21 research outputs found
Interactive Spaced Online Education in Pediatric Trauma
Pediatric resident trauma education is suboptimal due to lack of a curriculum and limited trauma experience and education resources. The objective of the study was to test knowledge retention and acceptability of interactive spaced education (ISE) in pediatric trauma. Prospective, randomized trial involving 40 physicians in a pediatric emergency department was used. Instrument was comprised of 48 multiple-choice questions (evaluative component) and answer critiques (educational component) on pediatric trauma divided into two modules. The instrument was assessed for test–retest reliability, item difficulty, and construct validity. Intervention consisted of online administration of each module as eight spaced emails (3 questions each) over a course of 4 weeks and was repeated after 2 and 4 months. Participants received an answer critique on committing to an answer. Primary outcome was difference in mean percentage of correct answers at 2 and 4 months versus baseline. Paired t test and effect size (d) were performed. Secondary outcome was exit-survey of ISE acceptability. There was significant improvement at 2 months (8.0, 95% confidence intervel [CI] = [3.6, 12.5], d = 0.75), but improvement at 4 months (1.6, 95% CI = [−4.5, 7.7], d = 0.18) was not significant. Sixty percent would retake and recommend ISE to others. Interactive, spaced education improves knowledge in pediatric trauma and is well accepted. Studies are required to determine the optimal spacing interval for this form of education
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
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Genome-wide identification of microRNAs regulating cholesterol and triglyceride homeostasis
Genome-wide association studies (GWASs) have linked genes to various pathological traits. However, the potential contribution of regulatory noncoding RNAs, such as microRNAs (miRNAs), to a genetic predisposition to pathological conditions has remained unclear. We leveraged GWAS meta-analysis data from >188,000 individuals to identify 69 miRNAs in physical proximity to single-nucleotide polymorphisms (SNPs) associated with abnormal levels of circulating lipids. Several of these miRNAs (miR-128-1, miR-148a, miR-130b, and miR-301b) control the expression of key proteins involved in cholesterol-lipoprotein trafficking, such as the low-density lipoprotein (LDL) receptor (LDLR) and the ATP-binding cassette A1 (ABCA1) cholesterol transporter. Consistent with human liver expression data and genetic links to abnormal blood lipid levels, overexpression and antisense targeting of miR-128-1 or miR-148a in high-fat diet–fed C57BL/6J and Apoe-null mice resulted in altered hepatic expression of proteins involved in lipid trafficking and metabolism, and in modulated levels of circulating lipoprotein-cholesterol and triglycerides. Taken together, these findings support the notion that altered expression of miRNAs may contribute to abnormal blood lipid levels, predisposing individuals to human cardiometabolic disorders.Organismic and Evolutionary Biolog
Highly efficient G-quadruplex recognition by bisquinolinium compounds.
International audienc
Interactive Spaced Online Education in Pediatric Trauma
Pediatric resident trauma education is suboptimal due to lack of a
curriculum and limited trauma experience and education resources. The objective of the
study was to test knowledge retention and acceptability of interactive spaced education
(ISE) in pediatric trauma. Prospective, randomized trial involving 40 physicians in a
pediatric emergency department was used. Instrument was comprised of 48 multiple-choice
questions (evaluative component) and answer critiques (educational component) on
pediatric trauma divided into two modules. The instrument was assessed for test–retest
reliability, item difficulty, and construct validity. Intervention consisted of online
administration of each module as eight spaced emails (3 questions each) over a course of
4 weeks and was repeated after 2 and 4 months. Participants received an answer critique
on committing to an answer. Primary outcome was difference in mean percentage of correct
answers at 2 and 4 months versus baseline. Paired t test and effect size (d) were
performed. Secondary outcome was exit-survey of ISE acceptability. There was significant
improvement at 2 months (8.0, 95% confidence intervel [CI] = [3.6, 12.5], d = 0.75), but
improvement at 4 months (1.6, 95% CI = [−4.5, 7.7], d = 0.18) was not significant. Sixty
percent would retake and recommend ISE to others. Interactive, spaced education improves
knowledge in pediatric trauma and is well accepted. Studies are required to determine
the optimal spacing interval for this form of education
Independent Ventilation and ECMO for Severe Unilateral Pulmonary Edema After SLT for Primary Pulmonary Hypertension
Evaluation of the time saved byprehospital initiation of reteplase forST-elevation myocardial infarction
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Proof-of-concept study to evaluate the safety and efficacy of saroglitazar in patients with primary biliary cholangitis
Saroglitazar is a novel peroxisome proliferator-activated receptor (PPAR) agonist with dual agonistic properties (α/γ). Due to a strong mechanistic rationale, we aimed to test the safety and efficacy of saroglitazar in patients with primary biliary cholangitis (PBC) who were either ursodeoxycholic acid (UDCA) resistant or intolerant.
In this double-blind, phase II proof-of-concept trial, 37 patients with PBC were randomized to saroglitazar 4 mg (n = 13), saroglitazar 2 mg (n = 14), or placebo (n = 10) daily for 16 weeks. The primary efficacy endpoint was the reduction in alkaline phosphatase (ALP) level at Week 16.
A significant reduction of mean ALP levels was observed at Week 16 relative to baseline in both the saroglitazar 4 mg (least-squares [LS] mean =-163.3 U/L, SE = 25.1, p <0.001) and 2 mg (LS mean =-155.8 U/L, SE = 24.4, p <0.001) groups, compared with placebo (LS mean =-21.1 U/L, SE = 28.9). Treatment with saroglitazar resulted in a rapid reduction of ALP concentration at Week 4 that was sustained through the study duration. At least 1 treatment-emergent adverse event occurred in 11 (84.6%) patients in the saroglitazar 4 mg group, in 12 (85.7%) patients in the 2 mg group and in 8 (80%) patients in the placebo group. Study drug was discontinued in 4 patients (3 patients in the 4 mg group and 1 patient in the 2 mg group) due to aminotransferase increases that promptly returned to baseline values after drug discontinuation.
Saroglitazar at 2 mg and 4 mg daily was tolerated and resulted in rapid and sustained improvements in ALP. Further studies are underway at a daily dose of 2 mg and 1 mg due to the higher incidence of elevated liver enzymes observed with the 4 mg dose.
NCT03112681
Saroglitazar resulted in a rapid and sustained improvement in alkaline phosphatase levels in patients with primary biliary cholangitis. The mean percentage reductions in alkaline phosphatase levels were 49% and 51% in the saroglitazar 4 mg and 2 mg groups compared to 3% in the placebo group.
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•Saroglitazar is a novel peroxisome proliferator-activated receptor (PPAR) agonist with dual agonistic properties (α/γ).•A statistically significant reduction in ALP levels was observed at Week 16 in saroglitazar 4 mg and 2 mg groups compared to placebo.•The reduction in ALP levels corresponded to a mean % reduction of 49% and 51% in the saroglitazar 4 mg and 2 mg groups, respectively