***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: Antifibrinolytic treatment for 4 weeks after a subarachnoid hemorrhage has been shown to have no effect on outcome since a reduction in the rate of rebleeding was offset by an increase in ischemic events . To determine if a shorter course ( 4 days ) of antifibrinolytic treatment before the expected onset of ischemic complications might reduce the rate of rebleeding yet avoid ischemic complications , we prospect ively studied a series of 119 patients with subarachnoid hemorrhage ; 479 patients with subarachnoid hemorrhage from our previous r and omized double-blind study ( 238 treated with placebo , 241 with long-term tranexamic acid ) served as historical control groups . At 3 months ' follow-up , the outcome of patients treated with short-term tranexamic acid was not different from that of patients treated with long-term tranexamic acid . The rate of rebleeding ( 24 of 119 , 20 % ) was near that with placebo ( 56 of 238 , 24 % ) . In contrast , the rate of cerebral infa rct ion ( 33 of 119 , 28 % ) was almost identical to that after long-term tranexamic acid ( 59 of 241 , 24 % ) , although mortality from cerebral infa rct ion was reduced . Compared with historical control groups , treatment with tranexamic acid for 4 days fails to reduce the incidence of rebleeding but still increases the rate of cerebral infa rct ion OBJECTIVE The aim of this study was to investigate prospect ively in an unselected series of patients with an aneurysmal subarachnoid haemorrhage what at present the complications are , what the outcome is , how many of these patients have “ modern treatment”—that is , early obliteration of the aneurysm and treatment with calcium antagonists — what factors cause a delay in surgical or endovascular treatment , and what the estimated effect on outcome will be of improved treatment . METHODS A prospect i ve , observational cohort study of all patients with aneurysmal subarachnoid haemorrhage in the hospitals of a specified region in The Netherl and s. The condition on admission , diagnostic procedures , and treatments were recorded . If a patient had a clinical deterioration , the change in Glasgow coma score ( GCS ) , the presence of focal neurological signs , the results of additional investigations , and the final diagnosed cause of the deterioration were recorded . Clinical outcome was assessed with the Glasgow outcome scale ( GOS ) at 3 month follow up . In patients with poor outcome at follow up , the cause was diagnosed . RESULTS Of the 110 patients , 47 ( 43 % ) had a poor outcome . Cerebral ischaemia , 31 patients ( 28 % ) , was the most often occurring complication . Major causes of poor outcome were the effects of the initial haemorrhage and rebleeding in 34 % and 30 % of the patients with poor outcome respectively . Of all patients 102 ( 93 % ) were treated with calcium antagonists and 45 ( 41 % ) patients had early treatment to obliterate the aneurysm . The major causes of delay of treatment were a poor condition on admission or deterioration shortly after admission , in 31 % and 23 % respectively . CONCLUSIONS In two thirds of the patients with poor outcome the causes of poor outcome are the effects of the initial bleeding and rebleeding . Improved treatment of delayed or postoperative ischaemia will have only minor effects on the outcome of patients with subarachnoid haemorrhage Summary Tranexamic acid as an antifibrinolytic agent has been investigated in a controlled study in patients with recent subarachnoid haemorrhage . It is concluded that tranexamic acid improves neither rebleeding rates , nor mortality . Predominantly thrombotic complications have been noted as a more serious side effect of tranexamic acid Summary Seventy-four patients with recent subarachnoid haemorrhage were r and omly allocated to placebo or tranexamic acid treatment . Fibrinolytic activity in the blood and cerebrospinal fluid was assessed before treatment , one week later and two weeks later . The natural history of fibrinolysis following subarachnoid haemorrhage was obtained from analysis of the placebo group . Following subarachnoid haemorrhage , fibrin degradation products and plasminogen activity in the cerebrospinal fluid were elevated . Subsequently , fibrin degradation products in the cerebrospinal fluid fell progressively over the following 2 weeks . Changes in cerebrospinal fluid plasminogen activity correlated with those of blood plasminogen activity . Complications such as rebleeding , hydrocephalus or cerebral thrombosis could not be predicted from analysis of fibrinolytic activity . Tranexamic acid treatment result ed in a reduction in cerebrospinal fluid and blood plasminogen activity . The relevance of fibrinolysis in cerebrospinal fluid and blood to the management of subarachnoid haemorrhage is discussed The outcome of treatment with an antifibrinolytic agent ( tranexamic acid ) for six weeks after rupture of an intracranial aneurysm was assessed in a r and omised controlled trial . Twenty-two out of 25 ( 88 % ) treated patients  survived at follow-up of three to 33 months compared with 14 out of 25 ( 56 % ) control patients . Among the patients who did not undergo operation the survival rate was 81 % ( 13 out of 16 ) in treated patients and 42 % ( 8 out of 19 ) in controls . Antifibrinolytic treatment has so far been assumed merely to postpone rebleeding and has been used to enable surgery to be deferred . These findings suggest that tranexamic acid may actually prevent rebleeding without operation . Prolonged antifibrinolysis may therefore prove useful in those patients in good condition whose aneurysms do not lend themselves to surgical obliteration Objective : To investigate whether antifibrinolytics in combination with treatment to prevent cerebral ischemia improve outcome in patients with subarachnoid hemorrhage ( SAH ) in whom occlusion of the aneurysm is delayed . Background : Antifibrinolytic treatment reduces rebleeding , but outcome does not improve because of a concurrent increase in the occurrence of cerebral ischemia . Because treatment of ischemia has improved , antifibrinolytics might now have a beneficial effect . Methods : A prospect i ve , double-blind , placebo-controlled multicenter clinical trial was performed . R and omized were 462 patients ( 229 received tranexamic acid , 233 placebo ) admitted within 96 hours after onset of SAH , in whom treatment of the aneurysm was delayed beyond 48 hours after SAH . All patients were treated with calcium antagonists and hypervolemia . At 3 months , outcome was assessed with the Glasgow Outcome Scale . The occurrence of cerebral ischemia and other complications were recorded , and the effects of treatment were related to the clinical condition on admission . Results : Antifibrinolytic treatment had no beneficial effect on outcome ( relative risk [ RR ] , 1.10 ; 95 % confidence limits [ CL ] , 0.91–1.34 ) . Antifibrinolytics significantly reduced the occurrence of rebleeding ( RR , 0.58 ; 95 % CL , 0.42–0.80 ) ; the occurrence of ischemic and other complications was the same in the two groups . Conclusion : Antifibrinolytic treatment combined with treatment to prevent cerebral ischemia does not improve outcome Summary One hundred patients with a verified subarachnoid haemorrhage were studied in a double blind , placebo-controlled trial at a single centre to determine the value and relative risks of tranexamic acid ( TXA ) in the management of ruptured intracranial aneurysms . The incidence of recurrent haemorrhage between active and placebo groups was identical ( 12 % ) and the mortality from recurrent haemorrhage was 7 % and 5 % , respectively . The overall incidence of cerebral infa rct ion before surgery , at discharge and at 6 months follow-up was greater in the TXA group ( 27 % ) than in the control group ( 11 % ) . Post-operative cerebral ischaemia was significantly more frequent in the active , 18 of 29 as compared to 6 of 32 patients , in the placebo group . In a fifth of the patients in whom cerebral blood flow was estimated there was a significant reduction of cerebral blood flow ( CBF ) on the side of the ruptured aneurysm in the TXA treated group . It is suggested that this may be the cause of the increased incidence of cerebral ischaemia in this group . There was no significant difference in the incidence of cerebral vasospasm , hydrocephalus , visual disturbances and gastrointestinal disturbances . More fatalities were encountered from ischaemia and recurrent haemorrhage in the TXA group but these differences did not reach statistical significance at the 5 % level . Given that disability was due to either vasospasm or recurrent haemorrhage then a patient under TXA treatment was significantly more likely to have disability due to vasospasm ( p<0.04 ) ; the reverse was true for the placebo patient ( p<0.05 ) In a series of 176 prospect ively studied patients who survived for at least 24 hours after aneurysmal subarachnoid hemorrhage , 39 had at least one computerized tomography (CT)-proven rebleed within 4 weeks after the first rupture . There were peaks in the incidence of rebleeding at the end of the 2nd and 3rd weeks . Sudden loss of consciousness occurred in 35 patients , preceded in one-third of them by headache . A sudden increase in headache was a symptom of rebleeding in only one patient . Loss of brain-stem reflexes was recorded in 13 patients , respiratory arrest in six , and both symptoms in eight patients . Apnea was temporary in 11 patients . Rebleeding occurred as gross intraventricular hemorrhage in 20 patients , as a space-occupying hematoma in four , as both types of hemorrhage in three , and as a purely subarachnoid hemorrhage in 12 . The location of the rebleed could not be inferred from the clinical features . Rebleeding was fatal in 51 % of cases ( two of 12 patients with a purely subarachnoid hemorrhage , and 18 of the other 27 patients ( p less than 0.005 ) ) . The risk of rebleeding could not be predicted from the patients ' clinical condition on admission or from the amount of subarachnoid blood identified on the initial CT scan . The risk of further rebleeding was significantly increased in survivors of a first rebleed ( 47 % : p less than 0.01 ) . Only seven ( 18 % ) of the 39 patients with rebleeding had survived at 3 months after the initial hemorrhage A r and omized controlled clinical trial was carried out to study the effect of tranexamic acid ( AMCA , Cyklokapron ; AB Kabi , Stockholm , Sweden ) in the prevention of early rebleeding after the rupture of an intracranial aneurysm . The incidence of vasospasm , hydrocephalus , cerebral ischemic and thromboembolic complications , morbidity , and mortality was also evaluated . The series comprises 59 patients , 30 treated with tranexamic acid and 29 controls .  The treatment was stopped if there was rebleeding , operation , or discharge from the hospital . There were 6 recurrent hemorrhages in 6 patients in the tranexamic acid-treated group and 11 recurrences in 7 patients in the control group . Recurrent hemorrhages occurred later in tranexamic acid-treated patients than in controls . Five patients in each group died from rebleeding . Five additional treated patients and 2 controls died from cerebral ischemic dysfunction . The results suggest that tranexamic acid may protect patients with ruptured aneurysms from rebleeding for 1 or 2 weeks , but that it also may produce cerebral ischemic complications A double‐blind clinical trial of tranexamic acid was carried out on 39 patients with fresh subarachnoid hemorrhage from a ruptured aneurysm . Twenty patients received tranexamic acid , 6 gm daily for 14 to 21 days , while 19 patients received conventional therapy of bedrest and dexamethasone when cerebral edema developed , plus isotonic saline . Rebleeding and mortality were reduced by one‐fourth and one‐fifth , respectively ( p < 0.001 ) . No side‐effects were observed . Tranexamic acid is valuable in the treatment of subarachnoid hemorrhage caused by ruptured intracranial aneurysms MODIFICATION of the blood-clotting mechanisms as an adjunct to , or a substitute for , surgery in intracranial aneurysms has interested several workers ( Uihlein et al. , 1966 ; Gibbs & O'Gorman , 1967 ; Mullan & Dawley , 1968 ; Uttley & Buckell , 1968 ; Mullan , 1969 , personal communication ) . Uihlein et al. ( 1966 ) used the anti-fibrinolytic agent epsilonamino caproic acid ( EACA ) with hypothermia in the surgery of aneurysms , and Mullan & Dawley ( 1968 ) reported two recurrent haemorrhages only among thirty cases of angiographically proved aneurysms treated with EACA but no surgery . Since then , Mullan ( personal communication ) has combined this treatment with lowering of the systemic blood pressure by hypotensive drugs . Gibbs & O'Gorman ( 1967 ) studied fibrinolysis in 109 cases of proved intracranial aneurys 
    Output:
    
REVIEW ER 'S CONCLUSIONS Treatment does not improve clinical outcome because the benefit is offset by an increase in poor outcome caused by cerebral ischemia as a result of treatment with antifibrinolytics .
These data do not support the routine use of antifibrinolytic drugs in the treatment of patients with aneurysmal subarachnoid haemorrhage