Background: Finite nucleos(t)ide analogue (NUC) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB). Aim:To quantify the incidence of severe hepatitis flares following NUC cessation in everyday clinical practice.Methods: This population-based cohort study enrolled 10,192 patients (male 71.7%, median age 50.9 years, cirrhosis 10.7%) who had received first-line NUCs for at least 1 year before discontinuing treatment. The primary outcome was severe flare with hepatic decompensation. We used competing risk analyses to assess event incidences and associated risk factors.Results: During a median follow-up of 2.2 years, 132 patients developed severe flares with hepatic decompensation, yielding a 4-year cumulative incidence of 1.8% (95% confidence interval [CI], 1.5%-2.2%). Significant risk factors were cirrhosis (adjusted sub-distributional hazard ratio [aSHR], 2.74; 95% CI, 1.82-4.12), manifestations of

1-Aminophytosphingosine and 6-aminogalactosyl phytosphingosine were prepared in 61% and 40% yield libraries with 44 carboxylic acids showed that a 4-butylbenzoic acid-derived product exe, respectively. Glycosylation using benzoylprotected lipid resulted in better -selectivity for ceramide analogs, but the yield was less than that obtained with benzyl moieties. Screening the amide rted less cytotoxicity. These analogs were purified for validation of immunological potencies and the -GalCer analog but not the sphingosine analog stimulated human iNKT cell population.

ImportanceThe incidence of inflammatory bowel disease (IBD) is increasing in newly industrialized countries but disease etiologies remain unclear.ObjectiveTo investigate the association between physical fitness and subsequent IBD risk among children and adolescents in Taiwan.Design, Setting, and ParticipantsThis nationwide cohort study was conducted between January 1, 2010, and December 31, 2018. Data sources included the Taiwan National Health Insurance Research Database, the National Student Fitness Tests Database, and the Air Quality Monitoring System Database. This study included students who were aged 10 years, completed physical fitness tests between grades 4 and 13, and had at least 1 year of follow-up. Data analysis was last performed on January 15, 2023.ExposuresPhysical fitness tests included cardiorespiratory endurance (CE; number of minutes to complete an 800-m run), musculoskeletal endurance (ME; number of bent-leg curl-ups in 1 minute), musculoskeletal power (MP; standing broad jump distance), and flexibility fitness (FF; 2-leg sit-and-reach distance).Main Outcomes and MeasuresSubsequent risk of IBD was compared among students based on physical fitness test results. Six-year cumulative incidences and hazard ratios (HRs) were calculated after adjusting for competing mortality. Performance was reported in quantiles, ranging from 1 (best) to 4 (poorest).ResultsThere were 4 552 866 students who completed physical fitness tests between grades 4 and 13; among these students, 1 393 641 were aged 10 years and were included in the analysis. Six-year cumulative incidence of IBD risk was lowest among students in the best-performing quantile of CE (quantile 1, 0.74% [95% CI, 0.63%-0.86%]; P < .001), ME (0.77% [0.65%-0.90%]; P < .001), and MP (0.81% [0.68%-0.93%]; P = .005) compared with students in quantiles 2 through 4, respectively; however, no association was observed for quantiles of FF. After adjusting for competing HRs for mortality and other confounders, better CE was inversely associated with IBD risk (adjusted HR, 0.36 [95% CI, 0.17-0.75]; P = .007). Other measures of physical fitness were not independently associated with IBD risk.Conclusions and RelevanceThe results of this study suggest that CE was inversely associated with IBD risk among children and adolescents, but ME, MP, and FF were not independently associated with IBD risk. Future studies that explore the mechanisms are needed.

Abstract Background Higher bullous pemphigoid (BP) risk has been reported to be associated with dipeptidyl peptidase 4 inhibitor (DPP4i). However, large-scale studies to investigate the association between BP and DPP4i treatment are limited. The aim of this study is to examine the association between BP risk and DPP4i treatment in diabetes patients. Methods We conducted a nationwide cohort study based on the Taiwan National Health Insurance Database between 2000 and 2015. 124,619 diabetic patients who were receiving DPP4i therapy were matched 1: 1 with diabetic patients who had never received DPP4i by age, sex, duration of diabetes, insulin usage, and propensity score-matching of comorbidities. Results Of the 124,619 diabetes patients in the two groups, the mean age at diabetes diagnosis was 52.4 ± 10.9 years, with a mean duration of diabetes of 6.0 ± 3.9 years. After adjusting for competing mortality risk, the 6-year cumulative incidence of BP in the DPP4i-treated cohort was significantly higher than that in the non-DPP4i group (0.74 per 1000; 95% confidence interval [CI]: 0.51–1.05 vs 0.38 per 1000; 95% CI: 0.26–0.53, P = .001). The DPP4i and insulin-treated group had the highest 6-year cumulative incidence for BP (0.93; 95% CI: 0.54–1.54 per 1000). Modified Cox regression analysis revealed that DPP4i treatment (HR: 2.15, 95% CI: 1.18–3.91, P = 0.01), age (HR: 1.06, P < .001), renal disease (HR: 2.32, P < .001), and metformin user (HR: 1.93, P = 0.006) were associated with increased BP risk. Conclusion DPP4i users had a 2.2-fold increase in the risk of BP, and the risk was the highest in those with concomitant use of DPP4i and insulin. The use of DPP4is as anti-diabetic medications must be monitored carefully and may be replaced by other anti-diabetic medications in BP patients.

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