Search

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.

Traumatic brain injury (TBI) can negatively impact patients' lives on many dimensions. Multiple instruments are available for evaluating TBI outcomes, but it is still unclear which instruments are the most sensitive for that purpose. This study examines the sensitivity of nine outcome instruments in terms of their ability to discriminate within and between specific patient groups, selected a priori as identified from the literature, at three different time points within a year after TBI (i.e., 3, 6, and 12 months post injury). The sensitivity of the instruments to sociodemographic (sex, age, education), premorbid (psychological health status), and injury-related (clinical care pathways, TBI and extracranial injury severity) factors was assessed by means of cross-sectional multivariate Wei-Lachin analyses. The Glasgow Outcome Scale Extended (GOSE)-the standard in the field of TBI for measuring functional recovery-demonstrated the highest sensitivity in most group comparisons. However, as single functional scale, it may not be able to reflect the multidimensional nature of the outcome. Therefore, the GOSE was used as a reference for further sensitivity analyses on more specific outcome scales, addressing further potential deficits following TBI. The physical component summary score (PCS) of the generic health-related quality of life (HRQOL) instruments (SF-36v2/-12v2) and the TBI-specific HRQOL instruments (QOLIBRI/-OS) were most sensitive in distinguishing recovery after TBI across all time points and patient groups, followed by the RPQ assessing post-concussion symptoms and the PHQ-9 measuring depression. The SF-36v2/-12v2 mental component summary score and the GAD-7 measuring anxiety were less sensitive in several group comparisons. The assessment of the functional recovery status combined with generic HRQOL (the PCS of the SF-12v2), disease-specific HRQOL (QOLIBRI-OS), and post-concussion symptoms (RPQ) can provide a sensitive, comprehensive, yet time-efficient evaluation of the health status of individuals after TBI in different patient groups., Competing Interests: The authors have read the journal’s policy and have the following competing interests: Johannes Vester is a senior biometric consultant of idv Datenanalyse und Versuchsplanung and received no personal fees related to the submitted work. Integra LifeSciences Corporation (USA) and NeuroTrauma Sciences (USA) provided additional financial support in respect to data curation. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare., (Copyright: © 2023 von Steinbuechel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Traumatic brain injury (TBI) remains one of the leading causes of death and disability worldwide. To better understand its impact on various outcome domains, this study pursues the following: (1) longitudinal outcome assessments at three, six, and twelve months post-injury; (2) an evaluation of sociodemographic, premorbid, and injury-related factors, and functional recovery contributing to worsening or improving outcomes after TBI. Using patient-reported outcome measures, recuperation trends after TBI were identified by applying Multivariate Latent Class Mixed Models (MLCMM). Instruments were grouped into TBI-specific and generic health-related quality of life (HRQoL; QOLIBRI-OS, SF-12v2), and psychological and post-concussion symptoms (GAD-7, PHQ-9, PCL-5, RPQ). Multinomial logistic regressions were carried out to identify contributing factors. For both outcome sets, the four-class solution provided the best match between goodness of fit indices and meaningful clinical interpretability. Both models revealed similar trajectory classes: stable good health status (HRQoL: n = 1944; symptoms: n = 1963), persistent health impairments (HRQoL: n = 442; symptoms: n = 179), improving health status (HRQoL: n = 83; symptoms: n = 243), and deteriorating health status (HRQoL: n = 86; symptoms: n = 170). Compared to individuals with stable good health status, the other groups were more likely to have a lower functional recovery status at three months after TBI (i.e., the GOSE), psychological problems, and a lower educational attainment. Outcome trajectories after TBI show clearly distinguishable patterns which are reproducible across different measures. Individuals characterized by persistent health impairments and deterioration require special attention and long-term clinical monitoring and therapy.

After traumatic brain injury (TBI), individuals may experience short- or long-term health burdens, often referred to as post-concussion symptoms (PCS). The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) is one of the commonly used instruments to assess self-reported PCS. To date, no reference values for RPQ have been provided, although they are crucial for clinical practice when evaluating a patient's health status relative to a comparable healthy population. Therefore, the aim of this study is to provide reference values for the United Kingdom, the Netherlands, and Italy. A total of 11,759 individuals (50.3% women) from representative general population samples participated in an online survey (4646 individuals from the UK, 3564 from the Netherlands, and 3549 from Italy). The factorial structure of the RPQ was examined using confirmatory factor analysis (CFA), and results from the general population samples were compared with those from respective TBI samples recruited within the international CENTER-TBI study using multigroup CFA. Reference values were stratified by sex, health status, age, and education using percentiles. The three-factorial model outperformed the one-factorial structure. The general population samples were largely comparable to the corresponding TBI samples, except for items such as dizziness, vision, and sensory sensitivity, which can be considered more TBI-specific. Because of the significant differences between the general population samples, we provided reference values for the total score and for the somatic, emotional, and cognitive scales for each country separately. The reference values provided can now be used in clinical practice and research. Future studies should obtain stratified reference values for other countries and languages to improve accuracy in the diagnosis and treatment of symptom burden after TBI.

Depression and anxiety are common following traumatic brain injury (TBI). Understanding their prevalence and interplay within the first year after TBI with differing severities may improve patients' outcomes after TBI. Individuals with a clinical diagnosis of TBI recruited for the large European collaborative longitudinal study CENTER-TBI were screened for patient-reported major depression (MD) and generalized anxiety disorder (GAD) at three, six, and twelve months post-injury (N = 1683). Data were analyzed using autoregressive cross-lagged models. Sociodemographic, premorbid and injury-related factors were examined as risk factors. 14.1-15.5% of TBI patients reported moderate to severe MD at three to twelve months after TBI, 7.9-9.5% reported GAD. Depression and anxiety after TBI presented high within-domain persistency and cross-domain concurrent associations. MD at three months post-TBI had a significant impact on GAD at six months post-TBI, while both acted bidirectionally at six to twelve months post-TBI. Being more severely disabled, having experienced major extracranial injuries, an intensive care unit stay, and being female were risk factors for more severe MD and GAD. Major trauma and the level of consciousness after TBI were additionally associated with more severe MD, whereas being younger was related to more severe GAD. Individuals after TBI should be screened and treated for MD and GAD early on, as both psychiatric disturbances are highly persistent and bi-directional in their impact. More severely disabled patients are particularly vulnerable, and thus warrant timely screening and intensive follow-up treatment.

Patients with mild traumatic brain injury (mTBI) are at risk for post-concussion (PC) symptoms and post-traumatic stress disorder (PTSD). The co-occurrence of PC and PTSD symptoms after mTBI in relation to health-related quality of life (HRQoL), health care utilization, and return to work has not yet been investigated. PC and PTSD symptoms were measured six months post-TBI by respectively the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) and the Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5). Of the 1566 individuals after mTBI who met the inclusion criteria, 26.1% experienced PC symptoms (RPQ ≥16). Additionally, 9.8% experienced PTSD symptoms (PCL-5 ≥ 33), of which the vast majority (81%) also reported experiencing PC symptoms. Differences between patients with no/mild symptoms, with only PC, only PTSD, and both PC and PTSD symptoms in HRQoL, return to work, and rehabilitation were analyzed using logistic and linear regression analyses. Patients with PC and/or PTSD symptoms reported lower HRQoL, higher rates of rehabilitation, and lower return to work rates compared to patients with no/mild symptoms. Patients with both PC and PTSD symptoms reported significantly lower HRQoL (B = -2.73, CI = -4.65; -0.83, p < 0.001) compared to those with only PC symptoms, while there were no significant differences in their ongoing rehabilitation care (OR = 1.39, CI = 0.77-2.49, p = 0.272) and return to work rates (OR = 0.49, CI = 0.15-1.63, p = 0.246) at six months. These results underline the importance of the diagnosis and appropriate treatment of patients with mTBI, experiencing PC and/or PTSD symptoms.

Background: Fatigue is one of the most commonly reported subjective symptoms following traumatic brain injury (TBI). The aims were to assess frequency of fatigue over the first 6 months after TBI, and examine whether fatigue changes could be predicted by demographic characteristics, injury severity and comorbidities., Methods: Patients with acute TBI admitted to 65 trauma centers were enrolled in the study Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI). Subjective fatigue was measured by single item on the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), administered at baseline, three and 6 months postinjury. Patients were categorized by clinical care pathway: admitted to an emergency room (ER), a ward (ADM) or an intensive care unit (ICU). Injury severity, preinjury somatic- and psychiatric conditions, depressive and sleep problems were registered at baseline. For prediction of fatigue changes, descriptive statistics and mixed effect logistic regression analysis are reported., Results: Fatigue was experienced by 47% of patients at baseline, 48% at 3 months and 46% at 6 months. Patients admitted to ICU had a higher probability of experiencing fatigue than those in ER and ADM strata. Females and individuals with lower age, higher education, more severe intracranial injury, preinjury somatic and psychiatric conditions, sleep disturbance and feeling depressed postinjury had a higher probability of fatigue., Conclusion: A high and stable frequency of fatigue was found during the first 6 months after TBI. Specific socio-demographic factors, comorbidities and injury severity characteristics were predictors of fatigue in this study.

Purpose: The Quality of Life after Brain Injury overall scale (QOLIBRI-OS) measures health-related quality of life (HRQoL) after traumatic brain injury (TBI). The aim of this study was to derive value sets for the QOLIBRI-OS in three European countries, which will allow calculation of utility scores for TBI health states., Methods: A QOLIBRI-OS value set was derived by using discrete choice experiments (DCEs) and visual analogue scales (VAS) in general population samples from the Netherlands, United Kingdom and Italy. A three-stage procedure was used: (1) A selection of health states, covering the entire spectrum of severity, was defined; (2) General population samples performed the health state valuation task using a web-based survey with three VAS questions and an at random selection of sixteen DCEs; (3) DCEs were analysed using a conditional logistic regression and were then anchored on the VAS data. Utility scores for QOLIBRI-OS health states were generated resulting in estimates for all potential health states., Results: The questionnaire was completed by 13,623 respondents. The biggest weight increase for all attributes is seen from "slightly" to "not at all satisfied", resulting in the largest impact on HRQoL. "Not at all satisfied with how brain is working" should receive the greatest weight in utility calculations in all three countries., Conclusion: By transforming the QOLIBRI-OS into utility scores, we enabled the application in economic evaluations and in summary measures of population health, which may be used to inform decision-makers on the best interventions and strategies for TBI patients.

A subset of mild traumatic brain injury (mTBI) patients experience post-concussion symptoms. When a cluster of post-concussion symptoms persists for over three months, it is referred to as post-concussion syndrome (PCS). Little is known about the association between PCS and Health-Related Quality of Life (HRQoL) after mTBI. The aims of this study were to assess the implications of PCS on HRQoL six months after mTBI and the relationship between PCS and HRQoL domains. A prospective observational cohort study was conducted among a sample of mTBI patients. Follow-up postal questionnaires at six months after emergency department (ED) admission included socio-demographic information, the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), and HRQoL measured with the 36-item Short-Form Health Survey (SF-36) and the Perceived Quality of Life Scale (PQoL). In total, 731 mTBI patients were included, of whom 38.7% were classified as suffering from PCS. Patients with PCS had significantly lower scores on all SF-36 domains, lower physical and mental component summary scores and lower mean PQoL scores compared to patients without PCS. All items of the RPQ were negatively correlated to all SF-36 domains and PQoL subscale scores, indicating that reporting problems on any of the RPQ symptoms was associated with a decrease on different aspects of an individuals' HRQoL. To conclude, PCS is common following mTBI and patients with PCS have a considerably lower HRQoL. A better understanding of the relationship between PCS and HRQoL and possible mediating factors in this relationship could improve intervention strategies, the recovery process for mTBI patients and benchmarking., (Copyright © 2018 Elsevier Ltd. All rights reserved.)