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Background: Chronic pain affects up to half of individuals taking opioid agonist therapy (OAT; i.e., methadone and buprenorphine) for opioid use disorder (OUD), and yoga-based interventions may be useful for decreasing pain-related disability. Whereas more yoga practice (i.e., higher "dosage") may improve pain-related outcomes, it can be challenging for people with chronic pain taking OAT to attend class regularly and sustain a regular personal yoga practice. Therefore, we plan to optimize a yoga-based intervention (YBI) package in order to support class attendance and personal practice, thus maximizing the yoga dose received., Study Design: Using the Multiphase Optimization Strategy (MOST) framework, we will conduct a factorial experiment to examine four intervention components that may be added to a weekly yoga class as part of a YBI. Components include: 1) personal practice videos featuring study yoga teachers, 2) two private sessions with a yoga teacher, 3) daily text messages to inspire personal practice, and 4) monetary incentives for class attendance. The primary outcome will be minutes per week engaged in yoga (including class attendance and personal practice). We plan to enroll 192 adults with chronic pain who are taking OAT for OUD in this 2x2x2x2 factorial experiment., Conclusion: Results of the study will guide development of an optimized yoga-based intervention package that maximizes dosage of yoga received. The final treatment package can be tested in a multisite efficacy trial of yoga to reduce pain interference in daily functioning in people with chronic pain who are taking OAT., Trial Registration: Pre-registration of the study was completed on ClinicalTrials.gov (identifier: NCT04641221)., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Uebelacker's spouse is employed by Abbvie Pharmaceuticals. No other authors have interests to declare., (Copyright © 2023. Published by Elsevier Inc.)

Background: Direct-acting antiviral medications have the potential to eliminate the hepatitis C virus (HCV) epidemic among people who inject drugs; yet, suboptimal adherence remains a barrier. Directly observed treatment (DOT), an effective strategy for optimizing adherence, has been frequently implemented in opioid treatment programs but less commonly in community health settings due to the heavy burden of daily visits. An alternative is video-observed therapy (VOT), which uses mobile health technology to monitor adherence. VOT has not been widely studied among people who inject drugs with HCV., Objective: This qualitative study, part of a larger implementation evaluation, investigates stakeholder perceptions and experiences with VOT in Project HERO (Hepatitis C Real Outcomes), a multisite pragmatic trial testing treatment delivery models for people who inject drugs with HCV. Our goal was to understand the potential barriers and facilitators to the implementation of the VOT technology., Methods: Qualitative interviews were conducted with 27 Project HERO study staff and 7 patients. Interviews focused on perceptions and experiences with the VOT app and barriers and facilitators to implementation. Team meeting minutes over the first 2 years of the project were transcribed. A coding system was developed and applied to the data. We summarized thematic data and compared participant perceptions to generate a close understanding of the data., Results: Frequent barriers to VOT included mechanical failure, stolen or lost phones, and a steep learning curve for participants and study staff. In sites with older and less technically skilled participants, staff found it difficult to implement the VOT app. Research staff found that the routine monitoring of app use led to closer engagement with participants. This was both a benefit and a potential threat to the validity of this pragmatic trial. Patient participants reported mixed experiences., Conclusions: VOT may be a useful alternative to DOT for some patients, but it may not be feasible for all. Significant staff involvement may be required., (©Alison Karasz, Krupa Merchant, Julia Arnsten, Judith Feinberg, Arthur Y Kim, Paula J Lum, Melissa Diane McKee, Shruti H Mehta, Paul Meissner, Brianna L Norton, Kimberly Page, Irene Pericot-Valverde, Reena Singh, Ellen Stein, Lynn E Taylor, Judith I Tsui, Katherine Wagner, Alain Litwin. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 02.06.2023.)

Background: Persons who inject drugs (PWID) are a key population for hepatitis C virus (HCV) treatment. Study aims were to describe injection practices of PWID during HCV treatment with direct-acting antivirals (DAAs) and assess whether injection practices were associated with not achieving a sustained virologic response (SVR)., Methods: Secondary analysis of the HERO Study (ClinicalTrials.gov, NCT02824640), a pragmatic randomized trial in 8 U.S. states to evaluate the effectiveness of HCV care models among active PWID seen in opioid treatment programs and community clinics. Frequency, sharing and reuse of injecting equipment were assessed at baseline, end-of-treatment (EOT) and quarterly visits up to 60 weeks post-treatment. Generalized Estimating Equations logistic regression models with linear spline were used to compare trends in injecting behaviors during vs. post-treatment. Multivariable logistic regression models explored associations between injecting behaviors during treatment and lack of SVR., Results: Among 501 participants, 27% were female, 35% were non-white, mean age was 44 (SD 11.5) years and nearly half (49%) were unhoused. At baseline, 41% reported receptive sharing of injecting equipment, declining to 16% at EOT visit. Receptive sharing of cookers, rinses, or needles/syringes during treatment was associated with a nearly 5-fold increase in not achieving SVR (adjusted odds ratio (aOR)=4.83; 95% CI: 2.26, 10.28) as was reuse of one's own needles/syringes (aOR=2.37; 95% CI: 1.11, 4.92)., Conclusions: PWID in the HERO study adopted safer injecting behaviors during DAA treatment; receptive sharing of injecting equipment and reuse of one's own equipment during treatment were associated with not achieving cure., Competing Interests: Declaration of Competing Interest FN has served on advisory panels for Gilead Sciences and reports research funds from AbbVie paid to Johns Hopkins University. JF has received research grant support from Gilead Sciences. AYK has served on advisory boards for Biomarin. AFL received research grant support from Gilead and Merck. The Task Force for Global Health receives funds for the general support of the Coalition for Global Hepatitis Elimination from Abbott, Gilead, AbbVie, Merck, Siemens, Roche, Pharco, Zydus-Cadila, governmental agencies, and philanthropic organizations. AHL has served on advisory boards for Gilead Sciences and Merck Pharmaceuticals and received research funding from Gilead Sciences. Dr. Mehta has received speaker fees from Gilead Sciences. LT has received UpToDate Royalties for peer review of viral hepatitis topics. All other authors had nothing to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: To achieve WHO targets for the elimination of hepatitis C virus (HCV) as a public threat, an increased uptake of HCV treatment among people who inject drugs (PWID) is urgently needed. Optimal HCV co-located treatment models for PWID have not yet been identified. We aimed to compare two patient-centred models of HCV care in PWID with active drug use., Methods: We did a pragmatic randomised controlled trial at eight US cities in eight opioid treatment programmes and 15 community health centres. PWID actively injecting within 90 days of study entry were randomly assigned (1:1) to either patient navigation or modified directly observed therapy (mDOT) using computer-generated variable block sizes of 2-6 stratified by city, clinical settings, and cirrhosis status. The randomisation code was concealed, in a centralised REDCap database platform, from all investigators and research staff except for an authorised data manager at the data coordinating centre. All participants received a fixed-dose combination tablet (sofosbuvir 400 mg plus velpatasvir 100 mg) orally once daily for 12 weeks. The primary outcome was sustained virological response (SVR; determined by chart review between 70 days and 365 days after end of treatment and if unavailable, by study blood draws), and secondary outcomes were treatment initiation, adherence (measured by electronic blister packs), and treatment completion. Analyses were conducted within the modified intention-to-treat (mITT; all who initiated treatment), intention-to-treat (all who were randomised), and per-protocol populations. This trial is registered with ClinicalTrials.gov, NCT02824640., Findings: Between Sept 15, 2016, and Aug 14, 2018, 1891 individuals were screened and 1136 were excluded (213 declined to participate and 923 did not meet the eligibility criteria). We randomly assigned 755 participants to patient navigation (n=379) or mDOT (n=376). In the mITT sample of participants who were randomised and initiated treatment (n=623), 226 (74% [95% CI 69-79]) of 306 participants in the mDOT group and 236 (76% [69-79]) of 317 in the patient navigation group had an SVR, with no significant difference between the groups (adjusted odds ratio [AOR] 0·97 [95% CI 0·66-1·42]; p=0·35). In the ITT sample (n=755), 226 (60% [95% CI 55-65]) of 376 participants in the mDOT group and 236 (62% [57-67]) of 379 in the patient navigation group had an SVR (AOR 0·92 [0·68-1·25]; p=0·61) and in the per-protocol sample (n=501), 226 (91% [87-94]) of 248 participants in the mDOT group and 235 (93% [89-96]) of 253 in the patient navigation group had an SVR (AOR 0·79 [0·41-1·55]; p=0·44). 306 (81%) of 376 participants in the mDOT group and 317 (84%) of 379 participants in the patient navigation group initiated treatment (AOR 0·86 [0·58-1·26]; p=0·44) and, among those, 251 (82%) participants in the mDOT group and 264 (83%) participants in the patient navigation group completed treatment (AOR 0·90 [0·58-1·39]; p=0·63). Mean daily adherence was higher in the mDOT group (78% [95% CI 75-81]) versus the patient navigation group (73% [70-77]), with a difference of 4·7% ([1·9-7·4]; p=0·0010). 421 serious adverse events were reported (217 in the mDOT group and 204 in the patient navigation group), with the most common being hospital admission (176 in the mDOT group vs 161 in the patient navigation group)., Interpretation: In this trial of active PWID, both models resulted in high SVR. Although adherence was significantly higher in the mDOT group versus the patient navigation group, there was no significant difference in SVR between the groups. Increases in adherence and treatment completion were associated with an increased likelihood of SVR. These results suggest that active PWID can reach high SVRs in diverse settings with either mDOT or patient navigation support., Funding: Patient-Centered Outcomes Research Institute, Gilead Sciences, Quest Diagnostics, Monogram Biosciences, and OraSure Technologies., Competing Interests: Declaration of interests OF-N has served on advisory panels for Gilead Sciences and reports research funds from AbbVie paid to Johns Hopkins University. JF has received research grant support from Gilead Sciences. AYK has served on advisory boards for Biomarin. AFL received research grant support from Gilead and Merck. The Task Force for Global Health receives funds for the general support of the Coalition for Global Hepatitis Elimination from Abbott, Gilead, AbbVie, Merck, Siemens, Roche, Pharco, Zydus-Cadila, governmental agencies, and philanthropic organisations. AHL has served on advisory boards for Gilead Sciences and Merck Pharmaceuticals and received research funding from Gilead Sciences. SHM has received speaker fees from Gilead Sciences. LET has received UpToDate Royalties for peer review of viral hepatitis topics. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Alcohol use contributes to the progression of liver disease in HIV-HCV co-infected persons, but alcohol interventions have never addressed low levels of alcohol use in this population. We enrolled 110 persons consuming at least 4 alcoholic drinks weekly in a clinical trial comparing two active 18-month long interventions, delivered every 3 months by phone, brief advice about drinking versus a motivational intervention. Final assessment was at 24 months. MI had larger reductions in alcohol use days than the BA arm at all follow-up assessments. The treatment by time effect was not significant for days of drinking (p = 0.470), mean drinks per day (p = 0.155), or for the continuous FIB-4 index (p = 0.175). Drinking declined in both conditions from baseline, but given the small sample, we do not have sufficient data to make any conclusion that one treatment is superior to the other.Trial Registry Trial registered at clinicaltrials.gov; Clinical Trial NCT02316184.

Telomere length dynamics and DNA damage responses were assessed before, during, and after one-year or shorter duration missions aboard the International Space Station (ISS) in a comparatively large cohort of astronauts (n = 11). Although generally healthy individuals, astronauts tended to have significantly shorter telomeres and lower telomerase activity than age- and sex-matched ground controls before and after spaceflight. Although telomeres were longer during spaceflight irrespective of mission duration, telomere length shortened rapidly upon return to Earth, and overall astronauts had shorter telomeres after spaceflight than they did before; inter-individual differences were identified. During spaceflight, all crewmembers experienced oxidative stress, which positively correlated with telomere length dynamics. Significantly increased frequencies of chromosomal inversions were observed during and after spaceflight; changes in cell populations were also detected. We propose a telomeric adaptive response to chronic oxidative damage in extreme environments, whereby the telomerase-independent Alternative Lengthening of Telomeres (ALT) pathway is transiently activated in normal somatic cells., Competing Interests: Declaration of Interests S.M.B. is a cofounder and Scientific Advisory Board member of KromaTiD, Inc. C.E.M. is a cofounder and board member for Biotia, Inc. and Onegevity Health, Inc., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Telomeres, repetitive terminal features of chromosomes essential for maintaining genome integrity, shorten with cell division, lifestyle factors and stresses, and environmental exposures, and so they provide a robust biomarker of health, aging, and age-related diseases. We assessed telomere length dynamics (changes over time) in three unrelated astronauts before, during, and after 1-year or 6-month missions aboard the International Space Station (ISS). Similar to our results for National Aeronautics and Space Administration's (NASA's) One-Year Mission twin astronaut (Garrett-Bakelman et al., 2019), significantly longer telomeres were observed during spaceflight for two 6-month mission astronauts. Furthermore, telomere length shortened rapidly after return to Earth for all three crewmembers and, overall, telomere length tended to be shorter after spaceflight than before spaceflight. Consistent with chronic exposure to the space radiation environment, signatures of persistent DNA damage responses were also detected, including mitochondrial and oxidative stress, inflammation, and telomeric and chromosomal aberrations, which together provide potential mechanistic insight into spaceflight-specific telomere elongation., Competing Interests: Declaration of Interests S.M.B. is a cofounder and Scientific Advisory Board member of KromaTiD. C.E.M. is a cofounder and board member for Biotia and Onegevity Health., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Recent epidemiologic data demonstrate increasing rates of neurosyphilis, particularly among those in the community of men who have sex with men and those coinfected with the human immunodeficiency virus (HIV). Here we discuss a case of early neurosyphilis and new HIV diagnosis in a 27-year-old previously-healthy trans woman presenting for the second time with progressive, ascending weakness and cranial nerve VI palsy. Emergency physicians should consider this rare but highly morbid diagnosis, given the rising prevalence of neurosyphilis among at-risk patients and those with new neurologic deficits., Competing Interests: Conflicts of Interest: By the CPC-EM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. The authors disclosed none., (Copyright: © 2020 Mercurio et al.)

Twinrix is the only licensed vaccine that provides dual protection against infection with hepatitis A virus (HAV) and hepatitis B virus (HBV). The standard vaccination schedule for Twinrix is 0, 1 and 6 months. However, many high-risk populations, such as injecting drug users (IDUs), do not complete the vaccination series and, thus, do not acquire sufficient immunity against HAV and HBV. Twinrix can be administered using an accelerated vaccination schedule of 0, 7 and 21 days, with a booster recommended at 12 months. This manuscript reviews the available literature on vaccinating IDUs against HAV and HBV. The authors conclude that there is insufficient evidence regarding whether the accelerated Twinrix HAV/HBV vaccination schedule would yield a greater number of IDUs protected against both HAV and HBV.

Injection drug use has fueled the epidemic of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection in the United States. Nevertheless, drug dependence is among the main reasons that coinfected persons are not being treated for HCV infection. This report describes the development and progress of an HIV clinic program (funded by the Ryan White Comprehensive AIDS Resources Emergency Act) to deliver care for HCV infection to HIV-seropositive injection drug users. To optimize safety and adherence, pegylated interferon is directly administered to patients in the context of integrated addiction, psychiatric, and HIV and HCV therapy. Ribavirin is packed weekly in pill boxes for patients to take at home. Thus far, adherence to weekly visits for treatment with interferon has been 99%. No one has had to stop treatment for HCV infection because of ongoing drug use, addiction relapse or exacerbation, or psychiatric complications. Presented here is a work in progress, rather than a finished research project or definitive model of care.