Naloxone Distribution Research Articles

State-Level History of Overdose Deaths Involving Stimulants in the United States, 1999‒2020.

Objectives. To examine the state-level history of US overdose deaths involving stimulants with and without opioids from 1999 to 2020. Methods. We used death certificate data from the National Center for Health Statistics to categorize deaths into 4 groups of interest: cocaine with and without opioids, and psychostimulants with and without opioids. We used a Bayesian multiple change point model to describe the timing and magnitude of changes in overdose death rates involving stimulants for each state and year. Results. There was little change in the death rates of cocaine without opioids. Death rates involving cocaine and opioids sharply increased around 2015, particularly in the Northeast and Mid-Atlantic. We also observed steady increases in deaths involving psychostimulants without opioids just before 2010, particularly in states in the West and South. Deaths involving psychostimulants with opioids increased around 2015 with largest increases concentrated in Appalachian states. Conclusions. There is significant geographic heterogeneity in the co-involvement of stimulants in the US overdose crisis. Results can inform public health efforts to inform state-level overdose efforts such as naloxone distribution. (Am J Public Health. 2023;113(9):991-999. https://doi.org/10.2105/AJPH.2023.307337).

Changes to opioid overdose deaths and community naloxone access among Black, Hispanic and White people from 2016 to 2021 with the onset of the COVID-19 pandemic: An interrupted time-series analysis in Massachusetts, USA.

The onset of the coronavirus disease 2019 (COVID-19) pandemic was associated with a surge in opioid overdose deaths in Massachusetts, particularly affecting racial and ethnic minority communities. We aimed to compare the impact of the pandemic on opioid overdose fatalities and naloxone distribution from community-based programs across racial and ethnic groups in Massachusetts. Interrupted time-series. Opioid overdose deaths (OODs) among non-Hispanic White, non-Hispanic Black, Hispanic and non-Hispanic other race people in Massachusetts, USA (January 2016 to June 2021). Rate of OODs per 100 000 people, rate of naloxone kits distributed per 100 000 people and ratio of naloxone kits per opioid overdose death as a measure of naloxone availability. We applied five imputation strategies using complete data in different periods to account for missingness of race and ethnicity for naloxone data. Before COVID-19 (January 2016 to February 2020), the rate of OODs declined among non-Hispanic White people [0.2% monthly reduction (95% confidence interval = 0.0-0.4%)], yet was relatively constant among all other population groups. The rate of naloxone kits increased across all groups (0.8-1.2% monthly increase) and the ratio of naloxone kits per OOD death among non-Hispanic White was 1.1% (0.8-1.4%) and among Hispanic people was 1.0% (0.2-1.8%). After the onset of the pandemic (March 2020+), non-Hispanic Black people experienced an immediate increase in the rate of OODs [63.6% (16.4-130%)], whereas rates among other groups remained similar. Trends in naloxone rescue kit distribution did not substantively change among any groups, and the ratio of naloxone kits per OOD death for non-Hispanic Black people did not compensate for the surge in OODs deaths in this group. With the onset of the COVID-19 pandemic, there was a surge in opioid overdose deaths among non-Hispanic Black people in Massachusetts, USA with no compensatory increase in naloxone rescue kit distribution. For non-Hispanic White and Hispanic people, opioid overdose deaths remained stable and naloxone kit distribution continued to increase.

Guidance on take-home naloxone distribution and use by community overdose responders in Canada.

The increasing toxicity of opioids in the unregulated drug market has led to escalating numbers of overdoses in Canada and worldwide; takehome naloxone (THN) is an evidence-based intervention that distributes kits containing naloxone to people in the community who may witness an overdose. The purpose of this guidance is to provide policy recommendations for territorial, provincial and federal THN programs, using evidence from scientific and grey literature and community evidence that reflects 11 years of THN distribution in Canada. The Naloxone Guidance Development Group - a multidisciplinary team including people with lived and living experience and expertise of drug use - used the Appraisal of Guidelines for Research & Evaluation (AGREE II) instrument to inform development of this guidance. We considered published evidence identified through systematic reviews of all literature types, along with community evidence and expertise, to generate recommendations between December 2021 and September 2022. We solicited feedback on preliminary recommendations through an External Review Committee and a public input process. The project was funded by the Canadian Institutes of Health Research through the Canadian Research Initiative in Substance Misuse. We used the Guideline International Network principles for managing competing interests. Existing evidence from the literature on THN was of low quality. We incorporated evidence from scientific and grey literature, and community expertise to develop our recommendations. These were in 3 areas: routes of naloxone administration, THN kit contents and overdose response. Take-home naloxone programs should offer the choice of both intramuscular and intranasal formulations of naloxone in THN kits. Recommended kit contents include naloxone, a naloxone delivery device, personal protective equipment, instructions and a carrying case. Trained community overdose responders should prioritize rescue breathing in the case of respiratory depression, and conventional cardiopulmonary resuscitation in the case of cardiac arrest, among other interventions. This guidance development project provides direction for THN programs in Canada in the context of limited published evidence, with recommendations developed in collaboration with diverse stakeholders.

Pharmacists’ perceptions regarding feasibility, acceptability, and usefulness of student-delivered naloxone education services in community pharmacy: A mixed methods study in Alabama

BackgroundGiven that Alabama has the highest opioid prescribing rate in the nation, efforts to promote safe opioid use and reduce overdose mortality are critical. To address this, the Auburn University Harrison College of Pharmacy developed and piloted a didactic-experiential naloxone learning model in the first-year PharmD curriculum in 2020-2021 consisting of lectures, skills laboratory, and 120-hour community pharmacy introductory pharmacy practice experience (IPPE). Student-delivered naloxone education services (SDNES), including naloxone counseling and dispensing, were incorporated into the IPPE. ObjectivesThe objective of this study was to evaluate the feasibility, acceptability, and usefulness of SDNES frovm the perspective of community pharmacy IPPE preceptors. MethodsThis study used a mixed methods design including cross-sectional online surveys and follow-up semistructured telephone interviews. Survey measures were informed by validated scales and included feasibility (11 items), acceptability (13 items), and usefulness (6 items) of SDNES. Survey outcomes were assessed via 5-point Likert-type scales (1 = strongly disagree, 5 = strongly agree) and analyzed using descriptive statistics. Follow-up semistructured telephone interview questions were guided by the Consolidated Framework for Implementation Research domains of inner and outer setting and focused on SDNES barriers and facilitators, recommended strategies for service enhancement, and resource needs. Interview transcripts were analyzed using deductive and inductive rapid content analysis to determine themes and subthemes. ResultsTwenty-five preceptor surveys were completed (22.52% response rate). Overall, SDNES was rated as feasible (mean [SD] scale score 4.04 [0.77]), acceptable (3.95 [0.83]), and useful (3.87 [0.98]). Interviewees (N = 8) discussed 13 barrier subthemes, 12 facilitator subthemes, 7 recommended strategies, and 8 resource needs across 3 overarching themes, most of which were related to the inner setting. ConclusionCommunity pharmacy IPPE preceptors found SDNES feasible, acceptable, and useful in their practices. The SDNES model may be used to build capacity for naloxone services delivery in community pharmacies, potentially increasing patient access to naloxone education and distribution.

Opioid Use Disorder Stigma and Support for Harm Reduction in Rural Counties

Background: The opioid crisis is a public health emergency in the United States, particularly in rural Pennsylvania. Stigma in rural communities is a treatment barrier and impacts harm reduction programming availability. Objectives: The current study utilized an observational, cross-sectional design to examine latent subgroups of stigma and differences in support for harm reduction strategies (i.e., safe injection facilities, syringe services programs, fentanyl test strips, Naloxone distribution). Participants included rural Pennsylvanians (n = 252), taken from a statewide survey of opioid use disorder (OUD) stigma. Participants reported OUD public stigma (i.e., attitudes/perceptions about OUD, willingness to engage with individuals with OUD) and support for harm reduction strategies. Results: Latent class analysis identified 4 stigma classes: 1) high stigma (HS), 2) high judgment/low stigmatizing behavior (HJ/LB), 3) high stigmatizing behavior/low stigmatizing attitude (HB/LA), and 4) low stigma (LS). ANCOVAs identified subgroup differences in harm reduction support. The HS group indicated less support for safe injection sites, syringe services programs, and fentanyl test strips, compared to the HB/LA and LS groups. The HS group indicated less support for Naloxone distribution compared to the HJ/LB, HB/LA, and LS groups. Lastly, the HJ/LB group indicated less support for each program compared to the LS group. Conclusions/Importance: Findings highlight that OUD stigma profiles differ across rural Pennsylvania and are associated with varying support for harm reduction strategies. Individuals with less stigma report more support for harm reduction strategies. Interventions to implement harm reduction strategies should consider varying levels of stigma and use a targeted approach to inform implementation and messaging strategies.

Overdose education and naloxone distribution program design informed by people who use drugs and naloxone distributors

People who use drugs (PWUD) are the most directly affected by the overdose epidemic. However, they are not often targets of overdose education and naloxone distribution (OEND) programs. Instead, these programs target friends or family members of people prescribed opioids or general community members. This study aimed to understand the perspectives of PWUD and community naloxone distributors on OEND program design. We used a community-based participatory research model to elucidate participant perspectives on what OEND programs should look like in the context of each individual’s specific risk environment. We conducted semi-structured in-depth interviews with PWUD and naloxone distributors (n = 30) in New Brunswick and Newark, New Jersey between February and November of 2022. We analyzed interviews using thematic analysis and identified the following themes: increasing naloxone knowledge, peer-based naloxone access, increasing PWUD-informed OEND program design, and desired broader OEND program scope. All Participants knew what naloxone was and emphasized that naloxone needed to be ubiquitous in the community. Participants prioritized peer-based distribution, integrating distribution into community organizations, and addressing psychosocial issues related to naloxone administration and drug use. In summary, PWUD and community naloxone distributors emphasized peer-led community naloxone distribution that prioritized novel ways for PWUD to access naloxone. OEND program design should prioritize PWUD’s perspectives and direct community naloxone distribution.

Evaluation of a large-scale health department naloxone distribution program: Per capita naloxone distribution and overdose morality.

To report per-capita distribution of take-home naloxone to lay bystanders and evaluate changes in opioid overdose mortality in the county over time. Hamilton County Public Health in southwestern Ohio led the program from Oct 2017-Dec 2019. Analyses included all cartons distributed within Hamilton County or in surrounding counties to people who reported a home address within Hamilton County. Per capita distribution was estimated using publicly available census data. Opioid overdose mortality was compared between the period before (Oct 2015-Sep 2017) and during (Oct 2017-Sep 2019) the program. A total of 10,416 cartons were included for analyses, with a total per capita distribution of 1,275 cartons per 100,000 county residents (average annual rate of 588/100,000). Median monthly opioid overdose mortality in the two years before (28 persons, 95% CI 25-31) and during (26, 95% CI 23-28) the program did not differ significantly. Massive and rapid naloxone distribution to lay bystanders is feasible. Even large-scale take-home naloxone distribution may not substantially reduce opioid overdose mortality rates.

Updated Estimates of Annual U.S. Health System Spending from a Hypothetical National Naloxone Co-Prescribing Mandate

Background: Naloxone-prescription opioid co-prescribing mandates have increasingly been proposed and adopted in the U.S., at both the national and state levels, as a public health intervention for mitigating the impacts of opioid overdoses. In this study, we assess whether a hypothetical national, naloxone co-prescribing mandate has become less costly for the U.S. health system since 2018. Methods: We expand and update an existing economic model of naloxone co-prescribing to estimate annual health system spending. We refresh the model inputs through 2021 to reflect changes to the opioid and naloxone landscapes, expand the model to account for more types of market responses, and develop additional scenarios around alternate implementation strategies such as bulk purchasing. Results: We estimate annual spending increases across all retail opioid patients of $1.4–$4.0 billion with naloxone nasal sprays and auto-injectors, and $0.6–$0.9 billion with traditional injectable naloxone formulations. We also find that bulk purchasing could lead to higher spending increases in some patient populations absent volume discounts. Conclusions: Our estimates are substantially lower than prior research. Key drivers include lower prices for naloxone, higher current naloxone distribution, a longer approved shelf life for naloxone, and lower estimated sizes for some patient populations. Additional research is needed to estimate the potential benefits of naloxone co-prescribing for mitigating opioid overdoses, and whether they could outweigh spending increases. Steps that could make this policy more beneficial or less costly include targeting higher risk patient populations and promoting large-scale purchasing agreements with volume discounts to help offset potential price increases.

Rural Community Pharmacy Approaches to Lethal Means Management for Suicide Prevention

ABSTRACT Introduction Medications are common means of suicide. Rural areas have high suicide rates, greater proportions of older adults and veterans, and few providers. We assessed the implementation potential of community pharmacy interventions for lethal means management (LMM). Methods The feasibility, acceptability, and appropriateness of 8 LMM interventions were assessed by pharmacists in seven southeastern states via an online survey. Descriptive statistics were calculated. Results Pharmacists (N = 61) responded from 42 zip codes. The majority indicated that five (62.5%) interventions were very/extremely feasible, appropriate and acceptable. The greatest proportion rated medication therapy management (MTM) as very or extremely feasible, appropriate and acceptable (82%) followed by limiting prescription drug days’ supplies (75.4%), blister packaging (68.9%), dispensing naloxone (62.3%), and suicide prevention training (59.0%). No pharmacies were currently distributing gun locks; however, some were already managing suicide risk with limited days’ supply (31.7%), MTM (26.7%), naloxone distribution with every opioid dispensed (15.0%), monitoring patients for suicidal adverse events (16.7%), limits on sales or stock of non-prescription products (16.7%) or blister packaging (1.7%). Discussion Pharmacists endorsed LMM interventions, and most were already offering the endorsed interventions but not for LMM. Clinical Implications The rural community pharmacists in this study believed several LMM services were highly feasible, acceptable and appropriate for use in preventing suicide.

Systems analysis and improvement approach to improve naloxone distribution within syringe service programs: study protocol of a randomized controlled trial

BackgroundMore than half a million Americans died of an opioid-related overdose between 1999 and 2020, the majority occurring between 2015 and 2020. The opioid overdose mortality epidemic disproportionately impacts Black, Indigenous, and people of color (BIPOC): since 2015, overdose mortality rates have increased substantially more among Black (114%) and Latinx (97%) populations compared with White populations (32%). This is in part due to disparities in access to naloxone, an opioid antagonist that can effectively reverse opioid overdose to prevent death. Our recent pilot work determined that many barriers to naloxone access can be identified and addressed by syringe service programs (SSPs) using the Systems Analysis and Improvement Approach to Naloxone distribution (SAIA-Naloxone). This randomized controlled trial will test SAIA-Naloxone’s ability to improve naloxone distribution in general and among BIPOC specifically.MethodsWe will conduct a trial with 32 SSPs across California, randomly assigning 16 to the SAIA-Naloxone arm and 16 to receive implementation as usual. SAIA-Naloxone is a multifaceted, multilevel implementation strategy through which trained facilitators work closely with SSPs to (1) assess organization-level barriers, (2) prioritize barriers for improvement, and (3) test solutions through iterative change cycles until achieving and sustaining improvements. SSPs receiving SAIA-Naloxone will work with a trained facilitator for a period of 12 months. We will test SAIA-Naloxone’s ability to improve SSPs’ naloxone distribution using an interrupted time series approach. Data collection will take place during a 3-month lead-in period, the 12-month active period, and for an additional 6 months afterward to determine whether impacts are sustained. We will use a structured approach to specify SAIA-Naloxone to ensure strategy activities are clearly defined and to assess SAIA-Naloxone fidelity to aid in interpreting study results. We will also assess the costs associated with SAIA-Naloxone and its cost-effectiveness.DiscussionThis trial takes a novel approach to improving equitable distribution of naloxone amid the ongoing epidemic and associated racial disparities. If successful, SAIA-Naloxone represents an important organizational-level solution to the multifaceted and multilevel barriers to equitable naloxone distribution.

Saving lives in our homes: Qualitative evaluation of a tenant overdose response program in supportive, single-room occupancy (SRO) housing.

People using opioids alone in private settings are at elevated risk of dying in the event of an overdose. In San Francisco, single room occupancy (SRO) tenants are 19 times more likely to die of overdose than non-SRO residents. The "SRO Project" pilot aimed to reduce fatal overdoses in SROs by recruiting and training tenants to distribute naloxone and provide overdose education in their buildings. We explore the implementation and program impacts of the SRO Project pilot in two permanent supportive housing SROs. We conducted eight months of ethnographic fieldwork (May 2021 - Feb 2022), including 35 days observing SRO Project pilot activities, and semi-structured interviews with 11 housing staff and 8 tenant overdose prevention specialists ('specialists'). Data were analyzed using a grounded theory approach to characterize program impacts, implementation strengths, and implementation challenges from the perspective of specialists and housing staff. We found that the SRO project increased awareness, access to, and understanding of naloxone; facilitated other mutual-aid practices; supported privacy and autonomy of tenants regarding their drug use; and improved rapport, communication and trust between tenants and housing staff. Strengths of the implementation process included involvement of tenants with diverse social locations and skill sets and, at one site, a team-based approach that fostered program innovation, tenant solidarity and a sense of collective ownership over the project. Program implementation was challenged by frequent turnover and capacity constraints of housing staff, particularly during overnight shifts when overdose risks were greatest. Additional challenges arose due to the psychosocial burden of overdose response work, gendered violence, issues with compensation methods, and scope creep in specialists' roles. This evaluation contributes further evidence regarding the effectiveness of tenant-led naloxone distribution and overdose education in permanent supportive and SRO housing environments. Findings indicate program implementation and sustainability can be improved by expanding tenant specialist training, compensating specialists in cash, and building stronger psychosocial support for tenants responding to overdoses in their homes.

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.

Comparison of a national commercial pharmacy naloxone data source to state and city pharmacy naloxone data sources-Rhode Island, Massachusetts, and New York City, 2013-2019.

Accurate naloxone distribution data are critical for planning and prevention purposes, yet sources of naloxone dispensing data vary by location, and completeness of local datasets is unknown. We sought to compare available datasets in Massachusetts, Rhode Island, and New York City (NYC) to a commercially available pharmacy national claims dataset (Symphony Health Solutions). We utilized retail pharmacy naloxone dispensing data from NYC (2018-2019), Rhode Island (2013-2019), and Massachusetts (2014-2018), and pharmaceutical claims data from Symphony Health Solutions (2013-2019). We conducted a descriptive, retrospective, and secondary analysis comparing naloxone dispensing events (NDEs) captured via Symphony to NDEs captured by local datasets from the three jurisdictions between 2013 and 2019, when data were available from both sources, using descriptive statistics, regressions, and heat maps. We defined an NDE as a dispensing event documented by the pharmacy and assumed that each dispensing event represented one naloxone kit (i.e., two doses). We extracted NDEs from local datasets and the Symphony claims dataset. The unit of analysis was the ZIP Code annual quarter. NDEs captured by Symphony exceeded those in local datasets for each time period and location, except in RI following legislation requiring NDEs to be reported to the PDMP. In regression analysis, absolute differences in NDEs between datasets increased substantially over time, except in RI before the PDMP. Heat maps of NDEs by ZIP code quarter showed important variations reflecting where pharmacies may not be reporting NDEs to Symphony or local datasets. Policymakers must be able to monitor the quantity and location of NDEs in order to combat the opioid crisis. In regions where NDEs are not required to be reported to PDMPs, proprietary pharmaceutical claims datasets may be useful alternatives, with a need for local expertise to assess dataset-specific variability.

Barriers and facilitators of naloxone and safe injection facility interventions to reduce opioid drug-related deaths: A qualitative analysis.

Opioid drug-related deaths continue to be a significant public health concern in the Republic of Ireland (ROI) and Northern Ireland (NI). While both regions have implemented naloxone to reduce drug related deaths, there remains a gap in the implementation of a supervised injection facility (SIF). This study aimed to identify barriers and facilitators to implementing naloxone and a SIF to reduce opioid drug-related deaths in ROI and NI. Semi-structured interviews (n=23) were conducted in ROI and NI with experts by experience (n=8), staff from low threshold services (n=9), and individuals involved in policy making (n= 6). Data were analyzed using coding reliability Thematic Analysis and were informed by the Risk Environmental Framework. The findings illustrated that stigma within the media, health centers, and the community was a significant barrier to naloxone distribution and SIF implementation. Policing and community intimidation were reported to hinder naloxone carriage in both the ROI and NI, while threats of paramilitary violence towards people who use drugs were unique to NI. Municipal government delays and policy maker apathy were reported to hinder SIF implementation in the ROI. Participants suggested peer-to-peer naloxone delivery and amending legislation to facilitate non-prescription naloxone would increase naloxone uptake. Participants recommended using webinars, Town Halls, and a Citizens' Assembly as tools to advocate for SIF implementation. Local and regional stigma reduction campaigns are needed in conjunction with policy changes to advance naloxone and a SIF. Tailoring stigma campaigns to incorporate the lived experience of people who use drugs, their family members, and the general community can aid in educating the public and change negative perceptions. This study highlights the need for ongoing efforts to reduce stigma and increase accessibility to evidence-based interventions to address opioid drug-related deaths in the ROI, NI, and internationally.

Intersections between syndemic conditions and stages along the continuum of overdose risk among women who inject drugs in Mexicali, Mexico

BackgroundResearch on women who inject drugs is scarce in low- and middle-income countries. Women experience unique harms such as sexism and sexual violence which translate into negative health outcomes. The present work aims to provide insight into the experiences of women who inject drugs at the US–Mexico border to identify social and health-related risk factors for overdose to guide harm reduction interventions across the Global South.MethodsWe recruited 25 women ≥ 18 years of age accessing harm reduction and sexual health services at a non-governmental harm reduction organization, “Verter”, in Mexicali, Mexico. We employed purposeful sampling to recruit women who inject drugs who met eligibility criteria. We collected quantitative survey data and in-depth interview data. Analyses of both data sources involved the examination of descriptive statistics and thematic analysis, respectively, and were guided by the syndemic and continuum of overdose risk frameworks.ResultsSurvey data demonstrated reports of initiating injection drug use at a young age, experiencing homelessness, engaging in sex work, being rejected by family members, experiencing physical violence, injecting in public spaces, and experiencing repeated overdose events. Interview data provided evidence of stigma and discrimination toward women, a lack of safe spaces and support systems, risk of overdose-related harms, sexual violence, and the overall need for harm reduction services.ConclusionWomen who inject drugs in Mexicali describe experiences of violence, overdose, and public injecting. Women are particularly vulnerable in the Mexicali context, as this area faces a noticeable lack of health and social services. Evidenced-based harm reduction strategies such as safe consumption sites and overdose prevention strategies (e.g., naloxone distribution and training) may benefit this population. Evidence from local organizations could help close the gap in service provision in low-resource settings like Mexico, where government action is almost nonexistent.

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

BackgroundOpioid 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. MethodsData 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-month 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. ResultsThere 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 during the 12-month 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. ConclusionsFindings 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.

Optimization of Mass Spectrometry Imaging for Drug Metabolism and Distribution Studies in the Zebrafish Larvae Model: A Case Study with the Opioid Antagonist Naloxone.

Zebrafish (ZF; Danio rerio) larvae have emerged as a promising in vivo model in drug metabolism studies. Here, we set out to ready this model for integrated mass spectrometry imaging (MSI) to comprehensively study the spatial distribution of drugs and their metabolites inside ZF larvae. In our pilot study with the overall goal to improve MSI protocols for ZF larvae, we investigated the metabolism of the opioid antagonist naloxone. We confirmed that the metabolic modification of naloxone is in high accordance with metabolites detected in HepaRG cells, human biosamples, and other in vivo models. In particular, all three major human metabolites were detected at high abundance in the ZF larvae model. Next, the in vivo distribution of naloxone was investigated in three body sections of ZF larvae using LC-HRMS/MS showing that the opioid antagonist is mainly present in the head and body sections, as suspected from published human pharmacological data. Having optimized sample preparation procedures for MSI (i.e., embedding layer composition, cryosectioning, and matrix composition and spraying), we were able to record MS images of naloxone and its metabolites in ZF larvae, providing highly informative distributional images. In conclusion, we demonstrate that all major ADMET (absorption, distribution, metabolism, excretion, and toxicity) parameters, as part of in vivo pharmacokinetic studies, can be assessed in a simple and cost-effective ZF larvae model. Our established protocols for ZF larvae using naloxone are broadly applicable, particularly for MSI sample preparation, to various types of compounds, and they will help to predict and understand human metabolism and pharmacokinetics.

Estimated Reductions in Opioid Overdose Deaths With Sustainment of Public Health Interventions in 4 US States

In 2021, more than 80 000 US residents died from an opioid overdose. Public health intervention initiatives, such as the Helping to End Addiction Long-term (HEALing) Communities Study (HCS), are being launched with the goal of reducing opioid-related overdose deaths (OODs). To estimate the change in the projected number of OODs under different scenarios of the duration of sustainment of interventions, compared with the status quo. This decision analytical model simulated the opioid epidemic in the 4 states participating in the HCS (ie, Kentucky, Massachusetts, New York, and Ohio) from 2020 to 2026. Participants were a simulated population transitioning from opioid misuse to opioid use disorder (OUD), overdose, treatment, and relapse. The model was calibrated using 2015 to 2020 data from the National Survey on Drug Use and Health, the US Centers for Disease Control and Prevention, and other sources for each state. The model accounts for reduced initiation of medications for OUD (MOUDs) and increased OODs during the COVID-19 pandemic. Increasing MOUD initiation by 2- or 5-fold, improving MOUD retention to the rates achieved in clinical trial settings, increasing naloxone distribution efforts, and furthering safe opioid prescribing. An initial 2-year duration of interventions was simulated, with potential sustainment for up to 3 additional years. Projected reduction in number of OODs under different combinations and durations of sustainment of interventions. Compared with the status quo, the estimated annual reduction in OODs at the end of the second year of interventions was 13% to 17% in Kentucky, 17% to 27% in Massachusetts, 15% to 22% in New York, and 15% to 22% in Ohio. Sustaining all interventions for an additional 3 years was estimated to reduce the annual number of OODs at the end of the fifth year by 18% to 27% in Kentucky, 28% to 46% in Massachusetts, 22% to 34% in New York, and 25% to 41% in Ohio. The longer the interventions were sustained, the better the outcomes; however, these positive gains would be washed out if interventions were not sustained. In this decision analytical model study of the opioid epidemic in 4 US states, sustained implementation of interventions, including increased delivery of MOUDs and naloxone supply, was found to be needed to reduce OODs and prevent deaths from increasing again.

Preliminary effectiveness of online opioid overdose and naloxone administration training and impact of naloxone possession on opioid use

BackgroundDespite the demonstrated value of opioid overdose education and naloxone distribution (OEND) programs, uptake and utilization remains low. Accessibility to OEND is limited and traditional programs may not reach many high-risk individuals. This study evaluated the effectiveness of online opioid overdose and naloxone administration education and the impact of naloxone possession. MethodsIndividuals with self-reported illicit use of opioids were recruited via Craigslist advertisements and completed all assessments and education online via REDCap. Participants watched a 20-minute video outlining signs of opioid overdose and how to administer naloxone. They were then randomized to either receive a naloxone kit or be given instructions on where to obtain a kit. Effectiveness of training was measured with pre- and post-training knowledge questionnaires. Naloxone kit possession, overdoses, opioid use frequency, and treatment interest were self-reported on monthly follow-up assessments. ResultsMean knowledge scores significantly increased from 6.82/9.00 to 8.22 after training (t(194)=6.85, p <0.001, 95% CI[1.00, 1.81], Cohen’s d=0.85). Difference in naloxone possession between randomized groups was significant with a large effect size (p <0.001, diff=0.60, 95% CI[0.47, 0.73]). A bidirectional relationship was found between naloxone possession and frequency of opioid use. Overdoses and treatment interest were similar across possession status. ConclusionsOverdose education is effective in online video format. Disparity in naloxone possession across groups indicates barriers to obtaining naloxone from pharmacies. Naloxone possession did not influence risky opioid use or treatment interest and its impact on frequency of use warrants further investigation. Trial registrationClinitaltrials.gov-NCT04303000.

EE434 Is Academic Detailing on Naloxone Distribution for Patients at Risk for an Opioid Overdose Good Value for Money? Application of a Probabilistic Sensitivity Analysis in a Cost-Effectiveness Framework

To assess the value of academic detailing (AD) on naloxone distribution among patients at-risk for an opioid-related overdose or death.