TY - JOUR
T1 - Effect of frailty on 6-month outcome after traumatic brain injury
T2 - a multicentre cohort study with external validation
AU - CENTER-TBI and TRACK-TBI participants and investigators
AU - Galimberti, Stefania
AU - Graziano, Francesca
AU - Maas, Andrew I.R.
AU - Isernia, Giulia
AU - Lecky, Fiona
AU - Jain, Sonia
AU - Sun, Xiaoying
AU - Gardner, Raquel C.
AU - Taylor, Sabrina R.
AU - Markowitz, Amy J.
AU - Manley, Geoffrey T.
AU - Valsecchi, Maria Grazia
AU - Bellelli, Giuseppe
AU - Citerio, Giuseppe
AU - Ackerlund, Cecilia
AU - Adams, Hadie
AU - Amrein, Krisztina
AU - Andelic, Nada
AU - Andreassen, Lasse
AU - Anke, Audny
AU - Antoni, Anna
AU - Audibert, Gérard
AU - Azouvi, Philippe
AU - Azzolini, Maria Luisa
AU - Bartels, Ronald
AU - Barzó, Pál
AU - Beauvais, Romuald
AU - Beer, Ronny
AU - Bellander, Bo Michael
AU - Belli, Antonio
AU - Benali, Habib
AU - Berardino, Maurizio
AU - Beretta, Luigi
AU - Blaabjerg, Morten
AU - Bragge, Peter
AU - Brazinova, Alexandra
AU - Brinck, Vibeke
AU - Brooker, Joanne
AU - Brorsson, Camilla
AU - Buki, Andras
AU - Bullinger, Monika
AU - Cabeleira, Manuel
AU - Caccioppola, Alessio
AU - Calappi, Emiliana
AU - Calvi, Maria Rosa
AU - Cameron, Peter
AU - Carbayo Lozano, Guillermo
AU - Carbonara, Marco
AU - Castaño-León, Ana M.
AU - Cavallo, Simona
AU - Chevallard, Giorgio
AU - Chieregato, Arturo
AU - Clusmann, Hans
AU - Coburn, Mark Steven
AU - Coles, Jonathan
AU - Cooper, Jamie D.
AU - Correia, Marta
AU - Covic, Amra
AU - Curry, Nicola
AU - Czeiter, Endre
AU - Czosnyka, Marek
AU - Dahyot-Fizelier, Claire
AU - Dark, Paul
AU - Dawes, Helen
AU - De Keyser, Véronique
AU - Degos, Vincent
AU - Della Corte, Francesco
AU - den Boogert, Hugo
AU - Depreitere, Bart
AU - Đilvesi, Đula
AU - Dixit, Abhishek
AU - Donoghue, Emma
AU - Dreier, Jens
AU - Dulière, Guy Loup
AU - Ercole, Ari
AU - Esser, Patrick
AU - Ezer, Erzsébet
AU - Fabricius, Martin
AU - Feigin, Valery L.
AU - Foks, Kelly
AU - Frisvold, Shirin
AU - Furmanov, Alex
AU - Gagliardo, Pablo
AU - Galanaud, Damien
AU - Gantner, Dashiell
AU - Gao, Guoyi
AU - George, Pradeep
AU - Ghuysen, Alexandre
AU - Giga, Lelde
AU - Glocker, Ben
AU - Golubovic, Jagoš
AU - Gomez, Pedro A.
AU - Gratz, Johannes
AU - Gravesteijn, Benjamin
AU - Grossi, Francesca
AU - Gruen, Russell L.
AU - Gupta, Deepak
AU - Haagsma, Juanita A.
AU - Haitsma, Iain
AU - Helbok, Raimund
AU - Helseth, Eirik
AU - Horton, Lindsay
AU - Huijben, Jilske
AU - Hutchinson, Peter J.
AU - Jacobs, Bram
AU - Jankowski, Stefan
AU - Jarrett, Mike
AU - Jiang, Ji yao
AU - Johnson, Faye
AU - Jones, Kelly
AU - Karan, Mladen
AU - Kolias, Angelos G.
AU - Kompanje, Erwin
AU - Kondziella, Daniel
AU - Koskinen, Lars Owe
AU - Kovács, Noémi
AU - Kowark, Ana
AU - Lagares, Alfonso
AU - Lanyon, Linda
AU - Laureys, Steven
AU - Ledoux, Didier
AU - Lefering, Rolf
AU - Legrand, Valerie
AU - Lejeune, Aurelie
AU - Levi, Leon
AU - Lightfoot, Roger
AU - Lingsma, Hester
AU - Maegele, Marc
AU - Majdan, Marek
AU - Manara, Alex
AU - Maréchal, Hugues
AU - Martino, Costanza
AU - Mattern, Julia
AU - McFadyen, Charles
AU - McMahon, Catherine
AU - Melegh, Béla
AU - Menon, David
AU - Menovsky, Tomas
AU - Mikolic, Ana
AU - Misset, Benoit
AU - Muraleedharan, Visakh
AU - Murray, Lynnette
AU - Negru, Ancuta
AU - Nelson, David
AU - Newcombe, Virginia
AU - Nieboer, Daan
AU - Nyirádi, József
AU - Oresic, Matej
AU - Ortolano, Fabrizio
AU - Otesile, Olubukola
AU - Palotie, Aarno
AU - Parizel, Paul M.
AU - Payen, Jean François
AU - Perera, Natascha
AU - Perlbarg, Vincent
AU - Persona, Paolo
AU - Peul, Wilco
AU - Piippo-Karjalainen, Anna
AU - Pirinen, Matti
AU - Pisica, Dana
AU - Ples, Horia
AU - Polinder, Suzanne
AU - Pomposo, Inigo
AU - Posti, Jussi P.
AU - Puybasset, Louis
AU - Radoi, Andreea
AU - Ragauskas, Arminas
AU - Raj, Rahul
AU - Rambadagalla, Malinka
AU - Rehorčíková, Veronika
AU - Retel Helmrich, Isabel
AU - Rhodes, Jonathan
AU - Richardson, Sylvia
AU - Richter, Sophie
AU - Ripatti, Samuli
AU - Rocka, Saulius
AU - Roe, Cecilie
AU - Roise, Olav
AU - Rosenfeld, Jeffrey
AU - Rosenlund, Christina
AU - Rosenthal, Guy
AU - Rossaint, Rolf
AU - Rossi, Sandra
AU - Rueckert, Daniel
AU - Rusnák, Martin
AU - Sahuquillo, Juan
AU - Sakowitz, Oliver
AU - Sanchez-Porras, Renan
AU - Sandor, Janos
AU - Schäfer, Nadine
AU - Schmidt, Silke
AU - Schoechl, Herbert
AU - Schoonman, Guus
AU - Schou, Rico Frederik
AU - Schwendenwein, Elisabeth
AU - Sewalt, Charlie
AU - Singh, Ranjit D.
AU - Skandsen, Toril
AU - Smielewski, Peter
AU - Adeoye, Opeolu
N1 - Funding Information:
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).
Funding Information:
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
PY - 2022/2
Y1 - 2022/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85122939948&partnerID=8YFLogxK
U2 - 10.1016/S1474-4422(21)00374-4
DO - 10.1016/S1474-4422(21)00374-4
M3 - Article
C2 - 35065038
AN - SCOPUS:85122939948
VL - 21
SP - 153
EP - 162
JO - The Lancet Neurology
JF - The Lancet Neurology
SN - 1474-4422
IS - 2
ER -