Pediatric respiratory failure carries a wide differential diagnosis. Toxic ingestion should remain on the differential even at very young ages. There have been increasing reports of fentanyl overdoses among adults; however, this should be considered for accidental pediatric ingestion, especially considering its high potential for mortality. A nine-month-old female presented to the pediatric emergency department with respiratory failure. The patient was noted to be bradypneic with miotic pupils, and therefore, naloxone was given intravenously (IV) with a positive response. The patient required numerous boluses of intravenous naloxone, which ultimately saved her from intubation. The patient’s laboratory results were later positive for fentanyl and cocaine. Fentanyl ingestion has a high mortality rate, especially in pediatrics. With increasing fentanyl use, there is a potential for exposure due to not only child abuse and intentional toxicity but also exploratory ingestions.
Psoriasis plaque test is a model that allows intra-individual comparison of multiple topical drugs and formulations, useful early in the development of topical psoriasis agents. GSK2981278 is a retinoic acid receptor-related orphan receptor gamma inverse agonist preclinically shown to inhibit the production of Th17 cytokines implicated in the pathogenesis of psoriasis. The safety, tolerability and preliminary clinical effect of GSK2981278 were evaluated in a psoriasis plaque test. In this first-inhuman , single-center, randomized, vehicle-and positive-controlled, subject-and evaluator-blind trial, 15 psoriasis patients were enrolled (Study 201465). All subjects received 6 study treatments (0%, 0.03%, 0.1%, 0.8%, and 4% GSK2981278 ointment and betamethasone valerate 0.1% cream [positive control]) each applied to one of 6 randomly assigned small test fields on stable plaque(s) once daily over 19 days. The change in inflammatory infiltrate thickness measured by sonography was the primary endpoint. Four 3 mm punch biopsies (from non-lesional skin, untreated lesion, vehicletreated lesion, and 4%-treated lesion) were collected at the end of the study in 13 consenting subjects for gene expression analysis on Th17 related cytokines. There were no safety or tolerability findings. While the positive control showed the expected reduction in infiltrate thickness, there was no reduction in infiltrate thickness with any strength of GSK2981278. No meaningful changes in IL-17 related biomarkers or psoriasis disease signature were detected. These results may be explained by several factors: GSK2981278 did not penetrate the skin and reach the target cells in the dermis; higher concentrations and/or longer treatment period were needed to induce clinical effects; this target requires a blockade of activity over the entire plaque rather than that in a small test field or systemic blockade to induce clinical effects. Further investigation is planned. 250 CADM1 is a diagnostic marker in early-stage mycosis fungoides
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