Development of Celiac Disease Therapeutics: The Sixth Gastroenterology Regulatory Endpoints and the Advancement of Therapeutics Workshop.

The Gastroenterology Regulatory Endpoints and the Advancement of Therapeutics VI Workshop, held on July 22, 2021, provided a forum for patients and representatives from academia, industry, patient advocacy groups, and Food and Drug Administration to discuss drug development for celiac disease (CeD). The workshop focused on the approach of histologic assessments in clinical trials, considerations for pediatric drug development, and the use of a gluten challenge (GC) in clinical trials. Given that no histologic scoring system is widely accepted for use in clinical trials at this time, early-phase clinical trials should ideally explore a variety of histologic scales and assess the histologic findings of CeD as individual measures to inform future trials. When planning pediatric drug development in CeD, appropriate use of extrapolation of efficacy data from adequate, well-controlled studies in adults could facilitate timely access to safe and effective therapies for pediatric patients. Identification of a fit-for-purpose pediatric clinical outcome assessment could further advance pediatric drug development. Histologic responses to the GC depend on exposure, dose, and duration; short exposures do not appear to cause long-term consequences. However, the GC should be incorporated into clinical trials in a thoughtful manner to generate interpretable results and ensure patient safety. Ongoing collaboration between all stakeholders will facilitate the development of safe and effective therapeutics for CeD.

The benefits, limitations and opportunities of preclinical models for neonatal drug development.

Increased research to improve preclinical models to inform the development of therapeutics for neonatal diseases is an area of great need. This article reviews five common neonatal diseases - bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, perinatal hypoxic-ischemic encephalopathy and neonatal sepsis - and the available in vivo, in vitro and in silico preclinical models for studying these diseases. Better understanding of the strengths and weaknesses of specialized neonatal disease models will help to improve their utility, may add to the understanding of the mode of action and efficacy of a therapeutic, and/or may improve the understanding of the disease pathology to aid in identification of new therapeutic targets. Although the diseases covered in this article are diverse and require specific approaches, several high-level, overarching key lessons can be learned by evaluating the strengths, weaknesses and gaps in the available models. This Review is intended to help guide current and future researchers toward successful development of therapeutics in these areas of high unmet medical need.

Effect of reading to preterm infants on measures of cardiorespiratory stability in the neonatal intensive care unit.

OBJECTIVE: To evaluate the impact of parental bedside reading (PR) on cardio-respiratory (CR) stability of preterm infants. METHODS/STUDY DESIGN: Prospective examination of the impact of PR on CR stability in preterm NICU infants. CR data from 3 time points: pre-reading (3 and 1 h before reading), during PR, and post-reading (1 h after reading) were compared. RESULTS: Eighteen infants born at 23-31wks gestation, and 8 to 56 days old, were enrolled. Episodes of oxygen desaturation to <85% were fewer during PR as compared to the pre-reading periods and were fewer with live and maternal PR. CONCLUSION: Preterm infants showed fewer desaturation events less than 85% during PR than prior to reading exposure. This effect persisted up to 1 h after reading exposure. Desaturation events were fewer with live and maternal PR. Voice exposure can be an important way for parents to participate in the care of their preterm infants.