***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Worldwide , over 10 million people are killed or hospitalized because of traumatic brain injury each year . About 90 % of deaths occur in low- and middle-income countries . The condition mostly affects young adults , and many experience long lasting or permanent disability . The social and economic burden is considerable . Tranexamic acid ( TXA ) is commonly given to surgical patients to reduce bleeding and the need for blood transfusion . It has been shown to reduce the number of patients receiving a blood transfusion by about a third , reduces the volume of blood transfused by about one unit , and halves the need for further surgery to control bleeding in elective surgical patients . Methods / design The CRASH-3 trial is an international , multicenter , pragmatic , r and omized , double-blind , placebo-controlled trial to quantify the effects of the early administration of TXA on death and disability in patients with traumatic brain injury . Ten thous and adult patients who fulfil the eligibility criteria will be r and omized to receive TXA or placebo .  Adults with traumatic brain injury , who are within 8 h of injury and have any intracranial bleeding on computerized tomography ( CT scan ) or Glasgow Coma Score ( GCS ) of 12 or less can be included if the responsible doctor is substantially uncertain as to whether or not to use TXA in this patient . Patients with significant extracranial bleeding will be excluded since there is evidence that TXA improves outcome in these patients . Treatment will entail a 1 g loading dose followed by a 1 g maintenance dose over 8 h . The main analyses will be on an ‘ intention-to-treat ’ basis , irrespective of whether the allocated treatment was received . Results will be presented as appropriate effect estimates with a measure of precision ( 95 % confidence intervals ) . Subgroup analyses for the primary outcome will be based on time from injury to r and omization , the severity of the injury , location of the bleeding , and baseline risk . Interaction tests will be used to test whether the effect of treatment differs across these subgroups . A study with 10,000 patients will have approximately 90 % power to detect a 15 % relative reduction from 20 % to 17 % in all-cause mortality . Trial registration Current Controlled Trials IS RCT N15088122 ; Clinical trials.gov Background Traumatic brain injury ( TBI ) is commonly accompanied by intracranial bleeding which can worsen after hospital admission . Tranexamic acid ( TXA ) has been shown to reduce bleeding in elective surgery and there is evidence that short courses of TXA can reduce rebleeding in spontaneous intracranial haemorrhage . We aim ed to determine the effectiveness and safety of TXA in preventing progressive intracranial haemorrhage in TBI . Methods This is a double blinded , placebo controlled r and omized trial . We enrolled 238 patients older than 16 years with moderate to severe TBI ( post-resuscitation Glasgow Coma Scale ( GCS ) 4 to 12 ) who had a computerized tomography ( CT ) brain scan within eight hours of injury and in whom there was no immediate indication for surgery . We excluded patients if they had a coagulopathy or a serum creatinine over than 2.0 milligrams% . The treatment was a single dose of 2 grams of TXA in addition to other st and ard treatments . The primary outcome was progressive intracranial haemorrhage ( PIH ) which was defined as an intracranial haemorrhage seen on the second CT scan that was not seen on the first CT scan , or an intracranial haemorrhage seen on the first scan that had exp and ed by 25 % or more on any dimension ( height , length , or width ) on the second scan . Results Progressive intracranial haemorrhage was present in 21 ( 18 % ) of 120 patients allocated to TXA and in 32 ( 27 % ) of 118 patients allocated to placebo . The difference was not statistically significant [ RR = 0.65 ( 95 % CI 0.40 to 1.05 ) ] . There were no significant difference in the risk of death from all causes in patients allocated to TXA compared with placebo [ RR = 0.69 ( 95 % CI 0.35 to 1.39 ) ] and the risk of unfavourable outcome on the Glasgow Outcome Scale [ RR = 0.76 ( 95 % CI 0.46 to 1.27 ) ] . There was no evidence of increased risk of thromboembolic events in those patients allocated to TXA . Conclusions TXA may reduce PIH in patients with TBI ; however , the difference was not statistically significant in this trial . Large clinical trials are needed to confirm and to assess the effect of TXA on death or disability after TBI BACKGROUND Tranexamic acid can reduce bleeding in patients undergoing elective surgery . We assessed the effects of early administration of a short course of tranexamic acid on death , vascular occlusive events , and the receipt of blood transfusion in trauma patients . METHODS This r and omised controlled trial was undertaken in 274 hospitals in 40 countries . 20 211 adult trauma patients with , or at risk of significant bleeding were r and omly assigned within 8 h of injury to either tranexamic acid ( loading dose 1 g over 10 min then infusion of 1 g over 8 h ) or matching placebo . R and omisation was balanced by centre , with an allocation sequence based on a block size of eight , generated with a computer r and om number generator Both participants and study staff ( site investigators and trial coordinating centre staff ) were masked to treatment allocation . The primary outcome was death in hospital within 4 weeks of injury , and was described with the following categories : bleeding , vascular occlusion ( myocardial infa rct ion , stroke and pulmonary embolism ) , multiorgan failure , head injury , and other AL analyses were by intention to treat . This study is registered as IS RCT N86750102 , Clinical trials.gov NCT00375258 , and South African Clinical Trial Register DOH-27 - 0607 - 1919 . RESULTS 10096 patients were allocated to tranexamic acid and 10 115 to placebo , of whom 10060 and 10067 , respectively , were analysed . All-cause mortality was significantly reduced with tranexamic acid ( 1463 [ 14.5 % ] tranexamic acid group vs 1613 [ 160 % ] placebo group ; relative risk 0.91 , 95 % CI 085 - 097 ; p = 00035 ) . The risk of death due to bleeding was significantly reduced ( 489 [ 49 % ] vs 574 [ 5 - 7 % ] ; relative risk 0 - 85 , 95 % CI 0.76 - 0.96 ; p = 0 - 0077 ) . CONCLUSION Tranexamic acid safely reduced the risk of death in bleeding trauma patients in this study On the basis of these results , tranexamic acid should be considered for use in bleeding trauma patients Summary A study was performed to detect the inhibitory effect of intravenously administered aprotinin ( Trasylol ® ) on brain and CSF protease activity in 25 patients with severe head injury . The data presented include measurements of CSF protease activity , alpha-1-antitrypsin , alpha-2-macroglobulin , haptoglobulin , polyacrylamidgel-electrophoresis pattern , total protein and hemoglobin content . The results indicate that increased protease activity is present and that this induces autolytic processes which can be inhibited by aprotinin treatment . The survival rate was higher after aprotinin treatment . Total CSF protein content was significantly higher in nonsurvivors than in survivors Introduction : We performed a prospect i ve , r and omized , double-blind study on 40 patients scheduled for primary total hip arthroplasty due to arthrosis or osteonecrosis to determine the effect of tranexamic acid on per- and postoperative blood losses and on the number of blood transfusions needed . Patients and methods : 40 patients were r and omized to tranexamic acid ( 10 mg/kg given as a bolus intravenous injection , followed by a continuous infusion of 1 mg/kg/hour for 10 hours ) or placebo ( 20 mL saline given intravenously ) 15 minutes before the incision . We recorded the peroperative and postoperative blood losses at removal of the drain 24 hours after the operation and the number of blood transfusions . Results : Patients receiving  tranexamic acid had a mean peroperative blood loss of 480 mL versus 622 mL in patients receiving placebo ( p= 0.3 ) , a postoperative blood loss of 334 mL versus 609 mL ( p= 0.001 ) , a total blood loss of 814 mL versus 1231 mL ( p= 0.001 ) and a total need for 4 blood transfusions versus 25 ( p= 0.04 ) . No patient in either group had symptoms of deep venous thrombosis , pulmonary embolism or prolonged wound drainage . Interpretation : Transemic acid is effective in reducing the postoperative blood loss , the total blood loss and the need for blood transfusion in primary total hip arthroplasty In a prospect i ve , r and omized study 35 patients with multiple injuries were examined for early changes of blood coagulation . Parameters suggesting a consumption coagulopathy were lower in patients who died subsequently than in survivors . No therapeutic influence of low dose Heparin therapy or of the proteinase inhibiting substance TrasylolR could be demonstrated In the years 1971 to 1973 the therapeutic effect of Trasylol ( aprotinin isolated from bovine organs ) in the treatment of the traumatic shock was investigated in a controlled field study at 31 hospitals in northern Germany . The study included 4686 patients . There could be proved a significant reduction in letality by Trasylol treatment even under the broad conditions of general field application . The therapeutic activity of Trasylol was most efficient when Trasylol was applied within 30 min after the trauma and consists especially of a better prognostic for further development . The letality after 12 h is remarkably reduced by an early application of Trasylol and posttraumatic surgical operations have a significantly lower risk In a prospect i ve double blind clinical study of 70 patients with bony trauma and shock , 35 patients were allocated into each group receiving either a placebo or Aprotinin . In both groups there was a high incidence of pulmonary insufficiency and thrombocytopaenia . In the placebo group there was a higher incidence of pulmonary insufficiency , but not its severity , with greater volumes of blood transufsion and the most severe form occurred only after decompensated shock . Thrombocytopaenia showed a similar pattern in all patients from both groups falling to a mean minimum on the 2nd day and rising thereafter . In the placebo group counts were lower in those with decompensated shock , and the fall was more profound , rapid and earlier in patients developing severe pulmonary insufficiency . Counts of less than 100,000 on the first day were associated with a high probability of severe pulmonary insufficiency subsequently occurring and this finding was not associated with greater volumes of blood transfusion . In those patients receiving Aprotinin , the subsequent incidence of severity of pulmonary insufficiency was less and not associated with increased volumes of blood transfusion . The platelet counts were not lower in decompensated shock and there was a more rapid rise from the minimum level BACKGROUND The aim of the CRASH-2 trial was to assess the effects of early administration of tranexamic acid on death , vascular occlusive events , and blood transfusion in trauma patients with significant haemorrhage .  Tranexamic acid significantly reduced all-cause mortality . Because tranexamic acid is thought to exert its effect through inhibition of fibrinolysis , we undertook exploratory analyses of its effect on death due to bleeding . METHODS The CRASH-2 trial was undertaken in 274 hospitals in 40 countries . 20,211 adult trauma patients with , or at risk of , significant bleeding were r and omly assigned within 8 h of injury to either tranexamic acid ( loading dose 1 g over 10 min followed by infusion of 1 g over 8 h ) or placebo . Patients were r and omly assigned by selection of the lowest numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number . Both participants and study staff ( site investigators and trial coordinating centre staff ) were masked to treatment allocation . We examined the effect of tranexamic acid on death due to bleeding according to time to treatment , severity of haemorrhage as assessed by systolic blood pressure , Glasgow coma score ( GCS ) , and type of injury . All analyses were by intention to treat . The trial is registered as IS RCT N86750102 , Clinical Trials.gov NCT00375258 , and South African Clinical Trial Register/Department of Health DOH-27 - 0607 - 1919 . FINDINGS 10,096 patients were allocated to tranexamic acid  and 10,115 to placebo , of whom 10,060 and 10,067 , respectively , were analysed . 1063 deaths ( 35 % ) were due to bleeding . We recorded strong evidence that the effect of tranexamic acid on death due to bleeding varied according to the time from injury to treatment ( test for interaction p<0.0001 ) . Early treatment ( ≤1 h from injury ) significantly reduced the risk of death due to 
    Output:
    
Stronger evidence exists for the possibility of TXA reducing intracranial bleeding in this population .
TXA safely reduces mortality in trauma patients with bleeding without increasing the risk of adverse events .
TXA should be given as early as possible and within three hours of injury , as further analysis of the CRASH-2 trial showed that treatment later than this is unlikely to be effective and may be harmful .