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.

     

Removal of surface bacteria by irrigation

We examined the efficacy of various irrigation solutions delivered through a power irrigator to remove bacteria from three different surfaces. Titanium, stainless-steel, and cortical bone surfaces were coated with three different bacterial species: Staphylococcus aureus, Pseudomonas aeruginosa, and Staphylococcus epidermidis. They were then irrigated with 1 L of fluid delivered by jet lavage. The fluids tested were normal saline and solutions of bacitracin, neomycin, and soap. One set of specimens was not irrigated, as a control. After irrigation, the specimens were sonicated to remove residual bacteria, and the sonicate was quantitatively cultured to allow evaluation of the amount of residual bacteria on the surface. The results showed that removal of bacteria reflects an interaction between bacterial species, surface characteristics, and irrigation solution. Fewer bacteria were present in all the irrigation groups than in the control. Soap solution was as good as or better than any other solution at removing all three types of bacteria from all three surfaces, although not all of the pairwise comparisons were statistically significant. There was a significant advantage to soap solution over antibiotic irrigant or saline alone in removing Staphylococcus epidermidis from metallic surfaces. The use of a soap solution for irrigation seems to improve the removal of some bacteria from some surfaces in this experimental model and may represent a better type of irrigation additive.     

PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells

PADGEM protein (PADGEM), also known as GMP140, is a platelet alpha- granule membrane protein that is translocated to the external membrane after platelet activation. Although the biosynthesis of this protein was originally thought to be confined to megakaryocytes, the synthesis of PADGEM in endothelial cells was recently demonstrated (McEver et al: Blood 70:1974a, 1987). We now describe the subcellular localization of this protein in endothelial cells. Immunofluorescence staining of permeabilized human umbilical vein endothelial cells with KC4, a well characterized monoclonal antibody to PADGEM, showed positively stained elongated structures similar in distribution and shape to Weibel-Palade bodies. Their identity as Weibel-Palade bodies was confirmed by double label immunofluorescence using KC4 and a polyclonal antiserum to von Willebrand factor (vWf), a protein known to be specifically stored in these organelles. All Weibel-Palade bodies were found to contain PADGEM. In contrast to strong perinuclear staining produced with anti- vWf antibodies, no significant perinuclear staining was obtained with KC4, indicating that relatively little PADGEM is present in the endoplasmic reticulum and in the Golgi apparatus. In endothelial cells treated with secretagogues that stimulate vWf release the elongated structures positive for PADGEM disappeared, further identifying these structures as Weibel-Palade bodies. This observation extends the parallels between Weibel-Palade bodies and alpha-granules and suggests a possible functional association between vWf and PADGEM.     

Systemic lupus erythematosus with rectal stenosis simulating tumour or diverticulosis. Case report

A case of systemic lupus erythematosus (SLE) with focal involvement of the rectum is reported. The lesion roentgenologically resembled a malignant tumour and was resected. Histologic examination disclosed only typical SLE changes in a very restricted area, with the remaining gastrointestinal tract unaffected. This appears to be the first report of focal colitis as a complication of SLE. The case points the importance of suspecting symptoms from any organ system in patients with connective tissue disorders to be manifestations of that underlying pathology.     

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.     

Clinical Observations of Porcelain Veneers: A Three-Year Report

One hundred and sixty-five Cerinate porcelain veneers were placed by 11 private practice clinicians from diverse locations throughout the USA. The veneers were evaluated over a 3-year service period using Kodachrome photographs and grading of clinical characteristics by evaluators. The following factors were evaluated: (1) esthetics; (2) margin fit; (3) margin discoloration; (4) breakage; (5) gingival irritation; (6) patient acceptance; and (7) caries. Specific characteristics and their evaluations over three years were: (1) Esthetics started out excellent and remained that way; (2) Margin fit was acceptable at the beginning of the study and was actually perceived to improve, perhaps related to cement at the margins wearing and smoothing; (3) Margin discoloration started very low and became slightly worse; (4) Breakage was present during each of the 3 years, and 13 percent of veneers had some breakage after 3 years. Changes in clinical procedures are suggested in this paper to diminish this problem; (5) Gingival irritation was minimal throughout the study; (6) Patient acceptance was excellent at the beginning of the study and improved; and (7) Dental caries involvement was minimal, with only one veneered tooth showing caries involvement. Over the 3-year period, the veneers provided excellent service overall.