human
***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 Citicoline is approved in some countries for the treatment of acute ischaemic stroke . The drug has shown some evidence of efficacy in a pooled analysis . We sought to confirm the efficacy of citicoline in a larger trial . METHODS We undertook a r and omised , placebo-controlled , sequential trial in patients with moderate-to-severe acute ischaemic stroke admitted at university hospitals in Germany , Portugal , and Spain . Using a central ised minimisation process , patients were r and omly assigned in a 1:1 ratio to receive citicoline or placebo within 24 h after the onset of symptoms ( 1000 mg every 12 h intravenously during the first 3 days and orally thereafter for a total of 6 weeks [ 2 × 500 mg oral tablets given every 12 h ] ) . All study participants were masked . The primary outcome was recovery at 90 days measured by a global test combining three measures of success : National Institutes of Health Stroke Scale ≤1 , modified Rankin score ≤1 , and Barthel Index ≥95 . Safety endpoints included symptomatic intracranial haemorrhage in patients treated with recombinant tissue plasminogen activator , neurological deterioration , and mortality . This trial is registered , NCT00331890 . RESULTS 2298 patients were enrolled into the study from Nov 26 , 2006 , to Oct 27 , 2011 . 37 centres in Spain , 11 in Portugal , and 11 in Germany recruited patients . Of the 2298 patients who gave informed consent and underwent r and omisation , 1148 were assigned to citicoline and 1150 to placebo . The trial was stopped for futility at the third interim analysis on the basis of complete data from 2078 patients . The final r and omised analysis was based on data for 2298 patients : 1148 in citicoline group and 1150 in  placebo group . Global recovery was similar in both groups ( odds ratio 1·03 , 95 % CI 0·86 - 1·25 ; p=0·364 ) . No significant differences were reported in the safety variables nor in the rate of adverse events . INTERPRETATION Under the circumstances of the ICTUS trial , citicoline is not efficacious in the treatment of moderate-to-severe acute ischaemic stroke . FUNDING Ferrer Grupo Some neuroprotective agents have shown benefits in animal models , but disappointing results in humans .  Citicoline is used in several countries as coadjuvant treatment in acute ischemic stroke ( AIS ) patients ; however , there are no retrospective postmarketing surveillances on the experience of citicoline in Mexico . The aim of this study was to evaluate the correlation between citicoline exposure and functional outcome at discharge and at 30 and 90 days post-stroke , in a retrospective case-control design on systematic descriptive data bases from three referral hospitals . Clinical records of 173 consecutively registered patients were analyzed , 86 of whom were treated with citicoline within the first 48 h after AIS and the remaining 87 were untreated , r and omly selected controls matched for age ( + /- 5 years ) , gender and NIHSS ( + /- 1 point ) at hospital admission . Pretreatment conditions were similar between groups . Compared with controls , exposure to citicoline was associated with a significantly lower 30-day mean and median modified Rankin score ( in both , P < 0.05 ) . After paired multivariate analyses ( controlled for NIHSS , age , gender , hospital arrival in < 24 h , thrombolysis and comorbidities ) citicoline was independently associated with a lower 90-day mortality risk ( P = 0.047 ) and with fewer in-hospital complications ( mainly infections and sepsis , P = 0.001 ) . In this observational study , citicoline use was associated with a better functional status and lower rates of short-term mortality , possibly due to fewer in-hospital systemic complications . The putative benefits should be interpreted as clinical associations , since this is not a r and omized , controlled clinical trial BACKGROUND AND PURPOSE Citicoline ( cytidine-5'-diphosphocholine ; CDP-choline ) may reduce central nervous system ischemic injury by stabilizing cell membranes and reducing free radical generation . A previous dose-comparison trial in patients with acute stroke found that 500 mg of citicoline appeared to improve neurological outcome with minimal side effects . METHODS The current trial was a 33-center , r and omized , double-blind , efficacy trial in 394 patients comparing placebo ( n=127 ) with citicoline ( n=267 ) ( 500 mg po daily ) for 6 weeks , with a 6-week posttreatment follow-up period . Patients with acute ( 24 hours ) ischemic strokes clinical ly assessed to be in the middle cerebral artery territory with National Institutes of Health Stroke Scale ( NIHSS ) > or = 5 were enrolled . RESULTS Mean time to treatment was 12 hours , and mean age was 71 for placebo and 70 for citicoline . Although mean baseline NIHSS were similar for both groups , there was a higher percentage of placebo patients with NIHSS < 8 ( 34 % vs 22 % ; P<0.01 ) . The incidence and type of side effects were similar between the groups . The planned primary analysis ( logistic regression : 5 categories Barthel ) failed the proportional odds assumption and was rendered unreliable . There were no between-group differences seen on the planned secondary assessment analyses at 90 days , including the Barthel Index > or = 95 at 12 weeks ( last observation carried forward : placebo 40 % ; citicoline 40 % ) or mortality rate  ( placebo 18 % ; citicoline 17 % ) . However , post hoc analyses in a subgroup of patients with baseline NIHSS > or = 8 found that citicoline-treated patients were more likely to have a full recovery ( Barthel > or = 95 ) : placebo 21 % ; citicoline 33 % ; P=0.05 ; whereas no difference was seen in patients with baseline NIHSS<8 ( placebo 77 % ; citicoline 69 % ; P>0.1 . CONCLUSIONS The results of this study indicate that citicoline was safe but ineffective in improving the outcome of patients with acute ischemic stroke who were enrolled in this trial . Post hoc analyses indicate that there may be a subgroup of patients with moderate to severe strokes who would benefit OBJECTIVE To investigate the clinical curative effect of soybean lecithin on cerebral infa rct ion . METHODS 542 patients with cerebral infa rct ion within 48 h after the onset with the nervous function defect scores of 31 - 35 were divided into 3 groups : basic treatment group , 60 cases , with conventional treatment ; citicoline group , 122 patients , with conventional treatment and citicoline ; and soybean lecithin group , 360 patients , with conventional treatment and soybean lecithin 10 g tid . For all patients , treatment began sometime within 48 hours after the onset . The treatment course lasted 28 days . RESULTS When the course was over , the infa rct volumes in basic group citicoline group , and soybean lecithin group , were 7.6 cm3 + /- 2.9 cm3 , 7.3 cm3 + /- 3.1 cm3 , and 6.4 cm3 + /- 2.7 cm3 respectively ( F = 7.371 , P = 0.0007 ) . The basic group and citicoline group being compared with the soybean group by Dunnett test , t = 4.387 and 3.969 respectively , P < 0.01 . The nervous function defect integral in the 3 groups decreased 14.2 + /- 10.93 , 15.0 + /- 9.0 , and 18.5 + /- 10.9 respectively . Two-way analysis of variance of drug kind and beginning time of treatment showed the value of F in drugs as 6.250 , P = 0.0021 , and value of F in times as 0.9417 , P = 0.4201 . In the order of death , deterioration , no improvement , improvement , significant improvement , and recovery , the Ridit values for the comprehensive curative effect in the 3 groups were 0.4003 , 0.4118 , and 0.54 5 respectively ; chi2 = 27.89 , P < 0.001 . CONCLUSION Soybean lecithin is effective in treatment of acute cerebral infa rct ion . The mechanism may be that soybean lecithin lowers the decrease of brain phospholipid content in brain ischemia Background and Purpose — Early initiated treatment of stroke increases the chances of a good recovery . This r and omized controlled study evaluates how an increased priority level for patients with stroke , from level 2 to 1 , from the Emergency Medical Communication Center influences thrombolysis frequency , time to stroke unit , and whether other medical emergencies reported negative consequences . Methods — Patients aged 18 to 85 years in Stockholm , Sweden , with symptoms of stroke within 6 hours were r and omized from the Emergency Medical Communication Center or emergency medical services to an intervention group , priority level 1 , immediate call of an ambulance , or to a control group with st and ard priority level  ,  that is ,  priority level 2 ( within 30 minutes ) .  Before study start , an educational program on identification of stroke and importance of early initiated treatment was directed to all medical dispatchers and ambulance and emergency department personnel . Results — During 2008 , 942 patients were r and omized of which 53 % ( n=496 ) had a final stroke/transient ischemic attack diagnosis .  Patients in the Emergency Medical Communication Center r and omized intervention group reached the stroke unit 26 minutes earlier than the control group ( P<0.001 ) after the emergency call . Thrombolysis was given to 24 % of the patients in the intervention group compared with 10 % of the control subjects ( P<0.001 ) . The higher priority level showed no negative effect on other critical ill patients requiring priority level 1 prehospital attention . Conclusion — This r and omized study shows negligible harm to other medical emergencies , a significant increase in thrombolysis frequency , and a shorter time to the stroke unit for patients with stroke up grade d to priority level 1 from the Emergency Medical Communication Center and through the acute chain of stroke care Background : The medical care of patients with acute stroke varies considerably between countries . This could lead to measurable differences in mortality and functional outcome . Objective : To compare case mix , clinical management , and functional outcome in stroke between 11 countries . Methods : All 1484 patients from 11 countries who were enrolled into the tinzaparin in acute ischaemic stroke trial ( TAIST ) were included in this sub study . Information collected prospect ively on demographics , risk factors , clinical features , measures of service quality ( for example , admission to a stroke unit ) , and outcome were assessed . Outcomes were adjusted for treatment assignment , case mix , and service relative to the British Isles . Results : Differences in case mix ( mostly minor ) and clinical service ( many of prognostic relevance ) were present between the countries . Significant differences in outcome were present between the countries . When assessed by geographical region , death or dependency were lower in North America ( odds ratio ( OR ) adjusted for treatment group only = 0.52 ( 95 % confidence interval , 0.39 to 0.71 ) and north west Europe ( OR = 0.54 ( 0.37 to 0.78 ) ) relative to the British Isles ; similar reductions were found when adjustments were made for 11 case mix variables and five service quality measures . Similarly , case fatality rates were lower in North America ( OR = 0.44 ( 0.30 to 0.66 ) ) and Sc and inavia ( OR = 0.50 ( 0.33 to 0.74 ) ) relative to the British Isles , whether crude or adjusted for case mix and service quality . Conclusions : Both functional outcome and case fatality vary considerably between countries , even when adjusted for prognostic case mix variables and measures of good stroke care . Differing health care systems and the management of patients with acute stroke may contribute to these findings A multicenter double-blind placebo-controlled study of cytidine 5'-diphosphocholine ( CDP-choline ) was conducted to evaluate possible clinical benefits of the drug in patients with acute , moderate to severe cerebral infa rct ion . The patients included also suffered from moderate to mild disturbances of consciousness , and all were admitted within 14 days of the ictus . Patients were allocated r and omly to treatment with either CDP-choline ( 1,000 mg/day i.v . once daily for 14 days ) or with placebo ( physiological saline ) .  One hundred thirty-three patients received CDP-choline treatment , and 139 received placebo .  The group treated with CDP-choline showed significant improvements in level of consciousness compared with the placebo-treated group , and CDP-choline was an entirely safe treatment Background / Aims : Kallikrein , a serine proteinase , has been reported to have many functions , such as selectively dilating arterioles in the ischemic area and enhancing angiogenesis and neurogenesis . Therefore , it may promote cerebral poststroke reorganization . We observed the effect of human tissue kallikrein on the brain motor activation of acute ischemic stroke patients and evaluated patient condition severity and prognosis . Methods : Forty-four cases suffering from cerebral infa rct ion between 6 and 7 
    Output:
    
agent
***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 Citicoline is approved in some countries for the treatment of acute ischaemic stroke . The drug has shown some evidence of efficacy in a pooled analysis . We sought to confirm the efficacy of citicoline in a larger trial . METHODS We undertook a r and omised , placebo-controlled , sequential trial in patients with moderate-to-severe acute ischaemic stroke admitted at university hospitals in Germany , Portugal , and Spain . Using a central ised minimisation process , patients were r and omly assigned in a 1:1 ratio to receive citicoline or placebo within 24 h after the onset of symptoms ( 1000 mg every 12 h intravenously during the first 3 days and orally thereafter for a total of 6 weeks [ 2 × 500 mg oral tablets given every 12 h ] ) . All study participants were masked . The primary outcome was recovery at 90 days measured by a global test combining three measures of success : National Institutes of Health Stroke Scale ≤1 , modified Rankin score ≤1 , and Barthel Index ≥95 . Safety endpoints included symptomatic intracranial haemorrhage in patients treated with recombinant tissue plasminogen activator , neurological deterioration , and mortality . This trial is registered , NCT00331890 . RESULTS 2298 patients were enrolled into the study from Nov 26 , 2006 , to Oct 27 , 2011 . 37 centres in Spain , 11 in Portugal , and 11 in Germany recruited patients . Of the 2298 patients who gave informed consent and underwent r and omisation , 1148 were assigned to citicoline and 1150 to placebo . The trial was stopped for futility at the third interim analysis on the basis of complete data from 2078 patients . The final r and omised analysis was based on data for 2298 patients : 1148 in citicoline group and 1150 in  placebo group . Global recovery was similar in both groups ( odds ratio 1·03 , 95 % CI 0·86 - 1·25 ; p=0·364 ) . No significant differences were reported in the safety variables nor in the rate of adverse events . INTERPRETATION Under the circumstances of the ICTUS trial , citicoline is not efficacious in the treatment of moderate-to-severe acute ischaemic stroke . FUNDING Ferrer Grupo Some neuroprotective agents have shown benefits in animal models , but disappointing results in humans .  Citicoline is used in several countries as coadjuvant treatment in acute ischemic stroke ( AIS ) patients ; however , there are no retrospective postmarketing surveillances on the experience of citicoline in Mexico . The aim of this study was to evaluate the correlation between citicoline exposure and functional outcome at discharge and at 30 and 90 days post-stroke , in a retrospective case-control design on systematic descriptive data bases from three referral hospitals . Clinical records of 173 consecutively registered patients were analyzed , 86 of whom were treated with citicoline within the first 48 h after AIS and the remaining 87 were untreated , r and omly selected controls matched for age ( + /- 5 years ) , gender and NIHSS ( + /- 1 point ) at hospital admission . Pretreatment conditions were similar between groups . Compared with controls , exposure to citicoline was associated with a significantly lower 30-day mean and median modified Rankin score ( in both , P < 0.05 ) . After paired multivariate analyses ( controlled for NIHSS , age , gender , hospital arrival in < 24 h , thrombolysis and comorbidities ) citicoline was independently associated with a lower 90-day mortality risk ( P = 0.047 ) and with fewer in-hospital complications ( mainly infections and sepsis , P = 0.001 ) . In this observational study , citicoline use was associated with a better functional status and lower rates of short-term mortality , possibly due to fewer in-hospital systemic complications . The putative benefits should be interpreted as clinical associations , since this is not a r and omized , controlled clinical trial BACKGROUND AND PURPOSE Citicoline ( cytidine-5'-diphosphocholine ; CDP-choline ) may reduce central nervous system ischemic injury by stabilizing cell membranes and reducing free radical generation . A previous dose-comparison trial in patients with acute stroke found that 500 mg of citicoline appeared to improve neurological outcome with minimal side effects . METHODS The current trial was a 33-center , r and omized , double-blind , efficacy trial in 394 patients comparing placebo ( n=127 ) with citicoline ( n=267 ) ( 500 mg po daily ) for 6 weeks , with a 6-week posttreatment follow-up period . Patients with acute ( 24 hours ) ischemic strokes clinical ly assessed to be in the middle cerebral artery territory with National Institutes of Health Stroke Scale ( NIHSS ) > or = 5 were enrolled . RESULTS Mean time to treatment was 12 hours , and mean age was 71 for placebo and 70 for citicoline . Although mean baseline NIHSS were similar for both groups , there was a higher percentage of placebo patients with NIHSS < 8 ( 34 % vs 22 % ; P<0.01 ) . The incidence and type of side effects were similar between the groups . The planned primary analysis ( logistic regression : 5 categories Barthel ) failed the proportional odds assumption and was rendered unreliable . There were no between-group differences seen on the planned secondary assessment analyses at 90 days , including the Barthel Index > or = 95 at 12 weeks ( last observation carried forward : placebo 40 % ; citicoline 40 % ) or mortality rate  ( placebo 18 % ; citicoline 17 % ) . However , post hoc analyses in a subgroup of patients with baseline NIHSS > or = 8 found that citicoline-treated patients were more likely to have a full recovery ( Barthel > or = 95 ) : placebo 21 % ; citicoline 33 % ; P=0.05 ; whereas no difference was seen in patients with baseline NIHSS<8 ( placebo 77 % ; citicoline 69 % ; P>0.1 . CONCLUSIONS The results of this study indicate that citicoline was safe but ineffective in improving the outcome of patients with acute ischemic stroke who were enrolled in this trial . Post hoc analyses indicate that there may be a subgroup of patients with moderate to severe strokes who would benefit OBJECTIVE To investigate the clinical curative effect of soybean lecithin on cerebral infa rct ion . METHODS 542 patients with cerebral infa rct ion within 48 h after the onset with the nervous function defect scores of 31 - 35 were divided into 3 groups : basic treatment group , 60 cases , with conventional treatment ; citicoline group , 122 patients , with conventional treatment and citicoline ; and soybean lecithin group , 360 patients , with conventional treatment and soybean lecithin 10 g tid . For all patients , treatment began sometime within 48 hours after the onset . The treatment course lasted 28 days . RESULTS When the course was over , the infa rct volumes in basic group citicoline group , and soybean lecithin group , were 7.6 cm3 + /- 2.9 cm3 , 7.3 cm3 + /- 3.1 cm3 , and 6.4 cm3 + /- 2.7 cm3 respectively ( F = 7.371 , P = 0.0007 ) . The basic group and citicoline group being compared with the soybean group by Dunnett test , t = 4.387 and 3.969 respectively , P < 0.01 . The nervous function defect integral in the 3 groups decreased 14.2 + /- 10.93 , 15.0 + /- 9.0 , and 18.5 + /- 10.9 respectively . Two-way analysis of variance of drug kind and beginning time of treatment showed the value of F in drugs as 6.250 , P = 0.0021 , and value of F in times as 0.9417 , P = 0.4201 . In the order of death , deterioration , no improvement , improvement , significant improvement , and recovery , the Ridit values for the comprehensive curative effect in the 3 groups were 0.4003 , 0.4118 , and 0.54 5 respectively ; chi2 = 27.89 , P < 0.001 . CONCLUSION Soybean lecithin is effective in treatment of acute cerebral infa rct ion . The mechanism may be that soybean lecithin lowers the decrease of brain phospholipid content in brain ischemia Background and Purpose — Early initiated treatment of stroke increases the chances of a good recovery . This r and omized controlled study evaluates how an increased priority level for patients with stroke , from level 2 to 1 , from the Emergency Medical Communication Center influences thrombolysis frequency , time to stroke unit , and whether other medical emergencies reported negative consequences . Methods — Patients aged 18 to 85 years in Stockholm , Sweden , with symptoms of stroke within 6 hours were r and omized from the Emergency Medical Communication Center or emergency medical services to an intervention group , priority level 1 , immediate call of an ambulance , or to a control group with st and ard priority level  ,  that is ,  priority level 2 ( within 30 minutes ) .  Before study start , an educational program on identification of stroke and importance of early initiated treatment was directed to all medical dispatchers and ambulance and emergency department personnel . Results — During 2008 , 942 patients were r and omized of which 53 % ( n=496 ) had a final stroke/transient ischemic attack diagnosis .  Patients in the Emergency Medical Communication Center r and omized intervention group reached the stroke unit 26 minutes earlier than the control group ( P<0.001 ) after the emergency call . Thrombolysis was given to 24 % of the patients in the intervention group compared with 10 % of the control subjects ( P<0.001 ) . The higher priority level showed no negative effect on other critical ill patients requiring priority level 1 prehospital attention . Conclusion — This r and omized study shows negligible harm to other medical emergencies , a significant increase in thrombolysis frequency , and a shorter time to the stroke unit for patients with stroke up grade d to priority level 1 from the Emergency Medical Communication Center and through the acute chain of stroke care Background : The medical care of patients with acute stroke varies considerably between countries . This could lead to measurable differences in mortality and functional outcome . Objective : To compare case mix , clinical management , and functional outcome in stroke between 11 countries . Methods : All 1484 patients from 11 countries who were enrolled into the tinzaparin in acute ischaemic stroke trial ( TAIST ) were included in this sub study . Information collected prospect ively on demographics , risk factors , clinical features , measures of service quality ( for example , admission to a stroke unit ) , and outcome were assessed . Outcomes were adjusted for treatment assignment , case mix , and service relative to the British Isles . Results : Differences in case mix ( mostly minor ) and clinical service ( many of prognostic relevance ) were present between the countries . Significant differences in outcome were present between the countries . When assessed by geographical region , death or dependency were lower in North America ( odds ratio ( OR ) adjusted for treatment group only = 0.52 ( 95 % confidence interval , 0.39 to 0.71 ) and north west Europe ( OR = 0.54 ( 0.37 to 0.78 ) ) relative to the British Isles ; similar reductions were found when adjustments were made for 11 case mix variables and five service quality measures . Similarly , case fatality rates were lower in North America ( OR = 0.44 ( 0.30 to 0.66 ) ) and Sc and inavia ( OR = 0.50 ( 0.33 to 0.74 ) ) relative to the British Isles , whether crude or adjusted for case mix and service quality . Conclusions : Both functional outcome and case fatality vary considerably between countries , even when adjusted for prognostic case mix variables and measures of good stroke care . Differing health care systems and the management of patients with acute stroke may contribute to these findings A multicenter double-blind placebo-controlled study of cytidine 5'-diphosphocholine ( CDP-choline ) was conducted to evaluate possible clinical benefits of the drug in patients with acute , moderate to severe cerebral infa rct ion . The patients included also suffered from moderate to mild disturbances of consciousness , and all were admitted within 14 days of the ictus . Patients were allocated r and omly to treatment with either CDP-choline ( 1,000 mg/day i.v . once daily for 14 days ) or with placebo ( physiological saline ) .  One hundred thirty-three patients received CDP-choline treatment , and 139 received placebo .  The group treated with CDP-choline showed significant improvements in level of consciousness compared with the placebo-treated group , and CDP-choline was an entirely safe treatment Background / Aims : Kallikrein , a serine proteinase , has been reported to have many functions , such as selectively dilating arterioles in the ischemic area and enhancing angiogenesis and neurogenesis . Therefore , it may promote cerebral poststroke reorganization . We observed the effect of human tissue kallikrein on the brain motor activation of acute ischemic stroke patients and evaluated patient condition severity and prognosis . Methods : Forty-four cases suffering from cerebral infa rct ion between 6 and 7 
    Output:
    