Associations of hepatitis C virus (HCV) antibody positivity with opioid, stimulant, and polysubstance injection among people who inject drugs (PWID) in rural U.S. communities.

BACKGROUND: People who inject drugs (PWID) in the rural U.S. often inject stimulants, alone or with opioids. The impact of these substance use patterns may influence HCV risk behaviors. This analysis examines the associations of HCV antibody positivity with injecting only opioids, only stimulants (methamphetamine/cocaine), and opioids and stimulants together among rural PWID. METHODS: The Rural Opioid Initiative (ROI) consists of eight research sites that enrolled people who use drugs in rural communities in ten U.S. states from 2018 to 2020. This cross-sectional analysis included adult participants who resided in a study area and injected any drug in the past 30 days. The primary outcome was HCV antibody positivity. The exposure of interest was injection drug use classified as only opioids, only stimulants, separate injections of opioids and stimulants, and same-syringe injection of both in the past 30 days. We used multivariable log-binomial regression with generalized linear mixed models to generate prevalence ratios (P.R.) adjusted for demographics, injection history, health insurance, and substance use treatment. RESULTS: Among 3,084 participants enrolled in the ROI, 1,982 met inclusion criteria. Most participants injected opioids and stimulants in the same syringe (34%) or separately (21%), followed by injecting only stimulants (26%), and injecting only opioids (19%). Half (51%) were HCV antibody positive. Compared to people who injected only stimulants, HCV antibody positivity was more prevalent among people who injected opioids alone (aPR=1.62, 95% CI:(1.29-2.03)), injected both opioids and stimulants separately (aPR=1.61, 95% CI:(1.32-1.95)), and in the same syringe (aPR=1.54, 95% CI:(1.28-1.85)). CONCLUSION: HCV antibody positivity, indicating prior exposure, was highest among those who had recently injected opioids, alone or with stimulants. Additional nucleic acid testing is necessary to confirm active infection. More research is needed to determine the underlying causes of HCV antibody positivity by injection use.

A randomized controlled trial for a peer-facilitated telemedicine hepatitis c treatment intervention for people who use drugs in rural communities: study protocol for the "peer tele-HCV" study.

BACKGROUND: Hepatitis C virus (HCV) transmission is primarily driven by injection drug use, and acute HCV infection rates are increased in rural communities with substantial barriers to care. Treatment of HCV in persons who use drugs (PWUD) is cost effective, decreases high risk behaviors and HCV transmission, and achieves high rates of treatment completion and sustained viral response. Adapting HCV care delivery to utilize peer support specialists, telemedicine technology, and streamlined testing and treatment strategies can better reach rural populations living with HCV. METHODS: This is an open label, two-arm, non-blinded, randomized controlled trial designed to test the superiority of peer-facilitated and streamlined telemedicine HCV care (peer tele-HCV) compared to enhanced usual care (EUC) among PWUD in rural Oregon. In the intervention arm, peers conduct HCV screening in the community, facilitate pretreatment evaluation and linkage to telemedicine hepatitis C treatment providers, and support participants in HCV medication adherence. For participants assigned to EUC, peers facilitate pretreatment evaluation and referral to community-based treatment providers. The primary outcome is sustained virologic response at 12 weeks post treatment (SVR12). Secondary outcomes include: (1) HCV treatment initiation, (2) HCV treatment completion, (3) engagement with harm reduction resources, (4) rates of substance use, and (5) engagement in addiction treatment resources. The primary and secondary outcomes are analyzed using intention-to-treat (ITT) comparisons between telemedicine and EUC. A qualitative analysis will assess patient, peer, and clinician experiences of peer-facilitated telemedicine hepatitis C treatment. DISCUSSION: This study uses a novel peer-based telemedicine delivery model with streamlined testing protocols to improve access to HCV treatment in rural communities with high rates of injection drug use and ongoing disease transmission. We hypothesize that the peer tele-HCV model will increase treatment initiation, treatment completion, SVR12 rates, and engagement with harm reduction services compared to EUC. Trial registration This trial has been registered with ClinicalTrials.gov (clinicaltrials.gov NCT04798521).

Knowledge, attitudes, and behaviors related to the fentanyl-adulterated drug supply among people who use drugs in Oregon.

INTRODUCTION: Nonpharmaceutical fentanyl has reconfigured the U.S. illicit drug market, contributing to a drastic increase in overdose drug deaths. While illicit fentanyl has subsumed the drug supply in the Northeast and Midwest, it has more recently reached the West. For this study, we explored knowledge, attitudes, and behaviors among people who use drugs in Oregon in the context of the emergence of fentanyl in the drug supply. METHODS: We conducted in-depth interviews by phone with 34 people who use drugs in Oregon from May to June 2021. We used thematic analysis to analyze transcripts and construct themes. RESULTS: People who use drugs knew about fentanyl, expressed doubt that fentanyl could be found in methamphetamine; believed those who were younger or less experienced were at higher risk for harm; and received information about fentanyl from drug dealers, syringe service programs, or peers (other people who use drugs). Preference for fentanyl's presence in drugs like heroin or methamphetamine was mixed. Some felt that their preference was irrelevant since fentanyl was unavoidable. Participants reported engaging in harm reduction practices, including communicating about fentanyl with dealers and peers, testing for fentanyl, using smaller quantities of drugs, switching from injecting to smoking, and using naloxone. CONCLUSION: People who use drugs are responding to the rise of fentanyl on the West Coast and are concerned about the increasing uncertainty and hazards of the drug supply. They are willing and motivated to adopt harm reduction behaviors. Harm reduction promotion from syringe service programs and public health agencies is essential to reduce injury and death from nonpharmaceutical fentanyl.

"It wasn't here, and now it is. It's everywhere": fentanyl's rising presence in Oregon's drug supply.

BACKGROUND: Illicit fentanyl has contributed to a drastic increase in overdose drug deaths. While fentanyl has subsumed the drug supply in the Northeastern and Midwestern USA, it has more recently reached the Western USA. For this study, we explored perspectives of people who use drugs (PWUD) on the changing drug supply in Oregon, experiences of and response to fentanyl-involved overdose, and recommendations from PWUD to reduce overdose risk within the context of illicit fentanyl's dramatic increase in the recreational drug supply over the past decade. METHODS: We conducted in-depth interviews by phone with 34 PWUD in Oregon from May to June of 2021. We used thematic analysis to analyze transcripts and construct themes. RESULTS: PWUD knew about fentanyl, expressed concern about fentanyl pills, and were aware of other illicit drugs containing fentanyl. Participants were aware of the increased risk of an overdose but remained reluctant to engage with professional first responders due to fear of arrest. Participants had recommendations for reducing fentanyl overdose risk, including increasing access to information, harm reduction supplies (e.g., naloxone, fentanyl test strips), and medications for opioid use disorder; establishing drug checking services and overdose prevention sites; legalizing and regulating the drug supply; and reducing stigma enacted by healthcare providers. CONCLUSION: PWUD in Oregon are aware of the rise of fentanyl and fentanyl pills and desire access to tools to reduce harm from fentanyl. As states in the Western USA face an inflection point of fentanyl in the drug supply, public health staff, behavioral health providers, and first responders can take action identified by the needs of PWUD.

Exploring how hospitalization can alter hepatitis c virus treatment prioritization and trajectories in people who use drugs: A qualitative analysis.

Background: People who use drugs (PWUD) have high rates of hepatitis C virus (HCV) infection. Hospitalization can be a time for PWUD to engage in addiction treatment, but little is known about how hospitalization shapes HCV treatment readiness. We aimed to describe how hospitalization and addiction medicine consult service (AMCS) can alter HCV prioritization of inpatient PWUD with HCV. Methods: We conducted a qualitative study consisting of semi-structured interviews (n = 27) of hospitalized adults with addiction and HCV infection seen by an AMCS at a single, urban, academic center. Interviews were audio-recorded, transcribed, and coded iteratively at the semantic level, and analyzed for themes. Results: Of the 27 participants, most identified as Caucasian (85%), male gender (67%), and they primarily used opioids (78%); approximately half (48%) reported HCV diagnosis over 5 years ago. We identified three main themes around hospitalization altering the prioritizations and HCV treatment preferences for PWUD: (1) HCV treatment non-engaged (2) HCV treatment urgency, and (3) HCV treatment in the future. Those wanting to treat HCV-whether urgently or in the future-shared the overlapping theme of hospitalization as a reachable moment for their addiction and HCV. These participants recognized the long-term benefits of addressing HCV and connected their hospitalization to substance use. Conclusion: In our study, PWUD with HCV expressed varying and competing priorities and life circumstances contributing to three main HCV treatment trajectories. Our results suggest ways hospitalization can serve as an HCV touchpoint for PWUD, especially in the context of addressing substance use, and could be used when designing and implementing targeted interventions to improve the HCV care continuum for PWUD.

Utilising an access to care integrated framework to explore the perceptions of hepatitis C treatment of hospital-based interventions among people who use drugs.

BACKGROUND: Gaps remain in the hepatitis C virus (HCV) care cascade for people who use drugs (PWUD). Acute medical or surgical illnesses requiring hospitalisation are an opportunity to address addiction, but how inpatient strategies could affect HCV care accessibility for PWUD remains unknown. We explored patient perspectives of hospital-based interventions using an integrated framework of access to HCV care. METHODS: We conducted a qualitative study of hospitalised adults (n=27) with HCV and addiction admitted to an urban academic medical centre in the United States between June and November 2019. Individual interviews were audio-recorded, transcribed, and dual-coded. We analysed data with coding specific for hospital-based interventions including screening, conducting HCV-related laboratory work-up, starting treatment, connecting with peers, and coordinating outpatient care. We analysed coded data at the semantic level for emergent themes using a framework approach based off an integrated framework of access to HCV care. RESULTS: The majority of participants primarily used opioids (78%), were white (85%) and men (67%). Participants frequently reported HCV screening during previous hospitalisation with rare inpatient connection to HCV-related services. Participants expressed willingness to discuss HCV treatment candidacy during hospitalisation; however, lack of inpatient conversations led to perception that "nothing could be done" during admission. Participants expressed interest in completing inpatient HCV work-up to "get the ball rollin'" - consolidating care would enhance outpatient service permeability by reducing barriers. Others resisted HCV care coordination, preferring to focus on "immediate" issues including health conditions and addiction treatment. Participants also expressed openness to engaging with peers about HCV, noting shared drug use experience as critical to a peer relationship when discussing HCV. CONCLUSION: Hospitalised PWUD have varied priorities, necessitating adaptable interventions for addressing HCV. Hospitalisation can be an opportunity to address HCV access to care including identification of treatment eligibility, consolidation of care, and facilitation of HCV-related referrals.

"Sobriety equals getting rid of hepatitis C": A qualitative study exploring the interplay of substance use disorder and hepatitis C among hospitalized adults.

BACKGROUND: People who use drugs (PWUD) commonly experience complex illness, psychosocial stressors, housing insecurity, and stigma, which may play key roles in their struggles with addiction. In a study of hospitalized PWUD with hepatitis C virus infection (HCV), participants described treating HCV as "part of recovery." These findings led us to explore how hospitalization and acute illness altered patients' perceptions of substance use disorder (SUD) and HCV. METHODS: Researchers audio recorded in-depth semi-structured individual interviews of 27 hospitalized adults with SUD and HCV seen by an addiction consult service (ACS) at an urban academic medical center between June and November 2019. Research staff transcribed interviews and dual coded them deductively and inductively at the semantic level. Researchers used a matrix visualization to discern relationships among codes and conducted a thematic analysis. RESULTS: Many participants believed addictions treatment should precede an HCV cure for varying reasons. Some wanted to avoid reinfection; others believed "getting clean" afforded the mental clarity to address health issues, including HCV. Patients newly engaged in SUD treatment described HCV treatment as a "step towards recovery" and could serve as motivation to continue SUD treatment. Participants believed HCV cure could facilitate sobriety by "mentally putting drugs in the past" and was a future-oriented action toward "better health." Many participants described the compounded stigma of having HCV infection and SUD by multiple groups, including friends/family who do not use drugs, other drug users, and health care workers. CONCLUSION: Hospitalized adults with SUD and HCV believed addictions engagement should precede HCV treatment and HCV cure could play an important role in their "recovery" journey. Discussing HCV treatment during hospitalization may be an opportunity to support engagement in SUD treatment and targets an untreated patient population critical for achieving HCV elimination.

Harm Reduction and Adaptations Among PWUD in Rural Oregon During COVID-19.

Coronavirus Disease 2019 (COVID-19) may influence HIV/HCV transmission risk behaviors in rural communities. We conducted semi-structured qualitative interviews with people who use drugs (PWUD) in five rural Oregon counties and asked about COVID-19 impact on substance use and harm reduction practices and their advice for improving public health responses. Participants (n = 36) reported using only methamphetamine (52.8%), only heroin (16.7%), or both (30.6%); 75% of participants reported recent injection. Three thematic categories emerged: SSP adaptations and accessibility, PWUD harm reduction practices, and policy suggestions. Participants noted the importance of SSPs to COVID-19 prevention and wellbeing, though some experienced increased barriers, leading to increased risky injection practices. Participants suggested need-based rather than one-for-one exchange, increasing syringe delivery services, encouraging secondary exchange by PWUD, and peers as trusted voices for information exchange. Rapid implementation of policy and practice changes are urgently required to improve SSP access, reinforce safer use, and prevent HIV/HCV and COVID-19 transmission.

The Impacts of COVID-19 on Mental Health, Substance Use, and Overdose Concerns of People Who Use Drugs in Rural Communities.

OBJECTIVES: The objective of this study was to investigate the impact of COVID-19 on the mental health, substance use, and overdose concerns among people who use drugs (PWUDs) in rural communities to explore reasons for changes and ways to mitigate COVID-19 impact in the future. METHODS: We conducted semi-structured in-depth interviews with PWUDs in 5 rural Oregon counties with high overdose rates. Participants were identified through participant-driven sampling along with flyer and text advertising (n = 36). Research staff conducted audio-recorded in-depth interviews via telephone, assessing COVID-19 effects on substance use, mental health, and overdose risk. Transcribed interviewers were coded for themes using a semantic approach. RESULTS: Participants reported various mental health symptoms and experiences due to COVID-19, including increased feelings of boredom, loneliness, and depression; increased worry and stress; and increased suicidal ideation. Participants described varying impacts of COVID-19 on substance use. Overall, participants who used only methamphetamine reported decreased use and people who used only heroin or heroin with methamphetamine reported increased use. Most participants reported that they were not concerned about overdose and that COVID-19 did not impact their concerns about overdose, despite increases in risky use and suicidal ideations. CONCLUSIONS: As rural communities respond to the evolving impacts of COVID-19, there is increasing need to identify strategies to address PWUD's mental, physical, and social health needs during COVID-19.

Life projects: the transformative potential of direct-acting antiviral treatment for hepatitis C among people who inject drugs.

BACKGROUND AND OBJECTIVES: People who inject drugs (PWID) are disproportionately affected by chronic hepatitis C (HCV) in high-income countries. The advent of direct-acting antivirals (DAAs) makes treatment of this underserved population more possible than ever. The dearth of programs adapted to the needs of PWID and stigma associated with drug use and chronic HCV pose significant barriers to the effective uptake of treatment among this population. We employed "life projects" as a conceptual framework to examine the social incentives of PWID being treated for HCV. This study advances the existing literature on the transformative potential of HCV treatment among PWID, explores how these transformations may affect treatment success, and discusses implications for decisions around whether and when to treat PWID. METHODS: We conducted in-depth interviews with participants of a pilot clinical trial testing the effective delivery of DAA treatment to PWID within two healthcare for the homeless clinic settings - one group receiving opioid agonist therapy (OAT) and another group frequenting a needle and syringe exchange program (NSP). A purposive sample of 27 participants was selected based on place of care. Interviews were transcribed, coded, and analysed for patterns using a priori domains and emergent themes. RESULTS: Participants in both treatment groups described significant life projects that motivated them to complete HCV treatment. These projects included social redemption, strengthening of relationships, pursuit of abstinence from substance use, and harm reduction. These themes were consistent between treatment groups, though more participants in the syringe exchange group relied on harm reduction than on pursuing abstinence to prevent reinfection after achieving virologic cure. CONCLUSION: Understanding the incentives that propel PWID to complete HCV treatment could help to enhance treatment uptake and adherence through dedicated programs that address current barriers to care.

Novel functional roles for PERIANTHIA and SEUSS during floral organ identity specification, floral meristem termination, and gynoecial development.

The gynoecium is the female reproductive structure of angiosperm flowers. In Arabidopsis thaliana the gynoecium is composed of two carpels that are fused into a tube-like structure. As the gynoecial primordium arises from the floral meristem, a specialized meristematic structure, the carpel margin meristem (CMM), develops from portions of the medial gynoecial domain. The CMM is critical for reproductive competence because it gives rise to the ovules, the precursors of the seeds. Here we report a functional role for the transcription factor PERIANTHIA (PAN) in the development of the gynoecial medial domain and the formation of ovule primordia. This function of PAN is revealed in pan aintegumenta (ant) as well as seuss (seu) pan double mutants that form reduced numbers of ovules. Previously, PAN was identified as a regulator of perianth organ number and as a direct activator of AGAMOUS (AG) expression in floral whorl four. However, the seu pan double mutants display enhanced ectopic AG expression in developing sepals and the partial transformation of sepals to petals indicating a novel role for PAN in the repression of AG in floral whorl one. These results indicate that PAN functions as an activator or repressor of AG expression in a whorl-specific fashion. The seu pan double mutants also display enhanced floral indeterminacy, resulting in the formation of "fifth whorl" structures and disruption of WUSCHEL (WUS) expression patterns revealing a novel role for SEU in floral meristem termination.