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

Parenting Styles: A Closer Look at a Well-Known Concept

Although parenting styles constitute a well-known concept in parenting research, two issues have largely been overlooked in existing studies. In particular, the psychological control dimension has rarely been explicitly modelled and there is limited insight into joint parenting styles that simultaneously characterize maternal and paternal practices and their impact on child development. Using data from a sample of 600 Flemish families raising an 8-to-10 year old child, we identified naturally occurring joint parenting styles. A cluster analysis based on two parenting dimensions (parental support and behavioral control) revealed four congruent parenting styles: an authoritative, positive authoritative, authoritarian and uninvolved parenting style. A subsequent cluster analysis comprising three parenting dimensions (parental support, behavioral and psychological control) yielded similar cluster profiles for the congruent (positive) authoritative and authoritarian parenting styles, while the fourth parenting style was relabeled as a congruent intrusive parenting style. ANOVAs demonstrated that having (positive) authoritative parents associated with the most favorable outcomes, while having authoritarian parents coincided with the least favorable outcomes. Although less pronounced than for the authoritarian style, having intrusive parents also associated with poorer child outcomes. Results demonstrated that accounting for parental psychological control did not yield additional parenting styles, but enhanced our understanding of the pattern among the three parenting dimensions within each parenting style and their association with child outcomes. More similarities than dissimilarities in the parenting of both parents emerged, although adding psychological control slightly enlarged the differences between the scores of mothers and fathers

New directions for teaching and learning

Publ. comme no 27, fall 1986 de la revue New directions for teaching and learningBibliogr. à la fin des textesIndex: p. 101-10

Isotherm, Kinetic, and Selectivity Studies for the Removal of Ba-133 and Cs-137 from Aqueous Solution Using Turkish Perlite

The efficiency of Ba-133 and Cs-137 removal from aqueous solution is vital to mitigate ecological concerns over spreading these radionuclides in the environment. The present work focused on the use of Turkish perlite for the sorptive removal of Ba-133 and Cs-137 from aqueous solution by the radioindicator method. Perlite was characterized by XRF, XRD, FTIR, SEM-EDX, and BET analyses. The maximum percentage removals of 88.2% and 78.7% were obtained for Ba-133 and Cs-137 at pH 6 and pH 9, respectively. For both ions, the sorption equilibrium was attained relatively rapidly. Experimental kinetic data were well described with pseudo-second-order and intraparticle diffusion models. The uptake of both ions increased with the increase in metal concentration (1 x 10(-5) to 5 x 10(-2) mol/L) in solution. The maximum uptake capacities of Ba-133 and Cs-137 were found to be 1.96 and 2.11 mmol/g, respectively. The effect of competing ions decreased in the order of Ca2+ > K+ > Ni2+ > Na+ for Ba-133 sorption, whereas for Cs-137 sorption, the order was determined as Ca2+ > Ni2+ > K+ > Na+. Selectivity studies pointed out that sorption of Ba-133 onto perlite is preferable to Cs-137. Therefore, Turkish perlite is a promising, cost-effective, and efficient natural material for the removal of Ba-133 and Cs-137 from relatively diluted aqueous solution.Ministry of Education Youth and Sports; MEYS [CZ.02.1.01/0.0/0.0/16_019/0000728]; European Union-European Structural and Investment Funds, Operational Programme Research, Development and EducationThis work was performed under the auspices of Ministry of Education Youth and Sports; Project Nr. CZ.02.1.01/0.0/0.0/16_019/0000728: RAMSES-Ultra-trace isotope research in social and environmental studies using accelerator mass spectrometry is funded by MEYS and European Union-European Structural and Investment Funds, Operational Programme Research, Development and Education