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Institution

Utrecht University

EducationUtrecht, Utrecht, Netherlands
About: Utrecht University is a education organization based out in Utrecht, Utrecht, Netherlands. It is known for research contribution in the topics: Population & Poison control. The organization has 58176 authors who have published 139351 publications receiving 6214282 citations. The organization is also known as: UU & Universiteit Utrecht.


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Journal ArticleDOI
06 Oct 2020-JAMA
TL;DR: To determine whether hydrocortisone improves outcome for patients with severe COVID-19, an ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin was conducted.
Abstract: Importance Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures The primary end point was organ support–free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned –1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support–free days were 0 (IQR, –1 to 15), 0 (IQR, –1 to 13), and 0 (–1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support–free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support–free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration ClinicalTrials.gov Identifier:NCT02735707

630 citations

Journal ArticleDOI
TL;DR: An updated list of 30 essential items that should be included in every report of a diagnostic accuracy study is presented, which incorporates recent evidence about sources of bias and variability in diagnostic accuracy and is intended to facilitate the use of STARD.
Abstract: Incomplete reporting has been identified as a major source of avoidable waste in biomedical research. Essential information is often not provided in study reports, impeding the identification, critical appraisal, and replication of studies. To improve the quality of reporting of diagnostic accuracy studies, the Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement was developed. Here we present STARD 2015, an updated list of 30 essential items that should be included in every report of a diagnostic accuracy study. This update incorporates recent evidence about sources of bias and variability in diagnostic accuracy and is intended to facilitate the use of STARD. As such, STARD 2015 may help to improve completeness and transparency in reporting of diagnostic accuracy studies.

630 citations

Journal Article
TL;DR: Understanding the impact of task-dependent cortical activation patterns in non-invasive methods requires not only information derived from longitudinal studies pertaining to functional outcomes, but also a better understanding of what is kinematically learned during the acquisition of new skills.
Abstract: Longitudinal studies show that almost all stroke patients experience at least some predictable degree of functional recovery in the first six months post stroke. However, the non-linear pattern as a function of time is not well understood. Several mechanisms are presumed to be involved, such as recovery of penumbral tissues, neural plasticity, resolution of diaschisis and behavioural compensation strategies. Rehabilitation is believed to modulate this logistic pattern of recovery, probably by interacting with these underlying processes. However, prediction models that are adjusted for the effects of time after stroke onset suggest that outcome is largely defined within the first weeks post stroke, although functional improvement has been found to extend beyond six months post stroke. In addition, kinematic studies show that functional improvement is more than recovery from impairments alone, suggesting that patients are able to improve in terms of gait or dexterity deficits using behavioural compensation strategies. Therefore, understanding the impact of task-dependent cortical activation patterns in non-invasive methods requires not only information derived from longitudinal studies pertaining to functional outcomes, but also a better understanding of what is kinematically learned during the acquisition of new skills.

629 citations

Journal ArticleDOI
01 Dec 1994-Nature
TL;DR: In this paper, the synthesis of polysilane dendrimers (high-branched macromolecules) with metal-containing catalytically active sites is described.
Abstract: AT the interface between heterogeneous and homogeneous catalysis there is great scope for the development of new materials that combine the advantages and/or minimize disadvantages associated with each of these classes. In particular there is a need for homogeneous catalysts with properties that allow their ready removal from a product-containing solution. One approach to such materials is to anchor homogeneous catalysts to soluble polymer supports1; we have recently prepared such catalytic materials in which the active centre is an organometallic species2,3. One disadvantage encountered when anchoring catalytic metal sites to polymers is the difficulty of accurate control of the number and location of these sites. Here we report an alternative approach—the synthesis of polysilane dendrimers (highly branched macromolecules4–6) which are functionalized at their periphery with metal-containing catalytically active sites. These dendrimers show regiospecific catalytic activity for the Kharasch addition of polyhalogenoalkanes to carbon–carbon double bonds. It should be possible to remove the nanoscale catalytic macromolecules of this type from the solution of products using filtration methods.

629 citations

Journal ArticleDOI
TL;DR: Genomic and metagenomic data predict a number of ecologically relevant capabilities for some acidobacteria, including the ability to: respond to soil macro-, micro nutrients and soil acidity, express multiple active transporters, degrade gellan gum and produce exopolysaccharide (EPS).
Abstract: The phylum Acidobacteria is one of the most widespread and abundant on the planet, yet remarkably our knowledge of the role of these diverse organisms in the functioning of terrestrial ecosystems remains surprisingly rudimentary. This blatant knowledge gap stems to a large degree from the difficulties associated with the cultivation of these bacteria by classical means. Given the phylogenetic breadth of the Acidobacteria, which is similar to the metabolically diverse Proteobacteria, it is clear that detailed and functional descriptions of acidobacterial assemblages are necessary. Fortunately, recent advances are providing a glimpse into the ecology of members of the phylum Acidobacteria. These include novel cultivation and enrichment strategies, genomic characterization and analyses of metagenomic DNA from environmental samples. Here, we couple the data from these complementary approaches for a better understanding of their role in the environment, thereby providing some initial insights into the ecology of this important phylum. All cultured acidobacterial type species are heterotrophic, and members of subdivisions 1, 3, and 4 appear to be more versatile in carbohydrate utilization. Genomic and metagenomic data predict a number of ecologically relevant capabilities for some acidobacteria, including the ability to: use of nitrite as N source, respond to soil macro-, micro nutrients and soil acidity, express multiple active transporters, degrade gellan gum and produce exopolysaccharide (EPS). Although these predicted properties allude to a competitive life style in soil, only very few of these prediction shave been confirmed via physiological studies. The increased availability of genomic and physiological information, coupled to distribution data in field surveys and experiments, should direct future progress in unraveling the ecology of this important but still enigmatic phylum.

629 citations


Authors

Showing all 58756 results

NameH-indexPapersCitations
Ronald C. Kessler2741332328983
Albert Hofman2672530321405
Douglas G. Altman2531001680344
Hans Clevers199793169673
Craig B. Thompson195557173172
Patrick W. Serruys1862427173210
Ruedi Aebersold182879141881
Dennis S. Charney179802122408
Kenneth S. Kendler1771327142251
Jean Louis Vincent1611667163721
Vilmundur Gudnason159837123802
Monique M.B. Breteler15954693762
Lex M. Bouter158767103034
Elio Riboli1581136110499
Roy F. Baumeister157650132987
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023429
20221,014
20218,992
20208,578
20197,862
20187,020