Clinical Pharmacology and Approach to Dose Selection of Emestedastat, a Novel Tissue Cortisol Synthesis Inhibitor for the Treatment of Central Nervous System Disease.

This review demonstrates the value of central pharmacodynamics (PD), including positron emission tomography (PET) and computerized cognitive testing, to supplement pharmacokinetic (PK) and peripheral PD for determining the target dose range for clinical efficacy testing of emestedastat, an 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitor. Combined data from 6 clinical trials in cognitively normal volunteers and patients with Alzheimer disease included a population PK model, endocrine PD, a human PET trial (11β-HSD1 brain imaging), and computerized cognitive testing. PK and PET findings were similar in volunteers and patients with Alzheimer disease.

CRKL Gene Deletion in Familial Zinner (OSVIRA) and OHVIRA Syndromes.

We present the first description of a family in which 2 siblings show alternative expression of CRKL gene deletion as the phenotypes of Zinner (OSVIRA, obstructed seminal vesicle and ipsilateral renal agenesis) and OHVIRA (obstructed hemivagina with an ipsilateral renal anomaly) syndromes. The male infant with Zinner syndrome and his sister aged 5 years with OHVIRA syndrome both have a paternally inherited 703-kb deletion at chromosome 22q11.21 that includes CRKL.

Ultra-Widefield Optical Coherence Tomography Beyond the Ora Serrata in Retinopathy of Prematurity.

Importance: Capturing high-quality images of the entire peripheral retina while minimizing the use of scleral depression could increase the quality of examinations for retinopathy of prematurity (ROP) while reducing neonatal stress.

Objective: To evaluate whether an investigational handheld ultra-widefield optical coherence tomography (UWF-OCT) device without scleral depression can be used to document high-quality images of the peripheral retina for use in ROP examinations.

Design, Setting, And Participants: This was a prospective, cross-sectional study in the neonatal intensive care unit at a single academic medical center.

Risk treatment thresholds for initiating cardiovascular disease pharmacotherapy: Synthesis of international evidence to support guideline recommendations.

Background: A new Australian guideline for cardiovascular disease (CVD) risk assessment and management was published in 2023, including new risk treatment thresholds.

Objective: This article summarises the published peer-reviewed global evidence that informed guideline recommendations on risk treatment thresholds for initiating blood pressure- and lipid-lowering therapy for CVD primary prevention.

Discussion: Evidence from 13 meta-analyses, randomised controlled trials and modelling studies involving more than 515,700 patients showed that preventive pharmacotherapy reduced the number of CVD events at all risk levels.