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 — Current American and European guidelines emphasize the importance of rate-control treatments in treating atrial fibrillation with a Class I recommendation , although data on the survival benefits of rate control are lacking . The goal of the present study was to investigate whether patients receiving rate-control drugs  had a better prognosis compared with those without rate-control treatment . Methods and Results — This study used the National Health Insurance Research Data base in Taiwan . There were 43 879 , 18 466 , and 38 898 patients with atrial fibrillation enrolled in the groups receiving & bgr;-blockers , calcium channel blockers , and digoxin  , respectively . The reference group consisted of 168 678 subjects who did not receive any rate-control drug .  The clinical end point was all-cause mortality . During a follow-up of 4.9±3.7 years , mortality occurred in 88 263 patients ( 32.7 % ) . After adjustment for baseline differences , the risk of mortality was lower in patients receiving & bgr;-blockers ( adjusted hazard ratio=0.76 ; 95 % confidence interval=0.74–0.78 ) and calcium channel blockers ( adjusted hazard ratio=0.93 ; 95 % confidence interval=0.90–0.96 ) compared with those who did not receive rate-control medications . On the contrary , the digoxin group had a higher risk of mortality with an adjusted hazard ratio of 1.12 ( 95 % confidence interval=1.10–1.14 ) . The results were observed consistently in subgroup analyses and among the cohorts after propensity matching . Conclusions — In this nationwide atrial fibrillation cohort  , the risk of mortality was lower for patients  receiving rate-control treatment with & bgr;-blockers or calcium channel blockers , and the use of & bgr;-blockers was associated with the largest risk reduction . Digoxin use was associated with greater mortality . Prospect i ve , r and omized trials are necessary to confirm these findings Objectives To assess whether screening improves the detection of atrial fibrillation  ( cluster r and omisation ) and to compare systematic and opportunistic screening . Design Multicentred cluster r and omised controlled trial , with subsidiary trial embedded within the intervention arm . Setting 50 primary care centres in Engl and , with further individual r and omisation of patients in the intervention practice s. Participants 14 802 patients aged 65 or over in 25 intervention and 25 control practice s. Interventions Patients in intervention practice s were r and omly allocated to systematic screening ( invitation for electrocardiography ) or opportunistic screening ( pulse taking and invitation for electrocardiography if the pulse was irregular ) . Screening took place over 12 months in each practice from October 2001 to February 2003 . No active screening took place in control practice s. Main outcome measure Newly identified atrial fibrillation . Results The detection rate of new cases of atrial fibrillation was 1.63 % a year in the intervention practice s and 1.04 % in control practice s ( difference 0.59 % , 95 % confidence interval 0.20 % to 0.98 % ) . Systematic and opportunistic screening detected similar numbers of new cases ( 1.62 % v 1.64 % , difference 0.02 % , −0.5 % to 0.5 % ) . Conclusion Active screening for atrial fibrillation detects additional cases over current practice . The preferred method of screening in patients aged 65 or over in primary care is opportunistic pulse taking with follow-up electrocardiography . Trial registration Current Controlled Trials IS RCT N19633732 BACKGROUND The Atrial Fibrillation Follow-up Investigation of Rhythm Management trial showed that digoxin was associated with increased mortality in patients with atrial fibrillation . OBJECTIVES To assess the association of digoxin with cardiovascular ( CV ) morbidity and mortality in patients with permanent atrial fibrillation enrolled in the Dutch Rate Control Efficacy in Permanent AF : A Comparison Between Lenient Versus Strict Rate Control II trial as well as to assess the role of digoxin to achieve heart rate targets . METHODS The primary outcome was a composite of CV morbidity and mortality . Secondary outcomes included CV hospitalization and all-cause mortality or heart failure ( HF ) hospitalization . Of the 614 patients , 608 ( 99 % ) completed the dose-adjustment phase . Outcome events were analyzed from the end of the dose-adjustment phase until the end of follow-up . The median follow-up period was 2.9 years ( interquartile range 2.7 - 3.0 years ) . RESULTS In total , 284 patients ( 46.7 % ) used digoxin after the dose-adjustment phase ( median dosage 0.250 mg ; interquartile range 0.0625 - 0.750 mg ) . These patients were more often women , previously admitted for HF , had an increased left ventricular end-systolic diameter , and more often r and omized to strict rate control . By using Cox proportional hazards regression analysis , the use of digoxin was not associated with an increased risk for the primary and secondary outcomes . For the primary outcome , the 3-year estimated cumulative incidence was 12.9 % vs 13.4 % in the digoxin group vs the no-digoxin group ( unadjusted hazard ratio [ HR ] 0.97 ; 95 % confidence interval [ CI ] 0.62 - 1.52 ) . Incidence was 19.4 % vs. 19.5 % for CV hospitalization ( unadjusted HR 1.00 ; 95 % CI 0.69 - 1.45 ) and 6.6 % vs. 9.9 % for all-cause mortality or HF hospitalization ( unadjusted HR 0.62 ; 95 % CI 0.34 - 1.13 ) in the digoxin group vs the no-digoxin group . CONCLUSION The use of digoxin was not associated with increased morbidity and mortality BACKGROUND Few epidemiologic cohort studies have evaluated atrial flutter ( flutter ) as an arrhythmia distinct from atrial fibrillation ( AF ) . OBJECTIVE The purpose of this study was to examine the clinical correlates of flutter and its associated outcomes to distinguish them from those associated with AF in the Framingham Heart Study . METHODS We review ed  and adjudicated electrocardiograms ( ECGs ) previously classified as flutter or AF/flutter and another 100 ECGs r and omly selected from AF cases . We examined the clinical correlates of flutter by matching up to 5 AF and 5 referents to each flutter case using a nested case referent design . We determined the 10-year outcomes associated with flutter with Cox models . RESULTS During mean follow-up of 33.0 ± 12.2 years , 112 participants ( mean age 72 ± 10 years , 30 % women ) developed flutter . In multivariable analyses , smoking ( odds ratio [ OR ] 2.84 , 95 % confidence interval [ CI ] 1.54 - 5.23 ) , increased PR interval ( OR 1.28 per SD , 95 % CI 1.03 - 1.60 ) , myocardial infa rct ion ( OR 2.25 , 95 % CI 1.05 - 4.80 ) and heart failure ( OR 5.22 , 95 % CI 1.26 - 21.64 ) were associated with incident flutter . In age- and sex-adjusted models , flutter ( vs referents ) was associated with 10-year increased risk of AF ( hazard ratio [ HR ] 5.01 , 95 % CI 3.14 - 7.99 ) , myocardial infa rct ion ( HR 3.05 , 95 % CI 1.42 - 6.59 ) , heart failure ( HR 4.14 , 95 % CI 1.90 - 8.99 ) , stroke ( HR 2.17 , 95 % CI 1.13 - 4.17 ) , and mortality ( HR 2.00 , 95 % CI 1.44 - 2.79 ) . CONCLUSION We identified the clinical correlates associated with flutter and observed that flutter was associated with multiple adverse outcomes BACKGROUND Atrial fibrillation is an important cause of morbidity and mortality worldwide , but scant data are available for long-term outcomes in individuals outside North America or Europe , especially in primary care setting s. METHODS We did a cohort study using a prospect i ve registry of patients in 47 countries who presented to a hospital emergency department with atrial fibrillation or atrial flutter as a primary or secondary diagnosis . 15 400 individuals were enrolled to determine the occurrence of death and strokes ( the primary outcomes ) in this cohort over eight geographical regions ( North America , western Europe , and Australia ; South America ; eastern Europe ; the Middle East and Mediterranean crescent ; sub-Saharan Africa ; India ; China ; and southeast Asia ) 1 year after attending the emergency department . Patients from North America , western Europe , and Australia were used as the reference population , and compared with patients from the other seven regions FINDINGS Between Dec 24 , 2007 , and Oct 21 , 2011 , we enrolled 15 400 individuals to the registry . Follow-up was complete for 15 361 ( 99·7 % ) , of whom 1758 ( 11 % ) died within 1 year . Fewer deaths occurred among patients presenting to the emergency department with a primary diagnosis of atrial fibrillation compared with patients who had atrial fibrillation as a secondary diagnosis ( 377 [ 6 % ] of 6825 patients vs 1381 [ 16 % ] of 8536 , p<0·0001 ) . Twice as many patients had died by 1 year in South America ( 192 [ 17 % ] of 1132 ) and Africa ( 225 [ 20 % ] of 1137 ) compared with North America , western Europe , and Australia ( 366 [ 10 % ] of 3800 , p<0·0001 ) . Heart failure was the most common cause of death ( 519 [ 30 % ] of 1758 ) ; stroke caused 148 ( 8 % ) deaths . 604 ( 4 % ) of 15361 patients had had a stroke by 1 year ; 170 ( 3 % ) of 6825 for whom atrial fibrillation was a primary diagnosis and 434 ( 5 % ) of 8536 for whom it was a secondary diagnosis ( p<0·0001 ) . The highest number of strokes occurred in patients in Africa ( 89 [ 8 % ] of 1137 ) , China ( 143 [ 7 % ] of 2023 ) , and southeast Asia ( 88 [ 7 % ] of 1331 ) and the lowest occurred in India ( 20 [ < 1 % ] of 2536 ) . 94 ( 3 % ) of 3800 patients in North America , western Europe , and Australia had a stroke . INTERPRETATION Marked unexplained inter-regional variations in the occurrence of stroke and mortality suggest that factors other than clinical variables might be important . Prevention of death from heart failure should be a major priority in the treatment of atrial fibrillation . FUNDING Boehringer Ingelheim OBJECTIVE Recommendations for optimal first-shock energies with biphasic waveforms are conflicting . We evaluated prospect ively the relation between type and duration of atrial tachyarrhythmias and the probability of successful cardioversion with a specific biphasic shock waveform to develop recommendations for the initial energy setting aim ing at the lowest total cumulative energy with 2 or less consecutive shocks . METHODS We analyzed 453 consecutive patients undergoing their first transthoracic electrical cardioversion , including 358 attempts for atrial fibrillation ( AF ) and 95 attempts for atrial flutter ( AFL ) or atrial tachycardia ( AT ) . A step-up protocol with a truncated exponential biphasic waveform starting at 50 J was used . Total cumulative energies were estimated under the assumption of a 2-tiered escalating shock protocol with different initial energy setting s and a " rescue shock " of 250 J for AFL/AT or 360 J for AF . The initial energy setting leading to the lowest total cumulative energy was regarded as the optimal first-shock level . RESULTS Cardioversion was successful in 448 patients ( cumulative efficacy , 99 % ) . In patients with AFL/AT , the lowest total cumulative energy was attained with an initial energy setting of 50 J. In patients with AF , lowest values were achieved with an initial energy of 100 J for arrhythmia duration s of 2 days or less and an initial energy of 150 J for arrhythmia duration s of more than 2 days . CONCLUSION We recommend an initial energy setting of 50 J in patients with AFL/AT , of 100 J in patients with AF 2 days or less , and of 150 J with AF more than 2 days Background Clinical evidence continues to exp and and is increasingly difficult to overview . We aim ed at conceptualizing a visual assessment tool , i.e. , a matrix for overviewing studies and their data in order to assess the clinical evidence at a glance . Methods A four-step matrix was constructed using the three dimensions of systematic error , r and om error , and design error . Matrix step I ranks the identified studies according to the dimensions of systematic errors and r and om errors . Matrix step II orders the studies according to the design errors . Matrix step III assesses the three dimensions of errors in studies 
    Output:
    
agent
Discussion The results of this systematic review have the potential to benefit thous and s of patients worldwide as well as healthcare systems and healthcare economy .
***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 — Current American and European guidelines emphasize the importance of rate-control treatments in treating atrial fibrillation with a Class I recommendation , although data on the survival benefits of rate control are lacking . The goal of the present study was to investigate whether patients receiving rate-control drugs  had a better prognosis compared with those without rate-control treatment . Methods and Results — This study used the National Health Insurance Research Data base in Taiwan . There were 43 879 , 18 466 , and 38 898 patients with atrial fibrillation enrolled in the groups receiving & bgr;-blockers , calcium channel blockers , and digoxin  , respectively . The reference group consisted of 168 678 subjects who did not receive any rate-control drug .  The clinical end point was all-cause mortality . During a follow-up of 4.9±3.7 years , mortality occurred in 88 263 patients ( 32.7 % ) . After adjustment for baseline differences , the risk of mortality was lower in patients receiving & bgr;-blockers ( adjusted hazard ratio=0.76 ; 95 % confidence interval=0.74–0.78 ) and calcium channel blockers ( adjusted hazard ratio=0.93 ; 95 % confidence interval=0.90–0.96 ) compared with those who did not receive rate-control medications . On the contrary , the digoxin group had a higher risk of mortality with an adjusted hazard ratio of 1.12 ( 95 % confidence interval=1.10–1.14 ) . The results were observed consistently in subgroup analyses and among the cohorts after propensity matching . Conclusions — In this nationwide atrial fibrillation cohort  , the risk of mortality was lower for patients  receiving rate-control treatment with & bgr;-blockers or calcium channel blockers , and the use of & bgr;-blockers was associated with the largest risk reduction . Digoxin use was associated with greater mortality . Prospect i ve , r and omized trials are necessary to confirm these findings Objectives To assess whether screening improves the detection of atrial fibrillation  ( cluster r and omisation ) and to compare systematic and opportunistic screening . Design Multicentred cluster r and omised controlled trial , with subsidiary trial embedded within the intervention arm . Setting 50 primary care centres in Engl and , with further individual r and omisation of patients in the intervention practice s. Participants 14 802 patients aged 65 or over in 25 intervention and 25 control practice s. Interventions Patients in intervention practice s were r and omly allocated to systematic screening ( invitation for electrocardiography ) or opportunistic screening ( pulse taking and invitation for electrocardiography if the pulse was irregular ) . Screening took place over 12 months in each practice from October 2001 to February 2003 . No active screening took place in control practice s. Main outcome measure Newly identified atrial fibrillation . Results The detection rate of new cases of atrial fibrillation was 1.63 % a year in the intervention practice s and 1.04 % in control practice s ( difference 0.59 % , 95 % confidence interval 0.20 % to 0.98 % ) . Systematic and opportunistic screening detected similar numbers of new cases ( 1.62 % v 1.64 % , difference 0.02 % , −0.5 % to 0.5 % ) . Conclusion Active screening for atrial fibrillation detects additional cases over current practice . The preferred method of screening in patients aged 65 or over in primary care is opportunistic pulse taking with follow-up electrocardiography . Trial registration Current Controlled Trials IS RCT N19633732 BACKGROUND The Atrial Fibrillation Follow-up Investigation of Rhythm Management trial showed that digoxin was associated with increased mortality in patients with atrial fibrillation . OBJECTIVES To assess the association of digoxin with cardiovascular ( CV ) morbidity and mortality in patients with permanent atrial fibrillation enrolled in the Dutch Rate Control Efficacy in Permanent AF : A Comparison Between Lenient Versus Strict Rate Control II trial as well as to assess the role of digoxin to achieve heart rate targets . METHODS The primary outcome was a composite of CV morbidity and mortality . Secondary outcomes included CV hospitalization and all-cause mortality or heart failure ( HF ) hospitalization . Of the 614 patients , 608 ( 99 % ) completed the dose-adjustment phase . Outcome events were analyzed from the end of the dose-adjustment phase until the end of follow-up . The median follow-up period was 2.9 years ( interquartile range 2.7 - 3.0 years ) . RESULTS In total , 284 patients ( 46.7 % ) used digoxin after the dose-adjustment phase ( median dosage 0.250 mg ; interquartile range 0.0625 - 0.750 mg ) . These patients were more often women , previously admitted for HF , had an increased left ventricular end-systolic diameter , and more often r and omized to strict rate control . By using Cox proportional hazards regression analysis , the use of digoxin was not associated with an increased risk for the primary and secondary outcomes . For the primary outcome , the 3-year estimated cumulative incidence was 12.9 % vs 13.4 % in the digoxin group vs the no-digoxin group ( unadjusted hazard ratio [ HR ] 0.97 ; 95 % confidence interval [ CI ] 0.62 - 1.52 ) . Incidence was 19.4 % vs. 19.5 % for CV hospitalization ( unadjusted HR 1.00 ; 95 % CI 0.69 - 1.45 ) and 6.6 % vs. 9.9 % for all-cause mortality or HF hospitalization ( unadjusted HR 0.62 ; 95 % CI 0.34 - 1.13 ) in the digoxin group vs the no-digoxin group . CONCLUSION The use of digoxin was not associated with increased morbidity and mortality BACKGROUND Few epidemiologic cohort studies have evaluated atrial flutter ( flutter ) as an arrhythmia distinct from atrial fibrillation ( AF ) . OBJECTIVE The purpose of this study was to examine the clinical correlates of flutter and its associated outcomes to distinguish them from those associated with AF in the Framingham Heart Study . METHODS We review ed  and adjudicated electrocardiograms ( ECGs ) previously classified as flutter or AF/flutter and another 100 ECGs r and omly selected from AF cases . We examined the clinical correlates of flutter by matching up to 5 AF and 5 referents to each flutter case using a nested case referent design . We determined the 10-year outcomes associated with flutter with Cox models . RESULTS During mean follow-up of 33.0 ± 12.2 years , 112 participants ( mean age 72 ± 10 years , 30 % women ) developed flutter . In multivariable analyses , smoking ( odds ratio [ OR ] 2.84 , 95 % confidence interval [ CI ] 1.54 - 5.23 ) , increased PR interval ( OR 1.28 per SD , 95 % CI 1.03 - 1.60 ) , myocardial infa rct ion ( OR 2.25 , 95 % CI 1.05 - 4.80 ) and heart failure ( OR 5.22 , 95 % CI 1.26 - 21.64 ) were associated with incident flutter . In age- and sex-adjusted models , flutter ( vs referents ) was associated with 10-year increased risk of AF ( hazard ratio [ HR ] 5.01 , 95 % CI 3.14 - 7.99 ) , myocardial infa rct ion ( HR 3.05 , 95 % CI 1.42 - 6.59 ) , heart failure ( HR 4.14 , 95 % CI 1.90 - 8.99 ) , stroke ( HR 2.17 , 95 % CI 1.13 - 4.17 ) , and mortality ( HR 2.00 , 95 % CI 1.44 - 2.79 ) . CONCLUSION We identified the clinical correlates associated with flutter and observed that flutter was associated with multiple adverse outcomes BACKGROUND Atrial fibrillation is an important cause of morbidity and mortality worldwide , but scant data are available for long-term outcomes in individuals outside North America or Europe , especially in primary care setting s. METHODS We did a cohort study using a prospect i ve registry of patients in 47 countries who presented to a hospital emergency department with atrial fibrillation or atrial flutter as a primary or secondary diagnosis . 15 400 individuals were enrolled to determine the occurrence of death and strokes ( the primary outcomes ) in this cohort over eight geographical regions ( North America , western Europe , and Australia ; South America ; eastern Europe ; the Middle East and Mediterranean crescent ; sub-Saharan Africa ; India ; China ; and southeast Asia ) 1 year after attending the emergency department . Patients from North America , western Europe , and Australia were used as the reference population , and compared with patients from the other seven regions FINDINGS Between Dec 24 , 2007 , and Oct 21 , 2011 , we enrolled 15 400 individuals to the registry . Follow-up was complete for 15 361 ( 99·7 % ) , of whom 1758 ( 11 % ) died within 1 year . Fewer deaths occurred among patients presenting to the emergency department with a primary diagnosis of atrial fibrillation compared with patients who had atrial fibrillation as a secondary diagnosis ( 377 [ 6 % ] of 6825 patients vs 1381 [ 16 % ] of 8536 , p<0·0001 ) . Twice as many patients had died by 1 year in South America ( 192 [ 17 % ] of 1132 ) and Africa ( 225 [ 20 % ] of 1137 ) compared with North America , western Europe , and Australia ( 366 [ 10 % ] of 3800 , p<0·0001 ) . Heart failure was the most common cause of death ( 519 [ 30 % ] of 1758 ) ; stroke caused 148 ( 8 % ) deaths . 604 ( 4 % ) of 15361 patients had had a stroke by 1 year ; 170 ( 3 % ) of 6825 for whom atrial fibrillation was a primary diagnosis and 434 ( 5 % ) of 8536 for whom it was a secondary diagnosis ( p<0·0001 ) . The highest number of strokes occurred in patients in Africa ( 89 [ 8 % ] of 1137 ) , China ( 143 [ 7 % ] of 2023 ) , and southeast Asia ( 88 [ 7 % ] of 1331 ) and the lowest occurred in India ( 20 [ < 1 % ] of 2536 ) . 94 ( 3 % ) of 3800 patients in North America , western Europe , and Australia had a stroke . INTERPRETATION Marked unexplained inter-regional variations in the occurrence of stroke and mortality suggest that factors other than clinical variables might be important . Prevention of death from heart failure should be a major priority in the treatment of atrial fibrillation . FUNDING Boehringer Ingelheim OBJECTIVE Recommendations for optimal first-shock energies with biphasic waveforms are conflicting . We evaluated prospect ively the relation between type and duration of atrial tachyarrhythmias and the probability of successful cardioversion with a specific biphasic shock waveform to develop recommendations for the initial energy setting aim ing at the lowest total cumulative energy with 2 or less consecutive shocks . METHODS We analyzed 453 consecutive patients undergoing their first transthoracic electrical cardioversion , including 358 attempts for atrial fibrillation ( AF ) and 95 attempts for atrial flutter ( AFL ) or atrial tachycardia ( AT ) . A step-up protocol with a truncated exponential biphasic waveform starting at 50 J was used . Total cumulative energies were estimated under the assumption of a 2-tiered escalating shock protocol with different initial energy setting s and a " rescue shock " of 250 J for AFL/AT or 360 J for AF . The initial energy setting leading to the lowest total cumulative energy was regarded as the optimal first-shock level . RESULTS Cardioversion was successful in 448 patients ( cumulative efficacy , 99 % ) . In patients with AFL/AT , the lowest total cumulative energy was attained with an initial energy setting of 50 J. In patients with AF , lowest values were achieved with an initial energy of 100 J for arrhythmia duration s of 2 days or less and an initial energy of 150 J for arrhythmia duration s of more than 2 days . CONCLUSION We recommend an initial energy setting of 50 J in patients with AFL/AT , of 100 J in patients with AF 2 days or less , and of 150 J with AF more than 2 days Background Clinical evidence continues to exp and and is increasingly difficult to overview . We aim ed at conceptualizing a visual assessment tool , i.e. , a matrix for overviewing studies and their data in order to assess the clinical evidence at a glance . Methods A four-step matrix was constructed using the three dimensions of systematic error , r and om error , and design error . Matrix step I ranks the identified studies according to the dimensions of systematic errors and r and om errors . Matrix step II orders the studies according to the design errors . Matrix step III assesses the three dimensions of errors in studies 
    Output:
    