Potentially Critical Driving Situations During "Blue-light" Driving: A Video Analysis.

Introduction: Driving with warning lights and sirens is highly demanding for ambulance drivers, and the crash risk is much higher than that during normal driving. In this study our goals were to establish a coding protocol to observe how often and how long potentially critical driving situations (PCDS) occur during "blue-light" driving (driving with emergency response lights) and to describe traffic and environmental conditions preceding and accompanying the PCDS.

Methods: We collected randomly drawn video data of real ambulance driving between 2014-2017 in two German federal states.

Traffic safety knowledge gain of ambulance drivers after simulator-based training.

Background: Compared to other road users, ambulance drivers are at a higher accident risk while driving with warning lights and sirens. No standard exists for training or education for emergency medical service employees driving ambulances. Training programs should positively influence knowledge.

Exposure-Response Analyses of Letermovir Following Oral and Intravenous Administration in Allogeneic Hematopoietic Cell Transplantation Recipients.

The cytomegalovirus (CMV) viral terminase inhibitor letermovir is approved for prophylaxis of CMV infection and disease in adult CMV-seropositive allogeneic hematopoietic stem cell transplantation recipients. In a phase III trial (NCT02137772), letermovir significantly reduced clinically significant CMV infection (CS-CMVi) rate vs. placebo through Week 24 (primary end point) and Week 14 (secondary end point) post transplantation.

Exposure-response analysis of adverse events associated with molibresib and its active metabolites in patients with solid tumors.

Molibresib (GSK525762) is an investigational orally bioavailable small-molecule bromodomain and extraterminal (BET) protein inhibitor for the treatment of advanced solid tumors. In the first-time-in-human BET115521 study of molibresib in patients with solid tumors, thrombocytopenia was the most frequent treatment-related adverse event (AE), QT prolongation was an AE of special interest based on preclinical signals, and gastrointestinal (GI) AEs (nausea, vomiting, diarrhea, and dysgeusia) were often observed. The aims of this analysis were the following: (i) develop a population pharmacokinetic (PK)/pharmacodynamic (PD) model capable of predicting platelet time courses in individual patients after administration of molibresib and identify covariates of clinical interest; (ii) evaluate the effects of molibresib (and/or its two active metabolites [GSK3529246]) exposure on cardiac repolarization by applying a systematic modeling approach using high-quality, intensive, PK time-matched 12-lead electrocardiogram measurements; (iii) evaluate the exposure-response (ER) relationship between molibresib and/or GSK3529246 exposures and the occurrence of Grade 2 or higher GI AEs.

Population pharmacokinetic modeling of molibresib and its active metabolites in patients with solid tumors: A semimechanistic autoinduction model.

Molibresib (GSK525762) is an investigational, orally bioavailable, small-molecule bromodomain and extraterminal (BET) protein inhibitor for the treatment of advanced solid tumors. Molibresib was initially evaluated in a first-time-in-human (FTIH) study BET115521 consisting of two parts: Part 1 of the study (dose escalation) was conducted in 94 patients with nuclear protein in testis midline carcinoma and other solid tumors, and Part 2 (expansion cohort) was conducted in 99 patients with different solid tumor types. Molibresib is metabolized by cytochrome P450 3A4 enzymes to produce two major active metabolites that are equipotent to the parent molecule.