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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.2.
This overview describes recent advances in molecular biology of neuronal ceroid lipofuscinoses (CLN). Despite intensive research during last 20 years, the basic defects of these autosomal recessive-progressive encephalopathies of childhood remain unknown. Consequently, no specific cure is available. Methods of positional cloning (reverse genetics) starting from random linkage approach have been applied to search for gene defects in the infantile and juvenile forms of the disease. The results of this random search for disease loci have for the first time revealed molecular heterogeneity of CLN diseases. The gene defect causing the infantile form has been assigned to 1p32 in the Finnish family material, whereas the disease locus of the juvenile form has been localized to 16p12 in European and Canadian families. Finally, the gene defect causing the late infantile form has been excluded from both 1p32 and 16p12 chromosomal regions, referring to a third, still unknown locus causing CLN disease. Consequently, reliable prenatal and carrier diagnostics have now become possible in families with the infantile and juvenile forms of the disease, and DNA-based prenatal diagnostics have been successfully applied in the infantile form. Most importantly, the assignment of gene loci has brought these fatal brain diseases within the reach of molecular cloning strategies that eventually will result in revealing both the infantile and juvenile CLN genes and in identifying corresponding gene products. 相似文献
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Lotte Höffner Jens Jung Nielsen Henning Langberg Ylva Hellsten 《The Journal of physiology》2003,550(1):217-225
In the present study we examined whether exercise and prostanoids have an effect on the muscle interstitial concentration of vascular endothelial growth factor (VEGF) and on the proliferative effect of muscle interstitial fluid. Dialysate from resting and exercising human skeletal muscle, obtained either during control conditions or during cyclooxygenase inhibition, was examined for its content of VEGF and for its effect on endothelial cell proliferation. Microdialysis probes with high (960 kDa) and low (5 kDa) molecular-mass cut-off membranes were placed in the vastus lateralis muscle of healthy young males. The subjects performed one-legged knee extensions (20 W). The concentration of VEGF in the 960 kDa dialysate was greater ( P < 0.05 ) during exercise compared to at rest (67 ± 28 vs. 230 ± 22 pg ml−1 ). The rate of endothelial cell proliferation was 2.7-fold higher ( P < 0.05 ) with the 960 kDa dialysate from resting muscle than with perfusate and was 5.8-fold higher ( P < 0.05 ) than the perfusate value with dialysate from exercising muscle. VEGF was not enhanced with exercise in the 5 kDa dialysate, yet the exercise dialysate induced a 1.9-fold higher ( P < 0.05 ) proliferation than the resting dialysate. Cyclooxygenase inhibition did not affect the VEGF concentration or the proliferating effect of the dialysates ( P > 0.05 ). This study demonstrates for the first time that VEGF is present in the interstitium of human skeletal muscle and that exercise enhances the interstitial concentration of VEGF and of other, as yet unidentified, angiogenic compounds. Products of cyclooxygenase do not appear to have an effect on the release of VEGF or other proliferative agents in human skeletal muscle. 相似文献
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Anders Widmark Per Flodgren Jan Erik Damber Sverker Hellsten Eva Cavallin-st hl 《Acta oncologica (Stockholm, Sweden)》2003,42(5):567-581
A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for urinary bladder cancer is based on data from 3 meta-analyses and 33 randomized trials. The studies include 4 333 patients. The results were compared with those of a similar overview from 1996 including 15 042 patients. The conclusions reached can be summarized as these points: There is moderate evidence for an overall survival benefit with preoperative radiotherapy followed by cystectomy compared to curative radiotherapy based on early studies (1964-1986). Since that time surgical as well as radiation techniques have developed considerably. Therefore, the conclusion may not be relevant to modern treatment of invasive urinary bladder carcinoma.There is only one small study reporting on curative radiotherapy where increased dose per fraction is compared with conventionally fractionated radiotherapy to the same total dose. Thus, no conclusions can be drawn concerning optimal fraction dose.A meta-analysis based on two studies on hyperfractionated radiotherapy gives moderate evidence of a survival benefit at 5 and 10 years and an increased local control rate compared with conventional fractionation.The documentation of local control and overall survival rate after split-course radiation treatment compared to continuous therapy is conflicting. No firm conclusions can be drawn.Four small and early studies have compared radiation treatment using neutrons with photon treatment. The reports favour therapy with photons with respect to overall treatment results. There is moderate evidence for this conclusion.There is fairly strong evidence in early studies that radiation treatment in combination with hyperbaric oxygen does not confer a treatment benefit compared to radiation in normal atmosphere.There is no indication of a treatment benefit with the addition of either hyperthermia or misonidazole.A large number of phase II studies, suggesting an increased possibility for bladder preservation with concomitant chemoradiotherapy compared to radiotherapy alone, have been reviewed in a previous SBU report on chemotherapy. Only one small randomized study has been reported where concomitant chemoradiotherapy with cisplatin is compared to radiation alone. No conclusion on the therapeutic benefit of combined treatment can be drawn. Large randomized studies are needed.There is some evidence that preoperative radiotherapy followed by cystectomy does not confer any significant survival benefit compared to cystectomy alone.There is moderate evidence that palliative radiotherapy of invasive bladder carcinoma can rapidly induce tumour-related symptom relief.There is moderate evidence that palliative hypofractionated radiotherapy, 3 fractions during one week, gives the same relief of symptoms as 10 fractions during 2 weeks. 相似文献
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Background: Vestibular-evoked myogenic potential (VEMP) is commonly conducted with air-conducted (AC) stimuli whose intensity may exceed the prudential levels of acoustic exposure in susceptible subjects.Objectives: To determine the diagnostic accuracy of AC VEMP for superior canal dehiscence syndrome (SCDS) at lowered acoustic stimulation levels.Material and methods: VEMP was tested in 10 SCDS patients and in 10 age/sex matched control subjects. VEMP were recorded on cervical muscles (cVEMP) and extraocular muscles (oVEMP) in response to short AC tone bursts at 500, 1000 and 2000?Hz delivered at 80?dB nHL (103?dB peSPL). Parameters of interest were the response amplitude and the frequency tuning.Results: VEMP evoked by AC stimuli at safe acoustic stimulation levels did effectively separate SCDS patients from healthy controls. The separation was optimal at all the frequencies tested, however 500?Hz resulted the best VEMP tuning frequency, especially at oVEMP.Conclusions: Lowering the AC stimulation to the levels compatible with testing of patients susceptible to acoustic exposure didn’t affect the VEMP diagnostic properties for SCDS.Significance: SCDS may be screened by VEMP even among subjects susceptible for acoustic exposure. 相似文献
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ABSTRACT: BACKGROUND: Introducing a new method into family planning programs requires careful attention to ensure it meets an actual need and has a positive effect on program goals. The Standard Days Method(R) is a fertility awareness-based method of family planning that is being introduced into family planning programs in countries around the world. It is different from other methods offered by programs, and may bring new couples into family planning, and increase contraceptive prevalence. The study assesses the effect on contraceptive use and prevalence of Introducing Standard Days Method into existing family planning services in whole regions of India, Peru, and Rwanda. METHODS: In collaboration with the Ministry of Health, health providers were given a contraceptive update on all methods, then trained in counseling on Standard Days Method. Efforts were made to promote demand in the context of informed choice. Routine monthly service statistics in control and intervention areas were used to assess the effect of Standard Days Method introduction at the clinic level; baseline and endline household-based surveys were undertaken to obtain results at the community level (n > 3400 women at endline). RESULTS: Demand for the method is evident in countries with different levels of contraceptive prevalence. The method attracts couples new to family planning, and introducing it into services may increase overall contraceptive prevalence. CONCLUSIONS: Introducing Standard Days Method into existing family planning has the potential of benefiting men and women in diverse settings and populations. This study illustrates the critical role of evidence in scaling up a health innovation. 相似文献