Classification challenges in the field of eating disorders: can severe and enduring anorexia nervosa be better defined?

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The impact of human herpesvirus detection in pemphigus vulgaris

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Evaluation of the effects of formulation, food, or a proton-pump inhibitor on the pharmacokinetics of glasdegib (PF-04449913) in healthy volunteers: a randomized phase I study

Abstract

Purpose

To demonstrate the bioequivalence of the planned maleate salt-based commercial glasdegib tablet formulation [International Council for Harmonization (ICH) glasdegib] to the clinical di-hydrochloride (di-HCl) salt-based glasdegib formulation (di-HCl glasdegib). Additionally, to estimate the effects of a high-fat, high-calorie meal and proton-pump inhibitor (PPI) on the pharmacokinetics of ICH glasdegib.

Methods

This Phase I open-label study (ClinicalTrials.gov: NCT03130556) enrolled 24 healthy subjects to receive two different tablet formulations of single-dose 100-mg glasdegib under fasted conditions. A subset of healthy volunteers (n = 12) received single-dose 100-mg ICH glasdegib following a high-fat, high-calorie meal or concurrently with a PPI (rabeprazole).

Results

The adjusted geometric mean ratio (ICH glasdegib:di-HCl glasdegib) and 90% confidence intervals (CI) of area under the plasma concentration–time curve from time zero to infinity (AUC_inf) and maximum plasma concentration (C_max) were 104.0% (99.7‒108.5%) and 101.6% (96.1‒107.4%), respectively, within the acceptance range for bioequivalence (80‒125%). The adjusted geometric mean ratio (90% CIs) for AUC_inf and C_max under fed conditions were 84.3% (78.6‒90.6%) and 69.0% (61.8‒77.0%), respectively, relative to fasted conditions. When ICH glasdegib was administered concurrently with the PPI, the adjusted geometric mean ratio (90% CI) of AUC_inf and C_max were 100.6% (93.2‒108.6%) and 80.5% (70.7‒91.6%), respectively, relative to fasted conditions. Glasdegib was generally well tolerated under all conditions studied.

Conclusions

The ICH glasdegib tablet formulation was bioequivalent to the clinical di-HCl formulation under fasted conditions. A high-fat, high-calorie meal or concurrent PPI treatment had a minimal effect on glasdegib exposure, and was not considered clinically meaningful.

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Dermatitis and alopecia in a patient treated with dupilumab: a new adverse effect?

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Large-scale comparative neuroimaging: Where are we and what do we need?

Publication date: Available online 8 December 2018

Source: Cortex

Author(s): Michel Thiebaut de Schotten, Paula L. Croxson, Rogier B. Mars

Abstract

Neuroimaging has a lot to offer comparative neuroscience. Although invasive "gold standard" techniques have a better spatial resolution, neuroimaging allows fast, whole-brain, repeatable, and multi-modal measurements of structure and function in living animals and post-mortem tissue. In the past years, comparative neuroimaging has increased in popularity. However, we argue that its most significant potential lies in its ability to collect large-scale datasets of many species to investigate principles of variability in brain organisation across whole orders of species—an ambition that is presently unfulfilled but achievable. We briefly review the current state of the field and explore what the current obstacles to such an approach are. We propose some calls to action.

https://ift.tt/2B62KEN

Large Font Patient Written Instructions

Publication date: Available online 8 December 2018

Source: Journal of the American Academy of Dermatology

Author(s): Christopher Dallo, Brett Neill, Zachary Bryan, Daniel Aires

https://ift.tt/2B5L4sV