Publications by authors named "G D Dear"

People with alternating hemiplegia of childhood undergoing general anesthesia are at risk for severe complications including critical bradycardia and hemiplegic incidents. We performed a 10-year historical cohort study and completed a subgroup analysis of patients who specifically underwent general anesthesia. Patients with ATP1A3 positive variants were compared with those without such variants.

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Operating rooms (ORs) use energy-intensive equipment such as anesthesia gas machines, patient monitors, and lights. They are major contributors to an institution's carbon footprint; yet ORs are unoccupied 40% of the time. Implementing an initiative to power down electrical devices can reduce energy consumption, equipment failure, and financial outlay.

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Background: Precise anesthesia delivery helps ensure amnesia, analgesia, and immobility. Conventionally, the end-tidal anesthetic concentration is maintained through manual adjustment of the fresh gas flow and anesthetic vaporizer output. Some anesthesia delivery systems can deliver and maintain clinician-selected end-tidal anesthetic agent (EtAA) concentration using a modified closed-loop system.

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Reactive metabolite formation is a major mechanism of hepatotoxicity. Although reactive electrophiles can be soft or hard in nature, screening strategies have generally focused on the use of glutathione trapping assays to screen for soft electrophiles, with many data sets available to support their use. The use of a similar assay for hard electrophiles using cyanide as the trapping agent is far less common, and there is a lack of studies with sufficient supporting data.

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The intent of this perspective is to share the recommendations of the International Consortium for Innovation and Quality in Pharmaceutical Development Metabolite Bioanalysis Working Group on the fit-for-purpose metabolite bioanalysis in support of drug development and registration. This report summarizes the considerations for the trigger, timing, and rigor of bioanalysis in the various assessments to address unique challenges due to metabolites, with respect to efficacy and safety, which may arise during drug development from investigational new drug (IND) enabling studies, and phase I, phase II, and phase III clinical trials to regulatory submission. The recommended approaches ensure that important drug metabolites are identified in a timely manner and properly characterized for efficient drug development.

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