| 1. |
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| 2. |
- Middeldorp, Christel M., et al.
(författare)
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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
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Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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| 3. |
- Yuh, Esther L, et al.
(författare)
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Pathological computed tomography features associated with adverse outcomes after mild traumatic brain injury : A TRACK-TBI study with external validation in CENTER-TBI.
- 2021
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 78:9, s. 1137-1148
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood.OBJECTIVE: To identify pathological CT features associated with adverse outcomes after mTBI.DESIGN, SETTING, AND PARTICIPANTS: The longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale-Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021.EXPOSURES: Acute nonpenetrating head trauma.MAIN OUTCOMES AND MEASURES: Frequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores <8 vs 8); and an unfavorable outcome (GOSE scores <5 vs ≥5) at 2 weeks and 3, 6, and 12 months.RESULTS: In 1935 patients with mTBI (mean [SD] age, 41.5 [17.6] years; 1286 men [66.5%]) in the TRACK-TBI cohort and 2594 patients with mTBI (mean [SD] age, 51.8 [20.3] years; 1658 men [63.9%]) in an external validation cohort, hierarchical cluster analysis identified 3 major clusters of CT features: contusion, subarachnoid hemorrhage, and/or subdural hematoma; intraventricular and/or petechial hemorrhage; and epidural hematoma. Contusion, subarachnoid hemorrhage, and/or subdural hematoma features were associated with incomplete recovery (odds ratios [ORs] for GOSE scores <8 at 1 year: TRACK-TBI, 1.80 [95% CI, 1.39-2.33]; CENTER-TBI, 2.73 [95% CI, 2.18-3.41]) and greater degrees of unfavorable outcomes (ORs for GOSE scores <5 at 1 year: TRACK-TBI, 3.23 [95% CI, 1.59-6.58]; CENTER-TBI, 1.68 [95% CI, 1.13-2.49]) out to 12 months after injury, but epidural hematoma was not. Intraventricular and/or petechial hemorrhage was associated with greater degrees of unfavorable outcomes up to 12 months after injury (eg, OR for GOSE scores <5 at 1 year in TRACK-TBI: 3.47 [95% CI, 1.66-7.26]). Some CT features were more strongly associated with outcomes than previously validated variables (eg, ORs for GOSE scores <5 at 1 year in TRACK-TBI: neuropsychiatric history, 1.43 [95% CI .98-2.10] vs contusion, subarachnoid hemorrhage, and/or subdural hematoma, 3.23 [95% CI 1.59-6.58]). Findings were externally validated in 2594 patients with mTBI enrolled in the CENTER-TBI study.CONCLUSIONS AND RELEVANCE: In this study, pathological CT features carried different prognostic implications after mTBI to 1 year postinjury. Some patterns of injury were associated with worse outcomes than others. These results support that patients with mTBI and these CT features need TBI-specific education and systematic follow-up.
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| 4. |
- Dijkland, Simone A., et al.
(författare)
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Outcome Prediction after Moderate and Severe Traumatic Brain Injury : External Validation of Two Established Prognostic Models in 1742 European Patients
- 2021
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 38:10, s. 1377-1388
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Tidskriftsartikel (refereegranskat)abstract
- 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 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.
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| 5. |
- Galimberti, Stefania, et al.
(författare)
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Effect of frailty on 6-month outcome after traumatic brain injury : a multicentre cohort study with external validation
- 2022
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 21:2, s. 153-162
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Frailty is known to be associated with poorer outcomes in individuals admitted to hospital for medical conditions requiring intensive care. However, little evidence is available for the effect of frailty on patients' outcomes after traumatic brain injury. Many frailty indices have been validated for clinical practice and show good performance to predict clinical outcomes. However, each is specific to a particular clinical context. We aimed to develop a frailty index to predict 6-month outcomes in patients after a traumatic brain injury.METHODS: A cumulative deficit approach was used to create a novel frailty index based on 30 items dealing with disease states, current medications, and laboratory values derived from data available from CENTER-TBI, a prospective, longitudinal observational study of patients with traumatic brain injury presenting within 24 h of injury and admitted to a ward or an intensive care unit at 65 centres in Europe between Dec 19, 2014, and Dec 17, 2017. From the individual cumulative CENTER-TBI frailty index (range 0-30), we obtained a standardised value (range 0-1), with high scores indicating higher levels of frailty. The effect of frailty on 6-month outcome evaluated with the extended Glasgow Outcome Scale (GOSE) was assessed through a proportional odds logistic model adjusted for known outcome predictors. An unfavourable outcome was defined as death or severe disability (GOSE score ≤4). External validation was performed on data from TRACK-TBI, a prospective observational study co-designed with CENTER-TBI, which enrolled patients with traumatic brain injury at 18 level I trauma centres in the USA from Feb 26, 2014, to July 27, 2018. CENTER-TBI is registered with ClinicalTrials.gov, NCT02210221; TRACK-TBI is registered at ClinicalTrials.gov, NCT02119182.FINDINGS: 2993 participants (median age was 51 years [IQR 30-67], 2058 [69%] were men) were included in this analysis. The overall median CENTER-TBI frailty index score was 0·07 (IQR 0·03-0·15), with a median score of 0·17 (0·08-0·27) in older adults (aged ≥65 years). The CENTER-TBI frailty index score was significantly associated with the probability of an increasingly unfavourable outcome (cumulative odds ratio [OR] 1·03, 95% CI 1·02-1·04; p<0·0001), and the association was stronger for participants admitted to hospital wards (1·04, 1·03-1·06, p<0·0001) compared with those admitted to the intensive care unit (1·02, 1·01-1·03 p<0·0001). External validation of the CENTER-TBI frailty index in data from the TRACK-TBI (n=1667) cohort supported the robustness and reliability of these findings. The overall median TRACK-TBI frailty index score was 0·03 (IQR 0-0·10), with the frailty index score significantly associated with the risk of an increasingly unfavourable outcome in patients admitted to hospital wards (cumulative OR 1·05, 95% CI 1·03-1·08; p<0·0001), but not in those admitted to the intensive care unit (1·01, 0·99-1·03; p=0·43).INTERPRETATION: We developed and externally validated a frailty index specific to traumatic brain injury. Risk of unfavourable outcome was significantly increased in participants with a higher CENTER-TBI frailty index score, regardless of age. Frailty identification could help to individualise rehabilitation approaches aimed at mitigating effects of frailty in patients with traumatic brain injury.FUNDING: European Union, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences Corporation, NeuroTrauma Sciences, NIH-NINDS-TRACK-TBI, US Department of Defense.
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| 6. |
- Huie, J. Russell, et al.
(författare)
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Biomarkers for Traumatic Brain Injury : Data Standards and Statistical Considerations
- 2021
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 38:18, s. 2514-2529
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Tidskriftsartikel (refereegranskat)abstract
- Recent biomarker innovations hold potential for transforming diagnosis, prognostic modeling, and precision therapeutic targeting of traumatic brain injury (TBI). However, many biomarkers, including brain imaging, genomics, and proteomics, involve vast quantities of high-throughput and high-content data. Management, curation, analysis, and evidence synthesis of these data are not trivial tasks. In this review, we discuss data management concepts and statistical and data sharing strategies when dealing with biomarker data in the context of TBI research. We propose that application of biomarkers involves three distinct steps-discovery, evaluation, and evidence synthesis. First, complex/big data has to be reduced to useful data elements at the stage of biomarker discovery. Second, inferential statistical approaches must be applied to these biomarker data elements for assessment of biomarker clinical utility and validity. Last, synthesis of relevant research is required to support practice guidelines and enable health decisions informed by the highest quality, up-to-date evidence available. We focus our discussion around recent experiences from the International Traumatic Brain Injury Research (InTBIR) initiative, with a specific focus on four major clinical projects (Transforming Research and Clinical Knowledge in TBI, Collaborative European NeuroTrauma Effectiveness Research in TBI, Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe, and Approaches and Decisions in Acute Pediatric TBI Trial), which are currently enrolling subjects in North America and Europe. We discuss common data elements, data collection efforts, data-sharing opportunities, and challenges, as well as examine the statistical techniques required to realize successful adoption and use of biomarkers in the clinic as a foundation for precision medicine in TBI.
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| 7. |
- Mikolić, Ana, et al.
(författare)
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Prediction of Global Functional Outcome and Post-Concussive Symptoms after Mild Traumatic Brain Injury : External Validation of Prognostic Models in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study
- 2021
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 38:2, s. 196-209
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Tidskriftsartikel (refereegranskat)abstract
- The majority of traumatic brain injuries (TBIs) are categorized as mild, according to a baseline Glasgow Coma Scale (GCS) score of 13-15. Prognostic models that were developed to predict functional outcome and persistent post-concussive symptoms (PPCS) after mild TBI have rarely been externally validated. We aimed to externally validate models predicting 3-12-month Glasgow Outcome Scale Extended (GOSE) or PPCS in adults with mild TBI. We analyzed data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) project, which included 2862 adults with mild TBI, with 6-month GOSE available for 2374 and Rivermead Post-Concussion Symptoms Questionnaire (RPQ) results available for 1605 participants. Model performance was evaluated based on calibration (graphically and characterized by slope and intercept) and discrimination (C-index). We validated five published models for 6-month GOSE and three for 6-month PPCS scores. The models used different cutoffs for outcome and some included symptoms measured 2 weeks post-injury. Discriminative ability varied substantially (C-index between 0.58 and 0.79). The models developed in the Corticosteroid Randomisation After Significant Head Injury (CRASH) trial for prediction of GOSE <5 discriminated best (C-index 0.78 and 0.79), but were poorly calibrated. The best performing models for PPCS included 2-week symptoms (C-index 0.75 and 0.76). In conclusion, none of the prognostic models for early prediction of GOSE and PPCS has both good calibration and discrimination in persons with mild TBI. In future studies, prognostic models should be tailored to the population with mild TBI, predicting relevant end-points based on readily available predictors.
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| 8. |
- Thomas, Ilias, 1987-, et al.
(författare)
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Serum metabolome associated with severity of acute traumatic brain injury
- 2022
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Ingår i: Nature Communications. - : Nature Research. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Complex metabolic disruption is a crucial aspect of the pathophysiology of traumatic brain injury (TBI). Associations between this and systemic metabolism and their potential prognostic value are poorly understood. Here, we aimed to describe the serum metabolome (including lipidome) associated with acute TBI within 24 h post-injury, and its relationship to severity of injury and patient outcome. We performed a comprehensive metabolomics study in a cohort of 716 patients with TBI and non-TBI reference patients (orthopedic, internal medicine, and other neurological patients) from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) cohort. We identified panels of metabolites specifically associated with TBI severity and patient outcomes. Choline phospholipids (lysophosphatidylcholines, ether phosphatidylcholines and sphingomyelins) were inversely associated with TBI severity and were among the strongest predictors of TBI patient outcomes, which was further confirmed in a separate validation dataset of 558 patients. The observed metabolic patterns may reflect different pathophysiological mechanisms, including protective changes of systemic lipid metabolism aiming to maintain lipid homeostasis in the brain.
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| 9. |
- van der Vlegel, Marjolein, et al.
(författare)
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Health care utilization and outcomes in older adults after Traumatic Brain Injury : a CENTER-TBI study
- 2022
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Ingår i: Injury. - : Elsevier. - 0020-1383 .- 1879-0267. ; 53:8, s. 2774-2782
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The incidence of Traumatic Brain Injury (TBI) is increasingly common in older adults aged ≥65 years, forming a growing public health problem. However, older adults are underrepresented in TBI research. Therefore, we aimed to provide an overview of health-care utilization, and of six-month outcomes after TBI and their determinants in older adults who sustained a TBI.METHODS: We used data from the prospective multi-center Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. In-hospital and post-hospital health care utilization and outcomes were described for patients aged ≥65 years. Ordinal and linear regression analyses were performed to identify determinants of the Glasgow Outcome Scale Extended (GOSE), health-related quality of life (HRQoL), and mental health symptoms six-months post-injury.RESULTS: Of 1254 older patients, 45% were admitted to an ICU with a mean length of stay of 9 days. Nearly 30% of the patients received inpatient rehabilitation. In total, 554/1254 older patients completed the six-month follow-up questionnaires. The mortality rate was 9% after mild and 60% after moderate/severe TBI, and full recovery based on GOSE was reported for 44% of patients after mild and 6% after moderate/severe TBI. Higher age and increased injury severity were primarily associated with functional impairment, while pre-injury systemic disease, psychiatric conditions and lower educational level were associated with functional impairment, lower generic and disease-specific HRQoL and mental health symptoms.CONCLUSION: The rate of impairment and disability following TBI in older adults is substantial, and poorer outcomes across domains are associated with worse preinjury health. Nonetheless, a considerable number of patients fully or partially returns to their preinjury functioning. There should not be pessimism about outcomes in older adults who survive.
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| 10. |
- Czeiter, Endre, et al.
(författare)
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Blood biomarkers on admission in acute traumatic brain injury : Relations to severity, CT findings and care path in the CENTER-TBI study
- 2020
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 56
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Serum biomarkers may inform and improve care in traumatic brain injury (TBI). We aimed to correlate serum biomarkers with clinical severity, care path and imaging abnormalities in TBI, and explore their incremental value over clinical characteristics in predicting computed tomographic (CT) abnormalities.METHODS: We analyzed six serum biomarkers (S100B, NSE, GFAP, UCH-L1, NFL and t-tau) obtained <24 h post-injury from 2867 patients with any severity of TBI in the Collaborative European NeuroTrauma Effectiveness Research (CENTER-TBI) Core Study, a prospective, multicenter, cohort study. Univariable and multivariable logistic regression analyses were performed. Discrimination was assessed by the area under the receiver operating characteristic curve (AUC) with 95% confidence intervals.FINDINGS: All biomarkers scaled with clinical severity and care path (ER only, ward admission, or ICU), and with presence of CT abnormalities. GFAP achieved the highest discrimination for predicting CT abnormalities (AUC 0•89 [95%CI: 0•87-0•90]), with a 99% likelihood of better discriminating CT-positive patients than clinical characteristics used in contemporary decision rules. In patients with mild TBI, GFAP also showed incremental diagnostic value: discrimination increased from 0•84 [95%CI: 0•83-0•86] to 0•89 [95%CI: 0•87-0•90] when GFAP was included. Results were consistent across strata, and injury severity. Combinations of biomarkers did not improve discrimination compared to GFAP alone.INTERPRETATION: Currently available biomarkers reflect injury severity, and serum GFAP, measured within 24 h after injury, outperforms clinical characteristics in predicting CT abnormalities. Our results support the further development of serum GFAP assays towards implementation in clinical practice, for which robust clinical assay platforms are required.FUNDING: CENTER-TBI study was supported by the European Union 7th Framework program (EC grant 602150).
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