Statistical models for outcome prediction are central to traumatic brain injury research and critical to baseline risk adjustment. Glasgow coma score (GCS) and pupil reactivity are crucial... Show moreStatistical models for outcome prediction are central to traumatic brain injury research and critical to baseline risk adjustment. Glasgow coma score (GCS) and pupil reactivity are crucial covariates in all such models but may be measured at multiple time points between the time of injury and hospital and are subject to a variable degree of unreliability and/or missingness. Imputation of missing data may be undertaken using full multiple imputation or by simple substitution of measurements from other time points. However, it is unknown which strategy is best or which time points are more predictive. We evaluated the pseudo-R-2 of logistic regression models (dichotomous survival) and proportional odds models (Glasgow Outcome Score-extended) using different imputation strategies on the The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study dataset. Substitution strategies were easy to implement, achieved low levels of missingness (<< 10%) and could outperform multiple imputation without the need for computationally costly calculations and pooling multiple final models. While model performance was sensitive to imputation strategy, this effect was small in absolute terms and clinical relevance. A strategy of using the emergency department discharge assessments and working back in time when these were missing generally performed well. Full multiple imputation had the advantage of preserving time-dependence in the models: the pre-hospital assessments were found to be relatively unreliable predictors of survival or outcome. The predictive performance of later assessments was model-dependent. In conclusion, simple substitution strategies for imputing baseline GCS and pupil response can perform well and may be a simple alternative to full multiple imputation in many cases. Show less
Wijk, R.P.J. van; Dijck, J.T.J.M. van; Timmers, M.; Veen, E. van; Citerio, G.; Lingsma, H.F.; ... ; CENTER-TB1 Investigators 2020
Purpose: Enrolling traumatic brain injury (731) patients with an inability to provide informed consent in research is challenging. Alternatives to patient consent are not sufficiently embedded in... Show morePurpose: Enrolling traumatic brain injury (731) patients with an inability to provide informed consent in research is challenging. Alternatives to patient consent are not sufficiently embedded in European and national legislation, which allows procedural variation and bias. We aimed to quantify variations in informed consent policy and practice.Methods: Variation was explored in the CENTER-TBI study. Policies were reported by using a questionnaire and national legislation. Data on used informed consent procedures were available for 4498 patients from 57 centres across 17 European countries.Results: Variation in the use of informed consent procedures was found between and within EU member states. Proxy informed consent (N = 1377;64%) was the most frequently used type of consent in the ICU, followed by patient informed consent (N 426;20%) and deferred consent (N 334;16%). Deferred consent was only actively used in 15 centres (26%), although it was considered valid in 47 centres (82%).Conclusions: Alternatives to patient consent are essential for TBI research. While there seems to be concordance amongst national legislations, there is regional variability in institutional practices with respect to the use of different informed consent procedures. Variation could be caused by several reasons, including inconsistencies in clear legislation or knowledge of such legislation amongst researchers. (C) 2020 Published by Elsevier Inc. Show less
Zeiler, F.A.; Aries, M.; Cabeleira, M.; Essen, T.A. van; Stocchetti, N.; Menon, D.K.; ... ; CENTER-TBI High Resolution ICU HR 2020
Decompressive craniectomy (DC) in traumatic brain injury (TBI) has been suggested to influence cerebrovascular reactivity. We aimed to determine if the statistical properties of vascular reactivity... Show moreDecompressive craniectomy (DC) in traumatic brain injury (TBI) has been suggested to influence cerebrovascular reactivity. We aimed to determine if the statistical properties of vascular reactivity metrics and slow-wave relationships were impacted after DC, as such information would allow us to comment on whether vascular reactivity monitoring remains reliable after craniectomy. Using the CENTER-TBI High Resolution Intensive Care Unit (ICU) Sub-Study cohort, we selected those secondary DC patients with high-frequency physiological data for both at least 24 h pre-DC, and more than 48 h post-DC. Data for all physiology measures were separated into the 24 h pre-DC, the first 48 h post-DC, and beyond 48 h post-DC. We produced slow-wave data sheets for intracranial pressure (ICP) and mean arterial pressure (MAP) per patient. We also derived a Pressure Reactivity Index (PRx) as a continuous cerebrovascular reactivity metric updated every minute. The time-series behavior of the PRx was modeled for each time period per patient. Finally, the relationship between ICP and MAP during these three time periods was assessed using time-series vector autoregressive integrative moving average (VARIMA) models, impulse response function (IRF) plots, and Granger causality testing. Ten patients were included in this study. Mean PRx and proportion of time above PRx thresholds were not affected by craniectomy. Similarly, PRx time-series structure was not affected by DC, when assessed in each individual patient. This was confirmed with Granger causality testing, and VARIMA IRF plotting for the MAP/ICP slow-wave relationship. PRx metrics and statistical time-series behavior appear not to be substantially influenced by DC. Similarly, there is little change in the relationship between slow waves of ICP and MAP before and after DC. This may suggest that cerebrovascular reactivity monitoring in the setting of DC may still provide valuable information regarding autoregulation. Show less