Post-traumatic growth, moral sensitivity and service behaviour among healthcare workers in the post-pandemic era of COVID-19 in mainland China: a cross-sectional study

Objectives
To investigate how post-traumatic growth (PTG) and moral sensitivity influence service behaviour among healthcare workers (HCWs) in mainland China post-COVID-19, with a focus on the mediating role of moral sensitivity.

Design
Cross- sectional survey design.

Setting
This study was conducted in 27 provinces across mainland China, from 16 March to 2 April 2023.

Participants
1,193 HCWs, including 378 physicians and 815 nurses, were selected using convenience and snowball sampling methods.

Methods
The survey included the Post-traumatic Growth Inventory-Chinese version (PTGI-C), the Moral Sensitivity Questionnaire-Revised Chinese Version (MSQ-R-CV) and a service behaviour scale. Structural equation modelling was employed to analyse the data, focusing on the associations between PTG, moral sensitivity, and service behaviours.

Results
The study found significant associations between PTG and moral sensitivity (r=0.49, p

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Novembre 2024

Post-COVID in healthcare workers and its consequences on quality of life, activities, participation, need for rehabilitation and care experiences: protocol of a cohort study

Introduction
Healthcare workers (HCWs) have been of particular relevance for overcoming the SARS-CoV-2 pandemic. At the same time they have been affected by SARS-CoV-2 infections with above average probability. Around 6.5% of the overall infected persons are likely to develop persistent symptoms resulting from the infection, known as long-COVID or post-COVID syndrome (PCS). The aim of this study is (1) to investigate the prevalence, course and characteristics of PCS in German HCWs, (2) to examine its effects on psychosocial variables, (3) to identify rehabilitation and healthcare needs and (4) to analyse treatment experiences.

Methods and analysis
In a cohort study with a randomised selection of participants (N=20 000) from the Employer’s Liability Insurance Association for Health and Welfare Care, the health status of HCWs, who had COVID-19 in their professional context will be examined. There will be two measurement points: baseline (T1) and a 12-month follow-up (T2). The outcome measures are the health status with a particular focus on persistent or newly occurring symptoms after a SARS-CoV-2 infection, health-related quality of life, functional capacity, the subjective need for and utilisation of healthcare services. Pre-existing conditions, the course of the acute infection and sociodemographic factors are considered as predictors. An advisory board made up of affected HCWs supports the study by contributing to the surveys’ contents.

Ethics and dissemination
The study has been approved by the Local Ethics Committee of the Center for Psychosocial Medicine at the University Hospital Hamburg-Eppendorf (LPEK-0518). For dissemination, the results will be published in peer-reviewed journals, presented at conferences and communicated to relevant stakeholders in general and rehabilitation medicine.

Trail registration number
https://drks.de/search/de/trial/DRKS00029314

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Novembre 2024

Completion and reporting of COVID-19 clinical trials registered on ClinicalTrials.gov during the first 6 months of the pandemic: cohort study

Background
Early in the COVID-19 pandemic, numerous clinical trials were initiated. Although concerns were raised regarding the quality of the trials, the eventual research output yielded from the trials remains unknown. The objective of this study was to include all clinical trials registered on ClinicalTrials.gov during the first 6 months of the pandemic and assess if and where their results had been reported, their completion and discontinuation rates, achieved enrolment and changes made to the primary outcome after trial registration.

Methods
We included all interventional studies related to COVID-19 first registered on ClinicalTrials.gov between 1 January 2020 and 1 July 2020. We systematically searched for trial results, reported through 15 May 2023, in scientific publications, preprints and ClinicalTrials.gov. We assessed the achieved trial enrolment, trial discontinuation (reaching

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Novembre 2024

Trajectories of functional limitations, health-related quality of life and societal costs in individuals with long COVID: a population-based longitudinal cohort study

Objectives
To examine trajectories of functional limitations, fatigue, health-related quality of life (HRQL) and societal costs of patients referred to long COVID clinics.

Design
A population-based longitudinal cohort study using real-time user data.

Setting
35 specialised long COVID clinics in the UK.

Participants
4087 adults diagnosed with long COVID in primary or secondary care deemed suitable for rehabilitation and registered in the Living With Covid Recovery (LWCR) programme between 4 August 2020 and 5 August 2022.

Main outcome measures
Generalised linear mixed models were fitted to estimate trajectories of functional limitations, using the Work and Social Adjustment Scale (WSAS); scores of ≥20 indicate moderately severe limitations. Other outcomes included fatigue using the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) reversed score (scores of ≥22 indicate impairment), HRQL using the EQ-5D-5L, and long COVID-related societal costs, encompassing healthcare costs and productivity losses.

Results
The mean WSAS score at 6 months after registration in the LWCR was 19.1 (95% CI 18.6, 19.6), with 46% of the participants (95% CI 40.3%, 52.4%) reporting a WSAS score above 20 (moderately severe or worse impairment). The mean change in the WSAS score over the 6-month period was –0.86 (95% CI –1.32, –0.41). The mean reversed FACIT-F score at 6 months was 29.1 (95% CI 22.7, 35.5) compared with 32.0 (95% CI 31.7, 32.3) at baseline. The mean EQ-5D-5L score remained relatively constant between baseline (0.63, 95% CI 0.62, 0.64) and 6 months (0.64, 95% CI 0.59, 0.69). The monthly societal cost per patient related to long COVID at 6 months was £931, mostly driven by the costs associated with working days lost.

Conclusions
Individuals referred to long COVID clinics in the UK reported small improvements in functional limitations, fatigue, HRQL and ability to work within 6 months of registering in the LWCR programme.

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Novembre 2024

COVID-19 Therapeutics for Nonhospitalized Older Adults

This Viewpoint summarizes the factors contributing to increased risk of severe outcomes and hospitalization associated with COVID-19 among older adults, stresses the importance of assessing COVID-19 risk before infection occurs, calls for all immunocompromised older adults to be considered for COVID-19 treatment, and details 3 recommended COVID-19 therapies.

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Novembre 2024

Targeting squalene epoxidase restores anti-PD-1 efficacy in metabolic dysfunction-associated steatohepatitis-induced hepatocellular carcinoma

Objective
Squalene epoxidase (SQLE) promotes metabolic dysfunction-associated steatohepatitis-associated hepatocellular carcinoma (MASH-HCC), but its role in modulating the tumour immune microenvironment in MASH-HCC remains unclear.

Design
We established hepatocyte-specific Sqle transgenic (tg) and knockout mice, which were subjected to a choline-deficient high-fat diet plus diethylnitrosamine to induce MASH-HCC. SQLE function was also determined in orthotopic and humanised mice. Immune landscape alterations of MASH-HCC mediated by SQLE were profiled by single-cell RNA sequencing and flow cytometry.

Results
Hepatocyte-specific Sqle tg mice exhibited a marked increase in MASH-HCC burden compared with wild-type littermates, together with decreased tumour-infiltrating functional IFN-+ and Granzyme B+ CD8+ T cells while enriching Arg-1+ myeloid-derived suppressor cells (MDSCs). Conversely, hepatocyte-specific Sqle knockout suppressed tumour growth with increased cytotoxic CD8+ T cells and reduced Arg-1+ MDSCs, inferring that SQLE promotes immunosuppression in MASH-HCC. Mechanistically, SQLE-driven cholesterol accumulation in tumour microenvironment underlies its effect on CD8+ T cells and MDSCs. SQLE and its metabolite, cholesterol, impaired CD8+ T cell activity by inducing mitochondrial dysfunction. Cholesterol depletion in vitro abolished the effect of SQLE-overexpressing MASH-HCC cell supernatant on CD8+ T cell suppression and MDSC activation, whereas cholesterol supplementation had contrasting functions on CD8+ T cells and MDSCs treated with SQLE-knockout supernatant. Targeting SQLE with genetic ablation or pharmacological inhibitor, terbinafine, rescued the efficacy of anti-PD-1 treatment in MASH-HCC models.

Conclusion
SQLE induces an impaired antitumour response in MASH-HCC via attenuating CD8+ T cell function and augmenting immunosuppressive MDSCs. SQLE is a promising target in boosting anti-PD-1 immunotherapy for MASH-HCC.

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Novembre 2024

Abstract 4136984: Low Occurence of Fetal Extranodal Findings and AV Interval Prolongation in Prospectively Followed High Titer Anti-Ro Pregnancies

Circulation, Volume 150, Issue Suppl_1, Page A4136984-A4136984, November 12, 2024. .Background:Third-degree atrioventricular block (AVB) is the most common manifestation of Anti-Ro antibody associated fetal cardiac disease. Extranodal findings of isolated cardiac echogenicity, valvulitis with insufficiency and AV interval prolongation have been reported but not described in large prospective series.Aims:To report the occurrence and outcomes of extranodal findings in subjects followed prospectively since 2020 in STOP BLOQ (Surveillance and Treatment to Prevent Fetal AV block Likely to Occur Quickly) and the Registry for Neonatal Lupus (RNL).Methods:We reviewed fetal echo reports from pregnant STOP BLOQ and RNL Anti-Ro antibody subjects. Pregnancies with high ( >1000 EU for anti-Ro52 or 60) antibody titers measured in a core research lab underwent surveillance with home fetal heart rate monitoring (FHRM) 3x/day and weekly or bi-weekly fetal echos from 17- 26 gestational weeks. Low titer subjects underwent echo or no surveillance based on local site protocol. We evaluated cardiac function, effusions, cardiac echogenicity and its location, any tricuspid (TV) or mitral (MV) insufficiency trivial or >trivial) and AV conduction times (170 ms)Results:Echo reports were available in 622 prospectively followed pregnancies (376 high (40/376 with a previously affected child) and 246 low-titer pregnancies. All had subjectively normal ventricular function and none had effusions. Seven fetuses, 2 low and 5 high titer at 19 (range 16.7-21.7) weeks demonstrated cardiac echogenicity (n=6), AV or semilunar valve insufficiency (n=2) or AV interval 150-170 ms (n=2) (Table). Subjects 1 and 2, both high titer and treated with prophylactic Plaquenil (400 mg/d before 10 gestational weeks), had prior fetal AVB. Subject #1 had normal AV conduction but MV and TV echogenicity and moderate insufficiency of both valves which resolved in days after IVIG and dexamethasone (dex) treatment, but 3° AVB developed at 19 weeks after dex wean. Subjects 2-7 received no treatment and extranodal findings did not progress to cardiac dysfunction or AVB. During the same time period, 10 high titer subjects developed 2° or 3° AVB.Conclusion:Anti-Ro associated extranodal findings are rare, occurring in 1% of pregnancies overall and in 5% of pregnancies with a previously affected child. Unlike AVB, extranodal findings can occur in low titer pregnancies. The role of treatment for isolated extranodal findings in the absence of cardiac dysfunction is unclear.

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Novembre 2024