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.

     

Pain and quality of life for patients with venous leg ulcers: proof of concept of the efficacy of Biatain®-Ibu, a new pain reducing wound dressing

Wound pain is a serious problem for elderly patients suffering from chronic leg ulcers, and it may lead to reduced wound healing rates and reduced quality of life. Biatain-Ibu Non-adhesive (Coloplast A/S), a new pain-reducing moist wound healing dressing containing ibuprofen was tested for pain reduction, safety, and efficacy on 10+2 patients in a single-blinded crossover study against Biatain Non-adhesive (Coloplast A/S). Pain was measured with a Numeric Box Scale before, during, and after dressing change. Quality of life was measured using the World Health Organization-5 Well-Being Index. Dressing moist wound healing properties such as absorption capacity and leakage were tested together with assessment of wound exudate and blood plasma content of ibuprofen. Use of the Biatain-Ibu foam dressing correlated with a decrease in pain intensity scores from 7 in the run-in period to approximately 2.5 in the Biatain-Ibu treatment phase. Quality of life measures were improved which together with the reduced pain could contribute to faster wound healing. The moist wound healing properties of Biatain-Ibu were similar to that of the Biatain Non-adhesive and ulcer size was reduced by 24% during the treatment period. Neither side effects nor systemic plasma concentrations of ibuprofen were observed. These data indicate that Biatain-Ibu could reduce persistent and temporary wound pain, increase Quality of life, was found safe to use, and had excellent moist wound healing properties.     

Intravenous Lidocaine Relieves Spinal Cord Injury Pain: A Randomized Controlled Trial

Background: Neuropathic pain in spinal cord injury is a common challenging therapeutic condition. The current study examines the analgesic effect of the sodium channel blocker lidocaine on neuropathic pain in patients with spinal cord injury and the predictive role of concomitant evoked pain on pain relief with lidocaine.

Methods: Twenty-four spinal cord injury patients with neuropathic pain at or below the level of injury were randomized and completed a double-blind crossover trial of 5 mg/kg lidocaine and placebo infused over 30 min. Twelve patients reported evoked pain, and 12 patients had no evoked pain. Spontaneous and evoked pains were assessed using a visual analog scale and quantitative sensory testing.

Results: Lidocaine significantly reduced spontaneous pain in all patients (P < 0.01) and in each of the two groups with (P < 0.01) and without (P = 0.048) evoked pain, with no difference in number of responders (pain reduction >= 33%) between the patients with (n = 6) and without (n = 5) evoked pain. Lidocaine significantly relieved both at-level and below-level neuropathic pain and decreased brush-evoked dysesthesia but not cold allodynia, pinprick hyperalgesia, or pain evoked by repetitive pinprick.     

Abnormal bone masses in Klippel-Feil syndrome.

Five female patients with Klippel-Feil syndrome (KFS) are presented with abnormal bony masses in the mandibular ramus region. The features of KFS are described with assessment and treatment of the five patients. Although congenital duplication of mandibular rami in KFS has been previously documented, we believe this is the first series of patients with this deformity.     

Mortality Rates and Predictors of Mortality Among Late-Middle-Aged and Older Substance Abuse Patients

This study describes mortality rates and predictors of mortality among late-middle-aged and older (55+) substance abuse inpatients ( n = 21, 139) in Department of Veterans Affairs (VA) Medical Centers in the 4 years after an index episode of care. A total of 24% of the patients died; this mortality rate was 2.64 times higher than expected. Predictors of earlier mortality included older age and nonmarried status, alcohol psychosis and organic brain disorder diagnoses, and several medical diagnoses, including neoplasms, liver cirrhosis, respiratory, endocrine and metabolic, and blood system disorders. Three proxy indicators of illness severity also predicted mortality: more prior inpatient and outpatient medical care and an index episode in an extended care unit. In contrast, more prior outpatient mental health care and remitted status predicted lower mortality. These diagnostic and treatment indicators can be used to identify patients at heightened risk for premature mortality. Moreover, they show that intensive mental health aftercare and remission of substance abuse may delay mortality, even among older patients who have longstanding substance abuse problems.     

Monoclonal antibodies to canine intra-acrosomal sperm proteins recognizing acrosomal status during capacitation and acrosome reaction

Summary.  Monoclonal antibodies Ds-1 and Ds-2 specifically labelling dog sperm acrosome were prepared by immunization of mice with acetic acid extracts of dog spermatozoa. Electron microscopy and indirect immunofluorescence localized the site of Ds-1 and Ds-2 proteins inside the acrosomal vesicle. Ds-1 antibody detected 55, 76, 115, 120 and 190kDa proteins under non-reducing conditions, and 73 kDa and 54 kDa proteins after reduction (p73/Ds-1 and p54/Ds-1). 92 kDa and 40 kDa proteins recognized by Ds-2 (p92/Ds-2 and p40/Ds-2) migrated at > 200 kDa in the absence of reducing agent. In vivo , p73/Ds-1 and p54/Ds-1 are therefore likely to be present both in free and complexed form, while all of p92/Ds-2 and p40/Ds-2 form disulfide-bonded complexes. Decrease in the rate of acrosomes stained with Ds-1 and Ds-2 was correlated with the progress of capacitation resulting in the increased rate of spontaneous acrosome reactions, as suggested by a dramatic effect of A23187. Monoclonal antibody to boar acrosin (ACR-2) recognized dog sperm acrosin homologue. A higher rate of ACR-2-negative spermatozoa was observed after capacitation and A23187 treatment compared to Ds-1 and Ds-2, indicating that proteins recognized by Ds-1 and Ds-2 are localized in a specific compartment of acrosome, distinct from acrosin and possibly representing fraction of acrosomal matrix.     

Ein Fall von Anbohrung des in Folge von Entzündung knöchern verschlossenen äusseren Gehörgangs

Ohne Zusammenfassung