87; 0.78 to 0.97) and within three hours (RR = 0.87; 0.80 to 0.94) of injury, the number of premature deaths averted was 52,000 (TXA ≤ 1 hr ≈ 12,000 to 88,000; TXA ≤ 3 hrs ≈ 24,000 to 80,000). When the analysis was repeated using relative risk estimate for death due to bleeding

when TXA is given at any time within eight hours of injury (RR = 0.85; 0.76 to Inhibitors,research,lifescience,medical 0.96), the number of premature deaths averted was 60,000 (UR ≈ 16,000 to 96,000). Finally, using the relative risk estimate for all-cause mortality when TXA is given within eight hours of injury (RR = 0.91; 0.85 to 0.97), an estimated 36,000 (UR ≈ 12,000 to 60,000) premature deaths could be averted. Discussion Based on WHO mortality data and a systematic review of the literature we estimate that there are about 400,000 in-hospital deaths from bleeding each year worldwide. If all hospitalised bleeding trauma patients could be treated with TXA within an hour of injury then up to

128,000 of these premature deaths could be averted. If they could be treated Inhibitors,research,lifescience,medical within three hours of injury then up to 112,000 premature deaths could averted. Although there is considerable uncertainty in the Temozolomide manufacturer estimates even the most conservative suggest that tens of thousands of deaths could be averted every year. We Inhibitors,research,lifescience,medical found no compelling evidence that the effect of TXA on death due to bleeding varies by geographical region. Our conclusion is based on a statistical test of interaction which is considered to be the most appropriate way to evaluate subgroup effects [29]. As recommended by methodologists, we pre-specified that unless there was strong evidence Inhibitors,research,lifescience,medical against the null hypothesis of homogeneity of effects (i.e. p < 0.001), that the overall risk ratio (RR) would be considered to be the most reliable guide to the approximate RRs in all regions. We found no statistical Inhibitors,research,lifescience,medical basis to reject the null hypothesis. The data sources used to parameterise the model are subject to a number of limitations which may have affected our results. First,

although the WHO database provides the best available country-level mortality data, poor coverage and coding of mortality registration systems may affect the accuracy of the number of trauma deaths for some countries. Second, our classification of trauma deaths into blunt or penetrating ADP ribosylation factor trauma based on the cause of death categories in the WHO data was somewhat arbitrary and would have resulted in some misclassification. However, in the absence of accurate country-specific data, we judged that this approach would provide the most reliable estimates. Third, due to the absence of country-specific data for the proportions of deaths occurring in hospital and the proportion of deaths caused by haemorrhage, we chose to apply average global estimates. We were therefore unable to incorporate between-country variations in these parameter estimates into our analysis.