***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 
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    Input: PURPOSE Initial heparinization followed by vitamin K antagonists is the treatment of choice for patients with venous thromboembolism . There is controversy whether known malignancy is a risk factor for recurrences and bleeding complications during this treatment . Furthermore , the incidence of such events in these patients is dependent on the achieved International Normalized Ratio ( INR ) . The aim of this study was to assess the incidence of venous thromboembolic recurrence and major bleeding among patients with venous thromboembolism in relation to both malignancy and the achieved INR . PATIENTS AND METHODS In a retrospective analysis , the INR-specific incidence of venous thromboembolic and major bleeding events during oral anticoagulant therapy was calculated separately for patients with and without malignancy . Eligible patients participated in two multicenter , r and omized clinical trials on the initial treatment of venous thromboembolism . Patients were initially treated with heparin ( st and ard or low-molecular weight ) . Treatment with vitamin K antagonists was started within 1 day and continued for 3 months , with a target INR of 2.0 to 3.0 . RESULTS In 1,303 eligible patients ( 264 with malignancy ) , 35  recurrences  and 12  bleeds occurred . Patients with malignancy , compared with nonmalignant patients , had a clinical ly and statistically significantly increased overall incidence of recurrence ( 27.1 v 9.0 , respectively , per 100 patient-years ) as well as bleeding ( 13.3 v 2.1 , respectively , per 100 patient-years ) . In both groups of patients , the incidence of recurrence was lower when the INR was above 2.0 compared with below 2.0 . CONCLUSION Although adequately dosed vitamin K antagonists are effective in patients with malignant disease , the incidence of thrombotic and bleeding complications remains higher than in patients without malignancy BACKGROUND There is increased pressure on primary care physicians to monitor oral anticoagulation . OBJECTIVE To test the null hypothesis that oral anticoagulation care can be provided at least as well in primary care through a nurse-led clinic , involving near-patient testing and computerized decision support software , compared with routine hospital management based on a variety of clinical outcome measures . METHODS A r and omized , controlled trial in 12 primary care practice s in Birmingham , Engl and ( 9 intervention and 3 control ) . Two control population s were used :  patients individually r and omly allocated as controls in the intervention practice s ( intra practice controls ) and all patients in control practice s ( inter practice controls ) . Intervention practice s ' patients were r and omized to the intervention ( practice -based anticoagulation clinic ) or control ( hospital clinic ) group . The main outcome measure was therapeutic control of the international normalized ratio . RESULTS Three hundred sixty-seven patients were recruited ( 122 intervention patients , 102 intra practice control patients , and 143 inter practice control patients ) . St and ard measures of control of the international normalized ratio ( point prevalence ) showed no significant difference between the intervention and control groups . Data on proportion of time spent in the international normalized ratio range showed significant improvement for patients in the intervention group ( paired t test , P = .008 ) . CONCLUSIONS Nurse-led anticoagulation clinics can be implemented in novice primary care setting s by means of computerized decision support software and near-patient testing . Care given by this model is at least as good as routine hospital follow-up . The model is generalizable to primary health care centers operating in developed health care systems BACKGROUND Bleeding is the most serious complication of the use of oral anticoagulation in the prevention and treatment of thromoboembolic complications . We studied the frequency of bleeding complications in out patients treated routinely in anticoagulation clinics . METHODS In a prospect i ve cohort from thirty-four Italian anticoagulation clinics , 2745 consecutive patients were studied from the start of their oral anticoagulation ( warfarin in 64 % , acenocourmarol in the rest ) . The target anticoagulation-intensity was low ( international normalised ratio [ INR ] < or = 2.8 ) in 71 % of the patients and high ( > 2.8 ) in the remainder . We recorded demographic details and the main indication for treatment and , every 3 - 4 months , INR and outcome events . Such events included all complications ( bleeding , thrombosis , other ) , although only bleeding events are reported here , and deaths . We divided bleeding into major and minor categories . FINDINGS 43 % of the patients were women . Nearly three-fifths of the patients were aged 60 - 79 ; 8 % were over 80 . The main indication for treatment was venous thrombolism ( 33 % ) , followed by non-ischaemic heart disease ( 17 % ) . Mean follow-up was 267 days . Over 2011 patient-years of follow-up , 153 bleeding complications occurred ( 7.6 per 100 patient-years ) . 5 were fatal ( all cerebral haemorrhages , 0.25 per 100 patient-years ) , 23 were major ( 1.1 ) , and 125 were minor ( 6.2 ) . The rate of events was similar between sexes , coumarin type , size of enrolling centre , and target INR . The rate was higher in older patients : 10.5 per 100 patient-years in those aged 70 or over , 6.0 in those aged under 70 ( relative risk 1.75 , 95 % Cl 1.29 - 2.39 , p < 0.001 ) . The rate was also higher when the indication was peripheral and /or cerebrovascular disease than venous thromboembolism plus other indications ( 12.5 vs 6.0 per 100 patient-years ) ( 1.80 , 1.2 - 2.7 , p < 0.01 ) , and during the first 90 days of treatment compared with later ( 11.0 vs 6.3 , 1.75 , 1.27 - 2.44 , p < 0.001 ) . A fifth of the bleeding events occurred at low anticoagulation intensity ( INR < 2 , rate 7.7 per 100 patient-years of follow-up ) . The rates were 4.8 , 9.5 , 40.5 , and 200 at INRs 2.0 - 2.9 , 3 - 4.4 , 4.5 - 6.9 , and over 7 , respectively ( relative risks for INR > 4.5 , 7.91 , 5.44 - 11.5 , p < 0.0001 ) . INTERPRETATION We saw fewer bleeding events than those recorded in other observational and experimental studies . Oral anticoagulation has become safer in recent years , especially if monitored in anticoagulation clinics . Caution is required in elderly patients and anticoagulation intensity should be closely monitored to reduce periods of overdosing During treatment with vitamin K antagonists , International Normalized Ratios ( INR ) are determined periodically to maintain a therapeutic level of anticoagulation . We evaluated two existing methods for therapeutic quality control ( linear interpolation and equidivision ) , with regard to their validity and reproducibility . In addition , we proposed and evaluated a ( hybrid ) method that takes into account potential effects of dosage modifications when INRs are far out of the target range . Validity was assessed by deleting intermediary INR results and estimating this INR based on the two surrounding INRs with each of the three methods . The estimated INRs were then compared with the observed INR . Reproducibility of time spent in an INR range was evaluated for each of the three methods by deleting at r and om increasing proportions of INRs and comparing these estimates with the situation without deletions . We found that estimates of time spent in INR categories obtained with equidivision were most reproducible , but least valid . The hybrid method showed slightly higher validity and reproducibility in comparison with linear interpolation . Since these differences were small , linear interpolation is preferable to the hybrid method , since the calculations involved are easier CONTEXT Control of oral anticoagulation therapy has been reported to often be inadequate . Previous retrospective investigations suggest that patients ' self-adjustment of oral anticoagulants may lead to improved control . OBJECTIVE To investigate the effects of patients ' self-management of oral anticoagulation therapy on accuracy of control and measures of treatment-related quality of life . DESIGN R and omized , single-blind , multicenter trial . SETTING AND PARTICIPANTS A total of 179 patients receiving long-term oral anticoagulation treatment were enrolled at 5 referral centers in Germany . INTERVENTION Patients were r and omized to an oral anticoagulation self-management group based on a structured treatment and teaching program and international normalized ratio ( INR ) self-monitoring . The control group received conventional care as provided by family physicians , including referral to specialists if necessary . MAIN OUTCOME MEASURES Deviation of INR values from the individual INR target range ( squared ) and the 5 categories of treatment-related quality of life . RESULTS Deviation of INR value from the mean of the INR target range was significantly lower in the intervention group at 3-month ( squared INR deviation , 0.59 vs 0.95 ; P<.001 ) and 6-month follow-up ( 0.65 vs 0.83 ; P=.03 ) compared with the control group . Also , the intervention group had INR values within the target range more often ( repeated measurement analysis for categorical data , P=.006 ) . The results were mainly due to less frequent suboptimal INR values in the intervention group ( 32.8 % vs 50.0 % [ P=.03 ] at 3-month , and 33.7 % vs 48.2 % [ P=.08 ] at 6-month follow-up ) . Treatment-related quality -of-life measures , especially treatment satisfaction scores , were significantly higher in the intervention group compared with controls . CONCLUSIONS An anticoagulation education program that includes self-management of anticoagulation therapy results in improved accuracy of anticoagulation control and in treatment-related quality -of-life measures . Further studies are needed to describe whether the program will reduce risk of bleeding or thromboembolism BACKGROUND A number of studies have demonstrated the efficacy of oral anticoagulant therapy in reducing the risk of stroke and systemic embolism in patients with nonrheumatic atrial fibrillation . However , both the targeted and the actual levels of anticoagulation differed widely among the studies , and a number of studies failed to report st and ardized prothrombin-time ratios as international normalized ratios ( INRs ) . We therefore performed an analysis to determine the intensity of oral anticoagulant therapy in nonrheumatic atrial fibrillation that provides the best balance between the prevention of thromboembolism and the occurrence of bleeding complications . METHODS We calculated INR-specific incidence rates for both ischemic and major hemorrhagic events occurring in 214 patients who received anticoagulant therapy in the European Atrial Fibrillation Trial , a secondary -prevention trial in patients with nonrheumatic atrial fibrillation and a recent episode of minor cerebral ischemia . RESULTS The optimal intensity of anticoagulation was found to lie between an INR of 2.0 and an INR of 3.9 . No treatment effect was apparent with anticoagulation below an INR of 2.0 . The rate of thromboembolic events was lowest at INRs from 2.0 to 3.9 , and most major bleeding complications occurred with treatment at intensities with INRs of 5.0 or above . CONCLUSIONS To achieve optimal levels of anticoagulation with the lowest risk in patients with atrial fibrillation and a recent episode of cerebral ischemia , the target value for the INR should be set at 3.0 , and values below 2.0 and above 5.0 should be avoided We have previously reported that long-term therapy with warfarin is effective for preventing recurrent venous thromboembolism in patients with proximal-vein thrombosis but that there is an appreciable risk of hemorrhage . To determine whether that risk could be reduced without a loss of effectiveness , we r and omly allocated 96 patients with proximal-vein thrombosis to a group receiving  less intense anticoagulant therapy , with a mean prothrombin time of 26.9 seconds using the Manchester comparative reagent ( corresponding Simplastin time , 15 seconds ) , or a group given more intense therapy , with a mean Simplastin time of 19.4 seconds ( corresponding prothrombin time 41 seconds with the Manchester comparative reagent ) ( P less than 0.001 ) . Two of 47 patients ( 4 per cent ) in the less intensely treated group had hemorrhagic complications , as compared with 11 of 49 patients ( 22 per cent ) in the more intensely anticoagulated group ( P = 0.015 by the two-tailed test ) . This difference was due to minor bleeding episodes . The frequency of recurrent venous thromboembolism was low in both groups ( 2 per cent ) . Our findings indicate that less intense anticoagulant therapy is associated with a low frequency of recurrent venous thromboembolism ( 2 per cent ) and a reduced risk of hemorrhage BACKGROUND Some elderly patients with nonvalvular atrial fibrillation ( NVAF ) who might benefit from warfarin therapy do not receive it . OBJECTIVE The goal of this cross-sectional study was to identify physicians ' attitudes and beliefs that are associated with their reported use of warfarin in case scenarios . METHODS A self-administered survey was mailed 
    Output:
    
The risks of hemorrhage and thromboemboli are minimized at international normalized ratios of 2 - 3 .
Ratios that are moderately higher than this therapeutic range appear safe and more effective than subtherapeutic ratios