Elsevier

The Lancet Neurology

Volume 18, Issue 10, October 2019, Pages 923-934
The Lancet Neurology

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

https://doi.org/10.1016/S1474-4422(19)30232-7Get rights and content

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.

Introduction

The burden of traumatic brain injury (TBI) is widely recognised as a large public health and societal problem. TBI results in 1·5 million hospital admissions and 57 000 deaths in the EU each year,1 but the landscape of TBI in European hospitals is poorly characterised. In November, 2017, a Commission in The Lancet Neurology2 on TBI highlighted the burden posed by TBI to patients, relatives, and society, and provided recommendations to improve patient outcomes through improved prevention, clinical care, and research. One recommendation was for large collaborative observational studies to collect longitudinal data, which could improve patient characterisation to allow better targeting of therapies and identify best practices through comparative effectiveness research.

Research in context

Evidence before this study

In November, 2017, the Commission onTraumatic brain injury: integrated approaches to improve prevention, clinical care, and research in The Lancet Neurology highlighted existing deficiencies in epidemiology and patient characterisation. An extensive literature search was undertaken as a basis for writing the Commission, which went beyond the academic literature and included national and international policy documents and statistical resources. These data were updated through more focused literature reviews for this manuscript. The Commission concluded that concerted efforts are urgently needed to address deficiencies in prevention, care, and research, and recommended that large collaborative studies be done, which could provide the framework for precision medicine and comparative effectiveness research.

Added value of this study

The CENTER-TBI registry and core study provide detailed insights into the contemporary landscape of traumatic brain injury (TBI) in Europe and constitute a unique resource for improving the characterisation of TBI, developing precision medicine approaches, and identification of best practices. The epidemiology of TBI as observed in the CENTER-TBI core study and registry differs from previous observational studies: patients were older, were most commonly injured by a fall, and many had comorbidities. Advanced neuroimaging and blood biomarkers can improve characterisation of injury type and severity. Differentiation of patients by care pathways provided novel insights. Around 95% of patients discharged from the emergency room or admitted to the ward, and a third of those primarily admitted to the ICU, had a so-called mild TBI. However, nearly a third of patients discharged from the emergency room and over half of those admitted to the hospital ward did not attain full recovery. There are substantial national and regional variations in care pathways and clinical management in Europe.

Implications of all the available evidence

The results from CENTER-TBI suggest that TBI should no longer be considered predominantly a disease of otherwise healthy young men. Falls were the most common cause of TBI and should motivate an increased focus for prevention. Mild TBI not only poses the greatest societal burden to health care, but also affects functional recovery and quality of life more than was commonly thought. Improved disease characterisation can contribute to precision medicine approaches through the development of multidimensional classifications of initial injury severity and outcome. Variations in care offer an opportunity for comparative effectiveness research to identify best practice.

The Collaborative European NeuroTrauma Effectiveness Research (CENTER-TBI) project is a European study, done within the InTBIR initiative,3 that was designed to address these needs.4 The project includes a multicentre, longitudinal, observational cohort study (core study) with highly granular data collection, which included detailed longitudinal clinical and outcome data, neuroimaging repositories, a DNA repository, and a blood and serum biobank; and a registry, which collected basic administrative data.

The main aims are to: (1) better characterise TBI as a disease and describe it in the European context, and (2) identify the most effective clinical interventions for managing TBI. Provider profiles of participating centres were established to characterise structures and processes of care in preparation for comparative effectiveness research.5, 6, 7, 8, 9, 10 We aim to describe the contemporary landscape of TBI in Europe, with a focus on the patient case-mix, care pathways, and outcomes in the core study, and to explore generalisability by comparison with data from the registry.

Section snippets

Study design and participants

CENTER-TBI includes a core study and a registry.4 65 centres initiated patient enrolment (figure 1). The core study was an observational, longitudinal, cohort study of patients with all severities of TBI, presenting between Dec 19, 2014, and Dec 17, 2017, to centres across Europe and Israel. Inclusion criteria were a clinical diagnosis of TBI, indication for CT scanning, presentation to study centre within 24 h of injury, and informed consent obtained according to local and national

Results

We enrolled 4559 patients in the core study and 22 849 patients in the registry from 65 sites in 19 countries. We analysed data from 4509 (98·9%) patients in the core study and 22 782 (99·7%) in the registry obtained from 18 countries (figure 1). The median number of enrolled patients by centre in the core study was 50 (IQR 21–107), with widely different distributions across strata (appendix pp 17, 18). In the core study, 848 (19%) patients in the ER stratum, 1523 (34%) in the admission

Discussion

This integrated analysis describes the landscape of TBI in the CENTER-TBI cohorts who presented in European hospitals, which differs substantially from previous observational studies.18, 19 Patients analysed in these cohorts were older, had more comorbidities, and injuries were most frequently caused by falls. The stratification of patients by care pathway showed clear discordances with the GCS-based classification of TBI severity, reflects the care that is provided, and sets a context for

Data sharing

Individual participant data, including data dictionary, and the study protocol, analytical code, and analysis scripts will be available immediately following publication, conditional to approved study proposal, with no end date. Data will be available to researchers who provide a methodologically sound study proposal that is approved by the management committee to achieve the aims in the approved proposal. Proposals can be submitted online at https://www.center-tbi.eu/data. A data access

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