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Pharmacology & Therapeutics May 2022Overdose deaths are often viewed as the leading edge of the opioid epidemic which has gripped the United States over the past two decades (Skolnick, 2018a). This... (Review)
Review
Overdose deaths are often viewed as the leading edge of the opioid epidemic which has gripped the United States over the past two decades (Skolnick, 2018a). This emphasis is perhaps unsurprising because opioid overdose is both the number-one cause of death for individuals between 25 and 64 years old (Dezfulian et al., 2021) and a significant contributor to the decline in average lifespan (Dowell et al., 2017). Exacerbated by the COVID 19 pandemic, it was estimated there were 93,400 drug overdose deaths in the United States during the 12 months ending December 2020, with more than 69,000 (that is, >74%) of these fatalities attributed to opioid overdose (Ahmad et al., 2021). However, the focus on mortality statistics (Ahmad et al., 2021; Shover et al., 2020) tends to obscure the broader medical impact of nonfatal opioid overdose. Analyses of multiple databases indicate that for each opioid-induced fatality, there are between 6.4 and 8.4 non-fatal overdoses, exacting a significant burden on both the individual and society. Over the past 7-8 years, there has been an alarming increase in the misuse of synthetic opioids ("synthetics"), primarily fentanyl and related piperidine-based analogs. Within the past 2-3 years, a structurally unrelated class of high potency synthetics, benzimidazoles exemplified by etonitazene and isotonitazene ("iso"), have also appeared in illicit drug markets (Thompson, 2020; Ujvary et al. 2021). In 2020, it was estimated that over 80% of fatal opioid overdoses in the United States now involve synthetics (Ahmad et al., 2021). The unique physicochemical and pharmacological properties of synthetics described in this review are responsible for both the morbidity and mortality associated with their misuse as well as their widespread availability. This dramatic increase in the misuse of synthetics is often referred to as the "3rd wave" (Pardo et al., 2019; Volkow and Blanco, 2020) of the opioid epidemic. Among the consequences resulting from misuse of these potent opioids is the need for higher doses of the competitive antagonist, naloxone, to reverse an overdose. The development of more effective reversal agents such as those described in this review is an essential component of a tripartite strategy (Volkow and Collins, 2017) to reduce the biopsychosocial impact of opioid misuse in the "synthetic era".
Topics: Adult; Analgesics, Opioid; Drug Overdose; Humans; Middle Aged; Naloxone; Opiate Overdose; United States; COVID-19 Drug Treatment
PubMed: 34637841
DOI: 10.1016/j.pharmthera.2021.108019 -
Drug and Alcohol Dependence Jan 2021The United States (U.S.) is experiencing an ongoing opioid crisis. Economic burden estimates that describe the impact of the crisis are needed when considering federal...
BACKGROUND
The United States (U.S.) is experiencing an ongoing opioid crisis. Economic burden estimates that describe the impact of the crisis are needed when considering federal and state resources devoted to addressing overdoses. In this study, we estimate the societal costs for opioid use disorder and fatal overdose from all opioids in 2017.
METHODS
We estimated costs of fatal overdose from all opioids and opioid use disorder based on the incidence of overdose deaths and the prevalence of past-year opioid use disorder for 2017. Incidence of fatal opioid overdose was obtained from the National Vital Statistics System; prevalence of past-year opioid use disorder was estimated from the National Survey of Drug Use and Health. Costs were estimated for health care, criminal justice and lost productivity. Costs for the reduced quality of life for opioid use disorder and life lost due to fatal opioid overdose were valued using U.S. Department of Health and Human Services guidelines for valuing reductions in morbidity and mortality.
RESULTS
Costs for opioid use disorder and fatal opioid overdose in 2017 were estimated to be $1.02 trillion. The majority of the economic burden is due to reduced quality of life from opioid use disorder and the value of life lost due to fatal opioid overdose.
CONCLUSIONS
These estimates can assist decision makers in understanding the magnitude of opioid use disorder and fatal overdose. Knowing the magnitude and distribution of the economic burden can inform public policy, clinical practice, research, and prevention and response activities.
Topics: Analgesics, Opioid; Cost of Illness; Criminal Law; Delivery of Health Care; Drug Overdose; Humans; Opiate Overdose; Opioid Epidemic; Opioid-Related Disorders; Prevalence; Quality of Life; United States
PubMed: 33121867
DOI: 10.1016/j.drugalcdep.2020.108350 -
Clinical Toxicology (Philadelphia, Pa.) Mar 2023Illicit opioids, consisting largely of fentanyl, novel synthetic opioids, and adulterants, are the primary cause of drug overdose fatality in the United States....
INTRODUCTION
Illicit opioids, consisting largely of fentanyl, novel synthetic opioids, and adulterants, are the primary cause of drug overdose fatality in the United States. Xylazine, an alpha-2 adrenergic agonist and veterinary tranquilizer, is being increasingly detected among decedents following illicit opioid overdose. Clinical outcomes in non-fatal overdose involving xylazine are unexplored. Therefore, among emergency department patients with illicit opioid overdose, we evaluated clinical outcome differences for patients with and without xylazine exposures.
METHODS
This multicenter, prospective cohort study enrolled adult patients with opioid overdose who presented to one of nine United States emergency departments between 21 September 2020, and 17 August 2021. Patients with opioid overdose were screened and included if they tested positive for an illicit opioid (heroin, fentanyl, fentanyl analog, or novel synthetic opioid) or xylazine. Patient serum was analyzed liquid chromatography quadrupole time-of-flight mass spectroscopy to detect current illicit opioids, novel synthetic opioids, xylazine and adulterants. Overdose severity surrogate outcomes were: (a) cardiac arrest requiring cardiopulmonary resuscitation (primary); and (b) coma within 4 h of arrival (secondary).
RESULTS
Three hundred and twenty-one patients met inclusion criteria: 90 tested positive for xylazine and 231 were negative. The primary outcome occurred in 37 patients, and the secondary outcome occurred in 111 patients. Using multivariable regression analysis, patients positive for xylazine had significantly lower adjusted odds of cardiac arrest (adjusted OR 0.30, 95% CI 0.10-0.92) and coma (adjusted OR 0.52, 95% CI 0.29-0.94).
CONCLUSIONS
In this large multicenter cohort, cardiac arrest and coma in emergency department patients with illicit opioid overdose were significantly less severe in those testing positive for xylazine.
Topics: Adult; Humans; United States; Analgesics, Opioid; Xylazine; Opiate Overdose; Prospective Studies; Coma; Fentanyl; Drug Overdose; Emergency Service, Hospital
PubMed: 37014353
DOI: 10.1080/15563650.2022.2159427 -
Substance Abuse 2022Opioid overdose is a preventable injury leading to high morbidity and premature mortality in communities across the United States. Overdoses take place where people use...
BACKGROUND
Opioid overdose is a preventable injury leading to high morbidity and premature mortality in communities across the United States. Overdoses take place where people use drugs, including commercial and public locations like community pharmacies, and necessitate swift detection and response to avoid harm and, even more seriously, death. The presence of emergency and safety protocols improves occupational health and safety for all in the workplace. The aim of this study was to assess the prevalence of experience with on-site pharmacy overdose and to explore pharmacist and site characteristics associated with having a known protocol for responding to on-site overdose emergencies.
UNLABELLED
: An anonymous, online survey about naloxone provision and opioid safety was delivered by email, through professional pharmacy associations and continuing education attendance lists, to 3,100 pharmacists in Massachusetts and Rhode Island between October 2017 and January 2018. Survey items gauged socio-demographics, practice site characteristics, safer opioid dispensing and naloxone provision. Summary statistics and bivariate analyses were conducted to describe characteristics associated with items pertaining to on-site overdose policy awareness.
UNLABELLED
: Of the 357 respondents (11.5% response rate), 154 (5.0%) answered the questions of interest: 17.5% reported having at least one suspected overdose on-site at their practice location, while 42.9% reported that they were knowledgeable about and could locate at their practice location an on-site overdose protocol detailing how to respond to an overdose. Pharmacists who were knowledgeable about protocols were also more likely to offer naloxone to patients ( = 0.02) and did not practice at a chain pharmacy ( = 0.01).
UNLABELLED
: Community pharmacies that stock and distribute naloxone are key parts of community efforts to address the opioid crisis. Pharmacies and other healthcare settings should develop and implement on-site overdose response protocols and cultivate a norm of naloxone provision to patients.
Topics: Analgesics, Opioid; Drug Overdose; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Pharmacies; Pharmacists; Pharmacy; United States
PubMed: 32186478
DOI: 10.1080/08897077.2020.1736236 -
Substance Abuse 2022As rates of overdose and substance use disorders (SUDs) increase, medical schools are starting to incorporate more content on SUDs and harm reduction in undergraduate...
As rates of overdose and substance use disorders (SUDs) increase, medical schools are starting to incorporate more content on SUDs and harm reduction in undergraduate medical education (UME). Initial data suggest these additions may improve medical student knowledge and attitudes toward patients with SUDs; however, there is no standard curriculum. This project uses a six-step approach to UME curricular development to identify needs and goals regarding SUDs and opioid overdose at a large single-campus medical school in the United States. We first developed and delivered a pilot curriculum to a small group of medical students. Pilot results and a larger survey led to implementing a one-hour Opioid Overdose Prevention and Response (OOPR) Training for first-year students. Effects of training were tracked using baseline and post-training surveys examining knowledge and attitudes toward opioid overdose and patients with SUDs. Needs assessment indicated desire and need for training. The pilot study ( = 66) resulted in significantly improved knowledge regarding opioid overdose; 100% of students enjoyed training and believed others should receive it. The larger replication study surveyed all incoming students ( = 266) to gauge initial knowledge and experiences with these topics. Results prompted enhancement of the OOPR Training curriculum, which was delivered to half of the first-year class. Post-training survey results replicated the pilot study findings. The majority (95.2%) of students enjoyed training and 98.4% believed all students should receive it. Delivering a thorough curriculum on SUDs and harm reduction in UME is critical. Although many schools are implementing training, there is no standard curriculum. We outline a low-resource training intervention for OOPR. Our findings identified key features to include in these UME curricula. This approach provides a replicable template for schools seeking to develop brief educational interventions and identify essential content for curricula in SUDs and harm reduction.
Topics: Curriculum; Drug Overdose; Education, Medical, Undergraduate; Humans; Opiate Overdose; Pilot Projects; Students, Medical; United States
PubMed: 34214397
DOI: 10.1080/08897077.2021.1941515 -
Substance Use & Misuse Nov 2018The rise in opioid use and overdose has increased the importance of improving data collection methods for the purpose of targeting resources to high-need populations and...
BACKGROUND
The rise in opioid use and overdose has increased the importance of improving data collection methods for the purpose of targeting resources to high-need populations and responding rapidly to emerging trends.
OBJECTIVE
To determine whether Twitter data could be used to identify geographic differences in opioid-related discussion and whether opioid topics were significantly correlated with opioid overdose death rate.
METHODS
We filtered approximately 10 billion tweets for keywords related to opioids between July 2009 and October 2015. The content of the messages was summarized into 50 topics generated using Latent Dirchlet Allocation, a machine learning analytic tool. The correlation between topic distribution and census region, census division, and opioid overdose death rate were quantified.
RESULTS
We evaluated a tweet cohort of 84,023 tweets from 72,211 unique users across the US. Unique opioid-related topics were significantly correlated with different Census Bureau divisions and with opioid overdose death rates at the state and county level. Drug-related crime, language of use, and online drug purchasing emerged as themes in various Census Bureau divisions. Drug-related crime, opioid-related news, and pop culture themes were significantly correlated with county-level opioid overdose death rates, and online drug purchasing was significantly correlated with state-level opioid overdoses.
CONCLUSIONS
Regional differences in opioid-related topics reflect geographic variation in the content of Twitter discussion about opioids. Analysis of Twitter data also produced topics significantly correlated with opioid overdose death rates. Ongoing analysis of Twitter data could provide a means of identifying emerging trends related to opioids.
Topics: Analgesics, Opioid; Cohort Studies; Communication; Correlation of Data; Crime; Cross-Sectional Studies; Drug Overdose; Epidemics; Geography; Humans; Opioid-Related Disorders; Social Media; United States
PubMed: 29659320
DOI: 10.1080/10826084.2018.1458319 -
International Journal of Environmental... Jan 2023Drug overdoses were a leading cause of injury and death in the United States in 2021. Solitary drug use and solitary overdose deaths have remained persistent challenges... (Review)
Review
Drug overdoses were a leading cause of injury and death in the United States in 2021. Solitary drug use and solitary overdose deaths have remained persistent challenges warranting additional attention throughout the overdose epidemic. The goal of this narrative review is to describe recent global innovations in overdose detection technologies (ODT) enabling rapid responses to overdose events, especially for people who use drugs alone. We found that only a small number of technologies designed to assist in overdose detection and response are currently commercially available, though several are in the early stages of development. Research, development, and scale-up of practical, cost-effective ODTs remains a public health imperative. Equipping places where people live, learn, work, worship, and play with the necessary tools to detect and prevent overdose deaths could complement ongoing overdose prevention efforts.
Topics: Humans; United States; Drug Overdose; Substance-Related Disorders; Public Health; Epidemics; Cost-Effectiveness Analysis; Analgesics, Opioid
PubMed: 36673987
DOI: 10.3390/ijerph20021230 -
Pain Medicine (Malden, Mass.) Apr 2018Sharp increases in opioid prescriptions, and associated increases in overdose deaths in the 2000s, evoked widespread calls to change perceptions of opioid analgesics.... (Review)
Review
OBJECTIVE
Sharp increases in opioid prescriptions, and associated increases in overdose deaths in the 2000s, evoked widespread calls to change perceptions of opioid analgesics. Medical literature discussions of opioid analgesics began emphasizing patient and public health hazards. Repetitive exposure to this information may influence physician assumptions. While highly consequential to patients with pain whose function and quality of life may benefit from opioid analgesics, current assumptions about prescription opioid analgesics, including their role in the ongoing opioid overdose epidemic, have not been scrutinized.
METHODS
Information was obtained by searching PubMed, governmental agency websites, and conference proceedings.
RESULTS
Opioid analgesic prescribing and associated overdose deaths both peaked around 2011 and are in long-term decline; the sharp overdose increase recorded in 2014 was driven by illicit fentanyl and heroin. Nonmethadone prescription opioid analgesic deaths, in the absence of co-ingested benzodiazepines, alcohol, or other central nervous system/respiratory depressants, are infrequent. Within five years of initial prescription opioid misuse, 3.6% initiate heroin use. The United States consumes 80% of the world opioid supply, but opioid access is nonexistent for 80% and severely restricted for 4.1% of the global population.
CONCLUSIONS
Many current assumptions about opioid analgesics are ill-founded. Illicit fentanyl and heroin, not opioid prescribing, now fuel the current opioid overdose epidemic. National discussion has often neglected the potentially devastating effects of uncontrolled chronic pain. Opioid analgesic prescribing and related overdoses are in decline, at great cost to patients with pain who have benefited or may benefit from, but cannot access, opioid analgesic therapy.
Topics: Analgesics, Opioid; Drug Overdose; Fentanyl; Heroin; Humans; Opioid-Related Disorders; Prescription Drugs; Substance-Related Disorders
PubMed: 28402482
DOI: 10.1093/pm/pnx048 -
Frontiers in Public Health 2023Opioid use disorder (OUD) is a major public health threat, contributing to morbidity and mortality from addiction, overdose, and related medical conditions. Despite our... (Review)
Review
Opioid use disorder (OUD) is a major public health threat, contributing to morbidity and mortality from addiction, overdose, and related medical conditions. Despite our increasing knowledge about the pathophysiology and existing medical treatments of OUD, it has remained a relapsing and remitting disorder for decades, with rising deaths from overdoses, rather than declining. The COVID-19 pandemic has accelerated the increase in overall substance use and interrupted access to treatment. If increased naloxone access, more buprenorphine prescribers, greater access to treatment, enhanced reimbursement, less stigma and various harm reduction strategies were effective for OUD, overdose deaths would not be at an all-time high. Different prevention and treatment approaches are needed to reverse the concerning trend in OUD. This article will review the recent trends and limitations on existing medications for OUD and briefly review novel approaches to treatment that have the potential to be more durable and effective than existing medications. The focus will be on promising interventional treatments, psychedelics, neuroimmune, neutraceutical, and electromagnetic therapies. At different phases of investigation and FDA approval, these novel approaches have the potential to not just reduce overdoses and deaths, but attenuate OUD, as well as address existing comorbid disorders.
Topics: Humans; Pandemics; Opiate Substitution Treatment; Opioid-Related Disorders; Buprenorphine; Naloxone; Drug Overdose
PubMed: 38332941
DOI: 10.3389/fpubh.2023.1274719 -
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