Inflammation across tissues: can shared cell biology help design smarter trials?

Immune-mediated inflammatory diseases (IMIDs) are responsible for substantial global disease burden and associated health-care costs. Traditional models of research and service delivery silo their management within organ-based medical disciplines. Very often patients with disease in one organ have comorbid involvement in another, suggesting shared pathogenic pathways. Moreover, different IMIDs are often treated with the same drugs (including glucocorticoids, immunoregulators and biologics). Unlocking the cellular basis of these diseases remains a major challenge, leading us to ask why, if these diseases have so much in common, they are not investigated in a common manner. A tissue-based, cellular understanding of inflammation might pave the way for cross-disease, cross-discipline basket trials (testing one drug across two or more diseases) to reduce the risk of failure of early-phase drug development in IMIDs. This new approach will enable rapid assessment of the efficacy of new therapeutic agents in cross-disease translational research in humans.

Dimenhydrinate in children with infectious gastroenteritis: a prospective, RCT.

OBJECTIVE: Vomiting is a common symptom in children with infectious gastroenteritis. It contributes to fluid loss and is a limiting factor for oral rehydration therapy. Dimenhydrinate has traditionally been used for children with gastroenteritis in countries such as Canada and Germany. We investigated the efficacy and safety of dimenhydrinate in children with acute gastroenteritis. METHODS: We performed a prospective, randomized, placebo-controlled, multicenter trial. We randomly assigned 243 children with presumed gastroenteritis and vomiting to rectal dimenhydrinate or placebo. Children with no or mild dehydration were included. All children received oral rehydration therapy. Primary outcome was defined as weight gain within 18 to 24 hours after randomization. Secondary outcomes were number of vomiting episodes, fluid intake, parents' assessment of well-being, number of diarrheal episodes, and admission rate to hospital. We recorded potential adverse effects. RESULTS: Change of weight did not differ between children who received dimenhydrinate or placebo. The mean number of vomiting episodes between randomization and follow-up visit was 0.64 in the dimenhydrinate group and 1.36 in the placebo group. In total, 69.6% of the children in the dimenhydrinate group versus 47.4% in the placebo group were free of vomiting between randomization and the follow-up visit. Hospital admission rate, fluid intake, general well-being of the children, and potential adverse effects, including the number of diarrhea episodes, were similar in both groups. CONCLUSIONS: Dimenhydrinate reduces the frequency of vomiting in children with mild dehydration; however, the overall benefit is low, because it does not improve oral rehydration and clinical outcome.