***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: The aim of this independent study was to demonstrate the rapidity of the clinical action of HR 0-(beta-hydroxyethyl)-rutosides , Venoruton ® ( Novartis Consumer Health ) in patients with chronic venous insufficiency ( CVI ) . Two groups of patients with venous hypertension and microangiopathy were treated with HR ( 1 or 2 g/day , for 8 weeks ) . Twelve patients ( age 56.4 ; range 44 - 66 ; M : F = 6:6 ) were included in group 1 ( 1 g/day ) ( moderate CVI and microangiopathy ) ; 10 patients ( age 57.4 ; range 42 - 67 ; M : F = 5:5 ) in group 2 ( 2 g/day ) with more severe CVI and microangiopathy .  Average ambulatory venous pressure ( AVP ) was 58.6 ( range 50 - 65 ) with a refilling time ( RT ) shorter than 10 seconds . There were no significant differences in AVP and RT between the 2 groups , but the duration of the disease was longer in group 2 : 3.5 years ( SD 2.0 ) in group 1 and 6.4 years ( SD 3.3 ) in group 2 . All included subjects completed the study and no dropouts were observed . In both dose groups there was a progressive decrease in laser Doppler resting flux ( RF ) , indicating improvement in microangiopathy and a significant decrease in capillary filtration ( RAS ) associated with a significant improvement in analogue scale line score ( ASLS ) and edema . Although the effect in the 2 g dose group was more rapid on the microcirculatory parameters with a significant effect on RF and RAS after 4 days ( effect of 1 g per day after 8 days and 6 days , respectively ) , there was no difference in the time to onset of a significant clinical improvement ( ie , the ASLS and the edema score ) : 4 days in both groups . Venous microangiopathy and edema were improved by the treatment with HR within a few days . The effects were visible with both dosages , in both severity groups The aim of this study was to demonstrate whether HR ( Paroven-Venoruton ; 0-(β-hydroxyethyl)-rutosides ) , was effective in improving the microcirculation in venous hypertension and microangiopathy . Sixty patients with severe venous hypertension due to chronic venous insufficiency , ankle swelling , and lipodermatosclerosis were included . After informed consent , patients were r and omized into a treatment group and a placebo group . Patients in the treatment group received oral HR ( 2 g/day for 8 weeks ) ; those in the placebo group received a comparable placebo . Results : The two groups were comparable for age and sex distribution . The mean age was 45 years ( SD 9 ) in the treatment group ( 31 patients ) and 45.5 ( SD 10 ) in the placebo group ( 29 patients ) . There were no differences between the placebo and treatment groups at inclusion . There was no change between inclusion and measurements at 8 weeks in the placebo group . A significant decrease ( P < 0.05 ) in flux at rest and rate of ankle swelling was observed in the treatment group . The decrease in capillary filtration was associated with improvement in signs and symptoms ( P < 0.05 ) . The difference in flux , sign and symptoms , and filtration was clinical ly important at 8 weeks in the treatment group when compared with the placebo group . No adverse effects were observed . Conclusion : Venous microangiopathy was improved by HR treatment A multi-centre , double blind r and omized clinical trial was design ed to assess the efficacy and safety of orally administered 0-(beta-hydroxyethyl)-rutosides ( HR ) capsules in the treatment of 101 patients with post-thrombotic syndrome . Seventeen patients were excluded from the analysis for violation of the study protocol , 41 received HR capsules ( 1,200 mg/day ) and 43 placebo . Mean follow-up scores at the 4th and 8th week show that the HR patients displayed an improved state of tiredness as compared to the placebo 's . The mean circumference of the calf for the HR group decreased from 390 ( + /- 33 ) mm at visit one to 382 ( + /- 33 ) mm at visit three , with a mean circumference reduction of 8.7 ( + /- 8) mm , compared to a steady placebo circumference of 387 ( + /- 31 ) mm at all 3 visits with a mean circumference reduction of only 2 mm ( + /- 9 ) . The estimated treatment effect at week 8 was -6.7 mm , 95 % confidence interval ( -10.3 , -3.0 ) . The mean circumference of the ankle , decreased from 243 ( + /- 20 ) mm to 238 ( + /- 20 ) mm at the 4th week , contrasted with a constant placebo circumference of 241 ( + /- 22 ) mm at both visits . The estimated treatment effect at week 4 was -5.4 mm , 95 % confidence interval ( -10.2 , -0.6 ) . However , at week 8 , the estimated treatment effect was only -3.4 mm , 95 % confidence interval ( -8.6 , + 1.8 ) . In conclusion , HR capsules may show an improvement in the clinical symptoms and may show a mean circumference reduction of the calf and ankle at the 8th week , in patients with post-thrombotic syndrome Deep venous thrombosis of the lower extremity is a serious disorder ; the estimated incidence is 1 per 1000 persons per year [ 1 - 3 ] . The disease can occur after surgical procedures and trauma and in the presence of cancer or inherited coagulation disorders ; it can also develop without any of these factors [ 3 ] . The clinical course of deep venous thrombosis might be complicated by pulmonary embolism , recurrent episodes of deep venous thrombosis , and the development of serious post-thrombotic sequelae , such as venous ulceration , debilitating pain , and intractable edema [ 3 ] . Patients with deep venous thrombosis are usually treated with an initial course of heparin ( 5 to 10 days ) followed by 3 to 6 months of oral anticoagulant therapy . This treatment regimen reduces the risk for short-term thromboembolic complications to approximately 5 % [ 4 , 5 ] . The long-term risk for recurrent venous thromboembolism and the incidence and severity of post-thrombotic sequelae in patients with symptomatic deep venous thrombosis have not been well documented . In a recent large r and omized , clinical trial comparing 6 weeks of oral anticoagulant therapy with 6 months of therapy [ 6 ] , patients with symptomatic deep venous thrombosis were followed for 2 years for recurrences and death . This trial showed a substantial reduction in the risk for recurrent venous thromboembolism among patients in the 6-month oral anticoagulant group , but the investigators did not report on the occurrence of the post-thrombotic syndrome . Another recent study [ 7 ] reported the 8-year incidence of recurrences and post-thrombotic manifestations in patients with confirmed symptomatic deep venous thrombosis . However , only a few patients were included in this study , and data were collected retrospectively . We assessed the clinical course of a first episode of symptomatic deep venous thrombosis in a large consecutive series of patients who had long-term follow-up . We assessed mortality and the long-term incidences of recurrent venous thromboembolism and the post-thrombotic syndrome . We also evaluated the potential risk factors for these three outcomes . Methods Identification of Inception Cohort The Department of Internal Medicine of the University of Padua , Padua , Italy , is a diagnostic facility for out patients with clinical ly suspected venous thromboembolism in a community of approximately 350 000 persons . All consecutive out patients with a first episode of clinical ly suspected deep venous thrombosis who were referred by their general practitioners between January 1986 and December 1991 had noninvasive testing [ 8 ] . Patients were potentially eligible for the study if confirmatory venography showed deep venous thrombosis . Patients were excluded from the study if they had been referred because of recurrent venous thrombosis , were geographically inaccessible for follow-up , or refused to give informed consent . The Institutional Review Board of the hospital of the University of Padua approved the study . Baseline Assessment At the time of referral , demographic characteristics were recorded and a medical history was taken ; information was elicited on the period between the onset of symptoms and presentation to the thrombosis service ( patientphysician delay ) , the presence of risk factors for thrombosis ( that is , cancer , surgery , trauma or fracture , immobilization for more than 7 days , pregnancy or childbirth , or estrogen use ) , and symptoms of pulmonary embolism . Information was also obtained on the history of venous thromboembolism in first-degree relatives .  Antithrombin , protein C and S , and lupus-like anticoagulant levels were subsequently measured . Assays were done , and previously described criteria for abnormality and deficiency were used [ 9 ] . The venograms obtained at baseline were divided into those representing proximal venous thrombosis ( with or without concurrent venous thrombosis of the calf ) and those indicating isolated venous thrombosis of the calf . Proximal venous thrombosis was defined as thrombosis located above the trifurcation of the calf veins that involved at least the popliteal vein , superficial femoral vein , common femoral vein , or iliac vein . The location and occlusiveness of proximal thrombi were also determined . A patient was considered to have nonocclusive deep venous thrombosis if contrast material was seen between the thrombus and the vessel wall along the entire thrombus . Treatment Patients were admitted to the hospital and treated with an initial course of high-dose intravenous st and ard heparin ( a bolus of 5000 U followed by continuous infusion of 30 000 U/d , subsequently adjusted to maintain an activated partial thromboplastin time between 1.5 and 2.5 times the normal value ) or subcutaneous low-molecular-weight heparin ( 90 U of anti-factor Xa/kg of body weight twice daily ) . Therapy with oral anticoagulant agents ( warfarin ) was started on day 5 to 7 of treatment and was continued for 3 months . The oral anticoagulant dose was adjusted daily to maintain an international normalized ratio between 2.0 and 3.0 . Treatment with low-molecular-weight heparin was discontinued on day 10 or later if the international normalized ratio was less than 2.0 . This treatment strategy deviated in the following groups of patients : those with cancer , protein deficiencies , or lupus anticoagulant , in whom oral anticoagulation therapy was prolonged ; those with small isolated venous thrombosis of the calf , who received oral anticoagulation alone ; those with contraindications to anticoagulant treatment , who received no treatment or an inferior caval-vein filter ; those who refused to be hospitalized , who received low-dose heparin and oral anticoagulant agents ; and those with threatened viability of the leg , who received thrombolytic therapy .  The actual type and duration of treatments were recorded . All patients were instructed to wear elastic graduated compression stockings ( providing 40 mm Hg of pressure at the ankle ) for at least 2 years . Follow-up All patients were seen 3 and 6 months after the initial referral and thereafter returned to the study center every 6 months for follow-up assessment s. Patients were asked to return to the thrombosis center immediately if symptoms suggestive of recurrent venous thromboembolism developed . Follow-up was continued for as long as 8 years or until July 1995 . To avoid diagnostic suspicion bias , the medical history on general health , symptoms of recurrent venous thromboembolism , and the post-thrombotic syndrome was obtained by using a st and ardized form . Patients who could not attend the follow-up sessions were visited at home . For all patients who died during follow-up , the date and cause of death were documented . Diagnosis of Recurrent Venous Thromboembolism and Hemorrhage Contrast venography of the symptomatic leg or legs was done as described previously [ 10 ] . The criteria for deep venous thrombosis were a constant intraluminal filling defect confirmed in at least two different projections or nonvisualization of a vein or a segment thereof , despite adequate technique and repeated injections with contrast material . The presence or absence of venous thrombosis was assessed by a panel of independent observers who were unaware of the patient 's other clinical features or previous test results . If a patient presented with clinical ly suspected recurrent venous thrombosis of the leg , venography was done . The criterion for recurrent venous thrombosis of the leg was a new intraluminal filling defect on the venogram . If the venogram was not diagnostic , recurrent venous thrombosis was diagnosed on the basis of an abnormal 125I-fibrinogen leg scan or results of noninvasive tests that had changed from normal to abnormal [ 11 , 12 ] . Patients with suspected pulmonary embolism had venography if they had concurrent leg symptoms or perfusion lung scanning in the absence of leg symptoms . Pulmonary embolism was excluded if the perfusion scan was normal . Because ventilation lung scanning was not available during the first years of the study and because pulmonary angiography could not routinely be done , we could not definitively diagnose pulmonary embolism in some patients . If a definitive diagnosis could not be made , patients were classified as not having recurrent venous throm 
    Output:
    
Lower rates of improvement in PTS were shown in the rutoside treated group when compared with an alternative venoactive remedy .
More PTS deterioration was shown in the placebo or no treatment group when compared with rutosides but this was not statistically significant .
Compared with ECS , rutosides showed higher odds of PTS deterioration but this was also not statistically significant .
There was no evidence that rutosides were superior to the use of placebo or ECS .
Overall , there is currently limited and low or very low quality evidence that ' venoactive ' or ' phlebotonic ' remedies such as rutosides reduce symptoms of PTS .
The three studies included in this review provide no evidence for the use of rutosides in the treatment of PTS