***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 
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    Input: Background and Purpose The etiology of ischemic stroke affects prognosis , outcome , and management . Trials of therapies for patients with acute stroke should include measurements of responses as influenced by subtype of ischemic stroke . A system for categorization of subtypes of ischemic stroke mainly based on etiology has been developed for the Trial of Org 10172 in Acute Stroke Treatment ( TOAST ) . Methods A classification of subtypes was prepared using clinical features and the results of ancillary diagnostic studies . “ Possible ” and “ probable ” diagnoses can be made based on the physician 's certainty of diagnosis . The usefulness and interrater agreement of the classification were tested by two neurologists who had not participated in the writing of the criteria . The neurologists independently used the TOAST classification system in their bedside evaluation of 20 patients , first based only on clinical features and then after review ing the results of diagnostic tests . Results The TOAST classification denotes five subtypes of ischemic stroke : 1 ) large-artery atherosclerosis , 2 ) cardioembolism , 3 ) small-vessel occlusion , 4 ) stroke of other determined etiology , and 5 ) stroke of undetermined etiology . Using this rating system , interphysician agreement was very high . The two physicians disagreed in only one patient . They were both able to reach a specific etiologic diagnosis in 11 patients , whereas the cause of stroke was not determined in nine . Conclusions The TOAST stroke subtype classification system is easy to use and has good interobserver agreement . This system should allow investigators to report responses to treatment among important subgroups of patients with ischemic stroke . Clinical trials testing treatments for acute ischemic stroke should include similar methods to diagnose subtypes of stroke CONTEXT Approved treatment options for acute ischemic stroke in the United States and Canada are limited at present to intravenous tissue-type plasminogen activator , but bleeding complications , including intracranial hemorrhage , are a recognized complication . OBJECTIVE To evaluate the efficacy and safety of the defibrinogenating agent ancrod in patients with acute ischemic stroke . DESIGN The Stroke Treatment with Ancrod Trial ( STAT ) , a r and omized , parallel-group , double-blind , placebo-controlled trial conducted between August 1993 and January 1998 . SETTING Forty-eight centers , primarily community hospitals , in the United States and Canada . PATIENTS A total of 500 patients with an acute or progressing ischemic neurological deficit were enrolled and included in the intent-to-treat analysis . INTERVENTIONS Patients were r and omly assigned to receive ancrod ( n=248 ) or placebo ( n = 252 ) as a continuous 72-hour intravenous infusion beginning within 3 hours of stroke onset , followed by infusions lasting approximately 1 hour at 96 and 120 hours . The ancrod regimen was design ed to decrease plasma fibrinogen levels to 1.18 to 2.03 micromol/L. MAIN OUTCOME MEASURES The primary efficacy end point was functional status , with favorable functional status defined as survival to day 90 with a Barthel Index of 95 or more or at least the prestroke value , compared by treatment group . Primary safety variables included symptomatic intracranial hemorrhage and mortality . RESULTS Favorable functional status was achieved by more patients in the ancrod group ( 42.2 % ) than in the placebo group ( 34.4 % ; P=.04 ) by the prespecified covariate-adjusted analysis . Mortality was not different between treatment groups ( at 90 days , 25.4 % for the ancrod group and 23 % for the placebo group ; P=.62 ) , and the proportion of severely disabled patients was less in the ancrod group than in the placebo group ( 11.8 % vs 19.8 % ; P=.01 ) . The favorable functional status observed with ancrod vs placebo was consistent in all subgroups defined for age , stroke severity , sex , prestroke disability , and time to treatment ( < or = 3 or > 3 hours after stroke onset ) . There was a trend toward more symptomatic intracranial hemorrhages in the ancrod group vs placebo ( 5.2 % vs 2.0 % ; P=.06 ) , as well as a significant increase in asymptomatic intracranial hemorrhages ( 19.0 % vs 10.7 % ; P=.01 ) . CONCLUSION In this study , ancrod  had a favorable benefit-risk profile for patients with acute ischemic stroke OBJECTIVE To assess the efficacy and safety of fibrinogen-depleting agents ( snake venom extracts ) in the treatment of acute ischemic stroke . METHODS A systematic review of all the relevant r and omized controlled trials ( RCTs ) was performed . RCTs were identified from the Cochrane Stroke Group 's Specialized Trial Register , additional electronic and h and search ing , and personal contact with pharmaceutical companies . We included all completed and unconfounded truly or quasi-r and omized trials in patients with ischemic stroke comparing fibrinogen depleting agents with control started within 14 days of the stroke onset . The Peto method was used for analysis . RESULTS Eight completed and two ongoing RCTs have been identified so far . Only three trials using ancrod ( 182 patients ) met the inclusion criteria . Ancrod was associated with a significant reduction in early deaths ( 5.6 % v 16 % ; odds ratio [ OR ] , 0.33 ; 95 % confidence interval [ CI ] , 0.13 to 0.85 ; 2P=.02 ) suggesting that treatment of 100 patients would avoid about 10 early deaths . The frequency of asymptomatic intracranial hemorrhage shown by computed tomography was similar between ancrod-treated and control groups ( 7.6 % v 9.6 % ; OR , 0.78 ; 95 % CI , 0.26 to 2.33 ; 2P=.65 ) . No major intracranial or extracranial hemorrhages or recurrent ischemic strokes occurred in the ancrod-allocated patients . There were nonsignificant trends in favor of ancrod in death from any cause ( OR , 0.57 ; 95 % CI , 0.27 to 1.23 ; 2P=.15 ) and death or disability ( OR , 0.52 ; 95 % CI , 0.26 to 1.03 ; 2P=.06 ) at the end of trial follow-up . CONCLUSIONS There were too few patients and outcome events to draw reliable conclusions from the present data . Although ancrod-like agents appeared promising , their routine use can not be recommended at the moment . Two ongoing trials ( including about 1,000 patients in total ) will provide more data . Future trials should test simpler fixed-dose regimens to allow better generalizability OBJECTIVE Hospital management of acute ischemic stroke varies greatly within and between different countries . This study assesses the current practice s and opinions of doctors in China routinely involved in the treatment of stroke , and compares them with those of British doctors . METHODS Question naires about the usual management of acute ischemic stroke were sent to 247 Chinese hospitals ( mostly urban ) collaborating in an acute stroke trial , seeking responses from five doctors ( one consultant , two registrars , and two house officers ) in each . After one mailing , 1,095 doctors ( 89 % ) responded . RESULTS Sixty-nine percent of the hospitals had computed tomography scanners , and 88 % of the doctors in those hospitals reported that they would routinely scan acute stroke patients ( 78 % usually within 24 hours of admission and 22 % only later ) . Sixty-two percent of doctors reported average hospital stays of 2 to 4 weeks , whereas 36 % reported longer average stays . Treatments reported to be used routinely within the first 48 hours of acute ischemic stroke included glycerol or mannitol ( 69 % of doctors ) , Chinese herb products ( 66 % ) , calcium antagonists ( 54 % ) , and aspirin ( 53 % ) ; for each of these treatments , over 70 % of all doctors believed it produced definite benefit . Reported routine use of dextran ( 44 % ) ,  snake venom  ( 32 % ) ,  " photo-therapy "  ( 22 % ) , and  steroids  ( 19 % ) was also moderately common , and about half of all doctors believed each was beneficial . In contrast , routine use of  thrombolytic agents  ( 4 % ) or  anticoagulants  ( 1 % ) was uncommon . Only one third of the doctors reported active treatment of hypertension immediately after admission . CONCLUSIONS Comparison with a similar survey in Britain showed reported use of most treatments for acute ischemic stroke was more extensive in China , but that within both countries there was wide variation . The substantial variations in clinical practice both within and between China , the United Kingdom and other countries reflect , at least in part , the substantial uncertainty about the effectiveness of many of the possible treatments for acute ischemic stroke . Large-scale r and omized evidence is needed to confirm or refute the efficacy of these and newer treatments for acute stroke There is no acute therapy proven to be of benefit for ischemic stroke .  Ancrod is a potentially effective therapy because of the advantageous consequences of fibrinogen lowering . Methods We studied the safety and efficacy of ancrod in patients with acute ischemic stroke administered within 6 hours of stroke onset . In a doubleblind , r and omized , placebocontrolled trial 64 patients received intravenous ancrod and 68 received placebo for 7 days .  Neurological outcome , disability , and brain infa rct volume were measured . Results There was no significant difference in overall mean scores on the Sc and inavian Stroke Scale . No increase in bleeding occurred in the ancrod-treated patients . The target reduction of plasma fibrinogen levels of less than 100 mg/dL was achieved in only 15 ( 23 % ) of 64 ancrod-treated patients . Those patients with ancrod-induced 6-hour fibrinogen levels 130 mg/dL or less had a marginally significantly better neurological outcome on the Sc and inavian Stroke Scale , mortality , and Barthel Index than ancrod-treated patients with higher fibrinogen levels . Conclusions Ancrod appears safe and potentially effective when administered to patients within 6 hours of onset of ischemic stroke Clot lysis is desirable in patients with thrombi in arteries and arterioles by a safe rapidly-acting thrombolytic agent . Ancrod cleaves fibrinogen ; the result ing circulating ancrod-fibrin stimulates fibrinolysis . Ancrod action and effect were studied in 20 patients with acute developing stroke in a double-blind , placebo-controlled study . Patients were r and omly assigned to one of two treatment groups , and received either normal saline or ancrod 0.5 mu/kg in normal saline administered as a constant-rate intravenous infusion over 6 hours . Subsequent doses of ancrod ( or saline placebo ) were determined daily thereafter for a total treatment period of 7 days . Neither bleeding nor re-thrombosis occurred within the 90 day follow-up period . That ancrod acted rapidly was shown by a significant decrease in functional plasminogen activator inhibitor ( PA-I ) within 60 minutes , and by significant elevations of fibrin(ogen ) degradation products ( FDP ) and D-dimer within 3 and 4 hours . The biological effect of fibrinolysis in ancrod infused patients was demonstrated by a greater improvement in stroke score when compared to those infused with saline In a r and omized , single-blind study , 30 patients with acute ischemic stroke were treated with either low-molecular weight dextran and mannitol alone  ( group A , mean age , 63.3 + /- 11.8 years , n = 15 ) or in combination with the viper venom enzyme ancrod  ( group B , mean age , 67.9 + /- 7.6 years , n = 15 ) . Lowering of plasma fibrinogen levels to 100 - 130 mg/dL with ancrod result ed in a significant reduction of the apparent blood viscosity , ie , of 37 % at a shear rate of 0.03 s-1 , compared with only 7 % in group A. Fibrin degradation products increased considerably from 3.1 + /- 0.4 to 154.3 + /- 31.6 mg/L on day 3 , while plasminogen decreased from 98.2 % + /- 2.0 % to 79.8 % + /- 2.9 % in group B. Global coagulation and platelet function tests were not influenced by either treatment . Neurological score improved by 1.1 arbitrary units ( AU ) in group A and by 2.6 AU in group B. Five patients in group A and two in group B died during the first two weeks . This preliminary study indicated a slightly better outcome in the ancrod treated patients . The beneficial effect may be due to the anticoagulative and fibrinolytic activity of ancrod rather than its effect on blood viscosity 
    Output:
    
REVIEW ER 'S CONCLUSIONS Fibrinogen depleting agents are promising .