Prevention of edema and flight microangiopathy with Venoruton (HR), (0-[beta-hydroxyethyl]-rutosides) in patients with varicose veins.

The aim of this open study was the evaluation of the effects of HR (Venoruton) at a dose of 1 g/day on the prevention and control of flight microangiopathy and edema in subjects with varicose veins and moderate chronic venous insufficiency flying for more than 11 hours. Patients with varicose veins, edema, but without initial skin alterations or complications, were included. Measurements of skin laser Doppler (LDF) resting flux (RF) venoarteriolar response (VAR), ankle swelling (RAS), and edema were made within 12 hours before and within 3 hours after the flights. The resulting edema after the flights was evaluated with a composite edema score (analogue scale line). A group of 20 subjects was treated with HR (1 g/day, starting 2 days before the flight and 1 g for every 12 hours on day of travel). Another group of 18 subjects formed the control group. The length of the flights was between 11 and 13 hours; all seats were in coach class. Fifty patients were enrolled and 38 patients were evaluable at the end of the trial. The 2 groups (treatment and control) were comparable for age and sex distribution. The decrease in RF was significant in both groups with a higher flux at the end of the flight in the HR group (p < 0.05). The venoarteriolar response was decreased at the end of the flights; the decrease was lower in the HR group (p < 0.05). The increase in RAS and the edema score were significantly lower in the HR group. In conclusion HR is useful for reducing the level of microangiopathy and the increased capillary filtration and in controlling edema in patients with venous disease in long flights. The higher level of flux and VAR and the reduction in edema indicate a positive effect of HR on the microcirculation. This study confirms that HR prophylaxis is effective to control flight microangiopathy associated with edema.

Prevention of recurrent deep venous thrombosis with sulodexide: the SanVal registry.

The aim of this study was to evaluate the prevention of recurrent deep vein thrombosis (R-DVT) with an oral antithrombotic agent (sulodexide) in moderate to high-risk subjects. A group of 405 patients was included into the multicenter registry. Both compression and an exercise program were used as well as a risk-factors control plan. After diagnosis of DVT, patients were treated with oral anticoagulants for 6 months. At the end of this period a coagulation study was made and patients started treatment with oral sulodexide capsules for a period of 24 months. The femoral, popliteal, tibial, and superficial veins were scanned with high-resolution ultrasound at inclusion;scans were repeated at 6, 12, 18, and 24 months. Of the 405 subjects included into the registry 178 in the control group (mean age 52.2; SD 11; M:F=90:88) and 189 in the treatment group (mean age 53.2; SD 10.3; M:F=93:96) completed the analysis period of 24 months. At 6 and 12 months the incidence of R-DVT was lower (p<0.05) in the treatment group. At 24 months the global incidence of R-DVT was 17.9% in the control group and 7.4% in the sulodexide group (p<0.05), 2.42 times lower than in controls. The 2 groups were comparable for age and sex distribution and for the localization of the thrombi at inclusion. Also the 2 groups of dropouts were comparable. In the control group there were 32 recurrent DVTs and 24 subjects lost to follow-up (total of 56) of 202 included subjects (27.7%) in comparison with 28 failures (14 recurrent DVTs and 14 lost subjects) of 203 subjects (13.8%) in the treatment group. This difference was statistically significant. In this analysis the incidence of DVT in controls was 2.07 times higher than in the treatment group subjects. In conclusion sulodexide was effective in reducing recurrent thrombotic events in high-risk subjects.

Prevention of venous thrombosis in long-haul flights with Flite Tabs: the LONFLIT-FLITE randomized, controlled trial.

The aim of this study was to evaluate the development of edema, and superficial and deep vein thrombosis (DVT) prophylaxis with an oral profibrinolytic agent (Flite Tabs, 150 mg pinokinase, Aidan, Tempe, AZ, USA) in long-haul flights (7-8 hours), in high-risk subjects. A group of 300 subjects was included; 76 were excluded for several problems including concomitant treatments; 204 were randomized into 2 groups (active treatment or placebo) to evaluate the effects of prophylaxis with Flite Tabs. An exercise program was used in both groups. The femoral, popliteal, tibial, and superficial veins were scanned with ultrasound before and within 90 minutes after flights. Of the included subjects, 92 of 103 controls and 94 of 101 treated subjects completed the study. Dropouts were due to connection problems. Age, gender, and risk distribution were comparable in the groups. In the treatment group, no DVT was observed. In the control group, 5 subjects (5.4%) had a DVT and there were 2 superficial thromboses (7 events in 92 subjects; 7.6%). At inclusion, edema was comparable in the 2 groups. After flights there was an increase in score in controls (+12%) in comparison with a decrease (-15%) in the Flite Tabs group (the difference in variation was statistically significant). Intention-to-treat analysis for thrombotic events shows 18 failures in controls (11 lost to follow-up + 7 thrombotic events) of 92 subjects (19.6%) in comparison with 7 failures (of 94 subjects, equivalent to 7.4%) in the treatment group (p < 0.05). Events were asymptomatic. In conclusion, Flite Tabs were effective in reducing thrombotic events and in controlling edema in high-risk subjects in long flights.

Prevention of venous thrombosis with elastic stockings during long-haul flights: the LONFLIT 5 JAP study.

The aim of this study was to evaluate deep venous thrombosis (DVT) prophylaxis with specific elastic stockings in long-haul flights (11-13 hours), in high-risk subjects. A group of 300 subjects was included; 76 were excluded for several problems including concomitant treatments; 224 were randomized into two groups (stockings vs. controls) to evaluate prophylaxis with below-knee stockings. An exercise program was used in both groups. Scholl (UK) Flight Socks (14-17 mmHg of pressure at the ankle) were used. DVT was diagnosed with ultrasound scanning. The femoral, popliteal, and tibia] veins were scanned before and within 90 minutes after the flights. Of the 205 included subjects, 102 controls and 103 treated subjects completed the study. Drop-outs were due to flight connection problems. Age, gender, and risk distributions were comparable in the two groups. In the treatment group (103 subjects; mean age, 42; SD 9; M:F, 55:48), one limited, distal DVT was observed (0.97%). In the control group (102 subjects; mean age, 42.1; SD 10.3; M:F, 56:46), six subjects (5.8%) had a DVT. There were no superficial thromboses. The difference in DVT incidence is significant (p<0.0025; six times greater in the control group). Intention-to-treat analysis counts 18 failures in the control group (12 lost to follow-up + six thromboses) of 112 subjects (15.8%) versus eight failures (7.3%) in the treatment group (p<0.05). The tolerability of the stockings was very good and there were no complaints or side effects. All events were asymptomatic. Considering these observations, Scholl Flight Socks are effective in reducing the incidence of DVT in high-risk subjects.

Evaluation of the local effects of vitamin E (E-Mousse) on free radicals in diabetic microangiopathy: a randomized, controlled trial.

The aims of the study were to evaluate the short-term effects of a new thermosensitive, vitamin E (V-E) mousse on local free radicals (FR) and skin flux in diabetic microangiopathy. A group of 40 patients with diabetic microangiopathy was included. The variation in measurements of skin FR was evaluated by the D-Rom test. Subjects were between 45 and 65 years with type II diabetes and good metabolic control. E-mousse, a thermoactive preparation of acetate vitamin E (20%), was applied twice daily on the whole surface of the leg (below knee) and foot for 3 weeks. The contralateral leg was untreated acting as control. Subjects with age between 45 and 65 years with type II diabetes (diagnosed at least 5 years before) and good metabolic control (blood sugar < 180 mg/dL) were included after informed consent. Patients with uncontrolled diabetes, peripheral vascular disease, and severe lower limbs infections were excluded. Local free radicals (FR) and laser Doppler flux including the venoarteriolar response (VAR) were evaluated. The tolerability was evaluated by a semiquantitative score. Of the 40 included patients 34 completed the study. The 2 groups were comparable. At 3 weeks there was no decrease in FR in controls; the decrease in the treatment group was 45.3% (p < 0.05). Also in the treatment group RF decreased (p < 0.05) and the VARveno improved from an average of 21% to an average of 38% (p < 0.05). No significant variations were observed in the control group. The variation in symptomatic score was from a total value of 8 to 5 in the control group and from 8 to 1 in the treatment group (p < 0.02). Their tolerability was good. In conclusion local treatment with E-mousse for 3 weeks in diabetic microangiopathy improves skin microcirculation and the metabolic condition as shown by the decrease in FR.

Flight microangiopathy on long-haul flights: prevention of edema and microcirculation alterations with Venoruton.

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.

Improvement of microcirculation and healing of venous hypertension and ulcers with Crystacide. Evaluation of free radicals, laser Doppler flux and PO2. A prospective-randomized-controlled study.

In 20 patients with chronic venous insufficiency and venous hypertension associated with ulcerations, the effects of a new compound, applied onto the skin (Crystacide) were assessed in a randomized, controlled study. Duplex scanning was used to assess the presence of venous obstruction and incompetence, and microcirculatory methods were used to assess and quantify venous microangiopathy and to follow up subjects after local treatment with Crystacide. Laser Doppler flowmetry (LDF) was used to assess skin perfusion in association with transcutaneous (tc) partial pressure of oxygen (PO2) measurements. Local plasma free radicals (PFR) were evaluated in the area surrounding the venous ulcer, with the D-Rom test. Crystacide was applied around and on the ulcer for 10 days. Crystacide was more effective than the control treatment: PO2 was increased, PFR and LDF were decreased (flux increase is associated with venous hypertension), and the ulcer area was significantly smaller at 10 days in the Crystacide group in comparison with the placebo group (p<0.05). In conclusion, in venous ulcerations, local treatment with Crystacide (10 days) improves the microcirculation and decreases skin free radicals improving healing.

Foam-sclerotherapy, surgery, sclerotherapy, and combined treatment for varicose veins: a 10-year, prospective, randomized, controlled, trial (VEDICO trial).

The study compared, by a prospective, randomized method, 6 treatment options: A: Sclerotherapy; B: High-dose sclerotherapy; C: Multiple ligations; D: Stab avulsion; E: Foam-sclerotherapy; F: Surgery (ligation) followed by sclerotherapy. Results were analyzed 10 years after inclusion and initial treatment. Endpoints of the study were variations in ambulatory venous pressure (AVP), refilling time (RT), presence of duplex-reflux, and number of recurrent or new incompetent venous sites. The number of patients, limbs, and treated venous segments were comparable in the 6 treatment groups, also comparable for age and sex distribution. The occurrence of new varicose veins at 5 years varied from 34% for group F (surgery + sclero) and ligation (C) to 44% for the foam + sclero group (E) and 48% for group A (dose 1 sclero). At 10 years the occurrence of new veins varied from 37% in F to 56% in A. At inclusion AVP was comparable in the different groups. At 10 years the decrease in AVP and the increase in RT (indicating decrease in reflux), was generally comparable in the different groups. Also at 10 years the number of new points of major incompetence was comparable in all treatment groups. These results indicate that, when correctly performed, all treatments may be similarly effective. "Standard," low-dose sclerotherapy appears to be less effective than high-dose sclero and foam-sclerotherapy which may obtain, in selected subjects, results comparable to surgery.