***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 Patients with acute proximal deep-vein thrombosis are usually treated first in the hospital with intravenous st and ard ( unfractionated ) heparin . However , the longer plasma half-life , better bioavailability after subcutaneous administration , and more predictable anticoagulant response of low-molecular-weight heparins make them attractive for possible home use . We compared these two approaches . METHODS Patients with acute proximal deep-vein thrombosis were r and omly assigned to receive either intravenous st and ard heparin in the hospital ( 253 patients ) or low-molecular-weight heparin ( 1 mg of enoxaparin per kilogram of body weight subcutaneously twice daily ) administered primarily at home ( 247 patients ) . The study design allowed out patients taking low-molecular-weight heparin  to go home immediately and hospitalized patients taking low-molecular-weight heparin to be discharged early . All the patients received warfarin starting on the second day . RESULTS Thirteen of the 247 patients receiving low-molecular-weight heparin  ( 5.3 percent ) had recurrent thromboembolism , as compared with 17 of the 253 patients receiving st and ard heparin ( 6.7 percent ; P=0.57 ; absolute difference , 1.4 percentage points ; 95 percent confidence interval , -3.0 to 5.7 ) . Five patients receiving low-molecular-weight heparin had major bleeding , as compared with three patients receiving st and ard heparin . After r and omization , the patients who received low-molecular-weight heparin spent a mean of 1.1 days in the hospital , as compared with 6.5 days for the st and ard-heparin group ; 120 patients in the low-molecular-weight- heparin group did not need to be hospitalized at all . CONCLUSIONS Low-molecular-weight heparin can be used safely and effectively to treat patients with proximal deep-vein thrombosis at home Warfarin induction is accomplished by titrating dosage to coagulation test results . Algorithms can guide this process but not identify the starting dose . We hypothesized that an initial warfarin dose approximating the maintenance value would safely enhance rapidity of induction . In a r and omized trial we compared a fixed-dose to a maintenance-dose strategy for beginning warfarin therapy . To predict the maintenance dose among patients with differing warfarin  requirements we performed regression analysis on clinical factors derived from chart review . Four community hospitals supplied records for retrospective analysis . The prospect i ve trial was conducted in one , a 350-bed teaching institution . A sample of in patients anticoagulated during 1998 formed the development set for retrospective study ; a 1999 sample formed the validation set . A one year trial recruited consecutive eligible in patients initiated on warfarin .  We r and omly assigned patients to a first warfarin dose calculated using our regression formula or fixed at 5 mg . All patients ' subsequent doses were determined ( as a percentage of initial ) from coagulation testing . We compared days to anticoagulation , hospitalized hours , complications , and activity of factor II and protein C in a patient sample at intervals after induction . Weight , age , serum albumin , and presence of malignancy explained 25 - 30 % of variance in maintenance dose . Ninety patients ( 44 calculated-dose and 46 st and ard-dose ) evaluated in the clinical trial . Mean time to anticoagulation ( among patients achieving anticoagulation ) was 4.2 and 5.0 days , respectively ( p = 0.007 ) . We observed no significant differences in other endpoints . Individualized initial dosing may safely hasten warfarin induction BACKGROUND Warfarin sodium therapy is usually initiated with a loading dose to reduce the time required to elevate the international normalized ratio ( INR ) .  Warfarin loading doses are associated with early overanticoagulation and the development of a potential hypercoagulable state ; they also may not hasten achieving an INR value between 2.0 and 3.0 . This study was design ed to prospect ively confirm our observation that a 5-mg warfarin sodium loading dose is as effective as a 10-mg loading dose in achieving a therapeutic INR for 2 consecutive days on days 3 and 4 or 4 and 5 of therapy . METHODS Fifty-three patients initiating warfarin therapy with a target INR of 2.0 to 3.0 were r and omly allocated to receive an initial dose of 5 or 10 mg of warfarin . Subsequent doses were based on dosing algorithms . The INR was measured daily for 5 days . The primary end point of the study was the proportion of patients whose INR values were between 2.0 and 3.0 on 2 consecutive daily determinations on days 3 , 4 , or 5 of the study and whose INR did not exceed 3.0 at any point during the study . RESULTS Five ( 24 % ) of 21 patients in the 10-mg group and 21 ( 66 % ) of 32 patients in the 5-mg group achieved the primary end point ( relative risk 2.22 , 95 % confidence interval 1.30 - 3.70 [ P < .003 ] ) . A trend toward less overanticoagulation was seen in the 5-mg warfarin group . CONCLUSION A 10-mg loading dose of warfarin is unlikely to be more effective than a 5-mg loading dose in achieving an INR of 2.0 to 3.0 by day 4 or 5 of therapy Context The optimal methods for achieving therapeutic levels of anticoagulation with warfarin remain uncertain . Contribution In this r and omized trial of two warfarin dosing nomograms , a 10-mg initiation dose led to a therapeutic international normalized ratio ( INR ) 1.4 days sooner than a 5-mg initiation dose . The two nomograms had the same rate of adverse events and the same proportion of INR values greater than 5.0 . Clinical Implication s Physicians can more quickly get their patients to a therapeutic INR with warfarin by using a dosing nomogram that starts with a 10-mg dose rather than a 5-mg initiation dose . The Editors The management of venous thromboembolism has improved substantially in the past 10 years . Conventional therapy consists of unfractionated or low-molecular-weight heparin for 5 to 7 days , together with oral anticoagulation with warfarin given for a minimum of 3 months ( 1 , 2 ) . Low-molecular-weight heparin facilitates outpatient treatment , and warfarin is usually initiated within 24 hours . Clinical trials have demonstrated that low-molecular-weight heparin may be safely discontinued after 5 days once the international normalized ratio ( INR ) has remained greater than 1.9 for 24 hours ( 2 , 3 ) . Nurses or pharmacists often coordinate outpatient management of venous thromboembolism with appropriate physician support ( 4 ) . For outpatient therapy , minimizing the time to a therapeutic INR is advantageous because it potentially decreases the cost and inconvenience of low-molecular-weight heparin therapy . The initiation of warfarin treatment is problematic , however , because of variations in dose response . A dosing nomogram to facilitate safe , timely warfarin initiation to achieve therapeutic INRs would be useful . We previously developed and tested a nomogram for the initiation of warfarin therapy using a 10-mg loading dose and found that it was superior to st and ard physician practice because it result ed in shorter time to a therapeutic INR ( 5 ) . This nomogram , however , required daily INR testing and was therefore not ideal for outpatient management . We subsequently revised the nomogram so that it requires INR assessment s only on days 3 and 5 during the first 8 days of therapy . We found that the revised nomogram was successful : Almost 90 % of patients had a therapeutic INR by the 5th day of treatment ( 6 ) . The objective of our current study was to perform a r and omized , controlled trial comparing the effectiveness and feasibility of a warfarin nomogram using a 10-mg loading dose with those of a nomogram using a 5-mg loading dose for the management of out patients with acute venous thromboembolism . Methods Patients Consecutive out patients with a diagnosis of objective ly confirmed acute venous thromboembolism ( deep venous thrombosis or pulmonary embolism ) who presented to the thrombosis clinics of four Canadian academic centers were c and i date s for study inclusion . Patients were not admitted to the study if they had a baseline INR greater than 1.4 , had thrombocytopenia ( platelet count < 50 109 cells/mL ) , were younger than 18 years of age , required hospitalization , had received oral anticoagulant therapy within the previous 2 weeks , or were at high risk for major bleeding ( as judged by the attending physician ) . Design This study was a r and omized , double-blind ( physicianpatient ) , controlled trial . R and omization was stratified by study center and presence of active malignant disease . The r and omization sequence was computer generated by the trial statistician . The details of the r and omization sequence , which were not known to the investigators or to the study coordinator , were contained in sets of sequentially numbered , opaque , sealed envelopes . The outside of each envelope was marked only with the name of the hospital , whether the patient had a malignant condition , and a patient number . Patients were assigned to 5-mg or 10-mg warfarin induction by using previously vali date d nomograms ( Table 1 and Figure 1 ) ( 6 , 7 ) . The 5-mg nomogram , as published , specifies a dose range on each day after the first day of treatment with no indication of how to choose the dose ( 7 ) . For the current study , we chose the higher dose whenever a range was indicated . The research ethics boards at each of the participating institutions approved the study , and informed consent was obtained from all participants . Table 1 . 5-mg Warfarin Initiation Nomogram Figure 1 . 10-mg warfarin initiation nomogram . Interventions Study participants were r and omly allocated to warfarin induction with a 10-mg or 5-mg warfarin nomogram ( Table 1 and Figure 1 ) ( 6 , 7 ) . Baseline data collected included demographic characteristics ( age , sex ) , diagnosis , weight , presence of active malignant disease , complete blood count , and INR . International normalized ratios were measured in local licensed clinical laboratories . Treatment was initiated on the first day ( day 1 ) with subcutaneous low-molecular-weight heparin ( dalteparin [ 200 U/kg of body weight ] or tinzaparin [ 175 U/kg ] ) . Low-molecular-weight heparin was continued for a minimum of five daily injections until the INR was therapeutic ( > 1.9 ) . The initial warfarin dose was determined by using treatment allocation . All warfarin doses were administered in the evening , and blood sample s for INR assessment s were drawn before 10:00 a.m. Patients in the 10-mg group received 10 mg of warfarin on each of the first 2 days , whereas patients in the 5-mg group were given 5 mg on each of the first 2 days . Subsequent dose adjustments after day 3 were made by using the respective nomograms . International normalized ratios were measured in all patients on the mornings of days 3 , 4 , and 5 . The 10-mg nomogram , unlike the 5-mg nomogram , did not require an INR measurement on day 4 for dosing ; however , a measurement was performed for study end point purpose s only . If a patient did not have a therapeutic INR by day 5 , the INR was measured daily until it was therapeutic . Local attending physicians directed management of warfarin monitoring from day 8 to day 90 . End Points The primary end point of the study was time in days to a therapeutic INR ( > 1.9 ) . The secondary end points included the proportion of patients whose INRs were within the therapeutic range ( 2.0 to 3.0 ) on the 5th day , incidence of recurrent venous thromboembolism within 90 days of diagnosis ( as defined by previously published criteria [ 2 , 3 ] ) , incidence of major bleeding within 28 days of diagnosis ( as defined by previously published criteria [ 2 , 3 ] ) , number of INR measurements greater than 5 , absolute number of INR assessment s in the first 28 days , and 90-day survival . An adjudication committee consisting of three study investigators evaluated all clinical events in a blinded fashion , and end points were determined by consensus . Hypothesis We tested the hypothesis that patients managed with a 10-mg warfarin induction nomogram would achieve therapeutic INRs more rapidly than patients managed with a 5-mg warfarin nomogram . We believed these improvements would occur without increased risk for bleeding . Sample Size Using data from our pilot nomogram to estimate st and ard deviation ( 1 day ) , we calculated that 92 patients per group would be required to show a 0.5-day difference in time to a therapeutic INR ( 90 % power ; two-sided = 0.05 ) . We considered a 0.5-day difference to be the minimal clinical ly important difference because it would yield a significant proportion of patients who would not require low-molecular-weight heparin therapy beyond 5 days . Statistical Analysis All statistical analyses were performed according to a pre-established analysis plan and by intention to treat . We used SPSS software for 
    Output:
    
In patients with acute thromboembolism ( DVT or PE ) aged 18 years or older , considerable uncertainty surrounds the use of a 10-mg or a 5-mg loading dose for initiation of warfarin to achieve an INR of 2.0 to 3.0 on the fifth day of therapy .