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 There is a marked lack of evidence on the optimal prevention of ischaemic stroke and other thromboembolic events in patients with non-valvular atrial fibrillation and a recent intracerebral haemorrhage during treatment with oral anticoagulation .  These patients are currently treated with oral anticoagulants , antiplatelet drugs , or no antithrombotic treatment , depending on personal and institutional preferences . Compared with warfarin , the direct oral anticoagulant apixaban reduces the risk of stroke or systemic embolism , intracranial haemorrhage , and case fatality in patients with atrial fibrillation . Compared with aspirin , apixaban reduces the risk of stroke or systemic embolism in patients with atrial fibrillation , and has a similar risk of intracerebral haemorrhage . Novel oral anticoagulants have not been evaluated in patients with atrial fibrillation and a recent intracerebral haemorrhage . To inform a phase III trial , the phase II Apixaban versus Antiplatelet drugs or no antithrombotic drugs after anticoagulation-associated intraCerebral HaEmorrhage in patients with Atrial Fibrillation ( APACHE-AF ) trial aims to obtain estimates of the rates of vascular death or non-fatal stroke in patients with atrial fibrillation and a recent anticoagulation-associated intracerebral haemorrhage treated with apixaban and in those in whom oral anticoagulation is avoided . Methods / Design APACHE-AF is a phase II , multicentre , open-label , parallel-group , r and omised clinical trial with masked outcome assessment . One hundred adults with a history of atrial fibrillation and a recent intracerebral haemorrhage during treatment with anticoagulation in whom clinical equipoise exists on the optimal stroke prevention strategy will be enrolled in 14 hospitals in The Netherl and s . These patients will be r and omly assigned in a 1:1 ratio to either apixaban or to avoiding oral anticoagulation . Patients in the control group may be treated with antiplatelet drugs at the discretion of the treating physician . The primary outcome is the composite of vascular death or non-fatal stroke during follow-up . We aim to include 100 patients in 2.5 years . All patients will be followed-up for the duration of the study , but at least for 1 year . Recruitment commenced in September 2014 and is ongoing . This trial is funded by the Dutch Heart Foundation ( 2012 T077 ) and ZonMW (015008048).Trial registration NTR4526 ( 16 April 2014 ) BACKGROUND Percutaneous left atrial appendage closure ( LAAC ) may be considered in patients with atrial fibrillation and contraindication for long-term anticoagulation . This study aim ed to assess the safety and efficacy of LAAC followed by single antiplatelet therapy in patients with atrial fibrillation and previous spontaneous intracerebral hemorrhage ( ICH ) . METHODS In this explorative , prospect i ve , single-center study , consecutive patients who underwent LAAC because of previous spontaneous ICH over a period of 4 years were analyzed . Risks of ischemic strokes and hemorrhagic complications were estimated using the CHA2DS2-VASc and HAS-BLED scores , respectively . Single antiplatelet therapy was given for at least 6 months post implantation . Clinical follow-up included cardiological evaluations at 1 , 3 , 6 , and 12 months , and neurological evaluations at 3 and 12 months . RESULTS A total of 46 patients  underwent LAAC with a mean follow-up of 12 ± 7 months . The observed annual rate of ischemic stroke was 4.35 % compared with an expected rate of 7.23 % according to the mean risk of the population based on CHA2DS2-VASc score , which translated into a 40 % risk reduction . The observed annual rate of major bleeding was 4.35 % compared with an expected rate of 8.05 % according to the mean risk of the population based on HAS-BLED score , which translated into a 46 % risk reduction . CONCLUSIONS LAAC followed by single antiplatelet therapy is feasible as an alternative to oral anticoagulation in high-risk patients with previous ICH , with an acceptable periprocedural risk . Longer follow-up in a larger number of patients will be needed to establish the effectiveness of LAAC relative to direct oral anticoagulants Background : For patients who survive intracerebral haemorrhage ( ICH ) during treatment with oral anticoagulation ( OAC )  , the balance between the benefits and risks of restarting OAC is unclear . The decision to restart OAC or to start antiplatelet therapy in these patients therefore poses a dilemma for all physicians involved . We assessed the long-term outcome of patients who did or did not restart antithrombotic therapy after OAC-associated ICH . Methods : We conducted a retrospective follow-up study of all patients discharged from our institution after OAC-associated ICH over a 10-year period . Data on the use of OAC or platelet inhibitors and the occurrence of vascular events during follow-up were assessed through question naires and patient files . The primary outcome was recurrent fatal or non-fatal stroke . Secondary outcomes were the occurrence of other haemorrhagic , thrombotic or thromboembolic events . With patients without antithrombotic treatment as reference , we calculated incidence ratios with corresponding 95 % confidence intervals ( CI ) for treatment with OAC and for treatment with antiplatelet therapy . Results : We included 38 patients , of whom 21 ( 55 % ) died during a mean follow-up of 3.5 years . The medication regime changed frequently during follow-up , illustrated by the fact that two thirds of the patients who had resumed OAC within 2 months of ICH terminated this at later points in time . Two recurrent strokes occurred during 35.4 patient-years without antithrombotic medication , 7 during 63.8 patient-years on antiplatelet medication ( incidence ratio 1.9 ; 95 % CI , 0.4 - 9.4 ) , and 3 during 19.5 patient-years on OAC ( incidence ratio 2.7 ; 95 % CI , 0.5 - 16.3 ) . There was only 1 recurrent ICH , which occurred during treatment with OAC . Conclusion : In this observational study , no significant difference in the primary outcome measure was found between the treatment groups , but there was a tendency towards a higher long-term risk of any stroke in patients who resumed OAC or started antiplatelet therapy . However , based on these results it is difficult to draw any concrete conclusions or make any strong recommendations . A r and omized trial to assess the optimal long-term strategy after OAC-related ICH is warranted . Based on the point estimates of our study , such a trial should involve at least 300 patient-years of follow-up BACKGROUND While warfarin-related intracranial hemorrhage ( ICH ) occurs in 0.25%-1.1 % patients per year , little is known about the practice and outcomes of anticoagulant reinitiation . METHODS We studied a cohort of consecutive patients with warfarin-related ICH ( intracerebral or subarachnoid ) admitted to 13 stroke centres in the Registry of the Canadian Stroke Network between July 2003 and March 2008 . We examined patterns of warfarin reinitiation and variables associated with 30-day and 1-year outcomes . RESULTS Among the 284 patients studied ( mean age 74 ± 12 years ) , warfarin was restarted in-hospital in 91 patients ( 32 % ) . Factors associated with restarting warfarin were lower stroke severity ( adjusted odds ratio [ aOR ] 2.07 , 95 % confidence interval [ CI ] ; 1.20 - 3.57 , P = 0.009 ) or presence of valve prosthesis ( aOR 3.07 , 95 % CI ; 1.29 - 7.27 , P = 0.011 ) . Mortality rates were not higher in those who restarted warfarin in-hospital : 31.9 % vs 54.4 % ( 30-day , P < 0.001 ) and 48 % vs 61 % ( 1-year , P = 0.04 ) , and bleeding was not increased . Multivariable predictors of mortality included initial international normalized ratio > 3.0 ( aOR , 3.28 [ 30-day , P < 0.001 ] and 3.32 [ 1-year , P = 0.003 ] ) , greater stroke severity ( aOR , 6.04 [ 30-day ] and 4.22 [ 1-year ] ; both P < 0.001 ) , and intraventricular hemorrhage ( aOR , 2.19 [ 30-day ; P = 0.03 ] and 2.04 [ 1-year ; P = 0.04 ] ) . In selected patients who reinitiated warfarin , there was no increase in 30-day ( aOR , 0.49 ; P = 0.03 ) or 1-year mortality ( aOR , 0.79 ; P = 0.43 ) . CONCLUSIONS In selected patients at high thrombosis risk , reinitiation of warfarin after ICH did not confer increased mortality or bleeding events BACKGROUND Warfarin sodium is highly effective for prevention of embolic stroke , particularly in nonvalvular atrial fibrillation , but its expected benefit can be offset by risk of intracerebral hemorrhage ( ICH ) . We studied the determinants of ICH outcome to quantify the independent effect of warfarin . METHODS Consecutive patients with supratentorial ICH treated in a tertiary care hospital with a neurointensive care unit were prospect ively identified during a 7-year period , and data on hemorrhage location , clinical characteristics , and warfarin use were collected . Independent predictors of 3-month mortality were determined using multiple logistic regression analysis . RESULTS Of 435 consecutive patients aged 55 years or older , 102 ( 23.4 % ) were taking warfarin at the time of ICH .  Three-month mortality was 25.8 % for those not taking warfarin and 52.0 % for those taking warfarin . Independent predictors of death were warfarin use ( odds ratio [ OR ] , 2.2 ; 95 % confidence interval [ CI ] , 1.3 - 3.8 ) , age 70 years or older ( OR , 2.4 ; 95 % CI , 1.4 - 4.0 ) , and presence of diabetes mellitus ( OR , 1.8 ; 95 % CI , 1.0 - 3.3 ) . Although 68.0 % of all warfarin-related hemorrhages occurred at an international normalized ratio ( INR ) of 3.0 or less , increasing degrees of anticoagulation were strongly associated with increasing risk of death compared with no warfarin use . CONCLUSIONS Patients taking warfarin  had a doubling in the rate of intracerebral hemorrhage mortality in a dose-dependent manner . The data suggest that careful control of the INR , already known to limit the risk of warfarin-related ICH , may also limit its severity OBJECTIVES The purpose of this study was to assess the safety and efficacy of left atrial appendage ( LAA ) closure in nonvalvular atrial fibrillation ( AF ) patients ineligible for warfarin therapy . BACKGROUND The PROTECT AF ( Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation ) trial demonstrated that LAA closure with the Watchman device ( Boston Scientific , Natick , Massachusetts ) was noninferior to warfarin therapy . However , the PROTECT AF trial only included patients who were c and i date s for warfarin , and even patients r and omly assigned to the LAA closure arm received concomitant warfarin  for 6 weeks after Watchman implantation . METHODS A multicenter , prospect i ve , nonr and omized study was conducted of LAA closure with the Watchman device in 150 patients with nonvalvular AF and CHADS₂ ( congestive heart failure , hypertension , age ≥75 years , diabetes mellitus , and prior stroke or transient ischemic attack ) score ≥1 , who were considered ineligible for warfarin . The primary efficacy endpoint was the combined events of ischemic stroke , hemorrhagic stroke , systemic embolism , and cardiovascular/unexplained death . RESULTS The mean CHADS₂ score and CHA₂DS₂-VASc ( CHADS₂ score plus 2 points for age ≥75 years and 1 point for vascular disease , age 65 to 74 years , or female sex ) score were 2.8 ± 1.2 and 4.4 ± 1.7 , respectively . History of hemorrhagic/bleeding tendencies ( 93 % ) was the most common reason for warfarin in eligibility . Mean duration of follow-up was 14.4 ± 8.6 months . Serious procedure- or device-related safety events occurred in 8.7 % of patients ( 13 of 150 patients ) . All-cause stroke or systemic embolism occurred in 4 patients ( 2.3 % per year ) : ischemic stroke in 3 patients ( 1.7 % per year ) and hemorrhagic stroke in 1 patient ( 0.6 % per year ) . This ischemic stroke rate was less than that expected ( 7.3 % per year ) based on the CHADS₂ scores of the patient cohort . CONCLUSIONS LAA closure with the Watchman device can be safely performed without a war 
    Output:
    
agent
In addition , 19 letters to the editor/ review s/editorials/experts ' surveys/experts ' opinion were used for discussion purpose s. Conclusions NVAF is highly prevalent among ICH survivors .
The risks of IS , recurrent ICH , and mortality are heightened in this group .
Most published data show a net benefit in terms of IS prevention and mortality when anticoagulation is restarted .
***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 There is a marked lack of evidence on the optimal prevention of ischaemic stroke and other thromboembolic events in patients with non-valvular atrial fibrillation and a recent intracerebral haemorrhage during treatment with oral anticoagulation .  These patients are currently treated with oral anticoagulants , antiplatelet drugs , or no antithrombotic treatment , depending on personal and institutional preferences . Compared with warfarin , the direct oral anticoagulant apixaban reduces the risk of stroke or systemic embolism , intracranial haemorrhage , and case fatality in patients with atrial fibrillation . Compared with aspirin , apixaban reduces the risk of stroke or systemic embolism in patients with atrial fibrillation , and has a similar risk of intracerebral haemorrhage . Novel oral anticoagulants have not been evaluated in patients with atrial fibrillation and a recent intracerebral haemorrhage . To inform a phase III trial , the phase II Apixaban versus Antiplatelet drugs or no antithrombotic drugs after anticoagulation-associated intraCerebral HaEmorrhage in patients with Atrial Fibrillation ( APACHE-AF ) trial aims to obtain estimates of the rates of vascular death or non-fatal stroke in patients with atrial fibrillation and a recent anticoagulation-associated intracerebral haemorrhage treated with apixaban and in those in whom oral anticoagulation is avoided . Methods / Design APACHE-AF is a phase II , multicentre , open-label , parallel-group , r and omised clinical trial with masked outcome assessment . One hundred adults with a history of atrial fibrillation and a recent intracerebral haemorrhage during treatment with anticoagulation in whom clinical equipoise exists on the optimal stroke prevention strategy will be enrolled in 14 hospitals in The Netherl and s . These patients will be r and omly assigned in a 1:1 ratio to either apixaban or to avoiding oral anticoagulation . Patients in the control group may be treated with antiplatelet drugs at the discretion of the treating physician . The primary outcome is the composite of vascular death or non-fatal stroke during follow-up . We aim to include 100 patients in 2.5 years . All patients will be followed-up for the duration of the study , but at least for 1 year . Recruitment commenced in September 2014 and is ongoing . This trial is funded by the Dutch Heart Foundation ( 2012 T077 ) and ZonMW (015008048).Trial registration NTR4526 ( 16 April 2014 ) BACKGROUND Percutaneous left atrial appendage closure ( LAAC ) may be considered in patients with atrial fibrillation and contraindication for long-term anticoagulation . This study aim ed to assess the safety and efficacy of LAAC followed by single antiplatelet therapy in patients with atrial fibrillation and previous spontaneous intracerebral hemorrhage ( ICH ) . METHODS In this explorative , prospect i ve , single-center study , consecutive patients who underwent LAAC because of previous spontaneous ICH over a period of 4 years were analyzed . Risks of ischemic strokes and hemorrhagic complications were estimated using the CHA2DS2-VASc and HAS-BLED scores , respectively . Single antiplatelet therapy was given for at least 6 months post implantation . Clinical follow-up included cardiological evaluations at 1 , 3 , 6 , and 12 months , and neurological evaluations at 3 and 12 months . RESULTS A total of 46 patients  underwent LAAC with a mean follow-up of 12 ± 7 months . The observed annual rate of ischemic stroke was 4.35 % compared with an expected rate of 7.23 % according to the mean risk of the population based on CHA2DS2-VASc score , which translated into a 40 % risk reduction . The observed annual rate of major bleeding was 4.35 % compared with an expected rate of 8.05 % according to the mean risk of the population based on HAS-BLED score , which translated into a 46 % risk reduction . CONCLUSIONS LAAC followed by single antiplatelet therapy is feasible as an alternative to oral anticoagulation in high-risk patients with previous ICH , with an acceptable periprocedural risk . Longer follow-up in a larger number of patients will be needed to establish the effectiveness of LAAC relative to direct oral anticoagulants Background : For patients who survive intracerebral haemorrhage ( ICH ) during treatment with oral anticoagulation ( OAC )  , the balance between the benefits and risks of restarting OAC is unclear . The decision to restart OAC or to start antiplatelet therapy in these patients therefore poses a dilemma for all physicians involved . We assessed the long-term outcome of patients who did or did not restart antithrombotic therapy after OAC-associated ICH . Methods : We conducted a retrospective follow-up study of all patients discharged from our institution after OAC-associated ICH over a 10-year period . Data on the use of OAC or platelet inhibitors and the occurrence of vascular events during follow-up were assessed through question naires and patient files . The primary outcome was recurrent fatal or non-fatal stroke . Secondary outcomes were the occurrence of other haemorrhagic , thrombotic or thromboembolic events . With patients without antithrombotic treatment as reference , we calculated incidence ratios with corresponding 95 % confidence intervals ( CI ) for treatment with OAC and for treatment with antiplatelet therapy . Results : We included 38 patients , of whom 21 ( 55 % ) died during a mean follow-up of 3.5 years . The medication regime changed frequently during follow-up , illustrated by the fact that two thirds of the patients who had resumed OAC within 2 months of ICH terminated this at later points in time . Two recurrent strokes occurred during 35.4 patient-years without antithrombotic medication , 7 during 63.8 patient-years on antiplatelet medication ( incidence ratio 1.9 ; 95 % CI , 0.4 - 9.4 ) , and 3 during 19.5 patient-years on OAC ( incidence ratio 2.7 ; 95 % CI , 0.5 - 16.3 ) . There was only 1 recurrent ICH , which occurred during treatment with OAC . Conclusion : In this observational study , no significant difference in the primary outcome measure was found between the treatment groups , but there was a tendency towards a higher long-term risk of any stroke in patients who resumed OAC or started antiplatelet therapy . However , based on these results it is difficult to draw any concrete conclusions or make any strong recommendations . A r and omized trial to assess the optimal long-term strategy after OAC-related ICH is warranted . Based on the point estimates of our study , such a trial should involve at least 300 patient-years of follow-up BACKGROUND While warfarin-related intracranial hemorrhage ( ICH ) occurs in 0.25%-1.1 % patients per year , little is known about the practice and outcomes of anticoagulant reinitiation . METHODS We studied a cohort of consecutive patients with warfarin-related ICH ( intracerebral or subarachnoid ) admitted to 13 stroke centres in the Registry of the Canadian Stroke Network between July 2003 and March 2008 . We examined patterns of warfarin reinitiation and variables associated with 30-day and 1-year outcomes . RESULTS Among the 284 patients studied ( mean age 74 ± 12 years ) , warfarin was restarted in-hospital in 91 patients ( 32 % ) . Factors associated with restarting warfarin were lower stroke severity ( adjusted odds ratio [ aOR ] 2.07 , 95 % confidence interval [ CI ] ; 1.20 - 3.57 , P = 0.009 ) or presence of valve prosthesis ( aOR 3.07 , 95 % CI ; 1.29 - 7.27 , P = 0.011 ) . Mortality rates were not higher in those who restarted warfarin in-hospital : 31.9 % vs 54.4 % ( 30-day , P < 0.001 ) and 48 % vs 61 % ( 1-year , P = 0.04 ) , and bleeding was not increased . Multivariable predictors of mortality included initial international normalized ratio > 3.0 ( aOR , 3.28 [ 30-day , P < 0.001 ] and 3.32 [ 1-year , P = 0.003 ] ) , greater stroke severity ( aOR , 6.04 [ 30-day ] and 4.22 [ 1-year ] ; both P < 0.001 ) , and intraventricular hemorrhage ( aOR , 2.19 [ 30-day ; P = 0.03 ] and 2.04 [ 1-year ; P = 0.04 ] ) . In selected patients who reinitiated warfarin , there was no increase in 30-day ( aOR , 0.49 ; P = 0.03 ) or 1-year mortality ( aOR , 0.79 ; P = 0.43 ) . CONCLUSIONS In selected patients at high thrombosis risk , reinitiation of warfarin after ICH did not confer increased mortality or bleeding events BACKGROUND Warfarin sodium is highly effective for prevention of embolic stroke , particularly in nonvalvular atrial fibrillation , but its expected benefit can be offset by risk of intracerebral hemorrhage ( ICH ) . We studied the determinants of ICH outcome to quantify the independent effect of warfarin . METHODS Consecutive patients with supratentorial ICH treated in a tertiary care hospital with a neurointensive care unit were prospect ively identified during a 7-year period , and data on hemorrhage location , clinical characteristics , and warfarin use were collected . Independent predictors of 3-month mortality were determined using multiple logistic regression analysis . RESULTS Of 435 consecutive patients aged 55 years or older , 102 ( 23.4 % ) were taking warfarin at the time of ICH .  Three-month mortality was 25.8 % for those not taking warfarin and 52.0 % for those taking warfarin . Independent predictors of death were warfarin use ( odds ratio [ OR ] , 2.2 ; 95 % confidence interval [ CI ] , 1.3 - 3.8 ) , age 70 years or older ( OR , 2.4 ; 95 % CI , 1.4 - 4.0 ) , and presence of diabetes mellitus ( OR , 1.8 ; 95 % CI , 1.0 - 3.3 ) . Although 68.0 % of all warfarin-related hemorrhages occurred at an international normalized ratio ( INR ) of 3.0 or less , increasing degrees of anticoagulation were strongly associated with increasing risk of death compared with no warfarin use . CONCLUSIONS Patients taking warfarin  had a doubling in the rate of intracerebral hemorrhage mortality in a dose-dependent manner . The data suggest that careful control of the INR , already known to limit the risk of warfarin-related ICH , may also limit its severity OBJECTIVES The purpose of this study was to assess the safety and efficacy of left atrial appendage ( LAA ) closure in nonvalvular atrial fibrillation ( AF ) patients ineligible for warfarin therapy . BACKGROUND The PROTECT AF ( Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation ) trial demonstrated that LAA closure with the Watchman device ( Boston Scientific , Natick , Massachusetts ) was noninferior to warfarin therapy . However , the PROTECT AF trial only included patients who were c and i date s for warfarin , and even patients r and omly assigned to the LAA closure arm received concomitant warfarin  for 6 weeks after Watchman implantation . METHODS A multicenter , prospect i ve , nonr and omized study was conducted of LAA closure with the Watchman device in 150 patients with nonvalvular AF and CHADS₂ ( congestive heart failure , hypertension , age ≥75 years , diabetes mellitus , and prior stroke or transient ischemic attack ) score ≥1 , who were considered ineligible for warfarin . The primary efficacy endpoint was the combined events of ischemic stroke , hemorrhagic stroke , systemic embolism , and cardiovascular/unexplained death . RESULTS The mean CHADS₂ score and CHA₂DS₂-VASc ( CHADS₂ score plus 2 points for age ≥75 years and 1 point for vascular disease , age 65 to 74 years , or female sex ) score were 2.8 ± 1.2 and 4.4 ± 1.7 , respectively . History of hemorrhagic/bleeding tendencies ( 93 % ) was the most common reason for warfarin in eligibility . Mean duration of follow-up was 14.4 ± 8.6 months . Serious procedure- or device-related safety events occurred in 8.7 % of patients ( 13 of 150 patients ) . All-cause stroke or systemic embolism occurred in 4 patients ( 2.3 % per year ) : ischemic stroke in 3 patients ( 1.7 % per year ) and hemorrhagic stroke in 1 patient ( 0.6 % per year ) . This ischemic stroke rate was less than that expected ( 7.3 % per year ) based on the CHADS₂ scores of the patient cohort . CONCLUSIONS LAA closure with the Watchman device can be safely performed without a war 
    Output:
    