Traumatic brain injury (TBI) is a global public health problem and a leading cause of mortality, morbidity, and disability. The increasing incidence combined with the heterogeneity and complexity... Show moreTraumatic brain injury (TBI) is a global public health problem and a leading cause of mortality, morbidity, and disability. The increasing incidence combined with the heterogeneity and complexity of TBI will inevitably place a substantial burden on health systems. These findings emphasize the importance of obtaining accurate and timely insights into healthcare consumption and costs on a multi-national scale. This study aimed to describe intramural healthcare consumption and costs across the full spectrum of TBI in Europe. The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) core study is a prospective observational study conducted in 18 countries across Europe and in Israel. The baseline Glasgow Coma Scale (GCS) was used to differentiate patients by brain injury severity in mild (GCS 13-15), moderate (GCS 9-12), or severe (GCS & LE;8) TBI. We analyzed seven main cost categories: pre-hospital care, hospital admission, surgical interventions, imaging, laboratory, blood products, and rehabilitation. Costs were estimated based on Dutch reference prices and converted to country-specific unit prices using gross domestic product (GDP)-purchasing power parity (PPP) adjustment. Mixed linear regression was used to identify between-country differences in length of stay (LOS), as a parameter of healthcare consumption. Mixed generalized linear models with gamma distribution and log link function quantified associations of patient characteristics with higher total costs. We included 4349 patients, of whom 2854 (66%) had mild, 371 (9%) had moderate, and 962 (22%) had severe TBI. Hospitalization accounted for the largest part of the intramural consumption and costs (60%). In the total study population, the mean LOS was 5.1 days at the intensive care unit (ICU) and 6.3 days at the ward. For mild, moderate, and severe TBI, mean LOS was, respectively, 1.8, 8.9, and 13.5 days at the ICU and 4.5, 10.1, and 10.3 days at the ward. Other large contributors to the total costs were rehabilitation (19%) and intracranial surgeries (8%). Total costs increased with higher age and greater trauma severity (mild; euro3,800 [IQR euro1,400-14,000], moderate; euro37,800 [IQR euro14,900-euro74,200], severe; euro60,400 [IQR euro24,400-euro112,700]). The adjusted analysis showed that female patients had lower costs than male patients (odds ratio (OR) 0.80 [CI 0.75-1.85]). Increasing TBI severity was associated with higher costs, OR 1.46 (confidence interval [CI] 1.31-1.63) and OR 1.67 [CI 1.52-1.84] for moderate and severe patients, respectively. A worse pre-morbid overall health state, increasing age and more severe systemic trauma, expressed in the Injury Severity Score (ISS), were also significantly associated with higher costs. Intramural costs of TBI are significant and are profoundly driven by hospitalization. Costs increased with trauma severity and age, and male patients incurred higher costs. Reducing LOS could be targeted with advanced care planning, in order to provide cost-effective care. Show less
Mikolic, A.; Steyerberg, E.W.; Polinder, S.; Wilson, L.; Zeldovich, M.; Steinbuechel, N. von; ... ; CENTER-TBI Participants 2023
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... Show moreAfter 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. Show less
Prognostic prediction of traumatic brain injury (TBI) in patients is crucial in clinical decision and health care policy making. This study aimed to develop and validate prediction models for in... Show morePrognostic prediction of traumatic brain injury (TBI) in patients is crucial in clinical decision and health care policy making. This study aimed to develop and validate prediction models for in-hospital mortality after severe traumatic brain injury (sTBI). We developed and validated logistic regression (LR), LASSO regression, and machine learning (ML) algorithms including support vector machines (SVM) and XGBoost models. Fifty-four candidate predictors were included. Model performance was expressed in terms of discrimination (C-statistic) and calibration (intercept and slope). For model development, 2804 patients with sTBI in the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) China Registry study were included. External validation was performed in 1113 patients with sTBI in the CENTER-TBI European Registry study. XGBoost achieved high discrimination in mortality prediction, and it outperformed logistic and LASSO regression. The XGBoost model established in this study also outperformed prediction models currently available, including the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) core and International Mission for Prognosis and Analysis of Clinical Trials (CRASH) basic models. When including 54 variables, XGBoost and SVM reached C-statistics of 0.87 (95% confidence interval [CI]: 0.81-0.92) and 0.85 (95% CI: 0.79-0.90) at internal validation, and 0.88 (95% CI: 0.87-0.88) and 0.86 (95% CI: 0.85-0.87) at external validation, respectively. A simplified version of XGBoost and SVM using 26 variables selected by recursive feature elimination (RFE) reached C-statistics of 0.87 (95% CI: 0.82-0.92) and 0.86 (95% CI: 0.80-0.91) at internal validation, and 0.87 (95% CI: 0.87-0.88) and 0.87 (95% CI: 0.86-0.87) at external validation, respectively. However, when the number of variables included decreased, the difference between ML and LR diminished. All the prediction models can be accessed via a web-based calculator. Glasgow Coma Scale (GCS) score, age, pupillary light reflex, Injury Severity Score (ISS) for brain region, and the presence of acute subdural hematoma were the five strongest predictors for mortality prediction. The study showed that ML techniques such as XGBoost may capture information hidden in demographic and clinical predictors of patients with sTBI and yield more precise predictions compared with LR approaches. Show less
Miah, I.P.; Blanter, A.; Tank, Y.; Zwet, E.W. van; Rosendaal, F.R.; Peul, W.C.; ... ; Gaag, N.A. van der 2022
The main treatment strategy for chronic subdural hematoma is surgical intervention. When a conservative pharmacological approach is considered in symptomatic patients, mainly dexamethasone therapy... Show moreThe main treatment strategy for chronic subdural hematoma is surgical intervention. When a conservative pharmacological approach is considered in symptomatic patients, mainly dexamethasone therapy is applied. Recent trials revealed dexamethasone therapy to be an ineffective treatment in symptomatic patients with chronic subdural hematoma. Whether the efficacy of dexamethasone therapy differs in radiological hematoma subtypes is unknown. The aim of this substudy was to identify which hematoma subtype might be favorable for dexamethasone therapy. As part of a randomized controlled trial, symptomatic chronic subdural hematoma patients received 19-days dexamethasone therapy. The primary outcome measure was the change in hematoma size as measured on follow-up computed tomography (CT) after 2 weeks of dexamethasone in six hematoma (architectural and density) subtypes: homogeneous total, laminar, separated and trabecular architecture types, and hematoma without hyperdense components (homogeneous hypodense, isodense) and with hyperdense components (homogeneous hyperdense, mixed density). We analyzed hematoma thickness, midline shift, and volume using multi-variable linear regression adjusting for age, sex and baseline value of the specific radiological parameter. From September 2016 until February 2021, 85 patients were included with a total of 114 chronic subdural hematoma. The mean age was 76 years and 25% were women. Larger decrease in hematoma thickness and midline shift was revealed in hematoma without hyperdense components compared with hematoma with hyperdense components (adjusted [adj.] b -2.2 mm, 95% confidence interval [CI] -4.1 to -0.3 and adj. b -1.3 mm, 95% CI -2.7 to 0.0 respectively). Additional surgery was performed in 57% of patients with the highest observed rate (81%) in separated hematoma. Largest hematoma reduction and better clinical improvement was observed in chronic subdural hematoma without hyperdense components after dexamethasone therapy. Evaluation of these parameters can be part of an individualized treatment strategy. Show less
Miah, I.P.; Blanter, A.; Tank, Y.; Zwet, E.W. van; Rosendaal, F.R.; Peul, W.C.; ... ; Gaag, N.A. van der 2022
The main treatment strategy for chronic subdural hematoma is surgical intervention. When a conservative pharmacological approach is considered in symptomatic patients, mainly dexamethasone therapy... Show moreThe main treatment strategy for chronic subdural hematoma is surgical intervention. When a conservative pharmacological approach is considered in symptomatic patients, mainly dexamethasone therapy is applied. Recent trials revealed dexamethasone therapy to be an ineffective treatment in symptomatic patients with chronic subdural hematoma. Whether the efficacy of dexamethasone therapy differs in radiological hematoma subtypes is unknown. The aim of this substudy was to identify which hematoma subtype might be favorable for dexamethasone therapy. As part of a randomized controlled trial, symptomatic chronic subdural hematoma patients received 19-days dexamethasone therapy. The primary outcome measure was the change in hematoma size as measured on follow-up computed tomography (CT) after 2 weeks of dexamethasone in six hematoma (architectural and density) subtypes: homogeneous total, laminar, separated and trabecular architecture types, and hematoma without hyperdense components (homogeneous hypodense, isodense) and with hyperdense components (homogeneous hyperdense, mixed density). We analyzed hematoma thickness, midline shift, and volume using multi-variable linear regression adjusting for age, sex and baseline value of the specific radiological parameter. From September 2016 until February 2021, 85 patients were included with a total of 114 chronic subdural hematoma. The mean age was 76 years and 25% were women. Larger decrease in hematoma thickness and midline shift was revealed in hematoma without hyperdense components compared with hematoma with hyperdense components (adjusted [adj.] b -2.2 mm, 95% confidence interval [CI] -4.1 to -0.3 and adj. b -1.3 mm, 95% CI -2.7 to 0.0 respectively). Additional surgery was performed in 57% of patients with the highest observed rate (81%) in separated hematoma. Largest hematoma reduction and better clinical improvement was observed in chronic subdural hematoma without hyperdense components after dexamethasone therapy. Evaluation of these parameters can be part of an individualized treatment strategy. Show less
Essen, T.A. van; Res, L.; Schoones, J.; Ruiter, G. de; Dekkers, O.; Maas, A.; ... ; Gaag, N.A. van der 2022
The rationale of performing surgery for acute subdural hematoma (ASDH) to reduce mortality is often compared with the self-evident effectiveness of a parachute when skydiving. Nevertheless, it is... Show moreThe rationale of performing surgery for acute subdural hematoma (ASDH) to reduce mortality is often compared with the self-evident effectiveness of a parachute when skydiving. Nevertheless, it is of clinical relevance to estimate the magnitude of the effectiveness of surgery. The aim of this study is to determine whether surgery reduces mortality in traumatic ASDH compared with initial conservative treatment. A systematic search was performed in the databases IndexCAT, PubMed, Embase, Web of Science, Cochrane library, CENTRAL, Academic Search Premier, Google Scholar, ScienceDirect, and CINAHL for studies investigating ASDH treated conservatively and surgically, without restriction to publication date, describing the mortality. Cohort studies or trials with at least five patients with ASDH, clearly describing surgical, conservative treatment, or both, with the mortality at discharge, reported in English or Dutch, were eligible. The search yielded 2025 reports of which 282 were considered for full-text review. After risk of bias assessment, we included 102 studies comprising 12,287 patients. The data were synthesized using meta-analysis of absolute risks; this was conducted in random-effects models, with dramatic effect estimation in subgroups.Overall mortality in surgically treated ASDH is 48% (95% confidence interval [CI] 44-53%). Mortality after surgery for comatose patients (Glasgow Coma Scale <= 8) is 41% (95% CI 31-51%) in contemporary series (after 2000). Mortality after surgery for non-comatose ASDH is 12% (95% CI 4-23%). Conservative treatment is associated with an overall mortality of 35% (95% CI 22-48%) and 81% (95% CI 56-98%) when restricting to comatose patients. The absolute risk reduction is 40% (95% CI 35-45%), with a number needed to treat of 2.5 (95% CI 2.2-2.9) to prevent one death in comatose ASDH. Thus, surgery is effective to reduce mortality among comatose patients with ASDH. The magnitude of the effect is large, although the effect size may not be sufficient to overcome any bias. Show less
Gantner, D.; Wiegers, E.; Bragge, P.; Finfer, S.; Delaney, A.; Essen, T. van; ... ; CENTER-TBI Investigators and Parti 2022
High quality evidence shows decompressive craniectomy (DC) following traumatic brain injury (TBI) may improve survival but increase the number of severely disabled survivors. Contemporary... Show moreHigh quality evidence shows decompressive craniectomy (DC) following traumatic brain injury (TBI) may improve survival but increase the number of severely disabled survivors. Contemporary international practice is unknown. We sought to describe international use of DC, and the alignment with evidence and clinical practice guidelines, by analyzing the harmonized Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) and Australia-Europe NeuroTrauma Effectiveness Research in Traumatic Brain Injury (OzENTER-TBI) core study datasets, which include patients admitted to intensive care units (ICUs) in Europe, the United Kingdom, and Australia between 2015 and 2017. Outcomes of interest were treatment with DC relative to clinical trial evidence and the Brain Trauma Foundation guidelines. Of 2336 people admitted to ICUs following TBI, DC was performed in 320 (13.7%): in 64/1422 (4.5%) patients with diffuse TBI and 195/640 (30.5%) patients with traumatic mass lesions. Secondary DC (for treatment of intracranial hypertension) was used infrequently in patients who met enrollment criteria of the two randomized clinical trials informing the guidelines-specifically, in 11/124 (8.9%) of those matching Decompressive Craniectomy in Diffuse Traumatic Brain Injury trial (DECRA) enrollment, and in 30/224 (13.4%) of those matching Randomised Evaluation of Surgery with Craniectomy for Uncontrollable Elevation of Intracranial Pressure (RESCUEicp). Of patients who underwent DC, 258/320 (80.6%) were ineligible for either trial: 149/320 (46.6%) underwent primary DC, 62/320 (19.4%) were outside the trials' age criteria, and 126/320 (39.4%) did not develop intracranial hypertension refractory to non-operative therapies prior to DC. Secondary DC was used infrequently in patients in whom it had been shown to increase survival with severe disability, indicating alignment between contemporaneous evidence and practice. However, most patients who underwent DC were ineligible for the key trials; whether they benefited from DC remains unknown. Show less
Living systematic reviews (LSRs) are online summaries of health care research that are updated as new research becomes available. This new development in evidence synthesis is being trialled as... Show moreLiving systematic reviews (LSRs) are online summaries of health care research that are updated as new research becomes available. This new development in evidence synthesis is being trialled as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) project. We will develop and sustain an international TBI knowledge community that maintains up-to-date, high quality LSRs of the current state of knowledge in the most important questions in TBI. Automatic search updates will be run three-monthly, and newly identified studies incorporated into the review. Review teams will seek to publish journal updates at regular intervals, with abridged updates available more frequently online. Future project stages include the integration of LSR and other study findings into "living" clinical practice guidance. It is hoped these efforts will go some way to bridging current temporal disconnects between evidence, guidelines, and practice in TBI. Show less
In medical research, missing data is common. In acute diseases, such as traumatic brain injury (TBI), even well-conducted prospective studies may suffer from missing data in baseline... Show moreIn medical research, missing data is common. In acute diseases, such as traumatic brain injury (TBI), even well-conducted prospective studies may suffer from missing data in baseline characteristics and outcomes. Statistical models may simply drop patients with any missing values, potentially leaving a selected subset of the original cohort. Imputation is widely accepted by methodologists as an appropriate way to deal with missing data. We aim to provide practical guidance on handling missing data for prediction modeling. We hereto propose a five-step approach, centered around single and multiple imputation: 1) explore the missing data patterns; 2) choose a method of imputation; 3) perform imputation; 4) assess diagnostics of the imputation; and 5) analyze the imputed data sets. We illustrate these five steps with the estimation and validation of the IMPACT (International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury) prognostic model in 1375 patients from the CENTER-TBI database, included in 53 centers across 17 countries, with moderate or severe TBI in the prospective European CENTER-TBI study. Future prediction modeling studies in acute diseases may benefit from following the suggested five steps for optimal statistical analysis and interpretation, after maximal effort has been made to minimize missing data. Show less
Dijkland, S.A.; Helmrich, I.R.A.R.; Nieboer, D.; Jagt, M. van der; Dippel, D.W.J.; Menon, D.K.; ... ; CENTER-TBI Participants Investig 2020
The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticoid Randomisation After Significant Head injury (CRASH) prognostic models predict... Show moreThe International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticoid Randomisation After Significant Head injury (CRASH) prognostic models predict functional outcome after moderate and severe traumatic brain injury (TBI). We aimed to assess their performance in a contemporary cohort of patients across Europe. The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) core study is a prospective, observational cohort study in patients presenting with TBI and an indication for brain computed tomography. The CENTER-TBI core cohort consists of 4509 TBI patients available for analyses from 59 centers in 18 countries across Europe and Israel. The IMPACT validation cohort included 1173 patients with GCS <= 12, age >= 14, and 6-month Glasgow Outcome Scale-Extended (GOSE) available. The CRASH validation cohort contained 1742 patients with GCS <= 14, age >= 16, and 14-day mortality or 6-month GOSE available. Performance of the three IMPACT and two CRASH model variants was assessed with discrimination (area under the receiver operating characteristic curve; AUC) and calibration (comparison of observed vs. predicted outcome rates). For IMPACT, model discrimination was good, with AUCs ranging between 0.77 and 0.85 in 1173 patients and between 0.80 and 0.88 in the broader CRASH selection (n = 1742). For CRASH, AUCs ranged between 0.82 and 0.88 in 1742 patients and between 0.66 and 0.80 in the stricter IMPACT selection (n = 1173). Calibration of the IMPACT and CRASH models was generally moderate, with calibration-in-the-large and calibration slopes ranging between -2.02 and 0.61 and between 0.48 and 1.39, respectively. The IMPACT and CRASH models adequately identify patients at high risk for mortality or unfavorable outcome, which supports their use in research settings and for benchmarking in the context of quality-of-care assessment. Show less
Loss to follow-up and missing outcomes data are important issues for longitudinal observational studies and clinical trials in traumatic brain injury. One popular solution to missing 6-month... Show moreLoss to follow-up and missing outcomes data are important issues for longitudinal observational studies and clinical trials in traumatic brain injury. One popular solution to missing 6-month outcomes has been to use the last observation carried forward (LOCF). The purpose of the current study was to compare the performance of model-based single-imputation methods with that of the LOCF approach. We hypothesized that model-based methods would perform better as they potentially make better use of available outcome data. The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study (n = 4509) included longitudinal outcome collection at 2 weeks, 3 months, 6 months, and 12 months post-injury; a total of 8185 Glasgow Outcome Scale extended (GOSe) observations were included in the database. We compared single imputation of 6-month outcomes using LOCF, a multiple imputation (MI) panel imputation, a mixed-effect model, a Gaussian process regression, and a multi-state model. Model performance was assessed via cross-validation on the subset of individuals with a valid GOSe value within 180 +/- 14 days post-injury (n = 1083). All models were fit on the entire available data after removing the 180 +/- 14 days post-injury observations from the respective test fold. The LOCF method showed lower accuracy (i.e., poorer agreement between imputed and observed values) than model-based methods of imputation, and showed a strong negative bias (i.e., it imputed lower than observed outcomes). Accuracy and bias for the model-based approaches were similar to one another, with the multi-state model having the best overall performance. All methods of imputation showed variation across different outcome categories, with better performance for more frequent outcomes. We conclude that model-based methods of single imputation have substantial performance advantages over LOCF, in addition to providing more complete outcome data. Show less
Mikolic, A.; Polinder, S.; Steyerberg, E.W.; Helmrich, I.R.A.R.; Giacino, J.T.; Maas, A.I.R.; ... ; CENTER TBI Study Pa 2020
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... Show moreThe 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. Show less
Blaauw, J.; Boxum, A.G.; Jacobs, B.; Groen, R.J.M.; Peul, W.C.; Jellema, K.; ... ; Naalt, J. van der 2020
Chronic subdural hematoma (CSDH) is a frequently occurring neurological disease associated with older age and use of anticoagulants. Symptoms vary from headaches to coma, but cognitive deficits can... Show moreChronic subdural hematoma (CSDH) is a frequently occurring neurological disease associated with older age and use of anticoagulants. Symptoms vary from headaches to coma, but cognitive deficits can also be present. However, exact prevalence and severity of cognitive deficits in CSDH are still unknown. In this systematic review, we aim to assess cognitive status of patients with CSDH, at presentation and after treatment. PubMed, Embase and PsycInfo were searched for articles concerning cognition in CSDH. We divided cognitive changes into subjective cognitive deficit (cognitive complaints [CC]) and objective cognitive deficit (cognitive impairment [CI]). Two reviewers independently selected studies for inclusion and subsequently extracted data. Quality assessment was done by means of the Newcastle-Ottawa Scale. Reported prevalence of CC and CI was pooled with random effects meta-analysis. Out of 799 identified references, 22 met inclusion criteria. Twenty-one articles reported on prevalence of CC/CI and one study reported solely on CSDH patients with cognitive deficit. Estimated pooled prevalence of both CC and CI in CSDH at presentation was 45% (95% confidence interval [CI]: 36-54%). Four studies concerned a prospective evaluation of the effect of surgical treatment on cognition. These proved to be of fair to good quality after quality assessment. The estimated pre-treatment prevalence of objectified cognitive impairment was 61% (95% CI: 51-70%) decreasing to 18% (95% CI: 8-32%) post-surgery. From this review it can be concluded that CC and CI are very common in CSDH, with a tendency to improve after treatment. Therefore, we underline the importance of increased attention to cognitive status of these patients, with proper testing methods and treatment-testing intervals. Show less
Prognostic assessment in traumatic brain injury (TBI) is embedded deeply in clinical care. Considering the limitations of current prognostic indicators, there is increasing interest in... Show morePrognostic assessment in traumatic brain injury (TBI) is embedded deeply in clinical care. Considering the limitations of current prognostic indicators, there is increasing interest in understanding the role of new biomarkers, and in finding other prognostic indicators of long-term outcomes following TBI. New prognostic indicators may result in the development of more accurate prediction models that could be useful for both risk stratification and clinical decision making. We aimed to review methodological issues and provide tentative guidelines for prognostic research in TBI. Prognostic factor research focuses on the role of a specific patient or disease-related characteristic in relation to outcome. Typically, univariable relations of the prognostic factor are studied, followed by analyses adjusting for other variables related to the outcome. Following existing guidelines, we emphasize the importance of transparent reporting of patient and specimen characteristics, study design, clinical end-points, and statistical analysis. Prognostic model research considers combinations of predictors, with challenges for model specification, estimation, evaluation, validation, and presentation. We highlight modern approaches and opportunities related to missing values, exploration of non-linear effects, and assessing between-study heterogeneity. Prognostic research in TBI can be improved if key methodological principles are adhered to and when research is performed in collaboration among multiple centers to ensure generalizability. Show less
Loss to follow-up or patient attrition is common in longitudinal studies of traumatic brain injury (TBI). Lack of understanding exists between the relation of study design and patient attrition.... Show moreLoss to follow-up or patient attrition is common in longitudinal studies of traumatic brain injury (TBI). Lack of understanding exists between the relation of study design and patient attrition. This review aimed to identify features of study design that are associated with attrition. We extended the analysis of a previous systematic review on missing data in 195 TBI studies using the Glasgow Outcome Scale Extended (GOSE) as an outcome measure. Studies that did not report attrition or had heterogeneous methodology were excluded, leaving 148 studies. Logistic regression found seven of the 14 design features studied to be associated with patient attrition. Four features were associated with an increase in attrition: greater follow-up frequency (odds ratio [OR]: 1.2, 95% confidence interval [CI]: 1.0-1.3), single rather than multi-center design (OR: 1.6, 95% CI: 1.2-2.2), enrollment of exclusively mild TBI patients (OR: 2.8, 95% CI: 1.6-4.9), and collection of the GOS by post or telephone without face-to-face contact (OR: 1.6, 95% CI:1.1-2.4). Conversely, two features were associated with a reduction in attrition: recruitment in an acute care setting defined as the ward or intensive care unit (OR: 0.58, 95% CI: 0.47-0.72) and a greater duration of time between injury and follow-up (OR: 0.93, 95% CI: 0.88-0.99). This review highlights design features that are associated with attrition and could be considered when planning for patient retention. Further work is needed to establish the mechanisms between the observed associations and potential remedies. Show less
Traumatic brain injury (TBI) is currently classified as mild, moderate, or severe TBI by trichotomizing the Glasgow Coma Scale (GCS). We aimed to explore directions for a more refined... Show moreTraumatic brain injury (TBI) is currently classified as mild, moderate, or severe TBI by trichotomizing the Glasgow Coma Scale (GCS). We aimed to explore directions for a more refined multidimensional classification system. For that purpose, we performed a hypothesis-free cluster analysis in the Collaborative European NeuroTrauma Effectiveness Research for TBI (CENTER-TBI) database: a European all-severity TBI cohort (n = 4509). The first building block consisted of key imaging characteristics, summarized using principal component analysis from 12 imaging characteristics. The other building blocks were demographics, clinical severity, secondary insults, and cause of injury. With these building blocks, the patients were clustered into four groups. We applied bootstrap resampling with replacement to study the stability of cluster allocation. The characteristics that predominantly defined the clusters were injury cause, major extracranial injury, and GCS. The clusters consisted of 1451, 1534, 1006, and 518 patients, respectively. The clustering method was quite stable: the proportion of patients staying in one cluster after resampling and reclustering was 97.4% (95% confidence interval [CI]: 85.6-99.9%). These clusters characterized groups of patients with different functional outcomes: from mild to severe, 12%, 19%, 36%, and 58% of patients had unfavorable 6 month outcome. Compared with the mild and the upper intermediate cluster, the lower intermediate and the severe cluster received more key interventions. To conclude, four types of TBI patients may be defined by injury mechanism, presence of major extracranial injury and GCS. Describing patients according to these three characteristics could potentially capture differences in etiology and care pathways better than with GCS only. Show less
Zeiler, F.A.; Aries, M.; Cabeleira, M.; Essen, T.A. van; Stocchetti, N.; Menon, D.K.; ... ; CENTER-TBI High Resolution ICU HR 2020
Decompressive craniectomy (DC) in traumatic brain injury (TBI) has been suggested to influence cerebrovascular reactivity. We aimed to determine if the statistical properties of vascular reactivity... Show moreDecompressive craniectomy (DC) in traumatic brain injury (TBI) has been suggested to influence cerebrovascular reactivity. We aimed to determine if the statistical properties of vascular reactivity metrics and slow-wave relationships were impacted after DC, as such information would allow us to comment on whether vascular reactivity monitoring remains reliable after craniectomy. Using the CENTER-TBI High Resolution Intensive Care Unit (ICU) Sub-Study cohort, we selected those secondary DC patients with high-frequency physiological data for both at least 24 h pre-DC, and more than 48 h post-DC. Data for all physiology measures were separated into the 24 h pre-DC, the first 48 h post-DC, and beyond 48 h post-DC. We produced slow-wave data sheets for intracranial pressure (ICP) and mean arterial pressure (MAP) per patient. We also derived a Pressure Reactivity Index (PRx) as a continuous cerebrovascular reactivity metric updated every minute. The time-series behavior of the PRx was modeled for each time period per patient. Finally, the relationship between ICP and MAP during these three time periods was assessed using time-series vector autoregressive integrative moving average (VARIMA) models, impulse response function (IRF) plots, and Granger causality testing. Ten patients were included in this study. Mean PRx and proportion of time above PRx thresholds were not affected by craniectomy. Similarly, PRx time-series structure was not affected by DC, when assessed in each individual patient. This was confirmed with Granger causality testing, and VARIMA IRF plotting for the MAP/ICP slow-wave relationship. PRx metrics and statistical time-series behavior appear not to be substantially influenced by DC. Similarly, there is little change in the relationship between slow waves of ICP and MAP before and after DC. This may suggest that cerebrovascular reactivity monitoring in the setting of DC may still provide valuable information regarding autoregulation. Show less
