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 and Purpose — Many ischemic strokes or transient ischemic attacks are labeled cryptogenic but may have undetected atrial fibrillation ( AF ) . We sought to identify those most likely to have sub clinical AF . Methods — We prospect ively studied patients with cryptogenic stroke or transient ischemic attack aged ≥55 years in sinus rhythm , without known AF , enrolled in the intervention arm of the 30 Day Event Monitoring Belt for Recording Atrial Fibrillation After a Cerebral Ischemic Event ( EMBRACE ) trial . Participants underwent baseline 24-hour Holter ECG poststroke ; if AF was not detected , they were r and omly assigned to 30-day ECG monitoring with an AF auto-detect external loop recorder . Multivariable logistic regression assessed the association between baseline variables ( Holter-detected atrial premature beats [ APBs ] , runs of atrial tachycardia , age , and left atrial enlargement ) and subsequent AF detection . Results — Among 237 participants , the median baseline Holter APB count/24 h was 629 ( interquartile range , 142–1973 ) among those who subsequently had AF detected versus 45 ( interquartile range , 14–250 ) in those without AF ( P<0.001 ) . APB count was the only significant predictor of AF detection by 30-day ECG ( P<0.0001 ) , and at 90 days ( P=0.0017 ) and 2 years ( P=0.0027 ) . Compared with the 16 % overall 90-day AF detection rate , the probability of AF increased from < 9 % among patients with < 100 APBs/24 h to 9 % to 24 % in those with 100 to 499 APBs/24 h , 25 % to 37 % with 500 to 999 APBs/24 h , 37 % to 40 % with 1000 to 1499 APBs/24 h , and 40 % beyond 1500 APBs/24 h. Conclusions — Among older cryptogenic stroke or transient ischemic attack patients , the number of APBs on a routine 24-hour Holter ECG was a strong dose-dependent independent predictor of prevalent sub clinical AF . Those with frequent APBs have a high probability of AF and represent ideal c and i date s for prolonged ECG monitoring for AF detection . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00846924 Background —It is unknown if brief episodes of device-detected atrial fibrillation ( AF ) increase thromboembolic event ( TE ) risk . Methods and Results —TRENDS was a prospect i ve , observational study enrolling patients with ≥1 stroke risk factor ( heart failure , hypertension , age ≥65 years , diabetes , or prior TE ) receiving pacemakers or defibrillators that monitor atrial tachycardia (AT)/AF burden ( defined as the longest total AT/AF duration on any given day during the prior 30-day period ) . This time-varying exposure was up date d daily during follow-up and related to TE risk . Annualized TE rates were determined according to AT/AF burden subsets : zero , low ( < 5.5 hours [ median duration of subsets with nonzero burden ] ) , and high ( ≥5.5 hours ) . A multivariate Cox model provided hazard ratios including terms for stroke risk factors and time-varying AT/AF burden and antithrombotic therapy . Patients ( n=2486 ) had at least 30 days of device data for analysis . During a mean follow-up of 1.4 years , annualized TE risk ( including transient ischemic attacks ) was 1.1 % for zero , 1.1 % for low , and 2.4 % for high burden subsets of 30-day windows . Compared with zero burden , adjusted hazard ratios ( 95 % CIs ) in the low and high burden subsets were 0.98 ( 0.34 to 2.82 , P=0.97 ) and 2.20 ( 0.96 to 5.05 , P=0.06 ) , respectively . Conclusions —The TE rate was low compared with patients with traditional AF with similar risk profiles . The data suggest that TE risk is a quantitative function of AT/AF burden . AT/AF burden ≥5.5 hours on any of 30 prior days appeared to double TE risk . Additional studies are needed to more precisely investigate the relationship between stroke risk and AT/AF burden Abstract Objectives . The aim of this study was to compare health-related quality of life ( HRQoL ) scores obtained from the instrument Short Form (SF)-36 through the so-called SF-6D utilities , and those obtained from 15D , in patients with ST-elevation myocardial infa rct ion ( STEMI ) , and to evaluate the consequences in estimation of quality adjusted life years ( QALYs ) . Design . This was a sub- study of the Norwegian District Treatment of STEMI , in which patients with STEMI treated with tenecteplase , were r and omized to early angioplasty or st and ard management ( n = 266 ) .  HRQoL data were collected at all visits ( 0 , 1 , 3 , 7 and 12 months ) . All patients with complete data were included ( n = 248 ) . Results . The score range was 0.33–1.0 for SF-6D and 0.49–1.0 for 15D  . Mean utility scores from 15D were higher and had different distribution compared to scores from SF-6D . Mean QALY for the whole group was higher using 15D than SF-6D ( 0.89 vs. 0.77 ) . The incremental number of QALYs with early angioplasty compared to st and ard treatment was 0.005 ( 95 % CI : − 0.018 to 0.028 ) using SF-6D , and 0.004 ( 95 % CI : − 0.010 to 0.018 ) using the 15D instrument . Conclusions . Choice of instrument may influence HRQoL scores , but not necessarily the gain in QALYs Background The impact of different types of extracranial bleeding events on health‐related quality of life and health‐state utility among patients with atrial fibrillation is not well understood . Methods and Results The ENGAGE AF‐TIMI 48 ( Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation – Thrombolysis in Myocardial Infa rct ion 48 ) Trial compared edoxaban with warfarin with respect to the prevention of stroke or systemic embolism in atrial fibrillation . Data from the EuroQol‐5D ( EQ‐5D‐3L ) question naire , prospect ively collected at 3‐month intervals for up to 48 months , were used to estimate the impact of different categories of bleeding events on health‐state utility over 12 months following the event . Longitudinal mixed‐effect models revealed that major gastrointestinal bleeds and major nongastrointestinal bleeds were associated with significant immediate decreases in utility scores ( −0.029 [ −0.044 to −0.014 ; P<0.001 ] and −0.029 [ −0.046 to −0.012 ; P=0.001 ] , respectively ) . These effects decreased in magnitude over time , and were no longer significant for major nongastrointestinal bleeds at 9 months , but remained borderline significant for major gastrointestinal bleeds at 12 months . Clinical ly relevant nonmajor and minor bleeds were associated with smaller but measurable immediate impacts on utility ( −0.010 [ −0.016 to −0.005 ] and −0.016 [ −0.024 to −0.008 ] ; P<0.001 for both ) , which remained relatively constant and statistically significant over the 12 months following the bleeding event . Conclusions All categories of bleeding events were associated with negative impacts on health‐state utility  in patients with atrial fibrillation . Major bleeds were associated with relatively large immediate decreases in utility scores that gradually diminished over 12 months ; clinical ly relevant nonmajor and minor bleeds were associated with smaller immediate decreases in utility that persisted over 12 months . Clinical Trial Registration URL : https://www . clinical trials.gov/. Unique identifier : NCT00781391 BACKGROUND Atrial fibrillation ( AF ) is a major risk factor of stroke , but the association between AF and transient ischemic attack ( TIA ) is less clear . Despite this , patients with TIA are included in stroke trials . AIMS To determine the 1-year incidence of AF in TIA patients using an insertable cardiac monitor ( ICM ) ; second , to determine factors associated with incident AF in these patients . METHODS Prospect i ve cohort study of patients with TIA with normal st and ard electrocardiogram ( ECG ) and 72-hour Holter monitoring ( HM ) . Exclusion criteria were as follows : age < 18 or > 81 years ; prior AF/stroke ; ongoing oral anticoagulation therapy or contraindication for it ; significant carotid artery stenosis ; uncertain TIA diagnosis . Eligible patients received an ICM and were followed for 12 months . RESULTS From November 2013 to October 2015 , 809 patients were diagnosed with TIA . In total , 235 patients were eligible . Nine ( 3.8 % ) of these had AF on st and ard ECG or HM . Of the remaining patients , 121 refused ICM implantation . In total , 105 patients ( median age 65.4 years [ range 27.1 - 80.8 ] , 46 % males ) received an ICM , which revealed AF in 7 ( 6.7 % ) . Factors associated with new-onset AF were a history of recurrent TIA ( odds ratio [ OR ] 11.5 , 95 % confidence interval [ CI ] 2.1 - 63.6 ) and heart failure ( OR 12.7 , 95 % CI 1.71 - 96.83 ) . CONCLUSIONS The 1-year incidence of AF in TIA patients with normal ECG and HM was 6.7 % using an ICM . Factors associated with development of AF were recurrent TIA and heart failure Abstract The EQ-5D question naire is a widely used generic instrument for describing and valuing health that was developed by the EuroQol Group . A primary objective of the EuroQol Group is the investigation of values for health states in the general population in different countries . As part of the EuroQol enterprise 11 population surveys were carried out in six Western European countries ( Finl and , Germany , The Netherl and s , Spain , Sweden and the UK ) to value health states as defined by the EQ-5D using a st and ardised visual analogue scale ( EQ-5D VAS ) . This contribution reports how a European set of general population preference weights was derived from the data collected in the 11 valuation studies . The scores from this set of preference weights can be applied to generate a VAS-based weighted health status index for all the potential 243 EQ-5D health states for use in multi-national studies . To estimate the preference weights a multi-level regression analysis was performed on 82,910 valuations of 44 EQ-5D health states elicited from 6,870 respondents . Stable and plausible solutions were found for the model parameters . The R2 value was 75 % . The analysis showed that the major source of variance , apart from ' r and om error ' , was variance between individuals ( 28.3 % of the total residual variance ) . These results suggest that VAS values for EQ-5D health states in six Western European countries can be described by a common model Stroke , as the leading cause of physical disability and cognitive impairment , has a very significant impact on patients ’ quality of life ( QoL ) . The objective of this study is to know the effect of citicoline treatment in Qol and cognitive performance in the long-term in patients with a first ischemic stroke . This is an open-label , r and omized , parallel study of citicoline vs. usual treatment . All subjects were selected 6 weeks after suffering a first ischemic stroke and r and omized into parallel arms . Neuropsychological evaluation was performed at 1 month , 6 months , 1 year and 2 years after stroke , and QoL was measured using the EuroQoL-5D question naire at 2 years . 163 patients were followed during 2 years . The mean age was 67.5 years-old , and 50.9 % were women . Age and absence of citicoline treatment were independent predictors of both utility and poor quality of life .  Patients with cognitive impairment  had a poorer QoL at 2 years ( 0.55 vs. 0.66 in utility , p = 0.015 ) . Citicoline treatment improved significantly cognitive status during follow-up ( p = 0.005 ) . In conclusion , treatment with long-term citicoline is associated with a better QoL and improves cognitive status 2 years after a first ischemic stroke Background —Atrial fibrillation ( AF ) can be a cause of previously diagnosed cryptogenic stroke . However , AF can be paroxysmal and asymptomatic , thereby making detection with routine ECG methods difficult . Oral anticoagulation is highly effective in reducing recurrent stroke in patients with AF , but its initiation is dependent on the detection of AF . Cryptogenic Stroke and Underlying Atrial Fibrillation ( CRYSTAL AF ) is the first r and omized study to report the detection of AF in cryptogenic stroke patients using continuous long-term monitoring via insertable cardiac monitors ( ICM ) . Methods and Results — Patients with prior cryptogenic stroke were r and omized to control ( n=220 ) or ICM ( n=221 ) and followed for �� 
    Output:
    
agent
When each device is compared incrementally , BioMonitor 2-AF dominates Reveal LINQ and Confirm RX .
***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 — Many ischemic strokes or transient ischemic attacks are labeled cryptogenic but may have undetected atrial fibrillation ( AF ) . We sought to identify those most likely to have sub clinical AF . Methods — We prospect ively studied patients with cryptogenic stroke or transient ischemic attack aged ≥55 years in sinus rhythm , without known AF , enrolled in the intervention arm of the 30 Day Event Monitoring Belt for Recording Atrial Fibrillation After a Cerebral Ischemic Event ( EMBRACE ) trial . Participants underwent baseline 24-hour Holter ECG poststroke ; if AF was not detected , they were r and omly assigned to 30-day ECG monitoring with an AF auto-detect external loop recorder . Multivariable logistic regression assessed the association between baseline variables ( Holter-detected atrial premature beats [ APBs ] , runs of atrial tachycardia , age , and left atrial enlargement ) and subsequent AF detection . Results — Among 237 participants , the median baseline Holter APB count/24 h was 629 ( interquartile range , 142–1973 ) among those who subsequently had AF detected versus 45 ( interquartile range , 14–250 ) in those without AF ( P<0.001 ) . APB count was the only significant predictor of AF detection by 30-day ECG ( P<0.0001 ) , and at 90 days ( P=0.0017 ) and 2 years ( P=0.0027 ) . Compared with the 16 % overall 90-day AF detection rate , the probability of AF increased from < 9 % among patients with < 100 APBs/24 h to 9 % to 24 % in those with 100 to 499 APBs/24 h , 25 % to 37 % with 500 to 999 APBs/24 h , 37 % to 40 % with 1000 to 1499 APBs/24 h , and 40 % beyond 1500 APBs/24 h. Conclusions — Among older cryptogenic stroke or transient ischemic attack patients , the number of APBs on a routine 24-hour Holter ECG was a strong dose-dependent independent predictor of prevalent sub clinical AF . Those with frequent APBs have a high probability of AF and represent ideal c and i date s for prolonged ECG monitoring for AF detection . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00846924 Background —It is unknown if brief episodes of device-detected atrial fibrillation ( AF ) increase thromboembolic event ( TE ) risk . Methods and Results —TRENDS was a prospect i ve , observational study enrolling patients with ≥1 stroke risk factor ( heart failure , hypertension , age ≥65 years , diabetes , or prior TE ) receiving pacemakers or defibrillators that monitor atrial tachycardia (AT)/AF burden ( defined as the longest total AT/AF duration on any given day during the prior 30-day period ) . This time-varying exposure was up date d daily during follow-up and related to TE risk . Annualized TE rates were determined according to AT/AF burden subsets : zero , low ( < 5.5 hours [ median duration of subsets with nonzero burden ] ) , and high ( ≥5.5 hours ) . A multivariate Cox model provided hazard ratios including terms for stroke risk factors and time-varying AT/AF burden and antithrombotic therapy . Patients ( n=2486 ) had at least 30 days of device data for analysis . During a mean follow-up of 1.4 years , annualized TE risk ( including transient ischemic attacks ) was 1.1 % for zero , 1.1 % for low , and 2.4 % for high burden subsets of 30-day windows . Compared with zero burden , adjusted hazard ratios ( 95 % CIs ) in the low and high burden subsets were 0.98 ( 0.34 to 2.82 , P=0.97 ) and 2.20 ( 0.96 to 5.05 , P=0.06 ) , respectively . Conclusions —The TE rate was low compared with patients with traditional AF with similar risk profiles . The data suggest that TE risk is a quantitative function of AT/AF burden . AT/AF burden ≥5.5 hours on any of 30 prior days appeared to double TE risk . Additional studies are needed to more precisely investigate the relationship between stroke risk and AT/AF burden Abstract Objectives . The aim of this study was to compare health-related quality of life ( HRQoL ) scores obtained from the instrument Short Form (SF)-36 through the so-called SF-6D utilities , and those obtained from 15D , in patients with ST-elevation myocardial infa rct ion ( STEMI ) , and to evaluate the consequences in estimation of quality adjusted life years ( QALYs ) . Design . This was a sub- study of the Norwegian District Treatment of STEMI , in which patients with STEMI treated with tenecteplase , were r and omized to early angioplasty or st and ard management ( n = 266 ) .  HRQoL data were collected at all visits ( 0 , 1 , 3 , 7 and 12 months ) . All patients with complete data were included ( n = 248 ) . Results . The score range was 0.33–1.0 for SF-6D and 0.49–1.0 for 15D  . Mean utility scores from 15D were higher and had different distribution compared to scores from SF-6D . Mean QALY for the whole group was higher using 15D than SF-6D ( 0.89 vs. 0.77 ) . The incremental number of QALYs with early angioplasty compared to st and ard treatment was 0.005 ( 95 % CI : − 0.018 to 0.028 ) using SF-6D , and 0.004 ( 95 % CI : − 0.010 to 0.018 ) using the 15D instrument . Conclusions . Choice of instrument may influence HRQoL scores , but not necessarily the gain in QALYs Background The impact of different types of extracranial bleeding events on health‐related quality of life and health‐state utility among patients with atrial fibrillation is not well understood . Methods and Results The ENGAGE AF‐TIMI 48 ( Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation – Thrombolysis in Myocardial Infa rct ion 48 ) Trial compared edoxaban with warfarin with respect to the prevention of stroke or systemic embolism in atrial fibrillation . Data from the EuroQol‐5D ( EQ‐5D‐3L ) question naire , prospect ively collected at 3‐month intervals for up to 48 months , were used to estimate the impact of different categories of bleeding events on health‐state utility over 12 months following the event . Longitudinal mixed‐effect models revealed that major gastrointestinal bleeds and major nongastrointestinal bleeds were associated with significant immediate decreases in utility scores ( −0.029 [ −0.044 to −0.014 ; P<0.001 ] and −0.029 [ −0.046 to −0.012 ; P=0.001 ] , respectively ) . These effects decreased in magnitude over time , and were no longer significant for major nongastrointestinal bleeds at 9 months , but remained borderline significant for major gastrointestinal bleeds at 12 months . Clinical ly relevant nonmajor and minor bleeds were associated with smaller but measurable immediate impacts on utility ( −0.010 [ −0.016 to −0.005 ] and −0.016 [ −0.024 to −0.008 ] ; P<0.001 for both ) , which remained relatively constant and statistically significant over the 12 months following the bleeding event . Conclusions All categories of bleeding events were associated with negative impacts on health‐state utility  in patients with atrial fibrillation . Major bleeds were associated with relatively large immediate decreases in utility scores that gradually diminished over 12 months ; clinical ly relevant nonmajor and minor bleeds were associated with smaller immediate decreases in utility that persisted over 12 months . Clinical Trial Registration URL : https://www . clinical trials.gov/. Unique identifier : NCT00781391 BACKGROUND Atrial fibrillation ( AF ) is a major risk factor of stroke , but the association between AF and transient ischemic attack ( TIA ) is less clear . Despite this , patients with TIA are included in stroke trials . AIMS To determine the 1-year incidence of AF in TIA patients using an insertable cardiac monitor ( ICM ) ; second , to determine factors associated with incident AF in these patients . METHODS Prospect i ve cohort study of patients with TIA with normal st and ard electrocardiogram ( ECG ) and 72-hour Holter monitoring ( HM ) . Exclusion criteria were as follows : age < 18 or > 81 years ; prior AF/stroke ; ongoing oral anticoagulation therapy or contraindication for it ; significant carotid artery stenosis ; uncertain TIA diagnosis . Eligible patients received an ICM and were followed for 12 months . RESULTS From November 2013 to October 2015 , 809 patients were diagnosed with TIA . In total , 235 patients were eligible . Nine ( 3.8 % ) of these had AF on st and ard ECG or HM . Of the remaining patients , 121 refused ICM implantation . In total , 105 patients ( median age 65.4 years [ range 27.1 - 80.8 ] , 46 % males ) received an ICM , which revealed AF in 7 ( 6.7 % ) . Factors associated with new-onset AF were a history of recurrent TIA ( odds ratio [ OR ] 11.5 , 95 % confidence interval [ CI ] 2.1 - 63.6 ) and heart failure ( OR 12.7 , 95 % CI 1.71 - 96.83 ) . CONCLUSIONS The 1-year incidence of AF in TIA patients with normal ECG and HM was 6.7 % using an ICM . Factors associated with development of AF were recurrent TIA and heart failure Abstract The EQ-5D question naire is a widely used generic instrument for describing and valuing health that was developed by the EuroQol Group . A primary objective of the EuroQol Group is the investigation of values for health states in the general population in different countries . As part of the EuroQol enterprise 11 population surveys were carried out in six Western European countries ( Finl and , Germany , The Netherl and s , Spain , Sweden and the UK ) to value health states as defined by the EQ-5D using a st and ardised visual analogue scale ( EQ-5D VAS ) . This contribution reports how a European set of general population preference weights was derived from the data collected in the 11 valuation studies . The scores from this set of preference weights can be applied to generate a VAS-based weighted health status index for all the potential 243 EQ-5D health states for use in multi-national studies . To estimate the preference weights a multi-level regression analysis was performed on 82,910 valuations of 44 EQ-5D health states elicited from 6,870 respondents . Stable and plausible solutions were found for the model parameters . The R2 value was 75 % . The analysis showed that the major source of variance , apart from ' r and om error ' , was variance between individuals ( 28.3 % of the total residual variance ) . These results suggest that VAS values for EQ-5D health states in six Western European countries can be described by a common model Stroke , as the leading cause of physical disability and cognitive impairment , has a very significant impact on patients ’ quality of life ( QoL ) . The objective of this study is to know the effect of citicoline treatment in Qol and cognitive performance in the long-term in patients with a first ischemic stroke . This is an open-label , r and omized , parallel study of citicoline vs. usual treatment . All subjects were selected 6 weeks after suffering a first ischemic stroke and r and omized into parallel arms . Neuropsychological evaluation was performed at 1 month , 6 months , 1 year and 2 years after stroke , and QoL was measured using the EuroQoL-5D question naire at 2 years . 163 patients were followed during 2 years . The mean age was 67.5 years-old , and 50.9 % were women . Age and absence of citicoline treatment were independent predictors of both utility and poor quality of life .  Patients with cognitive impairment  had a poorer QoL at 2 years ( 0.55 vs. 0.66 in utility , p = 0.015 ) . Citicoline treatment improved significantly cognitive status during follow-up ( p = 0.005 ) . In conclusion , treatment with long-term citicoline is associated with a better QoL and improves cognitive status 2 years after a first ischemic stroke Background —Atrial fibrillation ( AF ) can be a cause of previously diagnosed cryptogenic stroke . However , AF can be paroxysmal and asymptomatic , thereby making detection with routine ECG methods difficult . Oral anticoagulation is highly effective in reducing recurrent stroke in patients with AF , but its initiation is dependent on the detection of AF . Cryptogenic Stroke and Underlying Atrial Fibrillation ( CRYSTAL AF ) is the first r and omized study to report the detection of AF in cryptogenic stroke patients using continuous long-term monitoring via insertable cardiac monitors ( ICM ) . Methods and Results — Patients with prior cryptogenic stroke were r and omized to control ( n=220 ) or ICM ( n=221 ) and followed for �� 
    Output:
    