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Our study benefits from comparatively stronger external validity secondary to its representative real-world sample but unfortunately we were unable to assess the association between SBP and disability. However the IMPACT results suggest a similar shaped relationship to mortality across all Glasgow Outcome Scale categories. Zafar and colleagues recently also investigated ED SBP and mortality in a large retrospective cohort study, and using data from the National Traumatic Coma Databank reported a U-shaped relationship similar to our unadjusted effect estimates [39]. However, they did not condition on GCS in their logistic regression models and their observed association between higher SBP and mortality could conceivably be explained by confounding resulting from herniation syndromes and Cushing's reflex in patients with deteriorating GCS. Alternatively Berry et al. used logistic regression modelling to determine Fulvestrant solubility dmso a cut-point for defining hypotension, identifying Veliparib or selection bias arising from complete case analyses. Although emphasised less in current treatment guidelines [10], mean arterial blood pressure may be of greater relevance than SBP in TBI due to its direct influence on cerebral perfusion pressure [41]. Repeating the analyses using empirically calculated mean arterial pressure produced comparable results to SBP, with an increase in mortality evident below 80?mmHg (Fig. 6, additional results appendix). These findings accord with the limited number of previous studies examining mean arterial blood pressure [38], [39], [40], [41]?and?[42]. SBP?RRAD increasing mortality was evident at a slightly lower level of 110?mmHg. This may reflect the importance of even mild hypotension in increasing secondary brain injury. In summary there appears to be an emerging body of evidence demonstrating an association between admission SBP level and mortality following TBI. Although observational evidence is at risk of residual confounding and cannot prove causality, our findings may support revision of consensus TBI management guidelines to include a higher endpoint for significant TBI patients of 120?mmHg during emergency department resuscitation. Furthermore these results have important implications for future TBI research.