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1.
Marie Warrer Petersen  Tine Sylvest Meyhoff  Marie Helleberg  Maj-Brit Nørregaard Kjær  Anders Granholm  Carl Johan Steensen Hjortsø  Thomas Steen Jensen  Morten Hylander Møller  Peter Buhl Hjortrup  Mik Wetterslev  Gitte Kingo Vesterlund  Lene Russell  Vibeke Lind Jørgensen  Klaus Tjelle  Thomas Benfield  Charlotte Suppli Ulrik  Anne Sofie Andreasen  Thomas Mohr  Morten H. Bestle  Lone Musaeus Poulsen  Mette Friberg Hitz  Thomas Hildebrandt  Lene Surland Knudsen  Anders Møller  Christoffer Grant Sølling  Anne Craveiro Brøchner  Bodil Steen Rasmussen  Henrik Nielsen  Steffen Christensen  Thomas Strøm  Maria Cronhjort  Rebecka Rubenson Wahlin  Stephan Jakob  Luca Cioccari  Balasubramanian Venkatesh  Naomi Hammond  Vivekanand Jha  Sheila Nainan Myatra  Christian Gluud  Theis Lange  Anders Perner 《Acta anaesthesiologica Scandinavica》2020,64(9):1365-1375

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.
  相似文献   
2.
In a prospective, randomized trial, 104 consecutive patients with displaced femoral neck fractures were allocated either to fixation with a sliding screw plate or 4 ASIF cancellous bone screws. The patients were reexamined at fixed intervals to determine the time of union. The 2-year-cumulated rate of union was 64 per cent in the plate group and 84 per cent in the screw group.  相似文献   
3.
Caffeine is sequentially metabolized by cytochrome P4501A2 (CYP1A2), N-acetyltransferase (NAT) and/or xanthine oxidase (XO). In the present study the activity of these three enzymes was estimated from ratios of the metabolites formed from dietary caffeine and excreted into the urine collected as spot samples. In the urine samples from 10 out of 377 subjects concentrations of caffeine metabolites were too low to allow reliable measurements of the ratios. In 335 healthy subjects the NAT activity showed a typically bimodal distribution with 47% fast acetylators and 53% slow acetylators, consistent with a Danish population. The ratios reflecting CYP1A2 and XO activities were log normal and normal distributed, respectively. In 103 non-smoking men and 90 non-smoking women the ratio of caffeine metabolites expressing CYP1A2 activity was 4.7 +/- 1.6 and 4.3 +/- 1.9 as compared to 7.8 +/- 2.5 and 7.3 +/- 3.0 in 31 male and 25 female subjects smoking 10 cigarettes/day or more respectively, verifying induction of CYP1A2 by tobacco (P less than 0.05), but minimal sex-related differences. In 12 non-smoking pregnant women and in 28 women using oral contraceptives the CYP1A2 ratio was 29 and 20% reduced respectively (P less than 0.05). In a multivariate analysis the only significant predictor of the XO ratio was the consumption of caffeine with an increase of 2% per cup of coffee or equivalent (P less than 0.05). In 23 healthy male subjects 30 days of vigorous exercise increased the CYP1A2 ratio by 70% and the XO ratio by 42% (P less than 0.05), but left the NAT ratio unchanged. In nine healthy volunteers daily ingestion of 500 g of broccoli for 10 days increased the CYP1A2 ratio by an average of 12% (P less than 0.05), compared to a control period with ingestion of an equivalent weight of non-cruciferous green vegetables. The ratios of metabolites from dietary caffeine in spot urine samples offer ethical, non-invasive and reliable estimates of CYP1A2, NAT and XO. These enzymes are highly relevant for the bioactivation of potentially toxic compounds and the formation of oxygen radicals. The method is applicable in large-scale epidemiological studies, allowing, for example, prospective testing of the relationship between these enzyme activities and the development of disease. Exercise may increase CYP1A2 activity to a magnitude corresponding to heavy smoking, as well as XO by mechanisms that remain to be clarified.  相似文献   
4.
An increased lung cancer risk has been described among foundry workers. Polycyclic aromatic hydrocarbons (PAHs) and silica are possible aetiological factors. This study describes a urinary PAH metabolite, 1-hydroxypyrene (hpU), as well as the degree of cytochrome P450IA2 activity/induction as reflected by the urinary caffeine ratio (IA2) in 45 foundry workers and 52 controls; IA2 was defined as the ratio of paraxanthine 7-demethylation products to a paraxanthine 8-hydroxylation product (1,7-dimethyluric acid). Mean exposure concentrations for foundry workers were defined by breathing zone hygienic samples (respirable dust 1.2 to 3.52 mg/m3 (93 samples)) and as total PAH (0.46 micrograms/m3) and pyrene concentrations (0.28 micrograms/m3) (six samples). Non-smoking controls and foundry workers had similar IA2 ratios (5.63, 95% confidence interval (95% CI) 4.56-6.70 and 4.40, 95% CI 3.56-5.24). The same was true for smoking controls and foundry workers (9.10, 95% CI 8.00-10.20 and 8.69, 95% CI 7.37-10.01). Both smoking groups had raised IA2 ratios compared with non-smokers (p less than 0.01). Non-smoking controls and foundry workers had similar hpU concentrations (0.16, 95% CI 0.10-0.22 and 0.11, 95% CI 0.09-0.13 mumol/mol creatinine). Smoking foundry workers had raised hpU concentrations (0.42, 95% CI 0.25-0.59) compared with smoking controls (0.26, 95% CI 0.18-0.34) (p less than 0.01). A small subgroup of smoking foundry workers with the highest exposures to both silica and PAH also had the highest hpU concentrations (0.70, 95% CI - 0.07-1.47 mumol/mol creatinine) (p less than 0.04). Increased hpU concentrations in smoking foundry workers suggest a more than additive effect from smoking and foundry exposures resulting in increased PAH uptake. Increased P450IA2 enzyme activity was only found in smokers and no additional effect of foundry exposures was seen. These data suggest that smoking as well as work related PAH exposure may be casually related to increased risk of lung cancer in foundry workers.  相似文献   
5.
Six cases of inoperable arteriovenous malformations (AVM) treated with conventional megavoltage radiation therapy are reviewed. One of the six cases had complete angiographic clearance of the AVM. None of the cases have had recurrent bleeding. One has had uncontrolled epilepsy. There were no treatment complications.  相似文献   
6.
OBJECTIVE: To examine the association between socioeconomic position and coping strategies in musculoskeletal pain. DESIGN AND SUBJECTS: Cross-sectional study of a random sample of 40- and 50-year-old Danes, participation rate 69%, n=7,125. The study included 1,287 persons who reported functional limitations due to musculoskeletal pain. METHODS: Data was collected by postal questionnaires and scales were developed on problem-solving coping and avoidant coping, based on a range of preliminary studies. Multivariate logistic regression analyses was used to study the correlation with socioeconomic position, measured by occupational social class. RESULTS: Among women, there was no correlation between social class and avoidant coping, but a significant decrease in the use of problem-solving coping by decreasing social class, adjusted odds ratio (OR) = 2.64 (95% confidence interval (CI) 1.31-5.32) in social class V vs social classes I + II. Among men, there was no correlation between social class and problem-solving coping, but a significant increase in the use of avoidant coping with decreasing social class, adjusted OR = 3.31 (95% CI 1.75-6.25) in V vs I + II. CONCLUSION: It is important for clinicians who advise and support patients in their response to musculoskeletal pain to be aware of socioeconomic differences in coping strategies. Gender differences in the association between socioeconomic factors and coping should be further investigated.  相似文献   
7.
Nine human small-cell lung cancer cell lines were treated with transforming growth factor beta 1 (TGF-beta 1). Seven of the cell lines expressed receptors for transforming growth factor beta (TGF-beta-r) in different combinations between the three human subtypes I, II and III, and two were receptor negative. Growth suppression was induced by TGF-beta 1 exclusively in the five cell lines expressing the type II receptor. For the first time growth suppression by TGF-beta 1 of a cell line expressing the type II receptor without coexpression of the type I receptor is reported. No effect on growth was observed in two cell lines expressing only type III receptor and in TGF-beta-r negative cell lines. In two cell lines expressing all three receptor types, growth suppression was accompanied by morphological changes. To evaluate the possible involvement of the retinoblastoma protein (pRb) in mediating the growth-suppressive effect of TGF-beta 1, the expression of functional pRb, as characterised by nuclear localisation, was examined by immunocytochemistry. Nuclear association of pRb was only seen in two of the five TGF-beta 1-responsive cell lines. These results indicate that in SCLC pRb is not required for mediation of TGF-beta 1-induced growth suppression.  相似文献   
8.
Health behaviour during pregnancy was examined before and after a comprehensive health campaign targeted at pregnant women in Odense, Denmark. Furthermore, lifestyle habits were compared before and during the campaign with similar habits in Aalborg, Denmark. All 13,815 pregnant women (equal numbers from each city) were enrolled in the study, and 11,980 gave information on eating, drinking, and smoking habits during pregnancy. Data collection in both cities took place from April 1984 to April 1987. The campaign, which was entitled "Healthy Habits for Two", ran from April 1985 to April 1987 in the city of Odense only. No significant change in health behaviour in the Odense area was noted after the start of the campaign.  相似文献   
9.
10.
1. The effects of the Ca2+-ionophore A23187 and the non-metabolizable cholinergic agonist bethanechol on acinar cell membrane potentials and amylase release from the superfused mouse pancreas were studied. 2. In the presence of extracellular Ca2+ (2.56 mM), A23187 (10(-5)M) and bethanechol (3 X 10(-5)M) caused an equal increase in the release of amylase. Both stimulants depolarized theacinar cells, A23187 by 6-0 mV and bethanechol by 12-3 mV. 3. When Ca2+ and Mg2+ were removed from the superfusate, the ability of A23187 to increase the rate of amylase release was virtually abolished, while the effect of bethanechol remained unaltered. Similarly, in the absence of these divalent cations, A23187 did not cause depolarization of the acinar cells, while depolarization in response to bethanechol was largely normal. Consequently it is unlikely that cholinergic agonists initiate secretion by activating a Ca2+-ionophore-like mechanism in the cell membrane. 4. When the concentration of Ca2+ in the medium was raised to 10 mM was the only extracellular divalent cation present, the depolarization in response to A23187 was increased to 11-8 mV. When Mg2+ in a concentration of 10 mM was the only extracellular divalent cation, the depolarization was only 2-1 mV. 5. The Ca2+ dependent, A23187-induced depolarization was abolished in the absence of Na+ (Tris substitution). Addition of Na+ to the superfusate caused an immediate depolarization. 6. It is concluded that the Ca2+ dependent depolarization of pancreatic acinar cells induced by A23187 is not directly due to an increased divalent cation conductance. Our findings are consistent with the view that the depolarization is due to an increased influx of Na+ resulting from a Ca2+ mediated increase in Na+ permeability.  相似文献   
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