***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: PURPOSE To determine the incidence of major bleeding in out patients treated with warfarin  and to identify predictive factors known at the start of therapy . PATIENTS AND METHODS The records of 565 patients starting outpatient therapy with warfarin upon discharge from a university hospital were review ed . Follow-up information was obtained for 562 patients ( 99.5 % ) .  Bleeding was classified as major or minor using explicit criteria . The cumulative incidence of bleeding was estimated by means of survival analysis . Independent risk factors for major bleeding were identified using Cox regression analysis in 375 r and omly chosen patients ; they were tested in the remaining 187 patients . RESULTS Major bleeding occurred in 65 patients ( 12 % ) and was fatal in 10 patients ( 2 % ) . The cumulative incidences of major bleeding at one , 12 , and 48 months were 3 % , 11 % , and 22 % , respectively . The monthly risk of major bleeding decreased over time , from 3 % during the first month of outpatient therapy to 0.3 % per month after the first year of therapy . Five independent risk factors for major bleeding -- age 65 years or greater , history of stroke , history of gastrointestinal bleeding , a serious comorbid condition ( recent myocardial infa rct ion , renal insufficiency , or severe anemia ) , atrial fibrillation -- predicted major bleeding in the testing group ; the cumulative incidence of major bleeding at 48 months was 2 % in 57 low-risk patients , 17 % in 110 middle-risk patients , and 63 % in 20 high-risk patients . CONCLUSION These findings provide a quantitative basis for evaluating the risk of major bleeding in individual patients at the start of outpatient therapy with warfarin . Whether the risk of bleeding can be reduced in high-risk patients without reducing the benefit of therapy remains to be determined BACKGROUND The Outpatient Bleeding Risk Index  ( BRI ) prospect ively classified patients who were at high , intermediate , or low risk for warfarin-related major bleeding .  However , there are only 2 published validation studies of the index and neither included veterans . OBJECTIVE To determine the accuracy of the BRI in patients attending a Veterans Affairs ( VA ) anticoagulation clinic and to specifically evaluate the accuracy of the BRI in patients with atrial fibrillation . DESIGN Retrospective cohort study . PATIENTS AND MEASUREMENTS Using the BRI , all patients managed by the Anticoagulation Clinic between January 1 , 2001 and December 31 , 2002 were classified as high , intermediate , or low risk for major bleeding . Bleeds were identified via quality -assurance reports . Poisson regression was used to determine whether there was an association between the index and the development of bleeding . RESULTS The rate of major bleeding was 10.6 % , 2.5 % , and 0.8 % per patient-year of warfarin in the high- , intermediate- , and low-risk groups , respectively . Patients in the high-risk category had 14 times the rate of major bleeding of those in the low-risk group ( incidence rate ratio ( IRR ) 14 ; 95 % confidence interval ( CI ) , 1.9 to 104.7 ) . The rate of major bleeding was significantly different between the high- and intermediate-risk categories ( P<.001 ) . Among those with atrial fibrillation , patients in the high-risk category had 6 times the major bleeding rate of those in the intermediate- and low-risk groups combined ( IRR=6 ; 95 % CI , 2.4 to 15.3 ) . CONCLUSIONS The BRI discriminates between high- and intermediate-risk patients in a VA anticoagulation clinic , including those with atrial fibrillation PURPOSE To evaluate the accuracy and clinical utility of the Outpatient Bleeding Risk Index for estimating the probability of  major bleeding in out patients treated with warfarin .  The index was previously derived in a retrospective cohort of 556 patients from a different hospital ( derivation cohort ) . SUBJECTS AND METHODS We enrolled 264 out patients starting warfarin ( validation cohort ) to vali date the index prospect ively . All patients were identified upon hospital discharge , and physician estimates of the probability of major bleeding were obtained before discharge in the validation cohort . RESULTS Major bleeding occurred in 87 of 820 out patients ( 6.5%/yr ) . The index included four independent risk factors for major bleeding : age 65 years or greater ; history of gastrointestinal bleeding ; history of stroke ; and one or more of four specific comorbid conditions . In the validation cohort , the index predicted major bleeding : the cumulative incidence at 48 months was 3 % in 80 low-risk patients , 12 % in 166 intermediate-risk patients , and 53 % in 18 high-risk patients ( c index , 0.78 ) . The index performed better than physicians , who estimated the probability of major bleeding no better than expected by chance . Of the 18 episodes of major bleeding that occurred in high-risk patients , 17 were potentially preventable . CONCLUSIONS The Outpatient Bleeding Risk Index prospect ively classified patients according to risk of major bleeding and performed better than physicians . Major bleeding may be preventable in many high-risk patients by avoidance of over-anticoagulation and nonsteroidal anti-inflammatory agents This article concerning the pharmacokinetics and pharmacodynamics of vitamin K antagonists ( VKAs ) is part of the American College of Chest Physicians Evidence -Based Clinical Practice Guidelines ( 8th Edition ) . It describes the antithrombotic effect of the VKAs , the monitoring of anticoagulation intensity , and the clinical applications of VKA therapy and provides specific management recommendations . Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh the risks , burdens , and costs . Grade 2 recommendations suggest that the individual patient 's values may lead to different choices . ( For a full underst and ing of the grading , see the " Grade s of Recommendation " chapter by Guyatt et al , CHEST 2008 ; 133:123S-131S . ) Among the key recommendations in this article are the following : for dosing of VKAs , we recommend the initiation of oral anticoagulation therapy , with doses between 5 mg and 10 mg for the first 1 or 2 days for most individuals , with subsequent dosing based on the international normalized ratio ( INR ) response ( Grade 1B ) ; we suggest against pharmacogenetic-based dosing until r and omized data indicate that it is beneficial ( Grade 2C ) ; and in elderly and other patient subgroups who are debilitated or malnourished , we recommend a starting dose of < or = 5 mg ( Grade 1C ) . The article also includes several specific recommendations for the management of patients with nontherapeutic INRs , with INRs above the therapeutic range , and with bleeding whether the INR is therapeutic or elevated . For the use of vitamin K to reverse a mildly elevated INR , we recommend oral rather than subcutaneous administration ( Grade 1A ) . For patients with life-threatening bleeding or intracranial hemorrhage , we recommend the use of prothrombin complex concentrates or recombinant factor VIIa to immediately reverse the INR ( Grade 1C ) . For most patients who have a lupus inhibitor , we recommend a therapeutic target INR of 2.5 ( range , 2.0 to 3.0 ) [ Grade 1A ] . We recommend that physicians who manage oral anticoagulation therapy do so in a systematic and coordinated fashion , incorporating patient education , systematic INR testing , tracking , follow-up , and good patient communication of results and dose adjustments [ Grade 1B ] . In patients who are suitably selected and trained , patient self-testing or patient self-management of dosing are effective alternative treatment models that result in improved quality of anticoagulation management , with greater time in the therapeutic range and fewer adverse events . Patient self-monitoring or self-management , however , is a choice made by patients and physicians that depends on many factors . We suggest that such therapeutic management be implemented where suitable ( Grade 2B ) BACKGROUND After hip replacement surgery , prophylaxis following discharge from hospital is recommended to reduce the risk of venous thromboembolism . Our aim was to assess the oral , direct thrombin inhibitor dabigatran etexilate for such prophylaxis . METHODS In this double-blind study , we r and omised 3494 patients undergoing total hip replacement to treatment for 28 - 35 days with dabigatran etexilate 220 mg ( n=1157 ) or 150 mg ( 1174 ) once daily , starting with a half-dose 1 - 4 h after surgery ,  or subcutaneous enoxaparin  40 mg once  daily  ( 1162 ) , starting the evening before surgery . The primary efficacy outcome was the composite of total venous thromboembolism ( venographic or symptomatic ) and death from all causes during treatment . On the basis of the absolute difference in rates of venous thromboembolism with enoxaparin versus placebo , the non-inferiority margin for the difference in rates of thromboembolism was defined as 7.7 % . Efficacy analyses were done by modified intention to treat . This trial is registered with Clinical Trials.gov , number NCT00168818 . FINDINGS Median treatment duration was 33 days . 880 patients in the dabigatran etexilate 220 mg group , 874 in the dabigatran etexilate  150 mg group , and 897 in the enoxaparin group were available for the primary efficacy outcome analysis ; the main reasons for exclusion in all three groups were the lack of adequate venographic data . The primary efficacy outcome occurred in 60 ( 6.7 % ) of 897 individuals in the enoxaparin group versus 53 ( 6.0 % ) of 880 patients in the dabigatran etexilate 220 mg group ( absolute difference -0.7 % , 95 % CI -2.9 to 1.6 % ) and 75 ( 8.6 % ) of 874 people in the 150 mg group ( 1.9 % , -0.6 to 4.4 % ) . Both doses were thus non-inferior to enoxaparin . There was no significant difference in major bleeding rates with either dose of dabigatran etexilate compared with enoxaparin ( p=0.44 for 220 mg , p=0.60 for 150 mg ) . The frequency of increases in liver enzyme concentrations and of acute coronary events during the study did not differ significantly between the groups . INTERPRETATION Oral dabigatran etexilate was as effective as enoxaparin in reducing the risk of  venous thromboembolism after total hip replacement surgery , with a similar safety profile A score that can accurately determine the risk of major bleeding during anticoagulant therapy may help to make decisions on anticoagulant use . RIETE is an ongoing registry of consecutive patients with acute venous thromboembolism ( VTE ) . We composed a score to predict the risk for major bleeding within three months of anticoagulant therapy . Of 19,274 patients enrolled , 13,057 ( 67 % ) were r and omly assigned to the derivation sample , 6,572 to the validation sample . In the derivation sample 314 ( 2.4 % ) patients bled ( fatal bleeding , 105 ) . On multivariate analysis , age > 75 years , recent bleeding , cancer , creatinine levels > 1.2 mg/dl , anemia , or pulmonary embolism at baseline were independently associated with an increased risk for major bleeding . A score was composed assigning 2 points to recent bleeding , 1.5 to abnormal creatinine levels or anemia , 1 point to the remaining variables . In the derivation sample 2,654 ( 20 % ) patients scored 0 points ( low risk ) ; 9,645 ( 74 % ) 1 - 4 points ( intermediate ) ; 758 ( 5.8 % ) > 4 points ( high risk ) . The incidences of major bleeding were : 0.3 % ( 95 % confidence interval [ CI ] : 0.1 - 0.6 ) , 2.6 % ( 95 % CI : 2.3 - 2.9 ) , and 7.3 % ( 95 % CI : 5.6 - 9.3 ) , respectively . The likelihood ratio test was : 0.14 ( 95 % CI : 0.07 - 0.27 ) for patients at low risk;2.96 ( 95 % CI : 2.18 - 4.02 ) for those at high risk . In the validation sample the incidence of major bleeding was : 0.1 % , 2.8 % , and 6.2 % , respectively . In conclusion , a risk score based on six variables documented at entry can identify VTE patients at low , intermediate , or high risk for major bleeding during the first three months of therapy Abstract Objective : To determine and compare physicians ' and patients ' thresholds for how much reduction in risk of stroke is necessary and how much risk of excess bleeding is acceptable with antithrombotic treatment in people with atrial fibrillation . Design : Prospect i ve observational study . Setting : Tertiary and peripheral referral centres in Nova Scotia , Canada . Participants : 63 physicians who were treating patients with atrial fibrillation and 61 patients at high risk for atrial fibrillation . Main outcome measures : Participants under 
    Output:
    
A RIETE score of 0 point was moderately predictive of the absence of major bleeding .
None of the CPRs exhibited sufficient predictive accuracy or had sufficient validation to be recommended for routine use in practice .
None of the available CPRs exhibit sufficient predictive accuracy or have trials evaluating the impact of their use on patient outcomes .