Literature Collection

BACKGROUND: Despite the World Health Organization listing methadone as an essential medication, effective dose selection is challenging, especially in racial and ethnic minority populations. Subtherapeutic doses can result in withdrawal symptoms while supratherapeutic doses can result in overdose and death. Although CYP3A4 was conventionally considered the principal methadone metabolizing enzyme, more recent data have identified CYP2B6 as the principal enzyme. CYP2B6 has ethnically-associated polymorphisms that affect the metabolic rate. Our objective was to investigate the effects of genetic and nongenetic factors on methadone metabolism. METHODS: We measured trough plasma methadone levels in 100 participants with opioid use disorder. We assessed methadone metabolism by calculating the metabolite ratio (major metabolite: 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine [EDDP] divided by methadone concentration). We assessed hepatic fibrosis and steatosis by transient elastography and CYP2B6 alleles, principally responsible for methadone metabolism. Mixed effects models modeled the data in 97 participants. RESULTS: Participants were largely male (58%), minority (61% African American) and non-Hispanic (68%). Forty percent were HCV mono-infected, 40% were uninfected, and 20% were HCV/HIV co-infected. Female sex had significant effects on (R)- and (S)-methadone metabolism (p = 0.016 and p = 0.044, respectively). CYP2B6 loss of function (LOF) alleles significantly affected (S)-methadone metabolism (p = 0.012). Body mass index (BMI) significantly affected (R)-methadone metabolism (p = 0.034). Methadone metabolism appeared to be lower in males, in individuals with LOF alleles, and elevated BMI. CONCLUSIONS: Genetic analysis, especially in minority populations, is essential to delivering individualized treatments. Although the principal methadone metabolizing enzyme remains controversial, our results suggest that sex, CYP2B6 genotype, and BMI should be incorporated into multivariate models to create methadone dosing algorithms. Methadone dosing algorithms should facilitate medication delivery, improve patient satisfaction, and diminish overdose potential.

Medical education has increasingly shifted towards replacing large lectures with a combination of online and smaller in-person group sessions. This study compares the efficacy of a virtual Opioid Overdose Prevention and Response Training (OOPRT) for first-year medical students with an identical in-person training. During their first unit of medical school, students in the class of 2023 (cohort 1) received OOPRT in-person and students in the class of 2024 (cohort 2) received training via Zoom. Aside from the delivery format, trainings were identical. Both cohorts completed identical surveys at medical school entry and post-training to evaluate knowledge and experiences using the Opioid Overdose Knowledge Scale, Opioid Overdose Attitudes Scale, Medical Conditions Regard Scale, and Naloxone Related Risk Compensation Beliefs. Of 430 students, 84.2% (362: 124 in cohort 1; 238 in cohort 2) completed baseline and post-training surveys. Students reported significantly improved opioid overdose knowledge and attitudes in all 4 knowledge and 3 attitudes subscales after training. Only one outcome differed by training type: knowledge of opioid overdose signs. Cohorts did not differ in opinions of training; 97.2% enjoyed it and 99.4% believed future classes should receive it. Medical students' attitudes and knowledge significantly improved after OOPRT; only one of 13 outcomes showed a cohort difference. There were no differences in enjoyment, indicating that switching to virtual learning does not undermine the learning experience. Further studies are needed to confirm that these results can be extended to other medical school topics where small group interactive discussion is preferred.

Background: A cascade of care (CoC) model may improve understanding of gaps in addiction treatment availability and quality over current single measure methods. Despite increased funding, opioid overdose rates remain high. Therefore, it is critical to understand where the health-care system is failing to provide appropriate care for people with opioid use disorder (OUD) diagnoses, and to assess disparities in receipt of medication for OUD (MOUD).Objective: Using a CoC framework, assess treatment quality and outcomes for OUD in the Florida Medicaid population in 2017/2018 by demographics and primary vs. secondary diagnosis.Methods: Data from Florida Medicaid claims for 2017 and 2018 were used to calculate the number of enrollees who were diagnosed, began MOUD, were retained on medication for a minimum of 180 days, and who died.Results: Only 28% of those diagnosed with OUD began treatment with an FDA approved MOUD (buprenorphine, methadone, or injectable naltrexone). Once on medication, 38% of newly diagnosed enrollees were retained in treatment for180 days. Those who remained on MOUD for 180 days had a hazard ratio of death of 0.226 (95% CI = 0.174 to 0.294) compared to those that did not initiate MOUD, a reduction in mortality from 10% without MOUD to 2% with MOUD.Conclusions: Initiating medication after OUD diagnosis offers the greatest opportunity for intervention to reduce overdose deaths, though efforts to increase retention are also warranted. Analyzing claims data with CoC identifies system functioning for specific populations, and suggests policies and clinical pathways to target for improvement.

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.

BACKGROUND: Identifying solutions to the continued rise in overdose deaths is a public health priority. However, there is evidence of change in recent substance type associated with morbidity and mortality. To better understand the continued rise in overdose deaths, in particular those attributed to opioid and stimulant use disorders, increased knowledge of patterns of use is needed. METHODS: Retrospective cohort study of Veterans diagnosed with an opioid or stimulant use disorder between 2005 and 2019. The outcome of interest was diagnosis of substance use disorders, specifically examining combinations of opioid and stimulant use disorders among this population. RESULTS: A total of 1932,188 Veterans were diagnosed with at least one substance use disorder (SUD) during the study period, 2005 through 2019. While the annual prevalence of opioid use disorder (OUD) diagnoses increased more than 155%, OUD diagnoses absent of any other SUD diagnosis increased by an average of 6.9% (95% CI, 6.4, 7.5) per year between 2005 and 2019. Between 2011 and 2019, diagnoses of co-morbid methamphetamine use disorder (MUD) and OUD increased at a higher rate than other SUD combinations. CONCLUSIONS: The prevalence of comorbid SUD, in particular co-occurring opioid and methamphetamine use disorder, increased at a higher rate than other combinations between 2005 and 2019. These findings underscore the urgent need to offer patients a combination of evidence-based treatments for each co-morbid SUD, such MOUD and contingency management for persons with comorbid opioid and methamphetamine use disorders.

The US opioid epidemic has changed profoundly in the last 3 years, in ways that require substantial recalibration of the US policy response. This report summarizes the changing nature of overdose deaths in Jefferson County (home to Birmingham, Alabama) using data updated through June 30, 2016. Heroin and fentanyl have come to dominate an escalating epidemic of lethal opioid overdose, whereas opioids commonly obtained by prescription play a minor role, accounting for no more than 15% of reported deaths in 2015. Such local data, along with similar reports from other localities, augment the insights available from the Centers for Disease Control and Prevention's current overdose summary, which lacks data from 2015-2016 and lacks information regarding fentanyl in particular. The observed changes in the opioid epidemic are particularly remarkable because they have emerged despite sustained reductions in opioid prescribing and sustained reductions in prescription opioid misuse. Among US adults, past-year prescription opioid misuse is at its lowest level since 2002. Among 12th graders it is at its lowest level in 20 years. A credible epidemiologic account of the opioid epidemic is as follows: although opioid prescribing by physicians appears to have unleashed the epidemic prior to 2012, physician prescribing no longer plays a major role in sustaining it. The accelerating pace of the opioid epidemic in 2015-2016 requires a serious reconsideration of governmental policy initiatives that continue to focus on reductions in opioid prescribing. The dominant priority should be the assurance of subsidized access to evidence-based medication-assisted treatment for opioid use disorder. Such treatment is lacking across much of the United States at this time. Further aggressive focus on prescription reduction is likely to obtain diminishing returns while creating significant risks for patients.

Neonatal opiate withdrawal syndrome (NOWS), previously known as neonatal abstinence syndrome (NAS), is a growing public health concern as opiate misuse and opioid-related overdoses, from both prescription and illicit sources, continue to rise in the USA. As more than 90% of females abusing opioids are of child-bearing age, the failure to adequately address the opioid epidemic continues to negatively impact the next generations. Accurate and timely identification of infants at risk for withdrawal from in-utero exposure is critical to ensure high-quality perinatal and neonatal care. Beginning with an evaluation of current best practices and performing a literature review, we identify the challenges to current screening processes and how these limitations limit the ability to provide appropriate care to infants at the risk of withdrawal. We first describe the limitations of the available assays for the detection of opioid and opioid metabolites across different biological sources from both the mother and the infant. We then present a discussion surrounding factors that contribute to maternal willingness to disclose use. Particularly, in light of the limitations of biological screening, any barrier to maternal disclosure further complicates effective care delivery. Barriers to disclosure include legal ramifications and state policies, provider and societal behaviors and biases, and maternal factors. Moving forward, universal prenatal screening surveys coupled with enhanced outreach and education to providers centering on the limitations of both patient report and biological sampling, as well as comprehensive and supportive services for women of reproductive age with substance use disorders, are needed to both enhance detection for NOWS and improve long-term maternal-child health.