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JAMA Network Open Aug 2023Synthetic opioids, such as the fentanyl analogue and nitazene drug class, are among the fastest growing types of opioids being detected in patients in the emergency...
IMPORTANCE
Synthetic opioids, such as the fentanyl analogue and nitazene drug class, are among the fastest growing types of opioids being detected in patients in the emergency department (ED) with illicit opioid overdose (OD). However, clinical outcomes from OD of novel potent opioids (NPOs), specifically nitazenes, are unknown aside from small case series.
OBJECTIVE
To determine naloxone administration and clinical sequelae of patients who were in the ED with NPO overdose compared with fentanyl OD.
DESIGN, SETTING, AND PARTICIPANTS
This is a cohort study subgroup analysis of adults admitted to the ED and tested positive for NPOs among in the ongoing nationwide ToxIC Fentalog cohort study from 2020 to 2022. Patients who were in the ED with a presumed acute opioid OD and residual blood samples were included, and those testing positive for NPOs were analyzed. Patients were included in this analysis if their confirmatory testing was positive for an NPO analyte, such as brorphine, isotonitazene, metonitazene, and/or N-piperidinyl etonitazene. A comparison group included patients that were positive for fentanyl and devoid of any other analytes on toxicologic analysis.
EXPOSURES
Patients were exposed to NPOs, including brorphine, isotonitazene, metonitazene and/or N-piperidinyl etonitazene.
MAIN OUTCOMES AND MEASURES
The primary outcome was the total number of naloxone doses and total cumulative naloxone dose administered as part of routine clinical care following the OD. Naloxone requirements and clinical sequelae of NPO-positive patients were compared with those testing positive for fentanyl only.
RESULTS
During the study period, 2298 patients were screened, of whom 717 met inclusion criteria, 537 had complete laboratory testing data, with 11 (2.0%) positive for only fentanyl and 9 (1.7%) positive for NPOs (brorphine, isotonitazene, metonitazene, or N-piperidinyl etonitazene). The age range of patients was aged 20 to 57 years (4 males [44.4%] and 5 females [55.6%]). The NPO group received a statistically significantly higher mean (SD) number of naloxone boluses in-hospital (1.33 [1.50]) compared with the fentanyl group (0.36 [0.92]) (P = .02), which corresponded to a moderately large effect size (Cohen d = 0.78). Metonitazene overdose was associated with cardiac arrest and more naloxone doses overall. Metonitazene cases had a mean (SD) number of 3.0 (0) naloxone doses, and 2 of 2 patients (100%) with metonitazene overdoses were administered cardiopulmonary resuscitation.
CONCLUSIONS AND RELEVANCE
In this cohort study of patients admitted to the ED with confirmed opioid overdose testing positive for NPOs, in-hospital naloxone dosing was high compared with patients who tested positive for fentanyl alone. Further study is warranted to confirm these preliminary associations.
Topics: Adult; Female; Male; Humans; Young Adult; Middle Aged; Analgesics, Opioid; Opiate Overdose; Cohort Studies; Drug Overdose; Fentanyl; Disease Progression; Emergency Service, Hospital
PubMed: 37642962
DOI: 10.1001/jamanetworkopen.2023.31264 -
Drug and Alcohol Dependence Sep 2021Non-fatal opioid-related overdoses have increased significantly over the past two decades and there have been increasing reports of brain injuries and/or neurocognitive... (Review)
Review
BACKGROUND
Non-fatal opioid-related overdoses have increased significantly over the past two decades and there have been increasing reports of brain injuries and/or neurocognitive impairments following overdose events. Limited preclinical research suggests that opioid overdoses may cause brain injury; however, little is known about such injuries in humans. The purpose this systematic review is to summarize existing studies on neurocognitive impairments and/or brain abnormalities associated with an opioid-related overdose in humans.
METHODS
PubMed, Web of Science, Ovid MEDLINE and PsyINFO were searched, without year restrictions, and identified 3099 articles. An additional 24 articles were identified by reviewing references. Articles were included if they were published in English, reported study findings in humans, included individuals 18 years of age or older, and reported an objective measure of neurocognitive impairments and/or brain abnormalities resulting from an opioid-related overdose. Six domains of bias (selection, performance, attrition, detection (two dimensions) and reporting were evaluated and themes were summarized.
RESULTS
Seventy-nine journal articles, published between 1973-2020, were included in the review. More than half of the articles were case reports (n = 44) and there were 11 cohort studies, 18 case series, and 6 case-control studies. All of the studies were categorized as at-risk of bias, few controlled for confounding factors, and methodological differences made direct comparisons difficult. Less than half of the studies reported toxicology results confirming an opioid-related overdose; 64.6 % reported brain MRI results and 27.8 % reported results of neuropsychological testing. Only two studies had within subject comparative data to document changes in the brain possibly associated with an overdose. Despite these limitations, existing publications suggest that brain injuries and neurocognitive impairments are associated with opioid overdose. Additional research is needed to establish the incidence of overdose-related brain injuries and the potential impact on functioning, as well as engagement in treatment of substance use disorders.
CONCLUSIONS
Respiratory depression is a defining characteristic of opioid overdose and prolonged cerebral hypoxia may cause brain injuries and/or neurocognitive impairments. The onset, characteristics, and duration of such injuries is variable and additional research is needed to understand their clinical implications.
Topics: Adolescent; Adult; Analgesics, Opioid; Brain; Drug Overdose; Humans; Opiate Overdose; Substance-Related Disorders
PubMed: 34271512
DOI: 10.1016/j.drugalcdep.2021.108838 -
MMWR. Morbidity and Mortality Weekly... Jun 2023In 2022, provisional data indicated that more than two thirds (68%) of the reported 107,081 drug overdose deaths in the United States involved synthetic opioids other...
In 2022, provisional data indicated that more than two thirds (68%) of the reported 107,081 drug overdose deaths in the United States involved synthetic opioids other than methadone, principally illicitly manufactured fentanyls (IMFs) (1). Xylazine, a nonopioid sedative not approved for human use and with no known antidote, has been increasingly detected in IMF products in the U.S. drug supply* and in IMF-involved overdose deaths (2). Limited studies suggest xylazine can cause central nervous system depression, respiratory depression, bradycardia, and hypotension in humans (3,4); chronic use might lead to severe withdrawal symptoms as well as skin ulcerations (4). This report uses data from CDC's State Unintentional Drug Overdose Reporting System (SUDORS) to describe IMF-involved overdose deaths with and without xylazine detected that occurred during January 2019-June 2022. Among 21 jurisdictions, which included 20 states and the District of Columbia, the monthly percentage of IMF-involved deaths with xylazine detected increased 276%, from 2.9% to 10.9%. Among IMF-involved deaths during January 2021-June 2022 in 32 jurisdictions, xylazine was detected in a higher percentage of jurisdictions in the Northeast U.S. Census Bureau region; listing detected xylazine as a cause of death varied across jurisdictions. Expanded postmortem and illicit drug product testing for xylazine is needed to clarify prevalence in drug supplies; further investigation of xylazine's effects on humans is necessary to characterize morbidity and overdose risk. It is important for overdose prevention and response messages to highlight the potential presence of xylazine in IMF products and emphasize the need for respiratory and cardiovascular support to address the sedative effects of xylazine.
Topics: United States; Humans; Xylazine; Opiate Overdose; Drug Overdose; District of Columbia; Fentanyl
PubMed: 37384558
DOI: 10.15585/mmwr.mm7226a4 -
HCA Healthcare Journal of Medicine 2021Description The opioid crisis poses a substantial threat to youth throughout the nation. This crisis has been exacerbated by the COVID-19 pandemic, reversing some of the...
Description The opioid crisis poses a substantial threat to youth throughout the nation. This crisis has been exacerbated by the COVID-19 pandemic, reversing some of the positive national trends in the fight against the opioid epidemic. Some risk factors for youth opioid use have been identified nationally. The South Florida tri-county region of Miami-Dade, Broward and Palm Beach is a culturally distinct region which may not follow national trends and likely has unique risk and protective factors. To address the concerning spike in youth opioid use in South Florida, a community coalition was formed to identify factors unique to South Florida and create a plan for early awareness and prevention.
PubMed: 37425639
DOI: 10.36518/2689-0216.1304 -
Assessing opioid overdose risk: a review of clinical prediction models utilizing patient-level data.Translational Research : the Journal of... Aug 2021Drug, and specifically opioid-related, overdoses remain a major public health problem in the United States. Multiple studies have examined individual risk factors... (Review)
Review
Drug, and specifically opioid-related, overdoses remain a major public health problem in the United States. Multiple studies have examined individual risk factors associated with overdose risk, but research developing clinical risk prediction tools for overdose has only emerged in the last few years. We conducted a comprehensive review of the literature on patient-level factors associated with opioid-related overdose risk, with an emphasis on clinical risk prediction models for opioid-related overdose in the United States. Studies that developed and/or validated clinical prediction models were closely reviewed and evaluated to determine the state of the field. We identified 12 studies that reported risk prediction models for opioid-related overdose risk. Published models were developed from a variety of data sources, including Veterans Health Administration data, Medicare data, commercial insurance data, and statewide linked datasets. Studies reported model performance using measures of discrimination, usually at good-to-excellent levels, though they did not always assess calibration. C-statistics were better for models that included clinical predictors (c-statistics: 0.75-0.95) compared to models without them (c-statistics: 0.69-0.82). External validation of models was rare, and we found no studies evaluating implementation of models or risk prediction tools into clinical practice. A common feature of these models was a high rate of false positives, largely because opioid-related overdose is rare in the general population. Thus, efforts to implement prediction models into practice should take into account that published models overestimate overdose risk for many low-risk patients. Future prediction models assessing overdose risk should employ external validation and address model calibration. In order to translate findings from prediction models into clinical public health benefit, future studies should focus on developing clinical prediction tools based on prediction models, implementing these tools into clinical practice, and evaluating the impact of these models on treatment decisions, patient outcomes, and, ultimately, opioid overdose rates.
Topics: Humans; Models, Statistical; Opiate Overdose; Opioid Epidemic; Patient-Specific Modeling; Risk Factors; Translational Research, Biomedical; United States
PubMed: 33762186
DOI: 10.1016/j.trsl.2021.03.012 -
The International Journal on Drug Policy Apr 2022The dominant focus of North America's current overdose crisis has been opioids, resulting in considerable research and harm reduction efforts to address opioid-related...
BACKGROUND
The dominant focus of North America's current overdose crisis has been opioids, resulting in considerable research and harm reduction efforts to address opioid-related overdose risks. Less attention has been paid to people who use stimulants (PWUS) despite recent increases in stimulant use and stimulant-involved overdoses (i.e., "overamping"). Stimulant users' definitions, risk factors and experiences of, and responses to, overamping are poorly understood, thereby putting PWUS at heightened risk of adverse health outcomes. This study explores how PWUS understand, experience, and respond to overamping.
METHODS
In-depth qualitative interviews were conducted with 61 PWUS in Vancouver, Canada's Downtown Eastside neighbourhood. Thematic analysis of interviews focused on contextualizing stimulant overdoses, including how PWUS understand, define, experience, and respond to overamping.
RESULTS
Participants associated overamping experiences with commonly identified signs and symptoms, such as rapid onset, elevated heart rate, incontinence, and audiovisua hallucinations, but also reported more serious indicators of overamping, such as unconsciousness, cardiac arrests and seizures. Our findings demonstrate that, among PWUS, there was no unified understanding of overamping such as with opioid overdose and individual experiences had substantial variation in severity and presentation. This impacted the ability to adequately respond to stimulant overdoses, which were primarily self-managed through methods including stabilizing breathing, polysubstance use, and cold showers.
CONCLUSION
Given the growing role of stimulants in North America's overdose crisis, there is an urgent need to improve the identification of stimulant overdoses in real world settings. Our findings identify a gap in current understandings of stimulant overdose, and demonstrate the need for public health and harm reduction interventions to better address overamp risk among PWUS, including harm reduction campaigns to disseminate information regarding identifying signs of, and proper responses to, overamping.
Topics: Analgesics, Opioid; Central Nervous System Stimulants; Drug Overdose; Harm Reduction; Humans; Opiate Overdose; Qualitative Research
PubMed: 35114520
DOI: 10.1016/j.drugpo.2022.103592 -
Public Health Reports (Washington, D.C.... 2021Although trends in opioid-related death rates in the United States have been described, the association between state-level opioid overdose death rates in early waves...
OBJECTIVES
Although trends in opioid-related death rates in the United States have been described, the association between state-level opioid overdose death rates in early waves and substance-related overdose death rates in later waves has not been characterized. We examined the relationship between state-level opioid overdose death rates at the beginning of the crisis (1999-2004) and overdose death rates for opioids and other substances in later years.
METHODS
Using 1999-2018 multiple cause of death data from the Centers for Disease Control and Prevention, we first categorized each state by quartile of baseline (1999-2004) opioid overdose death rates. By baseline opioid overdose death rates, we then compared states' annual overdose death rates from any opioid, heroin, synthetic opioids, sedatives, stimulants/methamphetamine, and cocaine from 2005 through 2018. To test the association between baseline opioid overdose death rates and subsequent substance-related overdose death rates for all 6 substances, we estimated unadjusted and adjusted linear models controlling for annual state-level unemployment, median household income, age, sex, and race/ethnicity.
RESULTS
Our results suggest 2 characteristics of the opioid crisis: persistence and pervasiveness. In adjusted analyses, we found that for each additional opioid overdose death per 100 000 population at baseline, states had 23.5 more opioid deaths, 4.4 more heroin deaths, 8.0 more synthetic opioid deaths, 9.2 more sedative deaths, 3.3 more stimulant deaths, and 4.6 more cocaine deaths per 100 000 population from 2005 to 2018.
CONCLUSION
These findings have important implications for continued surveillance to assist policy makers in deciding how to deploy resources to combat not just opioid use disorder but also polysubstance use disorder and broader problems of substance use disorder.
Topics: Age Distribution; Centers for Disease Control and Prevention, U.S.; Central Nervous System Stimulants; Drug Overdose; Heroin; Humans; Hypnotics and Sedatives; Opiate Overdose; Opioid-Related Disorders; Sex Distribution; Socioeconomic Factors; Synthetic Drugs; United States
PubMed: 33301695
DOI: 10.1177/0033354920969171 -
Maternal and Child Health Journal Jul 2023Opioid overdose is a leading cause of maternal mortality, yet limited attention has been given to the consequences of opioid use disorder (OUD) in the year following... (Review)
Review
OBJECTIVE
Opioid overdose is a leading cause of maternal mortality, yet limited attention has been given to the consequences of opioid use disorder (OUD) in the year following delivery when most drug-related deaths occur. This article provides an overview of the literature on OUD and overdose in the first year postpartum and provides recommendations to advance maternal opioid research.
APPROACH
A rapid scoping review of peer-reviewed research (2010-2021) on OUD and overdose in the year following delivery was conducted in PubMed, PsycINFO, and Web of Science databases. This article discusses existing research, remaining knowledge gaps, and methodological considerations needed.
RESULTS
Seven studies were included. Medication for OUD (MOUD) was the only identified factor associated with a reduction in overdose rates. Key literature gaps include the role of mental health disorders and co-occurring substance use, as well as interpersonal, social, and environmental contexts that may contribute to postpartum opioid problems and overdose.
CONCLUSION
There remains a limited understanding of why women in the first year postpartum are particularly vulnerable to opioid overdose. Recommendations include: (1) identifying subgroups of women with OUD at highest risk for postpartum overdose, (2) assessing opioid use, overdose, and risks throughout the first year postpartum, (3) evaluating the effect of co-occurring physical and mental health conditions and substance use disorders, (4) investigating the social and contextual determinants of opioid use and overdose after delivery, (5) increasing MOUD retention and treatment engagement postpartum, and (6) utilizing rigorous and multidisciplinary research methods to understand and prevent postpartum overdose.
Topics: Humans; Female; Analgesics, Opioid; Opiate Overdose; Opioid-Related Disorders; Drug Overdose; Opiate Substitution Treatment; Postpartum Period
PubMed: 36840785
DOI: 10.1007/s10995-023-03614-7 -
Drug and Alcohol Dependence Apr 2020Nonfatal opioid overdose (OD) is an opportunity to identify patients who may benefit from interventions to reduce repeated overdose (rOD). In this study, we sought to...
BACKGROUND
Nonfatal opioid overdose (OD) is an opportunity to identify patients who may benefit from interventions to reduce repeated overdose (rOD). In this study, we sought to determine risk and protective factors associated with rOD.
METHODS
In this retrospective cohort study of 4,155 patients aged 18-64 who presented to one of 16 emergency departments in a single Western Pennsylvania health system between July 2015 and January 2018 for index opioid overdose (iOD) and survived to discharge, we identified demographic and clinical factors association with rOD within one-year. Relative risk of repeated opioid overdose was estimated using adjusted Cox proportional hazard ratios (aHRs).
RESULTS
14.9 % of patients (95 % CI 13.9-16.1) had a rOD, with 29 % occurring within 30 days from iOD. The adjusted hazard of opioid overdose was increased for male patients (aHR = 1.19; 95 % CI 1.01, 1.41), those with pre-iOD diagnoses of anxiety (aHR = 1.41; 95 % CI1.13, 1.77), depression (aHR = 1.44; 95 % CI 1.17, 1.78), substance use disorders (aHR = 1.30; 95 % CI 1.09, 1.55), and alcohol use disorder (aHR = 1.52; 95 % CI 1.02, 2.25). The hazard was lower for individuals prescribed an opioid in the 90 days prior to iOD (aHR = 0.59; 95 % CI 0.37, 0.97) and those admitted to the hospital for iOD (aHR = 0.56; 95 % CI 0.37, 0.86).
CONCLUSION
We found that, among ED patients who survive an initial OD, mental health and substance use diagnoses are associated with a higher hazard of repeated overdoses whereas opioids prescriptions and admission are associated with lower hazards.
Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Cohort Studies; Drug Prescriptions; Emergency Service, Hospital; Female; Humans; Male; Middle Aged; Opiate Overdose; Patient Discharge; Pennsylvania; Protective Factors; Retrospective Studies; Risk Factors; Survival; Young Adult
PubMed: 32058246
DOI: 10.1016/j.drugalcdep.2020.107890 -
Annual Review of Public Health Apr 2021More than 750,000 people in the United States died from an overdose between 1999 and 2018; two-thirds of those deaths involved an opioid. In this review, we present... (Review)
Review
More than 750,000 people in the United States died from an overdose between 1999 and 2018; two-thirds of those deaths involved an opioid. In this review, we present trends in opioid overdose rates during this period and discuss how the proliferation of opioid prescribing to treat chronic pain, changes in the heroin and illegally manufactured opioid synthetics markets, and social factors, including deindustrialization and concentrated poverty, contributed to the rise of the overdose epidemic. We also examine how current policies implemented to address the overdose epidemic may have contributed to reducing prescription opioid overdoses but increased overdoses involving illegal opioids. Finally, we identify new directions for research to understand the causes and solutions to this critical public health problem, including research on heterogeneous policy effects across social groups, effective approaches to reduce overdoses of illegal opioids, and the role of social contexts in shaping policy implementation and impact.
Topics: Analgesics, Opioid; Chronic Pain; Epidemics; Humans; Illicit Drugs; Opiate Overdose; Policy; Practice Patterns, Physicians'; Social Environment; United States
PubMed: 33256535
DOI: 10.1146/annurev-publhealth-090419-102727