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.

     

Sacrococcygeal teratoma in Sweden between 1978 and 1989: long-term functional results.

Thirty-four patients operated with sacrococcygeal teratoma in Sweden between 1978 and 1989 were reviewed. Twenty-five children were available for functional follow-up. The patients and their parents were interviewed for bowel and micturition habits. Fourteen patients from this number were subjected to anorectal manometry (56%). Fifteen children reported normal bowel habits (60%). In 10 patients (40%) soiling was observed. However, four of them were under 3 years of age and wearing diapers, which made the functional evaluation difficult. The manometries showed normal and resting tone and squeezing pressures in 10 patients and subnormal values in four patients who also had soiling problems. All investigated children showed normal rectoanal inhibition reflex. Twenty-one patients reported normal micturition, in four (16%) urinary incontinence was recorded. Two of the latter children required intermittent clean catheterization, one was on medication and the last one lives without any treatment. No difference in functional outcome was noted between patients with intrapelvic or extrapelvic tumor location. Retrospectively, it is not possible to know whether the observed functional outcome is due to tumor growth or the result of surgery. Preoperative clinical investigation and in some cases anorectal manometry and cystometry could theoretically resolve this problem.     

Outcome of a multicenter treatment program including autologous or allogeneic bone marrow transplantation for de novo acute myeloid leukemia

Abstract: The results of an intensive treatment program for patients 16–60 yr of age with de novo acute myeloid leukemia are presented. The patients were given conventional induction treatment with daunorubicin and cytarabine. Patients not entering complete remission (CR) after 1 course of daunorubicin/cytarabine were given 1 course of amsacrine/etoposide/cytarabine. Those entering complete remission received 3 consolidation courses using mitoxantrone, etoposide, amsacrine and cytarabine. One hundred and eighteen patients were enrolled. Complete remission was attained after 1–2 courses in 90 patients (76%). Another 6 patients reached CR after 3–4 induction courses for a total CR rate of 81%. If feasible, patients were offered either allogeneic or unpurged autologous bone marrow transplantation. Twenty-four patients underwent allogeneic bone marrow transplantation; 15 in first remission, 8 in second remission, 1 in early relapse. Thirty patients below 56 yr of age underwent autologous bone marrow transplantation in first remission. The overall probability of survival at 4 yr was 34%, and for patients below 40 yr of age 50%. Leukemia-free survival was 35% for the whole cohort of patients; 52% for patients below 40 yr of age. Patients undergoing allogeneic or autologous bone marrow transplantation in first remission had an overall survival of 86% and 47%, respectively, while the probability of leukemia-free survival in these groups was 87% vs. 40% at 4 yr. The CR rate and long-term results of this intensive treatment program compare favorably with other recent studies using intensive consolidation with allogeneic or autologous bone marrow transplantation or high dose cytarabine.     

Observations on two members of the Swedish family with congenital dyserythropoietic anaemia,type III

Abstract: Two affected individuals of the Swedish family with CDA, type III, in which the disease is transmitted as an autosomal dominant character, were studied. Both cases displayed features hitherto undescribed in this family but described in patients with CDA, type III, in whom the inheritance may have been as an autosomal recessive character. Such features were: (a) haemosiderinuria, (b) grossly disorganised erythroblast nuclei, (c) differences in the ultrastructural appearances of individual nuclei within the same multinucleate erythroblast and (d) intraerythroblastic inclusions resembling precipitated globin chains. In both cases the giant mononucleate erythroblasts and the multinucleate erythroblasts had total DNA contents up to 28c (1c = haploid DNA content) and 48c respectively, and some DNA synthesising bi- and multinucleate erythroblasts contained one or more nuclei which were unlabelled with ³H-thymidine. These findings are similar to those in patients with the autosomal recessive type of disease. Thus no major phenotypic differences are yet apparent between cases of CDA, type III, with different patterns of inheritance. Analysis of the surface erythrocyte proteins of the 2 Swedish CDA, type III, patients with monoclonal antibodies recognising Band 3, glycophorins A, B, C and D, Rh, CD44, CD47, CD55, CD58, CD59, Lutheran, Kell, LW and acetylcholinesterase did not reveal any gross abnormality of expression of these proteins. A slightly altered expression of blood group antigens A and H was revealed by the lectins Dolichos biflorus and Ulex europaeus and the Mr of Band 3 as judged by SDS polyacrylamide gel electrophoresis was also slightly reduced, suggesting that there may be minor alterations in the degree of N-glycosylation of some red cell membrane constituents.     

In vivo motor effects of loperamide on the rat urinary bladder.

Bladder motility recordings were performed in anaesthetized rats and the effect of the peripherally active opiate agonist loperamide on urinary bladder function was studied. Regional intra-arterial administration of loperamide (0.01-2 mg kg-1) induced weak bladder contraction per se. Loperamide caused an effective dose-dependent inhibition of bladder motility induced by regional injection of the receptor agonists acetylcholine (ACh) and substance P (SP), as well as by peripheral motor nerve stimulation (PNS). Pretreatment with naloxone (0.5 mg kg-1) partially antagonized the inhibitory action of loperamide on the nerve-mediated detrusor contraction. However, the depression of the motor responses induced by the receptor agonists ACh and SP was not influenced. It is suggested that the demonstrated inhibitory effect of loperamide on bladder motility is partially mediated by peripheral opioid receptors. The main non-opioid part of the inhibition might be a direct smooth muscle action.     

t(6;9) in bone marrow cells in two patients with sarcoidosis and acute myeloid leukemia

A t(6;9) was seen in bone marrow aspirates from two patients with sarcoidosis who developed acute myeloid leukemia. This is a new observation not previously reported.     

Involvement of central GABA receptors in the regulation of the urinary bladder function of anaesthetized rats

Summary Cystometric recordings were performed in pentobaribitone anaesthetized rats and the effects of gammaaminobutyric acid (GABA) mechanisms on urinary bladder function were evaluated as their influence on a bladder hyperactivity induced by 1-dihydroxyphenylalanine (l-DOPA) after peripheral decarboxylase inhibition. The bladder response was inhibited by intracerebroventricular (i.c.v., 4th ventricle) injections of GABA (250 g), muscimol (0.2 g) and glycine (1,000 g) as well as by systemically administered muscimol (4 mg/kg) and diazepam (2 mg/kg). Intravenous (i.v.) bicuculline, but not i.v. strychnine, antagonized the inhibitory actions of intraperitoneal (i.p.) and i.c.v. muscimol and i.v. diazepam while the opposite was true for the inhibitory action of i.c.v. glycine. In rats not pretreated with l-DOPA, i.p. administration of bicuculline (4 mg/kg) after 15 min caused prominent detrusor contractions that were prevented by an infracollicular brain transection.It is suggested that GABA synapses in the pontinemesencephalic brain region may be involved in the modulation of urinary bladder function.     

No benefit from adding GM-CSF to induction chemotherapy in transforming myelodysplastic syndromes: better outcome in patients with less proliferative disease.

In this prospective randomized multicenter trial 93 patients, median age 72 years, with RAEB-t (n=25) and myelodysplastic syndrome (MDS)-AML (n=68) were allocated to a standard induction chemotherapy regimen (TAD 2+7) with or without addition of granulocyte-macrophage-CSF (GM-CSF). The overall complete remission (CR) rate was 43% with no difference between the arms. Median survival times for all patients, CR patients, and non-CR patients were 280, 550, and 100 days, respectively, with no difference between the arms. Response rates were significantly better in patients with serum lactate dehydrogenase (S-LDH) levels 相似文献   

Changes in miRNA expression in sera and correlation to duration of disease in patients with multifocal mucosal lichen planus

J Oral Pathol Med (2012) 41 : 86–89 Background: Mucosal lichen planus is a severe variant of lichen planus, Lichen planus (LP), which in many ways affect patients’ lives. The aetiology is not fully understood, and there is no treatment clearing the disease once and for all. Oral LP has by the WHO been classified as a precancerous lesion. Micro‐RNAs, miRNAs, are non‐coding, small single‐stranded RNAs involved in biological processes like apoptosis, proliferation, differentiation, metastasis, angiogenesis and immune response. Methods and Results: In sera from 30 patients with multifocal mucosal LP, 15 miRNAs were identified as significantly differentially expressed compared with controls. The three most up‐regulated miRNAs are all connected to oral squamous cell carcinoma or epithelial carcinoma in general. Discussion: Even if no specific LP‐associated miRNA profile was found, data clearly indicate that miRNAs could play a role in the earlier phases of lichen planus.