Extramedicínské (zne)užívání buprenorfinu v Gruzii a efektivní léčebná intervence MUDr. David Otiashvili Abstrakt Background Since early 2000s, the nonmedical abuse of buprenorphine (Subutex®) tablets, presumably smuggled from EU countries, has represented major phenomena of the problem drug scene in the Republic of Georgia. In a country with relatively high level of injecting drug use (estimated 40,000 persons, i.e. 1.5 % of population aged 15-64, of whom over 50% inject buprenorphine), this represent a major public health problem that needs detailed description and comprehensive set of interventions. Aim (i) To describe the extent of nonmedical buprenorphine ab/use in the Republic of Georgia, the characteristics of the nonmedical ab/users and their motivations for seeking and using the black market buprenorphine. Subsequently, (ii) to plan and pilot-test a treatment intervention that would be more specific and effective than the simple detoxification and/or harm reduction modalities available in Georgian on a routine basis. Setting Four regional centres of Georgia were included into the descriptive part of the study: the cities of Tbilisi, Gori, Zugdidi, and Batumi. The intervention (sub)study was conducted in one Tbilisi addiction treatment clinic. Participants and methods For the descriptive part of the...

Extramedicínské (zne)užívání buprenorfinu v Gruzii a efektivní léčebná intervence MUDr. David Otiashvili Abstrakt Background Since early 2000s, the nonmedical abuse of buprenorphine (Subutex®) tablets, presumably smuggled from EU countries, has represented major phenomena of the problem drug scene in the Republic of Georgia. In a country with relatively high level of injecting drug use (estimated 40,000 persons, i.e. 1.5 % of population aged 15-64, of whom over 50% inject buprenorphine), this represent a major public health problem that needs detailed description and comprehensive set of interventions. Aim (i) To describe the extent of nonmedical buprenorphine ab/use in the Republic of Georgia, the characteristics of the nonmedical ab/users and their motivations for seeking and using the black market buprenorphine. Subsequently, (ii) to plan and pilot-test a treatment intervention that would be more specific and effective than the simple detoxification and/or harm reduction modalities available in Georgian on a routine basis. Setting Four regional centres of Georgia were included into the descriptive part of the study: the cities of Tbilisi, Gori, Zugdidi, and Batumi. The intervention (sub)study was conducted in one Tbilisi addiction treatment clinic. Participants and methods For the descriptive part of the...

As the opioid epidemic continues in Philadelphia, buprenorphine clinics are becoming a necessary mainstay in treatment of these patients. HIV and HCV rates are rising throughout the city due to injection drug use, and buprenorphine clinics could be a bridge to therapy for these conditions as well. This thesis explores the current data about HIV and HCV rates, their connection to injection drug use, and how these overlapping epidemics might be addressed in a comprehensive manner. Historical data, current trends, and first person reflections from clinicians in the TRUST buprenorphine clinic are used to inform our understanding of barriers to integrated screening and treatment. The thesis concludes with a discussion of a better integrated model of care.

Opioid misuse and addiction constitute a significant public health challenge in the 21st century, with opioids involved in the majority of drug overdose deaths since 1999. A vigorously researched area that contributes substantially to the opioid misuse and addiction challenge is pain. The impact of pain, however, on important health outcomes for individuals in recovery from opioid use is less well understood. The effects of pain on substance use and mental health outcomes was investigated among individuals in recovery from opioid use disorder. Two studies are reported. First, the relationships between pain status and severity on substance use, treatment utilization, and mental health outcomes (e.g., depressive symptoms) was characterized cross-sectionally. Second, subgroups of OUD recovery defined by depression, opioid withdrawal, and pain were identified. Relationships between recovery subgroups, OUD symptoms, remission, opioid use, and quality of life were assessed. Finally, transitions among subgroups across 4 years of recovery were characterized. The present findings support pain as a key dimension of opioid use disorder recovery, highlighting the distinction between acute and chronic pain, the dynamic nature of opioid use disorder recovery, and emphasizing the necessity of integrating pain into opioid use disorder treatment. / Doctor of Philosophy / Misuse of and addiction to opioids is a significant health challenge. Pain has played a central role in facilitating the opioid epidemic in the United States, but the impact of pain on substance use and mental health outcomes for individuals in recovery from opioid use is less well understood. The following two studies investigated how pain affects substance use and mental health outcomes among individuals in recovery from opioid use disorder. Study 1 examined how different types of pain (chronic pain, acute pain, no pain) affect substance use, treatment use, and mental health measures (e.g., depression, quality of life). Study 2 investigated the role that depression, opioid withdrawal, and pain have in defining different groups in opioid recovery. Together these studies support pain as an important factor in OUD recovery, highlight the distinction between acute and chronic pain, emphasize the importance of integrating treatment for opioid use disorder and pain, and demonstrate that opioid use disorder recovery is a dynamic process with individuals transitioning among different recovery groups over time.

Many pregnant women in the Appalachian Highlands region utilize buprenorphine as medication-assisted treatment (MAT) for opioid use disorder. This treatment is a tool used by medical teams to minimize patients’ drug cravings and optimize chances for a healthy pregnancy. Providers in our region have posited a relationship between MAT use and poor pregnancy weight gain based on clinical experience and observation. Appropriate weight gain in pregnancy is a critical determinant of pregnancy health; without it, pregnant mothers will possibly need nutritional supplementation. Therefore, understanding the association between buprenorphine use and weight gain may contribute to healthier pregnancies. In order to evaluate the association between buprenorphine use and weight gain in pregnant women using MAT, we conducted a retrospective chart review. A list of potential participants was generated by ETSU Population Health using ICD-10 codes. We enrolled patients who were cared for by ETSU Health and delivered babies between July 1, 2019 and June 30, 2021: a total of 504 patients. Of these, 96 were participants in the ETSU low-dose MAT clinic (Group 1), 109 were receiving MAT from other community clinics (Group 2), 97 were non-smoking women in the regular OB clinic (Group 3), and 202 were smoking women in the regular OB clinic (Group 4). Participants’ medical records were screened for inclusion and exclusion criteria. All patients were over age 18 with singleton pregnancies, had pregnancy care initiated in the first trimester, and delivered at or after 37 weeks’ gestation. Patients with confounding medical conditions including (but not limited to) Crohn’s disease, diabetes, heart disease, hypertension, fetal anomalies, or IUFD were excluded. In addition, patients were also excluded with BMI >30 or undocumented BMI, prenatal care initiated after the first trimester, transfer to another practice or lost to follow up, or other documented drug abuse other than opiate use disorder. After consideration of the above criteria, 262 patients were excluded and 242 patients remained in the study. Of these, 53 were in Group 1, 53 in Group 2, 45 in Group 3, and 90 in Group 4. All protected health information was stored in the ETSU HIPAA-compliant REDCap server. At this time, the project is in the data analysis stage, with results expected by the end of March 2023. If an association between buprenorphine use and lower weight gain in pregnancy is discovered, these results can be used to recommend additional measures such as nutritional supplementation to optimize maternal and fetal health during pregnancy. Final conclusions will be drawn after data analysis is complete and associations, or lack thereof, can be fully evaluated. Based on observations of obstetric providers in the region, some association between lower weight gain and buprenorphine use is anticipated.

Opioid abuse and opioid related deaths continue to affect families and communities across the United States. Medication-assisted treatment shows advantages over other types of interventions for opioid use disorder (OUD) (Bart, 2012). While buprenorphine, an approved medication for the treatment of OUD, has a wide research base to support its efficacy, there is little research or guidance on behavioral interventions to use in conjunction with the medication. Investigating clients' experiences in treatment can provide helpful and necessary information for improving treatment efforts. The following qualitative study used a phenomenological approach to explore the client experience of group therapy with buprenorphine for OUD. Results showed the importance of supportive, genuine relationships in recovery, as well as the need for accountability and a safe space for self-disclosure. This research highlights the importance of the therapeutic alliance, the 11 therapeutic factors of groups, and the necessity of building authentic relationships in treatment. / Doctor of Philosophy / As opioid overdoses continue to rise in the United States, it is essential that we improve addiction treatment. Medication-assisted treatment (MAT) combines the use of medications and counseling to treat the whole person. This type of approach shows advantages over counseling only interventions for opioid use disorder (OUD) (Bart, 2012). While MAT shows promise over counseling only approaches, there is little research or guidance on how to implement counseling with the medication. Investigating clients’ experiences in treatment can provide helpful and necessary information for improving counseling in MAT. The following qualitative study used in-depth interviews with participants who are currently in a MAT program to better understand their experiences in treatment. Results showed the importance of supportive, genuine relationships in recovery, as well as the need for accountability and a safe space for sharing. This research helps further knowledge of treatment for OUD to better serve those affected by addiction, as well as adding to the gaps in group therapy and addiction’s literature.

Through changes in the code of statutes, SOSFS 2009:27 (M), opioid addicts are excluded since March 1 2010 from possibilities to be accepted for substitution treatment. Opiate addicts are solitary admitted for substitution treatment from that date. Opioid addicts are excluded admission for treatment regardless of the fact that they fulfil the ICD-10 diagnosis F.11.2, i.e. opioid/opiate addictive criteria. The alteration in the statutes was carried out in reference to the fact that evidence for this kind of treatment intended for opioid addicts was missing. Both groups i.e. opiate – and opioid addicts, are nevertheless experienced in clinical work , to have extensive problems with addiction, health, social situation along with the risk of premature death.     The purpose with this study is to identify what differences and/or similarities there are in background varieties and the severity of the problems  between the groups. This is conducted with the use of a population (n=127) with comparable background material, e.g. collected Addictions Severe Index- interviews, scientifically survey and compare background factors and the severity of the problems.      The main discovery in this study is that one can demonstrate great similarities between the groups regarding background as well as the severity of the problems. It is therefore of great interest, on a individual as well as a social oriented level, that pursued studies regarding diagnostic safety and on processes in substitution program are needed to generate further knowledge as a foundation for development of future care and changes in the code of statutes.

This dissertation aimed at developing an inhibitor strategy to improve the oral bioavailability (Foral) and systemic exposure (AUC∞) of buprenorphine (BUP) as well as reduce the variability associated with them. Twenty-seven generally recognized as safe (GRAS) compounds or dietary substances were evaluated for their potential to inhibit the oxidative and conjugative metabolism of BUP, using pooled human intestinal and liver microsomes. In both the organs, oxidation appeared to be the major metabolic pathway with a 6 fold (intestine) and 4 fold (liver) higher intrinsic clearance than glucuronidation. Buprenorphine was predicted to show low and variable Foral, AUC∞, and a large total clearance. The biorelevant solubilities of 5 preferred inhibitors were incorporated in the final model. An inhibitor dosing strategy was identified to increase Foral and reduce the variability in oral BUP AUC∞. These results demonstrate the feasibility of the approach of using GRAS or dietary compounds to inhibit the presystemic metabolism of buprenorphine and thus improve its oral bioavailability. This inhibitor strategy has promising applicability to a variety of drugs suffering from low and variable oral bioavailability due to extensive presystemic oxidative and conjugative metabolism.

Background & Purpose: Opioid maintenance therapy (OMT) is an effective method of treating opioid addiction. Of incarcerated individuals in the U.S., 50-85% have a history of substance abuse, and >80% of inmates with opioid addiction history do not receive treatment. The purpose of this study was to explore individuals' experiences after being tapered from OMT upon incarceration. Methods: Interpretative phenomenological analysis (IPA) was employed using in-depth interviewing of 10 participants. Results: Analysis identified six themes that captured the essence of the participants' experiences. Implications & Conclusion: Losing OMT upon incarceration was described as an extremely stressful experience for many individuals, and may create issues for both inmates and facility staff. Further research is needed to discover ways in which to improve addiction treatment in prison.

Background: The misuse and addiction to opioids are one of the major health and social problem that is associated with an increase in morbidity and mortality. Both Buprenorphine (BUP) and Methadone (MET) are FDA-approved treatments for opioid dependence. This longitudinal study is to determine the effects of BUP and MET on hypertension in patients with opioid dependence using a Generalized Estimating Equation(GEE) Model. Methods: The data is from National Drug Abuse Treatment Clinical TrialsNetwork (CTN) protocol CTN-0027. This is a randomized study of 1,934 opioid dependence participants seeking treatment that followed for up to 32 weeks. A total of1,284 males and 631 females participated at the Baseline (visit1) of the study. At the endof 32 weeks (10 visits), 499 males and 243 female patients completed the study. Blood pressure of all the patients was checked at every visit beginning visit 1 to visit 10. For this analysis, the dependent variable was hypertension which was defined as having asystolic blood pressure higher than 140 mmHg and/or a diastolic blood pressure higher than 90 mmHg. These participants were randomly assigned to receive BUP (n= 740) or MET (n= 529). The GEE model with exchangeable correlation was used to determine the efficacy of both the drugs on hypertension. The analysis was performed using PROCGENMOD in SAS 9.4. Results: Time increased the odds of hypertension (adjusted odds ratio (aOR): 1.04, 95% confidence interval (CI): 1.02-1.06, pConclusion: Findings suggest that BUP had a slightly less chance of causing hypertension among patients with opioid dependence comparing with MET controlling for other risk factors, but neither one of Page 54 2017 Appalachian Student Research Forum them had any significant effect on hypertension among patients with opioid dependence. Further analysis will be essential to detect gender x treatment interaction.