| 1. |
- Mikolić, Ana, et al.
(author)
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Differences between Men and Women in Treatment and Outcome after Traumatic Brain Injury
- 2021
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In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 38:2, s. 235-251
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Journal article (peer-reviewed)abstract
- Traumatic brain injury (TBI) is a significant cause of disability, but little is known about sex and gender differences after TBI. We aimed to analyze the association between sex/gender, and the broad range of care pathways, treatment characteristics, and outcomes following mild and moderate/severe TBI. We performed mixed-effects regression analyses in the prospective multi-center Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, stratified for injury severity and age, and adjusted for baseline characteristics. Outcomes were various care pathway and treatment variables, and 6-month measures of functional outcome, health-related quality of life (HRQoL), post-concussion symptoms (PCS), and mental health symptoms. The study included 2862 adults (36% women) with mild (mTBI; Glasgow Coma Scale [GCS] score 13–15), and 1333 adults (26% women) with moderate/severe TBI (GCS score 3–12). Women were less likely to be admitted to the intensive care unit (ICU; odds ratios [OR] 0.6, 95% confidence interval [CI]: 0.4-0.8) following mTBI. Following moderate/severe TBI, women had a shorter median hospital stay (OR 0.7, 95% CI: 0.5-1.0). Following mTBI, women had poorer outcomes; lower Glasgow Outcome Scale Extended (GOSE; OR 1.4, 95% CI: 1.2-1.6), lower generic and disease-specific HRQoL, and more severe PCS, depression, and anxiety. Among them, women under age 45 and above age 65 years showed worse 6-month outcomes compared with men of the same age. Following moderate/severe TBI, there was no difference in GOSE (OR 0.9, 95% CI: 0.7-1.2), but women reported more severe PCS (OR 1.7, 95% CI: 1.1-2.6). Men and women differ in care pathways and outcomes following TBI. Women generally report worse 6-month outcomes, but the size of differences depend on TBI severity and age. Future studies should examine factors that explain these differences.
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| 2. |
- Mikolić, Ana, et al.
(author)
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Prediction of Global Functional Outcome and Post-Concussive Symptoms after Mild Traumatic Brain Injury : External Validation of Prognostic Models in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study
- 2021
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In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 38:2, s. 196-209
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Journal article (peer-reviewed)abstract
- The majority of traumatic brain injuries (TBIs) are categorized as mild, according to a baseline Glasgow Coma Scale (GCS) score of 13-15. Prognostic models that were developed to predict functional outcome and persistent post-concussive symptoms (PPCS) after mild TBI have rarely been externally validated. We aimed to externally validate models predicting 3-12-month Glasgow Outcome Scale Extended (GOSE) or PPCS in adults with mild TBI. We analyzed data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) project, which included 2862 adults with mild TBI, with 6-month GOSE available for 2374 and Rivermead Post-Concussion Symptoms Questionnaire (RPQ) results available for 1605 participants. Model performance was evaluated based on calibration (graphically and characterized by slope and intercept) and discrimination (C-index). We validated five published models for 6-month GOSE and three for 6-month PPCS scores. The models used different cutoffs for outcome and some included symptoms measured 2 weeks post-injury. Discriminative ability varied substantially (C-index between 0.58 and 0.79). The models developed in the Corticosteroid Randomisation After Significant Head Injury (CRASH) trial for prediction of GOSE <5 discriminated best (C-index 0.78 and 0.79), but were poorly calibrated. The best performing models for PPCS included 2-week symptoms (C-index 0.75 and 0.76). In conclusion, none of the prognostic models for early prediction of GOSE and PPCS has both good calibration and discrimination in persons with mild TBI. In future studies, prognostic models should be tailored to the population with mild TBI, predicting relevant end-points based on readily available predictors.
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| 3. |
- Mikolić, Ana, et al.
(author)
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Prognostic models for global functional outcome and post-concussion symptoms following mild traumatic brain injury : a collaborative european neurotrauma effectiveness research in traumatic brain injury (CENTER-TBI) study
- 2023
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In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 40:15-16, s. 1651-1670
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Journal article (peer-reviewed)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.
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| 4. |
- Richter, Sophie, et al.
(author)
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Prognostic Value of Serum Biomarkers in Patients With Moderate-Severe Traumatic Brain Injury, Differentiated by Marshall Computer Tomography Classification
- 2023
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In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 40:21-22, s. 2297-2310
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Journal article (peer-reviewed)abstract
- Prognostication is challenging in patients with traumatic brain injury (TBI) in whom computed tomography (CT) fails to fully explain a low level of consciousness. Serum biomarkers reflect the extent of structural damage in a different way than CT does, but it is unclear whether biomarkers provide additional prognostic value across the range of CT abnormalities. This study aimed to determine the added predictive value of biomarkers, differentiated by imaging severity. This prognostic study used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study (2014-2017). The analysis included patients aged & GE;16 years with a moderate-severe TBI (Glasgow Coma Scale [GCS] <13) who had an acute CT and serum biomarkers obtained & LE;24h of injury. Of six protein biomarkers (GFAP, NFL, NSE, S100B, Tau, UCH-L1), the most prognostic panel was selected using lasso regression. The performance of established prognostic models (CRASH and IMPACT) was assessed before and after the addition of the biomarker panel and compared between patients with different CT Marshall scores (Marshall score <3 vs. Marshall score & GE;3). Outcome was assessed at six months post-injury using the extended Glasgow Outcome Scale (GOSE), and dichotomized into favorable and unfavorable (GOSE <5). We included 872 patients with moderate-severe TBI. The mean age was 47 years (range 16-95); 647 (74%) were male and 438 (50%) had a Marshall CT score <3. The serum biomarkers GFAP, NFL, S100B and UCH-L1 provided complementary prognostic information; NSE and Tau showed no added value. The addition of the biomarker panel to established prognostic models increased the area under the curve (AUC) by 0.08 and 0.03, and the explained variation in outcome by 13-14% and 7-8%, for patients with a Marshall score of <3 and & GE;3, respectively. The incremental AUC of biomarkers for individual models was significantly greater when the Marshall score was <3 compared with & GE;3 (p < 0.001). Serum biomarkers improve outcome prediction after moderate-severe TBI across the range of imaging severities and especially in patients with a Marshall score <3.
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| 5. |
- Riemann, Lennart, et al.
(author)
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Computed tomography lesions and their association with global outcome in young people with mild traumatic brain injury
- 2023
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In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 40:11-12, s. 1243-1254
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Journal article (peer-reviewed)abstract
- Mild traumatic brain injury (mTBI) can be accompanied by structural damage to the brain. Here, we investigated how the presence of intracranial traumatic computed tomography (CT) pathologies relates to the global functional outcome in young patients one year after mTBI. All patients with mTBI (Glasgow Coma Scale: 13-15) ≤24 years in the multi-center, prospective, observational Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study were included. Patient demographics and CT findings were assessed at admission, and the Glasgow Outcome Scale Extended (GOSE) was evaluated at 12 months follow-up. The association between a "positive CT" (at least one of the following: epidural hematoma, subdural hematoma, traumatic subarachnoid hemorrhage (tSAH), intraventricular hemorrhage, subdural collection mixed density, contusion, traumatic axonal injury) and functional outcome (GOSE) was assessed using multi-variable mixed ordinal and logistic regression models. A total of 462 patients with mTBI and initial brain CT from 46 study centers were included. The median age was 19 (17-22) years, and 322 (70%) were males. CT imaging showed a traumatic intracranial pathology in 171 patients (37%), most commonly tSAH (48%), contusions (40%), and epidural hematomas (37%). Patients with a positive CT scan were less likely to achieve a complete recovery 12 months post-injury. The presence of any CT abnormality was associated with both lower GOSE scores (odds ratio [OR]: 0.39 [0.24-0.63]) and incomplete recovery (GOSE <8; OR: 0.41 [0.25-0.68]), also when adjusted for demographical and clinical baseline factors. The presence of intracranial traumatic CT pathologies was predictive of outcome 12 months after mTBI in young patients, which might help to identify candidates for early follow-up and additional care.
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| 6. |
- van der Vlegel, Marjolein, et al.
(author)
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Health care utilization and outcomes in older adults after Traumatic Brain Injury : a CENTER-TBI study
- 2022
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In: Injury. - : Elsevier. - 0020-1383 .- 1879-0267. ; 53:8, s. 2774-2782
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Journal article (peer-reviewed)abstract
- INTRODUCTION: The incidence of Traumatic Brain Injury (TBI) is increasingly common in older adults aged ≥65 years, forming a growing public health problem. However, older adults are underrepresented in TBI research. Therefore, we aimed to provide an overview of health-care utilization, and of six-month outcomes after TBI and their determinants in older adults who sustained a TBI.METHODS: We used data from the prospective multi-center Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. In-hospital and post-hospital health care utilization and outcomes were described for patients aged ≥65 years. Ordinal and linear regression analyses were performed to identify determinants of the Glasgow Outcome Scale Extended (GOSE), health-related quality of life (HRQoL), and mental health symptoms six-months post-injury.RESULTS: Of 1254 older patients, 45% were admitted to an ICU with a mean length of stay of 9 days. Nearly 30% of the patients received inpatient rehabilitation. In total, 554/1254 older patients completed the six-month follow-up questionnaires. The mortality rate was 9% after mild and 60% after moderate/severe TBI, and full recovery based on GOSE was reported for 44% of patients after mild and 6% after moderate/severe TBI. Higher age and increased injury severity were primarily associated with functional impairment, while pre-injury systemic disease, psychiatric conditions and lower educational level were associated with functional impairment, lower generic and disease-specific HRQoL and mental health symptoms.CONCLUSION: The rate of impairment and disability following TBI in older adults is substantial, and poorer outcomes across domains are associated with worse preinjury health. Nonetheless, a considerable number of patients fully or partially returns to their preinjury functioning. There should not be pessimism about outcomes in older adults who survive.
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| 7. |
- Zeldovich, Marina, et al.
(author)
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Influence of Sociodemographic, Premorbid, and Injury-Related Factors on Post-Concussion Symptoms after Traumatic Brain Injury
- 2020
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In: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 9:6
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Journal article (peer-reviewed)abstract
- Background: Post-concussion symptoms (PCS) are often reported as consequences of mild and moderate traumatic brain injury (TBI), but these symptoms are not well documented in severe TBI. There is a lack of agreement as to which factors and covariates affect the occurrence, frequency, and intensity of PCS among TBI severity groups. The present study therefore aims to examine the association between sociodemographic, premorbid, and injury-related factors and PCS.Methods: A total of 1391 individuals (65% male) from the CENTER-TBI study were included in the analyses. The occurrence, frequency (number of PCS), and intensity (severity) of PCS were assessed using the Rivermead Post-concussion Symptoms Questionnaire (RPQ) at six months after TBI. To examine the association between selected factors (age, sex, living situation, employment status, educational background, injury and TBI severity, and premorbid problems) and PCS, a zero-inflated negative binomial model (ZINB) for occurrence and frequency of PCS and a standard negative binomial regression (NB) for intensity were applied.Results: Of the total sample, 72% of individuals after TBI reported suffering from some form of PCS, with fatigue being the most frequent among all TBI severity groups, followed by forgetfulness, and poor concentration. Different factors contributed to the probability of occurrence, frequency, and intensity of PCS. While the occurrence of PCS seemed to be independent of the age and sex of the individuals, both the frequency and intensity of PCS are associated with them. Both injury and TBI severity influence the occurrence and frequency of PCS, but are associated less with its intensity (except “acute” symptoms such as nausea, vomiting, and headaches). Analyses focusing on the mTBI subgroup only yielded results comparable to those of the total sample.Discussion: In line with previous studies, the results support a multifactorial etiology of PCS and show the importance of differentiating between their occurrence, frequency, and intensity to better provide appropriate treatment for individual subgroups with different symptoms (e.g., multiple PCS or more intense PCS). Although PCS often occur in mild to moderate TBI, individuals after severe TBI also suffer from PCS or post-concussion-like symptoms that require appropriate treatment. The chosen statistical approaches (i.e., ZINB and NB models) permit an ameliorated differentiation between outcomes (occurrence, frequency, and intensity of PCS) and should be used more widely in TBI research.
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