Abstract
After mild traumatic brain injury (mTBI), a substantial proportion of individuals do not fully recover on the Glasgow Outcome Scale Extended (GOSE) or experience persistent post-concussion symptoms (PPCS). We aimed to develop prognostic models for the GOSE and PPCS at 6 months after mTBI and to assess the prognostic value of different categories of predictors (clinical variables; questionnaires; computed tomography [CT]; blood biomarkers). From the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, we included participants aged 16 or older with Glasgow Coma Score (GCS) 13-15. We used ordinal logistic regression to model the relationship between predictors and the GOSE, and linear regression to model the relationship between predictors and the Rivermead Post-concussion Symptoms Questionnaire (RPQ) total score. First, we studied a pre-specified Core model. Next, we extended the Core model with other clinical and sociodemographic variables available at presentation (Clinical model). The Clinical model was then extended with variables assessed before discharge from hospital: early post-concussion symptoms, CT variables, biomarkers, or all three categories (extended models). In a subset of patients mostly discharged home from the emergency department, the Clinical model was extended with 2-3–week post-concussion and mental health symptoms. Predictors were selected based on Akaike’s Information Criterion. Performance of ordinal models was expressed as a concordance index (C) and performance of linear models as proportion of variance explained (R2). Bootstrap validation was used to correct for optimism. We included 2376 mTBI patients with 6-month GOSE and 1605 patients with 6-month RPQ. The Core and Clinical models for GOSE showed moderate discrimination (C = 0.68 95% confidence interval 0.68 to 0.70 and C = 0.70[0.69 to 0.71], respectively) and injury severity was the strongest predictor. The extended models had better discriminative ability (C = 0.71[0.69 to 0.72] with early symptoms; 0.71[0.70 to 0.72] with CT variables or with blood biomarkers; 0.72[0.71 to 0.73] with all three categories). The performance of models for RPQ was modest (R2 = 4% Core; R2 = 9% Clinical), and extensions with early symptoms increased the R2 to 12%. The 2-3-week models had better performance for both outcomes in the subset of participants with these symptoms measured (C = 0.74 [0.71 to 0.78] vs. C = 0.63[0.61 to 0.67] for GOSE; R2 = 37% vs. 6% for RPQ). In conclusion, the models based on variables available before discharge have moderate performance for the prediction of GOSE and poor performance for the prediction of PPCS. Symptoms assessed at 2-3 weeks are required for better predictive ability of both outcomes. The performance of the proposed models should be examined in independent cohorts.
Original language | English |
---|---|
Pages (from-to) | 1651-1670 |
Number of pages | 20 |
Journal | Journal of Neurotrauma |
Volume | 40 |
Issue number | 15-16 |
DOIs | |
Publication status | Published - 16 Aug 2023 |
Keywords
- biomarkers
- Glasgow Outcome Scale Extended
- mild traumatic brain injury
- post-concussion symptoms
- predictors
- prognostic model
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In: Journal of Neurotrauma, Vol. 40, No. 15-16, 16.08.2023, p. 1651-1670.
Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Prognostic models for global functional outcome and post-concussion symptoms following mild traumatic brain injury
T2 - a Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study
AU - Mikolic, Ana
AU - Steyerberg, Ewout W.
AU - Polinder, Suzanne
AU - Wilson, Lindsay
AU - Zeldovich, Marina
AU - von Steinbueche, Nicole
AU - Newcombe, Virginia F.J.
AU - Menon, David
AU - van Der Naalt, Joukje
AU - Lingsma, Hester F.
AU - Maas, Andrew I.R.
AU - van Klaveren, David
AU - Åkerlund, Cecilia
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 - Cavallo, Simona
AU - Chevallard, Giorgio
AU - Chieregato, Arturo
AU - Citerio, Giuseppe
AU - Clusmann, Hans
AU - Coburn, Mark
AU - Coles, Jonathan
AU - Cooper, Jamie D.
AU - Correia, Marta
AU - Čović, Amra
AU - Curry, Nicola
AU - Czeiter, Endre
AU - Czosnyka, Marek
AU - Fizelier, Claire Dahyot
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 - Ðilvesi, Ðula
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, Jiyao
AU - Johnson, Faye
AU - Jones, Kelly
AU - Karan, Mladen
AU - Kolias, Angelos G.
AU - Kompanje, Erwin
AU - Kondziella, Daniel
AU - Kornaropoulos, Evgenios
AU - Koskinen, Lars Owe
AU - Kovács, Noémi
AU - Kowark, Ana
AU - Lagares, Alfonso
AU - Lanyon, Linda
AU - Laureys, Steven
AU - Lecky, Fiona
AU - Ledoux, Didier
AU - Lefering, Rolf
AU - Legrand, Valerie
AU - Lejeune, Aurelie
AU - Levi, Leon
AU - Lightfoot, Roger
AU - Lingsma, Hester
AU - Castaño León, Ana M.
AU - Maegele, Marc
AU - Majdan, Marek
AU - Manara, Alex
AU - Manley, Geoffrey
AU - Martino, Costanza
AU - Maréchal, Hugues
AU - Mattern, Julia
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 - Olubukola, Otesile
AU - Oresic, Matej
AU - Ortolano, Fabrizio
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 - 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 - Rosand, Jonathan
AU - Rosenfeld, Jeffrey V.
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 - Skandsen, Toril
AU - Smielewski, Peter
AU - Sorinola, Abayomi
AU - Stamatakis, Emmanuel
AU - Stanworth, Simon
AU - Stevens, Robert
AU - Stewart, William
AU - Stocchetti, Nino
AU - Sundström, Nina
AU - Takala, Riikka
AU - Tamás, Viktória
AU - Tamosuitis, Tomas
AU - Taylor, Mark Steven
AU - Te Ao, Braden
AU - Tenovuo, Olli
AU - Theadom, Alice
AU - Thomas, Matt
AU - Tibboel, Dick
AU - Timmers, Marjolein
AU - Tolias, Christos
AU - Trapani, Tony
AU - Tudora, Cristina Maria
AU - Unterberg, Andreas
AU - Vajkoczy, Peter
AU - Vallance, Shirley
AU - Valeinis, Egils
AU - Vámos, Zoltán
AU - van Der Jagt, Mathieu
AU - Van Der Steen, Gregory
AU - van Der Naalt, Joukje
AU - van Dijck, Jeroen T.J.M.
AU - van Essen, Thomas A.
AU - Van Hecke, Wim
AU - van Heugten, Caroline
AU - Van Praag, Dominique
AU - van Veen, Ernest
AU - Vande Vyvere, Thijs
AU - van Wijk, Roel P.J.
AU - Vargiolu, Alessia
AU - Vega, Emmanuel
AU - Velt, Kimberley
AU - Verheyden, Jan
AU - Vespa, Paul M.
AU - Vik, Anne
AU - Vilcinis, Rimantas
AU - Volovici, Victor
AU - von Steinbüchel, Nicole
AU - Voormolen, Daphne
AU - Vulekovic, Petar
AU - Wang, Kevin K.W.
AU - Wiegers, Eveline
AU - Williams, Guy
AU - Wilson, Lindsay
AU - Winzeck, Stefan
AU - the CENTER-TBI investigators and participants
N1 - Funding Information: The authors Mikolic, Steyerberg, Polinder, Wilson, Zeldovich, Steinbuechel, Newcombe, Menon, Lingsma and Maas were supported by the European Union 7th Framework programme (EC grant 602150). Additional support was obtained from the Hannelore Kohl Stiftung (Germany), OneMind (USA), Integra LifeSciences Corporation (USA), and Neurotrauma Sciences (USA). Funding Information: The authors Mikolic, Steyerberg, Polinder, Wilson, Zeldovich, Steinbuechel, Newcombe, Menon, Lingsma and Maas were supported by the European Union 7th Framework programme (EC grant 602150). Additional support was obtained from the Hannelore Kohl Stiftung (Germany), OneMind (USA), Integra LifeSciences Corporation (USA), and Neurotrauma Sciences (USA). Funding Information: DM received personal fees from Lantmannen AB, GlaxoSmithKline plc, Calico Life Sciences LLC, PresSura Neuro, Integra Neurosciences, and NeuroTrauma Sciences, LLC; grants from GlaxoSmithKline plc; and a shared National Institutes of Health grant from Gryphon Collaborators on a grant application outside the presented work. VFJN holds grants from Roche Pharmaceuticals for an analysis outside the presented work. AIRM declares personal fees from NeuroTrauma Sciences and Novartis and participated on the DSMB of PresSura Neuro during the conduct of the study. Publisher Copyright: © Ana Mikolić et al 2023;
PY - 2023/8/16
Y1 - 2023/8/16
N2 - After mild traumatic brain injury (mTBI), a substantial proportion of individuals do not fully recover on the Glasgow Outcome Scale Extended (GOSE) or experience persistent post-concussion symptoms (PPCS). We aimed to develop prognostic models for the GOSE and PPCS at 6 months after mTBI and to assess the prognostic value of different categories of predictors (clinical variables; questionnaires; computed tomography [CT]; blood biomarkers). From the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, we included participants aged 16 or older with Glasgow Coma Score (GCS) 13-15. We used ordinal logistic regression to model the relationship between predictors and the GOSE, and linear regression to model the relationship between predictors and the Rivermead Post-concussion Symptoms Questionnaire (RPQ) total score. First, we studied a pre-specified Core model. Next, we extended the Core model with other clinical and sociodemographic variables available at presentation (Clinical model). The Clinical model was then extended with variables assessed before discharge from hospital: early post-concussion symptoms, CT variables, biomarkers, or all three categories (extended models). In a subset of patients mostly discharged home from the emergency department, the Clinical model was extended with 2-3–week post-concussion and mental health symptoms. Predictors were selected based on Akaike’s Information Criterion. Performance of ordinal models was expressed as a concordance index (C) and performance of linear models as proportion of variance explained (R2). Bootstrap validation was used to correct for optimism. We included 2376 mTBI patients with 6-month GOSE and 1605 patients with 6-month RPQ. The Core and Clinical models for GOSE showed moderate discrimination (C = 0.68 95% confidence interval 0.68 to 0.70 and C = 0.70[0.69 to 0.71], respectively) and injury severity was the strongest predictor. The extended models had better discriminative ability (C = 0.71[0.69 to 0.72] with early symptoms; 0.71[0.70 to 0.72] with CT variables or with blood biomarkers; 0.72[0.71 to 0.73] with all three categories). The performance of models for RPQ was modest (R2 = 4% Core; R2 = 9% Clinical), and extensions with early symptoms increased the R2 to 12%. The 2-3-week models had better performance for both outcomes in the subset of participants with these symptoms measured (C = 0.74 [0.71 to 0.78] vs. C = 0.63[0.61 to 0.67] for GOSE; R2 = 37% vs. 6% for RPQ). In conclusion, the models based on variables available before discharge have moderate performance for the prediction of GOSE and poor performance for the prediction of PPCS. Symptoms assessed at 2-3 weeks are required for better predictive ability of both outcomes. The performance of the proposed models should be examined in independent cohorts.
AB - After mild traumatic brain injury (mTBI), a substantial proportion of individuals do not fully recover on the Glasgow Outcome Scale Extended (GOSE) or experience persistent post-concussion symptoms (PPCS). We aimed to develop prognostic models for the GOSE and PPCS at 6 months after mTBI and to assess the prognostic value of different categories of predictors (clinical variables; questionnaires; computed tomography [CT]; blood biomarkers). From the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, we included participants aged 16 or older with Glasgow Coma Score (GCS) 13-15. We used ordinal logistic regression to model the relationship between predictors and the GOSE, and linear regression to model the relationship between predictors and the Rivermead Post-concussion Symptoms Questionnaire (RPQ) total score. First, we studied a pre-specified Core model. Next, we extended the Core model with other clinical and sociodemographic variables available at presentation (Clinical model). The Clinical model was then extended with variables assessed before discharge from hospital: early post-concussion symptoms, CT variables, biomarkers, or all three categories (extended models). In a subset of patients mostly discharged home from the emergency department, the Clinical model was extended with 2-3–week post-concussion and mental health symptoms. Predictors were selected based on Akaike’s Information Criterion. Performance of ordinal models was expressed as a concordance index (C) and performance of linear models as proportion of variance explained (R2). Bootstrap validation was used to correct for optimism. We included 2376 mTBI patients with 6-month GOSE and 1605 patients with 6-month RPQ. The Core and Clinical models for GOSE showed moderate discrimination (C = 0.68 95% confidence interval 0.68 to 0.70 and C = 0.70[0.69 to 0.71], respectively) and injury severity was the strongest predictor. The extended models had better discriminative ability (C = 0.71[0.69 to 0.72] with early symptoms; 0.71[0.70 to 0.72] with CT variables or with blood biomarkers; 0.72[0.71 to 0.73] with all three categories). The performance of models for RPQ was modest (R2 = 4% Core; R2 = 9% Clinical), and extensions with early symptoms increased the R2 to 12%. The 2-3-week models had better performance for both outcomes in the subset of participants with these symptoms measured (C = 0.74 [0.71 to 0.78] vs. C = 0.63[0.61 to 0.67] for GOSE; R2 = 37% vs. 6% for RPQ). In conclusion, the models based on variables available before discharge have moderate performance for the prediction of GOSE and poor performance for the prediction of PPCS. Symptoms assessed at 2-3 weeks are required for better predictive ability of both outcomes. The performance of the proposed models should be examined in independent cohorts.
KW - biomarkers
KW - Glasgow Outcome Scale Extended
KW - mild traumatic brain injury
KW - post-concussion symptoms
KW - predictors
KW - prognostic model
UR - http://www.scopus.com/inward/record.url?scp=85168315877&partnerID=8YFLogxK
U2 - 10.1089/neu.2022.0320
DO - 10.1089/neu.2022.0320
M3 - Article
C2 - 37078144
AN - SCOPUS:85168315877
SN - 0897-7151
VL - 40
SP - 1651
EP - 1670
JO - Journal of Neurotrauma
JF - Journal of Neurotrauma
IS - 15-16
ER -