Assessing Experiences With Trofinetide for Rett Syndrome: Interviews With Caregivers of Participants in Clinical Trials.

Purpose: Rett syndrome (RTT) is a rare neurodevelopmental disorder that mainly affects girls and women. Trofinetide is approved for the treatment of RTT in adults and children aged ≥2 years. To gain insight into experiences with RTT and effects of trofinetide treatment at different stages of RTT, interviews with caregivers of individuals with RTT were conducted upon their exit from the open-label trofinetide trials.

Population Pharmacokinetics of Trofinetide in a Pediatric Population Aged 2-4 Years with Rett Syndrome.

Introduction: Weight-banded trofinetide dosing improved physician- and caregiver-rated efficacy measures and had acceptable tolerability in patients aged 2‒4 years (DAFFODIL study) and 5‒20 years (LAVENDER study) with Rett syndrome (RTT). Selection of weight-banded dosing regimens for these studies was based on population pharmacokinetic (popPK) modeling and exposure simulations. This study applied an updated popPK model to confirm steady-state trofinetide exposures achieved in DAFFODIL patients were within target range.

Population Pharmacokinetic Modeling to Support Trofinetide Dosing for the Treatment of Rett Syndrome.

Introduction: Oral trofinetide administered using a body weight-banded dosing regimen was approved in the US for the treatment of Rett syndrome (RTT) in patients aged ≥ 2 years. This approval was principally based on efficacy and safety findings of the phase 3 LAVENDER study in girls and women aged 5-20 years with RTT and extended to younger children aged 2-4 years with supporting data from the DAFFODIL study. Weight-banded dosing regimens were selected based on early clinical population pharmacokinetic (popPK) modeling and different scenario simulations.

Perspectives on using peat records to reconstruct past atmospheric Hg levels.

Anthropogenic mercury (Hg) emissions to the atmosphere have increased the concentration of this potent neurotoxin in terrestrial and aquatic ecosystems. The magnitude of regional variation in atmospheric Hg pollution levels raises questions about the interactions between natural processes and human activities at local and regional scales that are shaping global atmospheric Hg cycling. Peatlands are potentially valuable and widespread records of past atmospheric Hg levels that could help address these questions.