches for increasing support for OPCs. RESULTS: Participants described several strategies clustering around five distinct domains: (1) embedding OPC advocacy into broader overdose prevention coalitions to shape policy dialogs; (2) building rapport with a plurality of powerbrokers (e.g., lawmakers, health departments, law enforcement) who could amplify the impact of OPC advocacy; (3) emphasizing specific benefits of OPCs to different audiences in different contexts; (4) leveraging relationships with frontline workers (e.g., emergency medicine and substance use treatment providers) to challenge OPC opposition, including 'NIMBY-ism,' and misinformation; and (5) prioritizing transparency in OPC decision-making to foster public trust. CONCLUSION: While tailored to the specific socio-political context of each locality, multiple OPC advocacy strategies have been deployed to cultivate support for OPCs in the USA. Advocacy strategies that are multi-pronged, leverage partnerships with stakeholders at multiple levels, and tailor communications to different audiences and settings could yield the greatest impact in increasing support for, and diffusing opposition to, future OPC implementation.

Supervised Inhalation Sites: Preventing Overdose and Reducing Health Inequities among People Who Use Drugs.

Policy and research on the implementation of services for people who inhale drugs lag behind similar efforts for people who inject drugs, limiting access to adequate harm reduction resources for people who inhale drugs. This commentary considers why supervised inhalation sites (SIS) are needed, highlights operational characteristics of four existing services, and advocates for future SIS research. Our hope is to encourage the expansion of SIS worldwide for overdose prevention and reduction of health inequities. Given the limited literature regarding SIS, more extensive study of these programs is warranted to incorporate inhalation into the implementation of supervised consumption sites to provide fair opportunities for all people who use drugs to do so safely without fear of stigma and overdose.

Implementation of Overdose Prevention in Maryland: Implications for Resource Allocation, Program Scale-Up, and Evaluation.

Overdose mortality in the United States continues to climb, with Maryland being one of the hardest hit states. We summarized implementation of overdose prevention and response programs in Maryland and identified associations between opioid overdose deaths by jurisdiction in 2019 and implementation of overdose programs by 2021. Data on program implementation are from Maryland's Opioid Operational Command Center (OOCC) Program Inventory. OOCC coordinates the state's response to overdose, and their Program Inventory tracks implementation of 145 programs across 12 domains (e.g., public health, education, and judiciary), including 10 programs designed to broaden naloxone access. The level of program implementation was dichotomized as substantial implementation versus other levels (i.e., partial, planned, and none). We estimated associations between per capita opioid overdose deaths and substantial implementation of: all 145 programs in the Inventory, programs within each of 12 domains, and 10 naloxone programs. Data on program implementation and overdose mortality are summarized at the jurisdiction level. Across jurisdictions, the median proportion of programs with substantial implementation was 51% across all programs and 70% among naloxone programs. Overdose mortality was associated with subsequent substantial implementation of programs within the public health domain (p = .04), but not in the other 11 domains. We did not find evidence that per capita overdose deaths in 2019 spurred overdose program implementation by 2021, with the exception of public health programs. The OOCC Program Inventory is a novel way to track implementation across jurisdictions. Findings can inform the implementation and evaluation of overdose programs in other jurisdictions across the United States.

Costing analysis of a point-of-care drug checking program in Rhode Island.

BACKGROUND: Drug checking is a harm reduction strategy that provides greater awareness and information about the drug supply to the community. While fentanyl test strips are low-cost and available in most parts of the U.S., community-based organizations are considering using more sophisticated technologies, such as Fourier-transform infrared (FTIR) spectroscopy to test drugs. FTIR can detect multiple substances in a non-destructive manner that can be rapidly communicated to the program client by a trained technician, however implementation costs in community-based settings have not been assessed. METHODS: We conducted a costing analysis of a new pilot drug checking service that employed an FTIR spectrometer, fentanyl test strips and confirmatory testing in Rhode Island from January 2023-May 2023. We used microcosting methods to determine the overall cost during this period and cost per drug checked, reflecting realistic service capacity. RESULTS: Among 101 drug samples that were voluntarily submitted and tested, 53% tested positive for fentanyl, 39% for cocaine, 9% for methamphetamine and 13% for xylazine, a powerful sedative. The total cost during this period was $71,044 and the cost per drug checked was $474, though sensitivity analyses indicated that the cost would rise to $78,058 - $83,058 or $544 - $593 for programs needing to pay for specialized training. CONCLUSIONS: These findings demonstrate feasibility and inform the resources needed to scale-up drug checking services to reduce overdose risk.

Retention and Overdose Risk among Patients Receiving Substance Use Disorder Treatment, Mental Health Care and Peer Recovery Support: A Longitudinal Analysis.

BACKGROUND: Drug overdose remains a major crisis in the United States. Expanding substance use disorder (SUD) treatment and recovery support services is critical for reducing overdose risk during disasters such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic. We evaluated the outcomes of an innovative multicomponent service, inclusive of medications for SUD, and peer support, colocated in an outpatient infectious disease clinic in Baltimore City. Our goal was to examine whether a multicomponent SUD program can support patients in recovery during a pandemic. METHODS: One hundred five patients in the RESTORE service between 2019-2020 completed baseline, 3-month, and 6-month surveys. Telemedicine and phone-based support groups were implemented in March 2020 after statewide restrictions on face-to-face services due to SARS-CoV2. Data from surveys and electronic medical records were integrated and analyzed using mixed-effects regression models. RESULTS: At baseline, most patients (88%) reported using drugs/alcohol in the preceding 30 days; 48% of patients reported a history of drug overdose, as well anxiety (23%) and depression (28%) symptoms. Despite pandemic-related disruptions and procedural changes, retention in RESTORE was high (83% after 3 months, 76% after 6 months). Mixed-effects regression models indicated decreased anxiety, alcohol use, heroin use, and nonfatal overdose after 6 months of enrollment (all P < 0.05). CONCLUSIONS: Multicomponent SUD services that are colocated within infectious disease specialty services could help patients to successfully manage their overdose risk and mental health even during future disasters. This model of care could be implemented in other specialty settings that see high rates of SUD.

A survey of North American drug checking services operating in 2022.

BACKGROUND: Drug overdose deaths have reached record-breaking levels in North America. Drug checking services (DCS) provide localized information on the contents of drugs to individuals and communities. Depending on the design, individuals can submit drug samples for onsite "real-time" testing or offsite testing. The results can shed light on emerging drugs in the community and support ongoing prevention and surveillance efforts. We sought to describe and report aggregate outcomes of DCS operating in North America. METHODS: The North American Drug Checking Survey was launched in 2022 to characterize and monitor DCS operating in the region. Sixteen organizations from the US (n = 9), Canada (n = 5), and Mexico (n = 2) responded to the survey. Each organization reported on their program's operations and provided service delivery outcomes (site- or program-level) in the aggregate. RESULTS: Participating organizations reported testing a total of 49,786 drug samples between 2014 and 2022. DCS were run by community-led organizations (44%), health departments (25%), universities (19%), or clinical/private laboratories (19%). The types of samples tested differed between programs (e.g., solids vs. liquids, drug paraphernalia accepted). While most organizations tested onsite using fentanyl test strips (88%) and Fourier-transform infrared (FTIR) spectroscopy (63%), many sent samples offsite for confirmatory testing (63%), most often with mass spectrometry. Common facilitators of operating a DCS included: interest of clients (69%), interest of service providers (63%), and receiving external technical assistance (63%). Barriers included: the lack of funding (81%) or staff (50%), gaps in technical expertise (38%), as well as laws banning the possession and/or distribution of illicit drug samples, drug paraphernalia, or drug checking equipment (38%). CONCLUSION: DCS are scaling up in North America. Given the evolving and localized nature of illicit drug supplies, supporting the establishment and operations of DCS could enhance the public's understanding of local drug supplies to reduce drug-related harms over time.

Demographic patterns and disparities in new HIV diagnoses attributed to injection drug use in the United States.

People who inject drugs (PWID) exhibit disproportionate HIV burdens in the United States. We characterized longitudinal patterns and demographic disparities in new HIV diagnoses attributed to injection drug use (IDU) in 2008-2020. Although new IDU-attributed HIV diagnoses fell by 53.9%, new HIV diagnoses remained disproportionately elevated in female (100.9/100 000), Black (258.8/100 000), and Hispanic (131.0/100 000) PWID. Despite considerable declines in new HIV diagnoses, disparities by race/ethnicity and sex persist among US PWID.

Implementing a peer-supported, integrated strategy for substance use disorder care in an outpatient infectious disease clinic is associated with improved patient outcomes.

BACKGROUND: Substance use disorder (SUD) and infectious disease (ID) care integration may lead to improvements in SUD and ID outcomes. We assessed implementation of integrating peer-supported SUD care in an outpatient ID setting. METHODS: In this implementation study, we describe REcovery in Specialty care Through medication and OutREach (RESTORE), a low-threshold SUD program implemented in a Baltimore outpatient ID clinic. Key program components were clinician training and support in SUD care, prescription of SUD treatment medications, and peer-based psychosocial support provided by peer recovery specialists. We assessed clinician adoption of RESTORE and compared patient outcomes from baseline to 6 months. RESULTS: Between January 2019 and January 2022, the number of ID clinicians (N=61) who prescribed buprenorphine increased eightfold from 3 (5%) to 24 (39%). Of 258 ID patients referred to RESTORE, 182 (71%) engaged, 137 consented to study participation. Mean age in the study sample was 52.1 (SD=10.4), 63% were male, 84% were Black/African-American. Among 127 (93%) who completed 6-month follow-up, fewer participants reported illicit/non-prescribed opioid use in the past 30 days at follow-up (32%) compared to baseline (52%; p<0.001). Similar reductions were noted for cocaine use (47% to 34%; p=0.006), emergency department visits (23% to 9%; p=0.002), and inpatient hospitalizations (15% to 7%; p=0.025). CONCLUSION: SUD care integration into an outpatient ID care setting using a peer-supported implementation strategy was adopted by clinicians and improved clinical outcomes for patients. This strategy is a promising approach to treating people with infectious diseases and SUD.

Evaluating the Impact of Brave Technology Co-op's Novel Drug Overdose Detection and Response Devices in North America: a Retrospective Study.

Assess the preliminary impact of Brave Technology Co-op's overdose detection devices that have been implemented in housing, medical, social service facilities, and several private settings in North America. Administrative data was collected by Brave on their Buttons and Sensors during several proof-of-concept projects and full installations in Canada and United States (US) between December 2018 and July 2022. Data analyzed provided insights on the number of overdoses detected and reversed (averted overdose deaths) using Brave Sensors and Buttons, along with other programmatic and session-specific indicators. Implementation of 486 Brave Buttons and 148 Brave Sensors in Canada has detected and prevented 108 overdose deaths (100 using Buttons and 8 using Sensors) whereas implementation of 170 Buttons in the US has averted 2 overdose deaths to date, with the potential to save many more lives. Brave's devices hold promise for increasing rates of overdose detection and preventing overdose deaths.

High-Dose Naloxone Formulations Are Not as Essential as We Thought.

Naloxone is a U.S. Food and Drug Administration (FDA) approved opioid antagonist for reversing opioid overdoses. Naloxone is available to the public, and can be administered through intramuscular (IM), intravenous (IV), and intranasal spray (IN) routes. Our literature review aimed to improve understanding regarding the adequacy of the regularly distributed two doses of low-dose IM or IN naloxone in effectively reversing fentanyl overdoses and whether high-dose naloxone formulations (HDNF) formulations are an optimal solution to this problem. Moreover, our initiative incorporated the perspectives and experiences of people who use drugs (PWUD), enabling a more practical and contextually-grounded analysis. We began by discussing the knowledge and perspectives of Tennessee Harm Reduction, a small peer-led harm reduction organization. A comprehensive literature review was then conducted to gather relevant scholarly works on the subject matter. The evidence indicates that, although higher doses of naloxone have been administered in both clinical and community settings, the vast majority of fentanyl overdoses can be successfully reversed using standard IM dosages with the exception of carfentanil overdoses and other more potent fentanyl analogs, which necessitate three or more doses for effective reversal. Multiple studies documented the risk of precipitated withdrawal using high doses of naloxone. Notably, the possibility of recurring overdose symptoms after resuscitation exists, contingent upon the half-life of the specific opioid. Considering these findings and the current community practice of distributing multiple doses, we recommend providing at least four standard doses of IN or IM naloxone to each potential bystander, and training them to continue administration until the recipient achieves stability, ensuring appropriate intervals between each dose. Based on the evidence, we do not recommend HDNF in the place of providing four doses of standard naloxone due to the higher cost, risk of precipitated withdrawal and limited evidence compared to standard IN and IM. All results must be taken into consideration with the inclusion of the lived experiences, individual requirements, and consent of PWUD as crucial factors. It is imperative to refrain from formulating decisions concerning PWUD in their absence, as their participation and voices should be integral to the decision-making process.

Exploring the impact of the COVID-19 pandemic on healthcare and substance use service access among women who inject drugs: a qualitative study.

BACKGROUND: The COVID-19 pandemic disrupted healthcare and substance use services engagement, including primary and mental health services as well as residential and outpatient drug treatment. Women who inject drugs (WWID) face known barriers to healthcare and substance use service engagement, which pre-date the COVID-19 pandemic. The impact of COVID-19 on WWID's engagement with healthcare and substance use services, however, remains understudied. METHODS: To explore the impact of the COVID-19 pandemic on service-seeking and utilization, we conducted in-depth interviews with 27 cisgender WWID in Baltimore, Maryland, in April-September 2021. Iterative, team-based thematic analysis of interview transcripts identified disruptions and adaptations to healthcare and substance use services during the COVID-19 pandemic. RESULTS: The COVID-19 pandemic disrupted service engagement for WWID through service closures, pandemic safety measures restricting in-person service provision, and concerns related to contracting COVID-19 at service sites. However, participants also described various service adaptations, including telehealth, multi-month prescriptions, and expanded service delivery modalities (e.g., mobile and home delivery of harm reduction services), which overwhelmingly increased service engagement. CONCLUSION: To build upon service adaptations occurring during the pandemic and maximize expanded access for WWID, it is vital for healthcare and substance use service providers to continue prioritizing expansion of service delivery modality options, like telehealth and the provision of existing harm reduction services through alternative platforms (e.g., mobile services), that facilitate care continuity and increase coverage.

Disruptions to naloxone training among lay and occupational responders in Maryland during the emergence of COVID-19: early impacts, recovery, and lessons learned.

Background: : Opioid overdose death rates increased during the COVID-19 pandemic. Disruptions in community-based naloxone trainings could have reduced the likelihood of overdose reversal and increased the chances of a fatal overdose. We investigated changes in the number of people trained in naloxone administration and distribution in Maryland before, during, and after COVID-related stay-at-home orders. Methods: : Data on naloxone training are from the Maryland Department of Health. We used interrupted time series models to estimate changes in average monthly number of people trained: [1] pre-interruption (4/2019-3/2020), [2] 1-month post-interruption (4/2020-5/2020), and [3] 12-months post-interruption (4/2020-3/2021). Trainees were classified as lay (e.g., people who use drugs) or occupational (e.g., law enforcement officers and harm reduction workers) responders. Results: : There were 101,332 trainees; 54.1% lay, 21.5% occupational, and 23.4% unknown responder status. We observed a decrease in the average monthly number of trainees in the pre-interruption period (-235, p<0.001), a larger decrease of 93.2% during the 1-month post-interruption (-846, p=0.013), and an increase 12-months post-interruption (+217, p<0.001). There was a significant decrease among occupational responders 1-month post-interruption, and a significant increase among lay responders in the 12-month post-interruption period. Conclusions: : Findings suggest a marked decrease in naloxone trainees immediately after stay-at-home order, followed by a moderate rebound in the 12-months after stay-at-home order. The decrease in occupational responders trained may have limited access to naloxone, but would likely have been offset by increases in number of lay responders trained. Strengthening lay and occupational responder connections could maintain naloxone distribution during public health crises.

Overdose Detection Technologies-A New Frontier in Preventing Solitary Drug Overdose Deaths.

This Viewpoint examines current opioid overdose detection technologies and their utility in detecting potential drug overdose episodes and preventing solitary overdose deaths in the US.

A Novel Capacity-Strengthening Intervention for Frontline Harm Reduction Workers to Support Pre-exposure Prophylaxis Awareness-Building and Promotion Among People Who Use Drugs: Formative Research and Intervention Development.

BACKGROUND: HIV prevalence among people who use drugs (PWUD) in Baltimore, Maryland, is higher than among the general population. Pre-exposure prophylaxis (PrEP) is a widely available medication that prevents HIV transmission, yet its usefulness is low among PWUD in Baltimore City and the United States. Community-level interventions to promote PrEP uptake and adherence among PWUD are limited. OBJECTIVE: We describe the development of a capacity-strengthening intervention designed for frontline harm reduction workers (FHRWs) to support PrEP awareness-building and promotion among PWUD. METHODS: Our study was implemented in 2 phases in Baltimore City, Maryland. The formative phase focused on a qualitative exploration of the PrEP implementation environment, as well as facilitators and barriers to PrEP willingness and uptake, among cisgender women who use drugs. This work, as well as the existing literature, theory, and feedback from our community partners, informed the intervention development phase, which used an academic-community partnership model. The intervention involved a 1-time, 2-hour training with FHRWs aimed at increasing general PrEP knowledge and developing self-efficacy promoting PrEP in practice (eg, facilitating PrEP dialogues with clients, supporting client advancement along a model of PrEP readiness, and referring clients to PrEP services). In a separate paper, we describe the conduct and results of a mixed methods evaluation to assess changes in PrEP-related knowledge, attitudes, self-efficacy, and promotion practices among FHRWs participating in the training. RESULTS: The pilot was developed from October to December 2021 and implemented from December 2021 through April 2022. We leveraged existing relationships with community-based harm reduction organizations to recruit FHRWs into the intervention. A total of 39 FHRWs from 4 community-based organizations participated in the training across 4 sessions (1 in-person, 2 online synchronous, and 1 online asynchronous). FHRW training attendees represented a diverse range of work cadres, including peer workers, case managers, and organizational administrators. CONCLUSIONS: This intervention could prevent the HIV burden among PWUD by leveraging the relationships that FHRWs have with PWUD and by supporting advancement along the PrEP continuum. Given suboptimal PrEP uptake among PWUD and the limited number of interventions designed to address this gap, our intervention offers an innovative approach to a burgeoning public health problem. If effective, our intervention has the potential to be further developed and scaled up to increase PrEP awareness and uptake among PWUD worldwide.

Overdose Detection Technologies to Reduce Solitary Overdose Deaths: A Literature Review.

Drug overdoses were a leading cause of injury and death in the United States in 2021. Solitary drug use and solitary overdose deaths have remained persistent challenges warranting additional attention throughout the overdose epidemic. The goal of this narrative review is to describe recent global innovations in overdose detection technologies (ODT) enabling rapid responses to overdose events, especially for people who use drugs alone. We found that only a small number of technologies designed to assist in overdose detection and response are currently commercially available, though several are in the early stages of development. Research, development, and scale-up of practical, cost-effective ODTs remains a public health imperative. Equipping places where people live, learn, work, worship, and play with the necessary tools to detect and prevent overdose deaths could complement ongoing overdose prevention efforts.