Overdose responses among rural people who use drugs: A multi-regional qualitative study.

BACKGROUND: Efforts to distribute naloxone have equipped more people with the ability to reverse opioid overdoses but people who use drugs are often reluctant to call 911 due to concerns for legal repercussions. Rural communities face unique challenges in reducing overdose deaths compared to urban communities, including limited access to harm reduction services as well as greater concerns about stigma and privacy. METHODS: The Rural Opioid Initiative was funded in 2017 to better understand the health-related harms associated with the opioid crisis in rural US communities and consists of eight studies spanning ten states and 65 counties. Each study conducted semi-structured qualitative interviews with people who use drugs to understand contextual factors influencing drug use and health behaviors. We analyzed qualitative data from seven studies with data available at the time of analysis to understand peer response to overdose. RESULTS: Of the 304 participants interviewed, 55% were men, 70% were white, 80% reported current injection drug use, and 60% reported methamphetamine use. Similar to what has been found in studies focused on urban settings, people who use drugs in rural communities use a range of strategies to reverse overdoses, including non-evidence-based approaches. Several reported that multiple doses of naloxone are needed to reverse overdose. Three themes emerged around the willingness to call 911, including (1) hesitancy to call 911 for fear of legal consequences, (2) negative perceptions or experiences with law enforcement officers, and (3) efforts to obtain medical intervention while avoiding identification/law enforcement involvement. CONCLUSION: People who use drugs employ multiple strategies to attempt overdose reversal, including non-evidence-based approaches. Greater education about the most effective and least harmful strategies is needed. Reluctance to call 911 is rooted in concerns about potential legal consequences as well as perceptions about law enforcement officers, which may be heightened in rural communities where people who use drugs are more easily identified by law enforcement. People who use drugs will go to great strides to connect their peers to needed medical services, suggesting that comprehensive interventions to reduce interactions with law enforcement officers and eliminate legal consequences for reporting overdoses are critical.

Overdose prevention activities led by local public health departments, 2019-2023.

BACKGROUND: Drug overdose deaths in the United States increased to historic levels in recent years, with provisional estimates indicating more than 111,000 deaths in the 12 months ending July 2023. In 2019, the Centers for Disease Control and Prevention's Division of Overdose Prevention in collaboration with the National Association of City and County Health Officials, funded local health departments (LHDs) to work on overdose prevention activities. This paper aims to: 1) describe the overdose prevention activities that LHDs implemented during the four eighteen-month funding cycles; 2) identify programmatic successes and areas of opportunity for LHDs to consider when implementing future overdose prevention activities; and to 3) inform policy considerations and future overdose prevention programming at the local level. METHODS: We used programmatic data to identify overdose prevention activities implemented by 45 LHDs. Activities were double-coded according to the social-ecological model and the U.S. Department of Health and Human Services Overdose Prevention Strategies and Guiding Principles. We analyzed final codes to identify distribution and overlap of the Strategies and Guiding Principles across the social ecological model co-occurrences. RESULTS: Approximately 55.9% (n=123) of the 220 overdose prevention activities that were coded took place at the community level, 32.3% (n=71) at the individual level, 8.6% (n=19) at the relationship level, and 3.2% (n=7) at the policy level. Most of the activities were coded as coordination, collaboration, and integration (n=52, 23.6%), harm reduction (n=51, 23.1%), data and evidence (n=47, 21.4%) or reducing stigma (n=24, 10.9%). Few activities were related to primary prevention (n=14, 6.4%), equity (n=14, 6.4%), recovery support (n=11, 5.0%), and evidence-based treatment (n=7, 3.2%). CONCLUSIONS: Localities have primarily implemented activities focused on the community and individual levels, with most of these centered around coordination, collaboration, and integration; harm reduction; or data and evidence. This study identified gaps in overdose prevention for LHDs related to treatment and health equity and that more interventions should be implemented at the relationship and policy levels. Continuing these efforts is important as LHDs explore opportunities to enhance and expand their work in various strategy areas across the social ecology. Findings from this study may be used to inform localities as they design and implement future overdose prevention activities.

Efficacy of human prothrombin complex concentrate in the treatment of warfarin overdose in patients receiving warfarin for mechanical heart valve replacement.

Warfarin, a widely utilized anticoagulant, is paramount for preventing thromboembolic events in patients with mechanical heart valve replacements. However, its narrow therapeutic index can lead to over-anticoagulation and overdose, resulting in serious health risks. This study examines the efficacy of human prothrombin complex concentrate (PCC) in managing warfarin overdose, in comparison with traditional treatments. A retrospective analysis was conducted on 162 adults who presented with warfarin overdose (INR > 5.0) at a tertiary care hospital between 2016 and 2020. Participants were divided into 2 groups-those treated with PCC (n = 57) and those treated with conventional methods (n = 105), including vitamin K and fresh frozen plasma. The primary outcome was the rate of reaching the target (International Normalized Ratio) INR within 24 hours. Secondary outcomes included transfusion requirements, thromboembolic events, adverse reactions, 30-day mortality, and length of hospital stay. PCC demonstrated significant efficacy, with 89.5% of patients achieving the target INR within 24 hours, compared to 64.8% in the control group (P < .05). The PCC group also had reduced transfusion requirements and a shorter average hospital stay. There was no significant difference in thromboembolic events or adverse reactions between the 2 groups, and the reduced 30-day mortality in the PCC group was not statistically significant. Human prothrombin complex concentrate is associated with rapid reaching the target INR, decreased transfusion needs, and shortened hospitalization, making it a promising option for warfarin overdose management. While the results are encouraging, larger, multicenter, randomized controlled trials are necessary to further validate these findings and optimize PCC administration protocols.

Vaccines as Immunotherapies for Substance Use Disorders.

Substance use disorders (SUD) present a worldwide challenge with few effective therapies except for the relative efficacy of opioid pharmacotherapies, despite limited treatment access. However, the proliferation of illicit fentanyl use initiated a dramatic and cascading epidemic of lethal overdoses. This rise in fentanyl overdoses regenerated an interest in vaccine immunotherapy, which, despite an optimistic start in animal models over the past 50 years, yielded disappointing results in human clinical trials of vaccines against nicotine, stimulants (cocaine and methamphetamine), and opioids. After a brief review of clinical and selected preclinical vaccine studies, the "lessons learned" from the previous vaccine clinical trials are summarized, and then the newest challenge of a vaccine against fentanyl and its analogs is explored. Animal studies have made significant advances in vaccine technology for SUD treatment over the past 50 years, and the resulting anti-fentanyl vaccines show remarkable promise for ending this epidemic of fentanyl deaths.

Understanding and Addressing Widening Racial Inequalities in Drug Overdose.

The fourth wave of the United States overdose crisis-driven by the polysubstance use of fentanyl with stimulants and other synthetic substances-has driven sharply escalating racial/ethnic inequalities in drug overdose death rates. Here the authors present a detailed portrait of the latest overdose trends and synthesize the literature to describe where, how, and why these inequalities are worsening. By 2022 overdose deaths among Native and Black Americans rose to 1.8 and 1.4 times the rate seen among White Americans, respectively. This reflects that Black and Native Americans have been disproportionately affected by fentanyl and the combination of fentanyl and stimulants at the national level and in virtually every state. The highest overdose deaths rates are currently seen among Black Americans 55-64 years of age as well as younger cohorts of Native Americans 25-44 years of age. In 2022-the latest year of data available-deaths among White Americans decreased relative to 2021, whereas rates among all other groups assessed continued to rise. Moving forward, Fundamental Cause Theory shows us a relevant universal truth of implementation science: in socially unequal societies, new technologies typically end up favoring more privileged groups first, thereby widening inequalities unless underlying social inequalities are addressed. Therefore, interventions designed to reduce addiction and overdose death rates that are not explicitly designed to also improve racial/ethnic inequalities will often unintentionally end up worsening them. Well-funded community-based programs, with Black and Native leadership, providing harm reduction resources, naloxone, and medications for opioid use disorder in the context of comprehensive, culturally appropriate healthcare and other services, represent the highest priority interventions to decrease inequalities.

Use of Intravenous Lipid Emulsion Therapy and Insulin in a Case of Tarka Intoxication.

INTRODUCTION: Tarka (trandolapril/verapamil hydrohloride extended-release) is a fixed-dose combination antihypertensive drug formed from verapamil hydrochloride and trandolapril. Toxicologic manifestations of Tarka overdose are altered mental status, bradycardia, hypotension, atrioventricular block (first-degree), hyperglycemia, metabolic acidosis, and shock. CASE PRESENTATION: We report a case of Tarka toxicity in a 2-year-old girl who presented with altered mental status, cardiogenic shock, hypotension, bradycardia, severe metabolic acidosis, hyperglycemia, and first-degree atrioventricular block. We started fluid resuscitation, epinephrine, norepinephrine, and insulin. Because of the patient's hyperlactatemia and hypotension despite standard therapies, we initiated intravenous lipid emulsion (ILE) therapy, after which her condition improved promptly. DISCUSSION: Tarka overdose may be life-threatening as it can cause cardiogenic shock. In our patient, the regression of lactate elevation in a short time with ILE therapy and the improvement of her general condition highlight the importance of ILE. CONCLUSIONS: ILE is an alternative treatment method for acute lipophilic drug intoxications, such as Tarka.

Paracetamol overdose in Danish children and adolescents during the Covid-19 restrictions.

INTRODUCTION: To assess the effect of long-term isolation on the mental state of Danish youth. This study aimed to investigate trends in paracetamol overdoses among people under 18 years of age in Denmark during Covid-19 restrictions as an indicator of mental health. METHODS: All patients under the age of 18 years presenting with paracetamol overdose at one of the 18 paediatric departments in Denmark from 2016 to 2021 were included. They were identified in all Danish hospital databases using specific diagnostic codes. RESULTS: From 2016 to 2021, a total of 3,217 people under 18 years of age were admitted for paracetamol overdose. Among these, 86% (n = 2,755) were girls and 14% (n = 462) were boys. During 2020, a slight (7%) decrease in admissions was observed among both boys and girls compared with the preceding four-year mean value. In 2021, the number of overdoses among girls exceeded by 35% the former all-time high from 2016. Furthermore, the number of overdoses among girls exceeded the pre-four-year period mean value by 43%. Among boys, an 8% increase was seen from the highest ever previous value recorded in 2019 and a 23% increase compared with the previous four-year mean value. CONCLUSIONS: During the first year of restrictions, a slight decrease in paracetamol overdoses was observed, possibly associated with limited accessibility. The second year showed a considerable increase in paracetamol overdoses, which may imply an affected mental state among youth during the prolonged lockdown restrictions as seen in previous epidemics. Therefore, further studies are warranted to develop a pandemic preparedness plan to protect general mental health. FUNDING: None. TRIAL REGISTRATION: Not relevant.

How do we understand the value of drug checking as a component of harm reduction services? A qualitative exploration of client and provider perspectives.

BACKGROUND: Mortality related to opioid overdose in the U.S. has risen sharply in the past decade. In California, opioid overdose death rates more than tripled from 2018 to 2021, and deaths from synthetic opioids such as fentanyl increased more than seven times in those three years alone. Heightened attention to this crisis has attracted funding and programming opportunities for prevention and harm reduction interventions. Drug checking services offer people who use drugs the opportunity to test the chemical content of their own supply, but are not widely used in North America. We report on qualitative data from providers and clients of harm reduction and drug checking services, to explore how these services are used, experienced, and considered. METHODS: We conducted in-depth semi-structured key informant interviews across two samples of drug checking stakeholders: "clients" (individuals who use drugs and receive harm reduction services) and "providers" (subject matter experts and those providing clinical and harm reduction services to people who use drugs). Provider interviews were conducted via Zoom from June-November, 2022. Client interviews were conducted in person in San Francisco over a one-week period in November 2022. Data were analyzed following the tenets of thematic analysis. RESULTS: We found that the value of drug checking includes but extends well beyond overdose prevention. Participants discussed ways that drug checking can fill a regulatory vacuum, serve as a tool of informal market regulation at the community level, and empower public health surveillance systems and clinical response. We present our findings within three key themes: (1) the role of drug checking in overdose prevention; (2) benefits to the overall agency, health, and wellbeing of people who use drugs; and (3) impacts of drug checking services at the community and systems levels. CONCLUSION: This study contributes to growing evidence of the effectiveness of drug checking services in mitigating risks associated with substance use, including overdose, through enabling people who use and sell drugs to test their own supply. It further contributes to discussions around the utility of drug checking and harm reduction, in order to inform legislation and funding allocation.

"Fighting demons": Stigma and shifting norms in explicit mention of overdose in obituaries, 2010-2019.

Obituaries are often the only published record of an individual's life and elicit community reactions, including stigmatization. Because obituaries are typically written by the bereaved, their content reflects the writer's perceptions of mores governing the social context of the next-of-kin and decedent. When a cause of death is stigmatized, it can influence the way the bereaved write the obituary. However, what constitutes a stigmatized cause of death may change as larger societal discourses of morality shift and conditions or events become framed differently. Using a sample of obituaries (N = 210) from obituary aggregator Legacy.com of "off-time," or premature, deaths in West Virginia from 2010, 2015, 2017, and 2019, this article explores whether the presentation of overdose deaths in obituaries changes alongside the shift in the public framing of the opioid crisis as medical rather than criminal. I find obituaries including terms associated with drug use and overdose become both more common and explicit over the course of the study period. This suggests that the shift in public framing of the opioid crisis from criminalization to medicalization corresponds with a decrease in drug stigmatization in obituaries. Obituary analysis can be a useful means of exploring the stigmatization of other controversial causes of death, such as suicide, cirrhosis, and lung cancer.

Physiologic oxygen responses to smoking opioids: an observational study using continuous pulse oximetry at overdose prevention services in British Columbia, Canada.

BACKGROUND: In British Columbia, Canada, smoking is the most common modality of drug use among people who die of opioid toxicity. We aimed to assess oxygen saturation (SpO2) while people smoked opioids during a pilot study that introduced continuous pulse oximetry at overdose prevention services (OPS) sites. METHODS: This was an observational cohort study, using a participatory design. We implemented our monitoring protocol from March to August 2021 at four OPS. We included adults (≥ 18 years) presenting to smoke opioids. A sensor taped to participants' fingers transmitted real-time SpO2 readings to a remote monitor viewed by OPS staff. Peer researchers collected baseline data and observed the timing of participants' inhalations. We analyzed SpO2 on a per-event basis. In mixed-effects logistic regression models, drop in minimum SpO2 ≤ 90% in the current minute was our main outcome variable. Inhalation in that same minute was our main predictor. We also examined inhalation in the previous minute, cumulative inhalations, inhalation rate, demographics, co-morbidities, and substance use variables. RESULTS: We recorded 599 smoking events; 72.8% (436/599) had analyzable SpO2 data. Participants' mean age was 38.6 years (SD 11.3 years) and 73.1% were male. SpO2 was highly variable within and between individuals. Drop in SpO2 ≤ 90% was not significantly associated with inhalation in that same minute (OR: 1.2 [0.8-1.78], p = 0.261) or inhalation rate (OR 0.47 [0.20-1.10], p = 0.082). There was an association of SpO2 drop with six cumulative inhalations (OR 3.38 [1.04-11.03], p = 0.043); this was not maintained ≥ 7 inhalations. Demographics, co-morbidities, and drug use variables were non-contributory. CONCLUSIONS: Continuous pulse oximetry SpO2 monitoring is a safe adjunct to monitoring people who smoke opioids at OPS. Our data reflect challenges of real-world monitoring, indicating that greater supports are needed for frontline responders at OPS. Inconsistent association between inhalations and SpO2 suggests that complex factors (e.g., inhalation depth/duration, opioid tolerance, drug use setting) contribute to hypoxemia and overdose risk while people smoke opioids.

Public stigma against fentanyl overdose decedents in the United States: A conjoint vignette experiment.

The United States is facing a drug overdose crisis, and stigma against people who use drugs is a major roadblock to implementing solutions. Despite the public health importance of understanding and mitigating substance use stigma, prior research has focused mainly on perceptions of individuals with substance use disorders and a limited set of demographic traits. This leaves critical gaps in our understanding of stigma against fentanyl overdose decedents, who represent a much broader group, including people who use substances recreationally. This study develops a more robust understanding of these attitudes through an experimental vignette survey fielded to a national sample of American adults (n = 1432). Respondents were shown two fictional fentanyl overdose obituaries where a complex suite of decedent characteristics-including demographic traits and contexts of substance use-were randomly varied in a conjoint design. Respondents then endorsed one of the two decedents for each of several attitudinal outcomes, including blameworthiness and support for various interventions, and justified their choices in an open-ended format. Results indicate that the public assesses victims of fentanyl overdose meritocratically, making judgments based on personal history and life experience rather than traditional race, class, and gender status beliefs. While certainly a signal of progress on some fronts, this meritocratic lens conflicts with the public health model of addressing the overdose crisis and exposes the alarming persistence of explicit stigma against people who use drugs.

Innovation and adaptation: The rise of a fentanyl smoking culture in San Francisco.

BACKGROUND: Illicitly manufactured fentanyls and stimulants are implicated in the escalating US mortality from drug overdose. San Francisco, California (SF) has seen declining fentanyl injection while smoking has increased. Beliefs and behaviors surrounding this development are not well understood. METHODS: The study used rapid ethnography to explore fentanyl and methamphetamine use in SF. The team conducted semi-structured interviews (n = 34) with participants recruited from syringe service programs. Video-recorded smoking sequences (n = 12), photography and daily field notes supplemented interview data. RESULTS: Difficulty injecting and fear of overdose motivated transitions from injecting to smoking. Fentanyl was extremely cheap-$10/gram-with variability in quality. Foil was the most commonly used smoking material but glass bubbles, bongs and dabbing devices were also popular. No reliable visible methods for determining fentanyl quality existed, however, participants could gauge potency upon inhalation, and developed techniques to regulate dosage. Several participants reported at least hourly use, some reporting one or more grams of daily fentanyl consumption. Smoking was also very social, with people sharing equipment, drugs and information. Participants raised concerns about hygiene and overdose risk to others arising from shared equipment. Reportedly potent fentanyl 'residue' accumulated on smoking materials and was commonly shared/traded/stolen or consumed accidentally with diverse preferences for its use. CONCLUSION: Our data highlight fentanyl residue as a new overdose risk with potential mismatch between the potency of the residual drug and the recipient's tolerance. Further, large doses of fentanyl are being consumed (estimated at approximately 50 mg of pure fentanyl/day). Smoking fentanyl has potential health benefits over injecting and may be protective against overdose, but substantial uncertainty exists. However, SF overdose mortality hit a record high in 2023. Recommendations to reduce fentanyl smoking overdose risks through pacing, greater awareness of dosages consumed and checking tolerance of residue recipients are potentially viable interventions deserving further exploration.

Examining the relationship between social determinants of health, measures of structural racism and county-level overdose deaths from 2017-2020.

INTRODUCTION: Despite being an important determinant of health outcomes, measures of structural racism are lacking in studies examining the relationship between the social determinants of health (SDOH) and overdose deaths. The aim of this study is to examine the association between per capita revenue generated from fines and forfeitures, a novel measure of structural racism, and other SDOH with county-level overdose deaths from 2017-2020. METHODS: This longitudinal analysis of 2,846 counties from 2017-2020 used bivariate and multivariate Generalized Estimating Equations models to estimate associations between county overdose mortality rates and SDOH characteristics, including the fines and forfeitures measure. RESULTS: In our multivariate model, higher per capita fine and forfeiture revenue (5.76; CI: 4.76, 6.78), households receiving food stamps (1.15; CI: 0.77, 1.53), residents that are veterans (1.07; CI: 0.52, 1.63), substance use treatment availability (4.69; CI: 3.03, 6.33) and lower population density (-0.002; CI: -0.004, -0.001) and percent of Black residents (-0.7`; CI: -1.01, -0.42) were significantly associated with higher overdose death rates. There was a significant additive interaction between the fines and forfeitures measure (0.10; CI: 0.03, 0.17) and the percent of Black residents. CONCLUSIONS: Our findings suggest that structural racism, along with other SDOH, is associated with overdose deaths. Future research should focus on connecting individual-level data on fines and forfeitures to overdose deaths and other health outcomes, include measures of justice-related fines, such as court fees, and assess whether interventions aimed at increasing economic vitality in disadvantaged communities impact overdose deaths in a meaningful way.

Amifampridine overdose leading to refractory status epilepticus.

3,4-Aminopyridine or Amifampridine belongs to the aminopyridine class of drugs which is used to treat multiple sclerosis and Lambert-Eaton Myasthenic Syndrome (LEMS). Aminopyridine pharmaceuticals inhibit presynaptic potassium channels. This increases available acetylcholine in the nerve cleft which leads to improved strength in this patient population. While overdoses have been reported of 4-Aminopyridine, no case reports of acute 3.4-Aminopyridine overdose are currently available. A 67 year old man presented to the emergency department 30 min after ingesting 100 mg of amifampridine in a suicide attempt. Within an hour of ingestion he experienced tachycardia, tachypnea, hypertension and tremor. The patient then started to experience seizures and had a cardiac arrest 3 h after the ingestion. The patient achieved return of spontaneous circulation but proceeded to have refractory seizures. Despite significant and escalating doses of anti-epileptic medications, the patient continued to have seizures until 18 h after ingestion. His anti-epileptic medications were weaned over the following days and he had no more seizures. This is a report of a novel overdose of 3,4-Aminopyridine, a medication that belongs to the aminopyridine class of pharmaceuticals that have been well used for many years. Aminopyridine overdoses are commonly thought to carry low morbidity and mortality; however, our patient had both a cardiac arrest and refractory status epilepticus. Ultimately, this case suggests that patients who overdose on 3,4-Aminopyridine could become critically ill and their presentation may be far more severe than that of other medications of the same class.

Cost-effectiveness of drug consumption rooms in France: a modelling study.

BACKGROUND: People who inject drugs (PWID) experience many health problems which result in a heavy economic and public health burden. To tackle this issue, France opened two drug consumption rooms (DCRs) in Paris and Strasbourg in 2016. This study assessed their long-term health benefits, costs and cost-effectiveness. METHODS: We developed a model to simulate two fictive cohorts for each city (n=2,997 in Paris and n=2,971 in Strasbourg) i) PWID attending a DCR over the period 2016-2026, ii) PWID attending no DCR. The model accounted for HIV and HCV infections, skin abscesses and related infective endocarditis, drug overdoses and emergency department visits. We estimated the number of health events and associated costs over 2016-2026, the lifetime number of quality-adjusted life-years (QALYs) and costs, and the incremental cost-effectiveness ratio (ICER). RESULTS: The numbers of abscesses and associated infective endocarditis, drug overdoses, and emergency department visits decreased significantly in PWID attending DCRs (-77%, -69%, and -65%, respectively) but the impact on HIV and HCV infections was modest (-11% and -6%, respectively). This resulted in savings of €6.6 (Paris) and €5.8 (Strasbourg) millions of medical costs. The ICER of DRCs was €30,600/QALY (Paris) and €9,200/QALY (Strasbourg). In scenario analysis where drug consumption spaces are implemented inside existing harm reduction structures, these ICERs decreased to €21,400/QALY and €2,500/QALY, respectively. CONCLUSIONS: Our findings show that DCRs are highly effective and efficient to prevent harms in PWID in France, and advocate extending this intervention to other cities by adding drug consumption spaces inside existing harm reduction centers.

Reducing overdose deaths among persons with opioid use disorder in connecticut.

BACKGROUND: People in Connecticut are now more likely to die of a drug-related overdose than a traffic accident. While Connecticut has had some success in slowing the rise in overdose death rates, substantial additional progress is necessary. METHODS: We developed, verified, and calibrated a mechanistic simulation of alternative overdose prevention policy options, including scaling up naloxone (NLX) distribution in the community and medications for opioid use disorder (OUD) among people who are incarcerated (MOUD-INC) and in the community (MOUD-COM) in a simulated cohort of people with OUD in Connecticut. We estimated how maximally scaling up each option individually and in combinations would impact 5-year overdose deaths, life-years, and quality-adjusted life-years. All costs were assessed in 2021 USD, employing a health sector perspective in base-case analyses and a societal perspective in sensitivity analyses, using a 3% discount rate and 5-year and lifetime time horizons. RESULTS: Maximally scaling NLX alone reduces overdose deaths 20% in the next 5 years at a favorable incremental cost-effectiveness ratio (ICER); if injectable rather than intranasal NLX was distributed, 240 additional overdose deaths could be prevented. Maximally scaling MOUD-COM and MOUD-INC alone reduce overdose deaths by 14% and 6% respectively at favorable ICERS. Considering all permutations of scaling up policies, scaling NLX and MOUD-COM together is the cost-effective choice, reducing overdose deaths 32% at ICER $19,000/QALY. In sensitivity analyses using a societal perspective, all policy options were cost saving and overdose deaths reduced 33% over 5 years while saving society $338,000 per capita over the simulated cohort lifetime. CONCLUSIONS: Maximally scaling access to naloxone and MOUD in the community can reduce 5-year overdose deaths by 32% among people with OUD in Connecticut under realistic budget scenarios. If societal cost savings due to increased productivity and reduced crime costs are considered, one-third of overdose deaths can be reduced by maximally scaling all three policy options, while saving money.

Implementing Canada's first national virtual phone based overdose prevention service: lessons learned from creating the National Overdose Response Service (NORS).

The opioid epidemic remains one of the largest public health crises in North America to date. While there have been many diverse strategies developed to reduce the harms associated with substance use, these are primarily concentrated within a few large urban centers. As a result, there have been increased calls for equitable access to harm reduction services for those who cannot or choose not to access in-person harm reduction services. In December 2020, Canada's National Overdose Response Service (NORS) a telephone based overdose response hotline and virtual supervised consumption service, was established in collaboration with various agencies and people with lived and living experience of substance use (PWLLE) across Canada to expand access to harm reduction services using novel Opioid Response Technology. In this manuscript we explore the lessons learned from the establishment and continued operation of the service exploring topics related to the initial establishment of the service, securing a phone line, routing technology, EMS dispatch solutions, peer and volunteer recruitment, legal and ethical support, policy and procedure development, securing funding, and marketing. Furthermore, we detail how this service has grown and changed in response to the various needs of service users.