Integrated Hepatitis C-Opioid Use Disorder Care Through Facilitated Telemedicine: A Randomized Trial.

Importance: Facilitated telemedicine may promote hepatitis C virus elimination by mitigating geographic and temporal barriers. Objective: To compare sustained virologic responses for hepatitis C virus among persons with opioid use disorder treated through facilitated telemedicine integrated into opioid treatment programs compared with off-site hepatitis specialist referral. Design, Setting, and Participants: Prospective, cluster randomized clinical trial using a stepped wedge design. Twelve programs throughout New York State included hepatitis C-infected participants (n = 602) enrolled between March 1, 2017, and February 29, 2020. Data were analyzed from December 1, 2022, through September 1, 2023. Intervention: Hepatitis C treatment with direct-acting antivirals through comanagement with a hepatitis specialist either through facilitated telemedicine integrated into opioid treatment programs (n = 290) or standard-of-care off-site referral (n = 312). Main Outcomes and Measures: The primary outcome was hepatitis C virus cure. Twelve programs began with off-site referral, and every 9 months, 4 randomly selected sites transitioned to facilitated telemedicine during 3 steps without participant crossover. Participants completed 2-year follow-up for reinfection assessment. Inclusion criteria required 6-month enrollment in opioid treatment and insurance coverage of hepatitis C medications. Generalized linear mixed-effects models were used to test for the intervention effect, adjusted for time, clustering, and effect modification in individual-based intention-to-treat analysis. Results: Among 602 participants, 369 were male (61.3%); 296 (49.2%) were American Indian or Alaska Native, Asian, Black or African American, multiracial, or other (ie, no race category was selected, with race data collected according to the 5 standard National Institutes of Health categories); and 306 (50.8%) were White. The mean (SD) age of the enrolled participants in the telemedicine group was 47.1 (13.1) years; that of the referral group was 48.9 (12.8) years. In telemedicine, 268 of 290 participants (92.4%) initiated treatment compared with 126 of 312 participants (40.4%) in referral. Intention-to-treat cure percentages were 90.3% (262 of 290) in telemedicine and 39.4% (123 of 312) in referral, with an estimated logarithmic odds ratio of the study group effect of 2.9 (95% CI, 2.0-3.5; P < .001) with no effect modification. Observed cure percentages were 246 of 290 participants (84.8%) in telemedicine vs 106 of 312 participants (34.0%) in referral. Subgroup effects were not significant, including fibrosis stage, urban or rural participant residence location, or mental health (anxiety or depression) comorbid conditions. Illicit drug use decreased significantly (referral: 95% CI, 1.2-4.8; P = .001; telemedicine: 95% CI, 0.3-1.0; P < .001) among cured participants. Minimal reinfections (n = 13) occurred, with hepatitis C virus reinfection incidence of 2.5 per 100 person-years. Participants in both groups rated health care delivery satisfaction as high or very high. Conclusions and Relevance: Opioid treatment program-integrated facilitated telemedicine resulted in significantly higher hepatitis C virus cure rates compared with off-site referral, with high participant satisfaction. Illicit drug use declined significantly among cured participants with minimal reinfections. Trial Registration: ClinicalTrials.gov Identifier: NCT02933970.

The potent analgesia of intrathecal 2R, 6R-HNK via TRPA1 inhibition in LF-PENS-induced chronic primary pain model.

BACKGROUND: Chronic primary pain (CPP) is an intractable pain of unknown cause with significant emotional distress and/or dysfunction that is a leading factor of disability globally. The lack of a suitable animal model that mimic CPP in humans has frustrated efforts to curb disease progression. 2R, 6R-hydroxynorketamine (2R, 6R-HNK) is the major antidepressant metabolite of ketamine and also exerts antinociceptive action. However, the analgesic mechanism and whether it is effective for CPP are still unknown. METHODS: Based on nociplastic pain is evoked by long-term potentiation (LTP)-inducible high- or low-frequency electrical stimulation (HFS/LFS), we wanted to develop a novel CPP mouse model with mood and cognitive comorbidities by noninvasive low-frequency percutaneous electrical nerve stimulation (LF-PENS). Single/repeated 2R, 6R-HNK or other drug was intraperitoneally (i.p.) or intrathecally (i.t.) injected into naïve or CPP mice to investigate their analgesic effect in CPP model. A variety of behavioral tests were used to detect the changes in pain, mood and memory. Immunofluorescent staining, western blot, reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and calcium imaging of in cultured dorsal root ganglia (DRG) neurons by Fluo-8-AM were used to elucidate the role and mechanisms of 2R, 6R-HNK in vivo or in vitro. RESULTS: Intrathecal 2R, 6R-HNK, rather than intraperitoneal 2R, 6R-HNK or intrathecal S-Ketamine, successfully mitigated HFS-induced pain. Importantly, intrathecal 2R, 6R-HNK displayed effective relief of bilateral pain hypersensitivity and depressive and cognitive comorbidities in a dose-dependent manner in LF-PENS-induced CPP model. Mechanically, 2R, 6R-HNK markedly attenuated neuronal hyperexcitability and the upregulation of calcitonin gene-related peptide (CGRP), transient receptor potential ankyrin 1 (TRPA1) or vanilloid-1 (TRPV1), and vesicular glutamate transporter-2 (VGLUT2) in peripheral nociceptive pathway. In addition, 2R, 6R-HNK suppressed calcium responses and CGRP overexpression in cultured DRG neurons elicited by the agonists of TRPA1 or/and TRPV1. Strikingly, the inhibitory effects of 2R, 6R-HNK on these pain-related molecules and mechanical allodynia were substantially occluded by TRPA1 antagonist menthol. CONCLUSIONS: In the newly designed CPP model, our findings highlighted the potential utility of intrathecal 2R, 6R-HNK for preventing and therapeutic modality of CPP. TRPA1-mediated uprgulation of CGRP and neuronal hyperexcitability in nociceptive pathways may undertake both unique characteristics and solving process of CPP.

The potential role of betaine in enhancement of microbial-assisted phytoremediation of benzophenone-3 contaminated soil.

Benzophenone-3 (BP-3) is an emerging environmental pollutant used in personal care products, helping to reduce the risk of ultraviolet radiation to human skin. The BP-3 removal potential from soil by tobacco (Nicotiana tabacum) assisted with Methylophilus sp. FP-6 was explored in our previous study. However, the reduced BP-3 remediation efficiency by FP-6 in soil and the inhibited plant growth by BP-3 limited the application of this phytoremediation strategy. The aim of the present study was to reveal the potential roles of betaine, as the methyl donor of methylotrophic bacteria and plant regulator, in improving the strain FP-6-assisted phytoremediation capacity of BP-3 contaminated soil. The results revealed that strain FP-6 could use betaine as a co-metabolism substrate to enhance the BP-3 degradation activity. About 97.32% BP-3 in soil was effectively removed in the phytoremediation system using tobacco in combination with FP-6 and betaine for 40 d while the concentration of BP-3 in tobacco significantly reduced. Moreover, the biomass and photosynthetic efficiency of plants were remarkably improved through the combined treatment of betaine and strain FP-6. Simultaneously, inoculation of FP-6 in the presence of betaine stimulated the change of local microbial community structure, which might correlate with the production of a series of hydrolases and reductases involved in soil carbon, nitrogen and phosphorus cycling processes. Meantime, some of the dominant bacteria could secrete various multiple enzymes involved in degrading organic pollutants, such as laccase, to accelerate the demethylation and hydroxylation of BP-3. Overall, the results from this study proposed that the co-metabolic role of betaine could be utilized to strengthen microbial-assisted phytoremediation process by increasing the degradation ability of methylotrophic bacteria and enhancing plant tolerance to BP-3. The present results provide novel insights and perspectives for broadening the engineering application scope of microbial-assisted phytoremediation of organic pollutants without sacrificing economic crop safety.

Research Progress of Drug Treatment in Novel Coronavirus Pneumonia.

As of March 10, 2020, more than 100,000 novel coronavirus pneumonia cases have been confirmed globally. With the continuous spread of the new coronavirus pneumonia epidemic in even the world, prevention and treatment of the disease have become urgent tasks. The drugs currently being developed are not adequate to deal with this critical situation. In addition to being controlled through effective isolation, we need a rapid response from the healthcare and biotechnology industries to accelerate drug treatment research. By reviewing the currently available literature published at home and abroad, we summarize the current research progress of drug treatment during the epidemic period. At present, the drugs that can be used for treatment mainly include antiviral drugs, antimalarials, glucocorticoids, plasma therapy, biological agents, and traditional Chinese medicine. The effectiveness and safety of drug therapy need to be confirmed by more clinical studies.