Browsing by Subject "Opioid-related disorders"
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Item Association of Individual and Community Factors With Hepatitis C Infections Among Pregnant People and Newborns(American Medical Association, 2021-10-29) Patrick, Stephen W.; Dupont, William D.; McNeer, Elizabeth; McPheeters, Melissa; Cooper, William O.; Aronoff, David M.; Osmundson, Sarah; Stein, Bradley D.; Medicine, School of MedicineImportance: The opioid crisis has increasingly affected pregnant people and infants. Hepatitis C virus (HCV) infections, a known complication of opioid use, grew in parallel with opioid-related complications; however, the literature informing individual and community risks associated with maternal HCV infection is sparse. Objectives: To determine (1) individual and county-level factors associated with HCV among pregnant people and their newborn infants, and (2) how county-level factors influence individual risk among the highest risk individuals. Design setting and participants: This time-series analysis of retrospective, repeated cross-sectional data included pregnant people in all US counties from 2009 to 2019. We constructed mixed-effects logistic regression models to explore the association between HCV infection and individual and county-level covariates. Analyses were conducted between June 2019 and September 2021. Exposures: Individual-level: race and ethnicity, education, marital status, insurance type; county-level: rurality, employment, density of obstetricians. Main outcomes and measures: Hepatitis C virus as indicated on the newborn's birth certificate. Results: Between 2009 and 2019, there were 39 380 122 pregnant people who met inclusion criteria, among whom 138 343 (0.4%) were diagnosed with HCV. People with HCV were more likely to be White (79.9% vs 53.5%), American Indian or Alaska Native (AI/AN) (2.9% vs 0.9%), be without a 4-year degree (93.2% vs 68.6%), and be unmarried (73.7% vs 38.8%). The rate (per 1000 live births) of HCV among pregnant people increased from 1.8 to 5.1. In adjusted analyses, the following factors were associated with higher rates of HCV: individuals identified as White (adjusted odds ratio [aOR], 7.37; 95% CI, 7.20-7.55) and AI/AN (aOR, 7.94; 95% CI, 7.58-8.31) compared with Black individuals, those without a 4-year degree (aOR, 3.19; 95% CI, 3.11-3.28), those with Medicaid vs private insurance (aOR, 3.27; 95% CI, 3.21-3.33), and those who were unmarried (aOR, 2.80; 95% CI, 2.76-2.84); whereas, rural residence, higher rates of employment, and greater density of obstetricians was associated with lower risk of HCV. Among individuals at the highest risk of HCV, higher levels of county employment, accounting for other factors, were associated with less of a rise in HCV infections over time. Conclusions and relevance: In this cross-sectional study, maternal and newborn HCV infections increased substantially between 2009 and 2019, disproportionately among White and AI/AN people without a 4-year degree. County-level factors, including higher levels of employment, were associated with lower individual risks of acquiring the virus.Item Associations of opioid prescription dose and discontinuation with risk of substance-related morbidity in long-term opioid therapy(Wolters Kluwer, 2022) Quinn, Patrick D.; Chang, Zheng; Bair, Matthew J.; Rickert, Martin E.; Gibbons, Robert D.; Kroenke, Kurt; D’Onofrio, Brian M.; Medicine, School of MedicineEfforts to reduce opioid-related harms have decreased opioid prescription but have provoked concerns about unintended consequences, particularly for long-term opioid therapy (LtOT) recipients. Research is needed to address the knowledge gap regarding how risk of substance-related morbidity changes across LtOT and its discontinuation. This study used nationwide commercial insurance claims data and a within-individual design to examine associations of LtOT dose and discontinuation with substance-related morbidity. We identified 194,839 adolescents and adults who initiated opioid prescription in 2010 to 2018 and subsequently received LtOT. The cohort was followed for a median of 965 days (interquartile range, 525-1550), of which a median of 176 days (119-332) were covered by opioid prescription. During follow-up, there were 17,582 acute substance-related morbidity events, defined as claims for emergency visits, inpatient hospitalizations, and ambulance transportation with substance use disorder or overdose diagnoses. Relative to initial treatment, risk was greater within individual during subsequent periods of >60 to 120 (adjusted odds ratio [OR], 1.29; 95% CI, 1.12 to 1.49) and >120 (OR, 1.48; 95% CI, 1.24-1.76) daily morphine milligram equivalents. Risk was also greater during days 1 to 30 after discontinuations than during initial treatment (OR, 1.19; 95% CI, 1.05-1.35). However, it was no greater than during the 30 days before discontinuations, indicating that the risk may not be wholly attributable to discontinuation itself. Results were supported by a negative control pharmacotherapy analysis and additional sensitivity analyses. They suggest that LtOT recipients may experience increased substance-related morbidity risk during treatment subsequent to initial opioid prescription, particularly in periods involving higher doses.Item Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2B6 Genotype and Methadone Therapy(Wiley, 2024) Robinson, Katherine M.; Eum, Seenae; Desta, Zeruesenay; Tyndale, Rachel F.; Gaedigk, Andrea; Crist, Richard C.; Haidar, Cyrine E.; Myers, Alan L.; Samer, Caroline F.; Somogyi, Andrew A.; Zubiaur, Pablo; Iwuchukwu, Otito F.; Whirl-Carrillo, Michelle; Klein, Teri E.; Caudle, Kelly E.; Donnelly, Roseann S.; Kharasch, Evan D.; Medicine, School of MedicineMethadone is a mu (μ) opioid receptor agonist used clinically in adults and children to manage opioid use disorder, neonatal abstinence syndrome, and acute and chronic pain. It is typically marketed as a racemic mixture of R- and S-enantiomers. R-methadone has 30-to 50-fold higher analgesic potency than S-methadone, and S-methadone has a greater adverse effect (prolongation) on the cardiac QTc interval. Methadone undergoes stereoselective metabolism. CYP2B6 is the primary enzyme responsible for catalyzing the metabolism of both enantiomers to the inactive metabolites, S- and R-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (S- and R-EDDP). Genetic variation in the CYP2B6 gene has been investigated in the context of implications for methadone pharmacokinetics, dose, and clinical outcomes. Most CYP2B6 variants result in diminished or loss of CYP2B6 enzyme activity, which can lead to higher plasma methadone concentrations (affecting S- more than R-methadone). However, the data do not consistently indicate that CYP2B6-based metabolic variability has a clinically significant effect on methadone dose, efficacy, or QTc prolongation. Expert analysis of the published literature does not support a change from standard methadone prescribing based on CYP2B6 genotype (updates at www.cpicpgx.org).Item Expert Panel Consensus on State-Level Policies to Improve Engagement and Retention in Treatment for Opioid Use Disord(American Medical Association, 2022-09-02) Smart, Rosanna; Grant, Sean; Gordon, Adam J.; Pacula, Rosalie Liccardo; Stein, Bradley D.; Social and Behavioral Sciences, School of Public HealthImportance: In the US, recent legislation and regulations have been considered, proposed, and implemented to improve the quality of treatment for opioid use disorder (OUD). However, insufficient empirical evidence exists to identify which policies are feasible to implement and successfully improve patient and population-level outcomes. Objective: To examine expert consensus on the effectiveness and the ability to implement state-level OUD treatment policies. Evidence review: This qualitative study used the ExpertLens online platform to conduct a 3-round modified Delphi process to convene 66 stakeholders (health care clinicians, social service practitioners, addiction researchers, health policy decision-makers, policy advocates, and persons with lived experience). Stakeholders participated in 1 of 2 expert panels on 14 hypothetical state-level policies targeting treatment engagement and linkage, evidence-based and integrated care, treatment flexibility, and monitoring or support services. Participants rated policies in round 1, discussed results in round 2, and provided final ratings in round 3. Participants used 4 criteria associated with either the effectiveness or implementability to rate and discuss each policy. The effectiveness panel (n = 29) considered policy effects on treatment engagement, treatment retention, OUD remission, and opioid overdose mortality. The implementation panel (n = 34) considered the acceptability, feasibility, affordability, and equitability of each policy. We measured consensus using the interpercentile range adjusted for symmetry analysis technique from the RAND/UCLA appropriateness method. Findings: Both panels reached consensus on all items. Experts viewed 2 policies (facilitated access to medications for OUD and automatic Medicaid enrollment for citizens returning from correctional settings) as highly implementable and highly effective in improving patient and population-level outcomes. Participants rated hub-and-spoke-type policies and provision of financial incentives to emergency departments for treatment linkage as effective; however, they also rated these policies as facing implementation barriers associated with feasibility and affordability. Coercive policies and policies levying additional requirements on individuals with OUD receiving treatment (eg, drug toxicology testing, counseling requirements) were viewed as low-value policies (ie, decreasing treatment engagement and retention, increasing overdose mortality, and increasing health inequities). Conclusions and relevance: The findings of this study may provide urgently needed consensus on policies for states to consider either adopting or deimplementing in their efforts to address the opioid overdose crisis.Item Improving Uptake of Emergency Department-initiated Buprenorphine: Barriers and Solutions(Department of Emergency Medicine, School of Medicine, University of California, Irvine, 2022-07-11) Kelly, Timothy D.; Hawk, Kathryn F.; Samuels, Elizabeth A.; Strayer, Reuben J.; Hoppe, Jason A.; Emergency Medicine, School of MedicineEmergency departments (ED) are increasingly providing buprenorphine to persons with opioid use disorder. Buprenorphine programs in the ED have strong support from public health leaders and emergency medicine specialty societies and have proven to be clinically effective, cost effective, and feasible. Even so, few ED buprenorphine programs currently exist. Given this imbalance between evidence-based practice and current practice, proven behavior change approaches can be used to guide local efforts to expand ED buprenorphine capacity. In this paper, we use the theory of planned behavior to identify and address the 1) clinician factors, 2) institutional factors, and 3) external factors surrounding ED buprenorphine implementation. By doing so, we seek to provide actionable and pragmatic recommendations to increase ED buprenorphine availability across different practice settings.Item Incident and long-term opioid therapy among patients with psychiatric conditions and medications: a national study of commercial health care claims(Wolters Kluwer, 2017-01) Quinn, Patrick D.; Hur, Kwan; Chang, Zheng; Krebs, Erin E.; Bair, Matthew J.; Scott, Eric L.; Rickert, Martin E.; Gibbons, Robert D.; Kroenke, Kurt; D’Onofrio, Brian M.; Medicine, School of MedicineThere is growing evidence that opioid prescribing in the United States follows a pattern in which patients who are at the highest risk of adverse outcomes from opioids are more likely to receive long-term opioid therapy. These patients include, in particular, those with substance use disorders (SUDs) and other psychiatric conditions. This study examined health insurance claims among 10,311,961 patients who filled prescriptions for opioids. Specifically, we evaluated how opioid receipt differed among patients with and without a wide range of preexisting psychiatric and behavioral conditions (ie, opioid and nonopioid SUDs, suicide attempts or other self-injury, motor vehicle crashes, and depressive, anxiety, and sleep disorders) and psychoactive medications (ie, antidepressants, benzodiazepines, hypnotics, mood stabilizers, antipsychotics, and medications used for SUD, tobacco cessation, and attention-deficit/hyperactivity disorder). Relative to those without, patients with all assessed psychiatric conditions and medications had modestly greater odds of subsequently filling prescriptions for opioids and, in particular, substantially greater risk of long-term opioid receipt. Increases in risk for long-term opioid receipt in adjusted Cox regressions ranged from approximately 1.5-fold for prior attention-deficit/hyperactivity disorder medication prescriptions (hazard ratio [HR] = 1.53; 95% confidence interval [CI], 1.48-1.58) to approximately 3-fold for prior nonopioid SUD diagnoses (HR = 3.15; 95% CI, 3.06-3.24) and nearly 9-fold for prior opioid use disorder diagnoses (HR = 8.70; 95% CI, 8.20-9.24). In sum, we found evidence of greater opioid receipt among commercially insured patients with a breadth of psychiatric conditions. Future studies assessing behavioral outcomes associated with opioid prescribing should consider preexisting psychiatric conditions.Item Medication for Adolescents and Young Adults with Opioid Use Disorder(Elsevier, 2021) Hadland, Scott E.; Aalsma, Matthew C.; Akgül, Sinem; Alinsky, Rachel H.; Bruner, Ann; Chadi, Nicholas; Galagali, Preeti M.; Kreida, Ellen C.; Robinson, Camille A.; Wilson, J. Deanna; Pediatrics, School of MedicineOpioid-related morbidity and mortality have risen in many settings globally. It is critical that practitioners who work with adolescents and young adults (AYAs) provide timely, evidence-based treatment for opioid use disorder (OUD). Such treatment should include medications for opioid use disorder (MOUD), including buprenorphine, naltrexone, and methadone. Medication treatment is associated with reduced mortality, fewer relapses to opioid use, and enhanced recovery and retention in addiction care, among other positive health outcomes. Unfortunately, the vast majority of AYAs with OUD do not receive medication. The Society for Adolescent Health and Medicine recommends that AYAs be offered MOUD as a critical component of an integrated treatment approach. Barriers to receipt of medications are widespread; many are common to high-, middle-, and low-income countries alike, whereas others differ. Such barriers should be minimized to ensure equitable access to youth-friendly, affirming, and confidential addiction treatment that includes MOUD. Robust education on OUD and medication treatment should be provided to all practitioners who work with AYAs. Strategies to reduce stigma surrounding medication-and stigma experienced by individuals with substance use disorders more generally-should be widely implemented. A broad research agenda is proposed with the goal of expanding the evidence base for the use and delivery of MOUD for AYAs.Item Medications for Opioid Use Disorder for Youth: Patient, Caregiver, and Clinician Perspectives(Elsevier, 2024) Buchholz, Connor; Bell, Lauren A.; Adatia, Safina; Bagley, Sarah M.; Wilens, Timothy E.; Nurani, Alykhan; Hadland, Scott E.; Pediatrics, School of MedicinePurpose: Clinical trial data support use of medications for opioid use disorder (MOUD) in adolescents and young adults ("youth"), but qualitative data are lacking on the acceptability and importance of MOUD to youth, caregivers, and clinicians. We assessed how these stakeholders viewed the role of MOUD in treatment and recovery. Methods: We recruited youth aged from 15 to 25 years with opioid use disorder who had received buprenorphine, naltrexone, or methadone and caregivers from a primary care-based youth addiction treatment program. We also recruited clinicians with addiction expertise from social work, nursing, pediatrics, internal medicine, and psychiatry. We conducted semistructured interviews assessing special considerations for MOUD use in youth. Three coders performed inductive and deductive thematic analysis of transcripts. Results: Among 37 participants, including 15 youth (age range, 17-25 years), nine caregivers, and 13 clinicians, we identified three themes. (1) Medications support recovery in the short term: Youth described MOUD as beneficial in managing withdrawal symptoms. Notably, some youth and caregivers preferred to limit MOUD duration. (2) Medication adherence is affected by type of medication, dosing regimen, and route of administration. Participants endorsed long-acting, injectable MOUD for ease of use and youth's ability to continue engagement in "normal activities" without daily medication. (3) Caregiver involvement can support medication decisions and adherence. Youth and some clinicians described the need to assess caregiver involvement before incorporating them into treatment; caregivers and other clinicians described caregivers as critical in supporting accountability. Discussion: MOUD is evidence-based, and its provision should be developmentally responsive and youth- and family-centered, incorporating caregivers when appropriate.Item Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond(Springer Nature, 2022-10-07) Gaddis, Nathan; Mathur, Ravi; Marks, Jesse; Zhou, Linran; Quach, Bryan; Waldrop, Alex; Levran, Orna; Agrawal, Arpana; Randesi, Matthew; Adelson, Miriam; Jeffries, Paul W.; Martin, Nicholas G.; Degenhardt, Louisa; Montgomery, Grant W.; Wetherill, Leah; Lai, Dongbing; Bucholz, Kathleen; Foroud, Tatiana; Porjesz, Bernice; Runarsdottir, Valgerdur; Tyrfingsson, Thorarinn; Einarsson, Gudmundur; Gudbjartsson, Daniel F.; Webb, Bradley Todd; Crist, Richard C.; Kranzler, Henry R.; Sherva, Richard; Zhou, Hang; Hulse, Gary; Wildenauer, Dieter; Kelty, Erin; Attia, John; Holliday, Elizabeth G.; McEvoy, Mark; Scott, Rodney J.; Schwab, Sibylle G.; Maher, Brion S.; Gruza, Richard; Kreek, Mary Jeanne; Nelson, Elliot C.; Thorgeirsson, Thorgeir; Stefansson, Kari; Berrettini, Wade H.; Gelernter, Joel; Edenberg, Howard J.; Bierut, Laura; Hancock, Dana B.; Johnson, Eric Otto; Medical and Molecular Genetics, School of MedicineOpioid addiction (OA) is moderately heritable, yet only rs1799971, the A118G variant in OPRM1, has been identified as a genome-wide significant association with OA and independently replicated. We applied genomic structural equation modeling to conduct a GWAS of the new Genetics of Opioid Addiction Consortium (GENOA) data together with published studies (Psychiatric Genomics Consortium, Million Veteran Program, and Partners Health), comprising 23,367 cases and effective sample size of 88,114 individuals of European ancestry. Genetic correlations among the various OA phenotypes were uniformly high (rg > 0.9). We observed the strongest evidence to date for OPRM1: lead SNP rs9478500 (p = 2.56 × 10-9). Gene-based analyses identified novel genome-wide significant associations with PPP6C and FURIN. Variants within these loci appear to be pleiotropic for addiction and related traits.Item Obstetrical Providers’ Management of Chronic Pain in Pregnancy: A Vignette Study(Oxford University Press, 2017) Tucker Edmonds, Brownsyne; McKenzie, Fatima; Austgen, MacKenzie B.; Ashburn-Nardo, Leslie; Matthias, Marianne S.; Hirsh, Adam T.; Obstetrics and Gynecology, School of MedicineObjective: Describe obstetrical providers' management of a hypothetical case on chronic pain in pregnancy and determine whether practices differ based on patient race. Design and setting: This was a self-administered survey at a clinical conference. Subjects: Seventy-six obstetrician-gynecologists and one nurse practitioner were surveyed. Methods: A case-vignette described a pregnant patient presenting with worsening chronic lower back pain, requesting an opioid refill and increased dosage. We varied patient race (black/white) across two randomly assigned identical vignettes. Providers indicated their likelihood of prescribing opioids, drug testing, and referring on a 0 (definitely would not) to 10 (definitely would) scale; rated their suspicions/concerns about the patient on a 0-10 VAS scale; and ranked those concerns in order of importance. We calculated correlation coefficients, stratifying analyses by patient race. Results: Providers were not inclined to refill the opioid prescription (median = 3.0) or increase the dose (median = 1.0). They were more likely to conduct urine drug tests on white than black patients ( P = 0.008) and more likely to suspect that white patients would divert the medication ( P =0.021). For white patients, providers' highest-ranked concern was the patient's risk of abuse/addiction, whereas, for black patients, it was harm to the fetus. Suspicion about symptom exaggeration was more closely related to decisions about refilling the opioid prescriptions and increasing the dose for black patients (r = -0.357, -0.439, respectively), whereas these decisions were more closely correlated with concerns about overdose for white patients (r = -0.406, -0.494, respectively). Conclusions: Provider suspicion and concerns may differ by patient race, which may relate to differences in pain treatment and testing. Further study is warranted to better understand how chronic pain is managed in pregnancy.