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.

     

Use of an in vitro model of tissue-engineered human skin to study keratinocyte attachment and migration in the process of reepithelialization

To produce a stable epidermis, keratinocytes need to be firmly attached to the basement membrane. However, following wounding, keratinocytes are required to develop a migratory phenotype in order to reepithelialize the wound. To investigate some of the issues underlying reepithelialization, we have developed a three-dimensional in vitro model of tissue-engineered skin, comprising sterilized human dermis seeded with human keratinocytes and dermal fibroblasts. Using this model, we have shown that the inclusion of fibroblasts within the model increases the stability of keratinocyte attachment. We have also demonstrated that keratinocyte migration occurs most effectively in the absence of a basement membrane and following the inclusion of fibroblasts in the model. In addition, subjecting the keratinocyte layer to mechanical trauma induces a migratory phenotype. We conclude that this three-dimensional in vitro wound model can be used to increase our understanding of the factors that enhance keratinocyte migration and hence wound healing in vivo.     

Kawasaki disease in Auckland, 1979-1988

Records of 34 children diagnosed as having Kawasaki disease in the Auckland region from 1979 to 1988 inclusive were reviewed. Diagnostic and associated features were similar to those reported from North America and Japan. The incidence (average 5.1 per year per 100,000 less than 5 years of age) was similar to that reported in Europe and North America amongst nonorientals and was similar in Polynesians and nonPolynesians. Coronary artery abnormalities were found in five cases (15%), and two cases, both of whom presented before five months of age, died. Those with abnormal coronary arteries had fever for a significantly longer period than those with normal coronary arteries.     

BUILDING COMMUNITY: Developing Skills for Interprofessional Health Professions Education and Relationship-Centered Care

In 1995, the National League for Nursing commissioned a Panel on Interdisciplinary/Transdisciplinary Education. The focus of the Panel's work was to examine educational issues that transcend the health professions and to make recommendations for future implementation of an interdisciplinary approach to addressing them. This article is being simultaneously published by several professional journals. The goal is to seek as much feedback as possible.     

Community home-based care in a rural village: challenges and strategies.

In Botswana, there has been an increase in community home-based care (CHBC) following a shift from hospital care to CHBC because of the HIV/AIDS epidemic. Yet the health care system has limited resources. To fulfill one of the terms of reference of the World Health Organization Collaboration Centre at the Department of Nursing, University of Botswana, an outreach program was developed in collaboration with 18 lay volunteers in a nearby village, Mmopane. This article discusses the process of establishing the CHBC committee and the challenges faced by faculty, students, and lay caregivers in working with a diverse CHBC group to render culturally sensitive care. Strategies for dealing with these challenges are discussed.     

Physical activity patterns in chronic hemodialysis patients: comparison of dialysis and nondialysis days.

OBJECTIVE: To determine physical activity patterns in chronic hemodialysis patients with a specific emphasis on the difference between dialysis and nondialysis days. Design A cross-sectional single-center study. SETTING: Vanderbilt University Outpatient Dialysis Unit. PATIENTS: Twenty current chronic hemodialysis patients: 10 male, 10 female; 15 black, 5 white; mean age, 50.1 +/- 9.9 years; height, 164.5 +/- 10.9 cm; weight, 82.5 +/- 15.4 kg; length on dialysis, 57.3 +/- 45.3 months. METHODS: Minute-by-minute physical activity was assessed over a 7-day period using a triaxial accelerometer, which consists of raw numbers or counts calculated by the 3 axes of the accelerometer (PA counts). PA counts were extrapolated on a daily and hourly basis. Physical functioning tests included: sit-to-stand, 6-minute walk, and 1-repetition maximal leg press exercise. Laboratory values for serum concentrations of albumin, prealbumin, C-reactive protein, and cholesterol were also collected. MAIN OUTCOME MEASURE: PA counts. RESULTS: Total PA counts were significantly lower on dialysis days when compared with nondialysis days (128,279 +/- 74,009 versus 168,744 +/- 95,168, respectively, P = .025). The average PA counts during the 4-hour dialysis time period were significantly lower on dialysis days when compared with nondialysis days (3,086 +/- 3,749 versus 11,070 +/- 7,695, respectively, P = .001). At postdialysis hours 1 and 2, PA counts on dialysis days were significantly higher than on nondialysis days (11,410 +/- 5,340 versus 9,082 +/- 6,646, P = .008, and 14,048 +/- 9,728 versus 8,662 +/- 6,433, P = .016, respectively). By postdialysis hour 4, PA counts on dialysis days had significantly decreased when compared with nondialysis days (6,068 +/- 6,268 versus 10,512 +/- 7,420 PA counts, P = .01, respectively). From postdialysis hours 5 to 20, there was no significant difference in PA counts between dialysis and nondialysis days. CONCLUSION: This study shows that physical activity is lower on dialysis days when compared with nondialysis days, and this decrease is caused by the lack of activity during the 4-hour hemodialysis procedure. New behavior modification strategies involving physical activity, both during hemodialysis and on nondialysis days, must be examined in this patient population.     

'SOUND'AND THE 'SENSE'OF SOUND IN THE THERAPEUTIC RELATIONSHIP: A FACTOR IN THE MECHANISM OF PROJECTIVE IDENTIFICATION

ABSTRACT This paper will discuss the dual nature of sound and explore its effects in the therapeutic relationship. I will begin by looking at the auditory sensory perception of sound and its role in the development of the infant, our perception of the world, the self and others. I will then focus on the objective, physiological nature of sound in an attempt to answer some of the questions raised in my own mind about the possibility of this playing a vital role in our subjective experience of being with patients, with particular reference to the phenomenon of projective identification.