Browsing by Author "Marc J.M. Bonten"

Filter results by typing the first few letters
Now showing 1 - 3 of 3
  • No Thumbnail Available
    PublicationMetadata only
    Consumptive coagulopathy is associated with a disturbed host response in patients with sepsis
    (2021-04-01) Lonneke A. van Vught; Fabrice Uhel; Chao Ding; Cees van‘t Veer; Brendon P. Scicluna; Hessel Peters-Sengers; Peter M.C. Klein Klouwenberg; Peter Nürnberg; Olaf L. Cremer; Marcus J. Schultz; Tom van der Poll; Friso M. de Beer; Lieuwe D.J. Bos; Gerie J. Glas; Arie J. Hoogendijk; Roosmarijn T.M. van Hooijdonk; Janneke Horn; Mischa A. Huson; Laura R.A. Schouten; Marleen Straat; Luuk Wieske; Maryse A. Wiewel; Esther Witteveen; Marc J.M. Bonten; Olaf M. Cremer; David S.Y. Ong; Jos F. Frencken; Maria E. Koster-Brouwer; Kirsten van de Groep; Diana M. Verboom; Amsterdam institute for Infection and Immunity; Sun Yat-Sen University Cancer Center; University Medical Center Utrecht; University of Cologne; Mahidol University; Nuffield Department of Medicine; Amsterdam UMC - University of Amsterdam
    Background: A prolonged prothrombin time (PT) is a common feature in sepsis indicating consumptive coagulopathy. Objectives: To determine the association between a prolonged PT and aberrations in other host response mechanisms in sepsis. Methods: Patients admitted to the intensive care unit with sepsis were divided in quartiles according to the highest PT value measured within 24 h after admission. The host response was evaluated by measuring 19 plasma biomarkers reflecting pathways implicated in sepsis pathogenesis and by blood leukocyte gene expression profiling. Measurements and Main Results: Of 1524 admissions for sepsis, 386 (25.3%) involved patients with a normal PT (≤12.7 s); the remaining quartiles entailed 379 (24.9%) patients with a slightly prolonged PT (12.8 ≤ PT ≤ 15.0 s), 383 (25.1%) with an intermediately prolonged PT (15.1 ≤ PT ≤ 17.2 s), and 376 (24.7%) with an extremely prolonged PT (≥17.3 s). While patients with an extremely prolonged PT showed an increased crude mortality up to 1 year after admission, none of the prolonged PT groups was independently associated with 30-day adjusted mortality. Comparison of the host response between patients with a normal PT or an extremely prolonged PT matched for baseline characteristics including severity of disease showed that an extremely prolonged PT was associated with impaired anticoagulant mechanisms, a more disturbed endothelial barrier integrity and increased systemic inflammation, and blood leukocyte transcriptomes indicating more prominent metabolic reprogramming and protein catabolism. Conclusion: A prolonged PT is associated with stronger anomalies in pathways implicated in the pathogenesis of sepsis, suggesting that activation of coagulation impacts other host response mechanisms.
  • No Thumbnail Available
    PublicationMetadata only
    Elaboration of Consensus Clinical Endpoints to Evaluate Antimicrobial Treatment Efficacy in Future Hospital-acquired/Ventilator-associated Bacterial Pneumonia Clinical Trials
    (2019-11-13) Emmanuel Weiss; Jean Ralph Zahar; Jeff Alder; Karim Asehnoune; Matteo Bassetti; Marc J.M. Bonten; Jean Chastre; Jan De Waele; George Dimopoulos; Philippe Eggimann; Marc Engelhardt; Santiago Ewig; Marin Kollef; Jeffrey Lipman; Carlos Luna; Ignacio Martin-Loeches; Leonardo Pagani; Lucy B. Palmer; Laurent Papazian; Garyphallia Poulakou; Philippe Prokocimer; Jordi Rello; John H. Rex; Andrew F. Shorr; George H. Talbot; Visanu Thamlikitkul; Antoni Torres; Richard G. Wunderink; Jean François Timsit; F2G Limited; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias; Regional Hospital of Bolzano; Augusta Krankenanstalt; University Hospital of Ghent; University of Athens Medical School; University Medical Center Utrecht; Royal Brisbane and Women's Hospital; Washington Hospital Center; Sotiria General Hospital; Stony Brook University; Università degli Studi di Udine; Basilea Pharmaceutica Ltd.; Hôtel Dieu CHU de Nantes; Centre Hospitalier Universitaire Vaudois; Hôpital Bichat-Claude-Bernard AP-HP; Washington University School of Medicine in St. Louis; University of Witwatersrand; Hôpital Universitaire Pitié Salpêtrière; Attikon University Hospital; Northwestern University Feinberg School of Medicine; Hôpital Nord AP-HM; Faculty of Medicine, Siriraj Hospital, Mahidol University; Trinity College Dublin; Universite Paris 13; Hospital de Clinicas Jose de San Martin; Hopital Avicenne; Merck & Co., Inc.; Hopital Beaujon; Universite Paris 7- Denis Diderot; Universitat de Barcelona; Inserm; Bayer US LLC; Talbot Advisors LLC
    © 2019 The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. Background: Randomized clinical trials (RCTs) in hospital-acquired and ventilator-associated bacterial pneumonia (HABP and VABP, respectively) are important for the evaluation of new antimicrobials. However, the heterogeneity in endpoints used in RCTs evaluating treatment of HABP/VABP may puzzle clinicians. The aim of this work was to reach a consensus on clinical endpoints to consider in future clinical trials evaluating antimicrobial treatment efficacy for HABP/VABP. Methods: Twenty-six international experts from intensive care, infectious diseases, and the pharmaceutical industry were polled using the Delphi method. Results: The panel recommended a hierarchical composite endpoint including, by priority order, (1) survival at day 28, (2) mechanical ventilation-free days through day 28, and (3) clinical cure between study days 7 and 10 for VABP; and (1) survival (day 28) and (2) clinical cure (days 7-10) for HABP. Clinical cure was defined as the combination of resolution of signs and symptoms present at enrollment and improvement or lack of progression of radiological signs. More than 70% of the experts agreed to assess survival and mechanical ventilation-free days though day 28, and clinical cure between day 7 and day 10 after treatment initiation. Finally, the hierarchical order of endpoint components was reached after 3 Delphi rounds (72% agreement). Conclusions: We provide a multinational expert consensus on separate hierarchical composite endpoints for VABP and HABP, and on a definition of clinical cure that could be considered for use in future HABP/VABP clinical trials.
  • No Thumbnail Available
    PublicationMetadata only
    Interpreting and comparing risks in the presence of competing events
    (2014-08-21) Martin Wolkewitz; Ben S. Cooper; Marc J.M. Bonten; Adrian G. Barnett; Martin Schumacher; Universitat Freiburg im Breisgau; Mahidol University; University of Oxford; University Medical Center Utrecht; Queensland University of Technology QUT