Clinical trial NCT02210221: CENTER-TBI: Collaborative European NeuroTrauma Effectiveness Research in TBI
Official title: Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Traumatic Brain Injury
Keywords: TBI
Lead sponsor: University Hospital, Antwerp
Sponsor class: OTHER
Collaborators: name: University of Cambridge
name: Erasmus Medical Center
name: San Gerardo Hospital
name: University of Sheffield
name: University of California, San Francisco
name: Karolinska Institutet
name: ICON plc
name: GABO:mi
name: icometrix
First posted: 2014-08-06
Enrollment: 4559
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients presenting with traumatic brain injury.

The data collection will be stratified upon enrolment into 3 clinical groups differentiated by clinical care path:

* ER stratum: patients seen and discharged from the ER
* Admission stratum: patients admitted to hospital but not to the ICU
* ICU stratum: patients admitted directly to the ICU

Brief summary: The research aims of the CENTER-TBI study are to:

1. better characterize Traumatic Brain Injury (TBI) as a disease and describe it in a European context, and
2. identify the most effective clinical interventions for managing TBI.

Specific aims

1. To collect high quality clinical and epidemiological data with repositories for neuro-imaging, DNA, and serum from patients with TBI.
2. To refine and improve outcome assessment and develop health utility indices for TBI.
3. To develop multidimensional approaches to characterisation and prediction of TBI.
4. To define patient profiles which predict efficacy of specific interventions ("Precision Medicine").
5. To develop performance indicators for quality assurance and quality improvement in TBI care.
6. To validate the common data elements (CDEs) for broader use in international settings, and to develop a user-friendly web based data entry instrument and case report form builder.
7. To develop an open database compatible with Federal Interagency Traumatic Brain Injury Research (FITBIR).
8. To intensify networking activities and international collaborations in TBI.
9. To disseminate study results and management recommendations for TBI to health care professionals, policy makers and consumers, aiming to improve health care for TBI at individual and population levels.
10. To develop a "knowledge commons" for TBI, integrating CENTER-TBI outputs into systematic reviews.

Detailed description: • Introduction:

CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI) (www.center-tbi.eu) is a project embedded within the International Initiative on TBI Research (InTBIR) (http://intbir.nih.gov/), as a collaboration between the European Commission (EC), the US National Institute of Neurological Disorders and Stroke (NIH-NINDS) and the Canadian Institute of Health Research (CIHR).

* Research aims:

The basic concept of this project is to exploit the existing heterogeneity in biology, care and outcome of TBI patients to discover underlying pathophysiology, to refine characterisation, and to identify effective clinical interventions. The key driver of our research plan is to collect data from a large number of European centres and sufficiently large cohort to enable 'Comparative effectiveness research' (CER) analyses of differences in clinical care and management pathways in TBI.

Improved disease characterization will aid Precision Medicine, a concept recently enunciated by the US National Academy of Science. Such improved characterization and stratification will allow for more targeted therapies. Further, CER provides a promising framework to identify best practices and improve outcome after TBI. CER is the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition or to improve the delivery of care. The purpose of CER is to assist consumers, clinicians, purchasers, and policy makers to make informed decisions that will improve health care at both the individual and population levels.

* Cohort:

A large core cohort of patients across the severity spectrum in TBI will be recruited at approximately 77 sites in Europe and Israel (the CENTER-TBI Core Study): 5400 patients differentiated into 3 equal strata of approximately 1800:

* ER stratum: patients seen and discharged from the ER;
* Admission stratum: patients admitted to the hospital but not to the ICU;
* ICU stratum: patients admitted directly to the ICU. Balance in numbers between the strata will be aimed for, but sites will be allowed to arrange recruitment strategies to best suit their local requirements.

The core cohort will be underpinned by comparison with a larger registry (the CENTER-TBI registry) based on pragmatic data collection of all patients with TBI seen in participating centres (to establish the internal generalizability of our study), and by comparison with national trauma registries (to establish the external generalizability of our findings).

In the core cohort, detailed data will be collected on clinical parameters, neuroimaging studies, biomarker analyses, DNA analyses, and longitudinal outcome assessments. In selected centres, extended studies will additionally focus on advanced magnetic resonance (MR) imaging, detailed coagulation profiling and high resolution ICU monitoring.

* Sample size assessment:

The sample size estimate (n=5400) was based on:

* Practical logistic considerations
* Power calculations for the different strata, targeting comparative effectiveness analyses, assuming a between-centre and between-country heterogeneity as identified in previous research (expressed by variance parameter from a random effects model, Tau\^2 of 0.431)
* Postulated odds ratios for intervention effects of approximately 5% improvement in outcome.

Overall, these calculations provided a statistical power to detect odds ratios of \~1.2 associated with differences in process or intervention variables across the core dataset with a power of 80%; and require somewhat larger odds ratios in each of the three individual strata. In the registry we expect to be able to detect differences (predominantly in organizational or system variables) with an odds ratio of 1.2 with a power of 82%.

* Quality control and assurance:

Continuous monitoring of enrolment and completeness of data will be performed by ICON as contract research organization (CRO). Source data verification (SDV) will be performed in 10% of subjects by the CRO. The quality of data collection will be further enhanced by implementing automated data entry checks for impossible/implausible values and implementing data checks for consistency between variables. A task force of study personnel will evaluate the completeness, consistency and validity of submitted data and function as support desk for participating sites.

* Data management:

Prior to upload to the study database, all acquired data will be stored locally. All patients will be allocated a random Global Unique Personal Identification number (GUPI) which will be linked locally to hospital identifiers. All uploaded data will be de-identified and images will be defaced prior to upload. While blood samples and clinical data will be linked, both sets of data will be kept confidential and anonymised beyond the initial stage of correlation for analysis. All imaging and electronic data will be kept on individually password protected servers. All clinical data will be entered into electronic Case Report Forms (eCRFs) and managed by the 'QuesGen data management platform' (http://www.quesgen.com/) which will be developed in collaboration with Karolinska Institutet International Neuroinformatics Coordinating Faculty (KI-INCF). As data is entered into each form, the system will run data validation checks that include conditionally required data, validation across fields, and validation requirements based on subject type. If any validation check fails, the user is alerted immediately that the data does not meet Quality Assurance (QA) criteria and the issue can be addressed and corrected at that point. All de-identified electronic study data in the CENTER-TBI database will be stored securely in the European data space under supervision of KI-INCF for the duration of subject enrolment and follow-up and for a period afterwards for data analysis and preparation of publications. We estimate that the analysis and publication period will last for several years after the conclusion of subject enrolment.

Together with QuesGen Systems, KI-INCF will ensure that data standards are established for the data model e.g. conformity of field formats, field codes and names to ensure consistency across all datasets. Any approved changes will be fully documented with dataset updates to maintain data quality and accuracy. KI-INCF will be responsible for importing cleaned datasets to other analytic platforms as determined by the coordinators.

Where applicable, information relevant to the patient's care will be made available to the physician responsible. Data, including blood samples collected as part of this study will be shared in an anonymised form with collaborators from other European states (this is part of a European Commission Framework7 funded program), and with selected collaborators in other countries who form part of an emerging International Traumatic Brain Injury Research initiative.

* Computing platform and Neuroinformatics Resource:

The KI-INCF will coordinate the establishment of an informatics platform for acquisition, storage and analysis of CDE-based clinical data. The goal is to develop a next generation open standards-based platform to support advanced large-scale analytics and model building. Such a platform also provides a model for future clinical studies on brain diseases and disorders. This development will receive additional support from One Mind for Research.

* Statistical analysis plan:

Statistical analyses for the Comparative Effectiveness Research (CER) questions will primarily apply random effects modelling, in which center is included at the higher level, and patients are considered clustered within centers. In some analyses, higher levels of clustering will also be considered, e.g. country, or European region; or lower levels, e.g. physicians within hospitals. Confounding factors as measured at the individual patient and/or center level, will be considered extensively, and will be targeted to the specific research question.

Statistical analyses for better characterization of TBI will be exploratory, aiming to better understand the complexity of the disease and to discover new associations. In addition to standard statistical descriptive and inferential techniques, we will also employ novel machine learning techniques as appropriate.

Prognostic analyses will consider a range of variables, including genetic, demographic and clinical data, physiological signals, imaging results, and biomarkers as predictors of early endpoints and physiologic derangement (e.g. raised ICP), and late outcome, including mortality, functional outcome, quality of life and neuropsychological performance. Previously and newly developed prediction models will be validated by comparison of observed to predicted outcome risks, with predictive performance summarized by measures for model fit, discrimination, and calibration.

* Missing data:

Every effort will be made to limit the number of missing data in the CENTER-TBI study. Missing values are, however, inherent to any clinical study. Missing values may confound the descriptive, prognostic and CER analyses. Thus, appropriate techniques for dealing with missing values are required. First, we will evaluate the various reasons for missingness per centre. Next, we will explore the use of alternative statistical approaches, including inverse probability weighting and multiple imputation. We will consider missing values in baseline characteristics as well as in short and long term outcomes. Based on simulation studies and practical considerations we will develop standard operating procedures towards the analyses with missing values, respecting the differences in multiple research questions.

* Informed Consent:

Informed consent procedures will follow local and national requirements in all cases. We anticipate that many potential patients will not be able to consent themselves to participate in this project. The nature of TBI means that some patients may lack capacity to decide to participate in this study especially at the earliest time point. It is important to try and include these patients to ensure that representative samples of patients are included to avoid bias in the study findings. Every step will be taken to ensure that a test of capacity is undertaken before a decision on a person's capacity to consent or not to consent to participation in research is taken. If the subject is not capable of self-consent, all efforts will be made to locate a legally acceptable representative to act on behalf of the subject. When a legally acceptable representative (e.g. consultee/proxy) is identified, their opinion will be sought about the potential participant's wishes and feelings in relation to the project, and whether he or she would have wanted to take part in the study.

Subjects are free to withdraw, or be withdrawn by their consultee/proxy if appropriate, at any point in the study, and they need not state a reason.

* Impact:

The CENTER-TBI project will contribute towards the overall goals of InTBIR, by identifying more effective and efficient treatment provision, thus improving outcome and reducing costs. The science in the project will provide novel information on disease processes, treatment, outcome, and prognosis in TBI, identifying new therapeutic targets and therapies; while the CENTER-TBI repositories will ensure opportunities for legacy research. Thus, the project has the potential to improve current health care and its delivery at both population and individual levels, deliver early scientific advances that could improve the care of patients with TBI, and provide a rich investment for future biomedical research.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of TBI
* Clinical indication for CT scan
* Presentation within 24 hours of injury
* Informed consent obtained according to local and national requirements

Exclusion Criteria:

* Severe pre-existing neurological disorder that would confound outcome assessments

Primary outcomes:
measure: Glasgow Outcome Scale - Extended (GOSE) at 6 Months
timeFrame: 6 months
measure: SF-12v2 Health Survey (Short-Form Health Survey With 12 Questions) at 6 Months
timeFrame: 6 months
measure: 6 Month Quality of Life in Brain Injury (Qolibri-OS) <52 (Impaired)
timeFrame: 6 months
Secondary outcomes:
measure: 6 Month Post-traumatic Stress Disorder (PTSD) Checklist for DSM-5 (PCL-5) <33 (Impaired)
timeFrame: 6 months
measure: 6 Month Rivermead Post Concussion Questionnaire <16 (Impaired)
timeFrame: 6 months
measure: 6 Month Galveston Orientation and Amnesia Test (GOAT) < 75 (Impaired)
timeFrame: 6 months
measure: 6 Month Rey Auditory Verbal Learning Test (RAVLT) - Impaired
timeFrame: 6 months
measure: 6 Month Timed up and go Test - Impaired
timeFrame: 6 months
measure: 6 Month JK Coma Recovery Scale - Revised <23 (Impaired)
timeFrame: 6 months
measure: 6 Month Trail Making Test (TMT) Part A - Impaired
timeFrame: 6 months
measure: 6 Month Trail Making Test (TMT) Part B - Impaired
timeFrame: 6 months
measure: 6 Month Cambridge Neuropsychological Test Automated Battery (CANTAB) PAL (Paired Associate Learning Task) - Impaired
timeFrame: 6 months
measure: 6 Month Cambridge Neuropsychological Test Automated Battery (CANTAB) RTI (Reaction Time Task) - Impaired
timeFrame: 6 months
measure: 6 Month Cambridge Neuropsychological Test Automated Battery (CANTAB) SWM (Spatial Working Memory Task) - Impaired
timeFrame: 6 months
measure: 6 Month Cambridge Neuropsychological Test Automated Battery (CANTAB) RVP (Rapid Visual Information Processing Task) - Impaired
timeFrame: 6 months
measure: 6 Month Cambridge Neuropsychological Test Automated Battery (CANTAB) SOC (Stockings of Cambridge Task) - Impaired
timeFrame: 6 months
measure: 6 Month Cambridge Neuropsychological Test Automated Battery (CANTAB) AST (Attention Switching Task ) - Impaired
timeFrame: 6 months
measure: Early (2-3 Weeks) MRI Imaging - Traumatic Intracranial Abnormalities
timeFrame: Between 2-3 weeks after enrolment
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Innsbruck Medical University
city: Vienna
country: Austria
facility: Medical University Vienna
city: Edegem
country: Belgium
facility: Antwerp University Hospital
city: Leuven
country: Belgium
facility: University Hospitals Leuven
city: Liege
country: Belgium
facility: CHR Citadelle
city: Liege
country: Belgium
facility: CHU Liege
city: Copenhagen
country: Denmark
facility: Region Hovedstaden Rigshospitalet
city: Odense
country: Denmark
facility: Odense University Hospital
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Turku
country: Finland
facility: Turku University Hospital
city: Grenoble
country: France
facility: University Hospital of Grenoble
city: Lille
country: France
facility: Lille University Hospital
city: Nancy
country: France
facility: University Hospital Nancy
city: Paris
country: France
facility: APHP
city: Poitiers
country: France
facility: CHU Poitiers
city: Aachen
country: Germany
facility: University Hospital Aachen
city: Berlin
country: Germany
facility: Charité Campus Virchow
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg
city: Ludwigsburg
country: Germany
facility: Klinikum Ludwigsburg
city: Pecs
country: Hungary
facility: University of Pecs
city: Szeged
country: Hungary
facility: University of Szeged
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah-hebrew University Medical Center
city: Cesena
country: Italy
facility: Bufalini Hospital
city: Milan
country: Italy
facility: Fondazione IRCCS Cà Granda Ospedale Maggiore Poloclinico
city: Milan
country: Italy
facility: Niguarda Hospital
city: Milan
country: Italy
facility: S Raffaele University Hospital
city: Monza
country: Italy
facility: ASST di Monza
city: Novara
country: Italy
facility: Maggiore Della Carità Hospital
city: Padova
country: Italy
facility: Azienda Ospedaliera Università di Padova
city: Torino
country: Italy
facility: AOU Città della Salute e della Scienza di Torino
city: Rezekne
country: Latvia
facility: Rezekne Hospital
city: Riga
country: Latvia
facility: Pauls Stradins Clinical University Hospital
city: Riga
country: Latvia
facility: Riga Eastern Clinical University Hospital
city: Kaunas
country: Lithuania
facility: University of Health Sciences
city: Vilnius
country: Lithuania
facility: Center of neurovascular surgery, Clinic of neurology and neurosurgery, Vilnius University
city: Vilnius
country: Lithuania
facility: Kaunas University of technology and Vilnius University
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: The Hague
country: Netherlands
facility: Medical Center Haaglanden
city: The Hague
country: Netherlands
facility: The HAGA Hospital
city: Tilburg
country: Netherlands
facility: TweeSteden Ziekenhuis
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Tromso
country: Norway
facility: University Hospital Northern Norway
city: Trondheim
country: Norway
facility: St Olavs Hospital/Norwegian University of science and technology
city: Timisoara
country: Romania
facility: Emergency County Hospital Timisoara
city: Novi Sad
country: Serbia
facility: Clinical centre of Vojvodina
city: Barcelona
country: Spain
facility: Vall d'Hebron University Hospital
city: Bilbao
country: Spain
facility: Cruces University Hospital
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: Clínico Universitario de Valencia
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Umea
country: Sweden
facility: Umea University Hospital
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Bristol
country: United Kingdom
facility: Southmead Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: Edinburgh
country: United Kingdom
facility: Lothian Health Board
city: Liverpool
country: United Kingdom
facility: The Walton centre NHS Foundation Trust
city: London
country: United Kingdom
facility: Kings college London
city: Salford
country: United Kingdom
facility: Salford Royal Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
city: Southampton
country: United Kingdom
facility: University Hospitals Southampton NHS Trust
Study officials:
affiliation: Antwerp University Hospital / University of Antwerp, Edegem, Belgium
name: Andrew Maas, MD, PhD
role: STUDY_CHAIR
affiliation: University of Cambridge, Addenbrookes hospital, Cambridge, UK
name: David Menon, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Rezoagli E, Petrosino M, Rebora P, Menon DK, Mondello S, Cooper DJ, Maas AIR, Wiegers EJA, Galimberti S, Citerio G; CENTER-TBI, OzENTER-TBI Participants and Investigators. High arterial oxygen levels and supplemental oxygen administration in traumatic brain injury: insights from CENTER-TBI and OzENTER-TBI. Intensive Care Med. 2022 Dec;48(12):1709-1725. doi: 10.1007/s00134-022-06884-x. Epub 2022 Oct 20.
citation: Akerlund CAI, Holst A, Stocchetti N, Steyerberg EW, Menon DK, Ercole A, Nelson DW; CENTER-TBI Participants and Investigators. Clustering identifies endotypes of traumatic brain injury in an intensive care cohort: a CENTER-TBI study. Crit Care. 2022 Jul 27;26(1):228. doi: 10.1186/s13054-022-04079-w.
citation: Volovici V, Pisica D, Gravesteijn BY, Dirven CMF, Steyerberg EW, Ercole A, Stocchetti N, Nelson D, Menon DK, Citerio G, van der Jagt M, Maas AIR, Haitsma IK, Lingsma HF; CENTER-TBI investigators, participants for the ICU stratum. Comparative effectiveness of intracranial hypertension management guided by ventricular versus intraparenchymal pressure monitoring: a CENTER-TBI study. Acta Neurochir (Wien). 2022 Jul;164(7):1693-1705. doi: 10.1007/s00701-022-05257-z. Epub 2022 Jun 1.
citation: van Essen TA, Lingsma HF, Pisica D, Singh RD, Volovici V, den Boogert HF, Younsi A, Peppel LD, Heijenbrok-Kal MH, Ribbers GM, Walchenbach R, Menon DK, Hutchinson P, Depreitere B, Steyerberg EW, Maas AIR, de Ruiter GCW, Peul WC; CENTER-TBI Collaboration Group. Surgery versus conservative treatment for traumatic acute subdural haematoma: a prospective, multicentre, observational, comparative effectiveness study. Lancet Neurol. 2022 Jul;21(7):620-631. doi: 10.1016/S1474-4422(22)00166-1. Epub 2022 May 5.
citation: Holthe IL, Dahl HM, Rohrer-Baumgartner N, Eichler S, Elseth MF, Holthe O, Berntsen T, Yeates KO, Andelic N, Lovstad M. Neuropsychological Impairment, Brain Injury Symptoms, and Health-Related Quality of Life After Pediatric TBI in Oslo. Front Neurol. 2022 Jan 28;12:719915. doi: 10.3389/fneur.2021.719915. eCollection 2021.
citation: Huijben JA, Pisica D, Ceyisakar I, Stocchetti N, Citerio G, Maas AIR, Steyerberg EW, Menon DK, van der Jagt M, Lingsma HF. Pharmaceutical Venous Thrombosis Prophylaxis in Critically Ill Traumatic Brain Injury Patients. Neurotrauma Rep. 2022 Jan 7;2(1):4-14. doi: 10.1089/neur.2021.0037. eCollection 2022.
citation: Galimberti S, Graziano F, Maas AIR, Isernia G, Lecky F, Jain S, Sun X, Gardner RC, Taylor SR, Markowitz AJ, Manley GT, Valsecchi MG, Bellelli G, Citerio G; CENTER-TBI and TRACK-TBI participants and investigators. Effect of frailty on 6-month outcome after traumatic brain injury: a multicentre cohort study with external validation. Lancet Neurol. 2022 Feb;21(2):153-162. doi: 10.1016/S1474-4422(21)00374-4.
citation: Puybasset L, Perlbarg V, Unrug J, Cassereau D, Galanaud D, Torkomian G, Battisti V, Lefort M, Velly L, Degos V, Citerio G, Bayen E, Pelegrini-Issac M; MRI-COMA Investigators CENTER-TBI MRI Participants and MRI Only Investigators. Prognostic value of global deep white matter DTI metrics for 1-year outcome prediction in ICU traumatic brain injury patients: an MRI-COMA and CENTER-TBI combined study. Intensive Care Med. 2022 Feb;48(2):201-212. doi: 10.1007/s00134-021-06583-z. Epub 2022 Dec 14.
citation: Citerio G, Robba C, Rebora P, Petrosino M, Rossi E, Malgeri L, Stocchetti N, Galimberti S, Menon DK; Center-TBI participants and investigators. Management of arterial partial pressure of carbon dioxide in the first week after traumatic brain injury: results from the CENTER-TBI study. Intensive Care Med. 2021 Sep;47(9):961-973. doi: 10.1007/s00134-021-06470-7. Epub 2021 Jul 24.
citation: Robba C, Rebora P, Meyfroidt G, Citerio G. The authors reply. Crit Care Med. 2021 May 1;49(5):e554-e555. doi: 10.1097/CCM.0000000000004961. No abstract available.
citation: Huijben JA, Dixit A, Stocchetti N, Maas AIR, Lingsma HF, van der Jagt M, Nelson D, Citerio G, Wilson L, Menon DK, Ercole A; CENTER-TBI investigators and participants. Use and impact of high intensity treatments in patients with traumatic brain injury across Europe: a CENTER-TBI analysis. Crit Care. 2021 Feb 23;25(1):78. doi: 10.1186/s13054-020-03370-y.
citation: Borgen IMH, Roe C, Brunborg C, Tenovuo O, Azouvi P, Dawes H, Majdan M, Ranta J, Rusnak M, Wiegers EJA, Tverdal C, Jacob L, Cogne M, von Steinbuechel N, Andelic N; CENTER-TBI participants investigators. Care transitions in the first 6months following traumatic brain injury: Lessons from the CENTER-TBI study. Ann Phys Rehabil Med. 2021 Nov;64(6):101458. doi: 10.1016/j.rehab.2020.10.009. Epub 2021 Jul 23.
citation: Robba C, Banzato E, Rebora P, Iaquaniello C, Huang CY, Wiegers EJA, Meyfroidt G, Citerio G; Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) ICU Participants and Investigators. Acute Kidney Injury in Traumatic Brain Injury Patients: Results From the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Study. Crit Care Med. 2021 Jan 1;49(1):112-126. doi: 10.1097/CCM.0000000000004673.
citation: Gravesteijn BY, Sewalt CA, Nieboer D, Menon DK, Maas A, Lecky F, Klimek M, Lingsma HF; CENTER-TBI collaborators. Tracheal intubation in traumatic brain injury: a multicentre prospective observational study. Br J Anaesth. 2020 Oct;125(4):505-517. doi: 10.1016/j.bja.2020.05.067. Epub 2020 Jul 31.
citation: Gao G, Wu X, Feng J, Hui J, Mao Q, Lecky F, Lingsma H, Maas AIR, Jiang J; China CENTER-TBI Registry Participants. Clinical characteristics and outcomes in patients with traumatic brain injury in China: a prospective, multicentre, longitudinal, observational study. Lancet Neurol. 2020 Aug;19(8):670-677. doi: 10.1016/S1474-4422(20)30182-4.
citation: Robba C, Rebora P, Banzato E, Wiegers EJA, Stocchetti N, Menon DK, Citerio G; Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Participants and Investigators. Incidence, Risk Factors, and Effects on Outcome of Ventilator-Associated Pneumonia in Patients With Traumatic Brain Injury: Analysis of a Large, Multicenter, Prospective, Observational Longitudinal Study. Chest. 2020 Dec;158(6):2292-2303. doi: 10.1016/j.chest.2020.06.064. Epub 2020 Jul 4.
citation: Riemann L, Beqiri E, Smielewski P, Czosnyka M, Stocchetti N, Sakowitz O, Zweckberger K, Unterberg A, Younsi A; CENTER-TBI High Resolution ICU (HR ICU) Sub-Study Participants and Investigators. Low-resolution pressure reactivity index and its derived optimal cerebral perfusion pressure in adult traumatic brain injury: a CENTER-TBI study. Crit Care. 2020 May 26;24(1):266. doi: 10.1186/s13054-020-02974-8.
citation: Gravesteijn BY, Nieboer D, Ercole A, Lingsma HF, Nelson D, van Calster B, Steyerberg EW; CENTER-TBI collaborators. Machine learning algorithms performed no better than regression models for prognostication in traumatic brain injury. J Clin Epidemiol. 2020 Jun;122:95-107. doi: 10.1016/j.jclinepi.2020.03.005. Epub 2020 Mar 20.
citation: Huijben JA, Wiegers EJA, Ercole A, de Keizer NF, Maas AIR, Steyerberg EW, Citerio G, Wilson L, Polinder S, Nieboer D, Menon D, Lingsma HF, van der Jagt M; CENTER-TBI investigators and participants for the ICU stratum. Quality indicators for patients with traumatic brain injury in European intensive care units: a CENTER-TBI study. Crit Care. 2020 Mar 4;24(1):78. doi: 10.1186/s13054-020-2791-0.
citation: Van Essen TA, Volovici V, Cnossen MC, Kolias A, Ceyisakar I, Nieboer D, Peppel LD, Heijenbrok-Kal M, Ribbers G, Menon D, Hutchinson P, Depreitere B, de Ruiter GCW, Lingsma HF, Steyerberg EW, Maas AI, Peul WC. Comparative effectiveness of surgery in traumatic acute subdural and intracerebral haematoma: study protocol for a prospective observational study within CENTER-TBI and Net-QuRe. BMJ Open. 2019 Oct 16;9(10):e033513. doi: 10.1136/bmjopen-2019-033513.
citation: Steyerberg EW, Wiegers E, Sewalt C, Buki A, Citerio G, De Keyser V, Ercole A, Kunzmann K, Lanyon L, Lecky F, Lingsma H, Manley G, Nelson D, Peul W, Stocchetti N, von Steinbuchel N, Vande Vyvere T, Verheyden J, Wilson L, Maas AIR, Menon DK; CENTER-TBI Participants and Investigators. Case-mix, care pathways, and outcomes in patients with traumatic brain injury in CENTER-TBI: a European prospective, multicentre, longitudinal, cohort study. Lancet Neurol. 2019 Oct;18(10):923-934. doi: 10.1016/S1474-4422(19)30232-7.
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