Analysis of Depression and Anxiety Scores Following Initiation of Elexacaftor/Tezacaftor/Ivacaftor in Adults With Cystic Fibrosis.

Objective: Elexacaftor/tezacaftor/ivacaftor (E/T/I) has provided life-changing pharmacotherapy for many people with cystic fibrosis (CF), but conflicting literature exists regarding the effect on mental health. While some reports suggest E/T/I may induce adverse psychiatric symptoms, others report improvements in mental health symptoms. To add to this growing body of knowledge, we retrospectively analyzed depression and anxiety symptoms before and after E/T/I initiation in adults with CF at a single large US CF center.

A Workflow for Identifying Metabolically Active Chemicals to Complement Toxicity Screening.

The new paradigm of toxicity testing approaches involves rapid screening of thousands of chemicals across hundreds of biological targets through use of assays. Such assays may lead to false negatives when the complex metabolic processes that render a chemical bioactive in a living system are unable to be replicated in an environment. In the current study, a workflow is presented for complementing testing results with and techniques to identify inactive parents that may produce active metabolites.

Using exposure prediction tools to link exposure and dosimetry for risk-based decisions: A case study with phthalates.

A few different exposure prediction tools were evaluated for use in the new in vitro-based safety assessment paradigm using di-2-ethylhexyl phthalate (DEHP) and dibutyl phthalate (DnBP) as case compounds. Daily intake of each phthalate was estimated using both high-throughput (HT) prediction models such as the HT Stochastic Human Exposure and Dose Simulation model (SHEDS-HT) and the ExpoCast heuristic model and non-HT approaches based on chemical specific exposure estimations in the environment in conjunction with human exposure factors. Reverse dosimetry was performed using a published physiologically based pharmacokinetic (PBPK) model for phthalates and their metabolites to provide a comparison point.