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Case-mix, care pathways, and outcomes in patients with traumatic brain injury in CENTER-TBI: a European prospective, multicentre, longitudinal, cohort study - 13/09/19

Doi : 10.1016/S1474-4422(19)30232-7 
Ewout W Steyerberg, ProfPhD a, b, Eveline Wiegers, MSc a, *, Charlie Sewalt, MSc a, *, Andras Buki, ProfMD c, d, Giuseppe Citerio, ProfMD e, f, Véronique De Keyser, MA g, Ari Ercole, MD i, Kevin Kunzmann, PhD j, Linda Lanyon, PhD k, Fiona Lecky, ProfMD m, Hester Lingsma, PhD a, Geoffrey Manley, ProfMD n, David Nelson, MD l, Wilco Peul, ProfMD o, Nino Stocchetti, ProfMD p, q, Nicole von Steinbüchel, ProfPhD r, Thijs Vande Vyvere, MSc h, t, Jan Verheyden, MSc s, Lindsay Wilson, ProfPhD t, Andrew I R Maas, ProfMD g, u, * , David K Menon, Prof i, *
and the

CENTER-TBI Participants and Investigators

  Collaborators listed in the Supplementary Material
Cecilia Ackerlund, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Kaspars Auslands, Philippe Azouvi, Maria Luisa Azzolini, Rafael Badenes, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Ana M Castaño-León, Giorgio Chevallard, Arturo Chieregato, Maryse Cnossen, Mark Coburn, Jonathan Coles, Jamie D Cooper, Marta Correia, Amra Čović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot-Fizelier, Helen Dawes, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Simone Dijkland, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy-Loup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubović, Pedro A Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Ji-yao Jiang, Kelly Jones, Mladen Karan, Angelos G Kolias, Erwin Kompanje, Daniel Kondziella, Evgenios Koraropoulos, Lars-Owe Koskinen, Noémi Kovács, Alfonso Lagares, Linda Lanyon, Steven Laureys, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Angels Lozano, Marc Maegele, Marek Majdan, Alex Manara, Hugues Maréchal, Costanza Martino, Julia Mattern, Catherine McMahon, Béla Melegh, Tomas Menovsky, Davide Mulazzi, Visakh Muraleedharan, Lynnette Murray, Nandesh Nair, Ancuta Negru, Virginia Newcombe, Daan Nieboer, Quentin Noirhomme, József Nyirádi, Mauro Oddo, Matej Oresic, Fabrizio Ortolano, Olubukola Otesile, Aarno Palotie, Paul M Parizel, Jean-François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Anna Piippo-Karjalainen, Sébastien Pili Floury, Matti Pirinen, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P Posti, Louis Puybasset, Andreea Rădoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Ruben Real, Jonathan Rhodes, Sylvia Richardson, Sophie Richter, Samuli Ripatti, Saulius Rocka, Cecilie Roe, Olav Roise, Jonathan Rosand, Jeffrey V Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan Sanchez-Porras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Ana Stevanovic, Robert Stevens, William Stewart, Nina Sundström, Anneliese Synnot, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolijn Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Peter Vajkoczy, Egils Valeinis, Shirley Vallance, Zoltán Vámos, Joukje van der Naalt, Gregory Van der Steen, Jeroen T J M van Dijck, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Roel P J van Wijk, Thijs Vande Vyvere, Audrey Vanhaudenhuyse, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Daphne Voormolen, Petar Vulekovic, Kevin K W Wang, Guy Williams, Lindsay Wilson, Stefan Winzeck, Stefan Wolf, Zhihui Yang, Peter Ylén, Alexander Younsi, Frederick A Zeiler, Veronika Zelinkova, Agate Ziverte, Tommaso Zoerle

a Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands 
b Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands 
c Department of Neurosurgery, Medical School, University of Pécs, Pécs, Hungary 
d Neurotrauma Research Group, János Szentágothai Research Centre, University of Pécs, Pécs, Hungary 
e NeuroIntensive Care, ASST di Monza, Monza, Italy 
f School of Medicine and Surgery, Università Milano Bicocca, Milan, Italy 
g Department of Neurosurgery, Antwerp University Hospital, Edegem, Belgium 
h Department of Radiology, Antwerp University Hospital, Edegem, Belgium 
i Division of Anaesthesia, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK 
j MRC Biostatistics Unit, University of Cambridge, Cambridge, UK 
k International Neuroinformatics Coordinating Facility, Karolinska Institute, Stockholm, Sweden 
l Department of Physiology and Pharmacology, Section of Perioperative Medicine and Intensive Care, Karolinska Institute, Stockholm, Sweden 
m Centre for Urgent and Emergency Care Research, Health Services Research Section, School of Health and Related Research, University of Sheffield, Sheffield, UK 
n Department of Neurological Surgery, University of California, San Francisco, CA, USA 
o Leiden University Medical Centre and Haaglanden Medical Centre, University Neurosurgical Centre Holland, The Hague and Leiden, Netherlands 
p Department of Pathophysiology and Transplantation, Milan University, Milan, Italy 
q Neuroscience Intensive Care Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy 
r Institute of Medical Psychology and Medical Sociology, Universitätsmedizin Göttingen, Göttingen, Germany 
s Icometrix, Leuven, Belgium 
t Division of Psychology, University of Stirling, Stirling, UK 
u University of Antwerp, Edegem, Belgium 

* Correspondence to: Prof A I R Maas, Department of Neurosurgery, Antwerp University Hospital, Edegem 2650, Belgium Department of Neurosurgery Antwerp University Hospital Edegem 2650 Belgium

Summary

Background

The burden of traumatic brain injury (TBI) poses a large public health and societal problem, but the characteristics of patients and their care pathways in Europe are poorly understood. We aimed to characterise patient case-mix, care pathways, and outcomes of TBI.

Methods

CENTER-TBI is a Europe-based, observational cohort study, consisting of a core study and a registry. Inclusion criteria for the core study were a clinical diagnosis of TBI, presentation fewer than 24 h after injury, and an indication for CT. Patients were differentiated by care pathway and assigned to the emergency room (ER) stratum (patients who were discharged from an emergency room), admission stratum (patients who were admitted to a hospital ward), or intensive care unit (ICU) stratum (patients who were admitted to the ICU). Neuroimages and biospecimens were stored in repositories and outcome was assessed at 6 months after injury. We used the IMPACT core model for estimating the expected mortality and proportion with unfavourable Glasgow Outcome Scale Extended (GOSE) outcomes in patients with moderate or severe TBI (Glasgow Coma Scale [GCS] score ≤12). The core study was registered with ClinicalTrials.gov, number NCT02210221, and with Resource Identification Portal (RRID: SCR_015582).

Findings

Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study and from 22 782 patients in the registry. In the core study, 848 (19%) patients were in the ER stratum, 1523 (34%) in the admission stratum, and 2138 (47%) in the ICU stratum. In the ICU stratum, 720 (36%) patients had mild TBI (GCS score 13–15). Compared with the core cohort, the registry had a higher proportion of patients in the ER (9839 [43%]) and admission (8571 [38%]) strata, with more than 95% of patients classified as having mild TBI. Patients in the core study were older than those in previous studies (median age 50 years [IQR 30–66], 1254 [28%] aged >65 years), 462 (11%) had serious comorbidities, 772 (18%) were taking anticoagulant or antiplatelet medication, and alcohol was contributory in 1054 (25%) TBIs. MRI and blood biomarker measurement enhanced characterisation of injury severity and type. Substantial inter-country differences existed in care pathways and practice. Incomplete recovery at 6 months (GOSE <8) was found in 207 (30%) patients in the ER stratum, 665 (53%) in the admission stratum, and 1547 (84%) in the ICU stratum. Among patients with moderate-to-severe TBI in the ICU stratum, 623 (55%) patients had unfavourable outcome at 6 months (GOSE <5), similar to the proportion predicted by the IMPACT prognostic model (observed to expected ratio 1·06 [95% CI 0·97–1·14]), but mortality was lower than expected (0·70 [0·62–0·76]).

Interpretation

Patients with TBI who presented to European centres in the core study were older than were those in previous observational studies and often had comorbidities. Overall, most patients presented with mild TBI. The incomplete recovery of many patients should motivate precision medicine research and the identification of best practices to improve these outcomes.

Funding

European Union 7th Framework Programme, the Hannelore Kohl Stiftung, OneMind, and Integra LifeSciences Corporation.

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P. 923-934 - octobre 2019 Retour au numéro
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