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.

     

Cognitive function after on or off pump coronary artery bypass grafting.

OBJECTIVE: To investigate cognitive outcome after on and off pump coronary artery bypass grafting. METHODS: Seventy patients between 50 and 80 years with stable angina pectoris, ejection fraction >30%, serum creatinine <150 micromol/l, and lack of tight main stem stenosis were randomized to on or off pump coronary artery bypass grafting. Standardized neuropsychological tests evaluated attention, verbal and visuo-spatial short-term and working memory, verbal learning, delayed recall, visuo-motor speed, and aspects of executive functions. Levels of anxiety and depression were also investigated. Testing was performed before and at 1 week, 1 and 6 months after surgery. RESULTS: There was no difference in cognitive impairment (defined as a 20% reduction in at least 20% of the tests) between groups. The incidence at 1 week post-operatively was 57% in the on pump group and 58% in the off pump group, after 1 month 30% and 12% and after 6 months 19% and 15%, respectively (p for interaction=0.19). There was no difference between groups in anxiety (p=0.18) or depression (p=0.48). CONCLUSIONS: This prospective, randomized study showed no differences in post-operative cognitive function after on pump compared to off pump coronary artery bypass grafting in low risk patients.     

Renal growth after neonatal urinary tract infection

This study presents the result of 12–21 years' follow-up in a group of children with neonatal urinary tract infection (onset within 1 month after birth) in whom early renal growth retardation was noted without concomitant classical renal scarring. In all cases the neonatal infection was diagnosed and treated within a few days of onset and the patients were closely supervised thereafter. Renal length, parenchymal thickness and area were measured at urography. At first follow-up (22 children, mean age 4.1 years) a significant reduction of renal parenchymal thickness was noted. Long-term follow-up (18 patients, mean age 17 years) demonstrated a normalization of renal size in the entire group, although less complete in the subgroup with reflux. There were two major findings in the present study. Firstly, renal growth retardation was seen after neonatal infection, both with and without reflux. Secondly, normalization of renal size in previously small kidneys was demonstrated, suggesting that growth retardation can be a reversible phenomenon. The tendency for such normalization was slightly more marked in children without reflux. Reduction of parenchymal thickness without calyceal deformity, therefore, does not necessarily mean irreversible damage, and differentiation between permanent scarring and temporary growth retardation can thus only be made at later follow-up, possibly not until after puberty. The demonstration of renal growth retardation in spite of early diagnosis and treatment emphasizes the great vulnerability of the kidney in the newborn.     

Decreasing incidence of peptic ulcer complications after the introduction of the proton pump inhibitors, a study of the Swedish population from 1974–2002

Background  

Despite a decreasing incidence of peptic ulcer disease, most previous studies report a stabile incidence of ulcer complications. We wanted to investigate the incidence of peptic ulcer complications in Sweden before and after the introduction of the proton pump inhibitors (PPI) in 1988 and compare these data to the sales of non-steroid anti-inflammatory drugs (NSAID) and acetylsalicylic acid (ASA).     

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.