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.

     

New aspects of surgical treatment of cholelithiasis

The interventional endoscopy and new knowledge about the spontaneous course of the cholelithiasis have obtained a far-reaching influence on the indication for operation and the surgical approach. Now as ever the adequate therapy of the symptomatic cholecystolithiasis consists in the early cholecystectomy. Since in the natural course the risk of lethality is small the operation for indication depending on the age and the risk factors given must be made cautiously. This in a still higher degree concerns the asymptomatic cholelithiasis in which at present no general indication for operation is regarded necessary. Due to the low lethality of circa 1% the endoscopic papillotomy has become the therapeutic method of choice in residual and recurrent calculi after cholecystectomy, but also in risk patients with cholecystocholedocholithiasis. The endoscopic papillotomy with stone extraction before the operation suggests a decrease of the operation lethality of 3 to 5% after cholecystectomy with revision of the choledochus.     

Efficacy of anticholinergic and beta-adrenergic agonist treatment of maximal cholinergic bronchospasm in tracheally intubated rabbits.

Cholinergically induced bronchoconstriction is thought to be a major cause of bronchospasm during anesthesia. We used tracheally intubated rabbits (4-mm endotracheal tube) stimulated with methacholine to assess the efficacy of beta-adrenergic agonist and anticholinergic treatment in reversing the increases in respiratory system resistance. Four groups were compared: (a) inhaled metaproterenol, 20 puffs via metered dose inhaler (0.65 mg/puff); (b) inhaled ipratropium bromide, 20 puffs from a metered dose inhaler (18 micrograms/puff); (c) 2 mg of intravenous atropine; and (d) no treatment after methacholine challenge as a control group. Methacholine increased respiratory system resistance from 0.041 +/- 0.001 (mean +/- SEM) to 0.098 +/- 0.006 cm H2O.mL-1.s-1 (P < 0.001). Whereas beta-adrenergic agonist treatment was ineffective in ameliorating bronchoconstriction, inhaled ipratropium bromide and atropine were highly effective, causing an 86%-88% reversal in the methacholine-induced increase in respiratory system resistance. Both these agents were also effective in improving dynamic compliance. We conclude that inhaled ipratropium bromide is effective in treating cholinergic bronchospasm even when administered via a small endotracheal tube and that the beta-adrenergic agonist metaproterenol is ineffective in rabbits in the face of maximal cholinergic stimulation.     

Intramedullary pilocytic astrocytomas — a clinical and morphological study after combined surgical and photon or neutron therapy

Ten patients suffering from intramedullary pilocytic astrocytomas (WHO-classification: astrocytoma grade I) were investigated catamnesticly. Combined surgery and radiotherapy was performed. Seven patients received neutron irradiation postoperatively. In four cases the neurological symptoms were improved after follow-up periods ranging from 33 to 89 months. The three other patients died after 6 to 21 months. The autopsy findings of a 14 year old child are presented. Our results are compared with reports in the literature. In addition, long-term problems of the spinal column are discussed. It seems that the combined surgical and neutron therapy improves the prognosis of pencil gliomas.     

Prematurity Stereotyping by Mothers of Premature Infants

Previous research has experimentally documented a prematuritystereotype in college students and mothers of full-term infants.The present investigation extends the scope of earlier studiesto mothers of premature infants. Thirty-two mothers of prematureinfants viewed four videotapes of 9-month-old full-term infants,each labeled either full-term or premature and either male orfemale. When infants were labeled premature the mothers perceivedthem as littler, finer featured, weaker, more passive, and slowerthan infants labeled full-term. The mothers also perceived labeledboys as bigger than labeled girls. Differences in stereotypingbetween the mothers in this study and both mothers of full-terminfants and college students are identified and discussed. Resultssuggest that mothers of premature infants expect deficits inpremature infants' physical development but not in prematureinfants' mental or social development. The likely sources andpossible self-fulfilling nature of these biased perceptionsare considered     

Stem cell research and cell transplantation for myocardial regeneration.

Several human organs are not capable of functional regeneration following a tissue defect and react with scar formation. In stem cell transplantation, undifferentiated or partly differentiated precursor cells are applied to defective tissue for therapeutic regeneration. After promising preclinical investigations, the transplantation of autologous stem cells for myocardial infarction treatment is being transferred to clinical use. Mesenchymal stem cells and endothelial precursor cells derived from the bone marrow or circulating blood as well as skeletal myoblasts are employed in clinical trials. Furthermore, indications for cell transplantation and delivery routes vary considerably throughout current investigations. Initial results suggest a potential for restoration of cardiac function in stem cell-treated patients; however, the mechanisms are not fully understood. This overview will focus on objectives, recent achievements, and future perspectives of diverse stem cell transplantation approaches.     

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