***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: During chronic venous insufficiency ( CVI ) , microcirculatory changes , e.g. a decrease in transcutaneous oxygen pressure ( tcpO2 ) and an increase in transcutaneous carbon dioxide pressure ( tcpCO2 ) , are implicated in the pathophysiology of trophic disorders leading ultimately to venous ulcers . Daflon 500 mg1 , a micronized purified flavonoid fraction , has been shown to improve venous tone , capillary permeability and resistance , and lymphagogue activity at a daily dose of 2 tablets . To assess the effects of Daflon 500 mg on microcirculatory parameters by means of laser Doppler fluxmetry and transcutaneous oxiketry , a 3-month , double-blind , r and omized , parallel-group study was carried out in 104 patients divided into 3 groups according to the daily dose : 1 tablet ( group 1 , n = 34 ) , 2 tablets ( group 2 , n = 33 ) , on 4 tablets ( group 3 , n = 37 ) . All patients ( mean age 43.7 + /- 13.1 years ; 100 females , 4 males ) included in the study were affected by mild CVI . They were followed for 90 days with visits at 1 month ( day 28 ) and 3 months ( day 90 ) . At inclusion , there were no significant differences between groups as regards biometric data , mean tcpO2 ( group 1 , 62.7 + /- 4.5 mm Hg ; group 2 , 64.0 + /- 3.3 mm Hg ; group 3 , 64.1 + /- 3.5 mm Hg ) , mean tcpCO2 ( group 1 , 40.7 + /- 2.5 mm Hg ; group 2 , 39.3 + /- 2.9 mm Hg ; group 3 , 40.0 + /- 2.5 mm Hg ) and laser Doppler parameters .  Fourteen patients withdrew from the study ( group 1 , n = 4 ; group 2 , n = 3 ; group 3 , n = 7 ) : 9 for reasons not related to treatment , 3 for adverse events , 2 because they were lost to follow-up . From day 0 to day 90 , mean tcpO2 significantly increased ( p < 0.001 ) in each group ( group 1 , 3.0 + /- 2.1 mm Hg ; group 2 , 2.9 + /- 2.1 mm Hg ; group 3 , 2.5 + /- 1.6 mm Hg ) , mean tcpCO2 significantly decreased ( p < 0.001 ) in each group ( group 1 , 2.6 + /- 2.0 mm Hg ; group 2 , 1.7 + /- 1.9 mm Hg ; group 3 , 2.2 + /- 1.5 mm Hg ) . No significant differences were observed between groups . Laser Doppler parameters remained unchanged from day 0 to day 90 in the 3 groups . Symptoms ( discomfort , pain , heaviness , burning sensation ) and signs ( oedema ) of CVI as well as perimetric measurements of calf and supramalleolar area were significantly improved in the 3 groups . In conclusion , during this 3-month study , Daflon 500 mg improved oximetric measurements and did not alter laser Doppler parameters . These data suggest that Daflon 500 mg , at the early stages of CVI , acts favourably on the microcirculatory disturbances also involved in the pathophysiology of more severe stages of CVI Ninety-four patients suffering from venous insufficiency of the lower limbs participated in a multicenter , double-blind versus placebo study . After r and omization , they were allotted for a treatment period of two months to one of three groups : TECA 120 mg/day , TECA 60 mg/day , or placebo . A significant difference ( p < 0.05 ) in favor of TECA was shown for the symptoms of heaviness in the lower limbs and edema , as well as for the overall evaluation by the patient . The venous distensibility measured by a mercury strain gauge plethysmograph at three occlusion pressures was improved for the TECA groups but aggravated for the placebo group The acute effects of hydroxyethylrutosides on capillary filtration were studied in 12 normal subjects , 25 patients with venous hypertension and 22 diabetics with microangiopathy . The two groups of patients r and omly received a single oral dose ( 500 or 1000 mg ) of hydroxyethylrutosides . A single dose of 500 mg was used for normal volunteers . In the following 6 hours capillary filtration was studied with  straingauge plethysmography . The decrease in capillary filtration was evident within the first hour and was at its peak between the second and fourth hour . After 6 hours it was still significantly below baseline values in patients . The 1000 mg dose was significantly more effective in both groups of patients . This study confirms the efficacy of hydroxyethylrutosides in decreasing capillary filtration . It suggests that the effect of one dose lasts at least 6 hours and also that the higher dose is more effective Objectives Chronic venous insufficiency ( CVI ) is an important cause of discomfort and inability to work . Hydroxyethylrutosides ( Venoruton ® ; 0-[beta-hydroxyethyl]-rutosides ) has been used for decades for the treatment of CVI . Studies have reported symptomatic relief and a decreased capillary filtration after the administration of the oral preparations . Calcium dobesilate is a synthetic venoactive drug acting on several levels . It inhibits capillary permeability ; it has antioxidant properties ; and it inhibits the synthesis of prostagl and ins and thromboxanes , reducing platelet and erythrocyte aggregation , as well as blood viscosity . The aim of this study is to determine whether the combination of both drugs is more effective in decreasing patients ' complaints . Methods One hundred and fifty patients with primary venous insufficiency were r and omized into three groups : Group A receiving calcium dobesilate only , Group B receiving oxerutin only and Group C receiving both calcium dobesilate and oxerutin . Patients were evaluated with a question naire before and four weeks after treatment regarding following parameters : itching , fatigue , heaviness , numbness , cramp , swelling and sensitiveness . Patients rated their symptoms from 0 to 4 ( 0 : absent ; 1 : mild ; 2 : moderate ; 3 : severe ; 4 : very severe ) . Results Complaints , which were scored by patients before and after treatment , decreased . Among the single-drug groups , itching score decreased more in Group B , whereas scores of fatigue , heaviness , numbness , cramp and swelling decreased more in Group A. But the difference was not significant , statistically . But all complaints decreased significantly in Group C. Difference of scores after treatment revealed no statistical significance in Group A and B , but scores of Group C produced a significant difference when compared with Group A and B. Conclusion Results demonstrate that a combination of calcium dobesilate and oxerutin shows a better improvement of complaints . These observations have to be confirmed in larger series with objective tests . Changes of quality of life after a combination therapy might also be of interest The aim of this study was the evaluation of the effects of Venoruton ( HR ) on the prevention and control of flight microangiopathy and edema in subjects with varicose veins flying for more than 7 hours . A group of 80 patients with varicose veins , edema , and initial skin alterations due to chronic venous hypertension were included .  Measurements of skin laser Doppler ( LDF ) resting flux ( RF ) , Po2 and rate of ankle swelling ( RAS ) , were made before and after the flights ( within 2 hours before the flights and within 2 hours after the flights ) . The length of the flights was between 7 and 9 hours ; all seats were in coach class . The two groups ( treatment and control ) were comparable for age and sex distribution . The variation ( decrease ) in PO2 was significant in both groups . In subjects treated with HR the decrease in Po2 was smaller ( p<0.05 ) . The decrease in LDF-RF was significant in both groups with a higher flux at the end of the flight in the treated subjects ( p<0.05 ) . The venoarteriolar response was decreased at the end of the flights . The decrease was less evident in the treatment group ( p<0.05 ) . The increase in RAS was significant in the control group while it was limited in the HR group . In conclusion , HR is useful for reducing the increased capillary filtration and in controlling edema in patients with chronic venous disease in long-haul flights . HR is effective to control flight microangiopathy associated with edema The involvement of the microcirculation in diabetic microangiopathy ( DM ) may be cause of severe invalidity and ulceration . Diabetic microangiopathy ( DM ) is characterized by a diffuse increase in skin flux , reduction in venoarteriolar response , and increased capillary permeability result ing in edema ; skin PO2 is decreased and CO2 increased . In this condition , capillary exchanges are altered and nutritional alterations eventually lead to skin lesions and ulcers . The aim of this r and omized , placebo-controlled study was to evaluate the effect of local foot care and treatment with Essaven gel ( EG ) in 30 subjects with DM and neuropathy and localized , small ( < 0.5 cm in maximum diameter ) ulcers treated with a single acute application of EG .  Measurements of laser Doppler ( LDF ) flux , PO2 and PCO2 in st and ardized conditions showed positive microcirculatory changes ( a significant decrease of the abnormally increased flux and CO2 while PO2 increased ) in the active EG group lasting for at least 6 hours after application . Changes in the control group were not significant . In the placebo group variations were limited , mainly associated with skin manipulation and gel application . In conclusion , local treatment with one single st and ardized application of Essaven gel , in comparison with placebo , acutely improves the microcirculation in subjects with DM and small ulceration even with a single acute application . The microcirculatory changes are detectable even 10 hours after application The aim of this study was to investigate the clinical efficacy of oral Pycnogenol ® ( Horphag Research Ltd , UK ) in patients with severe chronic venous insufficiency . Patients with severe venous hypertension ( chronic venous insufficiency , ankle swelling ) and history of venous ulcerations were treated with Pycnogenol . Patients received oral Pycnogenol ( 50 mg capsules , 3 times daily for a total of 150 mg daily ) for 8 weeks . A group of 21 patients was included in the treatment group and 18 equivalent patients were observed as controls ( no treatment during the observation period ) . All 21 patients ( age 53 years ; range , 42 - 60 years ; M : F=11:10 ) in the treatment group completed the 8-week study . Also the 18 controls completed the follow-up period . There were no drop-outs . The average ambulatory venous pressure was 59.3 ( SD 7.2 ; range 50 - 68 ) with a refilling time shorter than 10 seconds ( average 7.6 ; SD 3 ) . There were no differences in ambulatory venous pressure or refilling time between the treatment and control patients . The duration of the disease — from the first signs/symptoms — was on average 5.7 years ( SD 2.1 ) . At 4 and 8 weeks , in all Pycnogenol-treated subjects , microcirculatory and clinical evaluations indicated a progressive decrease in skin flux , indicating an improvement in the level of microangiopathy ; a significant decrease in capillary filtration ; a significant improvement in the symptomatic score ; and a reduction in edema . There were no visible effects in controls . In conclusion , this study confirms the fast clinical efficacy of Pycnogenol in patients with chronic venous insufficiency and venous microangiopathy . The study indicates the significant clinical role of Pycnogenol in the management , treatment and control of this common clinical problem . The treatment may be also useful to prevent ulcerations by controlling the level of venous microangiopathy BACKGROUND The objective was to evaluate the oedema-protective effect of a vasoactive drug ( coumarin/troxerutin [ SB-LOT ] ) plus compression stockings in patients suffering from chronic venous insufficiency after decongestion of the legs as recommended by the new guidelines . PATIENTS AND METHODS 231 patients were r and omly assigned medical compression stockings plus SB-LOT ( 90 mg coumarin and 540 mg troxerutin per day ) or medical compression stockings plus placebo for the first 4 weeks and SB-LOT or placebo for the second 12 weeks of the study . The primary efficacy endpoint was the lower leg volume measured by well-established water plethysmometry . RESULTS 226 patients were evaluated . After ceasing compression stockings , an edema protective effect was detected in the SB-LOT-group but not in the controls . Recurrence of leg volume increase was by 6.5 + /- 12.1 ml and by 36.7 + /- 12.1 ml in the SB-LOT and placebo group , respectively ( p = 0.0402 ) . The local complaint score and general aspects of quality of life were also superior for the SB-LOT-group ( p = 0.0041 ) . Significant differences were also observed with regard to clinical global impression and therapeutic effect . No serious adverse drug reaction or clinical ly relevant impairment of laboratory parameters occur . CONCLUSION This study confirms the oedema-protective effect of SB-LOT in chronic venous insufficiency and provides a treatment option for patients who 
    Output:
    
No studies evaluating topical phlebotonics , chromocarbe , naftazone or disodium flavo date fulfilled the inclusion criteria .Moderate- quality evidence suggests that phlebotonics  reduced oedema in the lower legs compared with placebo .
In addition , phlebotonics showed greater efficacy for trophic disorders , cramps , restless legs , swelling and paraesthesia , when compared with placebo .
Moderate- quality evidence shows that phlebotonics may have beneficial effects on oedema and on some signs and symptoms related to CVI such as trophic disorders , cramps , restless legs , swelling and paraesthesia when compared with placebo but can produce more adverse effects .
Phlebotonics showed no differences compared with placebo in ulcer healing .