***TASK*** the task is to summarize 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 BACKGROUND Trials of patent foramen ovale ( PFO ) closure to prevent recurrent stroke have been inconclusive . We investigated whether patients with cryptogenic stroke and echocardiographic features representing risk of stroke would benefit from PFO closure or anticoagulation , as compared with antiplatelet therapy . METHODS In a multicenter , r and omized , open‐label trial , we assigned , in a 1:1:1 ratio , patients 16 to 60 years of age who had had a recent stroke attributed to PFO , with an associated atrial septal aneurysm or large interatrial shunt , to transcatheter PFO closure plus long‐term antiplatelet therapy ( PFO closure group ) , antiplatelet therapy alone ( antiplatelet‐only group ) , or oral anticoagulation ( anticoagulation group ) ( r and omization group 1 ) . Patients with contraindications to anticoagulants or to PFO closure were r and omly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy ( r and omization groups 2 and 3 ) . The primary outcome was occurrence of stroke . The comparison of PFO closure plus antiplatelet therapy with antiplatelet therapy alone was performed with combined data from r and omization groups 1 and 2 , and the comparison of oral anticoagulation with antiplatelet therapy alone was performed with combined data from r and omization groups 1 and 3 . RESULTS A total of 663 patients underwent r and omization and were followed for a mean ( ±SD ) of 5.3±2.0 years . In the analysis of r and omization groups 1 and 2 , no stroke occurred among the 238 patients in the PFO closure group , whereas stroke occurred in 14 of the 235 patients in the antiplatelet‐only group ( hazard ratio , 0.03 ; 95 % confidence interval , 0 to 0.26 ; P<0.001 ) . Procedural complications from PFO closure occurred in 14 patients ( 5.9 % ) . The rate of atrial fibrillation was higher in the PFO closure group than in the antiplatelet‐only group ( 4.6 % vs. 0.9 % , P=0.02 ) . The number of serious adverse events did not differ significantly between the treatment groups ( P=0.56 ) . In the analysis of r and omization groups 1 and 3 , stroke occurred in 3 of 187 patients assigned to oral anticoagulants and in 7 of 174 patients assigned to antiplatelet therapy alone . CONCLUSIONS Among patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt , the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone . PFO closure was associated with an increased risk of atrial fibrillation . ( Funded by the French Ministry of Health ; CLOSE Clinical Trials.gov number , NCT00562289 . BACKGROUND Whether closure of a patent foramen ovale reduces the risk of recurrence of ischemic stroke in patients who have had a cryptogenic ischemic stroke is unknown . METHODS In a multicenter , r and omized , open‐label trial , with blinded adjudication of end‐point events , we r and omly assigned patients 18 to 60 years of age who had a patent foramen ovale ( PFO ) and had had a cryptogenic ischemic stroke to undergo closure of the PFO ( PFO closure group ) or to receive medical therapy alone ( aspirin , warfarin , clopidogrel , or aspirin combined with extended‐release dipyridamole ; medical‐therapy group ) . The primary efficacy end point was a composite of recurrent nonfatal ischemic stroke , fatal ischemic stroke , or early death after r and omization . The results of the analysis of the primary outcome from the original trial period have been reported previously ; the current analysis of data from the extended follow‐up period was considered to be exploratory . RESULTS We enrolled 980 patients ( mean age , 45.9 years ) at 69 sites . Patients were followed for a median of 5.9 years . Treatment exposure in the two groups was unequal ( 3141 patient‐years in the PFO closure group vs. 2669 patient‐years in the medical‐therapy group ) , owing to a higher dropout rate in the medical‐therapy group . In the intention‐to‐treat population , recurrent ischemic stroke occurred in 18 patients in the PFO closure group and in 28 patients in the medical‐therapy group , result ing in rates of 0.58 events per 100 patient‐years and 1.07 events per 100 patient‐years , respectively ( hazard ratio with PFO closure vs. medical therapy , 0.55 ; 95 % confidence interval [ CI ] , 0.31 to 0.999 ; P=0.046 by the log‐rank test ) . Recurrent ischemic stroke of undetermined cause occurred in 10 patients in the PFO closure group and in 23 patients in the medical‐therapy group ( hazard ratio , 0.38 ; 95 % CI , 0.18 to 0.79 ; P=0.007 ) . Venous thromboembolism ( which comprised events of pulmonary embolism and deep‐vein thrombosis ) was more common in the PFO closure group than in the medical‐therapy group . CONCLUSIONS Among adults who had had a cryptogenic ischemic stroke , closure of a PFO was associated with a lower rate of recurrent ischemic strokes than medical therapy alone during extended follow‐up . ( Funded by St. Jude Medical ; RESPECT Clinical Trials.gov number , NCT00465270 . BACKGROUND The efficacy of closure of a patent foramen ovale ( PFO ) in the prevention of recurrent stroke after cryptogenic stroke is uncertain . We investigated the effect of PFO closure combined with antiplatelet therapy versus antiplatelet therapy alone on the risks of recurrent stroke and new brain infa rct ions . METHODS In this multinational trial involving patients with a PFO who had had a cryptogenic stroke , we r and omly assigned patients , in a 2:1 ratio , to undergo PFO closure plus antiplatelet therapy ( PFO closure group ) or to receive antiplatelet therapy alone ( antiplatelet‐only group ) . Imaging of the brain was performed at the baseline screening and at 24 months . The co primary end points were freedom from clinical evidence of ischemic stroke ( reported here as the percentage of patients who had a recurrence of stroke ) through at least 24 months after r and omization and the 24‐month incidence of new brain infa rct ion , which was a composite of clinical ischemic stroke or silent brain infa rct ion detected on imaging . RESULTS We enrolled 664 patients ( mean age , 45.2 years ) , of whom 81 % had moderate or large interatrial shunts . During a median follow‐up of 3.2 years , clinical ischemic stroke occurred in 6 of 441 patients ( 1.4 % ) in the PFO closure group and in 12 of 223 patients ( 5.4 % ) in the antiplatelet‐only group ( hazard ratio , 0.23 ; 95 % confidence interval [ CI ] , 0.09 to 0.62 ; P=0.002 ) . The incidence of new brain infa rct ions was significantly lower in the PFO closure group than in the antiplatelet‐only group ( 22 patients [ 5.7 % ] vs. 20 patients [ 11.3 % ] ; relative risk , 0.51 ; 95 % CI , 0.29 to 0.91 ; P=0.04 ) , but the incidence of silent brain infa rct ion did not differ significantly between the study groups ( P=0.97 ) . Serious adverse events occurred in 23.1 % of the patients in the PFO closure group and in 27.8 % of the patients in the antiplatelet‐only group ( P=0.22 ) . Serious device‐related adverse events occurred in 6 patients ( 1.4 % ) in the PFO closure group , and atrial fibrillation occurred in 29 patients ( 6.6 % ) after PFO closure . CONCLUSIONS Among patients with a PFO who had had a cryptogenic  stroke , the risk of subsequent ischemic stroke was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone ; however , PFO closure was associated with higher rates of device complications and atrial fibrillation . ( Funded by W.L. Gore and Associates ; Gore REDUCE Clinical Trials.gov number , NCT00738894 . BACKGROUND The incidence of stroke is predicted to rise because of the rapidly ageing population . However , over the past two decades , findings of r and omised trials have identified several interventions that are effective in prevention of stroke . Reliable data on time-trends in stroke incidence , major risk factors , and use of preventive treatments in an ageing population are required to ascertain whether implementation of preventive strategies can offset the predicted rise in stroke incidence . We aim ed to obtain these data . METHODS We ascertained changes in incidence of transient ischaemic attack and stroke , risk factors , and premorbid use of preventive treatments from 1981 - 84 ( Oxford Community Stroke Project ; OCSP ) to 2002 - 04 ( Oxford Vascular Study ; OXVASC ) . FINDINGS Of 476 patients with transient ischaemic attacks or strokes in OXVASC , 262 strokes and 93 transient ischaemic attacks were incident events . Despite more complete case-ascertainment than in OCSP , age-adjusted and sex-adjusted incidence of first-ever stroke fell by 29 % ( relative incidence 0.71 , 95 % CI 0.61 - 0.83 , p=0.0002 ) . Incidence declined by more than 50 % for primary intracerebral haemorrhage ( 0.47 , 0.27 - 0.83 , p=0.01 ) but was unchanged for subarachnoid haemorrhage ( 0.83 , 0.44 - 1.57 , p=0.57 ) . Thus , although 28 % more incident strokes ( 366 vs 286 ) were expected in OXVASC due to demographic change alone ( 33 % increase in those aged 75 or older ) , the observed number fell ( 262 vs 286 ) . Major reductions were recorded in mortality rates for incident stroke ( 0.63 , 0.44 - 0.90 , p=0.02 ) and in incidence of disabling or fatal stroke ( 0.60 , 0.50 - 0.73 , p<0.0001 ) , but no change was seen in case-fatality due to incident stroke ( 17.2 % vs 17.8 % ; age and sex adjusted relative risk 0.85 , 95 % CI 0.57 - 1.28 , p=0.45 ) . Comparison of premorbid risk factors revealed substantial reductions in the proportion of smokers , mean total cholesterol , and mean systolic and diastolic blood pressures and major increases in premorbid treatment with antiplatelet , lipid-lowering , and blood pressure lowering drugs ( all p<0.0001 ) . INTERPRETATION The age-specific incidence of major stroke in Oxfordshire has fallen by 40 % over the past 20 years in association with increased use of preventive treatments and major reductions in premorbid risk factors BACKGROUND Studies to date have shown an association between the presence of patent foramen ovale and cryptogenic stroke in patients younger than 55 years of age . This association has not been established in patients 55 years of age or older . METHODS We prospect ively examined 503 consecutive patients who had had a stroke , and we compared the 227 patients with cryptogenic stroke and the 276 control patients with stroke of known cause . We examined the prevalences of patent foramen ovale and of patent foramen ovale with concomit 
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INTERPRETATION Bubble-TCD was feasible in most older patients with transient ischaemic attack or non-disabling stroke , the association of RLS with cryptogenic events remained at older ages , and the population burden of PFO-associated events is substantial .