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In the last decade, the opioid overdose epidemic has been exacerbated by the emerging drug of abuse, xylazine. This veterinary anesthetic, an alpha-2 agonist, not only potentiates the fatal effects of opioids but also causes toxic endothelial effects. This review aims to assess the impact of xylazine use and overdoses within the context of the opioid crisis as a public health issue. The research used data from scientific publications, state health reports, and analyses from the Institute of Forensic Sciences of Puerto Rico. The databases PubMed, Google Scholar, and Scopus were searched for relevant publications. The search strategy employed two groups of terms: the drug of interest (xylazine) and types of exposure (drug use, overdose, substance abuse, etc.). The initial search in PubMed was then extrapolated, and the search terms were adjusted for appropriate database syntax. According to the most recent publications and CDC data in the USA, approximately 95 % of fentanyl overdose cases involve xylazine, while the other 5 % of overdose cases are attributed solely to xylazine, predominantly administered intravenously. In the last four years, more than 4000 overdose deaths have been related to xylazine use; the northeastern United States had reported the most significant number of deaths. This number changes daily as reanalysis results and new data are published. Less than 50 % of states perform tests for xylazine detection or maintain statistical monitoring of overdoses related to this drug. The absence of testing impedes emergency room physicians from making accurate diagnoses, increasing the likelihood of fatal overdoses. This review highlights five major concerns: (1) The recognition of intoxication as a primary concern and the unavailability of alpha-2 antagonists for treatment. (2) The challenges in the clinical setting linked to xylazine abuse and its co-administration with substances like fentanyl and its analogs. (3) The necessity for robust government statistical resources for the unification and dissemination of critical overdose and emerging drug abuse detection information. (4) The need for effective rehabilitation programs, including psychosocial support and treatment interventions, to respond to this public health crisis. (5) The urgency for further research to understand the prevalence, toxic effects of chronic or acute use, and the clinical implications in xylazine users, including the development of alpha-2 antagonists for treatment. We conclude that addressing these concerns is crucial to working with the xylazine abuse situation., Competing Interests: Declaration of competing interest The authors report no conflict, this study was not grant awarded., (Copyright © 2024 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Objectives: The United States faces an ongoing drug overdose crisis, but accurate information on the prevalence of opioid use disorder (OUD) remains limited. A recent analysis by Keyes et al used a multiplier approach with drug poisoning mortality data to estimate OUD prevalence. Although insightful, this approach made stringent and partly inconsistent assumptions in interpreting mortality data, particularly synthetic opioid (SO)-involved and non-opioid-involved mortality. We revise that approach and resulting estimates to resolve inconsistencies and examine several alternative assumptions., Methods: We examine 4 adjustments to Keyes and colleagues' estimation approach: (A) revising how the equations account for SO effects on mortality, (B) incorporating fentanyl prevalence data to inform estimates of SO lethality, (C) using opioid-involved drug poisoning data to estimate a plausible range for OUD prevalence, and (D) adjusting mortality data to account for underreporting of opioid involvement., Results: Revising the estimation equation and SO lethality effect (adj. A and B) while using Keyes and colleagues' original assumption that people with OUD account for all fatal drug poisonings yields slightly higher estimates, with OUD population reaching 9.3 million in 2016 before declining to 7.6 million by 2019. Using only opioid-involved drug poisoning data (adj. C and D) provides a lower range, peaking at 6.4 million in 2014-2015 and declining to 3.8 million in 2019., Conclusions: The revised estimation equation presented is feasible and addresses limitations of the earlier method and hence should be used in future estimations. Alternative assumptions around drug poisoning data can also provide a plausible range of estimates for OUD population., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 American Society of Addiction Medicine.)

Objectives: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Background: Acetaminophen and ibuprofen are the most common agents involved in adolescent self-poisoning. With increasing suicidality observed during the COVID-19 pandemic, we sought to compare overdose trends, severity, and outcomes for both agents., Methods: We performed a retrospective analysis of the National Poison Data System for acetaminophen and ibuprofen single-substance exposures in teenagers 13-19 years of age from 2017-2022. Acetaminophen and ibuprofen overdoses (per 100,000 persons) were plotted by year. Medical outcomes, clinical effects, and therapies were compared to determine if there were differences in overdose severity between the 2 agents., Results: From 2017 to 2022, US poison centers recorded 50,902 single-substance acetaminophen exposures and 41,674 single-substance ibuprofen exposures in teenagers. Cases peaked in 2021 with 40.0 versus 29.1 cases (per 100,000 persons) for acetaminophen and ibuprofen, respectively. Acetaminophen self-poisoning was significantly more likely to result in death (odds ratio, 13.92; 95% confidence interval, 2.18-581.75; P < 0.001) or inpatient admission (odds ratio, 7.38; 95% confidence interval, 7.10-7.66; P < 0.001) compared with ibuprofen. Abdominal pain and vomiting were the most common clinical effects for both agents, and unsurprisingly, acetaminophen was more likely to cause transaminitis and liver dysfunction, whereas ibuprofen was more likely to cause central nervous system depression and metabolic acidosis. For the acetaminophen group, 19 teenagers underwent organ transplantation., Conclusions: Given the increased hospitalization and treatment resources needed for acetaminophen overdoses compared with ibuprofen, it is time to implement acetaminophen packaging policy change to protect US adolescents., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Xylazine, a veterinary sedative, has emerged as a concerning element in the landscape of substance use in the United States. This integrative review synthesizes evidence from a systematic examination of 14 selected studies conducted between 2008 and 2023. The primary objective is to comprehensively understand the epidemiology and prevalence of xylazine use, particularly its involvement in drug-related deaths, regional variations, national impact, co-occurrence with opioids, and challenges associated with detection and intervention. The results underscore stark regional disparities in xylazine prevalence. West Virginia and Miami-Dade County have experienced alarming surges in xylazine-involved drug-related deaths. Nationally, its influence extends beyond regional boundaries, predominantly affecting white males in the Northeast. The co-occurrence of xylazine with opioids, especially fentanyl and heroin, significantly amplifies the risks of fatal overdoses. Detecting xylazine presents formidable challenges due to its frequent presence alongside other substances, necessitating enhanced surveillance and more effective detection methods. User perspectives emerge as pivotal, emphasizing the importance of user-informed harm reduction strategies. In conclusion, this review has significant policy implications. Tailored, region-specific strategies are imperative to address the diverse prevalence of xylazine use. A nationwide response is indispensable, prioritizing harm reduction initiatives, enhanced detection methods, and active user engagement. The multifaceted nature of the xylazine issue requires comprehensive approaches to mitigate its profound risks effectively. Policymakers are urged to consider regional disparities and the co-occurrence of xylazine with opioids when crafting targeted interventions. Immediate, user-informed harm reduction is vital to address the evolving landscape of xylazine use in the United States.

This pilot study explores the utilization of the Overdose Detection Mapping Application Program (ODMAP) as a tool for enhancing collaboration between the public health and public safety sectors to address the overdose epidemic in the United States. Through qualitative interviews with ODMAP users, key themes emerged, including the role of data sharing in facilitating collaboration, challenges posed by divergent data privacy standards, and the need for clearer guidance on cross-sector data sharing. Findings highlight ODMAP's potential to integrate data for targeted interventions at individual and population levels. Future research directions include overcoming data sharing barriers, strategically utilizing data across sectors, and rigorously evaluating the impact of cross-sector partnerships on overdose morbidity and mortality. Overall, this study underscores the importance of ODMAP in fostering coordinated responses to the overdose crisis and provides valuable insights for improving overdose surveillance and intervention efforts., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: The US is experiencing a protracted drug overdose crisis primarily associated with exposure to illicitly manufactured fentanyl (IMF), methamphetamine, and cocaine. Overdose risk and treatment responses may be directly affected by absolute drug exposure concentrations and drug use prevalence., Objective: To quantify changes in absolute drug exposure concentrations from 2013 to 2023., Design, Setting, and Participants: This cross-sectional study analyzed urine drug testing (UDT) results from urine specimens collected between January 1, 2013, and August 22, 2023, in 49 states and the District of Columbia. Urine specimens were obtained from patients aged 18 years or older who presented to substance use disorder treatment clinics. The UDT was ordered by clinicians based on medical necessity., Exposures: Urine specimens were analyzed for the following drugs or metabolites (analytes tested in parentheses): fentanyl (fentanyl), heroin (6-monoacetylmorphine), cocaine (benzoylecgonine), and methamphetamine (methamphetamine) using liquid chromatography with tandem mass spectrometry., Main Outcomes and Measures: Relative concentrations of fentanyl, heroin, cocaine, and methamphetamine. Creatinine-normalized drug concentration values were log-transformed prior to visualization and statistical analyses. The Mann-Kendall trend test was performed to examine trends over time. To estimate the geospatial and temporal patterns of drug concentration, a second series of models (1 for each drug) with an interaction effect for clinic location and collection year were fit., Results: A total of 921 931 unique UDT samples were collected from patients (549 042 males [59.6%]; median [IQR] age, 34 [27-44] years). The adjusted fentanyl concentration in urine specimens was 38.23 (95% CI, 35.93-40.67) ng/mg creatinine in 2023 and 4.61 (95% CI, 3.59-5.91) ng/mg creatinine in 2013. The adjusted methamphetamine concentration was 3461.59 (95% CI, 3271.88-3662.30) ng/mg creatinine in 2023 and 665.27 (95% CI, 608.51-727.32) ng/mg creatinine in 2013. The adjusted cocaine concentration was 1122.23 (95% CI, 1032.41-1219.87) ng/mg creatinine in 2023 and 559.71 (95% CI, 524.69-597.06) ng/mg creatinine in 2013. The adjusted heroin concentration was 58.36 (95% CI, 48.26-70.58) ng/mg creatinine in 2023 and 146.59 (95% CI, 136.06-157.92) ng/mg creatinine in 2013. Drug concentrations varied across US Census divisions., Conclusions and Relevance: This cross-sectional study found that absolute concentrations of fentanyl, methamphetamine, and cocaine in urine specimens increased from 2013 to 2023, with a decrease in heroin concentration during that period. The findings suggest that exposure to these substances, as well as the illicit drug supply, has fundamentally changed in many parts of the US, highlighting the need to reinforce surveillance initiatives and accelerate efforts to treat individuals with IMF and/or stimulant exposure.

Objective: Racialized health inequities in substance use-related harms might emerge from differential access to syringe service programs (SSPs). To explore this, we examined the association between county-level racialized environments, other factors, and (1) SSP presence, and (2) per capita syringe and (3) naloxone distribution., Methods: 2021 US National Survey of SSP data (n=295/412;72 % response rate) was used to identify SSP presence and the sum of syringes and naloxone doses distributed in 2020 by county. Study measures included racial residential segregation (RRS; i.e., divergence and dissimilarity indexes for Black:Non-Hispanic White & Hispanic:Non-Hispanic White) and covariates (i.e., demographic proportions, urban/suburban/rural classifications, 2020 US presidential Republican vote share, and overdose mortality from 2019). We used logit Generalized Estimating Equations to determine factors associated with county-level SSP presence, and zero inflated negative binomial regression models to determine factors associated with per capita syringe and naloxone distribution., Results: SSPs were reported in 9 % (283/3106) of US counties. SSP presence was associated with higher divergence and dissimilarity indexes, urban and suburban counties, higher opioid overdose mortality, and lower 2020 Republican presidential vote share. Per capita syringes distributed was associated with lower RRS (divergence and Hispanic:White dissimilarity), lower racially minoritized population proportions and rural counties, while per capita naloxone distribution was associated with lower Hispanic and "other" population proportions, and rural counties., Conclusions: Racialized environments are associated with SSP presence but not the scope of those programs. Preventing HIV and HCV outbreaks, and overdose deaths requires addressing community level factors that influence SSP implementation and accessibility., Competing Interests: Declaration of Competing Interest No conflict declared., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Federal, state, and municipal governments in the United States have been reluctant to authorize overdose prevention centers (OPCs), which are evidence-based approaches for preventing overdose deaths and blood-borne pathogen transmission., Methods: From July 2022 to February 2023, we explored how stigma manifests in OPC policymaking by conducting in-depth interviews with 17 advocates, legislators, service providers, and researchers involved with OPC advocacy and policymaking in Rhode Island, California, Pennsylvania, and New York., Results: We found that although jurisdictions differed in their OPC policymaking experiences, stigma manifested throughout the process, from planning to authorization. Participants described OPCs as a tool for destigmatizing overdose and substance use, yet confronted institutionalized stigma and discriminatory attitudes toward people who use drugs (PWUD) and harm reduction from multiple sources (eg, politicians, media, and members of the public). Opposition toward OPCs and harm reduction approaches more broadly intersected with public discourse on crime, homelessness, and public disorder. Employed stigma-mitigation strategies included humanizing PWUD, publicizing the benefits of OPCs to the wider community, and strategically engaging media., Conclusion: These findings illustrate the importance of understanding stigma at different stages of the policymaking process to better facilitate authorization and eventual implementation of OPCs in the United States., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JNP served as a technical consultant on a US Food and Drug Administration grant (U01FD00745501). The remaining authors have no conflicts of interest to disclose.

Background: Adolescents and young adults with risk factors for opioid misuse and opioid use disorder are at elevated risk for overdose. We examined prior non-fatal overdose experiences among at-risk adolescents/young adults to inform prevention efforts., Methods: Adolescents/young adults (ages 16-30) in two US emergency departments self-reporting past year opioid misuse or opioid use plus a misuse risk factor completed a baseline survey as part of an ongoing randomised controlled trial. We describe baseline factors associated with (a) overall non-fatal overdose experiences and (b) groups based on substance(s) used during the worst overdose experience., Results: Among 771 participants (27.9% male), 40.7% reported a non-fatal overdose experience. Compared with those without a prior overdose experience, those with prior overdose experience(s) were less likely to be heterosexual, and more likely to report a prior suicide attempt and greater peer substance misuse. Regarding the worst overdose experience, substance(s) included: 36.6% alcohol only, 28.0% alcohol and cannabis, 22.6% alcohol with other substance(s) and 12.7% other substance(s) only (eg, opioids). Compared with the alcohol only group, the alcohol and cannabis group were younger and less likely to be heterosexual; the alcohol with other substance(s) group were older and had greater peer substance misuse; and the other substance(s) only group were more likely to be male, receive public assistance, screen positive for anxiety and less likely to be heterosexual., Conclusions: Among at-risk adolescents/young adults, findings support the need for tailored overdose prevention efforts based on substance(s) used, with consideration of sexuality, mental health and peer substance use., Trial Registration Number: NCT04550715., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives. To examine trends in overdose deaths by intent and drug category to better understand the recent decrease in overdose suicides amid the overdose epidemic. Methods. We examined trends in rates of overdose deaths by intent (unintentional, suicide, or undetermined) across 9 drug categories from 1999 to 2022 using US National Vital Statistics System mortality data. Results. Unintentional overdoses involving synthetic opioids, polydrug toxicity involving synthetic opioids, psychostimulants, and cocaine increased exponentially with annual percentage changes ranging from 15.0% to 104.9% during 2010 to 2022. The death rates also increased for suicides involving these drugs, especially for psychostimulants (annual percentage change = 12.9% for 2010-2022; P  < .001). However, these drugs accounted for relatively small percentages of overdose suicides. The leading drug categories among suicides were antidepressants, prescription opioids, and benzodiazepines, though these deaths have decreased or leveled off in recent years. Conclusions. Different drugs commonly involved in suicides and unintentional overdoses may contribute to their divergent trends. Public Health Implications. Amid the overdose epidemic, safe storage of medications remains a crucial strategy to prevent overdose suicides. The large increases in suicides involving psychostimulants warrant monitoring. ( Am J Public Health . 2024;114(10):1081-1085. https://doi.org/10.2105/AJPH.2024.307745).

Fentanyl has emerged as the leading cause of fatal drug overdoses in the U.S. Individuals misusing drugs may not always be aware of exposure to fentanyl., To determine the prevalence of fentanyl use and extent of awareness of fentanyl exposure among a national sample of treatment-seeking individuals with opioid use disorder ( n  = 1098)., Participants provided oral fluid and urine specimens, which were tested for drugs by liquid chromatography/tandem mass spectrometry. Participants also provided self-reports of fentanyl use., 49.5% tested positive for fentanyl in oral fluid, urine, or both. Of those testing positive for fentanyl, 29.8% were unaware that they had been exposed to fentanyl. Participants testing positive for opioids methadone, and specifically 6-monoacetylmorphine (6-MAM), a unique metabolite of heroin, were significantly more likely to be unaware of fentanyl exposure than participants testing negative for these substances, with a similar trend for oxycodone and tramadol., These findings may be due to fentanyl's effect being difficult to distinguish from that of other opioids, whereas when other types of drugs are adulterated with fentanyl, the differences in effects are likely to be readily discernable. These results support the importance of expanded drug-checking services.

We examined a natural history of opioid overdose deaths from 1999-2021 in the United States to describe state-level spatio-temporal heterogeneity in the waves of the epidemic. We obtained overdose death counts by state from 1999-2021, categorized as involving prescription opioids, heroin, synthetic opioids, or unspecified drugs. We developed a Bayesian multivariate multiple change point model to flexibly estimate the timing and magnitude of state-specific changes in death rates involving each drug type. We found substantial variability around the timing and severity of each wave across states. The first wave of prescription-involved deaths started between 1999 and 2005, the second wave of heroin-involved deaths started between 2010 and 2014, and the third wave of synthetic opioid-involved deaths started between 2014 and 2021. The severity of the second and third waves was greater in states in the eastern half of the country. Our study highlights state-level variation in the timing and severity of the waves of the opioid epidemic by presenting a 23-year natural history of opioid overdose mortality in the United States. While reinforcing the general notion of three waves, we find that states did not uniformly experience the impacts of each wave., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Noa Krawczyk receives consulting fees for expert witness testimony in ongoing opioid litigation., (Copyright: © 2024 Kline et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The spread of illicitly manufactured fentanyl is driving steep increases in US overdose deaths. Fentanyl seizures are correlated with state-level opioid-related mortality; however, more granular seizure surveillance information has the potential to better inform overdose prevention and harm reduction efforts., Methods: Using data on fentanyl pill and powder seizures from High Intensity Drug Trafficking Areas (HIDTA), we tested associations between seizure prevalence and overdose mortality, from 2013 to 2020. The primary exposure-seizure burden-was constructed by identifying counties having high (above the median) prevalence of pill, powder, or combined pill/powder seizure burden per 100,000 population. Poisson models accounted for county demographic, law enforcement and time trends., Results: During the timeframe, there were 13,842 fentanyl seizures in 606 US counties. In adjusted models, counties with a high burden of pill or powder fentanyl seizures, or both (combined pills/powder) exhibited higher total overdose mortality than non-high burden counties (pills adjusted prevalence ratio [aPR]: 1.10 [95 % confidence interval [CI]: 1.08, 1.12]; powder aPR 1.12 [CI: 1.11, 1.13]; combined pills/powder aPR: 1.27 [CI: 1.25, 1.29]). A similar pattern of associations with fentanyl seizure burden was noted for overdose deaths involving synthetic opioids (pills [aPR]: 0.99 [CI: 0.96, 1.02]; powder aPR 1.29 [CI: 1.27, 1.30]; combined pills/powder aPR 1.55 [CI: 1.52, 1.58])., Conclusions: Law enforcement data on fentanyl seizures predicts drug overdose mortality at the county-level. Integrating these data with more traditional epidemiologic surveillance approaches has the potential to inform community overdose response efforts., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Abstract: The opioid crisis, particularly the "fourth wave" involving fentanyl and stimulants, has been responsible for an alarming increase in overdose deaths in the United States. Although fentanyl contamination in cocaine has gained significant attention, the converse-cocaine-adulterated fentanyl-has been largely overlooked despite its health implications. The rise in concurrent cocaine and fentanyl overdose deaths could be attributed to various factors, from intentional polysubstance use to unintentional adulterations. Cocaine-related health issues may amplify the problem. Four potential pathways for the increased risk of overdose with cocaine-adulterated opioids include enhanced drug reinforcement, potential overdose risk with switching drug samples, altered metabolism of medications used for opioid use disorder, and increased myocardial demand juxtaposed with opioid-induced respiratory depression. With these risks, the importance of drug testing becomes paramount in the unregulated drug market. As polysubstance use overdoses surge, there is an urgent need to understand how drug supplies are changing in order to effectively identify appropriate harm reduction strategies. Specifically, further research is needed evaluating complications of low-level cocaine exposure with chronic/persistent opioid use. The hazards associated with cocaine-adulterated fentanyl emphasize the significance of understanding not only fentanyl's presence in cocaine but also cocaine's role in the fentanyl supply., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 American Society of Addiction Medicine.)

Objective: The National Survey on Drug Use and Health (NSDUH), as the primary source of epidemiological substance use data in the United States, could illuminate trends in fentanyl use behaviors contributing to the opioid overdose crisis. We hypothesized that the trend in NSDUH prevalence of lifetime fentanyl injection would match the direction and magnitude of the trend in synthetic opioid overdose deaths., Method: Using logistic regression, we modeled the 2015-2020 trend in synthetic opioid overdose deaths as a proportion of all deaths. We modeled contemporary trends from cross-sectional NSDUH data for (a) lifetime fentanyl injection, (b) past-year prescription fentanyl misuse, (c) prescription tramadol misuse (the other synthetic opioid counted alongside fentanyl in the overdose deaths category), and (d) combined prescription fentanyl or tramadol misuse. The average annual NSDUH weighted sample size was 272,519,038 (51.5% female, 48.5% male)., Results: Synthetic opioid overdose deaths increased from 2015 to 2020 (odds ratio = 3.39, meaning that the odds of a death being from synthetic opioid overdose in 2020 were 3.39 times the odds of death from that cause in 2015, 95% CI [3.34, 3.44]). None of the substance use trends significantly increased., Conclusions: Per NSDUH data, the prevalence of fentanyl misuse did not significantly increase in tandem with synthetic opioid overdose deaths from 2015 to 2020. Scrutiny of NSDUH's approach to assessing fentanyl misuse casts doubt on the utility of NSDUH fentanyl data collection. We acknowledge recent changes to the survey and recommend two further changes to optimize a vital source of data on behaviors related to the opioid overdose crisis., Competing Interests: Ramin Mojtabai has received royalties from UpToDate. Eric C. Strain has consulted, done work for, or served on advisory boards to the following organizations: Cerevel, Fast Track Drugs and Biologics, Masimo/Innovative Health Solutions, Otsuka, Pear Therapeutics, UpToDate, and Wolters Kluwer.

Background: Opioid-involved overdoses, especially those involving synthetic opioids like fentanyl, have driven increases in overdose morbidity and mortality. Emergency medical services (EMS) and emergency department (ED) data can each provide near real-time information on trends in nonfatal opioid-involved overdoses; however, minimal data exist on the comparability of trends in these two data sources., Methods: EMS data from biospatial© and ED data from CDC's Drug Overdose Surveillance and Epidemiology system and National Syndromic Surveillance Program were queried for nine states. Counts of total encounters, opioid-involved overdose encounters, and rates of opioid-involved overdoses per 10,000 total encounters were calculated for each data source from 2020 to 2022. Trends in monthly counts and rates were assessed using Joinpoint regression., Results: On average, EMS data captured 1.8 times more monthly opioid-involved overdose encounters than ED data. Trends in the counts of opioid-involved overdose encounters were similar in both data sources with increases and decreases occurring during roughly the same periods. Overall, trends in rates of opioid-involved overdose encounters were also comparable., Conclusions: EMS and ED data provide complementary information for understanding overdose trends. Study findings underscore the importance of implementing post-overdose response protocols by both EMS and ED providers to ensure patients receive services irrespective of care setting., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Introduction: Recognized risk factors for acetaminophen overdose include alcohol, opioids, and mood disorders. The aim of this study is to assess additional risk factors for acetaminophen overdose evaluated in the emergency department (ED)., Methods: A retrospective study was performed using the 2018 US Nationwide Emergency Department Sample (NEDS). All adult ED visits for acetaminophen overdose were included in the study group and those without it were taken as control. STATA, 16.1 was used to perform multivariable logistic regression analysis and adjusted odds ratios (ORadj) were reported., Results: We identified 27,792 ED visits for acetaminophen overdose. Relative to non-acetaminophen ED visits, this group was younger (median age 32 vs 47 years; p < 0.0001), more often female (66.1% vs 57.0%; p < 0.0001), had higher ED charges ($3,506 vs $2,714; p < 0.0001), higher proportion of alcohol-related disorders (15.8% vs 3.5%; p < 0.0001), anxiety disorders (30.2% vs 8.3%; p < 0.0001), cannabis use (8.7% vs 1.4%; p < 0.0001), hematology/oncology diagnoses (13.3% vs 10.9%; p < 0.0001), mood disorders (52.4% vs 7.9%; p < 0.0001), opioid-related disorders (4.1% vs 1.0%; p < 0.0001), and suicide attempt/ideation (12.2% vs 1.1%; p < 0.0001). Multivariable analysis showed alcohol-related disorders (ORadj 2.67), anxiety disorders (ORadj 1.24), cannabis (ORadj 1.63), females (ORadj 1.45), Income Q3 (ORadj 1.09), hematology/oncology diagnoses (ORadj 1.40), mood disorders (ORadj 10.07), opioid-related disorders (ORadj 1.20), and suicide attempt/ideation (ORadj 1.68) were associated with acetaminophen overdose., Conclusion: In addition to previously recognized risks, our study demonstrated that cannabis use and hematologic/oncologic comorbidities were more common among acetaminophen-overdose ED visits. These new findings are concerning because of rapid legalization of cannabis and the increasing incidence of cancer worldwide. Additional investigation into these risks should be a priority for clinicians, policymakers, and researchers., (© 2024. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Objectives. To estimate children's exposure to family overdose in the United States. Methods. We used recent demographic kinship modeling advances and the Centers for Disease Control and Prevention's most recent underlying cause of death estimates to model how many children aged younger than 18 years in 2019 had lost 1 or more parents, siblings, grandparents, aunts or uncles, or cousins to overdose mortality since birth. We calculated the number and proportion of children with such exposures and considered age, cohort, and gender patterning. Results. More than 1.4 million children in the United States, mostly adolescents, experienced a family overdose death, often losing central figures like parents or grandparents. Cohort analyses suggest dramatic increases in these exposures, portending mounting prevalence. Conclusions. Attention to the large population with lives disrupted by overdose deaths should include affected children. The long-arm consequences of the overdose crisis will continue to define the public health landscape for decades. ( Am J Public Health . 2024;114(12):1394-1397. https://doi.org/10.2105/AJPH.2024.307847).

Introduction: The COVID-19 pandemic disrupted the traditional mode of methadone maintenance treatment (MMT) delivery through the imposition of lockdowns and social distancing measures. In response, policy makers granted flexibilities to providers delivering MMT to change their practices to maintain patient participation while accommodating the measures imposed to prevent the spread of COVID-19. This study examines the utilization of MMT and overdoses of patients receiving MMT during the COVID-19 pandemic in one mid-Atlantic state., Materials and Methods: We analyzed Medicaid claims data for 2018-2020, calculating weekly trends for starts, discontinuations, and medically-treated overdoses for beneficiaries receiving MMT who had been continuously enrolled in Medicaid for the previous 12 months, to account for changes in the composition of the Medicaid population following the COVID-19 public health emergency (PHE). We completed data analyses from January to June 2022., Results: We observed countervailing trends in new starts, which experienced an immediate, non-significant dip of -22.47 per 100,000 Medicaid beneficiaries (95%CI, -50.99 to 6.04) at the outset of the pandemic followed by an increasing upward trend of 1.41 per 100,000 beneficiaries per week (95%CI, 0.37 to 2.46), and in discontinuations, which also experienced an immediate dip of -3.23 per 1000 MMT enrollees (95%CI, -4.49 to -1.97) followed by an increasing upward trend of 0.14 per 1000 MMT enrollees per week (95%CI, 0.09 to 0.19). The net result of these shifts was a stable, slowly increasing rate of MMT treatment of 0.02 % per week before and after the PHE. We also found no statistically significant association of the PHE with medically-treated overdoses among beneficiaries enrolled in MMT (trend change = 0.02 overdoses per 10,000 MMT enrollees, 95%CI, -0.05 to 0.09)., Conclusions: New Jersey achieved overall stability in MMT treatment prevalence following the pandemic's onset, while some changes in treatment dynamics took place. This outcome may reflect that the extensive flexibilities granted to providers of MMT by the state and federal government successfully maintained access to MMT for Medicaid beneficiaries through the pandemic without increasing risk of medically-treated overdose. These findings should inform policy makers developing the post-COVID-19 legal and regulatory landscape., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The ongoing and evolving overdose epidemic highlights the need to translate research results into routine clinical practice to address urgent service delivery needs. Implementation science is a relatively new discipline intended to develop systematic, replicable, scalable strategies to accelerate this translation. This article presents a comprehensive review of implementation research funded by the National Institute on Drug Abuse (NIDA)., Methods: The study identified all NIDA-funded research grants awarded in fiscal years 2007 through 2023 in treatment services or prevention research (n = 1111) and screened them to find those with a pre-specified implementation science component (n = 248). Using the text of the grant application, two reviewers independently coded the key characteristics of each study., Results: The characteristics of these grants, and trends over time, are described, and priority gap areas are identified. NIDA's implementation research grants have demonstrated increasing rigor in design and measurement., Conclusions: Growth in the portfolio has been driven in part by NIDA's investments in research-practice partnerships in the criminal-legal system, and by recent efforts to address the overdose epidemic., Competing Interests: Declaration of competing interest Nothing to declare., (Published by Elsevier Inc.)

Aim: Illicitly manufactured fentanyl and its analogs are the primary drivers of opioid overdose deaths in the United States (U.S.). People who use drugs may be exposed to fentanyl or its analogs intentionally or unintentionally. This study sought to identify strategies used by rural people who use drugs to reduce harms associated with unintentional fentanyl exposure., Methods: This analysis focused on 349 semi-structured qualitative interviews across 10 states and 58 rural counties in the U.S conducted between 2018 and 2020. Interview guides were collaboratively standardized across sites and included questions about drug use history (including drugs currently used, frequency of use, mode of administration) and questions specific to fentanyl. Deductive coding was used to code all data, then inductive coding of overdose and fentanyl codes was conducted by an interdisciplinary writing team., Results: Participants described being concerned that fentanyl had saturated the drug market, in both stimulant and opioid supplies. Participants utilized strategies including: (1) avoiding drugs that were perceived to contain fentanyl, (2) buying drugs from trusted sources, (3) using fentanyl test strips, 4) using small doses and non-injection routes, (5) using with other people, (6) tasting, smelling, and looking at drugs before use, and (7) carrying and using naloxone. Most people who used drugs used a combination of these strategies as there was an overwhelming fear of fatal overdose., Conclusion: People who use drugs living in rural areas of the U.S. are aware that fentanyl is in their drug supply and use several strategies to prevent associated harms, including fatal overdose. Increasing access to harm reduction tools (e.g., fentanyl test strips, naloxone) and services (e.g., community drug checking, syringe services programs, overdose prevention centers) should be prioritized to address the polysubstance-involved overdose crisis. These efforts should target persons who use opioids and other drugs that may contain fentanyl., (© 2024. The Author(s).)

Objectives: Overdose mortality rates in the United States remain critical to population health. Economic , such as unemployment, are noted risk factors for drug overdoses. The COVID-19 pandemic exacerbated economic hardship; as a result, the US government enacted income protection programs in conjunction with existing unemployment insurance (UI) to dampen COVID-19-related economic consequences. We investigate whether UI, operationalized as the weekly benefit allowance (WBA) replacement rate, is negatively associated with drug-related overdoses., Methods: Data from the pooled 2014-2020 Detailed Restricted Mortality files for all counties from the Centers for Disease Control and Prevention, restricted to people ≥18 years of age, aggregated at the county-quarter level (n = 89,914). We included any fatal drug, opioid, and stimulant overdose. We modeled the association between WBA replacement rate (e.g., a greater proportion of weekly earnings replaced by UI) on each county-level age-adjusted mortality outcome using separate linear regression models during 2014-2020, pre-COVID (2014-2018), and post-COVID (2019-2020). We conducted sensitivity analyses using multi-level linear regression models., Results: Results indicated that a more robust WBA replacement rate any drug (Risk Difference [RD]: -0.06, 95 % Confidence Interval [CI]: -0.08, -0.05), opioid (RD: -0.04, 95 % CI: -0.06, -0.03), and stimulant (RD: -0.03, 95 % CI: -0.04, -0.02) across the entire study period (2014-2020). A more robust WBA replacement rate was associated with fewer fatal drug, opioid and stimulant overdoses in the pre-COVID-19 period and on fatal any drug and stimulant overdoses in the COVID-19 period., Conclusions: Findings support the notion that income protection policies, such as robust UI, can have a supportive role in preventing fatal drug overdoses, calling for a broader discussion onthe role of the safety net programs to buffer drug-related harms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We conduct this research with a two-fold aim: providing a quantitative analysis of the opioid epidemic in the United States (U.S.), and exploring the impact of the COVID-19 pandemic on opioid-related mortality. The duration and persistence of the opioid epidemic lends itself to the need for an overarching analysis with extensive scope. Additionally, studying the ramifications of these concurrent severe public health crises is vital for informing policies to avoid preventable mortality. Using data from CDC WONDER, we consider opioid-related deaths grouped by Census Region spanning January 1999 to October 2022 inclusive, and later add on a demographic component with gender-stratification. Through the lens of key events in the opioid epidemic, we build an interrupted time series model to reveal statistically significant drivers of opioid-related mortality. We then employ a counterfactual to approximate trends in the absence of COVID-19, and estimate excess opioid-related deaths (defined as observed opioid-related deaths minus projected opioid-related deaths) associated with the pandemic. According to our model, the proliferation of fentanyl contributed to sustained increases in opioid-related death rates across three of the four U.S. census regions, corroborating existing knowledge in the field. Critically, each region has an immediate increase to its opioid-related monthly death rate of at least 0.31 deaths per 100,000 persons at the start of the pandemic, highlighting the nationwide knock-on effects of COVID-19. There are consistent positive deviations from the expected monthly opioid-related death rate and a sizable burden from cumulative excess opioid-related deaths, surpassing 60,000 additional deaths nationally from March 2020 to October 2022, ∼70% of which were male. These results suggest that robust, multi-faceted measures are even more important in light of the COVID-19 pandemic to prevent overdoses and educate users on the risks associated with potent synthetic opioids such as fentanyl., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Laing, Donnelly. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Xylazine has been increasingly detected in illegally manufactured fentanyl (IMF) products and overdose deaths in the United States; most xylazine-involved overdose deaths involve IMF. A convenience sample of U.S. adults aged ≥18 years was identified from those evaluated for substance use treatment during July 2022-September 2023. Data were collected using the Addiction Severity Index-Multimedia Version clinical assessment tool. Among 43,947 adults, 6,415 (14.6%) reported IMF or heroin as their primary lifetime substance-use problem; 5,344 (12.2%) reported recent (i.e., past-30-day) IMF or heroin use. Among adults reporting IMF or heroin as their primary lifetime substance-use problem, 817 (12.7%) reported ever using xylazine. Among adults reporting recent IMF or heroin use, 443 (8.3%) reported recent xylazine use. Among adults reporting IMF or heroin use recently or as their primary lifetime substance-use problem, those reporting xylazine use reported a median of two past nonfatal overdoses from any drug compared with a median of one overdose among those who did not report xylazine use; as well, higher percentages of persons who reported xylazine use reported other recent substance use and polysubstance use. Provision of nonjudgmental care and services, including naloxone, wound care, and linkage to and retention of persons in effective substance use treatment, might reduce harms including overdose among persons reporting xylazine use., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Expanding access to naloxone through pharmacies is an important policy goal. Our objective was to characterize national county-level naloxone dispensing of chain versus independent pharmacies., Methods: The primary exposure in our longitudinal analysis was the proportion of chain pharmacies in a county, identified through the U.S. Department of Homeland Security 2010 Infrastructure Foundation-Level Data. We defined counties as having "higher proportion" of chain pharmacies if at least 50% of pharmacies were large national chains. The primary outcome was quarter-year (2016Q1-2019Q2) rate of pharmacy naloxone claims per 100,000 persons from Symphony Health at the county level. We compared the naloxone dispensing rate between county types using 2-sample t tests. We estimated the association between county-level chain pharmacy proportion and rate of naloxone claims using a linear model with year-quarter fixed effects., Results: Nearly one-third of counties (n = 946) were higher proportion. Higher proportion counties had a significantly higher rate of naloxone claims across the study period, in 4 of 6 urban-rural classifications, and in counties with and without naloxone access laws (NALs). The linear model confirmed that higher proportion counties had a significantly higher rate of naloxone claims, adjusting for urban-rural designation, income, population characteristics, opioid mortality rate, coprescribing laws, and NALs., Conclusion: In this national study, we found an association between naloxone dispensing rates and the county-level proportion of chain (vs. independent) pharmacies. Incentivizing naloxone dispensing through educational, regulatory, or legal efforts may improve naloxone availability and dispensing rates-particularly in counties with proportionately high numbers of independent pharmacies., Competing Interests: Disclosure The authors declare no relevant conflicts of interest or financial relationships., (Copyright © 2024 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Objectives. To identify relationships between US states' COVID-19 in-person activity limitation and economic support policies and drug overdose deaths among working-age adults in 2020. Methods. We used county-level data on 140 435 drug overdoses among adults aged 25 to 64 years during January 2019 to December 2020 from the National Vital Statistics System and data on states' COVID-19 policies from the Oxford COVID-19 Government Response Tracker to assess US trends in overdose deaths by sex in 3138 counties. Results. Policies limiting in-person activities significantly increased, whereas economic support policies significantly decreased, overdose rates. A 1-unit increase in policies restricting activities predicted a 15% average monthly increase in overdose rates for men (incident rate ratio [IRR] = 1.15; 95% confidence interval [CI] = 1.09, 1.20) and a 14% increase for women (IRR = 1.14; 95% CI = 1.09, 1.20). A 1-unit increase in economic support policies predicted a 3% average monthly decrease for men (IRR = 0.97; 95% CI = 0.95, 1.00) and a 4% decrease for women (IRR = 0.96; 95% CI = 0.93, 0.99). All states' policy combinations are predicted to have increased drug-poisoning mortality. Conclusions. The economic supports that states enacted were insufficient to fully mitigate the adverse relationship between activity limitations and drug overdoses. ( Am J Public Health . 2024;114(7):714-722. https://doi.org/10.2105/AJPH.2024.307621).

Background: Inadequate income is associated with higher likelihood of experiencing a substance use disorder (SUD). This study tests whether the earned income tax credit (EITC), which issues supplemental income for workers with children in the U.S., is associated with lower rates of SUD and fatal overdose., Methods: We examined the effects of state-level refundable EITC presence and generosity (i.e., state EITC rate as a % of federal rate) on SUD-related outcomes (SUD prevalence and intentional and unintentional fatal overdose) using a difference-in-difference methodology, with both two-way fixed-effects models and event study plots. Several sensitivity analyses were conducted to assess the robustness of findings. Five data sources were used to create a combined state-level longitudinal dataset., Results: We did not find significant effects of refundable EITC presence or generosity on unintentional or intentional fatal overdose or SUD prevalence in two-way models. Event study models detected a very slight upward shift in SUD prevalence following refundable EITC implementation (not seen in sensitivity analyses) and no significant effects of EITC implementation on any of the fatal overdose outcomes., Conclusions: Evidence regarding income support programs is being highly sought by policy makers as income support programs have become increasingly popular policy levers since the start of the COVID-19 pandemic. Our study indicates EITC policies likely have no impact on SUD or overdose, however, other income support programs without family restrictions are important to investigate further., Competing Interests: Declaration of Competing Interest No conflict declared., (Copyright © 2024. Published by Elsevier B.V.)

Objectives. To assess heterogeneity in pandemic-period excess fatal overdoses in the United States, by location (state, county) and substance type. Methods. We used seasonal autoregressive integrated moving average (SARIMA) models to estimate counterfactual death counts in the scenario that no pandemic had occurred. Such estimates were subtracted from actual death counts to assess the magnitude of pandemic-period excess mortality between March 2020 and August 2021. Results. Nationwide, we estimated 25 668 (95% prediction interval [PI] = 2811, 48 524) excess overdose deaths. Specifically, 17 of 47 states and 197 of 592 counties analyzed had statistically significant excess overdose-related mortality. West Virginia, Louisiana, Tennessee, Kentucky, and New Mexico had the highest rates (20-37 per 100 000). Nationally, there were 5.7 (95% PI = 1.0, 10.4), 3.1 (95% PI = 2.1, 4.2), and 1.4 (95% PI = 0.5, 2.4) excess deaths per 100 000 involving synthetic opioids, psychostimulants, and alcohol, respectively. Conclusions. The steep increase in overdose-related mortality affected primarily the southern and western United States. We identified synthetic opioids and psychostimulants as the main contributors. Public Health Implications. Characterizing overdose-related excess mortality across locations and substance types is critical for optimal allocation of public health resources. ( Am J Public Health . 2024;114(6):599-609. https://doi.org/10.2105/AJPH.2024.307618).

The high overdose mortality rates in the United States poses several questions: Why have they been increasing exponentially since 1979? Why are they so high? And how can they be greatly reduced? Building on past research, the causes of the increase seem to be deeply rooted in US social and economic structures and processes, rather than due only to opioid prescription patterns or the advent of synthetic opioids. Given this, we consider what changes might be needed to reverse the exponentially-increasing overdose mortality. We use a path dependency argument to argue that the United States political, economic, and public health systems have helped create this crisis and, unfortunately, continue to heighten it. These same systems suggest that proposals to expand harm reduction and drug treatment capacity, to decriminalize or legalize drugs, or to re-industrialize the country sufficiently to reduce "communities of despair" will not be enacted at a scale sufficient to end the overdose crisis. We thus suggest that in the United States serious improvements in overdose rates and related policies and structures require massive social movements with a broad social change agenda., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Importance: Youth (those aged <18 years) parental death has been associated with negative health outcomes. Understanding the burden of parental death due to drug poisoning (herein, drugs) and firearms is essential for informing interventions., Objective: To estimate the incidence of youth parental death due to drugs, firearms, and all other causes., Design, Setting, and Participants: This cross-sectional observational study was conducted using vital registration, including all US decedents, and census data from January 1990 through December 2020. Data were analyzed from May 30, 2023, to March 28, 2024., Exposures: Parental death due to drug poisoning or firearms., Main Outcomes and Measures: A demographic matrix projection model was used to estimate the number and incidence of youth experiencing parental death, defined as the death of 1 or more parents, per 1000 population aged less than 18 years. Analyses evaluated parental deaths by drugs, firearms, and all other causes from 1999 through 2020 by race and ethnicity., Results: Between 1999 and 2020, there were 931 785 drug poisoning deaths and 736 779 firearm-related deaths with a mean (SD) age of 42.6 (16.3) years. Most deaths occurred among males (73.8%) and White decedents (70.8%) followed by Black (17.5%) and Hispanic (9.5%) decedents. An estimated 759 000 (95% CI, 722 000-800 000) youth experienced parental death due to drugs and an estimated 434 000 (95% CI, 409 000-460 000) youth experienced parental death due to firearms, accounting for 17% of all parental deaths. From 1999 to 2020, the estimated number of youth who experienced parental death increased 345% (95% CI, 334%-361%) due to drugs and 39% (95% CI, 37%-41%) due to firearms compared with 24% (95% CI, 23%-25%) due to all other causes. Black youth experienced a disproportionate burden of parental deaths, based primarily on firearm deaths among fathers. In 2020, drugs and firearms accounted for 23% of all parental deaths, double the proportion in 1999 (12%)., Conclusions and Relevance: Results of this modeling study suggest that US youth are at high and increasing risk of experiencing parental death by drugs or firearms. Efforts to stem this problem should prioritize averting drug overdoses and firearm violence, especially among structurally marginalized groups.

Objective: To examine the association between prescriber workforce exit, long term opioid treatment discontinuation, and clinical outcomes., Design: Quasi-experimental difference-in-differences study SETTING: 20% sample of US Medicare beneficiaries, 2011-18., Participants: People receiving long term opioid treatment whose prescriber stopped providing office based patient care or exited the workforce, as in the case of retirement or death (n=48 079), and people whose prescriber did not exit the workforce (n=48 079)., Main Outcomes: Discontinuation from long term opioid treatment, drug overdose, mental health crises, admissions to hospital or emergency department visits, and death. Long term opioid treatment was defined as at least 60 days of opioids per quarter for four consecutive quarters, attributed to the plurality opioid prescriber. A difference-in-differences analysis was used to compare individuals who received long term opioid treatment and who had a prescriber leave the workforce to propensity-matched patients on long term opioid treatment who did not lose a prescriber, before and after prescriber exit., Results: Discontinuation of long term opioid treatment increased from 132 to 229 per 10 000 patients who had prescriber exit from the quarter before to the quarter after exit, compared with 97 to 100 for patients who had a continuation of prescriber (adjusted difference 1.22 percentage points, 95% confidence interval 1.02 to 1.42). In the first quarter after provider exit, when discontinuation rates were highest, a transient but significant elevation was noted between the two groups of patients in suicide attempts (adjusted difference 0.05 percentage points (95% confidence interval 0.01 to 0.09)), opioid or alcohol withdrawal (0.14 (0.01 to 0.27)), and admissions to hospital or emergency department visits (0.04 visits (0.01 to 0.06)). These differences receded after one to two quarters. No significant change in rates of overdose was noted. Across all four quarters after prescriber exit, an increase was reported in the rate of mental health crises (0.39 percentage points (95% confidence interval 0.08 to 0.69)) and opioid or alcohol withdrawal (0.31 (0.014 to 0.58)), but no change was seen for drug overdose (-0.12 (-0.41 to 0.18))., Conclusions: The loss of a prescriber was associated with increased occurrences of discontinuation of long term opioid treatment and transient increases in adverse outcomes, such as suicide attempts, but not other outcomes, such as overdoses. Long term opioid treatment discontinuation may be associated with a temporary period of adverse health impacts after accounting for unobserved confounding., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest and declare: funding from Supported by grants from the Retirement Research Foundation for Aging and the National Institute on Aging; no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Importance: Since 1999, over 1 million people have died of a drug overdose in the US. However, little is known about the bereaved, meaning their family, friends, and acquaintances, and their views on the importance of addiction as a policy priority., Objectives: To quantify the scope of the drug overdose crisis in terms of personal overdose loss (ie, knowing someone who died of a drug overdose) and to assess the policy implications of this loss., Design, Setting, and Participants: This cross-sectional study used data from a nationally representative survey of US adults (age ≥18 years), the fourth wave of the COVID-19 and Life Stressors Impact on Mental Health and Well-Being (CLIMB) study, which was conducted from March to April 2023., Main Outcomes and Measures: Respondents reported whether they knew someone who died of a drug overdose and the nature of their relationship with the decedent(s). They also reported their political party affiliation and rated the importance of addiction as a policy issue. Logistic regression models estimated the associations between sociodemographic characteristics and political party affiliation and the probability of experiencing a personal overdose loss and between the experience of overdose loss and the perceived salience of addiction as a policy issue. Survey weights adjusted for sampling design and nonresponse., Results: Of the 7802 panelists invited to participate, 2479 completed the survey (31.8% response rate); 153 were excluded because they did not know whether they knew someone who died of a drug overdose, resulting in a final analytic sample of 2326 (51.4% female; mean [SD] age, 48.12 [0.48] years). Of these respondents, 32.0% (95% CI, 28.8%-34.3%) reported any personal overdose loss, translating to 82.7 million US adults. A total of 18.9% (95% CI, 17.1%-20.8%) of all respondents, translating to 48.9 million US adults, reported having a family member or close friend die of drug overdose. Personal overdose loss was more prevalent among groups with lower income (<$30 000: 39.9%; ≥$100 000: 26.0%). The experience of overdose loss did not differ across political party groups (Democrat: 29.0%; Republican: 33.0%; independent or none: 34.2%). Experiencing overdose loss was associated with a greater odds of viewing addiction as an extremely or very important policy issue (adjusted odds ratio, 1.37; 95% CI, 1.09-1.72) after adjustment for sociodemographic and geographic characteristics and political party affiliation., Conclusions and Relevance: This cross-sectional study found that 32% of US adults reported knowing someone who died of a drug overdose and that personal overdose loss was associated with greater odds of endorsing addiction as an important policy issue. The findings suggest that mobilization of this group may be an avenue to facilitate greater policy change.

Background: Overdose rates in rural areas have been increasing globally, with large increases in the United States. Few studies, however, have identified correlates of non-fatal overdose among rural people who use drugs (PWUD). The present analysis describes correlates of nonfatal overdose among a large multistate sample of rural PWUD., Methods: This is a cross-sectional analysis of data gathered via surveys with PWUD recruited through seven Rural Opioid Initiative (ROI) sites. Descriptive analyses were conducted to assess the prevalence of past 30-day overdose. Generalized estimating equations were used to estimate a series of multivariable models quantifying relationships of select factors to past-month overdose; factors were selected using the Risk Environment Framework., Results: The multisite sample included 2711 PWUD, 6% of whom reported overdosing in the past 30 days. In the fully adjusted model, houselessness (AOR=2.27, 95%CI[1.48, 3.48]), a positive test result for Hepatitis C infection (AOR=1.73 95%CI[1.18, 2.52]) and heroin/fentanyl use (AOR= 8.58 95%CI [3.01, 24.50]) were associated with an increased risk of reporting past 30-day overdose, while having a high-school education or less was associated with reduced odds of overdose (AOR=0.52, 95% CI[0.37, 0.74])., Conclusion: As in urban areas, houselessness, Hepatitis C infection, and the use of heroin and fentanyl were significant correlates of overdose. Widespread access to overdose prevention interventions - including fentanyl test strips and naloxone - is critical in this rural context, with particular outreach needed to unhoused populations, people living with Hepatitis C, and people using opioids., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: The United States is in the midst of an opioid overdose epidemic; 28.3 per 100,000 people died of opioid overdose in 2020. Simulation models can help understand and address this complex, dynamic, and nonlinear social phenomenon. Using the HEALing Communities Study, aimed at reducing opioid overdoses, and an agent-based model, Simulation of Community-Level Overdose Prevention Strategy, we simulated increases in buprenorphine initiation and retention and naloxone distribution aimed at reducing overdose deaths by 40% in New York Counties., Methods: Our simulations covered 2020-2022. The eight counties contrasted urban or rural and high and low baseline rates of opioid use disorder treatment. The model calibrated agent characteristics for opioid use and use disorder, treatments and treatment access, and fatal and nonfatal overdose. Modeled interventions included increased buprenorphine initiation and retention, and naloxone distribution. We predicted a decrease in the rate of fatal opioid overdose 1 year after intervention, given various modeled intervention scenarios., Results: Counties required unique combinations of modeled interventions to achieve a 40% reduction in overdose deaths. Assuming a 200% increase in naloxone from current levels, high baseline treatment counties achieved a 40% reduction in overdose deaths with a simultaneous 150% increase in buprenorphine initiation. In comparison, low baseline treatment counties required 250-300% increases in buprenorphine initiation coupled with 200-1000% increases in naloxone, depending on the county., Conclusions: Results demonstrate the need for tailored county-level interventions to increase service utilization and reduce overdose deaths, as the modeled impact of interventions depended on the county's experience with past and current interventions., Competing Interests: K.M.K., C.R. and M.C. have received compensation for consultation on behalf of plaintiff counties in the National Prescription Opioid Litigation. Other authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Context: Health plan disenrollment may disrupt chronic or preventive care for patients prescribed long-term opioid therapy (LTOT)., Purpose: To assess whether overdose events in patients prescribed LTOT are associated with subsequent health plan disenrollment., Design: Retrospective cohort study., Setting and Dataset: Data from the Optum Labs Data Warehouse which includes de-identified medical and pharmacy claims and enrollment records for commercial and Medicare Advantage enrollees. The database contains longitudinal health information on patients, representing a mixture of ages and geographical regions across the United States., Patients: Adults prescribed stable opioid therapy (≥10 morphine milligram equivalents/day) for a 6-month baseline period prior to an index opioid prescription from January 1, 2018 to December 31, 2018., Main Measures: Health plan disenrollment during follow-up., Results: The cohort comprised 404,151 patients who were followed up after 800,250 baseline periods of stable opioid dosing. During a mean follow-up of 9.1 months, unadjusted disenrollment rates among primary commercial beneficiaries and Medicare Advantage enrollees were 37.2 and 13.9 per 100 person-years, respectively. Incident overdoses were associated with subsequent health plan disenrollment with a statistically significantly stronger association among primary commercial insurance beneficiaries [adjusted incidence rate ratio (aIRR) 1.48 (95% CI: 1.33-1.64)] as compared to Medicare Advantage enrollees [aIRR 1.15 (95% CI: 1.07-1.23)]., Conclusions: Among patients prescribed long-term opioids, overdose events were strongly associated with subsequent health plan disenrollment, especially among primary commercial insurance beneficiaries. These findings raise concerns about the social consequences of overdose, including potential health insurance loss, which may limit patient access to care at a time of heightened vulnerability., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Fentanyl, a type of opioid, in impaired driving cases increased across cities in the United States., Objectives: No empirical studies have examined motor vehicle overdoses with fentanyl use. We investigated the magnitude of the motor vehicle overdose problem in Providence, RI, and the environmental, socioeconomic, and geographic conditions associated with motor vehicle overdose occurrence., Methods: This was a retrospective observational study of emergency medical services data on all suspected opioid overdoses between January 1, 2017, and October 31, 2020. The data contain forced-choice fields, such as age and biological sex, and an open-ended narrative in which the paramedic documented clinical and situational information. The overdoses were geocoded, allowing for the extraction of sociodemographic data from the U.S. Census Bureau's American Community Survey. Seven other data sources were included in a logistic regression to understand key risk factors and spatial patterns of motor vehicle overdoses., Results: Of the 1,357 opioid overdose cases in this analysis, 15.2% were defined as motor vehicle overdoses. In adjusted models, we found a 61% increase in the odds of a motor vehicle overdose involvement for men versus women, a 16.8% decrease in the odds of a motor vehicle overdose for a one-unit increase in distance to the nearest gas station, and a 10.7% decrease in the odds of a motor vehicle overdose for a one-unit increase in distance to a buprenorphine clinic., Conclusion: There is a need to understand the interaction between drug use in vehicles to design interventions for decreasing driving after illicit drug use., Competing Interests: The authors have no conflicts of interest to report., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Chronic pain has been extensively explored as a risk factor for opioid misuse, resulting in increased focus on opioid prescribing practices for individuals with such conditions. Physical disability sometimes co-occurs with chronic pain but may also represent an independent risk factor for opioid misuse. However, previous research has not disentangled whether disability contributes to risk independent of chronic pain., Methods: Here, we estimate the independent and joint adjusted associations between having a physical disability and co-occurring chronic pain condition at time of Medicaid enrollment on subsequent 18-month risk of incident opioid use disorder (OUD) and non-fatal, unintentional opioid overdose among non-elderly, adult Medicaid beneficiaries (2016-2019)., Results: We find robust evidence that having a physical disability approximately doubles the risk of incident OUD or opioid overdose, and physical disability co-occurring with chronic pain increases the risks approximately sixfold as compared to having neither chronic pain nor disability. In absolute numbers, those with neither a physical disability nor chronic pain condition have a 1.8% adjusted risk of incident OUD over 18 months of follow-up, those with physical disability alone have an 2.9% incident risk, those with chronic pain alone have a 3.6% incident risk, and those with co-occurring physical disability and chronic pain have a 11.1% incident risk., Conclusions: These findings suggest that those with a physical disability should receive increased attention from the medical and healthcare communities to reduce their risk of opioid misuse and attendant negative outcomes.

Background: Opioid overdose was declared a public health emergency in the United States, but much of the focus has been on adults. Child and adolescent exposure and access to unused prescription-opioid medications is a big concern. More research is needed on the trend of pediatric (age 0-17) prescription-opioid overdose emergency department (ED) visits in the United States, particularly during the COVID-19 pandemic year., Methods: This retrospective epidemiological study used the 2008-2020 Nationwide Emergency Department Sample to provide a national estimate of ED visits related to prescription-opioid overdose. Inclusion criteria were 0-17-year-old patients treated at the ED due to prescription-opioid overdose. Eligible visits were identified if their medical records included any administrative billing codes for prescription-opioid overdose. National estimates were broken down by age groups, sex, geographic region, primary payer, median household income by zip code, ED disposition, and hospital location/teaching status. Incidence rate per 100,000 U.S. children was calculated for age groups, sex, and geographic region., Results: Overall, the prescription-opioid overdose ED visits for patients from 0-17 years old in the United States decreased by 22% from 2008 to 2019, then increased by 12% in 2020. Most patients were discharged to home following their ED visit; however, there was a 42% increase in patients admitted from 2019 to 2020. The prescription-opioid overdose rate per 100,000 U.S. children was highest in the 0 to 1 and 12 to 17 age groups, with the 12 to 17 group increasing by 27% in 2020. ED visits in the West and Midwest saw prescription-opioid visits increase by 58% and 20%, respectively, from 2019-2020., Conclusions: Prescription-opioid overdose ED visits among U.S. children and adolescents decreased over the past decade until 2019. However, there was a substantial increase in ED visits from 2019 to 2020, suggesting the potential impact due to the then-emerging COVID-19 pandemic. Findings suggest focusing on young children and adolescents to reduce further prescription-opioid overdoses in the United States., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To examine the association between prescription opioid use trajectories and risk of opioid use disorder (OUD) or overdose among nonmetastatic breast cancer survivors by treatment type., Methods: This retrospective cohort study included female nonmetastatic breast cancer survivors with at least 1 opioid prescription fill in 2010-2019 Surveillance, Epidemiology and End Results linked Medicare data. Opioid mean daily morphine milligram equivalents (MME) calculated within 1.5 years after initiating active breast cancer therapy. Group-based trajectory models identified distinct opioid use trajectory patterns. Risk of time to first OUD/overdose event within 1 year after the trajectory period was calculated for distinct trajectory groups using Cox proportional hazards models. Analyses were stratified by treatment type., Results: Four opioid use trajectories were identified for each treatment group. For 38,030 survivors with systemic endocrine therapy, 3 trajectories were associated with increased OUD/overdose risk compared with early discontinuation: minimal dose (< 5 MME; adjusted hazard ratio [aHR] = 1.73 [95% CI  1.43-2.09]), very low dose (5-25 MME; 2.67 [2.05-3.48]), and moderate dose (51-90 MME; 6.20 [4.69-8.19]). For 9477 survivors with adjuvant chemotherapy, low-dose opioid use was associated with higher OUD/overdose risk (aHR = 7.33 [95% CI 2.52-21.31]) compared with early discontinuation. For 3513 survivors with neoadjuvant chemotherapy, the differences in OUD/OD risks across the 4 trajectories were not significant., Conclusions: Among Medicare nonmetastatic breast cancer survivors receiving systemic endocrine therapy or adjuvant chemotherapy, compared with early discontinuation, low-dose or moderate-dose opioid use were associated with six- to sevenfold higher OUD/overdose risk. Breast cancer survivors at high-risk of OUD/overdose may benefit from targeted interventions (e.g., pain clinic referral)., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: In recent years, stimulant use has increased among persons who use opioids in the rural U.S., leading to high rates of overdose and death. We sought to understand motivations and contexts for stimulant use among persons who use opioids in a large, geographically diverse sample of persons who use drugs (PWUD) in the rural settings., Methods: We conducted semi-structured individual interviews with PWUD at 8 U.S. sites spanning 10 states and 65 counties. Content areas included general substance use, injection drug use, changes in drug use, and harm reduction practices. We used an iterative open-coding process to comprehensively itemize and categorize content shared by participants related to concurrent use., Results: We interviewed 349 PWUD (64% male, mean age 36). Of those discussing current use of stimulants in the context of opioid use (n = 137, 39%), the stimulant most used was methamphetamine (78%) followed by cocaine/crack (26%). Motivations for co-use included: 1) change in drug markets and cost considerations; 2) recreational goals, e.g., seeking stronger effects after heightened opioid tolerance; 3) practical goals, such as a desire to balance or alleviate the effects of the other drug, including the use of stimulants to avoid/reverse opioid overdose, and/or control symptoms of opioid withdrawal; and 4) functional goals, such as being simultaneously energized and pain-free in order to remain productive for employment., Conclusion: In a rural U.S. cohort of PWUD, use of both stimulants and opioids was highly prevalent. Reasons for dual use found in the rural context compared to urban studies included changes in drug availability, functional/productivity goals, and the use of methamphetamine to offset opioid overdose. Education efforts and harm reduction services and treatment, such as access to naloxone, fentanyl test strips, and accessible drug treatment for combined opioid and stimulant use, are urgently needed in the rural U.S. to reduce overdose and other adverse outcomes., (© 2024. The Author(s).)

Background: Overdose deaths in the United States rose substantially during the COVID-19 pandemic. Disruptions to the drug supply and service provision introduced significant instability into the lives of people who use drugs (PWUD), including volatility in their drug use behaviors., Methods: Using data from a multistate survey of PWUD, we examined sociodemographic and drug use correlates of volatile drug use during COVID-19 using multivariable linear regression. In a multivariable logistic regression model, we assessed the association between volatile drug use and past month overdose adjusting for sociodemographic and other drug use characteristics., Results: Among participants, 52% were male, 50% were white, 29% had less than a high school education, and 25% were experiencing homelessness. Indicators of volatile drug use were prevalent: 53% wanted to use more drugs; 45% used more drugs; 43% reported different triggers for drug use, and 23% used drugs that they did not typically use. 14% experienced a past-month overdose. In adjusted models, hunger (β=0.47, 95% CI: 0.21-0.72), transactional sex (β=0.50, 95% CI: 0.06-0.94), and the number of drugs used (β=0.16, 95% CI: 0.07-0.26) were associated with increased volatile drug use. Volatile drug use was associated with increased overdose risk (aOR=1.42, 95% CI: 1.17-1.71) in the adjusted model., Conclusions: Volatile drug use during the COVID-19 pandemic was common, appeared to be driven by structural vulnerability, and was associated with increased overdose risk. Addressing volatile drug use through interventions that ensure structural stability for PWUD and a safer drug supply is essential for mitigating the ongoing overdose crisis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Sherman has served as an expert witness in opioid litigation cases. The authors have no other financial interests/conflicts of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)