The North American opioid epidemic: opportunities and challenges for clinical laboratories.

Since 1999, the opioid epidemic in North America has resulted in over 1 million deaths, and it continues to escalate despite numerous efforts in various arenas to combat the upward trend. Clinical laboratories provide drug testing to support practices such as emergency medicine, substance use disorder treatment, and pain management; increasingly, these laboratories are collaborating in novel partnerships including drug-checking services (DCS) and multidisciplinary treatment teams. This review examines drug testing related to management of licit and illicit opioid use, new technologies and test strategies employed by clinical laboratories, barriers hindering laboratory response to the opioid epidemic, and areas for improvement and standardization within drug testing. Literature search terms included combinations of "opioid," "opiate," "fentanyl," "laboratory," "epidemic," "crisis," "mass spectrometry," "immunoassay," "drug screen," "drug test," "guidelines," plus review of PubMed "similar articles" and references within publications. While immunoassay (IA) and point-of-care (POC) test options for synthetic opioids are increasingly available, mass spectrometry (MS) platforms offer the greatest flexibility and sensitivity for detecting novel, potent opioids. Previously reserved as a second-tier application in most drug test algorithms, MS assays are gaining a larger role in initial screening for specific patients and DCS. However, there are substantial differences among laboratories in terms of updating test menus, algorithms, and technologies to meet changing clinical needs. While some clinical laboratories lack the resources and expertise to implement MS, many are also slow to adopt available IA and POC tests for newer opioids such as fentanyl. MS-based testing also presents challenges, including gaps in available guidance for assay validation and ongoing performance assessment that contribute to a dramatic lack of standardization among laboratories. We identify opportunities for improvement in laboratory operations, reporting, and interpretation of drug test results, including laboratorian and provider education and laboratory-focused guidelines. We also highlight the need for collaboration with providers, assay and instrument manufacturers, and national organizations to increase the effectiveness of clinical laboratory and provider efforts in preventing morbidity and mortality associated with opioid use and misuse.

Outcomes of patients with COVID-19 in the setting of chronic opioid use disorder.

BACKGROUND: There are limited studies regarding the effects of COVID-19 in patients with a concurrent diagnosis of opioid use disorder (OUD). Due to the rapidly developing nature and consequences of this disease, it is important to identify patients at an increased risk for serious illness. The aim of this study was to identify whether COVID-19 patients with OUD are at an increased risk of hospitalization and other adverse outcomes. METHODS: This retrospective chart review compared clinical parameters from patients with positive COVID-19 status as identified by a positive SARS-CoV-2 PCR test and diagnosed OUD at the University of Utah Health. The primary outcome variables were hospitalization for COVID-19, length of hospital stay, and the presence of comorbidities in the OUD patient population. Descriptive statistics and prevalence ratios (PRs) were generated. Log binomial models generated PRs adjusted by age, sex, and race, and comorbidities of asthma, pneumonia, hypertension, cardiovascular disease, and diabetes. RESULTS: COVID-19 patients with OUD were significantly more likely than patients without OUD to have asthma (p < 0.01), diabetes (p < 0.01), hypertension (p < 0.01), cardiovascular disease (p < 0.01), and chronic pneumonia (p < 0.01), and to be hospitalized (27.9 percent vs 3.6 percent; p < 0.01), admitted to the intensive care unit (11.5 percent vs 1.5 percent; p < 0.01), and receive mechanical ventilation (30.5 percent vs 0.1 percent; p < 0.01). After adjusting for age, sex, race, asthma, pneumonia, cardiovascular disease, hypertension, and diabetes, patients with OUD continued to be at increased risk for inpatient hospitalization (aPR = 4.27, 95 percent confidence interval [CI] = 1.66-10.94). Patients with OUD also averaged longer stays in the hospital than those without OUD (9.53 days vs 0.70 days, p < 0.001). CONCLUSION: Patients with a diagnosis of OUD in the presence of COVID-19 are more likely to be hospitalized, have underlying health issues, and have longer hospital inpatient stays compared to patients without OUD.

An adaptive design to screen, treat, and retain people with opioid use disorders who use methamphetamine in methadone clinics (STAR-OM): study protocol of a clinical trial.

BACKGROUND: Methamphetamine use could jeopardize the current efforts to address opioid use disorder and HIV infection. Evidence-based behavioral interventions (EBI) are effective in reducing methamphetamine use. However, evidence on optimal combinations of EBI is limited. This protocol presents a type-1 effectiveness-implementation hybrid design to evaluate the effectiveness, cost-effectiveness of adaptive methamphetamine use interventions, and their implementation barriers in Vietnam. METHOD: Design: Participants will be first randomized into two frontline interventions for 12 weeks. They will then be placed or randomized to three adaptive strategies for another 12 weeks. An economic evaluation and an ethnographic evaluation will be conducted alongside the interventions. PARTICIPANTS: We will recruit 600 participants in 20 methadone clinics. ELIGIBILITY CRITERIA: (1) age 16+; (2) Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) scores ≥ 10 for methamphetamine use or confirmed methamphetamine use with urine drug screening; (3) willing to provide three pieces of contact information; and (4) having a cell phone. OUTCOMES: Outcomes are measured at 13, 26, and 49 weeks and throughout the interventions. Primary outcomes include the (1) increase in HIV viral suppression, (2) reduction in HIV risk behaviors, and (3) reduction in methamphetamine use. COVID-19 response: We developed a response plan for interruptions caused by COVID-19 lockdowns to ensure data quality and intervention fidelity. DISCUSSION: This study will provide important evidence for scale-up of EBIs for methamphetamine use among methadone patients in limited-resource settings. As the EBIs will be delivered by methadone providers, they can be readily implemented if the trial demonstrates effectiveness and cost-effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov NCT04706624. Registered on 13 January 2021. https://clinicaltrials.gov/ct2/show/NCT04706624.

Impact of the COVID-19 pandemic on opioid overdose and other adverse events in the USA and Canada: a systematic review.

IMPORTANCE: The COVID-19 pandemic impacted healthcare beyond COVID-19 infections. A better understanding of how COVID-19 worsened the opioid crisis has potential to inform future response efforts. OBJECTIVE: To summarize changes from the COVID-19 pandemic on outcomes regarding opioid use and misuse in the USA and Canada. EVIDENCE REVIEW: We searched MEDLINE via PubMed, EMBASE, and CENTRAL for peer-reviewed articles published between March 2020 and December 2021 that examined outcomes relevant to patients with opioid use, misuse, and opioid use disorder by comparing the period before vs after COVID-19 onset in the USA and Canada. Two reviewers independently screened studies, extracted data, assessed methodological quality and bias via Newcastle-Ottawa Scale, and synthesized results. FINDINGS: Among 20 included studies, 13 (65%) analyzed service utilization, 6 (30%) analyzed urine drug testing results, and 2 (10%) analyzed naloxone dispensation. Opioid-related emergency medicine utilization increased in most studies (85%, 11/13) for both service calls (17% to 61%) and emergency department visits (42% to 122%). Urine drug testing positivity results increased in all studies (100%, 6/6) for fentanyl (34% to 138%), most (80%, 4/5) studies for heroin (-12% to 62%), and most (75%, 3/4) studies for oxycodone (0% to 44%). Naloxone dispensation was unchanged and decreased in one study each. INTERPRETATION: Significant increases in surrogate measures of the opioid crisis coincided with the onset of COVID-19. These findings serve as a call to action to redouble prevention, treatment, and harm reduction efforts for the opioid crisis as the pandemic evolves. PROSPERO REGISTRATION NUMBER: CRD42021236464.

Impact of Cannabis Use, Substance Use Disorders, and Psychiatric Diagnoses on COVID-19 Outcomes: A Retrospective Cohort Study.

Objective: While psychiatric disorders have been recognized as a risk factor for COVID-19 outcomes, the impact of substance use disorders (SUD) on COVID-19 outcomes has not, to date, been examined in a systematic manner. We examined the association between SUD (cannabis, cocaine, alcohol, opioid, and benzodiazepine) as well as psychiatric diagnoses (schizophrenia, mood disorders, anxiety disorders) and COVID-19 outcomes in a large, retrospective cohort study.Methods: COVID-19-positive patients admitted to a large health care system in the US between January and December 2020 were included in this study. SUD and psychiatric diagnoses were identified from urine toxicology reports and ICD-10 diagnosis codes in the electronic medical record, respectively. Multivariable logistic regression was performed controlling for potential confounders such as age, race, sex, smoking status, and medical comorbidities. COVID-19-relevant outcomes included mortality, need for intensive care unit (ICU) admission, need for ventilatory support, length of hospitalization, and number of hospitalizations.Results: Among COVID-19 patients (N = 6,291), those with SUD were more likely to require ICU admission (adjusted odds ratio [AOR] = 1.46, P = .003) and ventilatory support (AOR = 1.49, P = .01). The association between SUD and ICU admission was driven by alcohol use disorder (AUD), whereas that between SUD and ventilatory support was driven by both AUD and opioid use disorder (OUD). Patients with SUD were more likely to have a longer mean maximum length of hospitalization (11.32 vs 8.62 days, P < .0001) and a greater mean number of hospital admissions in 2020 (2.96 vs 2.33, P < .0001). These associations were significant for cannabis use disorder, AUD, OUD, and benzodiazepine use disorder. The association with greater number of admissions was also significant for cocaine use disorder. Patients with psychiatric diagnoses were also more likely to have a greater maximum length of hospitalization (11.93 vs 8.39 days, P < .0001) and hospital admissions (2.72 vs 2.31, P < .0001). These associations were significant for schizophrenia, mood disorders, and anxiety disorders.Conclusions: COVID-19 patients with SUD had greater likelihood of requiring critical interventions, such as ICU admission and ventilatory support. SUD and psychiatric diagnoses were also associated with a longer duration of hospitalization and greater number of hospital admissions. These findings identify COVID-19 patients with SUD and psychiatric comorbidities as a high-risk group.

Psychometric validation of the AOSL scale using confirmatory factor analysis: A nationally representative sample.

BACKGROUND: The opioid overdose epidemic has worsened during the COVID-19 pandemic. Recent data revealed a 28.5% increase in drug-related overdose deaths from 2019 to 2020. Adolescents often misuse family members' and friends' prescription opioid medications. Furthermore, adolescents may not possess the knowledge or understanding to safely manage opioid medications. There is a need for a validated scale to effectively measure adolescents' opioid misuse knowledge, attitudes, and interest in learning about prescription opioid safety. OBJECTIVE: The purpose of this study was to validate the Adolescent Opioid Safety and Learning (AOSL) scale with a nationally representative sample of adolescents and confirm the factor structure of the scale using confirmatory factor analysis (CFA). METHODS: Adolescent participants (aged 13-18 years) completed the 16-item AOSL scale in Qualtrics from November to December 2020. A total of 774 responses were analyzed. A CFA was performed to determine the fit of the data to the 4-factor model proposed by a prior exploratory factor analysis of the AOSL scale. Fit was assessed using the chi-square test, comparative fit index (CFI), Tucker-Lewis index (TLI), and root mean-squared error of approximation (RMSEA). RESULTS: Participants were 50% male and 62% white non-Hispanic. The CFI was 0.984, TLI was 0.980, and RMSEA was 0.048 ([95% CI 0.041-0.054], P-value that RMSEA ≤ 0.05 = 0.712). The chi-square test results were χ2 = 268.752 on 98 degrees of freedom (P < 0.001). Cronbach's alpha, a measure of internal consistency, was high within each factor. CFA indicated good fit of the current study's data to the 4-factor model. CONCLUSION: We found the AOSL scale measures adolescents' knowledge of opioid misuse, knowledge of opioid harm, interest in learning about prescription opioids, and likelihood to practice misuse behaviors. This scale can help researchers understand adolescent perceptions and opinions about opioid safety.

Clinical and demographic differences in the willingness to use self-administered at-home COVID-19 testing measures among persons with opioid use disorder.

Background: COVID-19 is disproportionately affecting disadvantaged populations, including persons with opioid use disorder (OUD). Persons with OUD are at greater risk for direct (e.g., COVID-19 diagnosis, severe symptoms) and indirect consequences (relapse, overdose) of COVID-19. Given stay at home orders, at-home testing options may serve as a viable tool to curb the increase in COVID-19 transmission and adverse effects of COVID-19. Methods: From May to September 2020, we surveyed 110 persons in treatment for OUD about their willingness to use various self-administered at-home COVID-19 testing measures. Participants were stratified by age, gender, and racial-ethnic identity to observe differences in willingness to use COVID-19 tests. The three COVID-19 tests included a throat swab sample, a saliva-based sample, and a blood prick test. Results: A high willingness to use at-home COVID-19 tests was observed in patients in treatment for OUD. A greater proportion of females were willing to use a saliva-based test; greater proportions of White participants were willing to use a saliva based COVID-19 test compared to racial-ethnic minorities. Older aged participants (≥45 years old) reported greater rates of willingness to use a self-administered at home blood prick test for COVID-19. Conclusions: At-home testing measures for COVID-19 appear highly acceptable among people with OUD.

How To Prepare for the Unexpected: a Public Health Laboratory Response.

Public health laboratories (PHLs) continue to face internal and external challenges to their abilities to provide successful, timely responses to public health crises and emerging threats. These laboratories are mandated to maintain the health of their communities by identifying, diagnosing, and warning constituents of potential and real health emergencies. Due to the changing characteristics of public health threats and their cross-jurisdictional nature, laboratories are facing increased pressure to ensure that they respond in a consistent and coordinated manner. Here, the Association of Public Health Laboratories (APHL) Emerging Leader Program Cohort 11 members have compiled stories from subject matter experts (SMEs) at PHLs with direct involvement in crises to determine the characteristics of a successful response. Experts examined a diverse selection of emerging threats from across PHLs, including infectious diseases, opioids, natural disasters, and government shutdowns. While no public health crisis will be identical to another, overarching themes were consistent across subjects. Experiences from SMEs that could improve future responses to emerging threats are highlighted.

Buprenorphine management in the perioperative period: educational review and recommendations from a multisociety expert panel.

BACKGROUND: The past two decades have witnessed an epidemic of opioid use disorder (OUD) in the USA, resulting in catastrophic loss of life secondary to opioid overdoses. Medication treatment of opioid use disorder (MOUD) is effective, yet barriers to care continue to result in a large proportion of untreated individuals. Optimal analgesia can be obtained in patients with MOUD within the perioperative period. Anesthesiologists and pain physicians can recommend and consider initiating MOUD in patients with suspected OUD at the point of care; this can serve as a bridge to comprehensive treatment and ultimately save lives. METHODS: The Board of Directors of the American Society of Regional Anesthesia and Pain Medicine, American Society of Anesthesiologists, American Academy of Pain Medicine, American Society of Addiction Medicine and American Society of Health System Pharmacists approved the creation of a Multisociety Working Group on Opioid Use Disorder, representing the fields of pain medicine, addiction, and pharmacy health sciences. An extensive literature search was performed by members of the working group. Multiple study types were included and reviewed for quality. A modified Delphi process was used to assess the literature and expert opinion for each topic, with 100% consensus being achieved on the statements and each recommendation. The consensus statements were then graded by the committee members using the United States Preventive Services Task Force grading of evidence guidelines. In addition to the consensus recommendations, a narrative overview of buprenorphine, including pharmacology and legal statutes, was performed. RESULTS: Two core topics were identified for the development of recommendations with >75% consensus as the goal for consensus; however, the working group achieved 100% consensus on both topics. Specific topics included (1) providing recommendations to aid physicians in the management of patients receiving buprenorphine for MOUD in the perioperative setting and (2) providing recommendations to aid physicians in the initiation of buprenorphine in patients with suspected OUD in the perioperative setting. CONCLUSIONS: To decrease the risk of OUD recurrence, buprenorphine should not be routinely discontinued in the perioperative setting. Buprenorphine can be initiated in untreated patients with OUD and acute pain in the perioperative setting to decrease the risk of opioid recurrence and death from overdose.

Treatment of opioid use disorder in primary care.

Opioid use disorder (OUD) is a common, treatable chronic disease that can be effectively managed in primary care settings. Untreated OUD is associated with considerable morbidity and mortality-notably, overdose, infectious complications of injecting drug use, and profoundly diminished quality of life. Withdrawal management and medication tapers are ineffective and are associated with increased rates of relapse and death. Pharmacotherapy is the evidence based mainstay of OUD treatment, and many studies support its integration into primary care settings. Evidence is strongest for the opioid agonists buprenorphine and methadone, which randomized controlled trials have shown to decrease illicit opioid use and mortality. Discontinuation of opioid agonist therapy is associated with increased rates of relapse and mortality. Less evidence is available for the opioid antagonist extended release naltrexone, with a meta-analysis of randomized controlled trials showing decreased illicit opioid use but no effect on mortality. Treating OUD in primary care settings is cost effective, improves outcomes for both OUD and other medical comorbidities, and is highly acceptable to patients. Evidence on whether behavioral interventions improve outcomes for patients receiving pharmacotherapy is mixed, with guidelines promoting voluntary engagement in psychosocial supports, including counseling. Further work is needed to promote the integration of OUD treatment into primary care and to overcome regulatory barriers to integrating methadone into primary care treatment in the US.

The Opioid Epidemic Within the COVID-19 Pandemic: Drug Testing in 2020.

The convergence of the opioid epidemic and the coronavirus disease 2019 (COVID-19) pandemic has created new health care challenges. The authors analyzed changes in clinical drug testing patterns and results at a national clinical laboratory, comparing data obtained before and during the pandemic. Testing for prescription and illicit drugs declined rapidly during the pandemic, with weekly test volumes falling by approximately 70% from the baseline period to the trough (the week beginning March 29) before rising in subsequent weeks. Among individuals tested, positivity increased by 35% for non-prescribed fentanyl and 44% for heroin during the pandemic. Positivity for non-prescribed fentanyl increased significantly among patients positive for other drugs: by 89% for specimens positive for amphetamines; 48% for benzodiazepines; 34% for cocaine; and 39% for opiates (P < 0.01 for all comparisons). These findings suggest significant increases in dangerous drug combinations. Positivity for non-prescribed use of many other drugs remained consistent or declined for some drugs, relative to pre-pandemic patterns. Models adjusting for potential confounding variables, including medication-assisted treatment and treatment at a substance use disorder facility indicated that the risk for non-prescribed fentanyl positivity rose by more than 50% during the pandemic. In summary, these findings demonstrate decreased drug testing overall, with increased positivity for high-risk drugs and dangerous drug combinations. The convergence of the drug abuse epidemic and COVID-19 pandemic has led to an increased need for health care and public health resources dedicated to supporting vulnerable patients and addressing the underlying causes of these disturbing trends.

Tales from the frontlines: An alarming rise in hospitalizations related to opioid use disorder in the era of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has had harmful effects on the opioid epidemic. While a negative effect was predicted, we report on this reality in the hospital setting. We have seen a sharp rise in hospitalized patients with opioid use disorder (OUD). Our data should encourage ongoing efforts to reduce barriers in accessing medications for treatment, harm reduction interventions and additional education for trainees, primary care providers, and hospitalists alike. In the current climate, these interventions are critical to save the lives of patients with OUD.

Addressing opioid overdose deaths: The vision for the HEALing communities study.

The United States is facing two devastating public health crises- the opioid epidemic and the COVID-19 pandemic. Within this context, one of the most ambitious implementation studies in addiction research is moving forward. Launched in May 2019, the HEALing Communities Study (HCS) was developed by the National Institutes of Health (NIH) and the Substance Abuse and Mental Health Services Administration (SAMHSA) as part of the Helping to End Addiction Long-termSM Initiative (National Institutes of Health, 2020). The goal for this research was to reduce opioid overdose deaths by 40 % in three years by enhancing and integrating the delivery of multiple evidence-based practices (EBPs) with proven effectiveness in reducing opioid overdose deaths across health care, justice, and community settings. This paper describes the initial vision, goals, and objectives of this initiative; the impact of COVID-19; and the potential for knowledge to be generated from HCS at the intersection of an unrelenting epidemic of opioid misuse and overdoses and the ravishing COVID-19 pandemic.

Down the drain: Reconsidering routine urine drug testing during the COVID-19 pandemic.

The COVID-19 pandemic and the move to telemedicine for office-based opioid treatment have made the practice of routine urine drug tests (UDT) obsolete. In this commentary we discuss how COVID-19 has demonstrated the limited usefulness and possible harms of routine UDT. We propose that practitioners should stop using routine UDT and instead use targeted UDT, paired with clinical reasoning, as part of a patient-centered approach to care.

Considering the harms of our habits: The reflexive urine drug screen in opioid use disorder treatment.

The COVID-19 pandemic has led to abrupt changes in the delivery of substance use treatment, notably the adoption of telehealth services and a departure from mandatory urine drug screens (UDS). Amid current circumstances, the UDS, which had evolved to signal a "successful" recovery, no longer seems feasible, safe, or necessary. Even prior to the pandemic, the UDS had notable drawbacks, including sending a message of mistrust and hierarchy, potentially causing psychological trauma, and incentivizing falsification. Nonetheless, certain patients may state that they depend on the UDS for motivation or structure while some providers may rely on it to discover which patients are struggling. While a combination of self-report and UDS is generally regarded as the strongest measure of substance use among patients, our experiences caring for patients without the results of the UDS during the COVID-19 pandemic have forced us to examine the use of other measures to define a successful recovery. Complete abstinence may not be the goal for all patients and those who achieve abstinence may have additional goals worth supporting. While the UDS will likely be incorporated back into our treatment plans, we suggest unseating it as the centerpiece of substance use care and discovering additional methods of measuring our patients' outcomes in less traumatizing and more patient-centered ways.

Evidence of increased Fentanyl use during the COVID-19 pandemic among opioid agonist treatment patients in Ontario, Canada.

BACKGROUND: Amid the opioid crisis, the health care system is restructuring to prevent and treat COVID-19. Individuals in opioid agonist treatment (OAT) are uniquely challenged because of disruption to treatment, medication diversion, and isolation during the pandemic. METHODS: Between January and September 2020, we utilized the electronic medical record from a chain of 67 opioid agonist treatment clinics in Ontario, Canada, to examine routinely collected urine drug screen results of patients in opioid agonist treatment by Public Health Units. RESULTS: We present evidence of a 108% increase in the percentage of fentanyl positive urine drug screens from April to September (p< 0.001). During the same period, health regions in northern and southwestern Ontario, areas with a high concentration of rural communities, have seen the most notable increase in the percent of fentanyl positive urine drug screen results. CONCLUSION: The use of fentanyl increased by 108% among OAT patients in Ontario during the COVID 19 pandemic. We argue that the persistent increase of fentanyl exposure over time, specifically in the OAT population, suggests that reduced monitoring may decrease OAT's effectiveness and negatively impact patient outcomes.