| 1. |
- Gravesteijn, Benjamin Yaël, et al.
(author)
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Missing Data in Prediction Research : A Five-Step Approach for Multiple Imputation, Illustrated in the CENTER-TBI Study
- 2021
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In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 38:13, s. 1842-1857
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Journal article (peer-reviewed)abstract
- 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 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.
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| 2. |
- Gravesteijn, Benjamin Y., et al.
(author)
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Toward a New Multi-Dimensional Classification of Traumatic Brain Injury : A Collaborative European NeuroTrauma Effectiveness Research for Traumatic Brain Injury Study
- 2020
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In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 37:7, s. 1002-1010
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Journal article (peer-reviewed)abstract
- 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 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.
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| 3. |
- Gravesteijn, Benjamin Yael, et al.
(author)
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Tracheal intubation in traumatic brain injury : a multicentreprospective observational study
- 2020
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In: British Journal of Anaesthesia. - : Elsevier. - 0007-0912 .- 1471-6771. ; 125:4, s. 505-517
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Journal article (peer-reviewed)abstract
- Background: We aimed to study the associations between pre- and in-hospital tracheal intubation and outcomes intraumatic brain injury (TBI), and whether the association varied according to injury severity.Methods: Data from the international prospective pan-European cohort study, Collaborative European NeuroTraumaEffectiveness Research for TBI (CENTER-TBI), were used (n¼4509). For prehospital intubation, we excluded selfpresenters. For in-hospital intubation, patients whose tracheas were intubated on-scene were excluded. The associationbetween intubation and outcome was analysed with ordinal regression with adjustment for the International Mission forPrognosis and Analysis of Clinical Trials in TBI variables and extracranial injury. We assessed whether the effect ofintubation varied by injury severity by testing the added value of an interaction term with likelihood ratio tests.Results: In the prehospital analysis, 890/3736 (24%) patients had their tracheas intubated at scene. In the in-hospitalanalysis, 460/2930 (16%) patients had their tracheas intubated in the emergency department. There was no adjustedoverall effect on functional outcome of prehospital intubation (odds ratio¼1.01; 95% confidence interval, 0.79e1.28;P¼0.96), and the adjusted overall effect of in-hospital intubation was not significant (odds ratio¼0.86; 95% confidenceinterval, 0.65e1.13; P¼0.28). However, prehospital intubation was associated with better functional outcome in patientswith higher thorax and abdominal Abbreviated Injury Scale scores (P¼0.009 and P¼0.02, respectively), whereas inhospital intubation was associated with better outcome in patients with lower Glasgow Coma Scale scores (P¼0.01): inhospital intubation was associated with better functional outcome in patients with Glasgow Coma Scale scores of 10 orlower.Conclusion: The benefits and harms of tracheal intubation should be carefully evaluated in patients with TBI to optimisebenefit. This study suggests that extracranial injury should influence the decision in the prehospital setting, and level ofconsciousness in the in-hospital setting.Clinical trial registration: NCT02210221.
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| 4. |
- Sewalt, Charlie Aletta, et al.
(author)
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Primary versus early secondary referral to a specialized neurotrauma center in patients with moderate/severe traumatic brain injury : a CENTER TBI study
- 2021
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In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : BioMed Central (BMC). - 1757-7241. ; 29:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Prehospital care for patients with traumatic brain injury (TBI) varies with some emergency medical systems recommending direct transport of patients with moderate to severe TBI to hospitals with specialist neurotrauma care (SNCs). The aim of this study is to assess variation in levels of early secondary referral within European SNCs and to compare the outcomes of directly admitted and secondarily transferred patients.METHODS: Patients with moderate and severe TBI (Glasgow Coma Scale < 13) from the prospective European CENTER-TBI study were included in this study. All participating hospitals were specialist neuroscience centers. First, adjusted between-country differences were analysed using random effects logistic regression where early secondary referral was the dependent variable, and a random intercept for country was included. Second, the adjusted effect of early secondary referral on survival to hospital discharge and functional outcome [6 months Glasgow Outcome Scale Extended (GOSE)] was estimated using logistic and ordinal mixed effects models, respectively.RESULTS: A total of 1347 moderate/severe TBI patients from 53 SNCs in 18 European countries were included. Of these 1347 patients, 195 (14.5%) were admitted after early secondary referral. Secondarily referred moderate/severe TBI patients presented more often with a CT abnormality: mass lesion (52% vs. 34%), midline shift (54% vs. 36%) and acute subdural hematoma (77% vs. 65%). After adjusting for case-mix, there was a large European variation in early secondary referral, with a median OR of 1.69 between countries. Early secondary referral was not associated with functional outcome (adjusted OR 1.07, 95% CI 0.78-1.69), nor with survival at discharge (1.05, 0.58-1.90).CONCLUSIONS: Across Europe, substantial practice variation exists in the proportion of secondarily referred TBI patients at SNCs that is not explained by case mix. Within SNCs early secondary referral does not seem to impact functional outcome and survival after stabilisation in a non-specialised hospital. Future research should identify which patients with TBI truly benefit from direct transportation.
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| 5. |
- Spronk, Inge, et al.
(author)
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Recovery of health-related quality of life after burn injuries: An individual participant data meta-analysis
- 2020
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In: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 15:1
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Journal article (peer-reviewed)abstract
- Background A prominent outcome measure within burn care is health related quality of life (HRQL). Until now, no model for long-term recovery of HRQL exists for adult burn patients which requires large samples with repeated measurements. Re-use and the combination of existing data is a way to achieve larger data samples that enable the estimation of long-term recovery models. The aim of this secondary data analysis was to assess the recovery of HRQL after a burn injury over time. Methods and findings Data from ten European studies on generic HRQL assessed in adult burn patients (either with the EQ-5D or SF-36) from five different countries were merged into one dataset. SF-36 outcomes were transformed into EQ-5D outcomes. A 24-month recovery of HRQL (EQ-5D utility) was modeled using a linear mixed-effects model and adjusted for important patient and burn characteristics. Subgroups of patients with mild and intermediate burns (<= 20% total body surface area (TBSA) burned) and with major burns (>20% TBSA burned) were compared. The combined database included 1687 patients with a mean age of 43 (SD 15) years and a median %TBSA burned of 9% (IQR 4-18). There was large improvement in HRQL up to six months after burns, and HRQL remained relatively stable afterwards (studied up to 24 months post burn). However, the estimated EQ-5D utility scores remained below the norm scores of the general population. In this large sample, females, patients with a long hospital stay and patients with major burns had a delayed and worse recovery. The proportion of patients that reported problems for the EQ-5D dimensions ranged from 100% (pain/discomfort at baseline in patients with major burns) to 10% (self-care >= 3 months after injury in patients with mild and intermediate burns). After 24 months, both subgroups of burn patients did not reach the level of the general population in the dimensions pain/discomfort and anxiety/depression, and patients with major burns in the dimension usual activities. A main limitation of the study includes that the variables in the model were limited to age, gender, %TBSA, LOS and time since burn as these were the only variables available in all datasets. Conclusions The 24-month recovery model can be used in clinical practice to inform patients on expected HRQL outcomes and provide clinicians insights into the expected recovery of HRQL. In this way, a delayed recovery can be recognized in an early stage and timely interventions can be started in order to improve patient outcomes. However, external validation of the developed model is needed before implementation into clinical practice. Furthermore, our study showed the benefit of secondary data usage within the field of burns.
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| 6. |
- Steyerberg., Ewout W, et al.
(author)
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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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In: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 18:10, s. 923-934
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Journal article (peer-reviewed)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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| 7. |
- Voormolen, Daphne C., et al.
(author)
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Post-Concussion Symptoms in Complicated vs. Uncomplicated Mild Traumatic Brain Injury Patients at Three and Six Months Post-Injury : Results from the CENTER-TBI Study
- 2019
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In: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 8:11
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Journal article (peer-reviewed)abstract
- The aim of this study was to assess the occurrence of post-concussion symptoms and post-concussion syndrome (PCS) in a large cohort of patients after complicated and uncomplicated mild traumatic brain injury (mTBI) at three and six months post-injury. Patients were included through the prospective cohort study: Collaborative European NeuroTrauma Effectiveness Research (CENTER-TBI). Patients enrolled with mTBI (Glasgow Coma Scale 13-15) were further differentiated into complicated and uncomplicated mTBI based on the presence or absence of computed tomography abnormalities, respectively. The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) assessed post-concussion symptoms and PCS according to the mapped ICD-10 classification method. The occurrence of post-concussion symptoms and syndrome at both time points was calculated. Chi square tests were used to test for differences between and within groups. Logistic regression was performed to analyse the association between complicated versus uncomplicated mTBI and the prevalence of PCS. Patients after complicated mTBI reported slightly more post-concussion symptoms compared to those after uncomplicated mTBI. A higher percentage of patients after complicated mTBI were classified as having PCS at three (complicated: 46% vs. uncomplicated: 35%) and six months (complicated: 43% vs. uncomplicated 34%). After adjusting for baseline covariates, the effect of complicated versus uncomplicated mTBI at three months appeared minimal: odds ratio 1.25 (95% confidence interval: 0.95-1.66). Although patients after complicated mTBI report slightly more post-concussion symptoms and show higher PCS rates compared to those after uncomplicated mTBI at three and six months, complicated mTBI was only found a weak indicator for these problems.
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