Reported Xylazine Use Among Adults Aged ≥18 Years Evaluated for Substance Use Treatment - United States, July 2022-September 2023.

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.

"We don't even know where it's kept": exploring perspectives on naloxone administration by provincial correctional workers in Manitoba, Canada.

PURPOSE: Prisonersare at disproportionate risk of suffering substance-related harms. The administration of naloxone is essential to reversing opioid overdose and minimizing substance-related harms in prison and the community. The purpose of this study is to examine how naloxone administration is practiced and perceived in prison settings. DESIGN/METHODOLOGY/APPROACH: The authors conducted surveys with correctional workers in Manitoba, Canada (n = 257) to examine how they understand and feel about the need for and practice of administering naloxone in their everyday work with criminalized populations. FINDINGS: Respondents reported feeling a great need to administer naloxone, but most did not feel adequately trained to administer naloxone, creating the perception that criminalized populations remain at enhanced risk. ORIGINALITY/VALUE: Findings provide emerging evidence of the need for training and accompanying policies and procedures for correctional workers on how to access and administer naloxone.

Evolution of an epidemic: Understanding the opioid epidemic in the United States and the impact of the COVID-19 pandemic on opioid-related mortality.

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.

Risk factors for persistent fatal opioid-involved overdose clusters in Massachusetts 2011-2021: a spatial statistical analysis with socio-economic, accessibility, and prescription factors.

BACKGROUND: Fatal opioid-involved overdose rates increased precipitously from 5.0 per 100,000 population to 33.5 in Massachusetts between 1999 and 2022. METHODS: We used spatial rate smoothing techniques to identify persistent opioid overdose-involved fatality clusters at the ZIP Code Tabulation Area (ZCTA) level. Rate smoothing techniques were employed to identify locations of high fatal opioid overdose rates where population counts were low. In Massachusetts, this included areas with both sparse data and low population density. We used Local Indicators of Spatial Association (LISA) cluster analyses with the raw incidence rates, and the Empirical Bayes smoothed rates to identify clusters from 2011 to 2021. We also estimated Empirical Bayes LISA cluster estimates to identify clusters during the same period. We constructed measures of the socio-built environment and potentially inappropriate prescribing using principal components analysis. The resulting measures were used as covariates in Conditional Autoregressive Bayesian models that acknowledge spatial autocorrelation to predict both, if a ZCTA was part of an opioid-involved cluster for fatal overdose rates, as well as the number of times that it was part of a cluster of high incidence rates. RESULTS: LISA clusters for smoothed data were able to identify whether a ZCTA was part of a opioid involved fatality incidence cluster earlier in the study period, when compared to LISA clusters based on raw rates. PCA helped in identifying unique socio-environmental factors, such as minoritized populations and poverty, potentially inappropriate prescribing, access to amenities, and rurality by combining socioeconomic, built environment and prescription variables that were highly correlated with each other. In all models except for those that used raw rates to estimate whether a ZCTA was part of a high fatality cluster, opioid overdose fatality clusters in Massachusetts had high percentages of Black and Hispanic residents, and households experiencing poverty. The models that were fitted on Empirical Bayes LISA identified this phenomenon earlier in the study period than the raw rate LISA. However, all the models identified minoritized populations and poverty as significant factors in predicting the persistence of a ZCTA being part of a high opioid overdose cluster during this time period. CONCLUSION: Conducting spatially robust analyses may help inform policies to identify community-level risks for opioid-involved overdose deaths sooner than depending on raw incidence rates alone. The results can help inform policy makers and planners about locations of persistent risk.

Exploration of weekly variation in naloxone possession and carriage among people who use opioids in New York City before, during, and after the COVID-19 pandemic.

BACKGROUND: Naloxone is critical for reversing opioid-related overdoses. However, there is a dearth of research examining how naloxone possession and carriage are impacted by time-varying individual and social determinants, and if this differed during the height of the COVID-related mitigation measures (e.g., shutdowns). METHODS: We utilized weekly ecological momentary assessments (EMA) to measure factors associated with naloxone possession and carriage among 40 people who use illicit opioids in New York City, for 24 months. Descriptive statistics were used to explore the frequency of weeks with consistent naloxone possession and carriage. Mixed effects binary and multivariable logistic regression was used to test for the impact of time-varying EMA- and baseline-level factors on each outcome. RESULTS: Approximately 70% of weekly EMAs were associated with consistent naloxone possession or carriage. In multivariable models, compared to during the height of the COVID-related shutdowns (March 12, 2020-May 19, 2021), the time before was associated with lower odds of consistent possession (Odds Ratio (OR) = 0.05, 95% Confidence Interval (CI) = 0.01-0.15) and consistent carriage (OR = 0.06, CI = 0.01-0.25). Additionally, being female (OR = 11.15, CI = 2.85-43.42), being White versus being Black or Hispanic/Latinx (OR = 8.05, CI = 1.96-33.06), and lifetime overdose (OR = 1.96, CI = 1.16-19.80) were associated with higher odds of consistent possession. Recent opioid injection (OR = 3.66, CI = 1.34-9.94), being female (OR = 7.91, CI = 3.91-8.23), and being White (OR = 5.77, CI = 1.35-24.55) were associated with higher odds of consistent carriage. Not wanting to be perceived as a drug user was reported in nearly one third (29.0%; 190/656) of EMAs where inconsistent possession was reported. CONCLUSIONS: Our findings paint a relatively positive picture of possession and carriage during COVID-related shutdowns, particularly among white and female participants, and highlight the importance of capturing time-varying factors to understand naloxone-related behavior. To curb growing disparities, outreach to equip Black and Hispanic/Latinx people with naloxone is needed as well as interventions to reduce stigma as a barrier to naloxone engagement.

Receipt of Opioid Agonist Treatment in provincial correctional facilities in British Columbia is associated with a reduced hazard of nonfatal overdose in the month following release.

BACKGROUND: In many jurisdictions, policies restrict access to Opioid Agonist Treatment (OAT) in correctional facilities. Receipt of OAT during incarceration is associated with reduced risk of fatal overdose after release but little is known about the effect on nonfatal overdose. This study aimed to examine the association between OAT use during incarceration and nonfatal overdose in the 30 days following release. METHODS AND FINDINGS: Using linked administrative healthcare and corrections data for a random sample of 20% of residents of British Columbia, Canada we examined releases from provincial correctional facilities between January 1, 2015 -December 1, 2018, among adults (aged 18 or older at the time of release) with Opioid Use Disorder. We fit Andersen-Gill models to examine the association between receipt of OAT in custody and the hazard of nonfatal following release. We conducted secondary analyses to examine the association among people continuing treatment initiated prior to their arrest and people who initiated a new episode of OAT in custody separately. We also conducted sex-based subgroup analyses. In this study there were 4,738 releases of 1,535 people with Opioid Use Disorder. In adjusted analysis, receipt of OAT in custody was associated with a reduced hazard of nonfatal overdose (aHR 0.55, 95% CI 0.41, 0.74). This was found for prescriptions continued from community (aHR 0.49, 95%CI 0.36, 0.67) and for episodes of OAT initiated in custody (aHR 0.58, 95%CI 0.41, 0.82). The effect was greater among women than men. CONCLUSIONS: OAT receipt during incarceration is associated with a reduced hazard of nonfatal overdose after release. Policies to expand access to OAT in correctional facilities, including initiating treatment, may help reduce harms related to nonfatal overdose in the weeks following release. Differences in the effect seen among women and men indicate a need for gender-responsive policies and programming.

Characteristics of drug overdose suicide attempts presenting to the psychiatric emergency department of Beijing Anding Hospital.

BACKGROUND: Overdose-related suicide attempts represent a significant portion of self-harm presentations in the psychiatric emergency department (ED). Identifying specific patient characteristics associated with these attempts holds promise for pinpointing drug classes with elevated risk and paving the way for tailored suicide prevention interventions. This study aims to examine the demographic profiles of ED patients who had experienced overdose-related suicide attempts. METHODS: This retrospective study was conducted at Beijing Anding Hospital, Capital Medical University, from January 2020 to December 2021. Patients with psychiatric drug overdose suicide attempts presenting to the psychiatric ED were included. Sociodemographic characteristics and the specific classes of drugs involved were collected, and analysed descriptively. RESULTS: This study examined 252 overdose patients, excluding 51 patients treated with alcohol or nonpsychiatric drugs, and a total 201 cases were included. The mean age of the patients was 28 ± 16 years (median 23, range 12-78), and 82% (n = 165) of the sample were females. Notably, nearly half (45%) of the patients were aged ≤ 20 years. While the number of cases decreased with increasing age, a significant increase was observed in 2021 compared to 2020. Benzodiazepines (BZDs) were the most frequently implicated substance class (n = 126, 63%), followed by antidepressants (n = 96, 48%), antipsychotics (n = 44, 22%), Z-drugs (n = 43, 21%), and mood stabilizers (n = 36, 18%). For adolescents, antidepressants (n = 52, 71%) overtook BZDs (n = 38, 52%) as the most common drug. The monthly distribution of cases revealed peaks in April and November. Furthermore, 21% (n = 42) of patients ingested more than two psychotropic medications concurrently. Finally, approximately half (n = 92) of the patients required inpatient admission for further treatment. Comparisons between hospitalized and nonhospitalized patients did not reveal any significant differences. CONCLUSIONS: The present study revealed a greater prevalence of suicide overdose attempts among young females receiving prescriptions for antidepressants and/or BZDs. This finding suggests a potential need for enhanced monitoring of suicidal behaviour in this specific population when prescribing psychotropic medications. These findings contribute to the growing body of knowledge regarding drug overdose suicide attempts in psychiatric emergency settings and underscore the importance of further research to develop targeted prevention interventions.

Overdose deaths before and during the COVID-19 pandemic in a US county.

Introduction: Globally, overdose deaths increased near the beginning of the COVID-19 pandemic, which created availability and access barriers to addiction and social services. Especially in times of a crisis like a pandemic, local exposures, service availability and access, and system responses have major influence on people who use drugs. For policy makers to be effective, an understanding at the local level is needed. Methods: This retrospective epidemiologic study from 2019 through 2021 compares immediate and 20-months changes in overdose deaths from the pandemic start to 16 months before its arrival in Pinellas County, FL We examine toxicologic death records of 1,701 overdoses to identify relations with interdiction, and service delivery. Results: There was an immediate 49% increase (95% CI 23-82%, p < 0.0001) in overdose deaths in the first month following the first COVID deaths. Immediate increases were found for deaths involving alcohol (171%), heroin (108%), fentanyl (78%), amphetamines (55%), and cocaine (45%). Overdose deaths remained 27% higher (CI 4-55%, p = 0.015) than before the pandemic through 2021.Abrupt service reductions occurred when the pandemic began: in-clinic methadone treatment dropped by two-thirds, counseling by 38%, opioid seizures by 29%, and drug arrests by 56%. Emergency transport for overdose and naloxone distributions increased at the pandemic onset (12%, 93%, respectively) and remained higher through 2021 (15%, 377%,). Regression results indicate that lower drug seizures predicted higher overdoses, and increased 911 transports predicted higher overdoses. The proportion of excess overdose deaths to excess non-COVID deaths after the pandemic relative to the year before was 0.28 in Pinellas County, larger than 75% of other US counties. Conclusions: Service and interdiction interruptions likely contributed to overdose death increases during the pandemic. Relaxing restrictions on medical treatment for opioid addiction and public health interventions could have immediate and long-lasting effects when a major disruption, such as a pandemic, occurs. County level data dashboards comprised of overdose toxicology, and interdiction and service data, can help explain changes in overdose deaths. As a next step in predicting which policies and practices will best reduce local overdoses, we propose using simulation modeling with agent-based models to examine complex interacting systems.

No change in substance use disorders or overdose after implementation of state Earned Income Tax Credit (EITC).

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.

Development of a Real-Time Dashboard for Overdose Touchpoints: User-Centered Design Approach.

BACKGROUND: Overdose Fatality Review (OFR) is an important public health tool for shaping overdose prevention strategies in communities. However, OFR teams review only a few cases at a time, which typically represent a small fraction of the total fatalities in their jurisdiction. Such limited review could result in a partial understanding of local overdose patterns, leading to policy recommendations that do not fully address the broader community needs. OBJECTIVE: This study explored the potential to enhance conventional OFRs with a data dashboard, incorporating visualizations of touchpoints-events that precede overdoses-to highlight prevention opportunities. METHODS: We conducted 2 focus groups and a survey of OFR experts to characterize their information needs and design a real-time dashboard that tracks and measures decedents' past interactions with services in Indiana. Experts (N=27) were engaged, yielding insights on essential data features to incorporate and providing feedback to guide the development of visualizations. RESULTS: The findings highlighted the importance of showing decedents' interactions with health services (emergency medical services) and the justice system (incarcerations). Emphasis was also placed on maintaining decedent anonymity, particularly in small communities, and the need for training OFR members in data interpretation. The developed dashboard summarizes key touchpoint metrics, including prevalence, interaction frequency, and time intervals between touchpoints and overdoses, with data viewable at the county and state levels. In an initial evaluation, the dashboard was well received for its comprehensive data coverage and its potential for enhancing OFR recommendations and case selection. CONCLUSIONS: The Indiana touchpoints dashboard is the first to display real-time visualizations that link administrative and overdose mortality data across the state. This resource equips local health officials and OFRs with timely, quantitative, and spatiotemporal insights into overdose risk factors in their communities, facilitating data-driven interventions and policy changes. However, fully integrating the dashboard into OFR practices will likely require training teams in data interpretation and decision-making.

Associations among drug acquisition and use behaviors, psychosocial attributes, and opioid-involved overdoses.

AIMS: This study sought to develop and assess an exploratory model of how demographic and psychosocial attributes, and drug use or acquisition behaviors interact to affect opioid-involved overdoses. DESIGN: We conducted exploratory and confirmatory factor analysis (EFA/CFA) to identify a factor structure for ten drug acquisition and use behaviors. We then evaluated alternative structural equation models incorporating the identified factors, adding demographic and psychosocial attributes as predictors of past-year opioid overdose. SETTING AND PARTICIPANTS: We used interview data collected for two studies recruiting opioid-misusing participants receiving services from a community-based syringe services program. The first investigated current attitudes toward drug-checking (N = 150). The second was an RCT assessing a telehealth versus in-person medical appointment for opioid use disorder treatment referral (N = 270). MEASUREMENTS: Demographics included gender, age, race/ethnicity, education, and socioeconomic status. Psychosocial measures were homelessness, psychological distress, and trauma. Self-reported drug-related risk behaviors included using alone, having a new supplier, using opioids with benzodiazepines/alcohol, and preferring fentanyl. Past-year opioid-involved overdoses were dichotomized into experiencing none or any. FINDINGS: The EFA/CFA revealed a two-factor structure with one factor reflecting drug acquisition and the second drug use behaviors. The selected model (CFI = .984, TLI = .981, RMSEA = .024) accounted for 13.1% of overdose probability variance. A latent variable representing psychosocial attributes was indirectly associated with an increase in past-year overdose probability (ß = .234, p = .001), as mediated by the EFA/CFA identified latent variables: drug acquisition (ß = .683, p < .001) and drug use (ß = .567, p = .001). Drug use behaviors (ß = .287, p = .04) but not drug acquisition (ß = .105, p = .461) also had a significant, positive direct effect on past-year overdose. No demographic attributes were significant direct or indirect overdose predictors. CONCLUSIONS: Psychosocial attributes, particularly homelessness, increase the probability of an overdose through associations with risky drug acquisition and drug-using behaviors. Further research is needed to replicate these findings with populations at high-risk of an opioid-related overdose to assess generalizability and refine the metrics used to assess psychosocial characteristics.

'It was like coming back from the clouds': a qualitative analysis of the lived experience of overdose consequent to drug use among a cohort of people who use drugs in Scotland.

BACKGROUND: Globally, non-fatal overdose (NFOD) rates consequent to drug use, typically opioids, continue increasing at a startling rate. Existing quantitative research has revealed myriad factors and characteristics linked to experiencing NFOD, but it is critically important to explore the lived context underlying these associations. In this qualitative study, we sought to understand the experiences of NFOD among people who use drugs in a Scottish region in order to: enhance public policy responses; inform potential intervention development to mitigate risk; and contribute to the literature documenting the lived experience of NFOD. METHODS: From June to July 2021, two peer researchers conducted face-to-face semi-structured interviews with people who use drugs who had experienced recent NFOD attending harm reduction services in Tayside, Scotland. These were transcribed verbatim and evaluated using thematic analysis with an inductive approach which had an experiential and essentialist orientation. RESULTS: Twenty people were interviewed across two sites. Of those, 15 (75%) were male and mean age was 38.2 (7.7) years. All had experienced at least one NFOD in the prior six months, and all reported polydrug use. Five themes were identified, within which 12 subthemes were situated. The themes were: social context; personal risk-taking triggers; planned and impulsive consumption; risk perception; and overdose reversal. The results spoke to the environmental, behavioural, cognitive, economic, and marketplace, factors which influence the context of NFOD in the region. CONCLUSIONS: A complex interplay of behavioural, psychological, and situational factors were found to impact the likelihood of experiencing NFOD. Structural inequities which policy professionals and civic leaders should seek to remedy were identified, while service providers may seek to reconfigure healthcare provision for people who use drugs to account for the interpersonal, psychological, and social factors identified, which appear to precipitate NFOD. TRIAL REGISTRATION: Not applicable.

GLP-1 Receptor Agonist Exposures Are Increasingly Common and Generally Associated with Mild Symptoms: A Single Poison Center Experience.

INTRODUCTION: Glucagon-like peptide-1 receptor agonist use has increased over the last decade for glycemic control in type 2 diabetes mellitus, cardiovascular risk reduction, and weight loss. Clinical trials indicate that gastrointestinal adverse effects are commonly experienced and severe hypoglycemia is rare; however, there is little data regarding glucagon-like peptide-1 receptor agonist in overdose. METHODS: We performed a retrospective chart review evaluating and characterizing glucagon-like peptide-1 receptor agonist exposures reported to a single poison center between 2006 and 2023. Patient demographics, circumstances of exposure, clinical effects, and outcomes were abstracted from charts. Descriptive statistics were utilized to summarize demographic information and clinical factor data. RESULTS: A total of 152 charts met inclusion criteria. Therapeutic errors accounted for 91% of exposures. Most patients (67%) reported no symptoms, although not all patients were followed to a definitive outcome. Nausea, vomiting, generalized weakness, and abdominal pain were the predominant symptoms reported. Most patients (62%) were monitored and closely followed in the home setting. Hypoglycemia was rare but occurred in the setting of a single agent glucagon-like peptide-1 receptor agonist exposure in two patients. Two additional patients who developed hypoglycemia involved co-administration of insulin. 21% of the exposures were related to errors on initial use of the pen. CONCLUSION: Exposures to glucagon-like peptide-1 receptor agonist have increased substantially over the years. Effects from an exposure tended to be mild and primarily involve gastrointestinal symptoms. Hypoglycemia was rare. Therapeutic and administration errors were common. Education on pen administration may help to reduce errors.

Intoxication cases in the Emergency Department at a Norwegian University Hospital 2019-20. / Pasienter med forgiftning vurdert ved akuttmottaket på St. Olavs hospital 2019­20.

Background: Acute intoxication is a common chief complaint in emergency medicine, but there is a lack of up-to-date studies from the emergency departments in Norway on the incidence and prevalence of various toxic substances. The aim of this study was to survey acute intoxications at the emergency department of St Olav's Hospital, Trondheim. Material and method: In this review of patient records, we used data from the emergency department at St Olav's Hospital in Trondheim in the period 1  January 2019-31  December 2020. All cases with 'acute intoxication' as the reason for the emergency department visit were included. Results: In a patient population of 836 unique patients, there were a total of 1423 intoxications, of which 168/836 patients (20.0 %) had more than one intoxication episode in the period. The median age was 31 years (interquartile range 22-47), and 395/836 (47.2 %) of the patients were women. Combined drug intoxication constituted 666/1423 (46.8 %) of the cases, and the most frequent intoxications were from ethanol: 802/1423 (56.4 %); benzodiazepines 314/1423 (24.0 %); and opioids 243/1423 (17.1 %). Altogether, 1146/1423 (80.5 %) incidents resulted in hospital admission. There were no deaths during their hospital stay. Interpretation: Emergency departments must be prepared to manage patients who have taken various poisoning agents. The antidotes must be available, and it must be possible to perform interventions.

Ambulance Services Attendance for Mental Health and Overdose Before and During COVID-19 in Canada and the United Kingdom: Interrupted Time Series Study.

BACKGROUND: The COVID-19 pandemic impacted mental health and health care systems worldwide. OBJECTIVE: This study examined the COVID-19 pandemic's impact on ambulance attendances for mental health and overdose, comparing similar regions in the United Kingdom and Canada that implemented different public health measures. METHODS: An interrupted time series study of ambulance attendances was conducted for mental health and overdose in the United Kingdom (East Midlands region) and Canada (Hamilton and Niagara regions). Data were obtained from 182,497 ambulance attendance records for the study period of December 29, 2019, to August 1, 2020. Negative binomial regressions modeled the count of attendances per week per 100,000 population in the weeks leading up to the lockdown, the week the lockdown was initiated, and the weeks following the lockdown. Stratified analyses were conducted by sex and age. RESULTS: Ambulance attendances for mental health and overdose had very small week-over-week increases prior to lockdown (United Kingdom: incidence rate ratio [IRR] 1.002, 95% CI 1.002-1.003 for mental health). However, substantial changes were observed at the time of lockdown; while there was a statistically significant drop in the rate of overdose attendances in the study regions of both countries (United Kingdom: IRR 0.573, 95% CI 0.518-0.635 and Canada: IRR 0.743, 95% CI 0.602-0.917), the rate of mental health attendances increased in the UK region only (United Kingdom: IRR 1.125, 95% CI 1.031-1.227 and Canada: IRR 0.922, 95% CI 0.794-1.071). Different trends were observed based on sex and age categories within and between study regions. CONCLUSIONS: The observed changes in ambulance attendances for mental health and overdose at the time of lockdown differed between the UK and Canada study regions. These results may inform future pandemic planning and further research on the public health measures that may explain observed regional differences.

What would it really take to solve the overdose epidemic in the United States?

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.

State COVID-19 Policies and Drug Overdose Mortality Among Working-Age Adults in the United States, 2020.

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).

Classics in Chemical Neuroscience: Xylazine.

Xylazine (also known as "tranq") is a potent nonopioid veterinary sedative that has recently experienced a surge in use as a drug adulterant, most often combined with illicitly manufactured fentanyl. This combination may heighten the risk of fatal overdose. Xylazine has no known antidote approved for use in humans, and age-adjusted overdose deaths involving xylazine were 35 times higher in 2021 than 2018. In April 2023, the Biden Administration declared xylazine-laced fentanyl an emerging drug threat in the United States. In 2022, the Drug Enforcement Agency (DEA) reported nearly a quarter of seized fentanyl powder contained xylazine. This dramatic increase in prevalence has solidified the status of xylazine as an emerging drug of abuse and an evolving threat to public health. The following narrative review outlines the synthesis, pharmacokinetics, pharmacodynamics, and adverse effects of xylazine, as well as the role it may play in the ongoing opioid epidemic.