Patients from low and middle-income countries were included in our analysis (Table ​(Table11). Table 1 Low and middle-income countries as defined by the World Bank included in the CRASH trial Outcomes CT

scan diagnosis of intracranial hemorrhage was defined as the presence of subarachnoid hemorrhage, petechial hemorrhages, obliteration Inhibitors,research,lifescience,medical of third ventricle or basal Cell Cycle inhibitor cisterns, mid-line shift, evacuated hematomas and non-evacuated hematomas. These were dichotomized to include all those diagnosed by CT-scan to have intracranial hemorrhage, and those with a CT-scan who did not. Patients were administered a CT-scan based on the clinical judgment of their physician. Prognostic variables We considered age, sex, Glasgow Coma Scale (GCS), time from injury to randomization, pupil reactivity, cause of injury, seizure and whether the patient had sustained a major extracranial injury. These variables were all pre- and post- injury factors included in the CRASH-1 trial excluding Inhibitors,research,lifescience,medical hematemesis or melena, the presence of a wound infection, or pneumonia. These were selected for inclusion in our study as prior research has demonstrated a relationship between these variables and the presence of intracranial hemorrhage [24,25]. The analysis was adjusted for randomization to Inhibitors,research,lifescience,medical corticosteroids as this was related to increased mortality

within the trial. We also assessed for the presence of interaction between treatment and potential prognostic factors as well as between prognostic factors for our model. Analyses All statistical analyses were conducted using STATA 10 (College Station, TX, USA). Univariate analysis was conducting using logistic regression modeling using the maximum likelihood theory to evaluate the relationship Inhibitors,research,lifescience,medical between prognostic variables and outcomes. We quantified

each variable’s predictive contribution by its z score (the model coefficient divided by its standard error). We graphically explored the relationship between Inhibitors,research,lifescience,medical age and intracranial hemorrhage, and GCS and intracranial hemorrhage to assess for linearity. Prognostic models The final all model in multivariate analyses was built using backwards elimination, where all variables were initially included [26]. Variables were selected for elimination using a p-value of 0.05, whereby a series of likelihood ratio tests with a p-value of <0.10 were utilized to determine which variables were kept in the final model. We explored for interaction between treatment and all other variables included in the final model using the likelihood ratio test. Ninety-five percent confidence intervals (CI) and p-values were calculated for all statistical tests of association. As there were few missing data, a complete case analysis was performed. Performance of the model The performance of the model was assessed through calibration and discrimination.