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6; 95% confidence interval, 0.4-0.7). Prior use of direct-acting oral anticoagulants and antiarrhythmics, and the presence of an implantable cardioverter-defibrillator were also predictors for CA treatment (P less then 0.05 for all). Conclusion In a real-world population, CA was infrequently used to treat AF among patients with HF, and the likelihood of CA was further reduced in women. Because patients with CA had few comorbidities, future studies need to be conducted to determine whether CA can be beneficial in subjects whose clinical characteristics are more representative of the AF-HF population.Background Transcatheter aortic valve implantation (TAVI) is an effective alternative to surgical valve replacement in high-risk patients with severe aortic stenosis. Although measures of frailty have been used to attempt to predict outcomes in this population, few studies have demonstrated changes in these measures. Methods We performed a prospective, observational study of 171 patients undergoing TAVI, of whom 44 had maximal follow-up of 1 month and 50 had maximal follow-up of 1 year. Quality of life was assessed using the Minnesota Living With Heart Failure Questionnaire, Katz Index of Independence in Activities of Daily Living questionnaire, and patient perception of overall well-being. Frailty was measured using the 10-m walk test and handgrip strength testing. Results In the overall cohort, participants demonstrated improvements in quality of life metrics, but deterioration in 10-m walk test and handgrip at 1 month. These trends continued at 1 year. However, patients in the lowest quintile of handgrip and 10-m walk test demonstrated a trend of improvements in these metrics during follow-up. Conclusions Despite improvements in quality of life after TAVI, no improvements in frailty were observed in patients at 1 year.Background & aims Nucleos(t)ide analogues (NUCs) effectively suppress serum HBV DNA. Previously, we have identified 21 patients with undetectable covalently closed circular DNA (cccDNA) upon long-term NUC therapy. This study investigated the effect of NUC withdrawal in patients with undetectable cccDNA. Methods Nineteen patients on long term NUCs (median 13.4 years) were recruited 13 were randomized to discontinue NUCs; 6 to continue taking NUCs. All had undetectable cccDNA at the time of last liver biopsy (median time 2.9 years prior to randomization). Serum HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg), liver biochemistry, and serum HBV RNA were monitored. learn more Results At the time of randomization, all patients had undetectable serum HBV DNA and HBV RNA. Twelve of the 13 patients had HBV DNA rebound to 100 IU/ml within 20 weeks of NUC discontinuation. The thirteenth patient had HBV DNA rebound at week 70. Three patients experienced biochemical flares after re-treatment win these patients and found that viral relapse could occur in patients with undetectable viral DNA. Further research is required to determine whether nucleos(t)ide analogue treatment can be discontinued in specific patients with chronic hepatitis B.Background Over 100 million children are parented by migrant workers in China. The aim of this study was to investigate how self-reported adolescent physical and mental health are associated with parental migration. Methods Based on cross-sectional data of 13996 students in 112 schools drawn from a nationally representative sample of middle school students in China, this study used self-reported measures for adolescent physical and mental health. Ordered logistic regression was used for the analysis of self-reported physical health, and linear regression was used for the analysis of self-reported mental health, both adjusting for socio-economic covariates and school fixed effects, to determine how adolescent health is associated with parental migration. Findings In urban areas, migrant adolescents were physically healthier (OR=1.19, 95% CI 1.03-1.36), and similarly mentally healthy (b=-0.07, 95% CI -0.37-0.23), compared to urban adolescents from intact families; in rural areas, left-behind adolescents were less physically (OR=0.84, 95% CI 0.76-0.94) and mentally (b=0.45, 95% CI 0.24-0.66) healthy than rural-intact adolescents, holding other variables constant. Left-behind adolescents had less close parent-adolescent relationships than rural-intact adolescents with both father (OR=0.63, 95% CI 0.56-0.71) and mother (OR=0.62, 95% CI 0.54-0.70). Interpretation Our study highlights a great need for health interventions aimed at left-behind adolescents in China and globally, and the important roles of parent-adolescent relationships in addressing the health needs of left-behind adolescents.Background End-of-life intensive care may be futile and can be a cause of distress to both patients and their families. This study aimed to understand the utilization of intensive care and its associated factors in patients with End-stage liver disease (ESLD) during terminal hospitalization. Methods Population-based retrospective cohort study using the National Health Institute Research Database of Taiwan. All adult patients with ESLD who died during their hospitalization in 2010-2013 were included. Findings Of the 14,247 patients with ESLD, the majority (60·8%) was comorbid with hepatocellular carcinoma (HCC). Patients with ESLD only were younger, more deprived, more alcohol-related, and less likely to receive palliative care prior to terminal hospitalization (6·0% vs 29·2% with HCC). Compared to patients with comorbid HCC, relatively more patients without HCC were admitted to ICU (59·6% vs 22·3%), receiving CPR (11·1% vs 4·3%) and mechanical ventilation (36·3% vs 12·5%) during terminal hospitalization. Etiology of alcoholic hepatitis, esophageal varices, septicemia, pneumonia and respiratory failure, and renal failure were associated with a higher probability of ICU admission (adjusted rate ratio (aRR) range 1·09-2·09). Prior palliative care was associated with lower probability of ICU admission (aRR range 0·24-0·38). Interpretation The intensive care utilization by patients with ESLD in their terminal hospitalization was substantial in Taiwan. Those who are not comorbid with HCC need more attention, especially in terms of their palliative care needs, choices regarding intensive care, and their healthcare utilization. Funding National Institute of Health Research Health Applied Research Collaboration (ARC) South London.Background Low vaccine uptake results in regular outbreaks of severe diseases, such as measles. Selective mandates, e.g. making measles vaccination mandatory (as currently implemented in Germany), could offer a viable solution to the problem. However, prior research has shown that making only some vaccinations mandatory, while leaving the rest to voluntary decisions, can result in psychological reactance (anger) and decreased uptake of voluntary vaccines. Since communicating the concept of herd immunity has been shown to increase willingness to vaccinate, this study assessed whether it can buffer such reactance effects. Methods A total of N = 576 participants completed a preregistered 2 (policy selective mandate vs. voluntary decision) × 2 (communication herd immunity explained yes vs. no) factorial online experiment (AsPredicted #26007). In a first scenario, the concept of herd immunity was either introduced or not and vaccination either mandatory or voluntary, depending on condition. The dependent variable was the intention to vaccinate in the second scenario, where vaccination was always voluntary. Additionally, we explored the mediating role of anger between policies and intentions. Findings Herd immunity communication generally increased vaccination intentions; selective mandates had no overall effect on intentions, and there was no interaction of the factors. However, selective mandates led to increased anger when herd immunity was not explained, leading in turn to lower subsequent vaccination intentions. Interpretation Explaining herd immunity can counter potential detrimental effects of selective mandates by preventing anger (reactance). Funding This study was funded by the University of Erfurt and the German Research Foundation (BE-3979/11-1).While granular active carbon (GAC) can effectively remove disinfection byproduct (DBP) precursors, its use has raised concerns over increased formation of some brominated DBP species in treated water following postchlorination, especially for waters with high bromide concentrations. The Information Collection Rule Treatment Study Database contains results of the most extensive GAC studies ever conducted nationwide. Data were analyzed to assess the extent of DBP speciation changes and overall reduction of brominated DBPs by GAC to gain new insights of the bromide effect. Results showed that formation of three brominated trihalomethanes (collectively, Br-THM3) varied greatly depending on TOC removal and bromide concentrations. Low TOC concentrations in GAC effluents resulted in greatly reduced Br-THM3 formation, except for a few cases where Br-THM3 formation increased. GAC followed by chloramination were likely to better control Br-THM3 formation for waters with high TOC and high bromide. Lastly, the chlorine demand reduction by GAC was quantified.Critical to the bacterial stringent response is the rapid relocation of resources from proliferation toward stress survival through the respective accumulation and degradation of (p)ppGpp by RelA and SpoT homologues. While mammalian genomes encode MESH1, a homologue of the bacterial (p)ppGpp hydrolase SpoT, neither (p)ppGpp nor its synthetase has been identified in mammalian cells. Here, we show that human MESH1 is an efficient cytosolic NADPH phosphatase that facilitates ferroptosis. Visualization of the MESH1-NADPH crystal structure revealed a bona fide affinity for the NADPH substrate. Ferroptosis-inducing erastin or cystine deprivation elevates MESH1, whose overexpression depletes NADPH and sensitizes cells to ferroptosis, whereas MESH1 depletion promotes ferroptosis survival by sustaining the levels of NADPH and GSH and by reducing lipid peroxidation. The ferroptotic protection by MESH1 depletion is ablated by suppression of the cytosolic NAD(H) kinase, NADK, but not its mitochondrial counterpart NADK2. Collectively, these data shed light on the importance of cytosolic NADPH levels and their regulation under ferroptosis-inducing conditions in mammalian cells.Introduction In the CASSINI study, rivaroxaban thromboprophylaxis significantly reduced primary venous thromboembolism (VTE) endpoints during the intervention period, but several thromboembolic events designated as secondary efficacy endpoints were not included in the primary analysis. This study was aimed to evaluate the full impact of rivaroxaban thromboprophylaxis on all prespecified thromboembolic endpoints occurring on study. Methods CASSINI was a double-blind, randomized, placebo-controlled study in adult ambulatory patients with cancer at risk for VTE (Khorana score ≥2). Patients were screened at baseline for deep-vein thrombosis (DVT) and randomized if none was found. The primary efficacy endpoint was a composite of lower extremity proximal DVT, symptomatic upper extremity, or lower extremity distal DVT, any pulmonary embolism, and VTE-related death. This analysis evaluated all prespecified thromboembolic endpoints occurring on study to determine the full benefit of rivaroxaban prophylaxis. All endpoints were independently adjudicated.
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