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. 相似文献
To evaluate morbidity associated with surgical lengthening of the gastrocnemius, medical records were reviewed retrospectively for 126 patients (mean age, 49.7 years; range, 8-78 years) who had undergone open gastrocnemius recession. Ten patients had isolated recession; 116 had gastrocnemius recession with an additional foot or ankle procedure on the ipsilateral limb. During a mean follow-up period of 19 months (range, 6-50 months), all patients were examined for any postoperative complications associated with the recession. Complications were defined as the presence of postoperative infection, wound dehiscence, nerve problems, decreased muscle strength, scar problems, or calcaneus gait (overlengthening). Uncomplicated outcome was defined as absence of all these complications and return to regular activity, both occurring during a follow-up of at least 6 months. Postsurgical complications developed in 9 (6%) of the 126 patients: 6 (4%) had scar problems, 2 (1.33%) had wound dehiscence, 2 (1.33%) had infection, 3 (2%) had nerve problems, and 1 (0.67%) developed complex regional pain syndrome. No patient complained of either a limp or gait disturbance. Neither persistent decrease in muscle strength nor calcaneus gait was seen. These data suggest that the open gastrocnemius recession procedure has low associated morbidity. 相似文献
Background: Previous studies have shown that propofol and sevoflurane enhance the function of [gamma]-aminobutyric acid type A (GABAA) receptors. However, it is not known whether these two drugs modulate the same molecular pathways. In addition, little is known about receptor function in the presence of both propofol and sevoflurane. The aim of this study was to better understand the interactions of propofol and sevoflurane with the GABAA receptor.
Methods: Wild-type [alpha]1, [beta]2, [gamma]2s GABAA receptor subunit complementary DNAs were transfected into human embryonic kidney cells grown on glass coverslips using a calcium phosphate transfection method. After transfection (36-72 h), cells were whole cell patch clamped and exposed to combinations of the following: 0.3-1,000 [mu]m [gamma]-aminobutyric acid (GABA), 0-10 [mu]m propofol, and 0-1,650 [mu]m sevoflurane. Chemicals were delivered to the cells using two 10-channel infusion pumps and a rapid solution exchanger.
Results: Both propofol and sevoflurane alone enhanced the amplitude of GABAA receptor responses to submaximal concentrations of GABA in a dose-dependent manner. The enhancement was underpinned by an increase in the apparent affinity of the receptor for GABA. Coapplication of both anesthetics further enhanced the apparent affinity of the receptor for GABA. 相似文献
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. 相似文献
Since the aminoglycoside antibiotic apramycin was licensed for veterinary use in 1980, all isolates of Escherichia coli and salmonellas received at the Central Veterinary Laboratory have been monitored for resistance to apramycin and the related antibiotic gentamicin. During the period 1982-4, the incidence of resistance in E. coli to apramycin increased from 0.6% in 1982 to 2.6% in 1984. In salmonellas the incidence of resistance to apramycin increased from 0.1% in 1982 to 1.4% in 1984. Resistance to both apramycin and gentamicin was detected in six different salmonella serotypes, although an isolate of Salmonella thompson from poultry was resistant to gentamicin but not apramycin. Most of the cultures were isolated from pigs, although the incidence of apramycin resistance in S. typhimurium (DT 204C) from calves has shown a recent dramatic increase. All the isolates with one exception produced the enzyme aminoglycoside 3-N-acetyltransferase IV (ACC(3)IV). The resistance was transferable by conjugation in most of the strains examined, and the plasmids specifying the resistance have been found to belong to a number of different incompatibility groups. Plasmids from three E. coli strains were compatible with all the reference plasmids and belonged to a previously undescribed group which was investigated further. It is suggested that bacteria from humans should be examined for resistance to apramycin and gentamicin to determine the possibility of the antibiotic-resistance bacteria, and their genes, spreading from animals to humans. 相似文献
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. 相似文献