Excess Fatal Overdoses in the United States During the COVID-19 Pandemic by Geography and Substance Type: March 2020-August 2021.

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

Understanding and Addressing Widening Racial Inequalities in Drug Overdose.

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

A Dynamic Model of Opioid Overdose Deaths in Canada during the Co-Occurring Opioid Overdose Crisis and COVID-19 Pandemic.

With over 40,000 opioid-related overdose deaths between January 2016 and June 2023, the opioid-overdose crisis is a significant public health concern for Canada. The opioid crisis arose from a complex system involving prescription opioid use, the use of prescription opioids not as prescribed, and non-medical opioid use. The increasing presence of fentanyl and its analogues in the illegal drugs supply has been an important driver of the crisis. In response to the overdose crisis, governments at the municipal, provincial/territorial, and federal levels have increased actions to address opioid-related harms. At the onset of the COVID-19 pandemic, concerns emerged over how the pandemic context may impact the opioid overdose crisis. Using evidence from a number of sources, we developed a dynamic mathematical model of opioid overdose death to simulate possible trajectories of overdose deaths during the COVID-19 pandemic. This model incorporates information on prescription opioid use, opioid use not as prescribed, non-medical opioid use, the level of fentanyl in the drug supply, and a measure of the proportion deaths preventable by new interventions. The simulated scenarios provided decision makers with insight into possible trajectories of the opioid crisis in Canada during the COVID-19 pandemic, highlighting the potential of the crisis to take a turn for the worse under certain assumptions, and thus, informing planning during a period when surveillance data were not yet available. This model provides a starting point for future models, and through its development, we have identified important data and evidence gaps that need to be filled in order to inform future action.

The effect of opioid use on traffic fatalities.

We use a difference-in-differences design to study the effect of opioid use on traffic fatalities. Following Alpert et al., we focus on the 1996 introduction and marketing of OxyContin, and we examine its long-term impacts on traffic fatalities involving Schedule II drugs or heroin. Based on the national fatal vehicle crash database, we find that the states heavily targeted by the initial marketing of OxyContin (i.e., non-triplicate states) experienced 2.4 times more traffic fatalities (1.6 additional deaths per million individuals) involving Schedule II drugs or heroin during 2011-2019, when overdose deaths from heroin and fentanyl became more prominent. We find no difference in traffic fatalities until after the mid-2000s between states with and without a triplicate prescription program. The effect is mainly concentrated in fatal crashes with drug involvement of drivers ages between 25 and 44. Our results highlight additional long-term detrimental consequences of the introduction and marketing of OxyContin.

"Deaths of despair" over the business cycle: New estimates from a shift-share instrumental variables approach.

This study presents new evidence of the effects of short-term economic fluctuations on suicide, fatal drug overdose, and alcohol-related mortality among working-age adults in the United States from 2003-2017. Using a shift-share instrumental variables approach, I find that a one percentage point increase in the aggregate employment rate decreases current-year non-drug suicides by 1.7 percent. These protective effects are concentrated among working-age men and likely reflect a combination of individual labor market experiences as well as the indirect effects of local economic growth. I find no consistent evidence that short-term business cycle changes affect drug or alcohol-related mortality. While the estimated protective effects are small relative to secular increases in suicide in recent decades, these findings are suggestive of important, short-term economic factors affecting specific causes of death and should be considered alongside the longer-term and multifaceted social, economic, and cultural determinants of America's "despair" epidemic.

State-level variation in distribution of oxycodone and opioid-related deaths from 2000 to 2021: an ecological study of ARCOS and CDC WONDER data in the USA.

OBJECTIVES: This study aims to characterise oxycodone's distribution and opioid-related overdoses in the USA by state from 2000 to 2021. DESIGN: This is an observational study. SETTING: More than 80 000 Americans died of an opioid overdose in 2021 as the USA continues to struggle with an opioid crisis. Prescription opioids play a substantial role, introducing patients to opioids and providing a supply of drugs that can be redirected to those seeking to misuse them. METHODS: The Drug Enforcement Administration annual summary reports from the Automation of Reports and Consolidated Orders System provided weights of oxycodone distributed per state by business type (pharmacies, hospitals and practitioners). Weights were converted to morphine milligram equivalents (MME) per capita and normalised for population. The Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research provided mortality data for heroin, other opioids, methadone, other synthetic narcotics and other/unspecified narcotics. RESULTS: There was a sharp 280.13% increase in total MME/person of oxycodone from 2000 to 2010, followed by a slower 54.34% decrease from 2010 to 2021. Florida (2007-2011), Delaware (2003-2020) and Tennessee (2012-2021) displayed consistent and substantial elevations in combined MME/person compared with other states. In the peak year (2010), there was a 15-fold difference between the highest and lowest states. MME/person from only pharmacies, which constituted >94% of the total, showed similar results. Hospitals in Alaska (2000-2001, 2008, 2010-2021), Colorado (2008-2021) and DC (2000-2011) distributed substantially more MME/person over many years compared with other states. Florida stood out in practitioner-distributed oxycodone, with an elevation of almost 15-fold the average state from 2006 to 2010. Opioid-related deaths increased +806% from 2000 to 2021, largely driven by heroin, other opioids and other synthetic narcotics. CONCLUSIONS: Oxycodone distribution across the USA showed marked differences between states and business types over time. Investigation of opioid policies in states of interest may provide insight for future actions to mitigate opioid misuse.

Elevated drug overdose mortality among Americans who visit Florida, 2003-2020.

OBJECTIVE: Florida state has played a conspicuous role in the current U.S. drug epidemic. Reports suggest that even non-Florida residents may suffer excessive overdose fatalities while visiting the state, possibly in connection to two sets of events: (1) the overprescribing of controlled substances, and more recently, (2) the exploitation of patients' insurance benefits by unscrupulous operators of substance use treatment facilities in Florida. To date, however, no research has examined the overdose fatalities of non-Florida residents inside Florida. METHODS: Death certificate data were used to calculate proportionate mortality ratios for overdoses among Florida residents and visitors. Deaths occurring in the rest of the USA were used as reference populations. RESULTS: Between 2003 and 2020, overdose mortality was slightly elevated for Florida residents within their home counties (106.7 (95% CI 105.8 to 107.5)) and in other Florida counties (113.0 (95% CI 110.0 to 116.0)). Significantly, this mortality was much higher among out-of-state visitors in Florida (163.1 (95% CI 157.5 to 168.8)). When analysed by year, greater overdose mortality among visitors coincided with years when drug prescribing in Florida was rampant, and with the advent of expanded insurance coverage for substance use treatment. During this more recent period (since 2014), overdose mortality was exceptionally high for out-of-state visitors in Palm Beach County, where reports of malpractice in the Florida treatment industry have been concentrated. CONCLUSIONS: Overdose mortality was disproportionately high among out-of-state visitors in Florida. The results suggest that the regulatory policies in Florida may be implicated in drug-related casualties of people who live in other parts of the USA.

Trends in Fatal Opioid-Related Overdose in American Indian and Alaska Native Communities, 1999-2021.

INTRODUCTION: Opioid-related overdose mortality rates have increased sharply in the U.S. over the past two decades, and inequities across racial and ethnic groups have been documented. Opioid-related overdose trends among American Indian and Alaska Natives require further quantification and assessment. METHODS: Observational, U.S. population-based registry data on opioid-related overdose mortality between 1999 and 2021 were extracted in 2023 using ICD-10 codes from the U.S. Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research multiple cause of death file by race, Hispanic ethnicity, sex, and age. Segmented time series analyses were conducted to estimate opioid-related overdose mortality growth rates among the American Indian and Alaska Native population between 1999 and 2021. Analyses were performed in 2023. RESULTS: Two distinct time segments revealed significantly different opioid-related overdose mortality growth rates within the overall American Indian and Alaska Native population, from 0.36 per 100,000 (95% CI=0.32, 0.41) between 1999 and 2019 to 6.5 (95% CI=5.7, 7.31) between 2019 and 2021, with the most pronounced increase among those aged 24-44 years. Similar patterns were observed within the American Indian and Alaska Native population with Hispanic ethnicity, but the estimated growth rates were generally steeper across most age groups than across the overall American Indian and Alaska Native population. Patterns of opioid-related overdose mortality growth rates were similar between American Indian and Alaska Native females and males between 2019 and 2021. CONCLUSIONS: Sharp increases in opioid-related overdose mortality rates among American Indian and Alaska Native communities are evident by age and Hispanic ethnicity, highlighting the need for culturally sensitive fatal opioid-related overdose prevention, opioid use disorder treatment, and harm-reduction efforts. Future research should aim to understand the underlying factors contributing to these high mortality rates and employ interventions that leverage the strengths of American Indian and Alaska Native culture, including the strong sense of community.

High levels of all-cause mortality among people who inject drugs from 2018 to 2022.

BACKGROUND: Mortality among people who inject drugs (PWID) is high, with overdose and HIV infection being the main causes of death. In Greece, there have been no data on mortality, and two HIV outbreaks have been recorded in this population in the past decade. In this study, we aim to estimate the all-cause crude mortality rate and the standardised mortality ratio in this population during 2018-2022. METHODS: PWID recruited from two community-based programs in Athens and Thessaloniki during 2018-2021 were interviewed and tested for HIV/HCV. Data on vital status (deceased/alive) and date of death were obtained from death registries through December 31, 2022. All-cause crude mortality rates (CMR) and standardised mortality ratios (SMR) were estimated. Determinants of mortality were assessed using Cox proportional-hazards model. RESULTS: Of 2,530 participants, 301 died over 8,543 person-years (PYs) of follow-up. The CMR (95 % CI) was 3.52 (3.15-3.94) deaths per 100 PYs; 3.10 per 100 PYs (2.68-3.58) in Athens and 4.48 per 100 PYs (3.74-5.37) in Thessaloniki. An increasing trend in CMR was identified over 2018-2022 in Athens (from 2.90 to 4.11 per 100 PYs, 41.5 % increase, p = 0.018). The pooled SMR (95 % CI) was 15.86 (14.17-17.76) for both cities and was particularly increased in younger individuals, females, those injecting daily, not enrolled to opioid agonist treatment and HIV-infected individuals. Older age, living in Thessaloniki, Greek origin, homelessness, history of injection in the past 12 months, and HIV infection were independently associated with higher risk of death. CONCLUSION: Mortality among PWID in the two largest cities (Athens and Thessaloniki) in Greece in 2018-2022 was high, with the population in Thessaloniki being particularly affected. The increasing trend in mortality in Athens may reflect the long-term impact of the COVID-19 pandemic. Preventive programs such as take-home naloxone, screening and treatment for HIV, are urgently needed.

Responding to 'wicked problems': policy and governance on drug-related deaths in English and Welsh prisons, 2015-2021.

BACKGROUND: Prison settings have been neglected in the growing literature on drug-related deaths. This paper explores policy and practice issues regarding the governance of drug-related deaths in prisons in England and Wales from 2015-2021. METHODS: Thematic documentary analysis was conducted on national level policy documents published between 2015-2021 (e.g. drug strategies, prison policy documents, Her Majesty's Inspectorate of Prisons and Prison and Probation Ombudsman (PPO) annual reports and guidance for staff). At the local (prison) level, all of the PPO fatal investigation reports and their associated action plans relating to 171 drug-related deaths from 2015-2021 were analysed thematically. Various modes of governance were identified using Head's 'wicked problems' conceptual framework including avoidance and denial, coercive controls, compartmentalised micro-management, incremental and pragmatic adjustment and technocratic problem-solving. RESULTS: There was strong evidence of the dominance of denial of the problem of drug-related deaths, coercive controls, micro-management and reliance on technological solutions in the early years (2015-2018). In some prisons, there developed a move towards the adoption of more pragmatic and incremental policies and push towards comprehensive policies over time. In others, remnants of denial and coercion remained. In our analysis, the focus on new psychoactive substances came to dominate attention, to the relative neglect of other substances and of the contribution of mental and physical illness to these deaths. Staff are not equipped, supported or resourced adequately to deal with the two 'wicked problems' of increasing rates of drug use and mental illness which collide in the prison setting. CONCLUSION: The PPO investigations repeatedly recommend reducing supply and improving monitoring and surveillance and the emergency response. There is less focus on prevention and reducing demand or improving the wider environmental context and culture in which the deaths occur. Policy needs to pay more attention to the fundamental issues driving the current deterioration in conditions in prisons.

Routes of Drug Use Among Drug Overdose Deaths - United States, 2020-2022.

Preliminary reports indicate that more than 109,000 drug overdose deaths occurred in the United States in 2022; nearly 70% of these involved synthetic opioids other than methadone, primarily illegally manufactured fentanyl and fentanyl analogs (IMFs). Data from the western United States suggested a transition from injecting heroin to smoking IMFs. CDC analyzed data from the State Unintentional Drug Overdose Reporting System to describe trends in routes of drug use in 27 states and the District of Columbia among overdose deaths that occurred during January 2020-December 2022, overall and by region and drugs detected. From January-June 2020 to July-December 2022, the percentage of overdose deaths with evidence of injection decreased 29.1%, from 22.7% to 16.1%, whereas the percentage with evidence of smoking increased 73.7%, from 13.3% to 23.1%. The number of deaths with evidence of smoking increased 109.1%, from 2,794 to 5,843, and by 2022, smoking was the most commonly documented route of use in overdose deaths. Trends were similar in all U.S. regions. Among deaths with only IMFs detected, the percentage with evidence of injection decreased 41.6%, from 20.9% during January-June 2020 to 12.2% during July-December 2022, whereas the percentage with evidence of smoking increased 78.9%, from 10.9% to 19.5%. Similar trends were observed among deaths with both IMFs and stimulants detected. Strengthening public health and harm reduction services to address overdose risk related to diverse routes of drug use, including smoking and other noninjection routes, might reduce drug overdose deaths.

Polysubstance mortality trends in White and Black Americans during the opioid epidemic, 1999-2018.

BACKGROUND: Psychoactive drug combinations are increasingly contributing to overdose deaths among White and Black Americans. To understand the evolving nature of overdose crisis, inform policies, and develop tailored and equitable interventions, this study provides a comprehensive assessment of polysubstance mortality trends by race and sex during the opioid epidemic. METHODS: We used serial cross-sectional US mortality data for White and Black populations from 1999 through 2018 to calculate annual age-adjusted death rates (AADR) involving any opioid, opioid subtypes, benzodiazepines, cocaine, psychostimulants, or combinations of these drugs, stratified by race and sex. Trend changes in AADR were analyzed using joinpoint regression models and expressed as average annual percent change (AAPC) during each period of the three waves of the opioid epidemic: 1999-2010 (wave 1), 2010-2013 (wave 2), and 2013-2018 (wave 3). Prevalence measures assessed the percent co-involvement of an investigated drug in the overall death from another drug. RESULTS: Polysubstance mortality has shifted from a modest rise in death rates due to benzodiazepine-opioid overdoses among White persons (wave 1) to a substantial increase in death rates due to illicit drug combinations impacting both White and Black populations (wave 3). Concurrent cocaine-opioid use had the highest polysubstance mortality rates in 2018 among Black (5.28 per 100,000) and White (3.53 per 100,000) persons. The steepest increase in death rates during wave 3 was observed across all psychoactive drugs when combined with synthetic opioids in both racial groups. Since 2013, Black persons have died faster from cocaine-opioid and psychostimulant-opioid overdoses. Between 2013 and 2018, opioids were highly prevalent in cocaine-related deaths, increasing by 33% in White persons compared to 135% in Blacks. By 2018, opioids contributed to approximately half of psychostimulant and 85% of benzodiazepine fatal overdoses in both groups. The magnitude and type of drug combinations with the highest death rates differed by race and sex, with Black men exhibiting the highest overdose burden beginning in 2013. CONCLUSIONS: The current drug crisis should be considered in the context of polysubstance use. Effective measures and policies are needed to curb synthetic opioid-involved deaths and address disparate mortality rates in Black communities.

Racial, Ethnic, and Regional Disparities in Cocaine-Involved Overdose Deaths in the US, 1999-2020.

BACKGROUND: Social inequalities among underrepresented communities may lead to higher overdose mortality involving cocaine use. We assessed the temporal trends in cocaine-involved overdose mortality rate in the US by race, ethnicity, and geographic region from 1999 to 2020. METHODS: We conducted a cross-sectional study among adults in the US using data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database (1999 to 2020). To identify cocaine-involved overdose decedents, we used the International Classification of Diseases Code, 10th Revision-T40.5. We used Joinpoint regression to examine the trends in age-adjusted cocaine-involved overdose mortality rates (AAMR) by race, ethnicity, and geographic region and estimated annual percentage changes (APC). RESULTS: Overall, cocaine-involved overdose mortality trends increased (APC, 11.3%; 95% CI, 0.6, 23.2) from 2017 to 2020. The latest trends have remained stable among Non-Hispanic Whites since 2017 (APC, 4.3%; 95% CI, -5.7%, 15.4%) but have significantly increased among Non-Hispanic Blacks (APC, 27.2%; 95% CI, 22.1%, 32.5%), Hispanics (APC, 26.9%; 95% CI, 20.6%, 33.5%), and American Indians/Alaska Natives (APC, 24.1%; 95% CI, 16.5%, 32.2%). CONCLUSION: Cocaine-related overdose deaths in the US significantly increased between 2017 and 2020, but the increase was among racial and ethnic minorities and not among Non-Hispanic Whites. These findings suggest a need to address the US' longstanding racial and ethnic healthcare inequities.

Pharmacobezoar-Related Fatalities: A Case Report and a Review of the Literature.

ABSTRACT: Pharmacobezoars develop after an acute overdose or during routine drug administration. Here, the authors present a case of fatal multidrug overdose involving a 62-year-old woman. Her usual treatment included tramadol extended-release, citalopram, and mirtazapine. Furthermore, she self-medicated and misused her husband's medications. The autopsy revealed the presence of a voluminous medication bezoar in the stomach. No mechanical complication was noted. Toxicologic analyses were performed using gas chromatography with flame ionization detection, liquid chromatography with diode array detection, gas chromatography with mass spectrometry detection, and liquid chromatography coupled to tandem mass spectrometry. Tramadol (34,000 mcg/L), O-desmethyltramadol (2200 mcg/L), propranolol (6000 mcg/L), bromazepam (2500 mcg/L), zopiclone (1200 mcg/L), and citalopram (700 mcg/L) were identified in femoral blood at toxic concentrations. Interestingly, the femoral blood and vitreous humor concentration ratio was approximately 0.7. Furthermore, an English exhaustive literature search was performed using several different electronic databases without any limiting period to identify published pharmacobezoar-related fatalities. Seventeen publications were identified reporting a total of 19 cases. Decedents' mean age was 47.6 years [0.8-79] and a clear female predominance emerged. Several drugs were involved in pharmacobezoar formation. Death was attributed to drug toxicity in 13 cases, and to mechanical complications and/or sepsis in 4 cases. A mixed cause of death was reported in 2 cases. Although rare, pharmacobezoars remain potentially lethal and raise challenges in therapeutic management.

Racial and Ethnic Disparities in Accidental and Undetermined Drug Overdose Deaths - Rhode Island, 2016-2021.

BACKGROUND: Over the last 21 years, drug overdose deaths have increased nationwide, particularly in Rhode Island (RI). The goal of this work is to identify populations that are disproportionately impacted by accidental drug overdose deaths to guide future intervention efforts.  Methods: We obtained data on accidental and undetermined drug overdose deaths from the RI State Unintentional Drug Overdose Reporting System (SUDORS) database from 2016 to 2021. We compared basic demographic factors stratified by decedent race and ethnicity. Chi Square and Fisher's exact tests were used to determine differences in characteristics across racial groups. FINDINGS: Across all race and ethnic groups, cocaine-involved (64.5%) fatal overdoses were higher among Black non-Hispanics. White, non-Hispanics (31.4%) were more likely to receive treatment for substance use disorder (SUD) when compared to minority groups. CONCLUSION: To help address the gaps in treatment for SUD among minority groups, culturally responsive intervention efforts should prioritize connecting minority groups to treatment.

Overdose deaths involving synthetic opioids: Racial/ethnic and educational disparities in the eastern and western US.

BACKGROUND: This study examined racial/ethnic and educational disparities in US synthetic opioid overdose mortality East and West of the Mississippi River. METHODS: Using restricted-access 2018-2021 mortality data from the Centers for Disease Control and Prevention and population estimates from the American Community Survey, age-standardized rate ratios (SRRs) and 95% Confidence Intervals (CIs) were used to compare rates of synthetic opioid mortality by race/ethnicity and educational attainment level in the regions East and West of the Mississippi River. RESULTS: Racial/ethnic disparities in synthetic opioid mortality rates, relative to the Non-Hispanic (NH) White population, were observed in the NH Black (SRR, 1.5 [95% CI, 1.5-1.6]) and NH American Indian/Alaska Native (SRR, 2.1 [95% CI, 1.9-2.2]) populations in the West, and the Puerto Rican (SRR, 1.3 [95% CI, 1.3-1.3]) and NH American Indian/Alaska Native (SRR, 1.5 [95% CI, 1.4-1.6]) populations in the East. Relative to those with a Bachelor's degree or higher: in the West, the synthetic opioid mortality rate was more than seven times as high for those with a high school diploma only (SRR 7.7 [95% CI, 7.4-8.0]), and in the East, approximately thirteen times as high for those with a high school diploma only (SRR, 13.0 [95% CI, 12.7-13.3]) or less than a high school diploma (SRR, 13.3 [95% CI, 13.0-13.7]). CONCLUSION: Disparities in rates of synthetic opioid mortality differ in the eastern and western US, supporting tailored responses within each region.