Brain Temperature Influences Intracranial Pressure and Cerebral Perfusion Pressure After Traumatic Brain Injury: A CENTER-TBI Study

Cited by: 8; All Open Access, Green Open Access, Hybrid Gold Open AccessPeer reviewe

Contribution of clinical course to outcome after traumatic brain injury: mining patient trajectories from European intensive care unit data

Existing methods to characterise the evolving condition of traumatic brain injury (TBI) patients in the intensive care unit (ICU) do not capture the context necessary for individualising treatment. We aimed to develop a modelling strategy which integrates all data stored in medical records to produce an interpretable disease course for each TBI patient's ICU stay. From a prospective, European cohort (n=1,550, 65 centres, 19 countries) of TBI patients, we extracted all 1,166 variables collected before or during ICU stay as well as 6-month functional outcome on the Glasgow Outcome Scale-Extended (GOSE). We trained recurrent neural network models to map a token-embedded time series representation of all variables (including missing data) to an ordinal GOSE prognosis every 2 hours. With repeated cross-validation, we evaluated calibration and the explanation of ordinal variance in GOSE with Somers' Dxy. Furthermore, we applied TimeSHAP to calculate the contribution of variables and prior timepoints towards transitions in patient trajectories. Our modelling strategy achieved calibration at 8 hours, and the full range of variables explained up to 52% (95% CI: 50-54%) of the variance in ordinal functional outcome. Up to 91% (90-91%) of this explanation was derived from pre-ICU and admission information. Information collected in the ICU increased explanation (by up to 5% [4-6%]), though not enough to counter poorer performance in longer-stay (>5.75 days) patients. Static variables with the highest contributions were physician prognoses and certain demographic and CT features. Among dynamic variables, markers of intracranial hypertension and neurological function contributed the most. Whilst static information currently accounts for the majority of functional outcome explanation, our data-driven analysis highlights investigative avenues to improve dynamic characterisation of longer-stay patients

Contrasting characteristics and outcomes of sports-related and non–sports-related traumatic brain injury

Importance Exposure to traumatic brain injury (TBI) has raised widespread concern over participation in sports, particularly over possible long-term consequences. However, little is known about the outcomes of individuals presenting to hospitals with sports-related TBI. Objective To compare the characteristics and outcomes of individuals presenting to hospitals with sports-related and non–sports-related TBI. Design, Setting, and Participants The CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI) observational cohort study was conducted at hospitals in 18 countries. The study enrolled 4509 patients who had TBI and had an indication for computed tomography (CT), of whom 4360 were 16 years or older. Outcomes were assessed at 3 and 6 months, and groups were compared using regression analyses adjusting for clinical and demographic differences. Data were collected between December 9, 2014, and December 17, 2017, and analyzed from August 2022 to March 2023. Exposure Sports-related and non–sports-related TBI with subgroups selected by severity of injury. Main Outcomes and Measures The main outcome was the Glasgow Outcome Scale–Extended (GOSE) at 6 months, with secondary outcomes covering postconcussion symptoms, health-related quality of life, and mental health. Results A total of 4360 patients were studied, including 256 (6%) with sports-related TBI (mean [SD] age, 38.9 [18.1] years; 161 [63%] male) and 4104 with non–sports-related TBI (mean [SD] age, 51.0 [20.2] years; 2773 [68%] male). Compared with patients with non–sports-related TBI, patients with sports-related TBI were younger, more likely to have tertiary education, more likely to be previously healthy, and less likely to have a major extracranial injury. After adjustment, the groups did not differ in incomplete recovery (GOSE scores <8) at 6 months (odds ratio [OR], 1.27; 95% CI, 0.90-1.78; P = .22 for all patients; OR, 1.20; 95% CI, 0.83-1.73; P = .34 for those with mild TBI; and OR, 1.19; 95% CI, 0.74-1.92; P = .65 for those with mild TBI and negative CT findings). At 6 months, there was incomplete recovery in 103 of 223 patients (46%) with outcomes in the sports-related TBI group, 65 of 168 (39%) in those with mild sports-related TBI, and 30 of 98 (31%) in those with mild sports-related TBI and negative CT findings. In contrast, at 6 months, the sports-related TBI group had lower prevalence of anxiety, depression, posttraumatic stress disorder, and postconcussion symptoms than the non–sports-related group. Conclusions and Relevance In this cohort study of 4360 patients with TBI, functional limitations 6 months after injury were common after sports-related TBI, even mild sports-related TBI. Persisting impairment was evident in the sports-related TBI group despite better recovery compared with non–sports-related TBI on measures of mental health and postconcussion symptoms. These findings caution against taking an overoptimistic view of outcomes after sports-related TBI, even if the initial injury appears mild

The impact of neurocognitive functioning on the course of posttraumatic stress symptoms following civilian traumatic brain injury

Background: One out of seven individuals who have suffered a traumatic brain injury (TBI) develops a posttraumatic stress disorder (PTSD), which is often associated with neurocognitive impairment. The present study explores the impact of neurocognitive functioning after mild, moderate, and severe TBI on the course of PTSD symptoms. Methods: The data of 671 adults admitted to hospital for a TBI was drawn from the Collaborative European Neurotrauma Effectiveness Research (CENTER-TBI) study. After six- and 12-months post-injury, participants completed the PTSD Checklist-5 (PCL-5), from which change scores were calculated. At six months, participants also completed a neurocognitive assessment including the Rey Auditory Verbal Learning Test, the Trail Making Test, and the Cambridge Neuropsychological Test Automated Battery (CANTAB). Linear regressions were performed to identify associations between cognitive functioning and PCL-5 change scores. Results: Overall, mean PCL-5 change scores showed no clear change (−0.20 ± 9.88), but 87 improved and 80 deteriorated by a change score of 10 or more. CANTAB Rapid Visual Information Processing scores were significantly associated with PCL-5 change scores. Conclusions: Strong sustained attention was associated with improvement in PTSD symptoms. Assessing cognitive performance may help identify individuals at risk of developing (persisting) PTSD post-TBI and offer opportunities for informing treatment strategies

Reference Values of the QOLIBRI from General Population Samples in the United Kingdom and The Netherlands

The Quality of Life after Traumatic Brain Injury (QOLIBRI) instrument is an internationally validated patient-reported outcome measure for assessing disease-specific health-related quality of life (HRQoL) in individuals after traumatic brain injury (TBI). However, no reference values for general populations are available yet for use in clinical practice and research in the field of TBI. The aim of the present study was, therefore, to establish these reference values for the United Kingdom (UK) and the Netherlands (NL). For this purpose, an online survey with a reworded version of the QOLIBRI for general populations was used to collect data on 4403 individuals in the UK and 3399 in the NL. This QOLIBRI version was validated by inspecting descriptive statistics, psychometric criteria, and comparability of the translations to the original version. In particular, measurement invariance (MI) was tested to examine whether the items of the instrument were understood in the same way by different individuals in the general population samples and in the TBI sample across the two countries, which is necessary in order to establish reference values. In the general population samples, the reworded QOLIBRI displayed good psychometric properties, including MI across countries and in the non-TBI and TBI samples. Therefore, differences in the QOLIBRI scores can be attributed to real differences in HRQoL. Individuals with and without a chronic health condition did differ significantly, with the latter reporting lower HRQoL. In conclusion, we provided reference values for healthy individuals and individuals with at least one chronic condition from general population samples in the UK and the NL. These can be used in the interpretation of disease-specific HRQoL assessments after TBI applying the QOLIBRI on the individual level in clinical as well as research contexts

Psychometric Characteristics of the Patient-Reported Outcome Measures Applied in the CENTER-TBI Study.

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 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

Understanding the relationship between cognitive performance and function in daily life after traumatic brain injury

Objective Cognitive impairment is a key cause of disability after traumatic brain injury (TBI) but relationships with overall functioning in daily life are often modest. The aim is to examine cognition at different levels of function and identify domains associated with disability. Methods 1554 patients with mild-to-severe TBI were assessed at 6 months post injury on the Glasgow Outcome Scale-Extended (GOSE), the Short Form-12v2 and a battery of cognitive tests. Outcomes across GOSE categories were compared using analysis of covariance adjusting for age, sex and education. Results Overall effect sizes were small to medium, and greatest for tests involving processing speed (eta(2)(p) 0.057-0.067) and learning and memory (eta(2)(p) 0.048-0.052). Deficits in cognitive performance were particularly evident in patients who were dependent (GOSE 3 or 4) or who were unable to participate in one or more major life activities (GOSE 5). At higher levels of function (GOSE 6-8), cognitive performance was surprisingly similar across categories. There were decreases in performance even in patients reporting complete recovery without significant symptoms. Medium to large effect sizes were present for summary measures of cognition (eta(2)(p) 0.111), mental health (eta(2)(p) 0.131) and physical health (eta(2)(p) 0.252). Conclusions This large-scale study provides novel insights into cognitive performance at different levels of disability and highlights the importance of processing speed in function in daily life. At upper levels of outcome, any influence of cognition on overall function is markedly attenuated and differences in mental health are salient.Peer reviewe

Quality indicators for patients with traumatic brain injury in European intensive care units: a CENTER-TBI study.

BACKGROUND:The aim of this study is to validate a previously published consensus-based quality indicator set for the management of patients with traumatic brain injury (TBI) at intensive care units (ICUs) in Europe and to study its potential for quality measurement and improvement. METHODS:Our analysis was based on 2006 adult patients admitted to 54 ICUs between 2014 and 2018, enrolled in the CENTER-TBI study. Indicator scores were calculated as percentage adherence for structure and process indicators and as event rates or median scores for outcome indicators. Feasibility was quantified by the completeness of the variables. Discriminability was determined by the between-centre variation, estimated with a random effect regression model adjusted for case-mix severity and quantified by the median odds ratio (MOR). Statistical uncertainty of outcome indicators was determined by the median number of events per centre, using a cut-off of 10. RESULTS:A total of 26/42 indicators could be calculated from the CENTER-TBI database. Most quality indicators proved feasible to obtain with more than 70% completeness. Sub-optimal adherence was found for most quality indicators, ranging from 26 to 93% and 20 to 99% for structure and process indicators. Significant (p < 0.001) between-centre variation was found in seven process and five outcome indicators with MORs ranging from 1.51 to 4.14. Statistical uncertainty of outcome indicators was generally high; five out of seven had less than 10 events per centre. CONCLUSIONS:Overall, nine structures, five processes, but none of the outcome indicators showed potential for quality improvement purposes for TBI patients in the ICU. Future research should focus on implementation efforts and continuous reevaluation of quality indicators. TRIAL REGISTRATION:The core study was registered with ClinicalTrials.gov, number NCT02210221, registered on August 06, 2014, with Resource Identification Portal (RRID: SCR_015582)

Impact of duration and magnitude of raised intracranial pressure on outcome after severe traumatic brain injury: A CENTER-TBI high-resolution group study

Magnitude of intracranial pressure (ICP) elevations and their duration have been associated with worse outcomes in patients with traumatic brain injuries (TBI), however published thresholds for injury vary and uncertainty about these levels has received relatively little attention. In this study, we have analyzed high-resolution ICP monitoring data in 227 adult patients in the CENTER-TBI dataset. Our aim was to identify thresholds of ICP intensity and duration associated with worse outcome, and to evaluate the uncertainty in any such thresholds. We present ICP intensity and duration plots to visualize the relationship between ICP events and outcome. We also introduced a novel bootstrap technique to evaluate uncertainty of the equipoise line. We found that an intensity threshold of 18 ± 4 mmHg (2 standard deviations) was associated with worse outcomes in this cohort. In contrast, the uncertainty in what duration is associated with harm was larger, and safe durations were found to be population dependent. The pressure and time dose (PTD) was also calculated as area under the curve above thresholds of ICP. A relationship between PTD and mortality could be established, as well as for unfavourable outcome. This relationship remained valid for mortality but not unfavourable outcome after adjusting for IMPACT core variables and maximum therapy intensity level. Importantly, during periods of impaired autoregulation (defined as pressure reactivity index (PRx)>0.3) ICP events were associated with worse outcomes for nearly all durations and ICP levels in this cohort and there was a stronger relationship between outcome and PTD. Whilst caution should be exercised in ascribing causation in observational analyses, these results suggest intracranial hypertension is poorly tolerated in the presence of impaired autoregulation. ICP level guidelines may need to be revised in the future taking into account cerebrovascular autoregulation status considered jointly with ICP levels

Impact of duration and magnitude of raised intracranial pressure on outcome after severe traumatic brain injury: A CENTER-TBI high-resolution group study

Magnitude of intracranial pressure (ICP) elevations and their duration have been associated with worse outcomes in patients with traumatic brain injuries (TBI), however published thresholds for injury vary and uncertainty about these levels has received relatively little attention. In this study, we have analyzed high-resolution ICP monitoring data in 227 adult patients in the CENTER-TBI dataset. Our aim was to identify thresholds of ICP intensity and duration associated with worse outcome, and to evaluate the uncertainty in any such thresholds. We present ICP intensity and duration plots to visualize the relationship between ICP events and outcome. We also introduced a novel bootstrap technique to evaluate uncertainty of the equipoise line. We found that an intensity threshold of 18 ± 4 mmHg (2 standard deviations) was associated with worse outcomes in this cohort. In contrast, the uncertainty in what duration is associated with harm was larger, and safe durations were found to be population dependent. The pressure and time dose (PTD) was also calculated as area under the curve above thresholds of ICP. A relationship between PTD and mortality could be established, as well as for unfavourable outcome. This relationship remained valid for mortality but not unfavourable outcome after adjusting for IMPACT core variables and maximum therapy intensity level. Importantly, during periods of impaired autoregulation (defined as pressure reactivity index (PRx)>0.3) ICP events were associated with worse outcomes for nearly all durations and ICP levels in this cohort and there was a stronger relationship between outcome and PTD. Whilst caution should be exercised in ascribing causation in observational analyses, these results suggest intracranial hypertension is poorly tolerated in the presence of impaired autoregulation. ICP level guidelines may need to be revised in the future taking into account cerebrovascular autoregulation status considered jointly with ICP levels