Pooled analysis of routine safety parameters observed in healthy participants at baseline and following placebo administration in early phase clinical studies.

Phase I trials inform on the initial safety profile of a new molecule and impact whether further development is pursued or not. Understanding the effect of non-pharmacological factors on the variability of routine safety parameters could improve decision making in these early clinical trials, helping to separate signals related to the new molecule from background "noise." To understand the impact of non-pharmacological factors on routine safety parameters, we evaluated pooled safety data from over 1000 healthy participants treated with placebo in phase I trials between 2009 and 2018.

Disruption of Vitamin D Signaling Impairs Adaptation of Cerebrocortical Microcirculation to Carotid Artery Occlusion in Hyperandrogenic Female Mice.

Vitamin D deficiency contributes to the pathogenesis of age-related cerebrovascular diseases, including ischemic stroke. Sex hormonal status may also influence the prevalence of these disorders, indicated by a heightened vulnerability among postmenopausal and hyperandrogenic women. To investigate the potential interaction between sex steroids and disrupted vitamin D signaling in the cerebral microcirculation, we examined the cerebrovascular adaptation to unilateral carotid artery occlusion (CAO) in intact, ovariectomized, and hyperandrogenic female mice with normal or functionally inactive vitamin D receptor (VDR).

Ad Hoc Percutaneous Coronary Intervention in Stable Patients With Multivessel or Unprotected Left Main Disease.

Background: There is very little information about the use of ad hoc percutaneous coronary intervention (PCI) in stable patients with multivessel (MV) disease or unprotected left main (LM) disease patients for whom a heart team approach is recommended.

Objective: To identify the extent of ad hoc PCI utilization for patients with multivessel disease or left main disease, and to explore the inter-hospital variation in ad hoc PCI utilization for those patients.

Methods: New York State's cardiac registries were used to examine the use and variation in use of ad hoc PCI for MV/LM disease as a percentage of all MV/LM PCIs and revascularizations (PCIs plus coronary artery bypass graft procedures) during 2018 to 2019 in New York.

Considerations for Cell and Gene Therapy Programs Entering the Clinical Space.

Cell and gene therapy (CGT) describes a broad category of medicinal products with potential applications to prevent and treat human disease in multiple therapeutic areas. These therapies leverage the use of modified nucleic acids, altered cells or tissue, or both. The modality, mechanism, route of administration, and therapeutic indication for a CGT product will influence the challenges and opportunities for early clinical development, some of which may be highly specific to the product under consideration.