Design and implementation of a Type-2 hybrid, prospective randomized trial of opioid agonist therapies integration into primary care clinics in Ukraine.

INTRODUCTION: Ukraine has high HIV prevalence, concentrated among people who inject drugs (PWID), mostly of opioids. Maintenance on opioid agonist therapies (OAT) is the most effective evidence-based treatment for opioid use disorder. As PWID experience high morbidity and mortality from preventable and treatable non-communicable diseases, international agencies recommend integrating OAT into primary care centers (PCC). METHODS: A randomized, type-2 hybrid implementation trial was carried out to compare outcomes of OAT integration in PCC to OAT delivery at specialty treatment centers (STC) - standard-of-care. Tele-education supporting PCC providers in managing OAT, HIV, tuberculosis and non-communicable diseases along with pay-for-performance incentives were used to facilitate implementation. Consenting patients underwent 1:2 randomization to either STC or PCC. Quality health indicators (QHIs), a composite percentage of recommended primary and specialty services accessed by patients (blood/urine tests, cancer screenings, etc.), were defined as efficacy outcomes and were assessed by participant self-report at baseline and every 6 months over 24 months and electronic chart reviews after the completion of the follow-up. The primary outcome is defined as the difference in composite QHI scores at 24 months, in which a repeated measures likelihood-based mixed model with missing at random assumptions will be used. Providers at PCC completed surveys at baseline, 12 and 24 months to assess implementation outcomes including changes in stigma and attitudes towards OAT and PWID. PRELIMINARY RESULTS: Among the 1459 participants allocated to STC (N = 509) or PCC (N = 950), there were no differences in clinical and demographic characteristics. Self-reported prevalences were available for HIV (42 %), HCV (57 %), and prior tuberculosis (17 %). Study retention at 6, 12, 18, and 24 months was as 91 %, 85 %, 80 %, and 74 %, respectively. CONCLUSION: PWID have a high prevalence of medical comorbidities and integrating OAT into primary care settings has the potential to improve the health of PWID. Findings from this study can help guide implementation of integrated care in Ukraine and throughout similar low-resource, high-burden countries in the Eastern European and Central Asian region.

The cascade of care for commercially-insured persons with opioid use disorder and comorbid HIV and HCV infections.

BACKGROUND: Opioid use disorder (OUD) significantly impacts individual and public health and exacerbated further by concurrent infectious diseases. A syndemic approach is needed to address the intertwined OUD, HIV, and HCV epidemics, including the expanded use of medications for opioid use disorder (MOUD). METHODS: To identify MOUD scale-up opportunities, we conducted a retrospective cohort study, representing commercially insured persons, and created the OUD care continuum, including HIV and HCV influences in adults (18-64 years) newly diagnosed with OUD in 2019 using Merative MarketSan data. RESULTS: Among 124,467,633 individuals, the prevalence of OUD was 0.4 % (95 % CI: 0.36 %-0.46 %; N = 497,871), with 327,277 (65.7 %, 95 % CI: 65.60 %-65.87 %) newly diagnosed in 2019. Among these newly diagnosed individuals (54 % men, mean age 44±0.01), 53,568 (27.0 %, 95 % CI: 26.4 %-27.5 %) were prescribed MOUD, with retention rates at 1, 3, and 6 months being 89.0 % (95 % CI: 88.2 %-89.8 %), 66.0 % (95 % CI: 64.8 %-67.2 %), and 50.3 % (95 % CI: 48.3 %-51.6 %), respectively. Buprenorphine was the most prescribed MOUD (79.6 %, 95 % CI: 78.6 %-80.7 %), followed by XR-NTX (14.9 %, 95 % CI:14.0 %-15.8 %) and methadone (5.5 %, 95 % CI: 4.9 %-6.1 %). Six-month retention was highest for methadone (73.4 %, 95 % CI: 73.0 %-73.8 %), however, followed by buprenorphine (55.7 %, 95 % CI: 55.3 %-57.1 %) and substantially lower for XR-NTX (12.6 %, 95 % CI: 10.6 %-14.6 %). Screening for HIV and HCV was low among OUD enrollees (11.1 %, 14.4 %), slightly higher for MOUD initiators (18.0 %, 21.6 %). Being prescribed MOUD was correlated with HCV infection (AOR: 2.54; 95 % CI: 2.41-2.68), HCV/HIV coinfection (AOR: 1.89; 95 % CI: 1.41-2.53), and hospitalization for OUD-related services (AOR: 1.14; 95 % CI: 1.11-1.17), yet hospitalization for OUD-related services was positively correlated with XR-NTX (AOR: 2.72; 95 % CI: 2.56-2.85) prescription and negatively with methadone (AOR: 0.19; 95 % CI: 0.16-0.23) prescription. Having HIV was negatively correlated with being prescribed methadone (AOR: 0.33; 95 % CI: 0.13-0.86). CONCLUSIONS: Substantial gaps in the OUD cascade persist, underscoring better implementation opportunities for MOUD prescription in hospital-based settings and expanding access to methadone beyond highly regulated sites given its low coverage yet high treatment retention.

The impact of emergency guidance to the COVID-19 pandemic on treatment entry, retention and mortality among patients on methadone in Ukraine.

BACKGROUND AND AIMS: Ukraine's Ministry of Health released urgent COVID-19 guidelines, allowing for early implementation of take-home dosing (THD) for opioid agonist therapies (OAT) such as methadone. Enrollment in OAT and retention in the program are the most effective HIV prevention strategies for people who inject drugs (PWID). This study aimed to evaluate the impact of Ukraine's COVID-19 emergency guidance on OAT treatment enrollment, retention on treatment and mortality. DESIGN AND SETTING: Using Ukraine's national OAT registry for 252 governmental clinics across 25 regions, we conducted a 12-month comparative prospective cohort survival analysis. This study compared newly enrolled methadone patients within the initial 6 months following the COVID-19 guidance (COVID) with patients from the preceding year (pre-COVID) in a country with high adult HIV prevalence (1.2%) that is concentrated in PWID. PARTICIPANTS: In the nation-wide sample of newly enrolled PWID in Ukraine, comprising 2798 individuals, 1423 were in the COVID cohort and 1375 were in the pre-COVID cohort. The majority were male (86.7%), with an average age of 39.3 years. MEASUREMENTS: Primary outcomes were average monthly enrollment per cohort, treatment retention and mortality, with internal time-dependent predictors, including THD and optimal (> 85 mg) methadone dosing. RESULTS: Relative to the pre-COVID period, the monthly average patient enrollment was statistically significantly higher during the COVID period (283.7 versus 236.0; P < 0.0001), where patients were more likely to transition to THD and achieve optimal dosing earlier. Significant differences were observed in the proportions of person-months on THD (41 versus 13%, P < 0.0001) and optimal dosing (38 versus 31%, P < 0.0001) between the COVID and pre-COVID cohorts. Predictors of treatment retention, expressed as adjusted hazard ratios (aHR), included early THD [aHR = 1.90, 95% confidence interval (CI) = 1.47-2.45], early optimal dosing (aHR = 1.71, 95% CI = 1.37-2.13) and prior methadone treatment (aHR = 1.39, 95% CI = 1.15-1.68). These factors persisted, respectively, in the pre-COVID (aHR = 2.28, 95% CI = 1.41-3.70; aHR = 1.84, 95% CI = 1.32-2.56; and aHR = 1.36, 95% CI = 1.06-1.74) and COVID (aHR = 1.91, 95% CI = 1.40-2.59; aHR = 1.61, 95% CI = 1.20-2.16; and aHR = 1.49, 95% CI = 1.08-1.94) cohorts. Survival did not differ significantly between the two prospective cohorts. CONCLUSION: Ukraine's prompt adoption of early take-home dosing for opioid agonist therapies, such as methadone, following the emergency COVID-19 guidance appears to have increased enrollment into methadone and improved treatment retention for people who inject drugs without adverse effects on patient survival.

Early disruptions to syringe services programs during the Russian invasion of Ukraine.

Introduction: The widespread HIV epidemic in Ukraine is concentrated among people who inject drugs (PWID), making access to sterile injection paraphernalia (SIP) like sterile needles and syringes a critical method of HIV/AIDS prevention; however, the Russian invasion has threatened to disrupt the operations of syringe services programs (SSPs), creating a risk of HIV outbreaks among PWID. Methods: We conducted 10 semi-structured interviews with outreach workers from SSPs. Interviews were purposively sampled to cover three prototypic regions of Ukraine: temporarily Russian-controlled, frontline, and destination. Qualitative results from interviews were then compared against a standardized, nationwide harm reduction database. Results: We found that the Russian invasion triggered both supply and demand challenges for SSPs. Demand increased for all regions due to client transitions from pharmacies that closed to SSPs, increases in illicit drug use, greater client openness to NGO support, and displacement of clients to destination regions. Supply decreased for all areas (except for remote destination regions) due to battle-related barriers like curfews, roadblocks, and Internet disruptions; diminished deliveries of SIP and funding; and staff displacement. Time series plots of the number of unique clients accessing harm reduction services showed that an initial decrease in service provision occurred at the start of the war but that most regions recovered within several months except for Russian-controlled regions, which continued to provide services to fewer clients relative to previous years. Conclusion: To ensure continued scale-up of SIP and other HIV prevention services, the SyrEx database should be leveraged to serve as a streamlined harm reduction locator that can inform workers and clients of open site locations and other pertinent information.

High perceived stress in patients on opioid agonist therapies during rapid transitional response to the COVID-19 pandemic in Ukraine.

Background: The COVID-19 pandemic resulted in marked disruptions in healthcare delivery in Ukraine related to emergency guidance in response to treating opioid use disorder (OUD). Patients with OUD, a group with high levels of comorbid medical and psychiatric disorders, and prescribed opioid agonist therapies (OAT) were rapidly shifted to take-home dosing if they were deemed clinically stable. The impact of these shifts on patient stress and related substance use during the pandemic, however, is unknown. Methods: In early May 2020, 269 randomly selected OAT patients in Ukraine were surveyed to assess their stress level and substance use using the validated Perceived Stress Scale and examined correlates of severe perceived stress. Results: Overall, 195 (72.5%) met criteria for moderate to severe levels of stress, which was independently correlated with having started OAT within the past 12 months (aOR: 1.33; 95%CI: 1.15-1.55), living in a large metropolitan area (aOR: 1.31; 95%CI: 1.18-1.46), having been asked by others to share their medication (aOR: 1.13; 95%CI: 1.02-1.25), and having an increase of over 10 min in transportation time to get to treatment (aOR: 1.16; 95%CI: 1.04-1.29). Twenty seven (10%) patients felt at high risk of relapse, while 24 (8.9%) patients reported purchasing drugs. Conclusion: During a time of great uncertainty soon after emergency guidance to the COVID-19 pandemic, there was extraordinary high levels of perceived stress reported. In response to emergency guidance, OAT patients should be screened for perceived stress and certain subgroups should be targeted for additional psychosocial support.

Design, implementation and preliminary results of a type-2 hybrid cluster-randomized trial of integrating screening and treatment for major depressive disorder into specialty clinics providing opioid agonist therapies in Ukraine.

INTRODUCTION: Ukraine has a high prevalence of co-occurring disorders (COD), defined as having both substance use (SUD) and psychiatric disorders. Major depressive disorder (MDD) is the most prevalent psychiatric disorder among people with SUD. People with COD experience poor health outcomes, and international agencies propose integrated COD care. In Ukraine, treatment for SUD is delivered in specialized substance use clinics, without providing any other medical services for comorbidities, including MDD. Here we present the protocol, along the with the preliminary results of the MEDIUM project, including observations over the first 6 months. METHODS: A cluster-randomized type-2 hybrid trial was conducted to integrate MDD treatment into specialty clinics providing opioid agonist therapies (OAT) in Ukraine. Twelve clinics in four regions underwent randomization to control (N = 1) vs experimental arms (N = 2) in each region. Clinicians at experimental sites received tele-education through modified project ECHO using a facilitated screening, evaluation, and treatment algorithm of depression, with or without financial incentives. Service-, patient- and provider-level data were collected for the analysis every 6 months for 24 months. PRELIMINARY RESULTS: For service delivery outcomes, 4421 patients enrolled on OAT across all sites were assessed for MDD for screening (76.7%), evaluation with diagnosis (43.5%) and treatment (30.7%) for MDD; 13.8% continued treatment at least for 6 months. For patient-level outcomes, 1345 patients and 54 providers participated in serial surveys every six months. CONCLUSION: This study will be the first to explore integrated COD care in Ukraine and generate evidence on effective service integration and delivery strategies for people with COD receiving treatment at substance use clinics with broader implications for Eastern Europe and Central Asia region.

Corrigendum: High perceived stress in patients on opioid agonist therapies during rapid transitional response to the COVID-19 pandemic in Ukraine.

[This corrects the article DOI: 10.3389/fpubh.2023.1231581.].

Implementation opportunities for scaling up methadone maintenance treatment in Kyrgyzstan: Methadone dosage and retention on treatment over two years.

Background: Methadone maintenance treatment (MMT) is the most effective and cost-effective strategy to control HIV in Central Asian countries, where the epidemic is concentrated among people who inject drugs (PWID) who use opioids. Methods: Using data from a prospective observational database of all people initiated on MMT in Kyrgyzstan since 2008, we analyzed a more contemporary subset of data for all persons receiving MMT from January 2017 through June 2021 after the national treatment guidelines were changed. Retention on MMT was assessed at 1, 6, 12, and 24 months and predictive variables included were dosage levels, HIV status, and type of clinical setting using survival analysis. Predictors of treatment dropout were estimated using Cox multivariate regression models. Results: Among the 940 MMT patients, the proportion receiving low (<40mg), medium (40-85mg), and high (>85mg) dosage levels was 37.9%, 42.2%, and 19.9%, respectively. Increasing MMT dosage level was significantly (p<0.0001) correlated with retention at 1 (90%, 98%, 100%), 6 (42%, 63%, 95%), 12 (33%, 55%, 89%), and 24 (16%, 45%, 80%) months, respectively, with no differences between community and correctional settings. Significant predictors of dropout at 12 months included low (aHR=8.0; 95%CL=5.8-11.0) and medium (aHR=3.5; 95%CL=2.5-4.9) methadone dosage level relative to high dose, receiving MMT in three administrative regions relative to the capital Bishkek, and lower in the tuberculosis-specialized clinic in Bishkek. Clients with HIV receive higher average MMT doses (79.5mg vs 63.1mg; p<0.0001), but MMT retention did not differ after controlling for dosage in this group. Conclusions: The proportion of patients receiving optimal dosage was low (19.9%). An implementation strategy that focused on getting a larger proportion of MMT on the optimal dosage to promote retention could potentially improve the quality of existing treatment and promote further scale-up of MMT in Kyrgyzstan.

Responding to health policy recommendations on managing opioid use disorder during Russia's invasion of Ukraine: Divergent responses from the frontline to the west.

Russia's invasion of Ukraine on February 24, 2022, followed by Ukraine's Martial law, has disrupted the routine delivery of healthcare services, including opioid agonist treatment (OAT) programs. Directors (chief addiction treatment physicians) of these programs in each region had flexibility with implementing a series of adaptations to their practice to respond to war disruptions like mass internal displacement and legislation updates allowing more flexibility with OAT distribution policies and take-home dosing regulations. We conducted 8 in-depth interviews with directors from seven regions of Ukraine to describe their experiences providing OAT during a specific time during the war and the local crisis-response approach under the emergency policy updates. We categorized their experiences according to the level of exposure to conflict in each region and displacement of patients across the country, which may provide future guidance for OAT provision during the conflict.