After two decades of liberal prescribing of opioids, there has been an increasing recognition of problems connected to the prolonged use of opioids for chronic pain. The aim of my thesis was to explore some consequences of long-term opioid treatment for chronic pain such as problematic opioid use, endocrine disorders, tolerance and genetic variations in pain and opioid response. Sixty patients with severe pain and problematic opioid use were treated with a structured methadone programme. Risk factors were musculoskeletal pain, psychiatric co-morbidity and previous addiction. Treatment resulted in good pain relief and improved quality of life, but function was impaired by side effects indicating endocrine dysregulation. The possibility of opioid-induced endocrine dysfunction was explored in the second paper, where 40 pain patients treated with strong opioids and 20 pain patients without treatment of strong opioids were investigated. The opioid-treated patients had significantly higher incidence of endocrine disturbance affecting gonadal and adrenal function and prolactin levels. The functionality of the μ-receptor after long-term treatment with morphine, saline and naloxone was explored in a cell-line expressing the μ-receptor. After one and four weeks of treatment the binding was tested with morphine, methadone, fentanyl and DAMGO and function measured by GTP γ-assay. The binding of DAMGO was significantly diminished after 4 weeks in cells treated with morphine compared with saline and naloxone. Genetic variation in three genes with functional impact on opioid response and pain sensitivity was investigated in 80 patients with chronic low-back pain and differential opioid sensitivity and in 56 healthy controls. The results indicated a higher incidence of opioid-related side effects and gender differences in patients with the minor allele of the ABCB1 gene, a correlation between increased opioid sensitivity and the major CACNA2D2 allele and a possible relationship between intrinsic protection against chronic pain and the minor allele of OPRM1.

BACKGROUND: Guidelines recommend long-term treatment for opioid use disorder including the use of buprenorphine; however, little is known about patients in long-term treatment. OBJECTIVE: Examine the prevalence and patient characteristics associated with long-term treatment retention (≥1 year) in an Office Based Opioid Treatment (OBOT) program with buprenorphine. Study Design: This is a 12-year retrospective cohort study of adults on buprenorphine in OBOT in a large urban safety-net primary care practice. METHODS: The primary outcome was retention in OBOT for ≥1 continuous year. Patients who re-enrolled multiple times in the program contributed repeated observations. Potential predictors of ≥1 year retention assessed were: age, race/ethnicity, psychiatric diagnoses, hepatitis C, employment, prior buprenorphine, ever heroin use, current cocaine, benzodiazepine and alcohol use on enrollment. Factors associated with ≥1 year OBOT retention were identified using generalized estimating equation logistic regression models. The different reasons for clinic disengagement by retention status (i.e. ≥1 year vs. <1 year) were also described. RESULTS: OBOT treatment periods (n=1605) among 1237 patients were assessed. Almost half, 44.7% (717/1605), of all treatment periods were ≥1 year and a majority, 53.7% (664/1237), of patients had at least one ≥ 1 year period. In adjusted analyses, female gender (Adjusted Odds Ratio [AOR] 1.55, 95% CI [1.20, 2.00]) psychiatric diagnosis (AOR 1.75 [1.35, 2.27]) and age (AOR 1.19 per 10 year increase [1.05, 1.34]) were associated with greater odds of ≥1 year retention. Unemployment (AOR 0.72 [0.56, 0.92]), Hepatitis C (AOR 0.59 [0.45, 0.76]), black race/ethnicity (AOR 0.53 [0.36, 0.78]) and Hispanic race/ethnicity (AOR 0.66 [0.48, 0.92]), compared to white, were associated with lower odds of ≥1 year retention. Relapse to substance use appeared to be a less common reason for disengagement for the ≥1 year (23.3%) compared to the <1 year (40.1%) treatment periods. CONCLUSIONS: Over half of patients were successfully retained in Office Based Opioid Treatment with buprenorphine for ≥1 year. However, significant disparities in one-year treatment retention were seen, including poorer retention for patients who were younger, black, Hispanic, unemployed, or with hepatitis C. / 2018-11-09T00:00:00Z

Indiana University-Purdue University Indianapolis (IUPUI) / The United States is experiencing a severe opioid use epidemic with more than 2 million people currently suffering from opioid use disorder (OUD), of which, over 1 million need treatment. Opioid treatment programs (OTPs) are evidence-based modality providing comprehensive care to individuals experiencing OUD. OTPs provide counseling, medical assessments, and medication-assisted treatment, which decrease the use of illicit opioids, reduce associated deaths, criminality, and improve the psychosocial wellbeing of its patients. However, OTPs have been extensively regulated at the federal, state, and local levels with little consistency and varying degrees of enforcement across the country, particularly at the state level, creating a “regulatory fog”. This complex regulatory environment has made it challenging to study new or changing regulations and their impact on health outcomes. In order to better understand the variation of OTP regulation, this dissertation: (1) employs public health law research methods to map the entire landscape of state-level regulation of OTPs and associated state characteristics in effect on January 1, 2017; (2) examine how state-level regulations affect the delivery of care from the perspective of OTP administrators through key-information interviews; and (3) examines associations between regulatory burden and related health outcomes of individuals experiencing OUD, by state.

The U.S. Department of Health and Human Services has declared the misuse of opioid prescription drugs as a public health emergency. The Affordable Care Act’s Medicaid expansion expanded the number of people with insurance and increased the demand for services related to substance abuse treatment. In the first part of this study, the researcher examines whether the Medicaid expansion reduced the likelihood of treatment delay. The second part of this study explores whether the length of stay for opioid use disorder treatment is significantly different in states that adopted Medicaid expansion versus states that did not. In both studies, the researcher analyzes administrative data from the Substance Abuse and Mental Health Services Administration to discover any treatment delays associated with the opioid treatments for the states that adopted the expansion versus the states that did not, and to determine whether there was a difference in the length of stay in the states that adopted the Medicaid versus the states that did not. A difference-in-difference approach is used in both studies to compare the states which adopted an optional Medicaid expansion to those non-adoption states. The evidence suggests that demand for opioid treatment services increased in expansion states as there is a decreased probability of obtaining treatment on the first day for initial requests for outpatient treatment. In addition, evidence suggests that Medicaid expansion increased the likelihood of staying longer in outpatient facilities, but not inpatient facilities. / Business Administration/Risk Management and Insurance

Introduction. While opioid medications are commonly prescribed for management of neuropathic pain (NP), long-term use has been associated with increased risk for overdose, drug interactions and addiction. New strategies are necessary to better manage chronic pain, thereby reducing need for opioid medications and their associated adverse consequences. N-acetyl-L-cysteine (NAC), an over-the-counter supplement, has shown promise in the treatment of psychiatric and addictive disorders. In addition, NAC has shown promise for reducing physiological signs of NP in laboratory rat models, prompting this study. Purpose. The present study was an open-label clinical trial of NAC as an adjuvant to opioid treatment for poorly controlled, chronic NP. It examined whether 1200 mg NAC twice daily for 4 weeks was associated with: lower ratings of patient-reported pain; reductions in PRN opioid medication for breakthrough pain; and improvements in physical and mental health quality of life (QoL). The study also examined whether appraisal of pain impacts response to medication. Method. Participants were N=28 chronic NP patients who consented to study participation. This consisted of 2 baseline assessments, 4 weeks of NAC and 1 post-trial follow-up visit. The majority (N=17) dropped out or were excluded during baseline. Of the remaining participants, N = 11 started the study medication and N=10 completed the study, with daily recordings of pain severity ratings and use of PRN opioid medication. Small sample size limited analyses to qualitative case reviews and effect sizes. Results. Over 90% of participants receiving NAC completed the study. Case review found varied results. While 4 of 10 participants showed decrease in average pain ratings during NAC, estimated effect sizes for the whole sample were small, bordering on negligible (ω² from .003 to .027) as were those for PRN opioids (Partial Eta-Squared=.0003). Effect size for mental health QoL was medium (Cohen's d=.421). Conclusions. With N=10, findings must be interpreted with caution. Nonetheless, the study found some albeit small evidence supporting NAC for improving mental health QoL and pain ratings. Several participants reported improvements in pain and mental health domains while taking NAC. NAC was well tolerated with minimal side effects. Lessons from this study will inform design and implementation of future NAC studies.

Aims: Untreated opioid use disorder (OUD) is associated with overdose, premature death and infectious disease, including human immunodeficiency virus (HIV) and Hepatitis C (HCV). While prior studies have shown that educational interventions are associated with improvements in HIV and HCV knowledge and reductions in risk behaviors, those examined to date have typically been time- and resource-intensive. We recently developed an HIV+HCV Education intervention which aims to improve HIV and HCV knowledge in a single visit using an automated iPad platform. In this project, we examined its ability, using a within-subject evaluation, to improve knowledge of HIV and HCV transmission and risks among adults with OUD. Methods: Participants were 25 adults with OUD who were enrolled in a 12-week randomized trial evaluating the efficacy of an Interim Buprenorphine Treatment (IBT) for reducing illicit opioid use while awaiting entry into community-based opioid treatment. Participants completed a baseline HIV+HCV knowledge assessment (Pre-Test) followed by corrective feedback, both administered via iPad. They then completed an interactive HIV flipbook and animated HCV video, also on iPad, followed by a second administration of the knowledge assessment (Post-Test). Finally, to evaluate whether any changes in knowledge persisted over time, the HIV+HCV assessment was administered again at 4 and 12 weeks following study intake. Results: At baseline (Pre-Test), participants answered 69% and 65% of items correctly on the HIV and HCV assessments, respectively. After completing the educational intervention, participants answered 86% of items correctly on both the HIV and HCV assessments (p’s<.001). These improvements in knowledge also persisted throughout the three-month study, with scores at Week 4 and 12 timepoints significantly greater than baseline (p’s<.001). Conclusion: An HIV+Hepatitis Education intervention delivered via a portable, automated iPad platform may produce significant and persistent improvements in HIV and HCV knowledge among adults with OUD. These data provide additional support for the use of mobile educational interventions for enhancing HIV and HCV knowledge in individuals at elevated risk for infectious disease. Support: This trial was supported by NIDA R34 DA3730385 (Sigmon) with additional support by NIDA T32 DA007242 (Higgins).

The COVID-19 pandemic adversely affected the lives of most Americans. People with Substance Use Disorder (SUD) were particularly vulnerable to the negative effects brought on by the pandemic. This study explored the increase in deaths due to opioid overdose during the pandemic exacerbated by factors such as increased stress, decrease in treatment options due to social distancing requirements and facility closures, social isolation, and an increase in spare time. Access to treatment for opioid use disorder (OUD) was interrupted by the measures meant to mitigate the spread of COVID-19. Through a systematic review of current literature, it was demonstrated that existing patients were able to maintain access to care, while few new patients were able to initiate treatment. Telehealth proved to be a vital means of assuring PWUD were able to access life-saving treatment amid a pandemic. Further research is needed to determine whether SUD treatment measures during the COVID-19 pandemic warrants changing the policies long term.