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The concurrent use of opioids and alcohol is particularly dangerous for individuals. Alcohol is commonly seen in opioid overdose death toxicology reports and, concurrent use of alcohol and opioids is often reported by individuals across a diverse range of opioid use profiles. This study investigates whether there is a community-level relationship between alcohol sales and opioid-related overdose deaths to inform the situating of harm reduction efforts in spaces most likely to reduce substance-related harms. Using an ecological design, zip code-level data for New Hampshire were combined from the US Census Bureau's American Community Survey (sociodemographics), the National Alcohol Beverage Control Association (alcohol retail sales), and the NH Office of the Chief Medical Examiner (zip code level opioid poisoning deaths) to investigate the relationship between alcohol sales and opioid-related poisoning deaths at a community level in a state with the third highest rate of opioid poisoning deaths for the year the current study represents. Using a spatial error regression model approach, opioid-related poisoning deaths were higher in zip codes with greater population density and on-premise alcohol sales and were lower in zip codes with greater off-premise alcohol sales and area disadvantage. The findings here co-locate higher levels of on-premise alcohol sales and opioid-related poisoning deaths at a community-level, mirroring individual-level findings on the danger of mixing these two substances. Results inform harm reduction approaches by identifying substance use spaces where overdose prevention messaging or policy change may be most effective., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: To assess (I) whether, in autopsy-proven lethal intoxications with opiates/opioids, a dilatation of the common bile duct (CBD) is still visible in postmortem computed tomography (PMCT) and (II) if a dilatation of the CBD might also be measurable for other substance groups (e.g., stimulants, hypnotics, antipsychotics, etc.)., Methods: We retrospectively measured the CBD using PMCT in cases with lethal intoxication ( n = 125) and as a control group in cases with a negative toxicological analysis ( n = 88). Intoxicating substances were classified into the subgroups (opiates, opioids, stimulants, hypnotics, antipsychotics, gasses, and others). Significance between the study and control groups was tested with the Mann-Whitney U test, and correlations were examined by using crosstables., Results: There was a statistically significant difference between the CBD diameters in the intoxication group overall, when compared to the CBD diameter in the control group ( p < 0.001). For both subgroups of "opiates" and "opioids", there was a strong statistically significant difference between the CBD diameter (being wider) in those groups compared to the control group (both p = 0.001). For the three subgroups "hypnotics", "stimulants", and "psychotropic drugs", there was no statistically significant difference between the CBD diameters in the intoxication subgroups when compared with the control group. The other subgroups were too small for statistical analysis., Conclusion: A dilated common bile duct in postmortem computed tomography might be used as an indication for a lethal opioid or opiate intoxication only in regard to the specific case circumstances or together with other indicative findings in a postmortem investigation.

Suicide remains a leading cause of death in the United States, and recent data suggest suicide deaths involving opioids are increasing. Given unprecedented increases in drug-poisoning deaths, suicidality, and suicide deaths in recent years, an updated examination of the trends in suicide deaths involving opioids is warranted. In this descriptive epidemiologic analysis, we leverage final and provisional mortality data from the US Centers for Disease Control and Prevention's WONDER database to examine trends in suicide deaths involving opioid poisoning from 1999 to 2021 by biological sex. Results reveal complex changes over time: the number and age-adjusted rate of suicide deaths involving opioid poisoning among male and female residents tended to track together, and both increased through 2010, but then diverged, with the number and rate of suicide deaths involving opioid poisoning among female residents outpacing that of male residents. However, the number and rate of suicide deaths involving opioid poisoning among male residents then began to stabilize, while that of female residents declined, closing the sex-based gap. Across all years of data, the proportion of suicide deaths that involved opioid poisoning was consistently higher among female decedents (5.8%-11.0%) compared with male decedents (1.4%-2.8%). Findings have implications for improved suicide prevention and harm reduction efforts. This article is part of a Special Collection on Mental Health., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: There is little understanding of the circumstances behind fatal pediatric opioid poisonings. Our objective was to characterize opioid fatalities according to child, family, and household factors., Methods: We used data from the National Fatality Review-Case Reporting System to describe the circumstances behind the deaths of children 0 to 17 years of age who died of an opioid poisoning (ie, prescription opioid, heroin, illicit fentanyl) between 2004 and 2020. Decedents were stratified into age groups: 0-4, 5-9, 10-14, and 15-17 years., Results: The majority (65.3%) of the 1696 fatal opioid poisonings occurred in the child's own home. Prescription opioids contributed to 91.8% of deaths, heroin contributed to 5.4%, and illicit fentanyl to 7.7%. Co-poisonings with nonopioid substances occurred in 43.2% of deaths. Among 0- to 4-year-olds, 33.9% died of homicide and 45.0% had a primary caregiver with a history of substance use/abuse. Among 10- to 14-year-olds and 15- to 17-year-olds, respectively, 42.0% and 72.8% of decedents had a history of substance use/abuse. In each age group, at least 25.0% of children were victims of previous child maltreatment., Conclusions: A history of maltreatment and substance use-whether on the part of the caregiver or the child-are common factors surrounding fatal pediatric opioid poisonings, the majority of which occur in the child's own home. Families with children of all ages would benefit from interventions focused on opioid prescribing, storage, disposal, and misuse. These findings also underscore the urgency of ensuring that access to naloxone becomes universal for families with a history of maltreatment and/or substance use., Competing Interests: CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2024 by the American Academy of Pediatrics.)

Across much of Canada, opioid poisoning deaths have been increasing due to a toxic, contaminated, and unpredictable drug supply. Multiple prescribed safer supply pilot projects are being implemented and evaluated in an attempt to save lives. In the province of Alberta, however, new regulations introduced in 2022 significantly constrain safer supply prescribing by banning the prescription, dispensing, and administration of safer supply outside of a very limited number of clinics. In this commentary, we review prescribed safer supply programs in Canada and outline how the Alberta Government's change in regulations conflict with emerging evidence and efforts by other jurisdictions to address the rising opioid poisoning deaths. We examine the development of these regulations and analyze how the Alberta government shaped and justified this restrictive policy. We conclude by identifying important lessons learned from the experience in Alberta for researchers, healthcare providers, and decisionmakers in other jurisdictions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Elaine Hyshka previously served in two (unpaid) scientific advisory roles relevant to this paper: Co-Chair Alberta Minister of Health's Opioid Emergency Response Commission; and Co-Chair, Health Canada's Expert Advisory Group on Safer Supply. She also reports receiving peer-reviewed research funding from the Canadian Institutes of Health Research to evaluate aspects of safer supply programs, and travel costs from the National Safer Supply Community of Practice to attend a scientific meeting. Kate Colizza received travel costs from the National Safer Supply Community of Practice to attend a scientific meeting. Patty Wilson received travel costs from the National Safer Supply Community of Practice to attend a scientific meeting., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: The objective of this study was to update and expand on previous studies of opioid exposures among young children reported to America's Poison Centers®, and to describe how fentanyl and medications for opioid use disorder have contributed., Methods: This retrospective study investigated 34,632 reports of single-substance opioid exposure from 2016 to 2023 involving pediatric patients aged one month to six years old. Descriptive statistics, tests for data normality, and significance testing were performed where applicable., Results: Of 34,632 reported exposures, 96.7% were unintentional. The median age of exposure was 2.0 years (IQR 1.33-3.0 years). Reported exposures decreased by 57.5% over the study period ( r  = -0.96; P  <0.001). However, there was a 300% absolute increase in deaths and major effects ( r  = 0.96; P  <0.001). Exposures resulting in minor, no effect, not followed, or unable to follow decreased 66.2% ( r  = -0.99; P  <0.001). Buprenorphine was most frequently involved, comprising 23.4% of reported exposures. Buprenorphine (OR 1.93; P  <0.001) and methadone (OR 14.98; P  <0.001) were associated with an increased risk of severe effects when compared to other prescription drugs (OR: 1). There was an absolute increase of 512% over time in reports of heroin, fentanyl, synthetic non-pharmaceutical opioids ( r  = 0.92; P  <0.001), which were also associated with severe effects (OR 20.1; P  <0.001)., Discussion: Pediatric opioid exposures have previously been reported to be relatively stable. It is likely the 57.5% reduction is exaggerated due to underreporting from health care providers. However, decreases in exposures are presumed to be balanced throughout the dataset and, therefore, without differential impact on other points of analysis. Our study highlights the continued need for enhanced poisoning prevention strategies., Conclusions: The relative severity of poisonings reported to poison centers worsened over the study period. The opioids implicated have shifted away from hydrocodone, oxycodone, and tramadol, and towards fentanyl and buprenorphine.

Objective: To describe analgesic-related deaths in France and report trends over a 10-year period., Study Design: The DTA ("Décès Toxiques par Antalgiques") register is a French database of analgesic-related deaths among people without a history of drug abuse, reported by forensic toxicology experts., Methods: We included analgesic-related deaths occurring from January 2013 to December 2022 in France. Subject demographic characteristics and medical history, forensic autopsy findings, and toxicology reports were evaluated., Results: Among the 1036 deceased individuals (mean [SD] age, 48.3 [15.6] years), there were slightly more women than men (M:F sex ratio, 0.89:1). Over the entire study period, tramadol was the leading cause of death, ahead of morphine. A relative increase in oxycodone-related mortality was observed (from 6.8% in 2013 to 21.1% in 2022) compared to a progressive decrease in tramadol, morphine, and codeine-related deaths (from 43.2%, 31.1% and 24.3% in 2013 to 37.5%, 26.6% and 20.3% in 2022, respectively). However, no statistically significant variations were found (Chi-squared tests of homogeneity). Other analgesics (buprenorphine, dihydrocodeine, fentanyl, gabapentin, ketamine, methadone, nefopam, and pregabalin) were also implicated in deaths, but with low and stable rates over the period studied., Conclusions: In France, no increase in fentanyl-related deaths and only a non-significant increase in oxycodone-related deaths were observed over the period 2013-2022. Tramadol was the leading cause of analgesic-related deaths throughout this period. Although close monitoring is still required, particularly for oxycodone, our data do not support the hypothesis of an opioid crisis in France., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

High dose and long-acting opioid overdose reversal drugs can precipitate withdrawal in people who are opioid dependent. Products recently brought to market for community use in the United States (US) have drawn international concern because of their increased risk of withdrawal. At the March 18-19, 2024, Compassionate Overdose Response Summit & Naloxone Dosing Meeting, a panel of harm reduction experts issued the following call to action: 1) people who use drugs should be directly involved in decisions regarding the research, development, selection, and distribution of opioid overdose reversal products; 2) regulatory agencies and pharmaceutical manufacturers should carefully consider and communicate the risk and duration of withdrawal associated with higher dose and longer-acting opioid antagonists; 3) take-home naloxone kits should include at least two doses of an intramuscular (IM) product containing 0.4 mg or an intranasal (IN) product containing ≤4 mg; 4) At this time, high dose and long-acting opioid antagonists have no use in acute opioid overdose response; and, 5) overdose response educational materials, instructions on overdose response, and training should emphasize the restoration of breathing, avoiding withdrawal, and compassionate post-overdose support and care. High dose and long-acting opioid overdose reversal drugs were approved without testing for withdrawal and are often aggressively marketed despite decades of evidence from naloxone distribution programs worldwide that the ideal dose of naloxone is one that restores breathing without inducing withdrawal. Government agencies should direct resources to harm reduction programs to make standard dose take-home naloxone products widely available among people who use drugs. Lay bystanders, people who use drugs, their families, and professional first responders can learn and apply a compassionate approach to opioid overdose response., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: 1. Erin Russell discloses that Harm Reduction Therapeutics is a client of Health Management Associates. HRT is a nonprofit organization based in the United States that manufactures a 3 mg naloxone nasal spray product. 2. In the last three years, Joanne Neale has secured, through her university, research funding from Mundipharma Research Ltd (for research on naloxone) and Camurus AB (for research on long-acting injectable buprenorphine). She has also received honoraria from Indivior and Camurus AB for presentations and from Figure 8 Consultancy Ltd for research advice on a study of residential rehabilitation., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In 2023, 3651 Ohioans died because of an opioid overdose. Of those opioid overdoses, 3579 (98%) of which were attributed to fentanyl. We evaluated the association between 180 candidate single nucleotide polymorphisms (SNPs) and self-reported, nonfatal opioid overdose history from a prospective sample of 1301 adult patients (≥18 years of age) seen in three urban emergency departments in Ohio. Candidate SNPs included 120 related to the dopamine reward pathway and 60 related to pharmacokinetics. Of the 821 patients who reported having been exposed to opioids in their lifetime, 95 (11.6%) also reported having experienced an opioid-related overdose. Logistic regression, adjusting for age and biologic sex, was used to characterize the association between each SNP and opioid overdose, correcting for multiple comparisons. Three SNPs, located in three different genes were associated with opioid overdose: increased odds with CYP3A5 (rs776746) and DRD2 (rs4436578), and decreased odds with NKIR (rs6715729). Homozygotic CYP3A5 (rs776746) had the highest adjusted odds ratio (OR) of 6.96 (95% CI [2.45, 29.23]) and homozygotic NK1R (rs6715729) had the lowest OR of 0.28 (95% CI [0.14, 0.54). Given that CYP3A5 (rs776746) has been associated with increased plasma concentrations of fentanyl, rs776746 could potentially be utilized as a prognostic risk indicator for the potential of an opioid overdose. NK1R regulates the expression of the neurokinin-1 receptor, a regulator of respiration and NK1R (rs6715729) represents a novel genetic marker for a decreased risk of opioid overdose risk., 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

Among the emerging investigative fields, forensic medicine and toxicology lead to analyzing fatalities in medico-legal expert opinion formulating. While discussing the problem, the authors have selected 96 fatal cases from their expert practice including the period from 2010 to 2023, in which deaths were connected with taking new psychoactive substances (NPS's) belonging to various chemical categories, mainly synthetic cathinones (SC), synthetic cannabinoids (SCan) and non-medical synthetic opioids (NSO). In the investigated cases, toxicological analysis revealed 37 NPS's and their 9 metabolites. The cases involved the use of SC's (64 cases - 67 %), Scan's, including their metabolites (10 cases - 10 %) and NSO's, including their metabolites (6 cases - 6 %). The remaining cases involved the simultaneous use of NSO with SC and/or SCan, including their metabolites (8 cases - 8 %), or SC with SCan (5 cases - 5 %). In three cases (3 %), compounds belonging to other groups were taken. In twenty-five cases, more than one NPS was found. Moreover, in twenty-seven cases, ethyl alcohol was also detected at the concentration range of 0.6-3.6 ‰. The concentration of xenobiotics determined in blood represented extensive ranges of concentration. The victims were at the age of 16-58 years of life. The group included eleven women (11 %). Generally, the deaths related to NPS's were predominantly of an accidental character (81 %), while the manner of death in sixteen cases (17 %) was suicide, including hanging (5 cases), jumping from a great height (3 cases), self-injury and exsanguination (1 case), as well as acute drug intoxication (6 cases) and intoxication with central nervous system hypoxia after an hanging (1 case). Among the analyzed cases there were two victims of homicide (2 %), in one of which the perpetrator being under the influence of the mixture of the synthetic opioid U-47700 and synthetic cannabinoid AB-FUBINACA. In twenty-eight cases, medications used in psychiatry were found, which suggested that the victims were struggling with mental problems before death. As it was implied by the available information, more than 36 % of the victims had mental problems., 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 The Authors. Published by Elsevier B.V. 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.)

We studied opioid agonist treatment (OAT) status before buprenorphine-related death in Finland, where buprenorphine is the principal OAT medicine and also the most misused opioid, through a retrospective population-based study using medico-legal cause-of-death investigation and OAT patient records. The study included all death cases (N = 570) between 2018 and 2020 with a buprenorphine or norbuprenorphine finding in post-mortem toxicology and with known drug misuse history or concomitant findings of illicit drugs. Of the deceased, 10% had received OAT in the year before death. Less than 1% of individuals < 25 years had received OAT, whereas the proportion in individuals ≥ 25 years was 13% (p < 0.001). There were significantly more females and more fatal poisonings (p < 0.001) among those < 25 years than among those ≥ 25 years. OAT medication at the time of death was sublingual buprenorphine-naloxone in 74% and subcutaneous buprenorphine in 23%. Except for significantly fewer benzodiazepine findings among those receiving OAT, minimal differences were found in terms of age, gender, cause and manner of death, or concomitant substance use between the deceased in and outside of OAT. Concomitant misuse of benzodiazepines, psychostimulants, alcohol, and gabapentinoids was frequent both in and outside of OAT and likely contributed to the death. These results suggest that access to OAT especially for young people and treatment of multiple addictions should be improved. Comprehensive information from medico-legal cause-of-death investigation as a starting point, combined with subsequent ante-mortem patient records, proved to be a successful approach to shed light on the Finnish scene of buprenorphine mortality., (© 2024. The Author(s).)

Introduction: This study aimed to assess the impact of the implementation of legally sanctioned supervised consumption sites (SCS) in the Canadian province of Ontario on opioid-related deaths, emergency department (ED) visits and hospitalisations at the public health unit (PHU) level., Methods: Monthly rates per 100,000 population of opioid-related deaths, ED visits and hospitalisations for PHUs in Ontario between December 2013 and March 2022 were collected. Aggregated and individual analyses of PHUs with one or more SCS were conducted, with PHUs that instituted an SCS being matched to control units that did not. Autoregressive integrated moving average models were used to estimate the impact of SCS implementation on opioid-related deaths, ED visits and hospitalisations., Results: Twenty-one legally sanctioned SCS were implemented across nine PHUs in Ontario during the study period. Interrupted time series analyses showed no statistically significant changes in opioid-related death rates in aggregated analyses of intervention PHUs (increase of 0.02 deaths/100,000 population/month; p = 0.27). Control PHUs saw a significant increase of 0.38 deaths/100,000 population/month; p < 0.001. No statistically significant changes were observed in the rates of opioid-related ED visits in intervention PHUs (decrease of 0.61 visits/100,000 population/month; p = 0.39) or controls (increase of 0.403 visits; p = 0.76). No statistically significant changes to the rates of opioid-related hospitalisations were observed in intervention PHUs (0 hospitalisations/100,000 population/month; p = 0.98) or controls (decrease of 0.05 hospitalisations; p = 0.95)., Discussion and Conclusions: This study did not find significant mortality or morbidity effects associated with SCS availability at the population level in Ontario. In the context of a highly toxic drug supply, additional interventions will be required to reduce opioid-related harms., (© 2024 The Author(s). Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

Objective: To evaluate a decade of reported paediatric opioid poisoning cases in the UK., Methods: The National Poisons Information Service (NPIS) telephone enquiries database (UK Poisons Information Database) was searched for calls regarding opioid poisoning in children under 18 years from 2012 to 2021. The NPIS online clinical guidance database TOXBASE was searched for accesses relating to opioids for both adults and children. The Office of National Statistics provided paediatric data for hospital admissions and deaths in those aged under 20 years old due to opioids., Results: The NPIS received 426 774 telephone enquiries from 2012 to 2021 from across the UK, 3600 in relation to opioid exposures regarding children under 18 years. Annual telephone enquiries regarding paediatric opiate poisoning reduced year on year, from around 450 to 300 calls/year. A rise in all age TOXBASE annual accesses relating to opioids from 71 642 in 2012 to 87 498 in 2021 was noted, a total of 838 455 during the study period. Hospital admissions from opioid poisoning remained consistent, with around 1500 admissions/year. Deaths were uncommon, but averaged 18 deaths annually. Co-codamol was the most reported substance to NPIS, with 1193 calls (36.5%), followed by codeine with 935 (26.1%)., Conclusions: Opioid poisoning in children is not uncommon. There is a general downward trend in telephone enquiries to NPIS, but many childhood exposures may have been dealt with through consultations via TOXBASE, where accesses relating to opioids have increased. Unfortunately, children still die from opioid exposure each year in the UK and this figure has changed little during 2012-2021., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: The HEALing Communities Study (HCS) evaluated the effectiveness of the Communities That HEAL (CTH) intervention in preventing fatal overdoses amidst the US opioid epidemic., Objective: To evaluate the impact of the CTH intervention on total drug overdose deaths and overdose deaths involving combinations of opioids with psychostimulants or benzodiazepines., Design, Setting, and Participants: This randomized clinical trial was a parallel-arm, multisite, community-randomized, open, and waitlisted controlled comparison trial of communities in 4 US states between 2020 and 2023. Eligible communities were those reporting high opioid overdose fatality rates in Kentucky, Massachusetts, New York, and Ohio. Covariate constrained randomization stratified by state allocated communities to the intervention or control group. Trial groups were balanced by urban or rural classification, 2016-2017 fatal opioid overdose rate, and community population. Data analysis was completed by December 2023., Intervention: Increased overdose education and naloxone distribution, treatment with medications for opioid use disorder, safer opioid prescribing practices, and communication campaigns to mitigate stigma and drive demand for evidence-based interventions., Main Outcomes and Measures: The primary outcome was the number of drug overdose deaths among adults (aged 18 years or older), with secondary outcomes of overdose deaths involving specific opioid-involved drug combinations from death certificates. Rates of overdose deaths per 100 000 adult community residents in intervention and control communities from July 2021 to June 2022 were compared with analyses performed in 2023., Results: In 67 participating communities (34 in the intervention group, 33 in the control group) and including 8 211 506 participants (4 251 903 female [51.8%]; 1 273 394 Black [15.5%], 603 983 Hispanic [7.4%], 5 979 602 White [72.8%], 354 527 other [4.3%]), the average rate of overdose deaths involving all substances was 57.6 per 100 000 population in the intervention group and 61.2 per 100 000 population in the control group. This was not a statistically significant difference (adjusted rate ratio [aRR], 0.92; 95% CI, 0.78-1.07; P = .26). There was a statistically significant 37% reduction (aRR, 0.63; 95% CI, 0.44-0.91; P = .02) in death rates involving an opioid and psychostimulants (other than cocaine), and nonsignificant reductions in overdose deaths for an opioid with cocaine (6%) and an opioid with benzodiazepine (1%)., Conclusion and Relevance: In this clinical trial of the CTH intervention, death rates involving an opioid and noncocaine psychostimulant were reduced; total deaths did not differ statistically. Community-focused data-driven interventions that scale up evidence-based practices with communications campaigns may effectively reduce some opioid-involved polysubstance overdose deaths., Trial Registration: ClinicalTrials.gov Identifier: NCT04111939.

Introduction: Naloxone is an effective antidote, but its short half-life means repeated doses, and infusions are often required. We investigated the effectiveness of adding intramuscular naloxone to titrated intravenous naloxone in opioid overdose in preventing recurrence of respiratory depression., Methods: This double-blinded randomised placebo-controlled trial was conducted in patients with suspected opioid poisoning and respiratory depression (respiratory rate <10 breaths/min or oxygen saturation <93%). Patients were randomised to receive either intramuscular naloxone 1,600 µg or saline placebo. All patients received titrated intravenous naloxone 100 µg and were managed on an opioid poisoning care pathway. The primary outcome was recurrence of respiratory depression within 4 h. Secondary outcomes were the proportion receiving naloxone infusions, number of naloxone boluses administered, reversal of respiratory depression at 10 min, and precipitation of opioid withdrawal (any symptom)., Results: Recurrence of respiratory depression within 4 h was less common in 28/69 (41%) patients receiving intramuscular naloxone versus 48/67 (72%) patients receiving placebo (difference 31%, 95% CI: 13-46%; P  < 0.001). Fewer naloxone infusions (5/69; 7% versus 25/67; 37%, difference 30%, 95% CI: 15 to 55%; P  < 0.001) and fewer naloxone doses were administered (median 2, IQR: 1 to 5, versus median 5, IQR: 2 to 8; P  = 0.001) in the intramuscular group. Reversal of respiratory depression at 10 min was similar between groups (51/69; 74% intramuscular naloxone versus 47/67; 70% placebo; P  = 0.703). Opioid withdrawal occurred in 35/69 (51%) given intramuscular naloxone compared to 28/67 (42%) in the placebo group (difference 9%; 95% CI: -8 to 27%; P  = 0.308)., Discussion: The favourable pharmacokinetics of intramuscular naloxone, particularly its longer duration of activity, likely explains the improved effectiveness with lower recurrence of respiratory depression., Conclusion: The addition of intramuscular naloxone 1,600 µg to titrated intravenous naloxone prolonged effective reversal of respiratory depression, with fewer naloxone doses and infusions given, and no significant difference in patients developing withdrawal.

Background: Our goal in this report was to quantify the degree to which opioid prescription rates and socioeconomic correlates of income inequality predicted overdose deaths in the 1055 U.S. Midwest counties. The study follows up a state-level analysis which reported that opioid prescription rates, social capital and unemployment explained much of the variance in opioid overdose death rates (Heyman, McVicar, & Brownell, 2019)., Methods: We created a data set that included drug overdose death rates, opioid prescription rates, and correlates of income inequality. Given that the variables of interest varied at the state and county level, multilevel regression was our statistical approach., Results: From 2006 to 2021, Midwest overdose drug deaths increased according to an exponential equation that closely approximated the equation that describes the increases in overdose deaths for the entire U.S. from 1978 to 2016 (e.g., Jalal et al., 2018). Retail opioid prescription sales increased from 2006 to 2012, but then declined so that by 2017 they were lower than in 2006. The regression analyses revealed that intergenerational income mobility was the strongest predictor of overdose deaths. The other consistently statistically significant predictors were opioid prescription rates, social capital, and unemployment rates. Together these predictors, plus pupil teacher ratios, single parent families, and attending college accounted for approximately 47 % of the variance in overdose death rates each year. In keeping with the decline in opioid prescription rates, the explanatory power of opioid prescription rates weakened over the course of the study., Conclusions: Overdose deaths increased at a constant exponential rate for the years that it was possible to apply our regression model. This occurred even though access to legal opioids decreased. What remained invariant was the predictive strength of intergenerational income mobility; each year it was the predictor that explained the most variance in overdose deaths., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Understanding opioid overdose risk perception may inform overdose prevention strategies., Methods: We used baseline data from a randomized overdose prevention trial, in San Francisco, CA, and Boston, MA, among people who used nonprescribed opioids, survived an overdose in the past 3 years, and had received naloxone. Participants were asked how likely they were to overdose in the next 4 months. We combined "extremely likely" and "likely" (higher risk perception) and "neutral," "unlikely," and "extremely unlikely" (lower risk perception). We performed bivariate analyses and separate multivariable logistic regression models of risk perception across (1) sociodemographic, (2) substance use, and (3) overdose risk behavior measures. Covariates were selected a priori or significant in bivariate analyses., Results: Among 268 participants, 88% reported at least 1 overdose risk behavior; however, only 21% reported higher risk perception. The adjusted odds ratio (AOR) of higher risk perception was 2.41 (95% confidence interval [CI]: 1.10-5.30) among those unhoused in the past 4 months, 2.06 (95% CI: 1.05-4.05) among those using opioids in a new place, and 5.61 (95% CI: 2.82-11.16) among those who had overdosed in the past 4 months. Living in Boston was associated with higher risk perception in all 3 models (AOR = 2.00-2.46, 95% CI: 1.04-4.88)., Conclusions: Despite prevalent risk behaviors, a minority of participants perceived themselves to be at higher risk of overdose. Nonetheless, some known risk factors for overdose were appropriately associated with risk perception. Fentanyl has been prevalent in Boston for longer than San Francisco, which may explain the higher risk perception there., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The Veterans Health Administration (VA) implemented academic detailing (AD) to support safer opioid prescribing and overdose prevention initiatives., Methods: Patient-level data were extracted monthly from VA's electronic health record to evaluate whether AD implementation was associated with changes in all-cause mortality, opioid poisoning inpatient admissions, and opioid poisoning emergency department (ED) visits in an observational cohort of patients with long-term opioid prescriptions (≥45-day supply of opioids 6 months prior to a given month with ≤15 days between prescriptions). A single-group interrupted time series analysis using segmented logistic regression for mortality and Poisson regression for counts of inpatient admissions and ED visits was used to identify whether the level and slope of these outcomes changed in response to AD implementation., Results: Among 955 376 unique patients (19 431 241 person-months), there were 53 369 deaths (29 025 pre-AD; 24 344 post-AD), 1927 opioid poisoning inpatient admissions (610 pre-AD; 1317 post-AD), and 408 opioid poisoning ED visits (207 pre-AD; 201 post-AD). Immediately after AD implementation, there was a 5.8% reduction in the odds of all-cause mortality (95% confidence interval [CI]: 0.897, 0.990). However, patients had a significantly increased incidence rate of inpatient admissions for opioid poisoning immediately after AD implementation (incidence rate ratio = 1.523; 95% CI: 1.118, 2.077). No significant differences in ED visits for opioid poisoning were observed., Conclusions: AD was associated with decreased all-cause mortality but increased inpatient hospitalization for opioid poisoning among patients prescribed long-term opioids. Mechanisms via which AD's efforts influenced opioid-related outcomes should be explored., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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).

Objective: Rates of death due to homicide, suicide and overdose during pregnancy and the first year postpartum have increased substantially in the USA in recent years. The aims of this study were to use 2018-2019 data on deaths identified for review by the North Carolina Maternal Mortality Review Committee (NC-MMRC), data from the North Carolina Violent Death Reporting System (NC-VDRS) and data from the Statewide Unintentional Drug Overdose Reporting System (NC-SUDORS) to examine homicide, suicide and unintentional opioid-involved overdose deaths during pregnancy and the first year postpartum., Methods: We linked data from the 2018-2019 NC-MMRC to suicide and homicide deaths among women ages 10-50 years from the 2018-2019 NC-VDRS and to unintentional opioid-involved overdose deaths among women ages 10-50 years from the 2018-2019 NC-SUDORS. We conducted descriptive analyses to examine the prevalence of demographic characteristics and the circumstances surrounding each cause of death., Results: From 2018 to 2019 in North Carolina, there were 23 homicides, nine suicides and 36 unintentional opioid-involved overdose deaths (9.7, 3.8 and 15.1 per 100 000 live births, respectively) during pregnancy and the first year postpartum. Most homicide deaths (87.0%) were by firearm, and more than half (52.5%) were related to intimate partner violence. More than two-thirds of women who died by suicide had a current mental health problem (77.8%). Less than one-fourth (22.2%) of those who died by unintentional opioid-involved overdose had a known history of substance use disorder treatment., Conclusion: Our approach to quantifying and describing these causes of pregnancy-associated death can serve as a framework for other states to inform data-driven prevention., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The opioid crisis is a serious public health issue in Canada. There have been many surveillance programs and research studies on opioid-related emergency department (ED) visits at a national, provincial, regional or municipal level. However, no published studies have investigated the in-depth contexts surrounding opioid-related ED visits. In addition, few studies have examined injuries other than poisonings in those visits. The objective of this study is to investigate the contextual factors and co-occurrence of poisonings and injuries among the opioid-related ED visits in a Canadian sentinel surveillance system on injuries and poisonings from 2011 to 2022., Methods: This study used a mixed methods design. The data source was the Canadian Hospitals Injury Reporting and Prevention Program. We first selected all opioid-related ED visits during our study period and then identified the contextual factors through a content analysis of the combination of the narrative description and other variables in the patients' records. The contextual factors were organized into themes as opioid use context, social resource utilization, bystander involvement, and prior naloxone use. The opioid use context was used as a co-variable to examine the other themes and ED presentations (poisonings and other injuries). Quantitative descriptive approach was used to analyze all the contexts and ED presentations., Results: The most common opioid use context was non-prescribed opioid use without intention to cause harm, followed by self-poisoning, children's exposure, and medication error. Various rare contexts occurred. Paramedics participated in 27.9% of visits. Police and security guards were involved in 5.1% and 2.3% of visits, respectively. Child welfare or social workers were involved in 0.4% of visits. Bystanders initiated 18.9% of the ED visits. Naloxone use before arriving at the ED occurred in 23.4% of the visits with a variety of administrators. The majority of patients presented with poisoning effects, either with poisoning effects only or with other injuries or conditions., Conclusions: Our study has provided an in-depth analysis of contextual factors and co-occurrence of poisonings and injuries among opioid-related ED visits in Canada. This information is important for ED programming and opioid-related poisoning and injury intervention and prevention., (© 2024. Crown.)

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.)

Importance: With the implementation of Measure 110 (M110) in 2021, Oregon became the first US state to decriminalize small amounts of any drug for personal use. To date, no analysis of the association of this law with overdose mortality has fully accounted for the introduction of fentanyl-a substance that is known to drive fatal overdose-to Oregon's unregulated drug market., Objective: To evaluate whether the decriminalization of drug possession in Oregon was associated with changes in fatal drug overdose rates after accounting for the rapid spread of fentanyl in Oregon's unregulated drug market., Design, Setting, and Participants: In this cohort study, the association between fatal overdose and enactment of M110 was analyzed using a matrix completion synthetic control method. The control group consisted of the 48 US states and Washington, DC, all of which did not decriminalize drugs. The rapid spread of fentanyl in unregulated drug markets was determined using the state-level percentage of all samples reported to the National Forensic Laboratory Information System that were identified as fentanyl or its analogues. Mortality data were obtained from the Centers for Disease Control and Prevention for January 1, 2008, to December 31, 2022. Data analysis was performed from fall 2023 through spring 2024., Exposures: Measure 110 took effect in Oregon on February 1, 2021., Main Outcomes and Measures: The primary outcome assessed was fatal drug overdose rates per half-year. A changepoint analysis also determined when each state experienced a rapid escalation of fentanyl in its unregulated drug market., Results: In this analysis, rapid spread of fentanyl in Oregon's unregulated drug supply occurred in the first half of 2021, contemporaneous with enactment of M110. A positive crude association was found between drug decriminalization and fatal overdose rate per 100 000 per half year (estimate [SE], 1.83 [0.47]; P < .001). After adjusting for the spread of fentanyl as a confounder, the effect size changed signs (estimate [SE], -0.51 [0.61]; P = .41) and there was no longer an association between decriminalization and overdose mortality in Oregon. Sensitivity analyses were consistent with this result., Conclusions and Relevance: In this cohort study of fatal drug overdose and the spread of fentanyl through Oregon's unregulated drug market, no association between M110 and fatal overdose rates was observed. Future evaluations of the health effects of drug policies should account for changes in the composition of unregulated drug markets.

Background/objective: Opioid overdose deaths have been on the rise in the last two decades in the United States, yet the economic burden remains unclear. Although prior studies have assessed the economic impact of total overdose deaths at a regional level, there remains a paucity of information surrounding the financial burden due to specific types of opioids on a national level. This analysis aims to examine the economic burden of the opioid overdose crisis by quantifying years of potential lives lost (YPLL) due to premature mortality and the value of those statistical lives (VSL) to estimate monetary losses., Methods: Death counts for overdose deaths due to fentanyl, hydrocodone, hydromorphone, oxycodone, and oxymorphone from 2018 to 2020 were obtained from the National Vitals Statistics System. Period life expectancy was extracted from the Social Security Administration. Resultant YPLL and VSL were then calculated., Results: Fentanyl accounted for an overwhelming proportion of opioid-induced deaths (77 percent of deaths in 2018 and 86 percent in 2020 resulting in 2.2 million YPLL and USD 527 billion in financial losses). The largest percentage of overdose deaths from fentanyl and oxymorphone occurred in the 25-34 age range; nearly two-thirds of all fatalities were men. There was also a significant increase in the number of opioid overdose deaths in the year 2020, compared to prior years., Conclusions: Our analysis suggests that fentanyl contributed a significant proportion of economic losses in this public health crisis. Understanding the distribution of opioid deaths by drug type and subsequent economic losses could guide targeted intervention strategies.

Abstract: Death due to fentanyl and its various analogs has resulted in an exponential rise in deaths throughout the United States, overwhelming many medical examiner offices for over a decade. Its potency and prevalence have caused fentanyl to become the most reported substance in overdose fatalities, with an accompanying increase in exposure of the most vulnerable, infants and children. This report provides information about fentanyl in the pediatric population, including case examples, proposed investigative practices, published therapeutic and lethal blood concentrations, and available resources for future cases. Nine cases of pediatric death between 2013 and 2023 due to fentanyl were reviewed. Five case summaries are presented that highlight classic features of fentanyl deaths in infants, children, and teenagers. Deaths due to fentanyl have continued to rise year after year. Infants and children, most of whom are opioid naive, are at ever increased risk for exposure to high levels of fentanyl. The legal ramifications of a positive fentanyl level in a child increase the need for caution on the part of the forensic pathologist. Understanding what can and cannot be proven by autopsy as well as what resources are available to strengthen one's justification for fentanyl being the primary cause of death is critical., Competing Interests: The authors report no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: We aimed to describe rates and toxicological findings of unintentional opioid and stimulant toxicity deaths, 2012-2021., Methods: The dataset included accidental deaths determined by the Coroner to be due to opioids or stimulants. We calculated annual crude mortality rates and described combinations of drugs identified in toxicological examinations of these deaths. We described temporal trends in the detection of specific opioids, stimulants, benzodiazepines (including novel benzodiazepines), gabapentinoids and z-drugs in deaths due to opioids and stimulants., Results: Mortality rates increased over time, reaching their peak in 2020 and remaining high in 2021. In deaths due to opioids, there was a decline in the proportion of deaths involving pharmaceutical opioids after 2019, and a corresponding increase in the proportion of deaths with fentanyl detected. Benzodiazepines were often present in deaths due to opioids, with novel benzodiazepines increasing rapidly from 2019 onwards. Cocaine was the most frequently detected drug in deaths due to stimulants, but amphetamine/methamphetamine was detected in around half of all stimulant deaths from 2016 onwards., Discussion and Conclusions: Despite availability of a multitude of overdose prevention interventions, mortality rates due to drug toxicity have increased in Québec. Toxicological findings of these deaths suggest concerning shifts in the illicit drug market, with Québec potentially having entered a new era of elevated overdose mortality. Intervention scale-up is essential, but unlikely to be sufficient, to reduce drug-related mortality. Policy reform to address the root causes of drug toxicity deaths, including an unpredictable drug supply, strained health systems and socio-economic precarity, is essential., (© 2024 The Author(s). Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

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.)

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.

Objectives: Previous reports have described variations in opioid overdose mortalities among different race/ethnicity groups. We have analyzed racial/ethnicity trends in opioid and polysubstance opioid overdose mortalities in adolescents and young adults to further characterize differences and potential sub-epidemics within this specific population., Methods: We used mortality data from the U.S. Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (WONDER) Multiple Cause of Death file from 1999 to 2020. Drug overdose mortalities were identified using International Classification of Diseases, Tenth Revision (ICD-10) codes. Joinpoint regression was used to examine mortality rates for all opioids, opioids with a stimulant, opioids with benzodiazepines, and opioids with alcohol among racial/ethnic groups (non-Hispanic white, non-Hispanic Black, Hispanic, non-Hispanic other) in adolescents and young adults., Results: The Average Annual Percent Change (AAPC) for mortality due to opioid and polysubstance opioid overdose increased for all racial/ethnic groups where data was available for analysis from 1999 to 2020. For mortality due to any opioid and any opioid with a stimulant, the greatest AAPC was seen among non-Hispanic Blacks., Conclusions: Unprecedented increases in mortality due to opioid overdose occurred in the last two decades among adolescents and young adults. Heterogenous trends support the notion that the previously defined opioid overdose epidemic "waves" may not accurately depict the effects of the crisis in all race/ethnicity groups. Additionally, alarming increases in opioid-stimulant overdose mortality starting in 2012 further characterize the interrelated effects of the third and fourth waves., 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 Ltd. All rights reserved.)

Background: Overdose 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., Methods: This 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., Results: Among 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)., Conclusions: Following 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., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Opioid-related overdose mortality disproportionally affects Black adults in Kentucky, particularly overdoses associated with prescription opioid misuse (POM). Black adults also face other consequences of POM, such as disparate health and legal outcomes. While several factors effect POM, such as generational factors and gender, these risk factors are understudied among Black adults with a history of POM. Current literature primarily focuses on White individuals who use opioids., Method: The present study qualitatively examined reasons for POM, prescription opioids misused, how prescription opioids are obtained, and initiation of POM among Black adults using thematic analysis. Participants included a sample (n = 39) of Black adults from a southern state, stratified by gender and age across four cohorts: born (1) 1995-2001, (2) 1980-1994, (3) 1970-1979, and (4) 1955-1969., Results: Results revealed similarities and differences in these themes across age cohorts and gender., Conclusions: Implications for findings include the importance of culturally responsive interventions that utilize dual diagnosis treatment and idiographic approaches due to heterogeneous experiences with POM among Black adults., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Novel synthetic opioids (NSOs) represent an emerging group of novel psychoactive substances, acting as agonists at the opioid receptors. NSOs include fentanyl-related compounds, e.g. methoxyacetylfentanyl (MeACF), and non-fentanyl analogs, e.g. "U compounds" including U-47700. Here we present three cases of death involving MeACF and U-47700, with particular reference to preliminary data on pharmacokinetics and tissue distribution.After a complete post-mortem examination, general unknown screenings and analysis of drugs of abuse were performed on postmortem samples by immunoassays, gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. To quantify the analytes of interest in post-mortem blood and tissues, the standard addition method was used. A toxicological significance score (TSS), weighing the role of the NSO in each death case, was assigned.Case 1 died at the hospital after consumption of U-47700, methadone (serum levels: 2,600 ng/ml and 37 ng/ml), tilidine and benzodiazepines. In case 2, U-47700 (204 ng/ml) together with methadone (290 ng/ml), flubromazepam (480 ng/ml) and diazepam (300 ng/ml) were detected in peripheral blood. In case 3, methoxyacetylfentanyl (266 ng/ml), furanylfentanyl (4.3 ng/ml) 4-ANPP (15 ng/ml) and alprazolam (69 ng/ml) were quantified in femoral blood. In all cases, the NSO likely contributed to the death (TSS = 3).NSOs appear to be often consumed in the setting of polydrug intoxications, especially in combination with other opioids and benzodiazepines, which often exert synergistic effects. The standard addition method remains the most reliable in post-mortem analysis and toxicological results should always be evaluated together with circumstantial and autopsy data., (© 2024. The Author(s).)

Methadone is an opioid receptor agonist with a high potential for abuse. The current study aimed to compare different machine learning models to predict the outcomes following methadone poisoning. This six-year retrospective longitudinal study utilizes National Poison Data System (NPDS) data. The severity of outcomes was derived from the NPDS Coding Manual. Our database was divided into training (70%) and test (30%) sets. We used a light gradient boosting machine (LGBM), extreme gradient boosting (XGBoost), random forest (RF), and logistic regression (LR) to predict the outcomes of methadone poisoning. A total of 3847 patients with methadone exposures were included. Our results demonstrated that machine learning models conferred high accuracy and reliability in determining the outcomes of methadone poisoning cases. The performance evaluation showed all models had high accuracy, precision, specificity, recall, and F 1-score values. All models could reach high specificity (more than 96%) and high precision (80% or more) for predicting major outcomes. The models could also achieve a high sensitivity to predict minor outcomes. Finally, the accuracy of all models was about 75%. However, XGBoost and LGBM models achieved the best performance among all models. This study showcased the accuracy and reliability of machine learning models in the outcome prediction of methadone poisoning.

This retrospective study analyzed 230 pediatric opioid exposures from a statewide poison control center over a 5-year period. Most exposures involved pharmaceutical opioids and children below 2-years-old. Narrative details were reviewed to identify uncommon sources of opioids involved in poisoning and highlight the need for tailored prevention strategies and guidance., Competing Interests: Declaration of Competing Interest No funding was secured for this study. The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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).)

Purpose: Fueled by the prescription opioid overdose crisis and increased influx of illicitly manufactured fentanyl, fentanyl overdoses continue to be a public health crisis that has cost the US economy over $1 trillion in reduced productivity, health care, family assistance, criminal justice, and accounted for over 74,000 deaths in 2023. A recent demographic shift in the opioid crisis has led to a rise in overdose deaths among the Latinx population. Harm reduction interventions, including the use of naloxone and fentanyl test strips, have been shown to be effective measures at reducing the number of opioid overdose deaths. The aim of this scoping review is to summarize naloxone and fentanyl test strip interventions and public health policies targeted to Latinx communities., Methods: PubMed, CINHAL, Web of Science, Embase, and PsycINFO research databases using the keywords "fentanyl," "Latinx," "Harm Reduction," "Naloxone," and "Fentanyl Test Strips'' to identify studies published between January 1, 2013 and December 31, 2023. Endnote and Covidence software were used to catalog and manage citations for review of studies. Subsequently, studies that met inclusion criteria were then summarized using resulting themes., Results: Twenty-seven articles met the inclusion criteria and were further abstracted for the scoping review. Of these articles, 77.7% (n = 21) included a naloxone intervention, while only 11.1% (n = 3) included a fentanyl test strip intervention. Furthermore, 30.1% (n = 8) of these studies were Latinx targeted, and 7.7% (n = 2) of the studies were adapted for Latinx populations. Four themes, including an overall lack of knowledge and awareness, a lack of access to harm reduction or opioid overdose prevention resources, an overall lack of culturally adapted and/or targeted interventions, and restrictive and punitive policies that limit the effectiveness of protective factors were highlighted in this scoping review., Conclusion: Limited published research exists on the use of emerging harm reduction behaviors, such as the use of naloxone and fentanyl test strips as community intervention strategies to prevent opioid overdose deaths. Even fewer publications exist on the targeting and cultural adaptation of harm reduction interventions responsive to Latinx communities, especially those using theoretical approaches or frameworks to support these interventions. Future research is needed to assess the unique needs of Latinx populations and to develop culturally responsive programs to prevent opioid-related overdose deaths among this population., (© 2024. The Author(s).)

Background: Illicit opioid overdose continues to rise in North America and is a leading cause of death. Mathematical modeling is a valuable tool to investigate the epidemiology of this public health issue, as it can characterize key features of population outcomes and quantify the broader effect of structural and interventional changes on overdose mortality. The aim of this study is to quantify and predict the impact of key harm reduction strategies at differing levels of scale-up on fatal and nonfatal overdose among a population of people engaging in unregulated opioid use in Toronto., Methods: An individual-based model for opioid overdose was built featuring demographic and behavioural variation among members of the population. Key individual attributes known to scale the risk of fatal and nonfatal overdose were identified and incorporated into a dynamic modeling framework, wherein every member of the simulated population encompasses a set of distinct characteristics that govern demographics, intervention usage, and overdose incidence. The model was parametrized to fatal and nonfatal overdose events reported in Toronto in 2019. The interventions considered were opioid agonist therapy (OAT), supervised consumption sites (SCS), take-home naloxone (THN), drug-checking, and reducing fentanyl in the drug supply. Harm reduction scenarios were explored relative to a baseline model to examine the impact of each intervention being scaled from 0% use to 100% use on overdose events., Results: Model simulations resulted in 3690.6 nonfatal and 295.4 fatal overdoses, coinciding with 2019 data from Toronto. From this baseline, at full scale-up, 290 deaths were averted by THN, 248 from eliminating fentanyl from the drug supply, 124 from SCS use, 173 from OAT, and 100 by drug-checking services. Drug-checking and reducing fentanyl in the drug supply were the only harm reduction strategies that reduced the number of nonfatal overdoses., Conclusions: Within a multi-faceted harm reduction approach, scaling up take-home naloxone, and reducing fentanyl in the drug supply led to the largest reduction in opioid overdose fatality in Toronto. Detailed model simulation studies provide an additional tool to assess and inform public health policy on harm reduction., (© 2024. The Author(s).)

Guided by the North Carolina Memorandum of Agreement (MOA), local governments are investing national opioid settlement funds to respond to the overdose crisis. Community Opioid Resources Engine for North Carolina (CORE-NC) partners have developed tools and resources that local governments are using as they plan, implement, and report on their opioid overdose response., Competing Interests: Disclosure of interests: The authors report no relevant conflicts of interest., (Copyright ©2024 by the North Carolina Institute of Medicine and The Duke Endowment. All rights reserved.)

Introduction: Multiple Canadian jurisdictions have reported a pattern of chronic pain among people who died from substance-related acute toxicity. This study examined the prevalence and characteristics of those with chronic pain using data from a national study of people who died of accidental acute toxicity., Methods: A cross-sectional analysis of accidental substance-related acute toxicity deaths that occurred in Canada between 1 January 2016 and 31 December 2017 was conducted. The prevalence of pain and pain-related conditions were summarized as counts and percentages of the overall sample. Subgroups of people with and without a documented history of chronic pain were compared across sociodemographic characteristics, health history, contextual factors and substances involved., Results: From the overall sample (n = 7902), 1056 (13%) people had a history of chronic pain while 6366 (81%) had no documented history. Those with chronic pain tended to be older (40 years and older), unemployed, retired and/or receiving disability supports around the time of death. History of mental health conditions, trauma and surgery or injury was significantly more prevalent among people with chronic pain. Of the substances that most frequently contributed to death, opioids typically prescribed for pain (hydromorphone and oxycodone) were detected in toxicology more often among those with chronic pain than those without., Conclusion: Findings underscore the cross-cutting role of multiple comorbidities and unmanaged pain, which could compound the risk of acute toxicity death. Continued prioritization of harm reduction and regular patient engagement to assess ongoing needs are among the various opportunities for intervention., Competing Interests: The authors have no conflicts of interest.

Background and Aim: Bromazolam, a novel designer benzodiazepine (NBD), exhibits potent sedative, hypnotic and anxiolytic effects, raising concerns regarding its potential for misuse and fatal outcomes, particularly when combined with opioids such as fentanyl. Despite limited documented fatalities globally, its use poses a significant threat, exacerbated by under-reporting and a lack of routine testing. This study analysed NBD-related deaths in a major US city over a 4-year period., Methods: Analysis of accidental overdose deaths involving NBDs in San Francisco, CA, USA from 2020 to 2023, was performed utilizing medico-legal death investigations including comprehensive forensic toxicology, pathology and demographic information. San Francisco conducts thorough investigations into all non-natural and sudden unexpected deaths, including routine alcohol and drug testing of decedents under its jurisdiction, including etizolam, flualprazolam, flubromazolam and bromazolam analysis., Results: There was a sudden surge in bromazolam-related deaths, with 44 fatalities documented in 2023, contrasting with relatively fewer deaths related to other NBDs. Bromazolam fatalities frequently involved co-ingestion with opioids, primarily fentanyl, and stimulants such as methamphetamine and cocaine. Demographic characteristics indicated a predominance of males, with a significant proportion lacking fixed addresses. Blood concentrations of bromazolam increased during the study period, suggesting heightened availability and/or purity in the community., Conclusion: There was a surge in bromazolam-related deaths during 2023 in San Francisco, CA, USA, contrasting with relatively stable numbers of deaths associated with other NBDs over the preceding years. The findings underscore the urgency for enhanced death investigation, testing and reporting to facilitate targeted harm reduction strategies for individuals at risk of bromazolam-related morbidity and mortality., (© 2024 Society for the Study of Addiction.)

Purpose: Opioid prescriptions continue to carry significant short- and long-term systemic risks, even after ophthalmic surgery. The goal of this study was to identify any association of opioid prescription, after ophthalmic surgery, with postoperative hospitalization, opioid overdose, opioid dependence, and all-cause mortality., Design: Retrospective, cross-sectional analysis., Participants: Patients undergoing an ophthalmic surgery in the OptumLabs Data Warehouse., Methods: We used deidentified administrative claims data from the OptumLabs Data Warehouse to create 3 cohorts of patients for analysis from January 1, 2016, to June 30, 2022. The first cohort consisted of 1-to-1 propensity score-matched patients who had undergone ophthalmic surgery and had filled a prescription for an opioid and not filled a prescription for an opioid. The second cohort consisted of patients who were considered opioid naïve and had filled a prescription for an opioid matched to patients who had not filled a prescription for an opioid. The last cohort consisted of opioid-naïve patients matched across the following morphine milligram equivalents (MME) groups: ≤ 40, 41-80, and > 80., Main Outcome Measures: Short- and long-term risks of hospitalization, opioid overdose, opioid dependency/abuse, and death were compared between the cohorts., Results: We identified 1 577 692 patients who had undergone an ophthalmic surgery, with 312 580 (20%) filling an opioid prescription. Among all patients, filling an opioid prescription after an ophthalmic surgery was associated with increased mortality (hazard rate [HR], 1.28; 95% confidence interval [CI], 1.25-1.31; P < 0.001), hospitalization (HR, 1.51; 95% CI, 1.49-1.53; P < 0.001), opioid overdose (HR, 7.31; 95% CI, 6.20-8.61, P < 0.001), and opioid dependency (HR, 13.05; 95% CI, 11.48-14.84; P < 0.001) compared with no opioid prescription. Furthermore, we found that higher MME doses of opioids were associated with higher rates of mortality, hospitalization, and abuse/dependence., Conclusions: Patients who filled an opioid prescription after an ophthalmic surgery experienced higher rates of mortality, hospitalization, episodes of opioid overdose, and opioid dependence compared with patients who did not fill an opioid prescription., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Introduction: Protonitazene is an opioid belonging to the 2-benzylbenzimidazole structural class. We describe two cases of opioid toxicity involving the reported inhalation of a delta-9-tetrahydrocannabinol vape product in which protonitazene was detected., Case Reports: Case 1 was a young male found unconscious after the reported use of a delta-9-tetrahydrocannabinol vape. He suffered two subsequent apnoeic episodes requiring bag-valve-mask ventilation before eventual recovery. Only protonitazene was detected in blood at a concentration of 0.74 µg/L. Case 2 was a young male who died shortly after being found unresponsive. The postmortem femoral blood concentrations of protonitazene and delta-9-tetrahydrocannabinol were 0.33 µg/L and 2 µg/L, respectively. Analysis of a pod vaping device found in the decedent's hand and a separate e-liquid bottle labelled as delta-9-tetrahydrocannabinol showed a mixture of protonitazene and delta-9-tetrahydrocannabinol., Discussion: The opioid effects of protonitazene are mediated through β-arrestin2 and mu opioid receptor signalling pathways. Benzimidazole opioids are lipophilic and, when mixed with a suitable solvent, can be used in a vape device. It is anticipated that naloxone would have provided effective reversal of toxicity in our cases., Conclusions: Novel routes of opioid administration, like vaping, may appear relatively innocuous in comparison to intravenous administration, but opioids may still be absorbed at high concentrations, resulting in severe opioid toxicity or death.

Importance: Recognizing and providing services to individuals at highest risk for drug overdose are paramount to addressing the drug overdose crisis., Objective: To examine receipt of medications for opioid use disorder (MOUD), naloxone, and behavioral health services in the 12 months after an index nonfatal drug overdose and the association between receipt of these interventions and fatal drug overdose., Design, Setting, and Participants: This cohort study was conducted in the US from January 2020 to December 2021 using claims, demographic, mortality, and other data from the Centers for Medicare & Medicaid Services, the Centers for Disease Control and Prevention, and other sources. The cohort comprised Medicare fee-for-service beneficiaries aged 18 years or older with International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes for a nonfatal drug overdose. Data analysis was performed from February to November 2023., Exposures: Demographic and clinical characteristics, substance use disorder, and psychiatric comorbidities., Main Outcomes and Measures: Receipt of MOUD, naloxone, and behavioral health services as well as subsequent nonfatal and fatal drug overdoses., Results: The cohort consisted of 136 762 Medicare beneficiaries (80 140 females [58.6%]; mean (SD) age of 68.2 [15.0] years) who experienced an index nonfatal drug overdose in 2020. The majority of individuals had Hispanic (5.8%), non-Hispanic Black (10.9%), and non-Hispanic White (78.8%) race and ethnicity and lived in metropolitan areas (78.9%). In the 12 months after their index nonfatal drug overdose, 23 815 beneficiaries (17.4%) experienced at least 1 subsequent nonfatal drug overdose and 1323 (1.0%) died of a fatal drug overdose. Opioids were involved in 72.2% of fatal drug overdoses. Among the cohort, 5556 (4.1%) received any MOUD and 8530 (6.2%) filled a naloxone prescription in the 12 months after the index nonfatal drug overdose. Filling a naloxone prescription (adjusted odds ratio [AOR], 0.70; 95% CI, 0.56-0.89), each percentage of days receiving methadone (AOR, 0.98; 95% CI, 0.98-0.99) or buprenorphine (AOR, 0.99; 95% CI, 0.98-0.99), and receiving behavioral health assessment or crisis services (AOR, 0.25; 95% CI, 0.22-0.28) were all associated with reduced adjusted odds of fatal drug overdose in the 12 months after the index nonfatal drug overdose., Conclusions and Relevance: This cohort study found that, despite their known association with reduced risk of a fatal drug overdose, only a small percentage of Medicare beneficiaries received MOUD or filled a naloxone prescription in the 12 months after a nonfatal drug overdose. Efforts to improve access to behavioral health services; MOUD; and overdose-prevention strategies, such as prescribing naloxone and linking individuals to community-based health care settings for ongoing care, are needed.