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.

Distribution of intranasal naloxone to potential opioid overdose bystanders in Sweden: effects on overdose mortality in a full region-wide study.

OBJECTIVES: Distribution of take-home naloxone is suggested to reduce opioid-related fatalities, but few studies have examined the effects on overdose deaths in the general population of an entire community. This study aimed to assess the effects on overdose deaths of a large-scale take-home naloxone programme starting in June 2018, using an observational design with a historic control period. DESIGN: From the national causes of death register, deaths diagnosed as X42 or Y12 (International Classification of Diseases, 10th revision, ICD-10) were registered as overdoses. Numbers of overdoses were calculated per 100 000 inhabitants in the general population, and controlled for data including only individuals with a prior substance use disorder in national patient registers, to focus on effects within the primary target population of the programme. The full intervention period (2019-2021) was compared with a historic control period (2013-2017). SETTING: Skåne county, Sweden. PARTICIPANTS: General population. INTERVENTIONS: Large-scale take-home naloxone distribution to individuals at risk of overdose. PRIMARY AND SECONDARY OUTCOME MEASURES: Decrease in overdose deaths per 100 000 inhabitants, in total and within the population with substance use disorder diagnosis. RESULTS: Annual average number of overdose deaths decreased significantly from 3.9 to 2.8 per 100 000 inhabitants from the control period to the intervention period (a significant decrease in men, from 6.7 to 4.3, but not in women, from 1.2 to 1.3). Significant changes remained when examining only prior substance use disorder patients, and decreases in overdose deaths could not be attributed to a change in treatment needs for opioid use disorders in healthcare and social services. CONCLUSIONS: The present study, involving 3 years of take-home naloxone distribution, demonstrated a decreased overdose mortality in the population, however, only in men. The findings call for further implementation of naloxone programmes, and for further studies of potential effects and barriers in women. TRIAL REGISTRATION NUMBER: NCT03570099.

Intranasal Naloxone for Opioid Overdose.

This JAMA Insights describes indications for naloxone use in preventing opioid overdoses and benefits vs barriers to its availability following FDA approval of its availability without a prescription.

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.

US drug overdose mortality rose faster among hispanics than non-hispanics from 2010 to 2021.

BACKGROUND: Historically, overdose mortality rates among Hispanics have been lower than non-Hispanics. The purpose of this analysis was to characterize the U.S. overdose crisis among Hispanics compared to non-Hispanics. METHODS: We used the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiological Research (WONDER) platform to obtain drug overdose mortality rates per 100,000 population between 2010 and 2021 for Hispanics and non-Hispanics. We examined the relative percent change and specific drug involvement (2010-2021) and state-level disparities (2010-2020) among Hispanics versus non-Hispanics. We calculated rate ratios by state and annual percent change in total and for each specific drug. Statistical analyses were performed using R software version 4.0.3 (R Project for Statistical Computing). RESULTS: Nationally, from 2010 to 2021, Hispanic overdose rates rose from 5.6 to 21.7 per 100,000, an increase of 287.5 % compared to 13.5-35.1 per 100,000, an increase of 160 % among non-Hispanics. The average annual percent change was 12 % for Hispanics and 9 % for non-Hispanics. The three most common drug classes involved in overdose deaths among both groups included: Fentanyls and synthetic opioids; cocaine; and prescription opioids. Hispanic overdose rates were higher than non-Hispanic rates in New Mexico, Colorado, Massachusetts, and Pennsylvania in 2020, versus only Michigan in 2010. CONCLUSIONS: We observed disparities in overdose mortality growth among Hispanics compared to non-Hispanics from 2010 to 2021. These disparities highlight the urgency to develop community-centered solutions that take into consideration the social and structural inequalities that exacerbate the effects of the opioid overdose crisis on Hispanic communities.

Changes in Opioid and Benzodiazepine Poisoning Deaths After Cannabis Legalization in the US: A County-level Analysis, 2002-2020.

BACKGROUND: Cannabis legalization for medical and recreational purposes has been suggested as an effective strategy to reduce opioid and benzodiazepine use and deaths. We examined the county-level association between medical and recreational cannabis laws and poisoning deaths involving opioids and benzodiazepines in the US from 2002 to 2020. METHODS: Our ecologic county-level, spatiotemporal study comprised 49 states. Exposures were state-level implementation of medical and recreational cannabis laws and state-level initiation of cannabis dispensary sales. Our main outcomes were poisoning deaths involving any opioid, any benzodiazepine, and opioids with benzodiazepines. Secondary analyses included overdoses involving natural and semi-synthetic opioids, synthetic opioids, and heroin. RESULTS: Implementation of medical cannabis laws was associated with increased deaths involving opioids (rate ratio [RR] = 1.14; 95% credible interval [CrI] = 1.11, 1.18), benzodiazepines (RR = 1.19; 95% CrI = 1.12, 1.26), and opioids+benzodiazepines (RR = 1.22; 95% CrI = 1.15, 1.30). Medical cannabis legalizations allowing dispensaries was associated with fewer deaths involving opioids (RR = 0.88; 95% CrI = 0.85, 0.91) but not benzodiazepine deaths; results for recreational cannabis implementation and opioid deaths were similar (RR = 0.81; 95% CrI = 0.75, 0.88). Recreational cannabis laws allowing dispensary sales was associated with consistent reductions in opioid- (RR = 0.83; 95% CrI = 0.76, 0.91), benzodiazepine- (RR = 0.79; 95% CrI = 0.68, 0.92), and opioid+benzodiazepine-related poisonings (RR = 0.83; 95% CrI = 0.70, 0.98). CONCLUSIONS: Implementation of medical cannabis laws was associated with higher rates of opioid- and benzodiazepine-related deaths, whereas laws permitting broader cannabis access, including implementation of recreational cannabis laws and medical and recreational dispensaries, were associated with lower rates. The estimated effects of the expanded availability of cannabis seem dependent on the type of law implemented and its provisions.

Fentanyl Overdose.

This JAMA Patient Page describes fentanyl and illicit fentanyl analogues, and the common signs and symptoms of fentanyl overdose, its treatment, and overdose prevention measures.

Cloud Computing Synthetic Syndromic Surveillance Systems: Opioid Epidemic in Illinois.

With an increasing number of overdose cases yearly, the city of Chicago is facing an opioid epidemic. Many of these overdose cases lead to 911 calls that necessitate timely response from our limited emergency medicine services. This paper demonstrates how data from these calls along with synthetic and geospatial data can help create a syndromic surveillance system to combat this opioid crisis. Chicago EMS data is obtained from the Illinois Department of Public Health with a database structure using the NEMSIS standard. This information is combined with information from the RTI U.S. Household Population database, before being transferred to an Azure Data Lake. Afterwards, the data is integrated with Azure Synapse before being refined in another data lake and filtered with ICD-10 codes. Afterwards, we moved the data to ArcGIS Enterprise to apply spatial statistics and geospatial analytics to create our surveillance system.

Emergency Medical Services and Syndromic Surveillance: A Comparison With Traditional Surveillance and Effects on Timeliness.

OBJECTIVE: Traditional public health surveillance of nonfatal opioid overdose relies on emergency department (ED) billing data, which can be delayed substantially. We compared the timeliness of 2 new data sources for rapid drug overdose surveillance-emergency medical services (EMS) and syndromic surveillance-with ED billing data. METHODS: We used data on nonfatal opioid overdoses in Kentucky captured in EMS, syndromic surveillance, and ED billing systems during 2018-2019. We evaluated the time-series relationships between EMS and ED billing data and syndromic surveillance and ED billing data by calculating cross-correlation functions, controlling for influences of autocorrelations. A case example demonstrates the usefulness of EMS and syndromic surveillance data to monitor rapid changes in opioid overdose encounters in Kentucky during the COVID-19 epidemic. RESULTS: EMS and syndromic surveillance data showed moderate-to-strong correlation with ED billing data on a lag of 0 (r = 0.694; 95% CI, 0.579-0.782; t = 9.73; df = 101; P < .001; and r = 0.656; 95% CI, 0.530-0.754; t = 8.73; df = 101; P < .001; respectively) at the week-aggregated level. After the COVID-19 emergency declaration, EMS and syndromic surveillance time series had steep increases in April and May 2020, followed by declines from June through September 2020. The ED billing data were available for analysis 3 months after the end of a calendar quarter but closely followed the trends identified by the EMS and syndromic surveillance data. CONCLUSION: Data from EMS and syndromic surveillance systems can be reliably used to monitor nonfatal opioid overdose trends in Kentucky in near-real time to inform timely public health response.

Association between opioid-related deaths and prescribed opioid dose and psychotropic medicines in England: a case-crossover study.

BACKGROUND: Opioid-overdose deaths are associated with poisoning with prescription and illicit opioids in the USA. In contrast, opioid-related deaths (ORDs) in the UK often involve drugs and substances of misuse, and may not be associated with a high dose of prescribed opioids. This study aimed to investigate the association between prescribed opioid dose and ORDs in UK primary care. METHODS: This case-crossover study used the Clinical Practice Research Datalink and death registration between 2000 and 2015 to identify ORDs. Daily oral morphine equivalent (OMEQ) dose was measured within a 90 day focal window before ORD and three earlier reference windows. Conditional logistic regression models assessed the adjusted odds ratio (aOR) and 95% confidence interval (95% CI) comparing daily OMEQ dose greater than 120 mg in the focal window against the reference windows. RESULTS: Of the 232 ORDs, 62 (26.7%) were not prescribed opioids in the year before death. Of the remaining 170 cases, 50 (29.4%) were never prescribed a daily OMEQ dose greater than 50 mg. Daily OMEQ doses over 120 mg (aOR 2.20; 95% CI: 1.06-4.56), co-prescribing gabapentinoids (aOR 2.32; 95% CI: 1.01-5.33), or some antidepressants (aOR 3.03; 95% CI: 1.02-9.04) significantly increased the risk of ORD. CONCLUSIONS: Daily OMEQ dose greater than 120 mg and the concomitant use of psychotropic medicines were related to ORDs in the UK. Prescribers should cautiously avoid prescribing opioids with a daily OMEQ dose greater than 120 mg day-1 and the combination of opioids and gabapentinoids, even with low opioid doses.

The discounting of death: Probability discounting of heroin use by fatal overdose likelihood and drug purity.

As fatal overdoses from synthetic opioids continue to rise, we need to understand decision-making processes underlying heroin and synthetic opioid use. This study evaluated the influence of sample impurity and fatal overdose risk on hypothetical heroin use. Individuals who currently use heroin (n = 69) were recruited online. Participants completed two probability-discounting tasks evaluating the likelihood of using a sample of heroin based on the likelihood of sample impurity and likelihood of fatal overdose, where greater discounting represented reduced use likelihood. Prior to completing the probability-discounting tasks, participants were randomized to read one of four prompts varying by the presence of information on heroin effects and active (e.g., fentanyl) or inert impurities. Influence of prompts on discounting processes and associations among probability-discounting measures, opioid use behaviors, and dependence severity were evaluated. Heroin use likelihood decreased with increased impurity or overdose risk and in a generally orderly fashion. Discounting was greater (i.e., reduced heroin use likelihood) when overdose risk, compared to sample impurity, was manipulated. Less discounting was associated with more severe opioid dependence. Discounting did not differ among prompts for either task. Individuals might adjust their heroin-use behavior to reduce harm with risk-related information. Greater discounting elicited by overdose relative to impurity risk suggests that equating adulteration and overdose risk is essential for harm reduction. Expanded access to drug checking services, which inform impurity and overdose risk, can reduce fatal overdoses. Due to fear of legal sanctions for these services, legislation and judicial decisions should explicitly protect these services. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Spatiotemporal Analysis of the Association Between Pain Management Clinic Laws and Opioid Prescribing and Overdose Deaths.

Pain management clinic (PMC) laws were enacted by 12 states to promote appropriate opioid prescribing, but their impact is inadequately understood. We analyzed county-level opioid overdose deaths (National Vital Statistics System) and patients filling long-duration (≥30 day) or high-dose (≥90 morphine milligram equivalents per day) opioid prescriptions (IQVIA, Inc.) in the United States in 2010-2018. We fitted Besag-York-Mollié spatiotemporal models to estimate annual relative rates (RRs) of overdose and prevalence ratios (PRs) of high-risk prescribing associated with any PMC law and 3 provisions: payment restrictions, site inspections, and criminal penalties. Laws with criminal penalties were significantly associated with reduced PRs of long-duration and high-dose opioid prescriptions (adjusted PR = 0.82, 95% credible interval (CrI): 0.82, 0.82, and adjusted PR = 0.73, 95% CI: 0.73, 0.74 respectively) and reduced RRs of total and natural/semisynthetic opioid overdoses (adjusted RR = 0.86, 95% CrI: 0.80, 0.92, and adjusted RR = 0.84, and 95% CrI: 0.77, 0.92, respectively). Conversely, PMC laws were associated with increased relative rates of synthetic opioid and heroin overdose deaths, especially criminal penalties (adjusted RR = 1.83, 95% CrI: 1.59, 2.11, and adjusted RR = 2.59, 95% CrI: 2.22, 3.02, respectively). Findings suggest that laws with criminal penalties were associated with intended reductions in high-risk opioid prescribing and some opioid overdoses but raise concerns regarding unintended consequences on heroin/synthetic overdoses.

The rise of illicit fentanyls, stimulants and the fourth wave of the opioid overdose crisis.

PURPOSE OF REVIEW: This review provides an update on recently published literature on the rise of illicit fentanyls, risks for overdose, combinations with other substances, e.g. stimulants, consequences, and treatment. RECENT FINDINGS: Overdose due to illicit synthetic opioids (e.g. fentanyl and fentanyl analogs) continues to rise in the US both preceding and during the COVID-19 pandemic. Fentanyl-related overdose is rising in new geographic areas e.g. the western USA. Stimulant-related overdose is also increasing nationwide driven by methamphetamine and cocaine. Polysubstance use, e.g. the use of a stimulant along with an opioid is driving stimulant-related overdose. Other medical consequences of injection drug use are rising including HIV and hepatitis C infections. Medication approaches to treating opioid use disorder remain the standard of care and there are new promising pharmacological approaches to treating methamphetamine use disorder. SUMMARY: A 'fourth wave' of high mortality involving methamphetamine and cocaine use has been gathering force in the USA. Availability and use of illicit fentanyls are still the major drivers of overdose deaths and the current rise in stimulant-related deaths appears entwined with the ongoing opioid epidemic.

A case report on fatal intoxication by tapentadol: Study of distribution and metabolism.

We report a case in which a tapentadol acute intoxication was suspected as the cause of death of a 39-year-old man: approximately two days after death, cardiac and femoral blood, as well as urine, bile, gastric content and chest hair, were collected during the autopsy. Tapentadol was detected before and after hydrolysis in femoral (530 ng/mL unconjugated and 1570 ng/mL conjugated) and cardiac (680 ng/mL unconjugated and 3440 ng/mL conjugated) blood, and additionally in bile (3200 ng/mL), urine (9300 ng/mL), chest hair (2850 pg/mg) and gastric content. LC-QTOF screening analysis confirmed the presence of five different tapentadol metabolites (tapentadol-O-glucuronide, tapentadol-O-sulfate, N-desmethyltapentadol, N-desmethyltapentadol-glucuronide and N-desmethyltapentadol-O-sulfate), in urine, bile, cardiac and femoral blood. Positivity of body hairs allowed us to conclude that the man had used tapentadol in the last weeks/months. Autopsy and toxicological results (also positive for clotiapine, diazepam and chlordesmethyldiazepam) suggested that tapentadol could have caused, even at low concentrations, a severe respiratory depression, which contributed to the death of the subject. This is one of the few cases in literature where tapentadol was detected in blood, together with its metabolites, and the only one in which the parent drug was identified in hairs.

Coprescription of Opioids With Other Medications and Risk of Opioid Overdose.

Polypharmacy is common among patients taking prescription opioids long-term, and the codispensing of interacting medications may further increase opioid overdose risk. To identify nonopioid medications that may increase opioid overdose risk in this population, we conducted a case-crossover-based screening of electronic claims data from IBM MarketScan and Optum Clinformatics Data Mart spanning 2003 through 2019. Eligible patients were 18 years of age or older and had at least 180 days of continuous enrollment and 90 days of prescription opioid use immediately before an opioid overdose resulting in an emergency room visit or hospitalization. The main analysis quantified the odds ratio (OR) between opioid overdose and each nonopioid medication dispensed in the 90 days immediately before the opioid overdose date after adjustment for prescription opioid dosage and benzodiazepine codispensing. Additional analyses restricted to patients without cancer diagnoses and individuals who used only oxycodone for 90 days immediately before the opioid overdose date. The false discovery rate (FDR) was used to account for multiple testing. We identified 24,866 individuals who experienced opioid overdose. Baclofen (OR 1.56; FDR < 0.01; 95% confidence interval (CI), 1.29 to 1.89), lorazepam (OR 1.53; FDR < 0.01; 95% CI, 1.25 to 1.88), and gabapentin (OR 1.16; FDR = 0.09; 95% CI, 1.04 to 1.28), among other nonopioid medications, were associated with opioid overdose. Similar patterns were observed in noncancer patients and individuals who used only oxycodone. Interventions may focus on prescribing safer alternatives when a potential for interaction exists.

Fentanyl contaminated "M30" pill overdoses in pediatric patients.

BACKGROUND: Fentanyl is a high potency opioid that has become an increasingly large proportion of the illicit drug supply. Fentanyl overdoses and deaths, including in pediatric patients, has concomitantly increased. PURPOSE: To describe two cases of pediatric fentanyl overdoses via "M30" pills illicitly sold as oxycodone. BASIC PROCEDURES: Two cases of pediatric opioid toxicity reportedly from oxycodone are presented in which mass spectrometry was used to confirm fentanyl and not oxycodone exposure. MAIN FINDINGS: Both pediatric patients required naloxone and admission to the intensive care unit following exposure. Both had urine drug screens that did not show the presence of opioids but mass spectrometry testing confirmed fentanyl exposure. CONCLUSIONS: Providers should be aware of these illicit tablets, know not to assume they are pharmaceutical, and consider the risk they pose to pediatric patients through exploratory ingestion or misuse. Further inquiry, including social investigation, should be considered for pediatric patients presenting with reported oxycodone ingestion, especially blue "M30" pills.