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.

     

Human interleukin 4 regulates the phenotype of lymphocytes generated during mixed lymphocyte culture and inhibits the IL-2-induced development of LAK function in normal and leukaemic cells

This study examined the immunoregulatory role of recombinant interleukin 4 (IL-4), also known as B-cell stimulating factor 1, on the generation of cytotoxic effector cells from normal and leukaemic human blood mononuclear cells. When tested on cells from normal individuals, the addition of IL-4 to mixed lymphocyte cultures led to a dose-dependent proliferation of T-helper cells (CD3, 4 positive) with a concomitant decrease in phenotypic and functional cytotoxic T cells and natural killer (NK) cells. IL-4 also inhibited the interleukin-2 (IL-2)-induced generation of lymphokine-activated killer (LAK) activity when added at the beginning of mixed lymphocyte culture. When tested on mature leukaemic NK cells, IL-4 also inhibited the ability of IL-2 to induce LAK function using a short-term culture system. These results show that IL-4 acts on both normal and leukaemic cells and suggests that it acts at more than one level during the development of LAK function.     

A digital test for pelvic muscle strength in older women with urinary incontinence

A digital test of pelvic muscle strength for evaluation of a pelvic muscle exercise (PME) program was developed with a sample of 338 incontinent women living at home. Factors of perceived pressure, alteration of the vertical plane, and time were combined to form a 7-point scale ranging from 0 to 4. Test-retest for the anteroposterior score was r = .65, p less than .01 with interrater reliability, r = .91, p less than .01. Relationship to other variables and further development of the measure are discussed.     

Disruptive behavior in elderly nursing home residents: a survey of nursing staff.

A significant number of nursing home residents exhibit behavior disturbances that are disruptive to the living and working environment in the nursing home. The most common disruptive behaviors cited by licensed nursing personnel included hitting/slapping, verbally aggressive remarks, screaming, pacing, wandering, and repetitive verbal requests. Self-injurious behavior, property destruction, and hiding things were not mentioned. Many of the nursing strategies listed by nursing staff as being used to alleviate disruptive behaviors are traditional care activities, eg, talking to and counseling patients, touching, or altering care. However, chemical and physical restraints were also frequently listed.     

Axillary recurrence in breast cancer.

AIM: To determine whether axillary recurrence reflects inadequate axillary treatment or adverse pathological features. METHODS: The case-records were reviewed of 2122 women aged under 75 years, treated for invasive breast cancer during the time-period 1/1/86-31/12/91 in a geographically defined area. Data were abstracted on operations performed, pathological features, post-operative treatments and details of axillary recurrence. The risk of axillary recurrence was examined by pathological, treatment and patient factors. RESULTS: Axillary recurrence was more than twice as likely after inadequate compared to adequate treatment of the axilla (adequate staging or axillary radiotherapy or clearance). Delayed treatment of the axilla was not as successful as adequate primary treatment: multiple axillary recurrences were twice as common, one third of which were uncontrolled at time of death. Inadequate surgical treatment was associated with increased rates of recurrence despite endocrine therapy, chemotherapy or radiotherapy. Lymphoedema was twice as common if axillary radiotherapy was combined with any axillary surgical procedure. CONCLUSIONS: Axillary recurrence is more common in tumours with adverse pathology but may also result from inadequate axillary treatment. In order to minimise axillary recurrence, optimal treatment of the axilla entails adequate staging (sampling of four or more nodes) and treatment (axillary clearance or radiotherapy and endocrine therapy) in all women.     

Armadillo IgG and IgM antibody responses to phenolic glycolipid-I during experimental infection with M. leprae

The kinetics of antibody responses of Mycobacterium leprae-infected armadillos to phenolic glycolipid-I (PGL-I) were studied by means of ELISA. The levels of both IgG and IgM antibodies to PGL-I increased with time. Some animals were less susceptible to disseminations of M. leprae infection and lived longer than others. These animals had high absorbance values (greater than 0.7) for IgG anti-PGL-I compared to more susceptible armadillos that had lower absorbance values for IgG anti-PGL-I.     

Metabolic alkalosis after pediatric cardiac surgery.

OBJECTIVE: To determine occurrence, causes and associated mortality of postoperative metabolic alkalosis in pediatric cardiac surgery. METHODS: We retrospectively analyzed clinical and biochemical variables of 186 consecutive cardiac operations other than ductal ligations on children less than 2 years old during the years 1999 and 2000. Metabolic alkalosis was defined as a pH>7.48 corrected for PCO2, with a base excess > or =5 on two or more consecutive measurements during an 8h period. RESULTS: Median age was 15 weeks [range 2 days-95 weeks] and median weight 4.5 kg [range 2.1-15.7 kg]. In 157 cases, cardiopulmonary bypass was used. In 92 [49%] procedures, metabolic alkalosis occurred with the highest corrected pH 24.3h after operation. Multivariate regression analysis associated age [P<0.001], cardiopulmonary bypass [P<0.001] and preoperative ductal dependency [P=0.04] with postoperative metabolic alkalosis. Of the surgical procedures the arterial switch for transposition of the great arteries [n=19] was strongly associated with metabolic alkalosis [100%, P<0.001]. Hemodilution appeared to enhance the development of alkalosis: those who experienced alkalosis had been hemodiluted to a greater extent [P=0.007]. Nearly 95% of patients experienced some increase in bicarbonate, but patients with metabolic alkalosis experienced more than those without [5.9 versus 3.5 mmol/l, P<0.001]. There were four postoperative deaths, only one coincidental with metabolic alkalosis. CONCLUSIONS: Metabolic alkalosis has a high incidence after pediatric cardiac surgery, strongly associated with younger age, cardiopulmonary bypass, preoperative ductal dependency and perioperative hemodilution. Early recognition allows for timely therapeutic intervention.