***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 and Purpose — Among patients with acute stroke , high blood pressure is often associated with poor outcome , although the reason is unclear . We analyzed data from the International Stroke Trial ( IST ) to explore the relationship between  systolic blood pressure ( SBP ) , subsequent clinical events over the next 2 weeks , and functional outcome at 6 months in patients with acute stroke . Methods — We included in the analysis 17 398 patients from IST with confirmed ischemic stroke . A single measurement of SBP was made immediately before r and omization . Clinical events within 14 days of r and omization were recorded : recurrent ischemic stroke , symptomatic intracranial hemorrhage , death result ing from presumed cerebral edema , fatal coronary heart disease , and death . Survival and dependency were assessed at 6 months . Outcomes were adjusted for age , sex , clinical stroke syndrome , time to r and omization , consciousness level , atrial fibrillation , and treatment allocation ( aspirin , unfractionated heparin , both , or neither ) . Results — A U-shaped relationship was found between baseline SBP and both early death and late death or dependency : early death increased by 17.9 % for every 10 mm Hg below 150 mm Hg ( P < 0.0001 ) and by 3.8 % for every 10 mm Hg above 150 mm Hg ( P = 0.016 ) . The rate of recurrent ischemic stroke within 14 days increased by 4.2 % for every 10–mm Hg increase in SBP ( P = 0.023 ) ; this association was present in both fatal and nonfatal recurrence . Death result ing from presumed cerebral edema was independently associated with high SBP ( P = 0.004 ) . No relationship between symptomatic intracranial hemorrhage and SBP was seen . Low SBP was associated with a severe clinical stroke ( total anterior circulation syndrome ) and an excess of deaths from coronary heart disease ( P = 0.002 ) . Conclusions — Both high blood pressure and low blood pressure were independent prognostic factors for poor outcome , relationships that appear to be mediated in part by increased rates of early recurrence and death result ing from presumed cerebral edema in patients with high blood pressure and increased coronary heart disease events in those with low blood pressure . The occurrence of symptomatic intracranial hemorrhage within 14 days was independent of SBP Background and Purpose — The practicalities of doing ambulance-based trials where paramedics perform all aspects of a clinical trial involving patients with ultra-acute stroke have not been assessed . Methods — We performed a r and omized controlled trial with screening , consent , r and omization , and treatment performed by paramedics prior to hospitalization . Patients with probable ultra-acute stroke ( < 4 hours ) and systolic blood pressure ( SBP ) > 140 mm Hg were r and omized to transdermal glyceryl trinitrate ( GTN ; 5 mg/24 hours ) or none ( blinding under gauze dressing ) for 7 days with the first dose given by paramedics . The primary outcome was SBP at 2 hours . Results — Of a planned 80 patients , 41 ( 25 GTN , 16 no GTN ) were enrolled > 22 months with median age [ interquartile range ] 79 [ 16 ] years ; men 22 ( 54 % ) ; SBP 168 [ 46 ] ; final diagnosis : stroke 33 ( 80 % ) and transient ischemic attack 3 ( 7 % ) .  Time to r and omization was 55 [ 75 ] minutes . After treatment with GTN versus no GTN , SBP at 2 hours was 153 [ 31 ] versus 174 [ 27 ] mm Hg , respectively , with difference −18 [ 30 ] mm Hg ( P=0.030 ) . GTN improved functional outcome with a shift in the modified Rankin Scale by 1 [ 3 ] point ( P=0.040 ) . The rates of death , 4 ( 16 % ) versus 6 ( 38 % ; P=0.15 ) , and serious adverse events , 14 ( 56 % ) versus 10 ( 63 % ; P=0.75 ) , did not differ between GTN and no GTN . Conclusions — Paramedics can successfully enroll patients with ultra-acute stroke into an ambulance-based trial . GTN  reduces SBP at 2 hours and seems to be safe in ultra-acute stroke . A larger trial is needed to assess whether GTN improves functional outcome . Clinical Trial Registration — URL : http://www.controlled-trials.com/IS RCT N66434824/66434824 . Unique identifier : 66434824 High blood pressure ( BP ) , pulse pressure ( PP ) , and rate pressure product ( RPP ) are each associated independently with a poor outcome in acute ischemic stroke . Whereas nitric oxide ( NO ) donors , such as glyceryl trinitrate ( GTN ) , lower blood pressure in acute ischemic stroke , their effect on other hemodynamic measures is not known . We performed a systematic review of the effects of NO donors on systemic hemodynamic measures in patients with acute/subacute stroke . R and omized controlled trials were identified from search es of the Cochrane Library , Pubmed , and Embase . Information on hemodynamic measures , including systolic BP ( SBP ) , diastolic BP ( DBP ) , and heart rate , were assessed , and hemodynamic derivatives of these were calculated : PP ( PP = SBP - DBP ) , mean arterial pressure ( MAP = DBP + PP/3 ) , mid blood pressure ( MBP = ( SBP + DBP)/2 ) , pulse pressure index ( PPI = PP/MAP ) , and RPP ( RPP = SBP x HR ) . The effect of treatment on hemodynamic measures was calculated as the weighted mean difference ( WMD ) between treated and control groups with adjustment for baseline . Three trials involving 145 patients were identified ; 93 patients received the NO donor , GTN , and 52 patients composed the control group .  Compared with placebo , GTN significantly reduced SBP ( WMD , -9.80 mm Hg ; P < .001 ) , DBP ( WMD , -4.43 mm Hg ; P < .001 ) , MAP ( WMD , - 6.41 mm Hg ; P < .001 ) , MBP ( WMD , -7.33 mm Hg ; P < .001 ) , PP ( WMD , -6.11 mm Hg ; P < .001 ) , and PPI ( WMD , -0.03 ; P = .04 ) . GTN increased HR ( WMD , + 3.87 bpm ; P < .001 ) and lowered RPP insignificantly ( WMD , -323 mm Hg.bpm ; P = .14 ) . Our findings indicate that the NO donor GTN reduces BP , PP , and other derivatives in acute and subacute stroke while increasing HR High blood pressure is common during the acute phase of stroke and is associated with a poor outcome . However , the management of high blood pressure remains unclear . The ‘ Efficacy of Nitric Oxide in Stroke ’ trial tested whether transdermal glyceryl trinitrate , a nitric oxide donor that lowers blood pressure , is safe and effective in improving outcome after acute stroke . Efficacy of Nitric Oxide in Stroke is an international multicenter , prospect i ve , r and omized , single-blind , blinded endpoint trial , with funding from the UK Medical Research Council . Patients with acute ischemic stroke or intracerebral hemorrhage and systolic blood pressure 140–220 mmHg were r and omized to glyceryl trinitrate or no glyceryl trinitrate and , where relevant , to continue or stop prestroke antihypertensive therapy . The primary outcome is shift in modified Rankin Scale at three-months . Patients or relatives gave written informed ( proxy ) consent , and all sites had research ethics approval . Analyses will be done by intention to treat . This paper and attachment describe the trial 's statistical analysis plan , developed prior to unblinding of date . The statistical analysis plan contains design and methods for analyses , and unpopulated tables and figures for the two primary publications and some secondary publications . The data base will be locked in late February 2014 in preparation for presentation of the results in May 2014 . The data from the trial will improve the precision of the estimates of the overall treatment effects ( efficacy and safety ) of results from completed trials of blood pressure management in acute stroke , and provide the first large-scale r and omized evidence on transdermal glyceryl trinitrate , and of continuing ( vs. stopping ) prestroke antihypertensive medications , in acute stroke High blood pressure in acute stroke is common and appears to be associated with a poor outcome . Lowering blood pressure might therefore improve outcome , provided that cerebral perfusion is not compromised . We assessed the effects of glyceryl trinitrate ( GTN ) on cerebral and systemic hemodynamic measures in acute stroke . Ninety patients with acute ischemic or hemorrhagic stroke were r and omized within 72 hours of ictus to transdermal GTN given daily for 10 days ( either 5 mg , 5 mg for 4 days then 10 mg , or 10 mg ) or control . Twenty-four hour blood pressure monitoring , middle cerebral artery blood velocity , cardiac output , augmentation index , and plasma nitric oxide levels were each measured at baseline and then on days 1 , 4 , 5 , and 10 . The primary outcome was blood pressure on day 1 . We found that GTN lowered mean peripheral arterial blood pressure on day 1 by 5.3 % to 6.7 % in a dose dependent manner as compared with control ( mean , SD ) : control , 108.8 ( 15.1 ) mmHg ; 5 mg , 102.5 ( 13.9 ) mmHg ; 5/10 mg , 103.4 ( 14.9 ) mmHg ; 10 mg , 101.5 ( 12.6 ) mmHg ; ( P = .005 ) . Increasing the dose from 5 to 10 mg on day 5 result ed in an overall reduction in blood pressure of 11.4 % as compared with leaving the dose at 5 mg ( P = .006 ) . GTN reduced peripheral pulse pressure , central aortic blood pressure , pulse pressure , and augmentation index on day 1 . Middle cerebral artery blood velocity and pulsatility index in the affected hemisphere , cardiac output , systemic peripheral resistance , and plasma nitric oxide levels were not altered by GTN . Treatment with GTN was associated with headache : control 0 ( 0 % ) , GTN 9 ( 15 % ) ( P = .027 ) ; no negative effect on end-of-treatment death or deterioration , or 3 month death or dependency was discernable . GTN reduced peripheral blood pressure in a dose-dependent fashion in patients with acute stroke at day 1 and also reduced central blood pressure and augmentation index . In contrast , GTN did not alter middle cerebral artery blood velocity or pulsatility index in the affected hemispheres , suggesting that cerebral blood flow did not change . A trial assessing the effect of lowering blood pressure with GTN on safety and functional outcome in patients with acute stroke is now warranted Background : Cellular phone conversations between on-scene patients or their legally authorized representatives ( LARs ) and off-scene enrolling physician-investigators require immediate and reliable connection systems to obtain explicit informed research consent in prehospital treatment trials . Methods : The NIH Field Administration of Stroke Therapy – Magnesium ( FAST-MAG ) Trial implemented a voice-over-internet protocol ( VOIP ) simultaneous ring system ( multiple investigator cell phones called simultaneously and first responder connected to call ) to enable physician-investigators to elicit consent immediately from competent patients or LARs encountered by 228 ambulances enrolling patients in a multicenter prehospital stroke trial . For 1 month , the number , origin , duration , and yield of enrolling line calls were monitored prospect ively . Results : Six investigators were connected to 106 enrolling line calls , with no identified unanswered calls . Thirty-five percent of new patient calls yielded an enrollment . The most common reasons for non-enrollment were last known well > 2 h ( n = 7 ) and uncon sentable patient without LAR available ( n = 7 ) . No non-enrollments were directly attributable to the VOIP system . In enrollments , consent was provided by the patient in 67 % and a LAR in 33 % . The duration of enrollment calls ( mean ± SD : 8.4 ± 2.5 min , range 6–14 ) was longer than non-enrollment calls ( 5.5 ± 3.5 , range 2–13 ; p < 0.001 ) . The median interval from last known well to study agent start was 46 min , and 70 % were enrolled within 60 min of onset . Conclusions : The simultaneous ring system was reliable and effective , permitting enrollment of a substantial number of patients within the first hour after stroke onset . VOIP cellular networks with simultaneous ring are a preferred means of facilitating consent in prehospital treatment trials High blood pressure ( BP ) is common in acute stroke and is independently associated with a poor outcome . Lowering BP might improve outcome if it did not adversely affect cerebral blood flow ( CBF ) or cerebral perfusion pressure . We investigated the effect of glyceryl trinitrate ( [ GTN ] an NO donor ) on quantitative CBF , BP , and cerebral perfusion pressure in patients with recent stroke . Eighteen patients with recent ( < 5 days ) ischemic ( n=16 ) 
    Output:
    
ENOS is a large completed international trial of blood pressure management in acute stroke and includes patients representative of many stroke services worldwide