Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

Xanthoma Tendinosum And Familial Hypercholesterolemia

A 40 year old female presented with multiple tendon xanthomas over extensor tendons of hands and feet, xanthelasma palpebrarum, arcus corneae and early atherosclerosis of retinal vessels. Investigations revealed normal triglycerides, very high plasma cholesterol and LDL levels, consistent with familial hypercholesterolemia (Fredrickson type lla). A work-up for cardiovascular involvement was normal and biopsy from one of the nodules showed xanthoma cells

Analytical mapping on trends of information technology in hydrometeorological disasters research

Hydrological and meteorological disasters have a massive global influence. These disasters result in colossal property loss, deaths, and societal disruption. Information and communication technologies can help to improve the disaster management process. This study presents an analytical mapping of hydrometeorological disasters and various ITs in hazard management. It assesses the global research state of IT-based hydrometeorological disaster management in terms of citations analysis, prolific journals, organizations, and countries’ contributions. Keyword co-occurrence analysis has been performed through visualization graphs to highlight research areas. VOSViewer and Bibliometrix R-package has been used for in-depth analysis and visualization requirements to identify the ICT patterns, core regions, academics, and research topics. The study highlights the emerging research areas in disaster management such as forecasting, disaster risk assessment, prediction, energy efficiency, alert generation, warning system and artificial intelligence, IoT, and cloud computing technologies have greater scope manage the disasters. This research illustrates the significance of information technology in hydrometeorological disasters and provides recommendations for future IT-assisted disaster management efforts

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Not AvailableH5N1 causes high mortality in domestic poultry. It is the causative agent of H5N1 flu and is the world's largest current pandemic threat. Haemagglutinin (HA) is a surface glycoprotein of the virus which facilitates viral attachment to target cell and its entry. HA frequently accumulates mutation to escape immune response of host. In this study, conserved amino acid sequences in HA2 subunit of H5N1 HA protein of both clade 2.2 and 2.3 were identified and the conserved sequence was further analyzed in silico for its antigenic index, hydrophilicity and surface probability. Six peptides showing potential antigenicity were selected and synthesized. Reactivity of the peptides were analysed by indirect ELISA using antisera against different subtypes of avian influenza. Five out of the six peptides showed reactivity. Thus, five epitopes in the conserved region of HA2 subunit of H5 could be identified which can detect positive serum against avian influenza.Not Availabl