Opioid Overdose Research Articles

Rapid jail-based implementation of overdose education and naloxone distribution in response to the COVID-19 pandemic

BackgroundPeople incarcerated in jails are highly impacted by the opioid epidemic, and overdose education and naloxone distribution (OEND) is an effective strategy to reduce opioid overdose deaths. This study examines barriers and facilitators of fast-track OEND implementation within the jails in the Wave 1 Kentucky counties of the HEALing Communities Study during the COVID-19 pandemic.MethodsMeeting minutes with jail stakeholders were qualitatively coded using the Practical, Robust Implementation and Sustainability Model (PRISM) as the coding framework. The analysis highlighted the top barriers and facilitators to fast-track OEND implementation within the PRISM framework.ResultsSpace and staffing shortages related to the COVID-19 pandemic, disruptions in interorganizational programming from pandemic-related service suspensions, and a lack of technological solutions (e.g., reliable Internet access) for socially distanced delivery were the top barriers to fast-track OEND implementation. In addition, there were limitations on non-jail staff access to jails during COVID-19. Top facilitators included jail leadership support, the option to prioritize high-risk groups, and the incorporation of OEND processes into existing communications and management software. While the COVID-19 pandemic strained jail infrastructure, jail and partner agency collaboration led to creative implementation strategies for the successful integration of OEND into jail operations. Urban jails were more likely than rural jails to be early adopters of OEND during the public health emergency.ConclusionsUnderstanding the barriers to and facilitators of OEND within jails will improve implementation efforts seeking to curb opioid overdose deaths. Jail leadership support and interorganizational efforts were key facilitators to implementation; therefore, it is recommended to increase buy-in with multiple agencies to promote success. Challenges brought on by COVID-19 have resulted in a need for innovative solutions for implementation.Clinical trial informationClinicalTrials.gov, NCT04111939, Submitted 30 September 2019, https://clinicaltrials.gov/study/NCT04111939?titles=HEALing%20Communities%20Study&rank=1.

Harm Reduction in the Field: First Responders' Perceptions of Opioid Overdose Interventions.

Recent policy changes in Washington State presented a unique opportunity to pair evidence-based interventions with first responder services to combat increasing opioid overdoses. However, little is known about how these interventions should be implemented. In partnership with the Research with Expert Advisors on Drug Use team, a group of academically trained and community-trained researchers with lived and living experience of substance use, we examined facilitators and barriers to adopting leave-behind naloxone, field-based buprenorphine initiation, and HIV and hepatitis C virus (HCV) testing for first responder programs. Our team completed semi-structured, qualitative interviews with 32 first responders, mobile integrated health staff, and emergency medical services (EMS) leaders in King County, Washington, from February-May 2022. Semi-structured interviews were recorded, transcribed, and coded using an integrated deductive and inductive thematic analysis approach grounded in community-engaged research principles. We collected data until saturation was achieved. Data collection and analysis were informed by the Consolidated Framework for Implementation Research. Two investigators coded independently until 100% consensus was reached. Our thematic analysis revealed several perceived facilitators (ie, tension for change, relative advantage, and compatibility) and barriers (ie, limited adaptability, lack of evidence strength and quality, and prohibitive cost) to the adoption of these evidence-based clinical interventions for first responder systems. There was widespread support for the distribution of leave-behind naloxone, although funding was identified as a barrier. Many believed field-based initiation of buprenorphine treatment could provide a more effective response to overdose management, but there were significant concerns that this intervention could run counter to the rapid care model. Lastly, participants worried that HIV and HCV testing was inappropriate for first responders to conduct but recommended that this service be provided by mobile integrated health staff. These results have informed local EMS strategic planning, which will inform roll out of process improvements in King County, Washington. Future work should evaluate the impact of these interventions on the health of overdose survivors.

From Patient Registry to Multi-Center Research Consortium: the Toxicology Investigators Consortium (ToxIC) Turns Fifteen.

The Toxicology Investigators Consortium (ToxIC) was launched as a prospective multi-center registry of cases who receive medical toxicology consultations. Now, with over 100,000 cases, the Core Registry continues to address many medical toxicology research questions and has served as the foundation for multiple sub-registries, including the North American Snakebite Registry and the Medications for Opioid Use Disorder sub-registry. ToxIC also has evolved a portfolio of non-registry-based projects utilizing medical toxicology physician site principal investigators who enroll patients through emergency departments, irrespective of whether they received a medical toxicology consultation. These studies include the FDA-ACMT COVID-19 ToxIC Pharmacovigilance Project, which identifies adverse drug reactions related to the treatment of COVID-19, the Fentalog Study a toxico-surveillance study of suspected opioid overdose cases, the Drug Overdose Toxico-Surveillance Reporting Program which enrolls either suspected stimulant or opioid overdose cases, and the just being launched Real-World Examination of Naloxone for Drug Overdose Reversal project. Given ToxIC's experience in multi-center studies and its well-developed infrastructure, it is well-positioned to provide a nimble response on the part of the medical toxicology community to addressing evolving toxicological threats, drug and chemical toxicosurveillance, and other important medical toxicology priorities.

Exploring Opioid Prescription Patterns and Overdose Rates in South Carolina (2017-2021): Insights into Rising Deaths in High-Risk Areas.

With opioid overdose rates on the rise, we aimed to develop a county-level risk stratification that specifically focused on access to medications for opioid use disorder (MOUDs) and high overdose rates. We examined over 15 million records from the South Carolina Prescription Tracking System (SCRIPTS) across 46 counties. Additionally, we incorporated data from opioid treatment programs, healthcare professionals prescribing naltrexone, clinicians with buprenorphine waivers, and county-level overdose fatality statistics. To assess the risk of opioid misuse, we classified counties into high-risk and low-risk categories based on their prescription rates, overdose fatalities, and treatment service availability. Statistical methods employed included the two-sample t-test and linear regression. The t-test assessed the differences in per capita prescription rates between high-risk and low-risk counties. Linear regression was used to analyze the trends over time. Our study showed that between 2017 and 2021, opioid prescriptions decreased from 64,223 to 41,214 per 100,000 residents, while fentanyl-related overdose deaths increased by 312%. High-risk counties had significantly higher rates of fentanyl prescriptions and relied more on out-of-state doctors. They also exhibited higher instances of doctor shopping and had fewer medical doctors per capita, with limited access to MOUDs. To effectively combat the opioid crisis, we advocate for improved local healthcare infrastructure, broader treatment access, stricter management of out-of-state prescriptions, and vigilant tracking of prescription patterns. Tailored local strategies are essential for mitigating the opioid epidemic in these communities.

Correlates of Staff Acceptability of a Novel Telemedicine-Delivered Medications for Opioid Use Disorder Program in a Rural Detention Center.

Opioid overdose death is significantly increased immediately following incarceration. Evidence-based medications are underutilized in rural jails and detention centers. We have reported our efforts to address this gap through telemedicine-based medications for opioid use disorder treatment (tele-MOUD) for incarcerated patients. Staff acceptance and perceptions are critically important factors in the assurance of program validation. We assessed tele-MOUD acceptability and perceptions of effectiveness and stigma in one detention center. Overall, we found that jail staff's general acceptability of the program was rather low, as was perceived effectiveness of MOUD, while stigmatizing beliefs were present. Furthermore, tele-MOUD acceptability was positively correlated with perceptions of MOUD effectiveness and negatively correlated with stigmatizing notions of MOUD (p's < 0.001). Findings suggest the need for educational interventions. Future research investigating the potential moderating effects of training on staff acceptability of jail-based tele-MOUD will support the implementation and sustainability of these life-saving programs.

The Association of Broadband Internet Use With Drug Overdose Mortality Rates in the United States: Cross-Sectional Analysis.

The availability and use of broadband internet play an increasingly important role in health care and public health. This study examined the associations between broadband internet availability and use with drug overdose deaths in the United States. We linked 2019 county-level drug overdose death data in restricted-access multiple causes of death files from the National Vital Statistics System at the US Centers for Disease Control and Prevention with the 2019 county-level broadband internet rollout data from the Federal Communications Commission and the 2019 county-level broadband usage data available from Microsoft's Airband Initiative. Cross-sectional analysis was performed with the fixed-effects regression method to assess the association of broadband internet availability and usage with opioid overdose deaths. Our model also controlled for county-level socioeconomic characteristics and county-level health policy variables. Overall, a 1% increase in broadband internet use was linked with a 1.2% increase in overall drug overdose deaths. No significant association was observed for broadband internet availability. Although similar positive associations were found for both male and female populations, the association varied across different age subgroups. The positive association on overall drug overdose deaths was the greatest among Hispanic and Non-Hispanic White populations. Broadband internet use was positively associated with increased drug overdose deaths among the overall US population and some subpopulations, even after controlling for broadband availability, sociodemographic characteristics, unemployment, and median household income.

Extended-Release Injection vs Sublingual Buprenorphine for Opioid Use Disorder With Fentanyl Use

Fentanyl has exacerbated the opioid use disorder (OUD) and opioid overdose epidemic. Data on the effectiveness of medications for OUD among patients using fentanyl are limited. To assess the effectiveness of sublingual or extended-release injection formulations of buprenorphine for the treatment of OUD among patients with and without fentanyl use. Post hoc analysis of a 24-week, randomized, double-blind clinical trial conducted at 35 outpatient sites in the US from December 2015 to November 2016 of sublingual buprenorphine-naloxone vs extended-release subcutaneous injection buprenorphine (CAM2038) for patients with OUD subgrouped by presence vs absence of fentanyl or norfentanyl in urine at baseline. Study visits with urine testing occurred weekly for 12 weeks, then 6 times between weeks 13 and 24. Data were analyzed on an intention-to-treat basis from March 2022 to August 2023. Weekly and monthly subcutaneous buprenorphine vs daily sublingual buprenorphine-naloxone. Retention in treatment, percentage of urine samples negative for any opioids (missing values imputed as positive), percentage of urine samples negative for fentanyl or norfentanyl (missing values not imputed), and scores on opiate withdrawal scales and visual analog craving scales. Of 428 participants, 123 (subcutaneous buprenorphine, n = 64; sublingual buprenorphine-naloxone, n = 59; mean [SD] age, 39.1 [10.8] years; 75 men [61.0%]) had evidence of baseline fentanyl use and 305 (subcutaneous buprenorphine, n = 149; buprenorphine-naloxone, n = 156; mean [SD] age, 38.1 [11.1] years; 188 men [61.6%]) did not have evidence of baseline fentanyl use. Study completion was similar between the fentanyl-positive (60.2% [74 of 123]) and fentanyl-negative (56.7% [173 of 305]) subgroups. The mean percentage of urine samples negative for any opioid were 28.5% among those receiving subcutaneous buprenorphine and 18.8% among those receiving buprenorphine-naloxone in the fentanyl-positive subgroup (difference, 9.6%; 95% CI, -3.0% to 22.3%) and 36.7% among those receiving subcutaneous buprenorphine and 30.6% among those receiving buprenorphine-naloxone in the fentanyl-negative subgroup (difference, 6.1%; 95% CI, -1.9% to 14.1%), with significant main associations of baseline fentanyl status and treatment group. In the fentanyl-positive subgroup, the mean percentage of urine samples negative for fentanyl during the study was 74.6% among those receiving subcutaneous buprenorphine vs 61.9% among those receiving sublingual buprenorphine-naloxone (difference, 12.7%; 95% CI, 9.6%-15.9%). Opioid withdrawal and craving scores decreased rapidly after treatment initiation across all groups. In this post hoc analysis of a randomized clinical trial of sublingual vs extended-release injection buprenorphine for OUD, buprenorphine appeared to be effective among patients with baseline fentanyl use. Patients with fentanyl use had fewer opioid-negative urine samples during the trial compared with the fentanyl-negative subgroup. These findings suggest that the subcutaneous buprenorphine formulation may be more effective at reducing fentanyl use. ClinicalTrials.gov Identifier: NCT02651584.

Standard Versus Rapid Inpatient Methadone Titration for Pregnant Patients With Opioid Use Disorder: A Retrospective Cohort Study.

Our study evaluated if rapid inpatient titration of methadone for pregnant patients with opioid use disorder (OUD) improved outcomes without increasing the risk for overdose. This is a retrospective cohort study of pregnant patients admitted for inpatient methadone titration from January 2020 to June 2022. Outcomes were compared between standard versus rapid titration protocols. Standard titration involved an initial methadone dose with additional doses every 6 hours if clinical opiate withdrawal score (COWS) is >9. Rapid titration involved an initial methadone dose with additional doses every 4 hours if COWS is >9. The primary outcome was time required to achieve stable dose. Secondary outcomes included elopement prior to achieving stable dose, methadone-related readmission, opioid overdose, and final dose. There were 97 patients in the standard titration (STP) and 97 patients in the rapid titration (RTP) groups. Demographic characteristics and substance use history did not differ between the 2 groups. Time to stable dose did not differ between the 2 groups (RTP, 5.0 days ±4.0; STP, 4.0 days ±3.0; P = 0.08). Patients in the rapid titration group were less likely to elope from the hospital prior to stabilization (RTP 23.0% vs STP 37.9%, P = 0.03) and had fewer methadone-related readmissions (P < 0.001). One patient (1.0%) in the RTP group required naloxone treatment while inpatient for concern for overdose, while none did in the STP group (P = 0.32). There was no difference in median final stable dose between the 2 groups (P = 0.07). Rapid titration of methadone for pregnant patients with OUD was associated with decreased medical elopement and methadone-related readmission, without increasing the risk for overdose.

Naloxone Use During Pregnancy-Data From 26 US Jurisdictions, 2019-2020.

We aimed to determine the prevalence of self-reported naloxone use during pregnancy among people in the United States with a recent live birth. A secondary objective was to characterize people at increased risk of overdose who did and did not use naloxone. We analyzed data from the Pregnancy Risk Assessment Monitoring System from 26 US jurisdictions that conducted an opioid supplement survey from 2019 to 2020. Respondents with increased risk of experiencing an opioid overdose were identified based on self-reported use of illicit amphetamines, heroin, cocaine, or receiving medication for opioid use disorder (MOUD) during pregnancy. Weighted prevalence estimates and 95% confidence intervals were calculated for reported naloxone use at any point during pregnancy among people with an increased risk of overdose. Naloxone use during pregnancy was reported by <1% of the overall study population (unweighted N = 88/34,528). Prevalence of naloxone use was 5.0% (95% CI: 0.0-10.6) among respondents who reported illicit amphetamine use, 15.2% (1.8-28.6) among those who reported heroin use, and 17.6% (0.0-38.1) among those who reported cocaine use. Naloxone use was 14.5% (8.4-20.6) among those who reported taking MOUD. Among people with increased risk of overdose, no significant differences in naloxone use were observed by age, race/ethnicity, education level, residential metropolitan status, or insurance status. Prevalence of naloxone use among people with an increased risk of overdose during pregnancy ranged from 5.0% to 17.6%. Access to naloxone, overdose prevention education, and treatment for substance use disorders may help reduce morbidity and mortality.

Trends in recurrent overdose and treatment initiation following emergency department visits for opioid overdose between 2016 and 2021

BackgroundOverdose remains a pressing public health concern in the United States, particularly with the emergence of fentanyl and other potent synthetic opioids in the drug supply. We evaluated trends in recurrent overdose and opioid use disorder (OUD) treatment initiation following emergency department (ED) visits for opioid overdose to inform response efforts. MethodsThis retrospective cohort study used electronic health record and statewide administrative data from Rhode Island residents who visited EDs for opioid overdose between July 1, 2016, and June 30, 2021, a period with fentanyl predominance in the local drug supply. The primary outcome was recurrent overdose in the 365 days following the initial ED visit. OUD treatment initiation within 180 days following the initial ED visit was considered as a secondary outcome. Trends in study outcomes were summarized by year of the initial ED visit. ResultsAmong 1745 patients attending EDs for opioid overdose, 20 % (n=352) experienced a recurrent overdose within 365 days, and this percentage was similar by year (p=0.12). Among patients who experienced any recurrent overdose, the median time to first recurrent overdose was 88 days (interquartile range=23–208), with 85 % (n=299/352) being non-fatal. Among patients not engaged in OUD treatment at their initial ED visit, 33 % (n=448/1370) initiated treatment within 180 days; this was similar by year (p=0.98). ConclusionsFollowing ED visits for opioid overdose in Rhode Island from 2016–2021, the one-year risk of recurrent overdose and six-month treatment initiation rate remained stable over time. Innovative prevention strategies and improved treatment access are needed.

Identification of N-piperidinyl etonitazene in alternative keratinous matrices from a decomposing cadaver

This short report describes research on N-piperidinyl etonitazene, also known as etonitazepipne, in keratinous matrices (hair and nails) after death related to a suspected opioid overdose. Etonitazepipne belongs to the family of benzimidazole opioids, a class of new synthetic opioids that has penetrated the illicit drug market. Analysis in the case under study showed the presence of etonitazepipne in both hair and nails, confirming that the substance accumulates in the body with repeated intake.

State-level factors associated with implementation of prescription drug monitoring program integration and mandatory use policies, United States, 2009-2020.

Prescription drug monitoring programs (PDMPs) have been widely adopted as a tool to address the prescription opioid epidemic in the United States. PDMP integration and mandatory use policies are 2 approaches states have implemented to increase use of PDMPs by prescribers. While the effectiveness of these approaches is mixed, it is unclear what factors motivated states to implement them. This study examines whether opioid dispensing, adverse health outcomes, or other non-health-related factors motivated implementation of these PDMP approaches. Time-to-event analysis was performed using lagged state-year covariates to reflect values from the year prior. Extended Cox regression estimated the association of states' rates of opioid dispensing, prescription opioid overdose deaths, and neonatal opioid withdrawal syndrome with implementation of PDMP integration and mandatory use policies from 2009 to 2020, controlling for demographic and economic factors, state government and political factors, and prior opioid policies. In our main model, prior opioid dispensing (HR 2.31, 95% CI 1.17, 4.57), neonatal opioid withdrawal syndrome hospitalizations (HR 1.55, 95% CI 1.09, 2.19), and number of prior opioid policies (HR 2.13, 95% CI 1.13, 4.00) were associated with mandatory use policies. Prior prescription opioid overdose deaths (HR 1.21, 95% CI 1.08, 1.35) were also associated with mandatory use policies in a model that did not include opioid dispensing or neonatal opioid withdrawal syndrome. No study variables were associated with implementation of PDMP integration. Understanding state-level factors associated with implementing PDMP approaches can provide insights into factors that motivate the adoption of future public health interventions.

Police officer knowledge of and attitudes to opioid overdose and naloxone administration: an evaluation of police training in Scotland

ABSTRACT In the context of escalating drug-related deaths, during 2021 Police Scotland implemented a pilot project incorporating naloxone training to test the carriage and administration of naloxone by officers. The current paper presents data from the evaluation of this pilot exploring knowledge of, and attitudes to, opioid overdose and naloxone administration. Police officers completed a three-stage survey which included a modified Opioid Overdose Knowledge Scale (OOKS) and Opioid Overdose Attitudes Scales (OOAS). In total, 167 police officers completed the survey before taking part in the training; 144 completed a post-training survey; and 88 completed a follow-up survey. Training improved officers’ knowledge and attitudes about drug overdose and naloxone administration. The OOKS mean total score improved from 35.8 pre-training to 37.6 at follow-up (‘small-medium’ effect size; Cohen’s d = 0.42). The OOAS mean total score improved from 87.8 pre-training to 100.7 at follow-up (‘large’ effect size; Cohen’s d = 1.05). Training was also reported to facilitate the acceptability of naloxone administration as part of a police officer’s role. However, over a third of officers questioned the relevance of the training to their role. There was evidence that some officers held stigmatising attitudes towards people who use drugs (PWUD). Future training should address officers’ knowledge of problem drug use and stigmatising attitudes towards PWUD, and train and support officers to respond to the emergent public health role of policing. The findings of this evaluation informed the decision of the Chief Constable of Police Scotland to mandate that all Police Scotland Officers routinely carry naloxone from August 2022.

Fentanyl and xylazine crisis: Crafting coherent strategies for opioid overdose prevention

The United States is in the throes of a severe opioid overdose epidemic, primarily fueled by the pervasive use of fentanyl and the emerging threat of xylazine, a veterinary sedative often mixed with fentanyl. The high potency and long duration of fentanyl is compounded by the added risks from xylazine, heightening the lethal danger faced by opioid users. Measures such as enhanced surveillance, public awareness campaigns, and the distribution of fentanyl-xylazine test kits, and naloxone have been undertaken to mitigate this crisis. Fentanyl-related overdose deaths persist despite these efforts, partly due to inconsistent policies across states and resistance towards adopting harm reduction strategies. A multifaceted approach is imperative in effectively combating the opioid overdose epidemic. This approach should include expansion of treatment access, broadening the availability of medications for opioid use disorder, implementation of harm reduction strategies, and enaction of legislative reforms and diminishing stigma associated with opioid use disorder.

Unmet needs and harm reduction preferences of syringe services program participants: differences by co-use of illicit opioids and methamphetamine

BackgroundThe current fourth wave of the United States opioid overdose epidemic is characterized by the co-use of opioids and stimulants, including illicit opioids and methamphetamine. The co-use of these two drugs, known as “goofballing,” is associated with higher risk for several adverse outcomes, including more frequent injections, greater health risks, and higher morbidity. Considering these differences, this unique subpopulation of people who inject drugs (PWID) may also have unique unmet needs and harm reduction preferences.MethodsWe collected self-reported data from participants (N = 50) of a syringe services program (SSP), including basic needs and harm reduction preferences. Using bivariate analyses, we examined differences between SSP participants who do and do not co-use illicit opioids and methamphetamine. Co-use was defined as reporting the use of both drugs, which may or may not have been used simultaneously.ResultsIn the overall sample, the mean level of need was highest for bus passes or other transportation, a person who can help you get the services you need, medication for opioid use disorder, and a job or job training. Additionally, all participants reported being either interested or very interested in fentanyl test strips, safe consumption sites, delivery of syringe service supplies, and delivery of naloxone. Those who endorsed co-use had a greater need for food, healthcare, substance use disorder treatment, a support person to help them access needed services, and bus passes or transportation.ConclusionsUnmet needs were prevalent, and the desire for more harm reduction services was high among these PWID. Results also suggest people who co-use illicit opioids and methamphetamine may have the greatest unmet needs and desire for additional harm reduction services.

Mobile addiction treatment and harm reduction services as tools to address health inequities: a community case study of the Brockton Neighborhood Health Center mobile unit.

Opioid overdose deaths continue to increase in the US. Recent data show disproportionately high and increasing overdose death rates among Black, Latine, and Indigenous individuals, and people experiencing homelessness. Medications for opioid use disorder (MOUD) can be lifesaving; however, only a fraction of eligible individuals receive them. Our goal was to describe our experience promoting equitable MOUD access using a mobile delivery model. We implemented a mobile MOUD unit aiming to improve equitable access in Brockton, a racially diverse, medium-sized city in Massachusetts. Brockton has a relatively high opioid overdose death rate with increasingly disproportionate death rates among Black residents. Brockton Neighborhood Health Center (BNHC), a community health center, provides brick-and-mortar MOUD access. Through the Communities That HEAL intervention as part of the HEALing Communities Study (HCS), Brockton convened a community coalition with the aim of selecting evidence-based practices to decrease overdose deaths. BNHC leadership and coalition members recognized that traditional brick-and-mortar treatment locations were inaccessible to marginalized populations, and that a mobile program could increase MOUD access. In September 2021, with support from the HCS coalition, BNHC launched its mobile initiative - Community Care-in-Reach® - to bring low-threshold buprenorphine, harm reduction, and preventive care to high-risk populations. During implementation, the team encountered several challenges including: securing local buy-in; navigating a complex licensure process; maintaining operations throughout the COVID-19 pandemic; and finally, planning for sustainability. In two years of operation, the mobile team cared for 297 unique patients during 1,286 total visits. More than one-third (36%) of patients received buprenorphine prescriptions. In contrast to BNHC's brick-and-mortar clinics, patients with OUD seen on the mobile unit were more representative of historically marginalized racial and ethnic groups, and people experiencing homelessness, evidencing improved, equitable addiction care access for these historically disadvantaged populations. Offering varied services on the mobile unit, such as wound care, syringe and safer smoking supplies, naloxone, and other basic medical care, was a key engagement strategy. This on-demand mobile model helped redress systemic disadvantages in access to addiction treatment and harm reduction services, reaching diverse individuals to offer lifesaving MOUD at a time of inequitable increases in overdose deaths.

Comparison of intranasal naloxone and intranasal nalmefene in a translational model assessing the impact of synthetic opioid overdose on respiratory depression and cardiac arrest.

Using a validated translational model that quantitatively predicts opioid-induced respiratory depression and cardiac arrest, we compared cardiac arrest events caused by synthetic opioids (fentanyl, carfentanil) following rescue by intranasal (IN) administration of the μ-opioid receptor antagonists naloxone and nalmefene. This translational model was originally developed by Mann et al. (Clin Pharmacol Ther 2022) to evaluate the effectiveness of intramuscular (IM) naloxone. We initially implemented this model using published codes, reproducing the effects reported by Mann et al. on the incidence of cardiac arrest events following intravenous doses of fentanyl and carfentanil as well as the reduction in cardiac arrest events following a standard 2 mg IM dose of naloxone. We then expanded the model in terms of pharmacokinetic and µ-opioid receptor binding parameters to simulate effects of 4 mg naloxone hydrochloride IN and 3 mg nalmefene hydrochloride IN, both FDA-approved for the treatment of opioid overdose. Model simulations were conducted to quantify the percentage of cardiac arrest in 2000 virtual patients in both the presence and absence of IN antagonist treatment. Following simulated overdoses with both fentanyl and carfentanil in chronic opioid users, IN nalmefene produced a substantially greater reduction in the incidence of cardiac arrest compared to IN naloxone. For example, following a dose of fentanyl (1.63 mg) producing cardiac arrest in 52.1% (95% confidence interval, 47.3-56.8) of simulated patients, IN nalmefene reduced this rate to 2.2% (1.0-3.8) compared to 19.2% (15.5-23.3) for IN naloxone. Nalmefene also produced large and clinically meaningful reductions in the incidence of cardiac arrests in opioid naïve subjects. Across dosing scenarios, simultaneous administration of four doses of IN naloxone were needed to reduce the percentage of cardiac arrest events to levels that approached those produced by a single dose of IN nalmefene. Simulations using this validated translational model of opioid overdose demonstrate that a single dose of IN nalmefene produces clinically meaningful reductions in the incidence of cardiac arrest compared to IN naloxone following a synthetic opioid overdose. These findings are especially impactful in an era when >90% of all opioid overdose deaths are linked to synthetic opioids such as fentanyl.

Impact of opioid overdoses on US life expectancy and years of life lost, by demographic group and stimulant co-involvement: a mortality data analysis from 2019 to 2022

The United States' opioid crisis is worsening, with the number of deaths reaching 81,806 in 2022 after more than tripling over the past decade. This study aimed to comprehensively characterize changes in burden of opioid overdose mortality in terms of life expectancy reduction and years of life lost between 2019 and 2022, including differential burden across demographic groups and the contribution of polysubstance use. Using life tables and counts for all-cause and opioid overdose deaths from the National Center for Health Statistics, we constructed cause-eliminated life tables to estimate mortality by age in the absence of opioid-related deaths. We calculated the loss in life expectancy at birth (LLE) and total years of life lost (YLL) due to opioid overdose deaths by state of residency, sex, racial/ethnic group, and co-involvement of cocaine and psychostimulants. Opioid-related deaths in the US led to an estimated 3.1 million years of life lost in 2022 (38 years per death), compared to 2.0 million years lost in 2019. Relative to a scenario with no opioid mortality, we estimate that opioid-related deaths reduced life expectancy nationally by 0.67 years in 2022 vs 0.52 years in 2019. This LLE worsened in all racial/ethnic groups during the study period: 0.76y-0.96y for white men, 0.36y-0.55y for white women, 0.59y-1.1y for Black men, 0.27y-0.53y for Black women, 0.31y-0.82y for Hispanic men, 0.19y-0.31y for Hispanic women, 0.62y-1.5y for American Indian/Alaska Native (AI/AN) men, 0.43y-1y for AI/AN women, 0.09y-0.2y for Asian men, and 0.08y-0.13y for Asian women. Nearly all states experienced an increase in years of life lost (YLL) per capita from 2019 to 2022, with YLL more than doubling in 16 states. Cocaine or psychostimulants with abuse potential (incl. methamphetamines) were involved in half of all deaths and years of life lost in 2022, with substantial variation in the predominant drug class by state and racial/ethnic group. The burden of opioid-related mortality increased dramatically in the US between 2019 and 2022, coinciding with the period of the COVID-19 pandemic and the associated disruptions to social, economic, and health systems. Opioid overdose deaths are an important contributor to decreasing US life expectancy, and Black, Hispanic, and Native Americans now experience mortality burdens approaching or exceeding white Americans. None.

Perceptions on Treatment Utilization and Risk of Overdose Among Opioid Users in Kolkata: A Qualitative Study

Objective: This study was performed to explore the perceptions of treatment utilization patterns and the risk of overdose of both opioid users and their peer educators in Kolkata, India. Methods: This study used a qualitative approach for data collection between September and December 2023. In-depth interviews (IDIs) of 20 opioid users from two authorized opioid substitution therapy (OST) centers (10 registered clients) and their respective field practice areas (10 unregistered clients) in Kolkata were conducted. Key informant interviews (KIIs) of six peer educators were also conducted. Semi-structured interviews were conducted; audio was recorded, transcribed, and translated for coding and analysis. An inductive thematic analysis was performed. Results: Six broad themes (individual knowledge, logistics, legal/administrative, treatment effectiveness, self-confidence of treatment, and poor knowledge about the antidote of opioid poisoning, i.e., naloxone) emerged from the data analysis of IDIs. Four broad themes (high-risk behavior, raising awareness, the benefits of OST, and poor knowledge about naloxone) emerged from the data analysis of KIIs. Both opioid users and their peer educators were aware of the dangers of opioid overdose. However, they lacked sufficient knowledge in recognizing and offering immediate assistance in instances of opioid overdose, including the administration of naloxone. Conclusion: The findings recognize the necessity of drawing and retaining opioid users in an efficient healthcare facility, such as OST centers, and providing them adequate training to identify and provide immediate assistance in cases of overdose, including naloxone administration. Our findings will assist policymakers in designing programs to prevent and treat opioid overdoses.

Community-Based Cluster-Randomized Trial to Reduce Opioid Overdose Deaths

BackgroundEvidence-based practices for reducing opioid-related overdose deaths include overdose education and naloxone distribution, the use of medications for the treatment of opioid use disorder, and prescription opioid safety. Data are needed on the effectiveness of a community-engaged intervention to reduce opioid-related overdose deaths through enhanced uptake of these practices.MethodsIn this community-level, cluster-randomized trial, we randomly assigned 67 communities in Kentucky, Massachusetts, New York, and Ohio to receive the intervention (34 communities) or a wait-list control (33 communities), stratified according to state. The trial was conducted within the context of both the coronavirus disease 2019 (Covid-19) pandemic and a national surge in the number of fentanyl-related overdose deaths. The trial groups were balanced within states according to urban or rural classification, previous overdose rate, and community population. The primary outcome was the number of opioid-related overdose deaths among community adults.ResultsDuring the comparison period from July 2021 through June 2022, the population-averaged rates of opioid-related overdose deaths were similar in the intervention group and the control group (47.2 deaths per 100,000 population vs. 51.7 per 100,000 population), for an adjusted rate ratio of 0.91 (95% confidence interval, 0.76 to 1.09; P=0.30). The effect of the intervention on the rate of opioid-related overdose deaths did not differ appreciably according to state, urban or rural category, age, sex, or race or ethnic group. Intervention communities implemented 615 evidence-based practice strategies from the 806 strategies selected by communities (254 involving overdose education and naloxone distribution, 256 involving the use of medications for opioid use disorder, and 105 involving prescription opioid safety). Of these evidence-based practice strategies, only 235 (38%) had been initiated by the start of the comparison year.ConclusionsIn this 12-month multimodal intervention trial involving community coalitions in the deployment of evidence-based practices to reduce opioid overdose deaths, death rates were similar in the intervention group and the control group in the context of the Covid-19 pandemic and the fentanyl-related overdose epidemic. (Funded by the National Institutes of Health; HCS ClinicalTrials.gov number, NCT04111939.)