Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial—Protocol and statistical analysis plan

Introduction

Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.

Methods

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

Discussion

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.

     

Bilateral Implantation of Centromedian‐Parafascicularis Complex and GPi: A New Combination of Unconventional Targets for Deep Brain Stimulation in Severe Parkinson Disease

Objectives. Traditional deep brain stimulation (DBS) at the subthalamic nucleus (STN) has proved to be efficacious on core Parkinsonian symptoms. However, very disabling l ‐dopa–induced abnormal involuntary movements (AIMs) and axial signs are slightly affected, suggesting that we target less conventional targets. Our candidates for DBS were the globus pallidus internus (GPi) plus the intralaminar thalamic complex (Pf or CM), given its extensive functional links with basal ganglia nuclei. Materials and Methods. The routine utilization of our innovative stereotactic apparatus allows us to implant, at the same time, both the CM‐Pf complex together with the GPi in six Parkinson disease patients. Both intraoperative and postoperative neurophysiologic assessments helped us recognize functional subregions while optimizing implantation of electrodes. Unified Parkinson disease rating scale (UPDRS) motor scores, AIMs, and freezing were carefully blindly evaluated for each condition. Results. A significant amelioration of UPDRS scores was achieved by simultaneous activation of both targets. CM‐Pf activation was only slightly effective in reducing rigidity and akinesia, but more efficacious on freezing. Not surprisingly, AIMs were peculiarly decreased by the activation of the permanent electro‐catheter in the posteroventral GPi. Conclusions. These findings confirm that, in selected patients, it is conceivable to target structures other than the conventional STN in order to maximize clinical benefit.     

Zinc sulfate addition to glass-ionomer-based cements: influence on physical and antibacterial properties, zinc and fluoride release.

OBJECTIVES: The aim of this study is to evaluate the effect of ZnSO(4) addition to a conventional glass ionomer and a resin-modified glass ionomer on solubility, flexural strength, zinc and fluoride (F) release, and Streptococcus mutans growth inhibition. METHODS: 5 or 10% ZnSO(4) was added to Vitremer and Ketac-Fil powders. Solubility test was performed based on ISO 7489. Flexural strength was determined by 3-point bending test based on ISO 4049. Zn release/uptake was determined by atomic emission spectrometry; F release/uptake was measured using a F-specific electrode. Both release measurements were performed for 15 d before and 15 d after recharging. Antibacterial test was conducted according to agar plate methods against S. mutans, by measuring the inhibition halos in 1-h and 15-d specimens. Data were analyzed by ANOVA. RESULTS: Solubility increased with higher ZnSO(4) content, but remained below the ISO 7489 limit. Flexural strength was not affected by ZnSO(4) addition, and Vitremer performed better than Ketac-Fil. The control materials released no zinc. Vitremer with 10% ZnSO(4) released the highest amount of zinc. Fluoride release was similar for Ketac-Fil and Vitremer. In both cases, the highest amounts were released in the first 24 h. The growth inhibition halo of S. mutans was similar for both materials with highest content of ZnSO(4) and occurred only with 1-h specimens. SIGNIFICANCE: Zinc addition decreased microorganisms growth and improved fluoride release, without significantly affecting the materials' flexural strength and solubility.