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.

     

Effect of respiratory training with a mouth-nose-mask in tetraplegics

Ten tetraplegics, 8 males and 2 females, with a median age of 32 years participated in a scheduled 6 weeks training programme with a respiratory muscle training mouth-nose-mask (RMT-mask) with a fixed expiratory and an increasing inspiratory resistance set by the tetraplegic in accordance to his/her increasing ability during the training period. During the 6 weeks the tetraplegics required to use the RMT-mask for 15 minutes three times a day. Before and after each training session they measured peak flow (PEF). Lung volumes, ventilatory and diffusion capacity were measured before and after the 6 weeks training period. The training resulted only in a significant change in the PEF, which increased with 11% from 371 l/min before to 412 l/min in average after the 6 weeks of training (p less than 0.025). This statistically significant increase was confirmed by the measurements of PEF performed by the tetraplegics themselves during the training period. In addition there was an increase in PEF from before to immediately after each 15 minutes training session, this trend reached statistically significance (p less than 0.025) in the third '2 weeks period'. These results might indicate a possibility of improving the tetraplegics ability to cough by use of a simple RMT-mask, which in turn might prevent certain lung complications including pneumonia, and atelectasia.     

Effects of growth hormone on glucose and fat metabolism in human subjects.

This article focuses on in vivo data from tests performed in normal subjects and in patients who had abnormal growth hormone (GH) status. Experimental data in human subjects demonstrate that GH acutely inhibits glucose disposal in skeletal muscle. At the same time GH stimulates the turnover and oxidation of free fatty acid (FFA), and experimental evidence suggests a causal link between elevated FFA levels and insulin resistance in skeletal muscle. Observational data in GH-deficient adults do not indicate that GH replacement is associated with significant impairment of glucose tolerance, but it is recommended that overdosing be avoided and glycemic control be monitored.     

Combined use of cryotherapy and diode laser photocoagulation for the treatment of threshold retinopathy of prematurity.

PURPOSE: Cryotherapy and indirect laser retinal photoablation are both effective in the treatment of retinopathy of prematurity (ROP). We describe the safety, efficiency, and effectiveness of combined cryotherapy and diode laser photocoagulation to treat threshold ROP. METHODS: Records of patients developing threshold ROP from January 1, 1996 through December 31, 1998, were retrospectively reviewed to identify those treated with combined cryotherapy and photocoagulation and followed up for at least 45 days postoperatively. Diode laser was used to ablate posterior avascular retina, and cryotherapy was used for anterior retina. Data reviewed included ocular and systemic complication rates, treatment duration, number of laser burns, most recent fundus examination, visual acuity, and refraction. RESULTS: In 13 patients, 23 eyes received combined treatment. No intraoperative complications occurred. Mean duration of anesthesia and treatment was 35 +/- 8 minutes/eye. A mean of 117 +/- 84 laser burns/eye were applied. In 20 of 23 eyes (87.0%), anatomic outcome was favorable at last examination. In 13 of 16 eyes (81.3%), functional (visual acuity) outcome was favorable (visual acuity better than 20/200) at 1 year. At 6 months or later, 14 of 16 eyes (87.5%) measured were myopic, of which 5 (31.3%) were highly myopic (> 6 diopters). CONCLUSIONS: The effectiveness of treating ROP with combined cryotherapy and diode laser photocoagulation compares with that of either modality alone. By decreasing the number of laser applications, combined therapy may be faster and technically easier for eyes with very posterior ROP. This may decrease the number of complications seen when either excessive cryotherapy or laser retinal photoablation is used.     

Migratory, invasive and metastatic capacity of NCAM transfected rat glioma cells

A cDNA encoding a transmembrane 140 kDa isoform of the neural cell adhesion molecule, NCAM, was transfected into the rat glioma cell line BT4Cn. Transfectants with a homogeneously high expression of NCAM-B showed a decreased capacity for penetration of an artificial basement membrane when compared to cells transfected with expression-vector alone or untransfected cells. However, when injected subcutaneously into nude mice, both NCAM expressing cells and control cells produced invasive tumors. Nude mice injected with NCAM positive cells developed tumors with slower growth rates as compared to those induced by NCAM negative cells. This implies that NCAM may not only be involved in adhesive and motile behaviour of glioma cells, but also in their growth regulation.     

Epidemiologie und Prävention von AIDS in der Bevölkerung

International Journal of Public Health - Die Übertragungswege des HIV, welche in der Bevölkerung eine Rolle spielen, sind heute bekannt. Neben der sexuellen Übertragung, der...     

Wear of the Christiansen hip prosthesis

The wear was examined in 39 Christiansen total hip prostheses, which were removed because of mechanical loosening after being used 5 (3-11) years. In the polyacetal acetabular cups, the head had made an eccentric defect, the mean volume of which was 680 (180-3310) mm³. The mean penetration of the head into the wall of the cup was 0.8 (0.1-3.2) mm. In two additional cups the head had penetrated right through the wall of the cup. In three prostheses the polyacetal sleeve of the trunnion was so worn that the head bore directly on the stem. There was a positive correlation between wear and the time the prostheses had been used before symptoms of loosening presented.     

Season of birth and risk of atopic disease among children and adolescents.

BACKGROUND: Season of birth (SOB) has been regarded as a risk factor for atopy. The aim of this study was to explore the relationship between season of birth (SOB) and later development of atopic disease in children and adolescents. METHODS: A total of 1,007 randomly selected subjects, 7 to 17 years of age, who were living in urban Copenhagen, Denmark were studied. All participants were interviewed about respiratory symptoms and possible risk factors for atopic disease. Skin test reactivity, serum total immunoglobulin E (IgE), and airway responsiveness were measured using standard techniques. RESULTS: The overall risk of atopy, as judged by skin test reactivity and serum total IgE, was the same regardless of SOB. On the contrary, asthma was more common in subjects born in the autumn compared with subjects born during the remaining part of the year (12.4% vs. 5.6%), OR = 2.40, 95% CI (1.56-3.94), p < 0.001. This was observed both for atopic asthma OR = 2.41, 95% CI (1.25-4.64), p = 0.007, non-atopic asthma, OR = 2.35, 95% CI (1.14-4.83), p = 0.02, and house dust mite (HDM) sensitive airway hyperresponsiveness, OR = 3.00, 95% CI (1.44-6.24), p = 0.002. Rhinitis and pollen allergy were not significantly related to SOB. CONCLUSIONS: Atopy itself is independent of season of birth, whereas asthma is more prevalent among subjects born during the autumn. Regarding asthma, these results suggest that the first months of life enclose a period of particular vulnerability towards environmental risk factors, especially exposure to aeroallergens like HDM.