Remdesivir and Mortality in Patients With Coronavirus Disease 2019.

BACKGROUND: The impact of remdesivir (RDV) on mortality rates in coronavirus disease 2019 (COVID-19) is controversial, and the mortality effect in subgroups of baseline disease severity has been incompletely explored. The purpose of this study was to assess the association of RDV with mortality rates in patients with COVID-19. METHODS: In this retrospective cohort study we compared persons receiving RDV with those receiving best supportive care (BSC). Patients hospitalized between 28 February and 28 May 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection were included with the development of COVID-19 pneumonia on chest radiography and hypoxia requiring supplemental oxygen or oxygen saturation ≤94% with room air. The primary outcome was overall survival, assessed with time-dependent Cox proportional hazards regression and multivariable adjustment, including calendar time, baseline patient characteristics, corticosteroid use, and random effects for hospital. RESULTS: A total of 1138 patients were enrolled, including 286 who received RDV and 852 treated with BSC, 400 of whom received hydroxychloroquine. Corticosteroids were used in 20.4% of the cohort (12.6% in RDV and 23% in BSC). Comparing persons receiving RDV with those receiving BSC, the hazard ratio (95% confidence interval) for death was 0.46 (.31-.69) in the univariate model (P < .001) and 0.60 (.40-.90) in the risk-adjusted model (P = .01). In the subgroup of persons with baseline use of low-flow oxygen, the hazard ratio (95% confidence interval) for death in RDV compared with BSC was 0.63 (.39-1.00; P = .049). CONCLUSION: Treatment with RDV was associated with lower mortality rates than BSC. These findings remain the same in the subgroup with baseline use of low-flow oxygen.

Brainstem dysfunction in chronic migraine as evidenced by neurophysiological and positron emission tomography studies.

BACKGROUND: The pathophysiology of chronic migraine (CM) is not fully understood. We aimed to examine transcranial magnetic stimulation (TMS) indices of cortical excitability in patients with CM and also performed PET studies to ascertain if there were any areas of activation and inhibition for possible correlation. METHODS: Excitability of the cortex was assessed by a reliable parameter of magnetic suppression of perceptual accuracy (MSPA) profiles using transcranial magnetic stimulation in 25 patients with CM. Of these 10 patients were also studied with ((18)F-FDG PET) scans. RESULTS: MSPA demonstrated decreased inhibition in CM compared to normal controls and episodic migraine. The percentage of letters reported correct at 100 ms was 84.37 for CM compared to 19.14 for normal controls and 57.41 for episodic migraine. The PET evaluation in 10 subjects demonstrated increased cerebral metabolism in areas of in the brainstem compared to the global flow. There were also decreased areas of cerebral metabolism in the medial frontal and parietal as well as the somatosensory cortex. CONCLUSIONS: Patients with CM appear to be characterized by reduced visual suppression correlating with high cortical excitability. In a cohort of these subjects there was brainstem activation and inhibition in certain areas of the cortex suggesting a potential dysfunction in the inhibitory pathways.