Trends in and Characteristics of Drug Overdose Deaths Involving Illicitly Manufactured Fentanyls - United States, 2019-2020.

During May 2020-April 2021, the estimated number of drug overdose deaths in the United States exceeded 100,000 over a 12-month period for the first time, with 64.0% of deaths involving synthetic opioids other than methadone (mainly illicitly manufactured fentanyls [IMFs], which include both fentanyl and illicit fentanyl analogs).* Introduced primarily as adulterants in or replacements for white powder heroin east of the Mississippi River (1), IMFs are now widespread in white powder heroin markets, increasingly pressed into counterfeit pills resembling oxycodone, alprazolam, or other prescription drugs, and are expanding into new markets, including in the western United States† (2). This report describes trends in overdose deaths involving IMFs (IMF-involved deaths) during July 2019-December 2020 (29 states and the District of Columbia [DC]), and characteristics of IMF-involved deaths during 2020 (39 states and DC) using data from CDC's State Unintentional Drug Overdose Reporting System (SUDORS). During July 2019-December 2020, IMF-involved deaths increased sharply in midwestern (33.1%), southern (64.7%), and western (93.9%) jurisdictions participating in SUDORS. Approximately four in 10 IMF-involved deaths also involved a stimulant. Highlighting the need for timely overdose response, 56.1% of decedents had no pulse when first responders arrived. Injection drug use was the most frequently reported individual route of drug use (24.5%), but evidence of snorting, smoking, or ingestion, but not injection drug use was found among 27.1% of decedents. Adapting and expanding overdose prevention, harm reduction, and response efforts is urgently needed to address the high potency (3), and various routes of use for IMFs. Enhanced treatment for substance use disorders is also needed to address the increased risk for overdose (4) and treatment complications (5) associated with using IMFs with stimulants.

Studying how state health services delivery policies can mitigate the effects of disasters on drug addiction treatment and overdose: Protocol for a mixed-methods study.

BACKGROUND: The United States is experiencing a drug addiction and overdose crisis, made worse by the COVID-19 pandemic. Relative to other types of health services, addiction treatment and overdose prevention services are particularly vulnerable to disaster-related disruptions for multiple reasons including fragmentation from the general medical system and stigma, which may lead decisionmakers and providers to de-prioritize these services during disasters. In response to the COVID-19 pandemic, U.S. states implemented multiple policies designed to mitigate disruptions to addiction treatment and overdose prevention services, for example policies expanding access to addiction treatment delivered via telehealth and policies designed to support continuity of naloxone distribution programs. There is limited evidence on the effects of these policies on addiction treatment and overdose. This evidence is needed to inform state policy design in future disasters, as well as to inform decisions regarding whether to sustain these policies post-pandemic. METHODS: The overall study uses a concurrent-embedded design. Aims 1-2 use difference-in-differences analyses of large-scale observational databases to examine how state policies designed to mitigate the effects of the COVID-19 pandemic on health services delivery influenced addiction treatment delivery and overdose during the pandemic. Aim 3 uses a qualitative embedded multiple case study approach, in which we characterize local implementation of the state policies of interest; most public health disaster policies are enacted at the state level but implemented at the local level by healthcare systems and local public health authorities. DISCUSSION: Triangulation of results across methods will yield robust understanding of whether and how state disaster-response policies influenced drug addiction treatment and overdose during the COVID-19 pandemic. Results will inform policy enactment and implementation in future public health disasters. Results will also inform decisions about whether to sustain COVID-19 pandemic-related changes to policies governing delivery addiction and overdose prevention services long-term.

Brief Report: The Impact of COVID-19 on Emergency Department Overdose Diagnoses and County Overdose Deaths.

BACKGROUND AND OBJECTIVES: We sought to understand the impact of COVID-19 on emergency department (ED) overdoses and county coroner verified overdose deaths. METHODS: Electronic medical health record and county coroner data were gathered and comparisons were made between three 16-week time periods. In the three time periods, 873 individuals had an overdose diagnosis in the ED and 440 individuals in the county died of drug overdose. RESULTS: While total ED patient volume decreased substantially, the number of ED overdose patients increased between March 6 and June 25, 2020. Furthermore, during this same period, coroner data revealed an increase in overdose deaths. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: This preliminary evidence provides a key insight into the impact of COVID-19 on both overdose presentations to the ED and county overdose deaths. These results emphasize the critical need for increasing vigilance to prevent overdose by continuously developing and optimizing both accessible and quality treatment as we navigate through this pandemic and its ongoing effects on persons with substance use disorder. (Am J Addict 2021;00:00-00).

Comparison of Characteristics of Deaths From Drug Overdose Before vs During the COVID-19 Pandemic in Rhode Island.

Importance: The rate of deaths from overdose has increased during the COVID-19 pandemic, and recent US overdose mortality rates have been markedly high. However, scant data are available on the causes of this increase or subpopulations at elevated risk. Objective: To evaluate the rates and characteristics of deaths from drug overdose before vs during the COVID-19 pandemic. Design, Setting, and Participants: This retrospective, population-based cohort study used data from 4 statewide databases linked at the person level via the Rhode Island Data Ecosystem on adults with deaths due to overdose in Rhode Island from January 1 to August 31, 2019, and January 1 to August 31, 2020. Main Outcomes and Measures: The rates of unintentional deaths from drug-related overdose during the 2019 and 2020 observation periods overall and by sociodemographic characteristics, drugs contributing to the cause of death, location of death, and socioeconomic factors were evaluated. In subgroup analyses restricted to Medicaid beneficiaries (n = 271), the proportions of deaths from overdose by behavioral health treatment and diagnosis claims in the year before death were also examined. Results: A total of 470 adults who died of drug overdose were included in the analysis (353 men [75%]; mean [SD] age, 43.5 [12.1] years). The rate of deaths from overdose in Rhode Island increased 28.1%, from 29.2 per 100 000 person-years in 2019 to 37.4 per 100 000 person-years in 2020 (P = .009). Compared with 2019, rates of deaths due to overdose during 2020 were higher among men (43.2 vs 59.2 per 100 000 person-years; P = .003), non-Hispanic White individuals (31.0 vs 42.0 per 100 000 person-years; P = .005), single individuals (54.8 vs 70.4 per 100 000 person-years; P = .04), deaths involving synthetic opioids (20.8 vs 28.3 per 100 000 person-years; P = .005), and deaths occurring in a personal residence (13.2 vs 19.7 per 100 000 person-years; P = .003). A decrease in the proportion of deaths from overdose involving heroin (11 of 206 [5%] vs <2% [exact value suppressed]; P = .02) and an increase among persons experiencing job loss (16 of 206 [8%] vs 41 of 264 [16%]; P = .01) from 2019 to 2020 were observed. Among individuals who died of overdose and were Medicaid beneficiaries, the proportions of those aged 50 to 59 years with anxiety (11 of 121 [9%] vs 29 of 150 [19%]; P = .03), men with depression (27 of 121 [22%] vs 57 of 150 [38%]; P = .008), and men with anxiety (28 of 121 [23%] vs 55 of 150 [37%]; P = .02) increased during 2020 compared with 2019. Conclusions and Relevance: In this cohort study, during the first 8 months of 2020, the rate of deaths from overdose increased in Rhode Island compared with the same period in 2019, and several emerging characteristics of deaths from drug overdose during the first year of the COVID-19 pandemic were identified. These findings may inform interventions that address macroenvironmental changes associated with the pandemic.

The impact of COVID-19 on healthcare delivery for people who use opioids: a scoping review.

RESEARCH OBJECTIVE: The COVID-19 pandemic disrupted healthcare delivery worldwide with likely negative effects on people who use opioids (PWUO). This scoping review of the original research literature describes the impact of the COVID-19 pandemic on healthcare delivery for PWUO and identifies gaps in the literature. METHODS: This scoping review of the original research literature maps the available knowledge regarding the impact of the COVID-19 pandemic on healthcare delivery for PWUO. We utilized the methodology developed by the Joanna Briggs Institute for scoping reviews, and content analyses methodology to characterize the current state of the literature. RESULTS: Of the 14 included studies, administrative database (n = 11), cross-sectional (n = 1) or qualitative (n = 2) studies demonstrated service gaps (n = 7), patient/provider experiences (n = 3), and patient outcomes for PWUO (n = 4). In March 2020, healthcare utilization dropped quickly, sharply increasing only for reasons of opioid overdose by May 2020. Service gaps existed in accessing treatment for new patients during the pandemic due to capacity and infrastructure limits. Physicians reported difficulty referring patients to begin an outpatient opioid treatment program due to increased restrictions in capacity and infrastructure. Patients also reported uncertainty about accessing outpatient treatment, but that telehealth initiation of buprenorphine increased access to treatment from home. Disproportionate increases in overdose rates among African Americans were reported in two studies, with differences by race and gender not examined in most studies. Fatal overdoses increased 60% in African Americans during the pandemic, while fatal overdoses in Non-Hispanic White individuals decreased. CONCLUSIONS: In summary, this beginning evidence demonstrates that despite early reluctance to use the healthcare system, opioid overdose-related use of healthcare increased throughout the pandemic. Service delivery for medications to treat OUD remained at or above pre-pandemic levels, indicating the ability of telehealth to meet demand. Yet, racial disparities that existed pre-pandemic for PWUO are intensifying, and targeted intervention for high-risk groups is warranted to prevent further mortality. As the pandemic progresses, future research must focus on identifying and supporting subgroups of PWUO who are at heightened risk for experiencing negative outcomes and lack of access to care.

Policing pain: A qualitative study of non-criminal justice approaches to managing opioid overdose during the COVID-19 pandemic.

Opioid related drug overdose deaths are a leading cause of death and injury in the United States. While research demonstrates that where people live has a major impact on drug use and abuse, most work looks at social dynamics at the county level or under the rubric of the urban/rural divide. Only recently, scholarship has become attuned to the post-industrialized areas located on the fringes of urban cores. Data presented in here are from field research conducted in McKeesport, Pennsylvania, a small river town located east of Pittsburgh. Once a thriving industrial city, it is now deteriorated and has documented high levels of overdose experience. Preliminary results suggest that McKeesport residents, even before the emergence of SARS-CoV-2 (COVID-19), practice social and physical distancing as a way of life; data indicate how the pandemic potentially exacerbates the risk of accidental opioid overdose among a population defined by both geographic and social isolation.

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.

Reimagining patient-centered care in opioid treatment programs: Lessons from the Bronx during COVID-19.

Opioid treatment programs (OTPs) operate within a rigid set of clinical guidelines and regulations that specify the number of required OTP visits for supervised administration of methadone. To ensure physical distancing in light of COVID-19, the federal government loosened regulations to allow for additional flexibility. As OTP providers in the Bronx, NY, caring for more than 3600 patients in the epicenter of both the overdose and COVID-19 pandemics, we describe how our clinical practice changed with COVID-19. We halted toxicology testing, and to promote physical distancing and prevent interruptions in access to treatment for medications for opioid use disorder (MOUD), we drastically increased unsupervised take-home doses of MOUD. Within two weeks, we reduced the proportion of patients with 5-6 OTP visits per week from 47.2% to 9.4%. To guide treatment decision-making, we shifted focus from toxicology tests to other patient-centered measures, such as engagement in care and patient goals. In the initial three months, our patients experienced six nonfatal overdoses, no fatal overdoses, and 20 deaths attributable to COVID-19. This experience provides an opportunity to re-imagine care in OTPs going forward. We advocate that OTPs rely less on toxicology testing and more on the other patient-centered measures to guide decisions about distribution of take-home doses of MOUD. To minimize financial risk to OTPs and facilitate their transition to a more flexible model of care, we advocate for the reassessment of OTP reimbursement models.

Naloxone Use by Emergency Medical Services During the COVID-19 Pandemic: A National Survey.

OBJECTIVES: The COVID-19 epidemic in the United States has hit in the midst of the opioid overdose crisis. Emergency medical services (EMS) clinicians may limit their use of intranasal naloxone due to concerns of novel coronavirus infection. We sought to determine changes in overdose events and naloxone administration practices by EMS clinicians. METHODS: Between April 29, 2020 and May 15, 2020, we surveyed directors of EMS fellowship programs across the US about how overdose events and naloxone administration practices had changed in their catchment areas since March 2020. RESULTS: Based on 60 respondents across all regions of the country, one fifth of surveyed communities have experienced an increase in opioid overdoses and events during which naloxone was administered, and 40% have experienced a decrease. The findings varied by region of the country. Eighteen percent of respondents have discouraged or prohibited the use of intranasal naloxone with 10% encouraging the use of intramuscular naloxone. CONCLUSIONS: These findings may provide insight into changes in opioid overdose mortality during this time and assist in future disaster planning.

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.

Medicaid prescription limits and their implications for naloxone accessibility.

BACKGROUND: Expanding access to and utilization of naloxone is a vitally important harm reduction strategy for preventing opioid overdose deaths, particularly in vulnerable populations like Medicaid beneficiaries. The objective of this study was to characterize the landscape of monthly prescription fill limit policies in Medicaid programs and their potential implications for expanding naloxone use for opioid overdose harm reduction. METHODS: A cross-sectional, multi-modal online and telephonic data collection strategy was used to identify and describe the presence and characteristics of monthly prescription fill limit policies across state Medicaid programs. Contextual characteristics were described regarding each state's Medicaid enrollment, opioid prescribing rates, and overdose death rates. Data collection and analysis occurred between February and May 2020. RESULTS: Medicaid-covered naloxone fills are currently subject to monthly prescription fill limit policies in 10 state Medicaid programs, which cover 20 % of the Medicaid population nationwide. Seven of these programs are located in states ranking in the top 10 highest per-capita opioid prescribing rates in the country. However, 8 of these programs are located in states with opioid overdose death rates below the national average. CONCLUSIONS: Medicaid beneficiaries at high risk of opioid overdose living in states with monthly prescription fill limits may experience significant barriers to obtaining naloxone. Exempting naloxone from Medicaid prescription limit restrictions may help spur broader adoption of naloxone for opioid overdose mortality prevention, especially in states with high opioid prescribing rates. Achieving unfettered naloxone coverage in Medicaid is critical as opioid overdoses and Medicaid enrollment increase amid the COVID-19 pandemic.

Update: COVID-19 Upends Progress on Opioid Crisis.

The pandemic has stretched resources and complicated the delivery of care.

Concentration-dependent mortality of chloroquine in overdose.

Hydroxychloroquine and chloroquine are used extensively in malaria and rheumatological conditions, and now in COVID-19 prevention and treatment. Although generally safe they are potentially lethal in overdose. In-vitro data suggest that high concentrations and thus high doses are needed for COVID-19 infections, but as yet there is no convincing evidence of clinical efficacy. Bayesian regression models were fitted to survival outcomes and electrocardiograph QRS durations from 302 prospectively studied French patients who had taken intentional chloroquine overdoses, of whom 33 died (11%), and 16 healthy volunteers who took 620 mg base chloroquine single doses. Whole blood concentrations of 13.5 µmol/L (95% credible interval 10.1-17.7) were associated with 1% mortality. Prolongation of ventricular depolarization is concentration-dependent with a QRS duration >150 msec independently highly predictive of mortality in chloroquine self-poisoning. Pharmacokinetic modeling predicts that most high dose regimens trialled in COVID-19 are unlikely to cause serious cardiovascular toxicity.

Hydroxychloroquine and chloroquine are closely-related drugs used for the treatment of malaria and rheumatological conditions, such as lupus. Laboratory tests have indicated that these drugs could also be used against the virus that causes COVID-19. Given the urgent need, these drugs have been fast-tracked into large-scale clinical trials, bypassing the usual stages that would provide estimates for suitable dosage. The dosage is a critical factor in a clinical trial: too low and the drug will not have an effect, too high and the side effects may counteract any potential benefits. Laboratory tests suggest that higher doses of chloroquine or hydroxychloroquine are needed for treating COVID-19 compared to malaria or lupus. However, there are concerns about the high doses used in some trials, as the drugs can have lethal side effects. Indeed, chloroquine has been used extensively in suicide attempts, particularly in France. To address these concerns, Watson et al. set out to determine the highest dosage of chloroquine (and thus of hydroxychloroquine, approximately) that does not cause unacceptable side effects. First, data was analysed regarding the concentration of chloroquine in the blood of 302 patients who had intentionally overdosed on the drug, since this concentration is tightly correlated with their risk of death. Watson et al. used a statistical model to calculate the maximal chloroquine concentration in a person's blood associated with a one per cent risk of death. This is taken to be the threshold above which any potential benefit of chloroquine treatment would be outweighed by the possibility of lethal toxicity. Watson et al. also estimated the relationship between chloroquine concentrations and changes in electrocardiogram patterns, which record the electrical activity of the heart. This makes it possible to determine whether a high dose of chloroquine has led to dangerous levels in the blood. Using a mathematical model of how chloroquine is metabolised, Watson et al. predicted that most of the trials that tested chloroquine as a treatment for COVID-19 did not reach the calculated threshold concentration. An exception was the CloroCovid-19 trial in Brazil, which was stopped early because people in the higher dosage group suffered more heart problems and died in greater numbers than those in the lower dosage group. Two large randomised trials, RECOVERY and SOLIDARITY, have shown no benefit of hydroxychloroquine or chloroquine in the treatment of COVID-19, changing clinical practice worldwide. Both of these trials used high doses resulting in higher hydroxychloroquine or chloroquine concentrations than normally observed in the treatment of malaria or rheumatological conditions. The results from Watson et al demonstrate that the lack of benefit seen in these two large clinical trials is not due to the drug dosage being too high.

Overdose and risk factors for coronavirus disease 2019.

BACKGROUND: There have been significant efforts to respond to the two public health emergencies of coronavirus disease 2019 (COVID-19) and overdose in British Columbia (BC), Canada. The purpose of this study was to quantify the prevalence of known risk factors associated with mortality due to COVID-19 for persons who have had a non-fatal overdose during 2015-2017 in comparison to persons who have not had an overdose. METHODS: Data were extracted from the BC Provincial Overdose Cohort which includes a 20 % random sample of BC residents and persons who have had a non-fatal overdose in BC from January 2015 to December 2017. Chi-square tests and logistic regression were used to compare risk factors by overdose history. RESULTS: Persons who had a non-fatal overdose were significantly more likely to have three (chronic pulmonary disease, diabetes, coronary heart disease) of the four known chronic conditions associated with the development of severe illness due to COVID-19 compared to persons who did not have a previous non-fatal overdose event. CONCLUSION: Persons who had an overdose were more likely to have several chronic conditions associated with the development of severe illness due to COVID-19. The increased likelihood of having these risk factors is reflective of the social and health inequities experienced by persons who have a history of overdose.