Objective. A novel COVID-19 therapeutic, nirmatrelvir/ritonavir (Paxlovid), is commonly associated with reports of dysgeusia. The Food and Drug Administration Adverse Event Reporting System (FAERS) database was used to determine the real-world reporting of Paxlovid-associated dysgeusia (PAD), identify associated factors, and describe the relative reporting rates of dysgeusia for Paxlovid compared to other COVID-19 therapeutics (OCT), ritonavir alone, and other protease inhibitors (OPI).Study Design. Observational retrospective.Setting. Tertiary academic medical center.Methods. We collected patient and adverse event characteristics reported in the FAERS database between January 1968 and September 2022. Disproportionality analyses were used to compare the reporting of PAD to dysgeusia reported for OCT, ritonavir, and OPI.Results. 345,229 adverse events were included in the present study. Dysgeusia was a frequently reported Paxlovidassociated adverse event (17.5%) and was associated with nonserious COVID-19 infection (reporting odds ratio [ROR] 1.4; 95% confidence interval [CI] 1.2, 1.7) and female sex (ROR = 1.7; 95% CI 1.6, 1.9). Paxlovid was more likely to be associated with the reporting of dysgeusia compared to OCT
Objectives: Age-related changes to the larynx are associated with dysphonia and contribute to reduced quality of life. This study utilizes recurrent laryngeal motor nerve conduction studies (rlMNCS) to determine if neurophysiologic changes occur in the aging larynx using an aging rat model.Study Design: Animal study.Methods: In vivo rlMNCS were performed in 10 young hemi-larynges (3-4 months) and 10 aged hemi-larynges (18-19 months) rats (Fischer 344 Â Brown Norway F344BN). Recording electrodes were placed into the thyroarytenoid (TA) muscle through direct laryngoscopy. Recurrent laryngeal nerves (RLNs) were directly stimulated with bipolar electrodes. Compound motor action potentials (CMAPs) were obtained. RLN cross-sections were stained with toluidine blue. Axon count, myelination, and g-ratio were quantified utilizing AxonDeepSeg analysis software.Results: rlMNCS were successfully obtained in all animals. Mean CMAP amplitude and negative durations in young rats were 3.58 ± 2.20 mV and 0.93 ± 0.14 mS (mean dif: 0.17; 95% CI: À2.21 to 2.54), respectively, and 3.74 ± 2.81 mV and 0.98 ± 0.11 mS (mean dif: 0.050; 95% CI: À0.07 to 0.17). No significant differences in onset latency or negative area were observed. Mean axon count in young rats (176 ± 35) was comparable to that in old rats (173 ± 31). Myelin thickness and g-ratio did not differ between groups.Conclusions: There were no statistically significant differences in RLN conduction or axon histology between young and aged rats in this pilot study. This work provides a basis for future, adequately powered studies, and may lead to a tractable animal model to study the aging larynx.
Introduction/AimsDisease or injury can cause neuromuscular changes to the larynx that can affect voice, breathing, and swallowing. Motor nerve conduction studies have had limited use in the study of laryngeal neurophysiology, despite their importance in other anatomic sites. The aim of this study was to explore the feasibility of performing recurrent laryngeal motor nerve conduction studies (rlMNCS) in a rat model.MethodsrlMNCS were performed in 15 rats under anesthesia. A bipolar stimulating electrode was placed on the recurrent laryngeal nerve (RLN) 5 mm below the cricoid cartilage. Via direct laryngoscopy, a recording electrode was placed transorally into the thyroarytenoid muscle. The RLN was maximally stimulated to determine the compound muscle action potential (CMAP). Three consecutive trials were averaged.ResultsThe mean stimulating threshold to the RLN to achieve a CMAP from the thyroarytenoid was 1.7 ± 0.6 mA. RLN stimulation caused a visible adductor twitch of the vocal fold in all animals. The mean negative amplitude was 2.0 ± 0.8 mV, and the total area was 1.0 ± 0.4 mV ms. The CMAP latency and negative duration were 1.0 ± 0.1 ms and 0.9 ± 0.2 ms, respectively.DiscussionrlMNCS are feasible and may be useful in understanding laryngeal neurophysiology with disease or injury. This work could provide a tractable animal model for studying and monitoring treatment of neuromuscular conditions affecting voice, breathing, and swallowing.
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