Discovery of a Novel Potent and Selective Calcium Release-Activated Calcium Channel Inhibitor: 2,6-Difluoro--(2'-methyl-3'-(4-methyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)-[1,1'-biphenyl]-4-yl)benzamide. Structure-Activity Relationship and Preclinical Characterization.

The role of calcium release-activated calcium (CRAC) channels is well characterized and is of particular importance in T-cell function. CRAC channels are involved in the pathogenesis of several autoimmune diseases, making it an attractive therapeutic target for treating inflammatory diseases, like rheumatoid arthritis (RA). A systematic structure-activity relationship study with the goal of optimizing lipophilicity successfully yielded two lead compounds, and .

Prasugrel Versus Ticagrelor in Patients With CYP2C19 Loss-of-Function Genotypes: Results of a Randomized Pharmacodynamic Study in a Feasibility Investigation of Rapid Genetic Testing.

The feasibility of rapid genetic testing in patients undergoing percutaneous coronary intervention (PCI) and the comparison of the pharmacodynamic effects of prasugrel versus ticagrelor among carriers of cytochrome P450 2C19 loss-of-function alleles treated with PCI has been poorly explored. Rapid genetic testing using the Spartan assay was shown to be feasible and provides results in a timely fashion in a real-world setting of patients undergoing coronary angiography (n = 781). Among patients (n = 223, 28.

Pharmacodynamic Effects of Vorapaxar in Prior Myocardial Infarction Patients Treated With Potent Oral P2Y Receptor Inhibitors With and Without Aspirin: Results of the VORA-PRATIC Study.

Background Vorapaxar as an adjunct to dual antiplatelet therapy (DAPT) reduces thrombotic events in patients with prior myocardial infarction at the expense of increased bleeding. Withdrawal of aspirin has emerged as a bleeding reduction strategy. The pharmacodynamic effects of vorapaxar with potent P2Y inhibitors as well as the impact of dropping aspirin is unexplored and represented the aim of the VORA-PRATIC (Vorapaxar Therapy in Patients With Prior Myocardial Infarction Treated With Newer Generation P2Y Receptor Inhibitors Prasugrel and Ticagrelor) study.

Pharmacodynamic Effects of Vorapaxar in Patients With and Without Diabetes Mellitus: Results of the OPTIMUS-5 Study.

Vorapaxar reduces thrombotic cardiovascular events at the expense of increased bleeding. However, the differential pharmacodynamic (PD) effects of vorapaxar according to diabetes mellitus (DM) status are unknown. Moreover, although withdrawal of aspirin has emerged as a bleeding reduction strategy, the PD effects of stopping aspirin in patients treated with vorapaxar also are unknown.

Platelet Inhibition With Cangrelor and Crushed Ticagrelor in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

Background: The platelet inhibitory effects induced by oral P2Y receptor antagonists are delayed in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention (P-PCI). In turn, this leads to a gap in platelet inhibition, exposing patients to an increased risk of early thrombotic complications and underscoring the need to define strategies associated with more effective platelet inhibition in the peri-primary percutaneous coronary intervention period. Cangrelor is an intravenous P2Y inhibitor with prompt and potent antiplatelet effects.

Pharmacodynamic Effects of Switching From Ticagrelor to Clopidogrel in Patients With Coronary Artery Disease: Results of the SWAP-4 Study.

Background: Switching between different classes of P2Y inhibitors, including de-escalation from ticagrelor to clopidogrel, commonly occurs in clinical practice. However, the pharmacodynamic profiles of this strategy have been poorly explored.

Methods: This was a prospective, randomized, open-label study conducted in patients on maintenance dosing (MD) of aspirin (81 mg/d) and clopidogrel (75 mg/d).

Health informatics to optimize complex laboratory developed test configurations.

Background: Configuration of complex Laboratory Developed Tests (LDTs) is a time-consuming and complicated task, potentially leading to inconsistent LDTs in which features constraints remain unresolved and important features could remain unselected.

Objective: Our objective is to address these issues by presenting an automated, health informatics solution which autonomously optimizes feature selection in complex LDTs through Particle Swarm Optimization (PSO). The optimization goal is to minimize inconsistencies and configuration time, and maximize the number of selected features.

Cerebral venous sinus thrombosis in children: a multicenter cohort from the United States.

This study presents a large multicenter cohort of children with cerebral venous thrombosis from 5 centers in the United States and analyzes their clinical findings and risk factors. Seventy patients were included in the study (25 neonates, 35%). The age ranged from 6 days to 12 years.