Effect of frailty on 6-month outcome after traumatic brain injury: a multicentre cohort study with external validation

Stefania Galimberti, Francesca Graziano, CENTER-TBI and TRACK-TBI participants and investigators, Andrew I.R. Maas, Giulia Isernia, Fiona Lecky, Sonia Jain, Xiaoying Sun, Raquel C. Gardner, Sabrina R. Taylor, Amy J. Markowitz, Geoffrey T. Manley, Maria Grazia Valsecchi, Giuseppe Bellelli, Giuseppe Citerio*, Cecilia Ackerlund, Hadie Adams, Krisztina Amrein, Nada Andelic, Lasse AndreassenAudny Anke, Anna Antoni, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó, Kelly Foks, Benjamin Gravesteijn, Juanita A. Haagsma, Iain Haitsma, Jilske Huijben, Erwin Kompanje, Hester Lingsma, Ana Mikolic, Daan Nieboer, Dana Pisica, Suzanne Polinder, Isabel Retel Helmrich, Charlie Sewalt, Ranjit D. Singh, Ewout W. Steyerberg, Dick Tibboel, Mathieu van der Jagt, Thomas A. van Essen, Ernest van Veen, Kimberley Velt, Victor Volovici, Daphne Voormolen, Eveline Wiegers, Andrea Schneider

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

32 Citations (Scopus)


Background: Frailty is known to be associated with poorer outcomes in individuals admitted to hospital for medical conditions requiring intensive care. However, little evidence is available for the effect of frailty on patients’ outcomes after traumatic brain injury. Many frailty indices have been validated for clinical practice and show good performance to predict clinical outcomes. However, each is specific to a particular clinical context. We aimed to develop a frailty index to predict 6-month outcomes in patients after a traumatic brain injury. Methods: A cumulative deficit approach was used to create a novel frailty index based on 30 items dealing with disease states, current medications, and laboratory values derived from data available from CENTER-TBI, a prospective, longitudinal observational study of patients with traumatic brain injury presenting within 24 h of injury and admitted to a ward or an intensive care unit at 65 centres in Europe between Dec 19, 2014, and Dec 17, 2017. From the individual cumulative CENTER-TBI frailty index (range 0–30), we obtained a standardised value (range 0–1), with high scores indicating higher levels of frailty. The effect of frailty on 6-month outcome evaluated with the extended Glasgow Outcome Scale (GOSE) was assessed through a proportional odds logistic model adjusted for known outcome predictors. An unfavourable outcome was defined as death or severe disability (GOSE score ≤4). External validation was performed on data from TRACK-TBI, a prospective observational study co-designed with CENTER-TBI, which enrolled patients with traumatic brain injury at 18 level I trauma centres in the USA from Feb 26, 2014, to July 27, 2018. CENTER-TBI is registered with ClinicalTrials.gov, NCT02210221; TRACK-TBI is registered at ClinicalTrials.gov, NCT02119182. Findings: 2993 participants (median age was 51 years [IQR 30–67], 2058 [69%] were men) were included in this analysis. The overall median CENTER-TBI frailty index score was 0·07 (IQR 0·03–0·15), with a median score of 0·17 (0·08–0·27) in older adults (aged ≥65 years). The CENTER-TBI frailty index score was significantly associated with the probability of an increasingly unfavourable outcome (cumulative odds ratio [OR] 1·03, 95% CI 1·02–1·04; p<0·0001), and the association was stronger for participants admitted to hospital wards (1·04, 1·03–1·06, p<0·0001) compared with those admitted to the intensive care unit (1·02, 1·01–1·03 p<0·0001). External validation of the CENTER-TBI frailty index in data from the TRACK-TBI (n=1667) cohort supported the robustness and reliability of these findings. The overall median TRACK-TBI frailty index score was 0·03 (IQR 0–0·10), with the frailty index score significantly associated with the risk of an increasingly unfavourable outcome in patients admitted to hospital wards (cumulative OR 1·05, 95% CI 1·03–1·08; p<0·0001), but not in those admitted to the intensive care unit (1·01, 0·99–1·03; p=0·43). Interpretation: We developed and externally validated a frailty index specific to traumatic brain injury. Risk of unfavourable outcome was significantly increased in participants with a higher CENTER-TBI frailty index score, regardless of age. Frailty identification could help to individualise rehabilitation approaches aimed at mitigating effects of frailty in patients with traumatic brain injury. Funding: European Union, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences Corporation, NeuroTrauma Sciences, NIH-NINDS–TRACK-TBI, US Department of Defense.

Original languageEnglish
Pages (from-to)153-162
Number of pages10
JournalThe Lancet Neurology
Issue number2
Publication statusPublished - Feb 2022

Bibliographical note

Data used in the preparation of this manuscript were obtained in the context of the CENTER-TBI study, a large collaborative project, supported by the Framework 7 programme of the European Union (grant 602150). Additional funding was obtained from the Hannelore Kohl Stiftung (Germany), OneMind (USA), Integra LifeSciences Corporation (USA), and NeuroTrauma Sciences (USA). TRACK-TBI was supported by National Institute of Neurological Disorders and Stroke TRACK-TBI (grant #U01NS086090) and the US Department of Defense (TBI Endpoints Development Initiative, grant #W81XWH-14–2-0176).

Publisher Copyright: © 2022 Elsevier Ltd


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