Browsing by Author "Yang, William E"

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Open Access
Pediatric Antibacterial and Antifungal Trials From 2007 to 2017.
(Pediatrics, 2018-09) Thaden, Joshua T; Chiswell, Karen; Jaffe, Ian; Bergin, Stephen P; Yang, William E; Romaine, Andrew; Roberts, Jamie; Nambiar, Sumathi; Farley, John; Benjamin, Daniel K; Smith, P Brian; Tsalik, Ephraim L
BACKGROUND AND OBJECTIVES:The impact of the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA) on pediatric antibacterial or antifungal drug trials is unknown. Our objective was to identify and characterize trials conducted under the BPCA and/or the PREA. METHODS:Pediatric antibacterial and antifungal drug trials with industry or US federal funding registered in clinicaltrials.gov from 2007 to 2017 were identified. Those conducted under BPCA and/or PREA were identified through US Food and Drug Administration and National Institute of Child Health and Human Development databases. RESULTS:Of 17 495 pediatric trials registered on clinicaltrials.gov between October 2007 and September 2017, 122 systemic antibacterial or antifungal drug trials with industry or US federal funding were identified. Of these 122 trials, 98 (80%) involved antibacterials only, 23 (19%) antifungals only, and 1 (1%) both antibacterials and antifungals. These represented <1% (122 of 17 495) of pediatric trials. Neither pediatric antibacterial nor antifungal drug trials commonly enrolled neonates 0 to 30 days old (30% [30 of 99] vs 42% [10 of 24], respectively). Pediatric antibacterial and antifungal trials were commonly industry funded (79% [78 of 99] and 83% [20 of 24], respectively). In total, 65% (79 of 122) of pediatric antibacterial and/or antifungal drug trials were conducted under BPCA and/or PREA. Researchers in trials conducted under BPCA and/or PREA, relative to non-BPCA and/or PREA trials, more often collected pharmacokinetic data (70% [55 of 79] vs 26% [11 of 43]). CONCLUSIONS:Although the majority of pediatric antibacterial and/or antifungal drug trials were conducted under BPCA and/or PREA, the overall number was low. Greater effort is needed to stimulate such trials.
Open Access
Transcriptomic Analysis of the Host Response and Innate Resilience to Enterotoxigenic Escherichia coli Infection in Humans.
(J Infect Dis, 2016-05-01) Yang, William E; Suchindran, Sunil; Nicholson, Bradly P; McClain, Micah T; Burke, Thomas; Ginsburg, Geoffrey S; Harro, Clayton D; Chakraborty, Subhra; Sack, David A; Woods, Christopher W; Tsalik, Ephraim L
BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is a globally prevalent cause of diarrhea. Though usually self-limited, it can be severe and debilitating. Little is known about the host transcriptional response to infection. We report the first gene expression analysis of the human host response to experimental challenge with ETEC. METHODS: We challenged 30 healthy adults with an unattenuated ETEC strain, and collected serial blood samples shortly after inoculation and daily for 8 days. We performed gene expression analysis on whole peripheral blood RNA samples from subjects in whom severe symptoms developed (n = 6) and a subset of those who remained asymptomatic (n = 6) despite shedding. RESULTS: Compared with baseline, symptomatic subjects demonstrated significantly different expression of 406 genes highlighting increased immune response and decreased protein synthesis. Compared with asymptomatic subjects, symptomatic subjects differentially expressed 254 genes primarily associated with immune response. This comparison also revealed 29 genes differentially expressed between groups at baseline, suggesting innate resilience to infection. Drug repositioning analysis identified several drug classes with potential utility in augmenting immune response or mitigating symptoms. CONCLUSIONS: There are statistically significant and biologically plausible differences in host gene expression induced by ETEC infection. Differential baseline expression of some genes may indicate resilience to infection.