External validation of the international mission for prognosis and analysis of clinical trials model and the role of markers of coagulation.

*Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland
Neurosurgery (Impact Factor: 3.03). 08/2013; 73(2):305-11. DOI: 10.1227/
Source: PubMed

ABSTRACT Markers of coagulation have shown to have important value in predicting traumatic brain injury outcome.
To externally validate and investigate the role of markers of coagulation for outcome prediction by using the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) model while adjusting for overall injury severity.
A retrospective chart analysis of traumatic brain injury patients admitted to Helsinki University Central Hospital between 2009 and 2010 was performed. Outcome was estimated by using the criteria of the IMPACT model. Admission international normalized ratio (INR) and platelet count were used as markers of coagulation. Overall injury severity was categorized with the injury severity score (ISS). Variables were added to the calculated IMPACT risk, generating new models. Model performance was assessed by analyzing and comparing the area under the curve (AUC) of the models.
For 342 included patients, 6-month mortality was 32% and unfavorable neurological outcome was 36%. Patients with a poor outcome had lower platelets and higher INR and ISS than those with good outcome (P < .001). The IMPACT model had an AUC of 0.85 for predicting mortality and 0.81 for neurological outcome. Addition of INR but not ISS or platelets to the IMPACT predicted risk improved the predictive validity for mortality ([INCREMENT]AUC 0.02, P = .034) but not neurological outcome ([INCREMENT]AUC 0.00, P = .401). In multivariate analysis, INR remained significant for mortality but not for neurological outcome when adjusting for IMPACT risk and ISS (P = .012).
The IMPACT model showed excellent performance, and INR was an independent predictor for mortality, independent of overall injury severity.
AC, anticoagulationAP, antiplateletAUC, area under the curveCI, confidence intervalGOS, Glasgow Outcome ScaleIMPACT, International Mission for Prognosis and Analysis of Clinical TrialsINR, international normalized ratioIQR, interquartile rangeISS, injury severity scoreTBI, traumatic brain injury.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Research in traumatic brain injury (TBI) is challenging for several reasons; in particular, the heterogeneity between patients regarding causes, pathophysiology, treatment, and outcome. Advances in basic science have failed to translate into successful clinical treatments, and the evidence underpinning guideline recommendations is weak. Because clinical research has been hampered by non-standardised data collection, restricted multidisciplinary collaboration, and the lack of sensitivity of classification and efficacy analyses, multidisciplinary collaborations are now being fostered. Approaches to deal with heterogeneity have been developed by the IMPACT study group. These approaches can increase statistical power in clinical trials by up to 50% and are also relevant to other heterogeneous neurological diseases, such as stroke and subarachnoid haemorrhage. Rather than trying to limit heterogeneity, we might also be able to exploit it by analysing differences in treatment and outcome between countries and centres in comparative effectiveness research. This approach has great potential to advance care in patients with TBI.
    The Lancet Neurology 12/2013; 12(12):1200–1210. DOI:10.1016/S1474-4422(13)70234-5 · 21.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background External validation on different TBI populations is important in order to assess the generalizability of prognostic models to different settings. We aimed to externally validate recently developed models for prediction of six month unfavourable outcome and six month mortality.Methods The International Neurotrauma Research Organization ¿ Prehospital dataset (INRO-PH) was collected within an observational study between 2009-2012 in Austria and includes 778 patients with TBI of GCS¿<¿= 12. Three sets of prognostic models were externally validated: the IMPACT core and extended models, CRASH basic models and the Nijmegen models developed by Jacobs et al ¿ all for prediction of six month unfavourable outcome and six month mortality. The external validity of the models was assessed by discrimination (Area Under the receiver operating characteristic Curve, AUC) and calibration (calibration statistics and plots).ResultsMedian age in the validation cohort was 50 years and 44% had an admission GSC motor score of 1-3. Six-month mortality was 27%. Mortality could better be predicted (AUCs around 0.85) than unfavourable outcome (AUCs around 0.80). Calibration plots showed that the observed outcomes were systematically better than was predicted for all models considered. The best performance was noted for the original Nijmegen model, but refitting led to similar performance for the IMPACT Extended, CRASH Basic, and Nijmegen models.Conclusions In conclusion, all the prognostic models we validated in this study possess good discriminative ability for prediction of six month outcome in patients with moderate or severe TBI but outcomes were systemically better than predicted. After adjustment for this under prediction in locally adapted models, these may well be used for recent TBI patients.
    Scandinavian Journal of Trauma Resuscitation and Emergency Medicine 11/2014; 22(1):68. DOI:10.1186/s13049-014-0068-9 · 1.93 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction By analysing risk-adjusted mortality ratios, weaknesses in the process of care might be identified. Traumatic brain injury (TBI) is the main cause of death in trauma, and thus it is crucial that trauma prediction models are valid for TBI patients. Accordingly, we assessed the validity of the RISC score in TBI patients by internal and external validation analyses. Methods Patients with moderate-to-severe TBI admitted to the TraumaRegister DGU® (TR-DGU) and the trauma registry of Helsinki University Hospital (TR-THEL) in 2006-2011 were included in this retrospective open cohort study. Definition of moderate-to-severe TBI was head abbreviated injury scale of 3 or higher. Subgroup analysis for patients with isolated and polytrauma TBI was performed. The performance of the RISC score was evaluated by assessing its discrimination (area under the curve, AUC) and calibration (Hosmer–Lemeshow [H–L] test). Results Among the 9,106 and 809 patients with moderate-to-severe TBI admitted to TR-DGU and TR-THEL, unadjusted mortality was 26% and 23%, respectively. Internal and external validation of the RISC score showed good discrimination (TR-DGU AUC 0.89, 95% confidence interval [CI] 0.88-0.90 and TR-THEL AUC 0.84, 95% CI 0.81-0.87), but poor calibration (p < 0.001) in patients with moderate-to-severe TBI. Subgroup analysis found the discrimination only to be modest in isolated TBI (AUC 0.76) and calibration to be particularly poor in polytrauma TBI (TR-DGU H–L = 4356, p < 0.001; TR-THEL H-L 112, p < 0.001). Conclusion The RISC score was found to be of limited predictive value in patients with moderate-to-severe TBI. A new general trauma scoring system that includes TBI specific prognostic factors is warranted.
    Injury 01/2014; 46(1). DOI:10.1016/j.injury.2014.08.026 · 2.46 Impact Factor