***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 Therapeutic decisions in atrial fibrillation ( AF ) are often influenced by assessment of bleeding risk . However , existing bleeding risk scores have limitations . Objectives We sought to develop and vali date a novel bleeding risk score using routinely available clinical information to predict major bleeding in a large , community-based AF population . Methods We analysed data from Outcomes Registry for Better Informed Treatment of Atrial Fibrillation ( ORBIT-AF ) , a prospect i ve registry that enrolled incident and prevalent AF patients at 176 US sites . Using Cox proportional hazards regression , we identified factors independently associated with major bleeding among patients taking oral anticoagulation ( OAC ) over a median follow-up of 2 years ( interquartile range = 1.6–2.5 ) . We also created a numerical bedside risk score that included the five most predictive risk factors weighted according to their strength of association with major bleeding . The predictive performance of the full model , the simple five-item score , and two existing risk scores ( hypertension , abnormal renal/liver function , stroke , bleeding history or predisposition , labile INR , elderly , drugs/alcohol concomitantly , HAS-BLED , and anticoagulation and risk factors in atrial fibrillation , ATRIA ) were then assessed in both the ORBIT-AF cohort and a separate clinical trial population , Rivaroxaban Once-daily oral direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation ( ROCKET-AF ) . Results Among 7411 ORBIT-AF patients taking OAC , the rate of major bleeding was 4.0/100 person-years . The full continuous model ( 12 variables ) and five-factor ORBIT risk score ( older age [ 75 + years ] , reduced haemoglobin/haematocrit/history of anaemia , bleeding history , insufficient kidney function , and treatment with antiplatelet ) both had good ability to identify those who bled vs. not ( C-index 0.69 and 0.67 , respectively ) . These scores both had similar discrimination , but markedly better calibration when compared with the HAS-BLED and ATRIA scores in an external validation population from the ROCKET-AF trial . Conclusions The five-element ORBIT bleeding risk score had better ability to predict major bleeding in AF patients when compared with HAS-BLED and ATRIA risk scores . The ORBIT risk score can provide a simple , easily remembered tool to support clinical decision making OBJECTIVES The objective of this study was to compare the predictive performance of bleeding risk-estimation tools in a cohort of patients with atrial fibrillation ( AF ) undergoing anticoagulation . BACKGROUND Three bleeding risk-prediction schemes have been derived for and vali date d in patients with AF : HEMORR(2)HAGES ( Hepatic or Renal Disease , Ethanol Abuse , Malignancy , Older Age , Reduced Platelet Count or Function , Re-Bleeding , Hypertension , Anemia , Genetic Factors , Excessive Fall Risk and Stroke ) , ATRIA ( Anticoagulation and Risk Factors in Atrial Fibrillation ) , and HAS-BLED ( Hypertension , Abnormal Renal/Liver Function , Stroke , Bleeding History or Predisposition , Labile International Normalized Ratio , Elderly , Drugs/Alcohol ) . Τhe relative predictive values of these bleeding scores have not previously been compared . METHODS We analyzed the data set from the AMADEUS ( Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation ) trial , a multicenter , r and omized , open-label noninferiority study that compared fixed-dose idraparinux with adjustable-dose oral vitamin K antagonist therapy  in patients with AF . The principal safety outcome was any clinical ly relevant bleeding event , which was a composite of major bleeding plus clinical ly relevant nonmajor bleeding . RESULTS The HAS-BLED score performed best in predicting any clinical ly relevant bleeding , reflected both in net reclassification improvement ( 10.3 % and 13 % improvement compared with HEMORR(2)HAGES and ATRIA , respectively ) and receiver-operating characteristic ( ROC ) analyses ( c-indexes : 0.60 vs. 0.55 and 0.50 for HAS-BLED vs. HEMORR(2)AGES and ATRIA , respectively ) . Using decision-curve analysis , the HAS-BLED score demonstrated superior performance compared with ATRIA and HEMORR(2)HAGES at any threshold probability for clinical ly relevant bleeding . HAS-BLED was the only score that demonstrated a significant predictive performance for intracranial hemorrhage ( c-index : 0.75 ; p = 0.03 ) . An ATRIA score > 3 was not significantly associated with the risk for any clinical ly relevant bleeding on Cox regression or on ROC analysis ( c-index : 0.50 ; p = 0.87 ) . CONCLUSIONS All 3 tested bleeding risk-prediction scores demonstrated only modest performance in predicting any clinical ly relevant bleeding , although the HAS-BLED score performed better than the HEMORR(2)HAGES and ATRIA scores , as reflected by ROC analysis , reclassification analysis , and decision-curve analysis . Only HAS-BLED demonstrated a significant predictive performance for intracranial hemorrhage . Given its simplicity , the HAS-BLED score may be an attractive method for the estimation of oral anticoagulant-related bleeding risk for use in clinical practice , supporting recommendations in international guidelines Context Guidelines for prescribing anticoagulants in atrial fibrillation do not use contemporary stroke rates or account for intracranial bleeding risk . Contribution The authors studied 6-year rates of ischemic stroke and intracranial hemorrhage in 13559 adults with nonvalvular atrial fibrillation . They calculated ischemic stroke rates in patients receiving and not receiving warfarin ( treatment benefit ) and intracranial hemorrhage rates ( treatment harm ) . Benefit minus harm ( net treatment benefit ) was highest in patients with previous stroke , age older than 84 years , and others with high stroke risk . Caution Patients received warfarin according to clinical judgment , not r and omly . Implication Age and other stroke risk factors should drive the decision to use warfarin in atrial fibrillation . The Editors Warfarin anticoagulation is very efficacious in preventing thromboembolism ( primarily ischemic stroke but also systemic thromboembolism ) in patients with atrial fibrillation and is highly effective in practice ( 1 , 2 ) . Nonetheless , warfarin therapy increases the risk for major hemorrhage and is burdensome for both physicians and patients . Therefore , clinical guidelines ( 3 , 4 ) recommend warfarin only for patients with atrial fibrillation who are considered to be at intermediate or high risk for ischemic stroke . However , these risk-based anticoagulation guidelines have substantial limitations . First , they do not explicitly account for the risk for fatal and disabling hemorrhage due to warfarin . Second , they are primarily based on studies conducted more than 15 years ago . Recent studies ( 2 , 5 , 6 ) of patients with atrial fibrillation suggest a lower absolute risk for stroke while not receiving warfarin therapy , perhaps reflecting better treatment of hypertension or other risk factors . Finally , the net clinical benefit of risk-based recommendations for anticoagulation in patients with atrial fibrillation has not been demonstrated in large population s followed for long periods . In our observational study , we quantify the net clinical benefit of warfarin anticoagulation , defined as the estimated reduction in rate of thromboembolism , mainly ischemic stroke , minus 1.5 times the estimated increase in rate of intracranial hemorrhage attributable to warfarin therapy in st and ard stroke risk subgroups in the community-based cohort of patients in the ATRIA ( AnTicoagulation and Risk Factors In Atrial Fibrillation ) Study . Methods Study Population The ATRIA Study cohort consists of 13559 adults with diagnosed nonvalvular atrial fibrillation who received care within Kaiser Permanente of Northern California , a large integrated health care delivery system . Cohort assembly is described in detail elsewhere ( 2 , 7 ) . In brief , we identified patients with a diagnosis of atrial fibrillation between 1 July 1996 and 31 December 1997 by search ing outpatient data bases for internal medicine or cardiology visits in which an International Classification of Diseases , Ninth Revision , Clinical Modification ( ICD-9-CM ) , diagnosis of atrial fibrillation ( 427.31 ) was assigned and by search ing electrocardiographic data bases for a diagnosis of atrial fibrillation . The date of the first diagnosis of atrial fibrillation during the period of cohort assembly was considered the patient 's index date . Cohort assembly was finalized by November 1998 , and the cohort was followed through 30 September 2003 with a combination of retrospective ( back to July 1996 ) and prospect i ve ( through September 2003 ) review of health plan data bases and medical records . Patients who died or withdrew from the health plan during follow-up were censored at their date of death or on the last day of the month in which they terminated their membership . Date of death was ascertained from health plan clinical or administrative files , the California Automated Mortality Linkage System , or the Social Security Administration Death Master File . The institutional review boards at Massachusetts General Hospital and the Kaiser Foundation Research Institute approved the research . Patient Characteristics We search ed data bases of clinical inpatient and ambulatory visits ( outpatient clinic and emergency department ) during the 5 years before each patient 's index date to identify previously diagnosed ischemic stroke , heart failure , coronary heart disease , and hypertension by using relevant ICD-9-CM codes ( 2 ) . We used a vali date d , comprehensive health plan diabetes registry to identify patients with diabetes mellitus . Ascertainment of these stroke risk factors was vali date d against review of sample s of outpatient medical records ; crude agreement was high ( 78 % to 96 % ) , and corresponding statistics ranged from 0.51 to 0.89 . Of note , stroke risk prediction based on risk factors ascertained in the ATRIA Study was in good agreement with risk schemes generated by pooled r and omized trial and chart-based cohort study data ( 2 , 810 ) . Information from medical care received at both health plan and nonhealth plan facilities was obtained through these data bases . Data on age and sex were obtained from administrative data bases . Warfarin Exposure We determined warfarin exposure on the basis of information from automated clinical , pharmacy , and laboratory data bases by using methods described elsewhere ( 2 ) . We vali date d this computerized approach in 1207 patients by comparing it with warfarin status documented in their medical record at the time of an outcome event ; the result ing statistic was 0.84 . Nearly all discrepancies were due to transient discontinuation of warfarin treatment . If medical chart review of an outcome event showed that the patient stopped receiving warfarin within 5 days before the event , the event was considered to take place while the patient was receiving warfarin . For patients considered to be receiving warfarin  , an adapted linear interpolation method was used to determine the person-time spent in the therapeutic international normalized ratio ( INR ) range of 2.0 to 3.0 ( 11 ) . If the interval between consecutive INR measurements was greater than 8 weeks , the INR person-time for this period was considered not available . Outcome Assessment Thromboembolic Events We search ed hospitalization and billing cl aims data bases through 30 September 2003 for primary ICD-9-CM discharge diagnoses that indicated potential thromboembolism , including ischemic stroke and other systemic embolism ( ICD-9-CM codes available on request ) ( 2 ) . For both potential thromboembolic events and hemorrhagic events , medical record analysts obtained the relevant medical records by using a structured protocol . We did not investigate hospitalizations with the selected discharge diagnosis codes in a secondary position , because such hospitalizations rarely were prompted by new thromboembolic events . We estimate that our rates of ischemic stroke would have been increased relatively by 6 % had we review ed all such hospitalizations ( 2 ) . We defined a vali date d ischemic stroke as a sudden neurologic deficit lasting more than 24 hours , corresponding to a vascular territory in the absence of primary hemorrhage , that was not explained by other causes ( for example , trauma or infection ) . We defined a valid peripheral embolism as being identified by radiographic imaging , intraoperative examination , or pathologic findings ( with no atherosclerotic disease in the affected artery ) . Thromboembolic events occurring after hospital admission , generally as a complication of medical care , were not included as outcome events . Two members of the physician outcomes review committee review ed all potential thromboembolic events by using a formal protocol . Disagreements were resolved by a third committee member or by a consulting neurologist , if needed . Intracranial Hemorrhage We search ed hospitalization and billing data bases for primary and secondary discharge diagnoses of intracranial hemorrhage , including intraparenchymal , subdural , subarachnoid , and other hemorrhage ( ICD-9-CM codes available on request ) . We excluded intracranial hemorrhage associated with a concomitant discharge diagnosis of major trauma ( ICD-9-CM codes 852.1 , 852.3 , 852.5 , and 853.1 ) and events not leading to hospitalization or those that occurred as a complication of a hospitalization for another problem . Net Clinical Benefit We defined the core net clinical benefit of warfarin therapy in atrial fibrillation as the annualized rate of thromboembolic events ( TE rate ) prevented minus the annualized rate of intracran 
    Output:
    
Conclusions Compared with HAS-BLED , the ORBIT score does not perform better in predicting major bleeding events in anticoagulated atrial fibrillation patients .
More anticoagulated AF patients and major bleeding events were categorized as low risk when using ORBIT