Management of Varicose Veins and Chronic Venous Insufficiency in a Comparative Registry with Nine Venoactive Products in Comparison with Stockings.

The aim of this registry study was to compare products used to control symptoms of CVI. Endpoints of the study were microcirculation, effects on volume changes, and symptoms (analogue scale). Pycnogenol, venoruton, troxerutin, the complex diosmin-hesperidin, Antistax, Mirtoselect (bilberry), escin, and the combination Venoruton-Pycnogenol (VE-PY) were compared with compressions. No safety or tolerability problems were observed. At inclusion, measurements in the groups were comparable: 1,051 patients completed the registry. Best performers : Venoruton, Pycnogenol, and the combination VE-PY produced the best effects on skin flux. These products and the combination VE-PY better improved PO 2 and PCO 2 . The edema score was decreased more effectively with the combination and with Pycnogenol. Venoruton; Antistax also had good results. Considering volumetry, the best performers were the combination PY-VE and the two single products Venoruton and Pycnogenol. Antistax results for edema were also good. The best improvement in symptoms score were obtained with Pycnogenol and compression. A larger decrease in oxidative stress was observed with Pycnogenol, Venoruton, and with the VE-PY combination. Good effects of Antistax were also observed. Parestesias were lower with Pycnogenol and with Antistax. Considering the need for interventions, the best performers were Pycnogenol, VE-PY, and compression. The efficacy of Pycnogenol and the combination are competitive with stockings that do not have the same tolerability in warmer climates. A larger and more prolonged evaluation is suggested to evaluate cost-efficacy (and non-interference with drugs) of these products in the management of CVI. The registry is in progress; other products are in evaluation.

Supplementary management of benign prostatic hypertrophy with Prostaquil. An 8-week registry.

The aim of this registry was to evaluate the management of initial symptoms of benign prostatic hyperthrophy (BPH) in otherwise healthy subjects, using Prostaquil® (Alchem) in a 8-week registry. Prostaquil was used at the dosage of 200 mg/day. The product includes Pygeum extract (100 mg) and Saw palmetto oil (35 mg). The two resulting groups standard management and supplement) were comparable. RESULTS: No side effects or comparability problems were observed and compliance was optimal with more than 95% of the capsules correctly used. Empting, frequency, intermittency, urgency, weak flow, straining, nocturia were all significantly improved with Prostaquil (p<0.05) and the improvement - globally and evaluating any single item - was significantly superior to the one observed in controls (p<0.05). Quality of life with the supplement was also significantly better in comparison with controls (p<0.05). The residual vescical volume was 94.7;5,8 ml in the supplement group at inclusion and decreased to 39.3;5 ml (p<0.05) at 8 weeks. This decrease was equivalent to a reduction of 58.5%(vs a decrease of 27.9% in controls)(p<0.05; ANOVA). In conclusion, the most common symptoms of BPH are controlled by Prostaquil a new standardized supplement including Pygeum.

Effects of Pycnogenol® on endothelial dysfunction in borderline hypertensive, hyperlipidemic, and hyperglycemic individuals: the borderline study.

AIM: This registry study aimed to evaluate the effects of supplementation with pycnogenol on altered endothelial function (EF) in borderline hypertensive, hyperlipidemic and hyperglycemic subjects without atherosclerotic changes in their main arteries and no coronary artery disease. METHODS: Flow mediated dilatation (FMD) and endothelium-independent (EID) dilatation were measured with brachial ultrasound after occlusion. Also, after occlusion, laser Doppler (LDF) flux and distal straingauge flow were measured. Oxidative stress (oxstress) was evaluated at 8 and 12 weeks. 93 subjects with borderline symptoms were enrolled into the study: 32 hypertensives, 31 hyperlipidemics, 30 hyperglycemics. All participants were instructed to follow the best available management to control their symptoms. In addition to best management, half of the subjects in each group used 150 mg/day Pycnogenol(®). 31 normal subjects were included as control. RESULTS: After 12 weeks metabolic values and blood pressure were back to normal in all subjects. Values were slightly better under Pycnogenol(®). FMD increased after 8 weeks from an average 5.3;3.4% to 8.2;2.2% with a further increase to 8.8;3.1% (P<0.05) at 12 weeks. No effects were found in controls and normal subjects. EID of normal subjects was consistently higher with 26%. LDF skin flux increased with Pycnogenol(®) at 8 weeks and 12 weeks. The final flux increase was not different from normal values. In controls flux after occlusion was not improved at 8 weeks; there was a significant but minor increase at 12 weeks. Flux increases were superior in all Pycnogenol(®) subjects. In Pycnogenol(®) subjects, limb flow after occlusion increased at 8 weeks with a further increase at 12 weeks. In controls inclusion flow after occlusion was comparable at 8 and 12 weeks. Oxidative stress was significantly decreased in Pycnogenol(®) subjects at 8 and 12 weeks. Minor differences were observed in controls. CONCLUSION: This open registry study indicates that Pycnogenol(®) improves EF in preclinical, borderline subjects in a macro-microcirculatory model. This observation may suggest an important preventive possibility for borderline hypertensive, hyperglycemic and hyperlipidemic subjects.

Pycnogenol® in postpartum symptomatic hemorrhoids.

AIM: The aim of this registry study was to evaluate the efficacy of Pycnogenol® (Horphag Research Ltd.), a standardized extract from the French maritime pine bark, to control signs/symptoms and prevent complications associated with hemorrhoids in the months after delivery in healthy women. METHODS: Women with hemorrhoids after their second pregnancy were included within the third month after pregnancy. Pycnogenol dosage was 150 mg/day for 6 months. Symptoms for 4th and 3rd degree hemorrhoids were evaluated. RESULTS: The registry groups were comparable. For 4th degree hemorrhoids, main symptoms were reduced after 6 months in all patients, but the group using Pycnogenol in addition to standard best management showed more improvement. In patients with 3rd degree hemorrhoids, symptoms were reduced in both management groups at 6 months; with Pycnogenol the reduction in symptoms scores was significantly better. At 6 months 18/24 subjects (75%) in the Pycnogenol group were symptom-free in comparison with 14/25 (56%) in controls. In the 4th degree hemorrhoid group, 7/10 patients (70%) in the Pycnogenol group were symptom-free at 6 months in comparison with 4/11 subjects (36%) in the best management group. No significant side effects were observed. CONCLUSION: Pycnogenol appears to positively affect hemorrhoid signs and symptoms in the months after pregnancy.

Meriva®, a lecithinized curcumin delivery system, in diabetic microangiopathy and retinopathy.

BACKGROUND: In the present study, the improvement of diabetic microangiopathy and retinopathy was evaluated in 38 diabetic patients treated with a novel curcumin phospholipids delivery form (Meriva®). METHODS: Diabetes was diagnosed at least 5 years before inclusion and all patients had signs of retinal oedema and of peripheral microangiopathy. Meriva® was administered at the dosage of 2 tablets/day (each tablet containing 500 mg Meriva® corresponding to 100 mg curcumin) for a period of at least 4 weeks in addition to the standard management plan, while a comparable group of subjects (n = 39) followed the standard management plan alone. RESULTS: All subjects (treatment and controls) completed the follow-up period, there were no dropouts and Meriva® showed an optimal tolerability. At 4 weeks, microcirculatory and clinical evaluations indicated an improvement of microangiopathy. In terms of peripheral microangiopathy, in the Meriva® group, there was a significant improvement in the venoarteriolar response (p<0.05) and a decrease in the score of peripheral oedema (p<0.05), a sign typically associated with the failure of the venoarteriolar response. At the retinal level, high-resolution, duplex scanning, used to measure retinal flow, showed improvements in the Meriva® treated patients. The evaluation of retinal oedema (Steigerwalt's scale) showed an improvement associated with improved visual acuity (Snellen scale). There were no clinical or microcirculatory effects in controls. CONCLUSION: These preliminary observations, indicate the value of curcumin, when administered in a bioavailable form as with Meriva®, in the management of diabetic microangiopathy and retinopathy.

[Severe intermittent claudication: PGE1 treatment. A 40-week registry, efficacy and costs]. / Claudicatio intermittens severa: trattamento con PGE1. Registry, follow up (40 settimane), efficacia e costi.

AIM: Intermittent claudication (IC) in peripheral vascular disease is characterized by lower limb pain appearing on effort. Treatment with PGE1 has been successfully used to manage IC patients. This registry has evaluated safety and costs of PGE1 in the management of IC. METHODS: In this study a long-term treatment protocol (LTP), a short-term protocol (STP) and an outpatient (OP), "on-demand" treatment have been compared. A treadmill effort test has been used to evaluate walking distance. The follow up for these three protocols was 40 weeks. PGE1 treatment was associated to a risk reduction plan and to an exercise program. RESULTS: The final analysis has included 252 LTP patients, 223 STP patients and 284 OP patients (total 659 valid cases). A group of 171 comparable patients not treated with PGE1 was used for a parallel comparison. Cardiovascular mortality and morbidity has been evaluated in 731 PGE1 patients completing 24 months of follow up. All protocols have been well tolerated. No side effects were observed. The lower cost has been observed for OP patients. In the long term, mortality and morbidity were lower in patients treated with PGE1 in comparison with patients not treated with PGE1. CONCLUSION: Considering costs and results (increase in walking distance) and improvement in Karnofsky scale the STP plan appears to be better than LTP for IC patients. The OP, "on-demand" treatment offers further improvements. This last treatment plan is simpler; the plan allows better timing for exercise. The treatment can be used even in non-specialized centers.

Venoruton®: post thrombotic syndrome. Clinical improvement in venous insufficiency (signs and symptoms) with Venoruton®. A five-year, open-registry, efficacy study.

AIM: This registry evaluation was conducted in post-thrombotic syndrome (PTS) patients (with a minimum five-year follow up). The study evaluated: 1) variations in peripheral edema with an analogue scoring system; 2) ankle circumference at the PTS limb in comparison with the normal contralateral limb. METHODS: The difference was expressed in percent increase in circumference measured at the PTS limb; 3) other end-points were observed in a five-year follow-up that created a specific PTS registry. Subjects could follow a management system including: 1) compression; 2) compression and Venoruton® (1 g/day); 3) compression and Venoruton® (2 g/day). RESULTS: The groups of patients with chronic venous insufficiency (CVI) resulted comparable. The occurrence of a new deep venous thrombosis (DVT) episode was considered a drop out. At five years there were four new DVTs (in 90 patients) in the compression group. There was one case (90 patients included) in the compression and HR (1 g) group and no DVT in group 3. The outcome in groups 2 and 3 was significantly better (0.05) than in group 1. The need for surgery or sclerotherapy (for larger varicose veins), the occurrence of lipodermatosclerosis and ulcerations were significantly lower in the HR groups with a better outcome in the higher dose group (P<0.05). The number of ulcerations were also significantly reduced in the HR groups. The difference in ulcerations was significantly better in the higher dose group in comparison with the other groups (P<0.05). The edema score was significantly reduced at five years in the HR groups (P<0.05) in comparison with the compression group. The higher dose resulted more effective in controlling edema. Both edema score and ankle circumference at five years were significantly lower (P<0.05) in the HR-treated groups with a significant decrease in edema score and ankle circumference in the higher dosage group. CONCLUSION: The study confirms the long-term efficacy of HR in PTS, CVI patients. Controlling signs/symptoms and edema in CVI with HR prevents the most severe complications of CVI including lipodermatosclerosis and venous ulcerations. An early therapeutic program including exercise, risk factor controls, compression an edema-controlling treatment with HR is effective in decreasing the classic complications of PTS syndrome. The important restrictions and difficulties to the use of elastic stockings (in regions with warmer climates) are not applicable to HR that is well tolerated and can be used all the time alone or in association with compression.

Prevention of post thrombotic syndrome with Pycnogenol® in a twelve month study.

AIM: Post-thrombotic syndrome is a common complication following deep vein thrombosis. The aim of this twelve month registry study was to compare the efficacy of compression stockings and per oral administration of Pycnogenol® standardized pine bark extract on the severity and incidence of post thrombotic syndrome signs and symptoms. METHODS: One hundred fifty-six patients with a single, major episode of proximal deep vein thrombosis (DVT) were assigned to one of three groups receiving treatment with either compression stockings (group 1), Pycnogenol® (group 2) or the combination of both (group 3) over an investigational period of one year. The study evaluated treatment on edema using a scoring system, the ankle circumference, and the limb volume as ratio to the healthy contralateral limb. RESULTS: Two new incidents of DVT occurred in the group of 55 patients wearing compression stockings between the third and sixth months, whereas no DVT cases occurred in the two other groups which took Pycnogenol®. The edema symptom score was gradually decreased in all three groups during the one year treatment period. Pycnogenol® was significantly more effective from six months onwards than compression stockings for relieving edema symptoms (P<0.05). Symptoms were more effectively reduced with the combination of Pycnogenol® and compression stockings than with the individual regimen alone (P<0.05). Limb volume and ankle circumference were likewise more effectively reduced with Pycnogenol® plus stockings than with compression stockings alone after six months. Ambulatory venous pressure progressively decreased in all three groups after twelve months treatment as compared to baseline. Compression stockings and Pycnogenol® were of comparable efficacy, there were no significant differences of ambulatory venous pressure between groups following twelve months treatment. Laser Doppler flowmetry at the dorsum of feet showed improved micro-circulation which was further demonstrated by increased pO2 and decreased pCO2. Importantly, none of the patients developed ulcerations during the observational period. CONCLUSION: This study suggests that Pycnogenol® may have significant long-term protective efficacy for individuals following a thrombotic event. Moreover, Pycnogenol® appears to be at least as effective for post-thrombosis management as compression stockings, while the combination of both is superior. An important aspect is the patient compliance which was found to be much better in the Pycnogenol® group with two drop-outs due to non-medical reasons, whereas in the compression stockings group eighteen patients were lost to follow-up because wearing stockings at higher temperatures is bothersome.

Silver oxide ointment wound dressing in venous ulcerations: home, self-management.

AIM: Venous ulcers are a common, chronic medical and social problem. These ulcers are difficult to heal in most patients with sustained venous hypertension. This pilot product evaluation registry study has evaluated the efficacy and safety of an antimicrobial silver oxide wound dressing ointment ("Silver Oxide Ointment") as part of the treatment of 'difficult' venous ulcerations. METHODS: The study was conducted measuring the variations in the area of the ulceration and microcirculatory parameters. RESULTS: After four weeks, treatment with the Silver Oxide Ointment proved more effective than the 'best management' used in controls. Transcutaneous PO2 was increased (improved); Laser Doppler skin flux and transcutaneous PCO2 were improved (decreased). Also in the silver oxide group a significantly higher number of venous ulcers were completely healed at four weeks. The silver oxide ointment improved both the microcirculation and the healing rate of their ulcers. No significant tolerability problems were observed. CONCLUSION: In difficult venous ulcerations, local treatment with this Silver Oxide Ointment, as one component of the total wound dressing, improved microcirculation measurements and healing rate. Most of the treatments were done at home by the patients or by their tutors. This study indicates the important role of this type of treatment and indicates the need to plan larger and more prolonged studies.

Potential role of curcumin phytosome (Meriva) in controlling the evolution of diabetic microangiopathy. A pilot study.

AIM: The aim of the present study was to evaluate the improvement of diabetic microangiopathy in patients suffering from this condition since at least five years, and whose disease was managed without insulin. METHODS: Curcumin, the orange pigment of turmeric, has recently received increasing attention because of its antioxidant properties, mediated by both direct oxygen radical quenching and by induction of anti-oxidant responses via Nrf2 activation. This aspect, combined with the beneficial effects on endothelial function and on tissue and plasma inflammatory status, makes curcumin potentially useful for the management of diabetic microangiopathy. To further evaluate this, Meriva, a lecithinized formulation of curcumin, was administered at the dosage of two tablets/day (1 g Meriva/day) to 25 diabetic patients for four weeks. A comparable group of subjects followed the best possible management for this type of patients. RESULTS: All subjects in the treatment and control group completed the follow-up period; there were no dropouts. In the treatment group, at four weeks, microcirculatory and clinical evaluations indicated a decrease in skin flux (P<0.05) at the surface of the foot, a finding diagnostic of an improvement in microangiopathy, the flux being generally increased in patients affected by diabetic microangiopathy. Also, a significant decrease in the edema score (P<0.05) and a corresponding improvement in the venoarteriolar response (P<0.05) were observed. The PO2 increased at four weeks (P<0.05), as expected from a better oxygen diffusion into the skin due to the decreased edema. These findings were present in all subjects using Meriva, while no clinical or microcirculatory effects were observed in the control group. CONCLUSION: Meriva was, in general, well tolerated, and these preliminary findings suggest the usefulness of this curcumin formulation for the management of diabetic microangiopathy, opening a window of opportunities to be evaluated in more prolonged and larger studies. The molecular mechanisms involved in the beneficial effects of curcumin on microcirculation and edema are also worth investigation.

Gore external valve support for superficial saphenous vein incompetence: a 10-year, follow-up registry.

AIM: This long-term (10-year) study evaluated the safety and efficacy of expanded polytetrafluoroethylene (ePTFE) external valve support (EVS) implants used for external valvuloplasty in the treatment of incompetence of the proximal long saphenous veins. METHODS: During a 10-year follow-up, patients with superficial venous disease and venous hypertension due to pure superficial vein incompetence underwent an external valvuloplasty using an EVS with a PTFE suture. Forty-nine patients were included in the EVS group and 47 in the control group. Patients with superficial venous disease and venous hypertension due to pure superficial venous incompetence were randomised into two treatment groups. The first group was treated with what was considered "conventional treatment" (ligation or stripping) and the second with external valvuloplasty with EVS. This report deals with controls treated with ligation as only 6 cases (not mentioned in this report) were treated with stripping. There were no significant differences in the two groups concerning age, sex, or type of venous insufficiency. The procedures focused on only one single limb per patient. RESULTS: 46.9% of limbs treated with EVS developed varices in comparison with 73% in the control group. New surgical procedures (localized ligation) were needed in 32.6% of the EVS patients vs. 55.3% in controls. Sclerotherapy was used in 42% of the EVS patients vs. 72.34% in controls. At 10 years the SFJ was incompetent (reflux) in 2 EVS patients (4%); one after 5 years and one after 7 years. There was no incompetence at the level of the ligated junction in controls. There were 62 incompetent venous sites (1.26 per limb) in the EVS group vs. 96 new incompetent venous sites (2.04 per limb) in controls. In controls 10.63% of the limbs developed minor discolorations and signs due to mild CVI; none was observed in the EVS group. In all ESV implants there was full restoration of competence at 1 year. CONCLUSION: EVS implants used to correct superficial venous incompetence at 10 years were well tolerated and produced good results on incompetence and on the evolution of varicose veins.

Pycnogenol® improvements in asthma management.

AIM: The simplification of the management of asthma in the different clinical phases of this common chronic inflammatory disorder is the main goal of therapy. Pycnogenol®, a standardized extract of French maritime pine bark, inhibits expression of 5-lipoxygenase and consequently decreases leukotriene levels in asthmatic patients. Pycnogenol® anti-inflammatory activities may be supportive when taken in addition to inhalation corticosteroid (ICS), putatively allowing for a reduction in dosage and frequency of ICS administration. METHODS: This study evaluated the efficacy of Pycnogenol® during a period of six months for improving allergic (mite in house dust) asthma management in patients with stable, controlled conditions. Pycnogenol® was used at a daily dosage of 100 mg, distributed as 50 mg in the morning at 9 am and again in the evening at 9 pm). An individual patient's asthma condition was graded in five steps based on the daily dosage of inhaled fluticasone propionate with step 1 indicating 0 µg and step 5 the maximum dose of 500 µg ICS twice daily. RESULTS: A total 76 patients were enrolled for this study. The group taking Pycnogenol® in addition to ICS and the group taking only ICS were comparable for age, gender and clinical characteristics including FEV1. The analysis of therapeutic ranking steps showed that 55% of patients taking Pycnogenol® improved as judged by passing to a lower ICS dose step. In comparison, only 6% of patients depending exclusively on ICS progressed to a lower (ICS dose) therapeutic step. No deterioration (passage to a higher ICS therapeutic step) was observed in the Pycnogenol® group, whereas in 18.8% of patients depending exclusively on corticosteroids a deterioration requiring a higher dosage step was observed. The passage to different therapeutic steps was statistical significant between groups (P<0.05). Drop-outs were associated entirely to irregularities in follow-up and not due to medical reasons. No serious adverse events were observed in both groups and tolerability of Pycnogenol® was very good. The levels of asthma control in the 6 interventional months as compared to the same period in the previous year were compared. In the Pycnogenol® group, night-awakenings were less frequent, the number of days with PEF<80% were decreased, days with asthma score >1 were lower, requirement for salbutamol and additional asthma medication less frequent, and consultation of general practitioner and specialist required less commonly. All these parameters were statistical significantly improved in Pycnogenol® + ICS group versus the ICS control group where no considerable changes were observed. Various common signs and symptoms were evaluated by visual analog scale, (dry) cough, severity of chest symptoms, wheezing, dyspnea and daytime symptoms. In the ICS-only group values did not improve while they did improve significantly in the ICS + Pycnogenol® group (P<0.05 vs. ICS only group). A decrease by 15.2% of the specific IgE titer was found in the Pycnogenol® + ICS group, whereas the titer increased by 13.4% in the ICS-only group, while IgG1 and IgG4 remained unchanged in both groups. CONCLUSION: Pycnogenol® administration was effective for better control of signs and symptoms of allergic asthma and reduced the need for medication.

Osteoporosis of the jaw. Product evaluation: mf Odontovis Calcium®.

AIM: The aim of this study was to test mf Odondovis Calcium® as a food supplement in a 3-month product evaluation study measuring how the low jaw bone density, could be improved. The upper jaw density was tested with an ultrasound method, evaluating the grey scale median of the images (GSM). METHODS: Seventy nine subjects were enrolled; 22 normal subjects (group A) and 57 with upper jaw osteoporosis (according to DEXA values). Patients were divided into 2 groups (group B and C, respectively 28 and 29 cases). These subjects were treated with what was considered the' best treatment' and in the group B only was added mf Odontovis Calcium®, consisting of calcium salts, Vitamin D and physiological modulators with antioxidant activity. This treatment continued for 3 months. RESULTS: The GSM of osteoporotic patients was significantly lower in comparison with GSM in normal subjects. No changes were observed (between the inclusion and 3 month values) in normal subjects and minimal, non-significant changes were observed in control osteoporosis patients. Before-after treatment values of GSM in treatment patients showed a significant increase (P<0.022) at 3 months. The increase in GSM in these patients was significantly higher (P<0.05) in comparison with control patient with osteoporosis. The Tolerability of the product was very good and the compliance corresponded to 98%. CONCLUSION: the jaw density in patients with osteoporosis is increased in only 3 months with supplementation with mf Odontovis Calcium®. Long-term clinical implications should be observed in more prolonged studies.

Faster healing of venous ulcers with crystacide: a clinical and microcirculatory 8-week registry study.

AIM: This registry evaluated the result of treatment with Crystacide in 73 patients with chronic venous insufficiency (CVI) and ulcerations. The local application of a hydrogen peroxide cream (Crystacide, Sandoz) onto the skin was evaluated with clinical and microcirculatory parameters. After briefing, one group used Crystacide and standard management for ulcers, including compression. A comparable group that did not use Crystacide was also evaluated. METHODS: Laser Doppler flowmetry (LDF) was used to measure skin perfusion in association with skin TcP02 and TcPCO2. Crystacide was applied around and on the ulcer area for a period between 6 and 9 weeks (with a target time of observation of 8 weeks). RESULTS: Treatment with Crystacide was more effective. The increased skin flux at inclusion (indicating venus hypertension and microangiopathy) decreased in both groups (improving); TcO2 was increased (P<0.05) and TcCO2 was decreased (P<0.05) in both groups. However, changes in the microcirculatory parameters were significantly larger in the Crystacide group. The average ulcer area was significantly smaller at the average target time of 8 weeks in the Crystacide group in comparison with controls (P<0.05). In the Crystacide group 64.86% of the ulcers were completely healed at 8 weeks versus 38.88% in controls. The difference (+25.98%) in the treatment group is significant (P<0.002). CONCLUSION: Local treatment with Crystacide improves the healing of venous ulcerations by improving skin perfusion.

Patency of arteriovenous fistula for dialysis improbe with topical spraygel heparin.

AIM: Vascular access for hemodialysis can be provided by a native arteriovenous fistula (AVF), a synthetic arteriovenous graft (AVG), or a central venous catheter. The mature, native fistula is considered the preferred type of vascular access. This study evaluates the results of a retrospective registry assessing topically applied heparin (added to antiplatelet therapy) efficacy in patients with newly created AVF. METHODS: To the current "best treatment", a number of patients also added topical heparin spray, a formulation containing a high concentration of heparin sodium for topical administration. At present, the average followup time is 7.9 months (range 3-12). RESULTS: In all patients using topical heparin, AVF remained patent and suitable for dialysis at three months. One fistula occluded at six months, and one more become unsuitable for dialysis. In patients using only antiplatelets, three fistulas occluded at three months and another two at six months of follow-up. In all, after six months of follow-up, there were two patients using heparin for whom the dialysis access was not suitable for dialysis; in the group treated with antiplatelets only, the access could not be used any longer in six patients. Addition of heparin reduced the risk for patency loss by 16.7% at three months and by 22.2% at six months. The risk of reduced dialysis suitability of the fistula was reduced by 27.6% and 22.2%, respectively. The odds for the loss of fistula patency and dialysis suitability at six months follow-up in patients treated with antiplatelet versus combined treatment was 6.5 and 4, respectively. Also, the number of patients needed to treat (NNT) with the addition of heparin spray to achieve AVF patency and suitability at three and/or six months suggests the benefit of combined adjuvant medical treatments for prevention of early AV shunt failure. The safety and tolerability of both treatments were good. CONCLUSION: Considering these results, it appears that topically applied heparin may sustain AVF patency and suitability for dialysis.

Venous and diabetic ulcerations: management with topical multivalent silver oxide ointment.

AIM: In addition to contemporary compression therapy, one of the therapeutic approaches is the use of a topical wound care agent. The goal of this pilot registry study is to evaluate the efficacy and safety of a uniquely designed ointment containing multivalent silver oxide (Ag4O4) in the healing of difficult diabetic or venous ulcerations. METHODS: Patients who had ulcers resulting from chronic venous insufficiency or diabetes participated in this open-label, randomized registry study. All patients were evaluated by measuring both the area of the ulceration and microcirculatory parameters. 148 patients were included in the study and categorized into two main groups: venous ulcers and diabetic ulcers. Each main group was then randomized into two sub-groups: topical treatment with silver oxide ointment and the control group (standard cleaning and compression management methods, without silver ointment). All patients were treated with accepted cleaning and compression management. RESULTS. In subjects with venous ulcers: After 4 weeks, the silver treatment was more effective than the control group treatment: Skin PO2 was increased 2.1 times more than the control group (17.4% to 8.2%) and skin flux (RF) was improved 1.6 times more than the control group (-38.7% to -24.2%). The total surface area of the ulcer was significantly reduced in the silver treatment group by 1.9 times the control group (-88.7% to -46.9%). In addition, in the silver treatment group we observed complete closure of the ulceration in 42% of subjects compared to 22% in the control group (P=<0.05). In subjects with diabetic ulcers: after 4 weeks, the silver treatment was more effective than the control group treatment: Skin PO2 increased 2.6 times more than the control group (23.3% to 9.1%) and skin flux (RF) was significantly improved 4.3 times more than the control group(-26.7% to -6.2%). The total surface area of the ulcer was significantly reduced in the silver treatment group by 3.7 times the control group (-89.0% to -23.9%). In addition, in the silver treatment group we observed complete closure of the ulceration in 39% of subjects compared to 16% in the control group (P

Variations in C-reactive protein, plasma free radicals and fibrinogen values in patients with osteoarthritis treated with Pycnogenol.

In a previous, double-blind, placebo-controlled study we evaluated the efficacy of a 3-month treatment with Pycnogenol for 156 patients with osteoarthritis of the knee. Pycnogenol significantly decreased joint pain and improved joint function as evaluated using the WOMAC score and walking performance of patients on a treadmill. In this study, we further investigated the anti-inflammatory and antioxidant activity of Pycnogenol in a subset of the osteoarthritis patients presenting with elevated C-reactive protein (CRP) and plasma-free radicals. Elevated CRP levels have been suggested to be associated with disease progression in osteoarthritis. In our study, 29 subjects of the Pycnogenol group and 26 patients in the placebo group showed CRP levels higher than 3 mg/l at baseline. Comparison of blood specimens drawn at baseline and after 3-month treatment showed that Pycnogenol significantly decreased plasma free radicals to 70.1% of baseline values. Plasma CRP levels decreased from baseline 3.9 mg/l to 1.1 mg/l in the Pycnogenol group whereas the control group had initial values of 3.9 mg/l which decreased to 3.6 mg/l. The CRP decrease in the Pycnogenol was statistical significant as compared to the control group (P < 0.05). Fibrinogen levels were found to be lowered to 62.8% of initial values (P < 0.05) in response to Pycnogenol. No significant changes for plasma free radicals, CRP and fibrinogen were found in the placebo-treated group. The decrease of systemic inflammatory markers suggests that Pycnogenol may exert anti-inflammatory activity in osteoarthritic joints and patients did not present with other ailments or infections. The nature of the anti-inflammatory effects of Pycnogenol with regard to CRP warrants further investigation.

Treatment of osteoarthritis with Pycnogenol. The SVOS (San Valentino Osteo-arthrosis Study). Evaluation of signs, symptoms, physical performance and vascular aspects.

The aim of this double-blind, placebo-controlled study was to evaluate the efficacy of 100 mg Pycnogenol daily (oral capsules) in a 3 month study in patients with osteoarthritis (OA). OA symptoms were evaluated by WOMAC scores, mobility by recording their walking performance (treadmill). Treatment (77 patients) and placebo group (79) were comparable for age, sex distribution, WOMAC scores, walking distances and use of antiinflammatory drugs. The global WOMAC score decreased by 56% (p < 0.05) in the treatment group versus 9.6% in the placebo group. Walking distance in the treadmill test was prolonged from 68 m at the start to 198 m after 3 months treatment (p < 0.05), under placebo, from 65 m to 88 m (NS). The use of drugs decreased by 58% in the treatment group (p < 0.05) versus 1% under placebo. Gastrointestinal complications decreased by 63% in the treatment group, but only 3% under placebo. Overall, treatment costs were reduced significantly compared with placebo. Foot edema was present in 76% of the patients of the treatment group at inclusion and in 79% of the controls. After 3 months edema decreased in 79% of Pycnogenol patients (p < 0.05) vs 1% in controls. In conclusion, Pycnogenol offers an option for reduction of treatment costs and side effects by sparing antiinflammatory drugs.

Management of uncomplicated ankle sprains with topical or oral ketoprofen treatment. A registry study.

Ankle sprains mainly caused by accidents or strenuous sport activities can often be quite painful and impair motility. If not treated immediately and correctly, sprains may lead to severe complications. The aim of the present study was to compare the efficacy and safety of topically applied ketoprofen versus orally administered ketoprofen in 20 patients with grade I ankle sprain and 34 patients with grade II sprain. The patients were divide into in two treatment groups and received either topically applied ketoprofen treatment (ketoprofen 10% spray-gel; Prontoflex; 360 mg/die) or orally administered ketoprofen treatment (ketoprofen tablets; 3x50 mg/die). Treatment duration was one week. After 3 and 7 days of treatment, reduction of spontaneous pain and pain on active movement in the Prontoflex group was significantly bigger greater in the oral treatment group, irrespective of sprain severity. Regarding secondary parameters as mobility impairment and ankle swelling topically applied ketoprofen treatment turned out to be significantly superior to orally administered ketoprofen treatment. Additionally, Prontoflex was well tolerated, whereas ketoprofen tablets caused gastrointestinal side effects in some patients. The good efficacy in pain reduction and absence of side effects in the present study distinguished the topically applied ketoprofen as a favorable treatment for patients with accidental or sport soft tissue injuries.

Management of superficial vein thrombosis and thrombophlebitis: status and expert opinion document.

Superficial vein thrombosis is characterized by clotting of superficial veins (ie, following direct trauma) with minimal inflammatory components. Superficial thrombophlebitis is a minimally thrombotic process of superficial veins associated with inflammatory changes and/or infection. Treatments generally include analgesics, elastic compression, anti-inflammatory agents, exercise and ambulation, and, in some cases, local or systemic anticoagulants. It is better to avoid bed rest and reduced mobility. Topical analgesia with nonsteroidal, anti-inflammatory creams applied locally to the superficial vein thrombosis/superficial thrombophlebitis area controls symptoms. Hirudoid cream (heparinoid) shortens the duration of signs/symptoms. Locally acting anticoagulants/antithrombotics (Viatromb, Lipohep, spray Na-heparin) have positive effects on pain and on the reduction in thrombus size. Intravenous catheters should be changed every 24 to 48 hours (depending on venous flow and clinical parameters) to prevent superficial vein thrombosis/superficial thrombophlebitis and removed in case of events. Low molecular weight heparin prophylaxis and nitroglycerin patches distal to peripheral lines may reduce the incidence of superficial vein thrombosis/superficial thrombophlebitis in patients with vein catheters. In case of superficial vein thrombosis/superficial thrombophlebitis, vein lines should be removed. In neoplastic diseases and hematological disorders, anticoagulants may be necessary. Exercise reduces pain and the possibility of deep vein thrombosis. Only in cases in which pain is very severe is bed rest necessary. Deep vein thrombosis prophylaxis should be established in patients with reduced mobility. Antibiotics usually do not have a place in superficial vein thrombosis/superficial thrombophlebitis unless there are documented infections. Prevention of superficial vein thrombosis should be considered on the basis of patient's history and clinical evaluation.