| 1. |
- Kals, Mart, et al.
(författare)
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A genome-wide association study of outcome from traumatic brain injury
- 2022
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 77
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Factors such as age, pre-injury health, and injury severity, account for less than 35% of outcome variability in traumatic brain injury (TBI). While some residual outcome variability may be attributable to genetic factors, published candidate gene association studies have often been underpowered and subject to publication bias.METHODS: We performed the first genome- and transcriptome-wide association studies (GWAS, TWAS) of genetic effects on outcome in TBI. The study population consisted of 5268 patients from prospective European and US studies, who attended hospital within 24 h of TBI, and satisfied local protocols for computed tomography.FINDINGS: The estimated heritability of TBI outcome was 0·26. GWAS revealed no genetic variants with genome-wide significance (p < 5 × 10-8), but identified 83 variants in 13 independent loci which met a lower pre-specified sub-genomic statistical threshold (p < 10-5). Similarly, none of the genes tested in TWAS met tissue-wide significance. An exploratory analysis of 75 published candidate variants associated with 28 genes revealed one replicable variant (rs1800450 in the MBL2 gene) which retained significance after correction for multiple comparison (p = 5·24 × 10-4).INTERPRETATION: While multiple novel loci reached less stringent thresholds, none achieved genome-wide significance. The overall heritability estimate, however, is consistent with the hypothesis that common genetic variation substantially contributes to inter-individual variability in TBI outcome. The meta-analytic approach to the GWAS and the availability of summary data allows for a continuous extension with additional cohorts as data becomes available.FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.
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| 2. |
- Steyerberg., Ewout W, et al.
(författare)
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Case-mix, care pathways, and outcomes in patients with traumatic brain injury in CENTER-TBI : a European prospective, multicentre, longitudinal, cohort study
- 2019
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 18:10, s. 923-934
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The burden of traumatic brain injury (TBI) poses a large public health and societal problem, but the characteristics of patients and their care pathways in Europe are poorly understood. We aimed to characterise patient case-mix, care pathways, and outcomes of TBI.METHODS: CENTER-TBI is a Europe-based, observational cohort study, consisting of a core study and a registry. Inclusion criteria for the core study were a clinical diagnosis of TBI, presentation fewer than 24 h after injury, and an indication for CT. Patients were differentiated by care pathway and assigned to the emergency room (ER) stratum (patients who were discharged from an emergency room), admission stratum (patients who were admitted to a hospital ward), or intensive care unit (ICU) stratum (patients who were admitted to the ICU). Neuroimages and biospecimens were stored in repositories and outcome was assessed at 6 months after injury. We used the IMPACT core model for estimating the expected mortality and proportion with unfavourable Glasgow Outcome Scale Extended (GOSE) outcomes in patients with moderate or severe TBI (Glasgow Coma Scale [GCS] score ≤12). The core study was registered with ClinicalTrials.gov, number NCT02210221, and with Resource Identification Portal (RRID: SCR_015582).FINDINGS: Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study and from 22 782 patients in the registry. In the core study, 848 (19%) patients were in the ER stratum, 1523 (34%) in the admission stratum, and 2138 (47%) in the ICU stratum. In the ICU stratum, 720 (36%) patients had mild TBI (GCS score 13-15). Compared with the core cohort, the registry had a higher proportion of patients in the ER (9839 [43%]) and admission (8571 [38%]) strata, with more than 95% of patients classified as having mild TBI. Patients in the core study were older than those in previous studies (median age 50 years [IQR 30-66], 1254 [28%] aged >65 years), 462 (11%) had serious comorbidities, 772 (18%) were taking anticoagulant or antiplatelet medication, and alcohol was contributory in 1054 (25%) TBIs. MRI and blood biomarker measurement enhanced characterisation of injury severity and type. Substantial inter-country differences existed in care pathways and practice. Incomplete recovery at 6 months (GOSE <8) was found in 207 (30%) patients in the ER stratum, 665 (53%) in the admission stratum, and 1547 (84%) in the ICU stratum. Among patients with moderate-to-severe TBI in the ICU stratum, 623 (55%) patients had unfavourable outcome at 6 months (GOSE <5), similar to the proportion predicted by the IMPACT prognostic model (observed to expected ratio 1·06 [95% CI 0·97-1·14]), but mortality was lower than expected (0·70 [0·62-0·76]).INTERPRETATION: Patients with TBI who presented to European centres in the core study were older than were those in previous observational studies and often had comorbidities. Overall, most patients presented with mild TBI. The incomplete recovery of many patients should motivate precision medicine research and the identification of best practices to improve these outcomes.FUNDING: European Union 7th Framework Programme, the Hannelore Kohl Stiftung, OneMind, and Integra LifeSciences Corporation.
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| 3. |
- Wilson, Lindsay, et al.
(författare)
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Understanding the relationship between cognitive performance and function in daily life after traumatic brain injury
- 2020
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group Ltd. - 0022-3050 .- 1468-330X.
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Tidskriftsartikel (refereegranskat)abstract
- 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 (ηp2 0.057-0.067) and learning and memory (ηp2 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 (ηp2 0.111), mental health (ηp2 0.131) and physical health (ηp2 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.
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