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Background: The advent of short-course, curative treatment with direct-acting antivirals (DAA) has given promise for the global elimination of hepatitis C virus (HCV) infections by 2030. Virological failure occurs in 2%-12% of persons receiving curative DAA treatment and may be presaged by pre-existing polymorphisms or result from selection of drug resistant variants during therapy., Methods: We conducted a systematic review to assess the prevalence of HCV resistance associated substitutions (RAS) among individuals with chronic hepatitis C infection who had virological failure following initial or re-treatment with pan-genotypic DAA regimens. We included 34 and 22 studies assessing RAS in people with virological failure published between January 2014 and July 2023. Pooled RAS prevalence was estimated using random-effects meta-analysis., Results: The pooled prevalence of RAS in people with virological failure following initial DAA treatment was 78.0% (95% confidence interval [CI]: 62.0-92.0) for sofosbuvir/velpatasvir, 81.0% (95% CI: 67.0-93.0) for sofosbuvir/daclatasvir, and 79.0% (95% CI: 70.0-87.0) for glecaprevir/pibrentasvir, with a high prevalence of resistance to the NS5A inhibitors. Among those with virological failure following re-treatment regimens, RAS were present in 93.0% (95% CI: 83.0-99.0) for sofosbuvir/velpatasvir/voxilepravir and in 100% (95% CI: 92.0-100) for glecaprevir/pibrentasvir, with resistance driven by RAS to NS5A inhibitors., Discussion: At least 1 RAS is present in a high proportion of the few individuals with virological failure following initial or re-treatment with pan-genotypic DAA regimens. There is a need for ongoing surveillance for DAA-associated resistance, to assess risk factors for their development and clinical impact to inform best practice strategies for re-treatment., Competing Interests: Potential conflicts of interest. W. I. reports personal fees from Roche diagnostics, Gilead Sciences, and Source Bioscience Limited outside of the submitted work and stock or stock options in GlaxoSmithKline. P. C. M. reports funding from Francis Crick Institute and University College London Biomedical Research Centre (BRC) and Wellcome Trust during the submitted work, as well as royalties from Oxford University Press and funding from GlaxoSmithKline outside of the submitted work. S. T. reports funding or personal fees ViiV Healthcare and Gilead Sciences outside of the submitted work. D. A. reports funding from Gilead Sciences and Pfizer outside of the submitted work. R. H. serves as the president of World Hepatitis Alliance. All other authors declare no competing interests. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Physical activity is recommended as part of guideline-based care for managing chronic obstructive pulmonary disease (COPD) at all stages of the disease. However, physical activity interventions are less effective in individuals with co-occurring emotional distress (i.e., depression and/or anxiety symptoms). Interventions that dually promote improved physical and mental health in COPD are needed. The first step for intervention development is understanding individuals' experience of these factors., Purpose: To understand the experience of emotional distress in U.S. Veterans diagnosed with COPD and to explore how emotional distress impacts physical activity engagement., Methods: Structured interviews informed by the cognitive and behavioral models of psychopathology were conducted with 29 United States Veterans with COPD (89.66% male, age 67.72 ± 6.55 years, 93.10% White) at the VA Boston Healthcare System. Interviews were audio recorded, transcribed, and underwent thematic analysis., Results: Three major themes encapsulating 17 codes emerged through thematic analysis: (i) the experience of emotional distress in Veterans with COPD; (ii) the complex relationship between emotional distress, physical activity engagement, and COPD; (iii) contextual and personal factors., Conclusions: Veterans' interpretation of their COPD symptoms as unpredictable and uncontrollable and COPD-related physical limitations influenced their experience of emotional distress, while the experience of emotional distress both promoted and deterred physical activity engagement. Veterans were motivated to engage in physical activity despite experiencing emotional distress when they faced a responsibility in daily life. They identified motivational strategies and self-regulation techniques to manage emotional distress and to foster physical activity., (Published by Oxford University Press on behalf of the Society of Behavioral Medicine 2024.)

Background: health-related quality of life (HRQoL) is an important patient-centred outcome in patients surviving ICU admission for COVID-19. It is currently not clear which domains of the HRQoL are most affected., Objective: to quantify HRQoL in order to identify areas of interventions., Design: prospective observation study., Setting: admissions to European ICUs between March 2020 and February 2021., Subjects: patients aged 70 years or older admitted with COVID-19 disease., Methods: collected determinants include SOFA-score, Clinical Frailty Scale (CFS), number and timing of ICU procedures and limitation of care, Katz Activities of Daily Living (ADL) dependence score. HRQoL was assessed at 3 months after ICU admission with the Euro-QoL-5D-5L questionnaire. An outcome of ≥4 on any of Euro-QoL-5D-5L domains was considered unfavourable., Results: in total 3,140 patients from 14 European countries were included in this study. Three months after inclusion, 1,224 patients (39.0%) were alive and the EQ-5D-5L from was obtained. The CFS was associated with an increased odds ratio for an unfavourable HRQoL outcome after 3 months; OR 1.15 (95% confidence interval (CI): 0.71-1.87) for CFS 2 to OR 4.33 (95% CI: 1.57-11.9) for CFS ≧ 7. The Katz ADL was not statistically significantly associated with HRQoL after 3 months., Conclusions: in critically ill old intensive care patients suffering from COVID-19, the CFS is associated with the subjectively perceived quality of life. The CFS on admission can be used to inform patients and relatives on the risk of an unfavourable qualitative outcome if such patients survive., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Concerns about the large-scale European crisis of bovine spongiform encephalopathy, the finding of 1 infected cow in Alberta, Canada, in 2003, and the theoretical concern of prion transmissibility in blood have renewed interest in the development of rapid, minimally invasive diagnostic assays for prion diseases. Herein we review the pathologic features, clinical manifestations, diagnostic criteria, and recent developments that may lead to new diagnostic screening assays for prion diseases.