Methodological approaches for the prediction of opioid use-related epidemics in the United States: a narrative review and cross-disciplinary call to action.

The opioid crisis in the United States has been defined by waves of drug- and locality-specific Opioid use-Related Epidemics (OREs) of overdose and bloodborne infections, among a range of health harms. The ability to identify localities at risk of such OREs, and better yet, to predict which ones will experience them, holds the potential to mitigate further morbidity and mortality. This narrative review was conducted to identify and describe quantitative approaches aimed at the "risk assessment," "detection" or "prediction" of OREs in the United States. We implemented a PubMed search composed of the: (1) objective (eg, prediction), (2) epidemiologic outcome (eg, outbreak), (3) underlying cause (ie, opioid use), (4) health outcome (eg, overdose, HIV), (5) location (ie, US). In total, 46 studies were included, and the following information extracted: discipline, objective, health outcome, drug/substance type, geographic region/unit of analysis, and data sources. Studies identified relied on clinical, epidemiological, behavioral and drug markets surveillance and applied a range of methods including statistical regression, geospatial analyses, dynamic modeling, phylogenetic analyses and machine learning. Studies for the prediction of overdose mortality at national/state/county and zip code level are rapidly emerging. Geospatial methods are increasingly used to identify hotspots of opioid use and overdose. In the context of infectious disease OREs, routine genetic sequencing of patient samples to identify growing transmission clusters via phylogenetic methods could increase early detection capacity. A coordinated implementation of multiple, complementary approaches would increase our ability to successfully anticipate outbreak risk and respond preemptively. We present a multi-disciplinary framework for the prediction of OREs in the US and reflect on challenges research teams will face in implementing such strategies along with good practices.

The opioid crisis and HIV in the USA: deadly synergies.

The opioid epidemic is one of the greatest public health problems that the USA faces. Opioid overdose death rates have increased steadily for more than a decade and doubled in 2013-17, as the highly potent synthetic opioid fentanyl entered the drug supply. Demographics of new HIV diagnoses among people who inject drugs are also changing, with more new HIV diagnoses occurring among White people, young people (aged 13-34 years), and people who reside outside large central metropolitan areas. Racial differences also exist in syringe sharing, which decreased among Black people and Hispanic people but remained unchanged among White people in 2005-15. Recent HIV outbreaks have occurred in rural areas of the USA, as well as among marginalised people in urban areas with robust HIV prevention and treatment services (eg, Seattle, WA). Multiple evidence-based interventions can effectively treat opioid use disorder and prevent HIV acquisition. However, considerable barriers exist precluding delivery of these solutions to many people who inject drugs. If the USA is serious about HIV prevention among this group, stigma must be eliminated, discriminatory policies must change, and comprehensive health care must be accessible to all. Finally, root causes of the opioid epidemic such as hopelessness need to be identified and addressed.

The drug war must end: The right to life, liberty and security of the person during the COVID-19 pandemic for people who use drugs.

Since the start of the opioid epidemic in 2016, the Downtown Eastside community of Vancouver, Canada, has lost many pioneering leaders, activists and visionaries to the war on drugs. The Vancouver Area Network of Drug Users (VANDU), the Western Aboriginal Harm Reduction Society (WAHRS), and the British Columbia Association People on Opiate Maintenance (BCAPOM) are truly concerned about the increasing overdose deaths that have continued since 2016 and have been exacerbated by the novel coronavirus (SARS-COVID-19) despite many unique and timely harm reduction announcements by the British Columbia (B.C.) government. Some of these unique interventions in B.C., although in many cases only mere announcements with limited scope, are based on the philosophy of safe supply to illegal street drugs. Despite all the efforts during the pandemic, overdose deaths have spiked by over 100% compared to the previous year. Therefore, we urge the Canadian federal government, specifically the Honorable Patty Hajdu, the federal Minister of Health, to decriminalize simple possession immediately by granting exemption under the Controlled Drugs and Substances Act. The Canadian federal government has a moral obligation under Sect. 7 of the Canadian Charter of Rights and Freedoms to protect the basic human rights of marginalized Canadians.

The Surge in Deceased Liver Donors Due to the Opioid Epidemic: Is It Time to Split the Difference?

BACKGROUND: This study aimed to compare trends in use of drug overdose (DO) donors in adult versus pediatric liver transplants and the utilization of split liver transplantation in this donor population. METHODS: The United Network for Organ Sharing database was reviewed for deceased donor liver transplants from March 2002 to December 2017. Recipients were categorized by donor mechanism of death. Donor splitting criteria was defined as age <40 y, single vasopressor or less, transaminases no >3 times the normal limit, and body mass index ≤ 28 kg/m2. RESULTS: Adult liver transplants from DO donors increased from 2% in 2002 to 15% in 2017, while pediatric liver transplants from DO donors only increased from <1% to 3% in the same time. While 28% of DO donors met splitting criteria, only 3% of those meeting splitting criteria were used as a split graft. Both pediatric and adult recipients of DO donor livers achieved excellent patient and graft survival. CONCLUSIONS: DO donors are underutilized in pediatric liver transplantation. Increased splitting of DO donor livers could significantly decrease, if not eliminate, the pediatric liver waiting list.

Opioid Overdose Deaths with Buprenorphine Detected in Postmortem Toxicology: a Retrospective Analysis.

BACKGROUND: Buprenorphine is a unique µ-opioid receptor partial agonist with avid receptor binding, nominal euphoric reward, and a ceiling effect on sedation and respiratory depression. Despite a pharmacologic profile that enhances safety, cases of fatal opioid overdose with buprenorphine on postmortem toxicology are reported, but details of these cases in the literature are limited. METHODS: A retrospective review of opioid-involved drug overdose fatalities in Rhode Island (RI) from 2016 to 2018 using the RI Department of Health State Unintentional Drug Overdose Reporting System (SUDORS) database. Deaths with buprenorphine on toxicology testing versus opioid-involved overdose deaths without buprenorphine were compared to assess the type and number of co-exposures. RESULTS: Of 534 opioid-involved deaths, 29 (5.4%) included buprenorphine and/or norbuprenorphine on toxicology. Most frequent co-exposures are as follows: fentanyl (75.9%), norfentanyl (72.4%), cocaine (41.4%), benzoylecgonine (41.4%), cannabinoids (31.0%), ethanol (31.0%), levamisole (31.0%), and free morphine (31.0%). An average number of co-exposures for fatalities with buprenorphine were 9.24 versus 6.68 in those without buprenorphine. In one case buprenorphine was the only drug listed to cause death; all other fatalities with buprenorphine on toxicology reported additional drugs contributing to death. CONCLUSION: Decedents with buprenorphine detected on toxicology testing commonly had documented polysubstance use. Although data are limited, buprenorphine may provide some risk mitigation against full agonist opioid overdose including fentanyl. Further work should explore the use of postmortem concentrations of buprenorphine, norbuprenorphine, and other opioid metabolites to determine the role of buprenorphine in fatal overdose pharmacology.

Countermeasures for Preventing and Treating Opioid Overdose.

The only medication available currently to prevent and treat opioid overdose (naloxone) was approved by the US Food and Drug Administration (FDA) nearly 50 years ago. Because of its pharmacokinetic and pharmacodynamic properties, naloxone has limited utility under some conditions and would not be effective to counteract mass casualties involving large-scale deployment of weaponized synthetic opioids. To address shortcomings of current medical countermeasures for opioid toxicity, a trans-agency scientific meeting was convened by the US National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIAID/NIH) on August 6 and 7, 2019, to explore emerging alternative approaches for treating opioid overdose in the event of weaponization of synthetic opioids. The meeting was initiated by the Chemical Countermeasures Research Program (CCRP), was organized by NIAID, and was a collaboration with the National Institute on Drug Abuse/NIH (NIDA/NIH), the FDA, the Defense Threat Reduction Agency (DTRA), and the Biomedical Advanced Research and Development Authority (BARDA). This paper provides an overview of several presentations at that meeting that discussed emerging new approaches for treating opioid overdose, including the following: (1) intranasal nalmefene, a competitive, reversible opioid receptor antagonist with a longer duration of action than naloxone; (2) methocinnamox, a novel opioid receptor antagonist; (3) covalent naloxone nanoparticles; (4) serotonin (5-HT)1A receptor agonists; (5) fentanyl-binding cyclodextrin scaffolds; (6) detoxifying biomimetic "nanosponge" decoy receptors; and (7) antibody-based strategies. These approaches could also be applied to treat opioid use disorder.

Missouri's Fentanyl Problem: The China Connection.

Recently, Missouri has followed an overall upward trend in opioid overdose deaths. In 2018, Missouri was the state with the largest absolute and percentage increase in opioid-related overdose fatality rates per capita over the previous year (18.3% and 3.1/100,000). This increase occurred despite an overall decrease in U.S. opioid-related death rates in the same period. This report identifies illicitly manufactured fentanyl (IMF) (and analogues) as the drug most responsible for this rise in opioid deaths in Missouri, with stimulant overdoses (primarily from methamphetamine) in second place. Within Missouri, we find the areas where opioid deaths are highest: St. Louis and the city's fringe areas, following the national trend for high rates in fringe areas. Based on reports from CDC Wonder data, county medical examiners, law enforcement agencies, and drug addiction prevention agencies, we conclude that IMF and related synthetic opioids arriving from China are primarily responsible for fatal narcotic overdoses in Missouri. Despite the COVID-19 disruption of fentanyl manufacturing and distribution centers in and around Wuhan, China early in the pandemic, preliminary 2020 data from medical examiners' offices show an upswing in opioid deaths, an indicator that Chinese fentanyl producers have restored the supply chain.

Situating the Continuum of Overdose Risk in the Social Determinants of Health: A New Conceptual Framework.

Policy Points This article reconceptualizes our understanding of the opioid epidemic and proposes six strategies that address the epidemic's social roots. In order to successfully reduce drug-related mortality over the long term, policymakers and public health leaders should develop partnerships with people who use drugs, incorporate harm reduction interventions, and reverse decades of drug criminalization policies. CONTEXT: Drug overdose is the leading cause of injury-related death in the United States. Synthetic opioids, predominantly illicit fentanyl and its analogs, surpassed prescription opioids and heroin in associated mortality rates in 2016. Unfortunately, interventions fail to fully address the current wave of the opioid epidemic and often omit the voices of people with lived experiences regarding drug use. Every overdose death is a culmination of a long series of policy failures and lost opportunities for harm reduction. METHODS: In this article, we conducted a scoping review of the opioid literature to propose a novel framework designed to foreground social determinants more directly into our understanding of this national emergency. The "continuum of overdose risk" framework is our synthesis of the global evidence base and is grounded in contemporary theories, models, and policies that have been successfully applied both domestically and internationally. FINDINGS: De-escalating overdose risk in the long term will require scaling up innovative and comprehensive solutions that have been designed through partnerships with people who use drugs and are rooted in harm reduction. CONCLUSIONS: Without recognizing the full drug-use continuum and the role of social determinants, the current responses to drug overdose will continue to aggravate the problem they are trying to solve.

What Is Driving the Drug Overdose Epidemic in the United States?

The demand-side perspective argues that the drug overdose epidemic is a consequence of changes in the economy that leave behind working-class people who lack a college education. In contrast, the supply-side perspective maintains that the epidemic is primarily due to changes in the licit and illicit drug environment, whereas a third, distinct perspective argues that income inequality is likely a key driver of the epidemic. To evaluate these competing perspectives, we use a two-level random intercept model and U.S. state-level data from 2006 to 2017. Contrary to the demand-side approach, we find that educational attainment is not associated with drug-related mortality. In support of the supply-side approach, we provide evidence indicating that opioid prescription rates are positively associated with drug-related mortality. We also find that income inequality is a key driver of the epidemic, particularly the lack of resources going to the bottom 20% of earners. We conclude by arguing that considerations of income inequality are an important way to link the arguments made by the demand-side and the supply-side perspectives.

The impact of the prescription opioid epidemic on young children: Trends and mortality.

BACKGROUND: Our objective was to describe trends and deaths in young children associated with opioid analgesics. METHODS: Analysis of pediatric exposures using the RADARS System Poison Center Program from July 1, 2010 through December 31, 2018. Cases involving a child < 6 years, with an exposure to one or more opioids: buprenorphine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, oxymorphone, and tramadol. Poisson regression was used to model the shape of the time response curve. RESULTS: 48,560 cases were identified, median age 2 years (IQR 1.4, 2.0), 52.4 % male. The most commonly involved opioid was hydrocodone (32.5 %); buprenorphine and methadone had the highest exposure rates when adjusted for dispensed prescriptions (0.84 and 0.73 per 10,000 prescriptions). There were 28 deaths, methadone being the most commonly involved opioid (16). Exposures decreased significantly accounting for population (from 8.39 to 4.19 exposures per 100,000 children) and per prescription (from 0.33 to 0.25 exposures per 10,000 prescriptions). After adjustment for prescriptions, the exposure rate for hydromorphone and fentanyl increased over the study period, while buprenorphine had the greatest decrease in exposure rate. Among 28 deaths, 11 (39 %) were known or suspected to have been exposed, but medical care was not sought or was delayed. CONCLUSION: Pediatric opioid exposure rates by prescription and population decreased from July 2010 through December 2018. However, with over 48,000 exposures and 28 deaths, the opioid epidemic continues to impact young children. Many exposures including deaths were preventable. Continued improvements in prevention require a multifaceted approach.

Statewide collaborative partnerships among American Indian and Alaska Native (AI/AN) communities in California to target the opioid epidemic: Preliminary results of the Tribal Medication Assisted Treatment (MAT) key informant needs assessment.

American Indian and Alaska Native (AI/AN) communities have disproportionately been impacted by the opioid epidemic with the second highest opioid-related overdose death rates compared to other ethnic groups. The diversity among California AI/AN tribes, including regional differences in economic opportunities, tribal affiliation and organization, resources and infrastructure, requires a strong community-based partnership approach to assess global statewide patterns in service availability, acceptability, and utilization, as well as capturing the unique challenges and service needs within each region. This article describes a statewide community-based needs assessment of strengths and weakness among key informants in CA to identify facilitators and barriers to treatment of substance use disorders (SUD) and opioid use disorders (OUD). We conducted structured interviews of 21 healthcare professionals from Urban Indian Health Programs, Tribal clinics and community-based organizations throughout California. The interview assessed (1) barriers to accessing services; (2) risk factors; (3) protective factors; (4) community substance use description; (5) SUD and OUD services available; and (6) service system needs. Findings indicate an overall increase in SUD and OUD in AI/AN communities. Key informants discussed the importance of comprehensive and culturally centered care, wrap-around services, such as treatment of mental health issues alongside substance abuse, and the need for AI/AN-specific treatment facilities that integrate traditional and cultural activities into western health services.

National Institutes of Health (NIH) Executive Meeting Summary: Developing Medical Countermeasures to Rescue Opioid-Induced Respiratory Depression (a Trans-Agency Scientific Meeting)-August 6/7, 2019.

On August 6th, 2019, a two-day trans-agency scientific meeting was convened by the United States (U.S.) National Institute of Allergy and Infectious Diseases (NIAID/NIH) on the research and development of medical countermeasures (MCMs) and treatment strategies to mitigate synthetic opioid-induced toxicities. This trans-agency meeting was an initiative of the Chemical Countermeasures Research Program (CCRP) and organized by the NIAID in collaboration with the National Institute of Drug Abuse (NIDA), the Biomedical Advanced Research and Development Authority (BARDA), the Food and Drug Administration (FDA), and the Defense Threat Reduction Agency (DTRA). The CCRP is part of the larger NIH biodefense research program coordinated by NIAID, which also includes MCM research and development programs against biological, radiological, and nuclear threats. Its overarching goal is to integrate cutting-edge research and technological advances in science and medicine to enhance the nation's medical response capabilities during and after a public health emergency involving the deliberate or accidental release of toxic chemicals. The potential of a mass casualty public health event involving synthetic opioids is a rapidly growing concern. As such, the overall goals of this trans-agency meeting are to better understand opioid-induced toxicities and advance the development of MCMs to mitigate and reverse opioid-induced respiratory depression (OIRD) to prevent consequential mortality. The primary objectives of the meeting were (1) highlight the latest research on mechanisms of OIRD and related toxicities, animal models, diagnostics, delivery technologies, and emerging new treatment options to prevent lethality; (2) identify current knowledge gaps to advance medical countermeasure development; (3) hear from the U.S. FDA on regulatory considerations to support new technology and treatment approaches; and (4) provide a forum for networking and collaborative partnerships. To accomplish this, a diverse group of almost 200 US domestic and international subject matter experts spanning fundamental and translational research from academia, industry, and government came together in-person to share their collective expertise and experience in this important field. This report briefly summarizes the information presented throughout the meeting, which was also webcast live in its entirety to registered remote attendees.

'It's our safe sanctuary': Experiences of using an unsanctioned overdose prevention site in Toronto, Ontario.

BACKGROUND: Overdose prevention sites (OPSs) are spaces where people can consume drugs under the supervision of trained volunteers or staff and receive help in the event of an overdose. Unsanctioned OPSs are a grassroots response to the current opioid crisis in Canada. METHODS: We used rapid evaluation methods to study the experiences of 30 individuals accessing the smoking and injection services at the first unsanctioned OPS in Toronto, Ontario using semi-structured interviews. Data were analyzed using an applied thematic analysis approach to identify emergent themes related to service user experiences, characteristics of the risk environment, and recommended changes to the service model. RESULTS: The OPS represented a safe sanctuary and brought a sense of belonging to a community that often experiences discrimination. Valued aspects included: shelter; protection from violence; safety from overdoses; free equipment; information about health and social services; food and beverages; and socializing and connecting with others. Integrating peer workers in the design and delivery of services encouraged service users to visit the site. The OPS changed the risk environment by: providing access to the first supervised smoking service in Toronto; having few explicit rules and a communal approach to making new rules; allowing assisted injection, and negotiating with police to allow people to access the site with minimal contact. Service users noted the need to ensure a safe space for women and recommended extended hours of operation and moving to a more permanent space with heat and lighting for both smoking and injecting drugs. CONCLUSION: The unsanctioned OPS in Toronto served an important role in defining new, community-led, flexible responses to opioid overdose-related deaths at a time of markedly increasing mortality. Providing harm reduction services in diverse settings and expanding services to include smoking and assisted injection may increase access for marginalized people who use drugs.