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.

     

MR imaging of the labral-capsular complex: normal variations

Understanding the normal anatomy of the shoulder and its variations is important for the proper interpretation of MR images. This study was performed to describe variations in the normal labral-capsular complex as seen on MR images. MR images of 52 shoulders in 30 asymptomatic volunteers and 27 shoulders of symptomatic patients who had subsequent arthroscopy and/or reconstructive surgery were obtained with 1.5-T MR. The 52 scans of the asymptomatic group were reviewed by three radiologists in conference, and the assessment of labral shapes and capsular insertions was done by consensus. The 27 MR scans of the shoulders in the symptomatic group were reviewed by one radiologist before and after the asymptomatic cases were interpreted. Differences in these two interpretations were shown on receiver-operating-characteristic curves by using the results of subsequent arthroscopy and surgery as the gold standard. The anterior and posterior parts of the labra, respectively, varied in shape but showed several dominant features: triangular (45%, 73%), round (19%, 12%), cleaved (15%, 0%), notched (8%, 0%), flat (7%, 6%), and absent (6%, 8%). Most capsules inserted anteriorly on the labrum (47%) or glenoid rim (49%). All posterior insertions were on the labrum (100%). Intrinsic labral signal was noted on proton density-weighted images, but never on T2-weighted images. Receiver-operating-characteristic curves from interpretations of the symptomatic and clinical cases made before and after evaluation of the asymptomatic shoulders showed the interpretations improved considerably after scans of asymptomatic volunteers were studied. Our study reveals a wide variability in the MR appearance of the labral-capsular complex in asymptomatic shoulders.     

Radiation dose reduction during hysterosalpingography: an application of scanning-beam digital radiography

Hysterosalpingography was performed in 31 patients by means of a low-dose scanning-beam digital radiographic system. The technique permits adequate evaluation of gynecologic abnormalities while allowing significant reduction in radiation: 2.4-mR (6.1 X 10(-7) C/kg) exposure to the skin and 0.7-mrad (7 X 10(-6) Gy) mean dose to the ovaries per image obtained. Sixteen patients demonstrated readily recognizable and documented abnormalities, corroborated by laparoscopy, laparotomy, or other supportive evidence.     

Initially Accelerated Fractionation of the R1H Tumor of the Rat Increases Local Tumor Control and Might Reduce Impact of Overall Treatment Time

PURPOSE: To study the effect of treatment time prolongation following initial dose acceleration on the response of subcutaneously growing R1H tumor. MATERIAL AND METHODS: Continuous standard fractionation (30 fractions/40 days) was compared to initially accelerated treatment (30 fractions/21 days) followed by five to two fractions per week yielding total treatment times from 40 to 72 days. Local tumor control was assessed as endpoint. RESULTS: Radiation dose to control 50% of the tumors (TCD50%) decreased statistically significant from 83.5 Gy (95% confidence interval [CI]: 78.6 .. 88.4) for standard fractionation to 74.1 Gy (95% CI: 72.7 .. 75.5) determined for all accelerated treatment arms (p = 0.003). Prolongation of treatment time after initial acceleration from 40 to 72 days led to a small but statistically not significant increase in TCD50% from 72.0 Gy (95% CI: 71.0 .. 72.9) to 76.2 Gy (95% CI: 69.9 .. 82.4) corresponding to a repopulated dose of 0.9 Gy per week. This time factor is considerably smaller than for conventional radiation treatment as determined in previous experiments. CONCLUSION: The results indicate that initially accelerated irradiation not only improves local tumor control but also minimizes the negative effect of treatment time prolongation. This might be due to changes in tumor cell repopulation kinetics.     

Simultaneous assessment of blood flow in UVB-inflamed human skin by laser Doppler flowmetry and the 133-xenon washout technique.

The purpose of the study was to compare skin blood flow by laser Doppler flowmetry (LDF) and the 133-Xenon washout technique in UVB-inflamed human skin. Six healthy subjects participated in the study. Forearm skin blood flow was measured prior to irradiation and then 8, 24, 48 and 72 h after the exposure to twice the minimal erythema dose of UVB. Baseline blood flow as measured by the 133-Xenon washout method was 5.2 (range 3.0 to 10.4) ml/100g/min and LDF flux was 3.1 (range 2.7 to 5.7) arbitrary units. Following irradiation, maximum blood flow increase as evaluated by the 133-Xenon washout was 10.8 (95% confidence interval 3.7 to 11.3) times baseline blood flow, corresponding to an absolute blood flow of 47.5 (range 33.8 to 56.3) ml/100g/min. Maximum increase after induction of inflammation as assessed by LDF was 34.6 (95% confidence interval 24.6 to 56.5) times baseline flux. The two methods showed comparable time courses in all subjects. A significant correlation between the two methods was found, Spearman's rho = 0.54, p = 0.006. The relative LDF blood flow increase was 4.2-fold (95% confidence interval 2.7 to 5.0) greater than the increase measured by the 133-Xenon washout method. These results are at variance with previous comparative studies of the two methods. Some explanations are discussed.     

High Prevalence of Developmental Disabilities in Children Admitted to a General Pediatric Inpatient Unit

Objective: Evaluate a) the prevalence of developmental disabilities (DD) in children admitted to a general pediatrics inpatient unit, and b) the number of children admitted to the unit with previously undiagnosed developmental disability. Methods: Prevalence was evaluated through retrospective record review. Subjects: One hundred ninety children older than five months of age admitted to a general pediatric unit. Results: Of 190 children admitted, 155 (81.6%) had adequate developmental screening documented in the record. Forty-nine (25.7% of total, 31.6% of screened) had a developmental disability, 22 (12.1% of total, 14.8% of screened) had a previously unrecognized disability. Sample prevalence of DD was: cerebral palsy (6.8%), developmental delay or mental retardation (8.4%), language delay (4.6%), learning disability (8.2%), and hearing loss (1.5%). New diagnoses included: three children with probable mental retardation (MR), nine with learning disability (may include mild MR), seven with language delay, three with abnormal motor skills (fine and/or gross motor), one each of: neurofibromatosis type I, hearing loss, cerebral palsy, dysphagia. Some children had more than one new diagnosis. Conclusion: The prevalence of disabilities in a general pediatrics inpatient unit is much higher than the prevalence in the community. Because almost half of the disabilities were previously unrecognized, acute hospitalization is an excellent opportunity to conduct developmental screening.