Background Analgo-sedation plays an important role during intensive care management of traumatic brain injury (TBI) patients, however, limited evidence is available to guide practice. We sought to... Show moreBackground Analgo-sedation plays an important role during intensive care management of traumatic brain injury (TBI) patients, however, limited evidence is available to guide practice. We sought to quantify practice-pattern variation in neurotrauma sedation management, surveying an international sample of providers. Methods: An electronic survey consisting of 56 questions was distributed internationally to neurocritical care providers utilizing the Research Electronic Data Capture platform. Descriptive statistics were used to quantitatively describe and summarize the responses. Results: Ninety-five providers from 37 countries responded. 56.8% were attending physicians with primary medical training most commonly in intensive care medicine (68.4%) and anesthesiology (26.3%). Institutional sedation guidelines for TBI patients were available in 43.2%. Most common sedative agents for induction and maintenance, respectively, were propofol (87.5% and 88.4%), opioids (60.2% and 70.5%), and benzodiazepines (53.4% and 68.4%). Induction and maintenance sedatives, respectively, are mostly chosen according to provider preference (68.2% and 58.9%) rather than institutional guidelines (26.1% and 35.8%). Sedation duration for patients with intracranial hypertension ranged from 24 h to 14 days. Neurological wake-up testing (NWT) was routinely performed in 70.5%. The most common NWT frequency was every 24 h (47.8%), although 20.8% performed NWT at least every 2 h. Richmond Agitation and Sedation Scale targets varied from deep sedation (34.7%) to alert and calm (17.9%). Conclusions: Among critically ill TBI patients, sedation management follows provider preference rather than institutional sedation guidelines. Wide practice-pattern variation exists for the type, duration, and target of sedative management and NWT performance. Future comparative effectiveness research investigating these differences may help optimize sedation strategies to promote recovery. Show less
Kaplan, Z.L.R.; Vlegel, M. van der; Dijck, J.T.J.M. van; Pisica, D.; Leeuwen, N. van; Lingsma, H.F.; ... ; CENTER TBI Participants Invest 2023
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
Allonsius, F.; Kloet, A.J. de; Markus-Doornbosch, F. van; Vlieland, T.P.M.V.; Holst, M. van der 2023
PurposeBrain injuries (traumatic-/nontraumatic, TBI/nTBI) in young patients may lead to problems e.g., decreased health-related quality of life (HRQoL), and causes family impact. Knowledge... Show morePurposeBrain injuries (traumatic-/nontraumatic, TBI/nTBI) in young patients may lead to problems e.g., decreased health-related quality of life (HRQoL), and causes family impact. Knowledge regarding the family impact and the relationship with patients' HRQoL over time is scarce. This follow-up study describes family impact/HRQoL and their mutual relationship in young patients (5-24 years) after TBI/nTBI.Materials and methodsParents of patients that were referred to outpatient rehabilitation completed the PedsQL (TM) Family-Impact-Module questionnaire to assess the family impact and the parent-reported PedsQL (TM) Generic-core-set-4.0 to assess patients' HRQoL (lower scores: more family impact/worse HRQoL). Questionnaires were completed at the time of referral to rehabilitation (baseline) and one/two years later (T1/T2). Linear-mixed models were used to examine family impact/HRQoL change scores, and repeated-measure correlations (r) to determine longitudinal relationships.ResultsTwo-hundred-forty-six parents participated at baseline, 72 (at T2), median patient's age at baseline was 14 years (IQR:11-16), and 181 (74%) had TBI. Mean (SD) PedsQL (TM) Family-Impact-Module score at baseline was 71.7 (SD:16.4) and PedsQL (TM) Generic-core-set-4.0: 61.4 (SD:17.0). Over time, PedsQL (TM) Family-Impact-Module scores remained stable, while PedsQL (TM) Generic-core-set-4.0 scores improved significantly(p < 0.05). A moderately strong longitudinal correlation was found between family impact&HRQoL (r = 0.51).ConclusionsFamily impact does not tend to decrease over time but remained a considerable problem, although patients' HRQoL improved. Next to focusing on patients' HRQoL, it remains important to consider family impact and offer family support throughout rehabilitation. 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
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)... Show moreTraumatic 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. Show less
Background and Purpose: PTSD and mTBI are persistent and frequently comorbid after combat, yet current therapies often achieve only modest impact. A novel exposure-based “walk and talk” cognitive... Show moreBackground and Purpose: PTSD and mTBI are persistent and frequently comorbid after combat, yet current therapies often achieve only modest impact. A novel exposure-based “walk and talk” cognitive therapy, Motion-Assisted, Multi-Modal Memory Desensitization and Reconsolidation (3MDR), featuring participant-selected music and pictures and an eye movement (EM) task in an immersive virtual environment, has shown efficacy in treatment-resistant male veterans, but has not been studied in women or after TBI. The EM task is adapted from eye movement desensitization and reprocessing (EMDR) therapy, but dismantling studies of EMDR have questioned EM benefit. This pilot study assesses 3MDR in male and female veterans with comorbid PTSD and mTBI, and the impact of EM on response. We hypothesized that 3MDR would prove efficacious, both with (EM+) and without EM (EM-).Design: Participants with probable PTSD (PCL-5 ≥ 34) and mTBI were randomized to EM + or EM-across 10 sessions. Participants provided songs and pictures that they rated on impactfulness. While walking in the 3MDR virtual environment, participants started with a song to bring them back to the time of their trauma, and then traversed two hallways, actively walking toward emotionally evocative pictures that they then discussed with their therapist. Key words or feelings they expressed were superimposed over the picture, then read aloud, whereupon EM + participants recited numbers flashing on a ball crisscrossing the picture. These procedures were repeated for multiple pictures per session. A song to return the participant to present day closed each session. Change in PCL-5 score from pre-to post-intervention was the primary outcome, with additional measures at 3 and 6 months.Results: Sixteen (80%) of 20 participants completed the intervention (8 EM+, 8 EM-); 9 (6 EM+, 3 EM-) had resolution of PTSD diagnosis and two improved significantly without resolution. Average PCL-5 score declined from 52.0 (95% confidence intervals: 46.3, 57.7) at baseline to 33.6 (24.3, 42.9) post-intervention (p < 0.01). The EM + group achieved statistically significant improvement (p = 0.01) while the EM-did not (p = 0.10).Conclusion: For veterans with PTSD and comorbid mTBI, 3MDR is effective, and the EM component may add value. Confirmation with larger studies is important. Show less
Objective: To select a set of rehabilitation outcome instruments for a national Neurotrauma Quality Registry (Net-QuRe) among professionals involved in the care of patients with traumatic brain... Show moreObjective: To select a set of rehabilitation outcome instruments for a national Neurotrauma Quality Registry (Net-QuRe) among professionals involved in the care of patients with traumatic brain injury. Design: A 3-round online Delphi procedure. Subjects: Eighty professionals from multiple disciplines working in 1 of the 8 participating rehabilitation centres were invited to participate. The response rate varied from 70% to 76% per round. Methods: For the Delphi procedure, multiple outcome categories were defined based on the International Classification of Functioning, Disability and Health (ICF) with concomitant measurement instruments. For each category we strived for consensus on one instrument of at least 75%. Results: After the first round, consensus was reached for the category subjective cognitive functioning. After the second round for quality of life, pain, general functioning, anxiety and depression, general psychological functioning, communication (impairment), and personal factors. Finally, after the third round, consensus was reached for activities of daily living, participation, self-awareness, and aphasia. No consensus was reached for the categories motor function, cognitive function, comorbidity, fatigue, and employment status. Conclusion: Consensus was reached in 12 out of 17 outcome categories. A Delphi procedure seems to be a feasible method to collectively select measurement instruments for a multicentre study. 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
Patients suffering from familial hemiplegic migraine type 1 (FHM1) may have a disproportionally severe outcome after head trauma, but the underlying mechanisms are unclear. Hence, we subjected... Show morePatients suffering from familial hemiplegic migraine type 1 (FHM1) may have a disproportionally severe outcome after head trauma, but the underlying mechanisms are unclear. Hence, we subjected knock-in mice carrying the severer S218L or milder R192Q FHM1 gain-of-function missense mutation in the CACNA1A gene that encodes the alpha(1A) subunit of neuronal voltage-gated Ca(V)2.1 (P/Q-type) calcium channels and their wild-type (WT) littermates to experimental traumatic brain injury (TBI) by controlled cortical impact and investigated cortical spreading depolarizations (CSDs), lesion volume, brain edema formation, and functional outcome. After TBI, all mutant mice displayed considerably more CSDs and seizures than WT mice, while S218L mutant mice had a substantially higher mortality. Brain edema formation and the resulting increase in intracranial pressure were more pronounced in mutant mice, while only S218L mutant mice had larger lesion volumes and worse functional outcome. Here, we show that gain of Ca(V)2.1 channel function worsens histopathological and functional outcome after TBI in mice. This phenotype was associated with a higher number of CSDs, increased seizure activity, and more pronounced brain edema formation. Hence, our results suggest increased susceptibility for CSDs and seizures as potential mechanisms for bad outcome after TBI in FHM1 mutation carriers. Show less
Background Chronic subdural hematoma (CSDH) is a frequent pathological entity in daily clinical practice. However, evidence-based CSDH-guidelines are lacking and level I evidence from randomized... Show moreBackground Chronic subdural hematoma (CSDH) is a frequent pathological entity in daily clinical practice. However, evidence-based CSDH-guidelines are lacking and level I evidence from randomized clinical trials (RCTs) is limited. In order to establish and subsequently implement a guideline, insight into current clinical practice and attitudes toward CSDH-treatment is required. The aim is to explore current practice and attitudes toward CSDH-management in the Netherlands. Methods A national online survey was distributed among Dutch neurologists and neurosurgeons, examining variation in current CSDH-management through questions on treatment options, (peri)operative management, willingness to adopt new treatments and by presenting four CSDH-cases. Results One hundred nineteen full responses were received (8% of neurologists, N = 66 and 35% of neurosurgeons, N = 53). A majority of the respondents had a positive experience with burr-hole craniostomy (93%) and with a conservative policy (56%). Around a third had a positive experience with the use of dexamethasone as primary (30%) and additional (33.6%) treatment. These numbers were also reflected in the treatment preferences in the presented cases. (Peri)operative management corresponded among responding neurosurgeons. Most respondents would be willing to implement dexamethasone (98%) if equally effective as surgery and tranexamic acid (93%) if effective in CSDH-management. Conclusion Variation was found regarding preferential CSDH-treatment. However, this is considered not to be insurmountable when implementing evidence-based treatments. This baseline inventory on current clinical practice and current attitudes toward CSDH-treatment is a stepping-stone in the eventual development and implementation of a national guideline. Show less
Markus-Doornbosch, F. van; Meesters, J.J.; Volker, G.; Ijzereef, W.A.; Hout, W.B. van den; Vlieland, T.P.V.; Kloet, A.J. de 2022
BACKGROUND: Persons with disabilities are at risk for unemployment with negative long-term consequences.OBJECTIVE: This study aimed to explore the process and outcomes of a novel vocational... Show moreBACKGROUND: Persons with disabilities are at risk for unemployment with negative long-term consequences.OBJECTIVE: This study aimed to explore the process and outcomes of a novel vocational rehabilitation (VR) program based on the concept of mentorship.METHODS: Observational, retrospective study including unemployed young adults with acquired brain injury (ABI) taking part in a VR program including assessment, training, individual counselling and mentor support from volunteering professionals. Adherence to the program and work status were registered and at follow-up all patients were invited to complete a general questionnaire and EuroQol 5D.RESULTS: 49 patients started the program, with 41 completing the follow-up. Median age was 31 years and 19 were male. Median duration of the program was 8 months. At follow-up, 9 patients had acquired paid employment, 7 with the support of a mentor; 6 of whom were bothered by health problems at work. Nine patients left the program prematurely, with insufficient financial support for continuation being the primary reason for withdrawal (n = 6).CONCLUSIONS: A VR program including a mentor may be a promising program for patients who are unemployed at onset of ABI. Lack of financial support to complete the program and concurrent health problems were found to hamper the process and outcomes of the program, respectively. Show less
Steinbuechel, N. von; Rauen, K.; Krenz, U.; Wu, Y.J.; Covic, A.; Plass, A.M.; ... ; Linguistic Validation Grp CENTER 2021
Assessing outcomes in multinational studies on traumatic brain injury (TBI) poses major challenges and requires relevant instruments in languages other than English. Of the 19 outcome instruments... Show moreAssessing outcomes in multinational studies on traumatic brain injury (TBI) poses major challenges and requires relevant instruments in languages other than English. Of the 19 outcome instruments selected for use in the observational Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study, 17 measures lacked translations in at least one target language. To fill this gap, we aimed to develop well-translated linguistically and psychometrically validated instruments. We performed translations and linguistic validations of patient-reported measures (PROMs), clinician-reported (ClinRO), and performance-based (PerfO) outcome instruments, using forward and backward translations, reconciliations, cognitive debriefings with up to 10 participants, iterative revisions, and international harmonization with input from over 150 international collaborators. In total, 237 translations and 211 linguistic validations were carried out in up to 20 languages. Translations were evaluated at the linguistic and cultural level by coding changes when the original versions are compared with subsequent translation steps, using the output of cognitive debriefings, and using comprehension rates. The average comprehension rate per instrument varied from 88% to 98%, indicating a good quality of the translations. These outcome instruments provide a solid basis for future TBI research and clinical practice and allow the aggregation and analysis of data across different countries and languages. Show less
Traumatic brain injury (TBI) may lead to impairments in various outcome domains. Since most instruments assessing these are only available in a limited number of languages, psychometrically... Show moreTraumatic brain injury (TBI) may lead to impairments in various outcome domains. Since most instruments assessing these are only available in a limited number of languages, psychometrically validated translations are important for research and clinical practice. Thus, our aim was to investigate the psychometric properties of the patient-reported outcome measures (PROM) applied in the CENTER-TBI study. The study sample comprised individuals who filled in the six-months assessments (GAD-7, PHQ-9, PCL-5, RPQ, QOLIBRI/-OS, SF-36v2/-12v2). Classical psychometric characteristics were investigated and compared with those of the original English versions. The reliability was satisfactory to excellent; the instruments were comparable to each other and to the original versions. Validity analyses demonstrated medium to high correlations with well-established measures. The original factor structure was replicated by all the translations, except for the RPQ, SF-36v2/-12v2 and some language samples for the PCL-5, most probably due to the factor structure of the original instruments. The translation of one to two items of the PHQ-9, RPQ, PCL-5, and QOLIBRI in three languages could be improved in the future to enhance scoring and application at the individual level. Researchers and clinicians now have access to reliable and valid instruments to improve outcome assessment after TBI in national and international health care. 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
OBJECTIVE The incidence of venous thromboembolism (VTE) in patients with traumatic brain injury (TBI) has in-creased significantly. The Eastern Association for the Surgery of Trauma recommends... Show moreOBJECTIVE The incidence of venous thromboembolism (VTE) in patients with traumatic brain injury (TBI) has in-creased significantly. The Eastern Association for the Surgery of Trauma recommends using low-molecular-weight hepa- rin (LMWH) over unfractionated heparin (UH) in pediatric patients requiring VTE prophylaxis, although this strategy is unsupported by the literature. In this study, the authors compare the outcomes of pediatric TBI patients receiving LMWH versus UH.METHODS The authors performed a 4-year (2014 & ndash;2017) analysis of the pediatric American College of Surgeons Trau-ma Quality Improvement Program. All trauma patients (age <= 18 years) with TBI requiring thromboprophylaxis with UH or LMWH were potentially eligible for inclusion. Patients who had been transferred, had died in the emergency department, or had penetrating trauma were excluded. Patients were stratified into either the LMWH or the UH group on the basis of the prophylaxis they had received. Patients were matched on the basis of demographics, injury characteristics, vital signs, and transfusion requirements using propensity score matching (PSM). The study endpoints were VTE, death, and craniotomy after initiation of prophylaxis. Univariate analysis was performed after PSM to compare outcomes.RESULTS A total of 2479 patients met the inclusion criteria (mean age 15.5 +/- 3.7 years and 32.0% female), of which 1570 (63.3%) had received LMWH and 909 (36.7%) had received UH. Before PSM, patients receiving UH were younger, had a lower Glasgow Coma Scale score, and had a higher Injury Severity Score. Patients treated in pediatric hospitals were more likely to receive UH (12.9% vs 9.0%, p < 0.001) than patients treated in adult hospitals. Matched patients re-ceiving UH had a higher incidence of VTE (5.1% vs 2.9%, p = 0.03).CONCLUSIONS LMWH prophylaxis in pediatric TBI appears to be more effective than UH in preventing VTE. Large, multicenter prospective studies are warranted to confirm the superiority of LMWH over UH in pediatric patients with TBI. Moreover, outcomes of VTE prophylaxis in the very young remain understudied; therefore, dedicated studies to evaluate this are needed. Show less
BackgroundAcute alcohol intoxication is very common in patients with severe traumatic brain injury (TBI). Whether there is an independent association between alcohol intoxication and mortality is... Show moreBackgroundAcute alcohol intoxication is very common in patients with severe traumatic brain injury (TBI). Whether there is an independent association between alcohol intoxication and mortality is debated. This study hypothesized that alcohol intoxication is independently associated with less mortality after severe TBI (sTBI).MethodsThis retrospective observational cohort study included all patients with sTBI [head-Abbreviated Injury Score (AIS) >= 3, corresponding to serious head injury or worse] admitted from 1 January 2011 to 31 December 2016 in an academic level I trauma center. Patients were classified as with alcohol intoxication or without intoxication based on blood alcohol concentration or description of alcohol intoxication on admission. The primary endpoint was in-hospital mortality. Multivariable logistic regression analysis, including patient and injury characteristics, was used to assess independent association with alcohol intoxication.ResultsOf the 2865 TBI patients, 715 (25%) suffered from alcohol intoxication. They were younger (mean age 46 vs. 68 years), more often male (80 vs. 57%) and had a lower median Glasgow Coma Scale upon arrival (14 vs. 15) compared to the no-intoxication group. There was no difference in injury severity by head AIS or Rotterdam CT. Alcohol intoxication had an unadjusted association with in-hospital mortality [unadjusted odds ratio (OR) 0.51; 95% confidence interval (CI), 0.38-0.68]; however, there was no independent association after adjusting for potentially confounding patient and injury characteristics (adjusted OR 0.72; 95% CI, 0.48-1.09).ConclusionIn this retrospective study, there was no independent association between alcohol intoxication and higher in-hospital mortality in emergency patients with sTBI. 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
