Autonomic cardiac function in children and adolescents with long COVID: a case-controlled study.

Although the mechanisms underlying the pathophysiology of long COVID condition are still debated, there is growing evidence that autonomic dysfunction may play a role in the long-term complications or persisting symptoms observed in a significant proportion of patients after SARS-CoV-2 infection. However, studies focused on autonomic dysfunction have primarily been conducted in adults, while autonomic function has not yet been investigated in pediatric subjects. In this study, for the first time, we assessed whether pediatric patients with long COVID present abnormalities in autonomic cardiac function. Fifty-six long COVID pediatric patients (mean age 10.3 ± 3.8 y) and 27 age-, sex-, and body surface area-matched healthy controls (mean age 10.4 ± 4.5y) underwent a standard 12-lead electrocardiography (ECG) and 24-h ECG Holter monitoring. Autonomic cardiac function was assessed by time-domain and frequency-domain heart rate variability parameters. A comprehensive echocardiographic study was also obtained by two-dimensional echocardiography and tissue Doppler imaging. Data analysis showed that pediatric patients with long COVID had significant changes in HRV variables compared to healthy controls: significantly lower r-MSSD (root mean square of successive RR interval differences, 47.4 ± 16.9 versus 60.4 ± 29.1, p = 0.02), significant higher values VLF (very low frequency, 2077.8 ± 1023.3 versus 494.3 ± 1015.5 ms, p = 0.000), LF (low frequency, 1340.3 ± 635.6 versus 354.6 ± 816.8 ms, p = 0.000), and HF (high frequency, 895.7 ± 575.8 versus 278.9 ± 616.7 ms, p = 0.000). No significant differences were observed between the two groups both in systolic and diastolic parameters by echocardiography.  Conclusion: These findings suggest that pediatric patients with long COVID have an imbalance of cardiac autonomic function toward a relative predominance of parasympathetic tone, as already reported in adult patients with long COVID. Further studies are needed to clarify the clinical significance of this autonomic dysfunction and demonstrate its role as a pathophysiological mechanism of long COVID, paving the way for effective therapeutic and preventive strategies. What is Known: • Long Covid in children has been described globally, but studies have mostly focused on collecting the temporal evolution of persisting symptoms. What is New: • Cardiac autonomic imbalance toward a relative predominance of parasympathetic tone is a mechanism underlying Long Covid in children, as also described in adults.

Outer retina dysfunction and choriocapillaris impairment in type 1 diabetes.

To study the outer retina morpho-functional characteristics and the choriocapillaris (CC) features in type 1 diabetic (T1D) patients, with and without signs of diabetic retinopathy (NPDR and NoDR). Twenty-five NPDR and 18 NoDR eyes were imaged by Optical Coherence Tomography Angiography. Ellipsoid zone (EZ) "normalized" reflectivity and CC perfusion density parameters, as flow deficits number (FDn), flow deficit average area (FDa) and flow deficit percentage (FD%), were analysed. Multifocal electroretinogram (mfERG) response amplitude densities (RADs) were measured. Mean EZ "normalized" reflectivity, CC FDn and FD% values, were similar (p > 0.05) in both groups, FDa was significant greater (p > 0.05) in NPDR compared with NoDR eyes. MfERG-RADs were similar in both groups. NPDR eyes showed a significant (p < 0.05) linear correlation between RADs and both, CC FDa and FD%. The EZ "normalized" reflectivity was negatively correlated with CC FD% in NoDR eyes. In NPDR T1D eyes a significant relationship between abnormal outer retina functional responses and CC impairment was observed, while in NoDR eyes the photoreceptor reflectivity was correlated to CC abnormalities. The outer retina dysfunction in NPDR correlated to CC drop-out let hypothesize that the outer retinal elements are functionally impaired in proportion to the CC vascular supply deficit.

Pycnogenol may alleviate adverse effects in oncologic treatment.

AIM: A large variety of adverse reactions are well known to frequently occur during chemotherapy and radiotherapy in oncology. Specific medications exist to target individual side effects. The aim of this study was to explore in a pilot trial whether supplementation with French maritime pine bark extract Pycnogenol could alleviate side effects and improve patient's quality of life. METHODS: Cancer patients who previously underwent surgery and who were in view of their pathology in relatively good condition, both physically and psychologically, were recruited for this study and divided into two groups. These patients received their first cycle of radiotherapy or chemotherapy, which lasted from 10 days up to 1 month. Then one group of patients received 150 mg Pycnogenol, the control group comparable placebo in a single-blinded fashion. The authors studied the occurrence of side effects and made attempts to judge their severity on a semi-quantitative visual analogue scale over a 2 months period starting after patients completed their first cycle of chemo- or radiotherapy, respectively. RESULTS: Twenty five radiotherapy patients receiving Pycnogenol showed a decreased frequency of essentially all investigated side-effects as compared to 21 patients receiving placebo, though in many categories the difference was limited. The most apparent improvements of acute side effects related to decreased soreness and ulceration in the mouth and throat as well as less dryness of the mouth and the eyes. A decreased incidence of nausea /vomiting, diarrhoea, edema and weakness was noticed, which was reflected by semi-quantitative evaluation suggesting that severity was only half or even less pronounced than in the control group. Only one case of deep vein thrombosis occurred in the Pycnogenol group whereas 2 cases of superficial vein thromboses and one case of deep vein thrombosis occurred in the control group (2.9% vs 10%). Thirty four chemotherapy patients were supplemented with Pycnogenol and another 30 patients were in the control group. For all patients this was the first chemotherapy treatment period. The Pycnogenol group presented with a lowered incidence of all investigated side effects as compared to the control group, though in many cases to a limited extent. The most prominent improvements were found for nausea, vomiting, diarrhoea and weight loss. Semi-quantitative evaluation showed that here again symptom severity was half or less pronounced than in the control group. Various further symptoms improved such as cognitive impairment and also cardiotoxicity and neutropenia. Effects on anemia could not be investigated as several patients received erythrocyte transfusion. In the Pycnogenol group one case of superficial vein thrombosis was indentified while 3 cases of superficial vein thromboses and one deep vein thrombosis were detected in the control group (4% vs 19%). In both chemotherapy and radiotherapy patients Pycnogenol lowered the requirement for medication to address side effects. This was reflected by less days of hospitalisation the patients required. The authors did not investigate a possible interference with the anti-neoplastic efficacy of chemo- and radiotherapy. This possibility requires attention in future studies with Pycnogenol. From their previous clinical experience the authors suggest that alleviation of side effects described in this study results from Pycnogenol activities related to endothelial protection, and anti-inflammatory anti-edema activities. CONCLUSION: The results of this pilot trial warrant further prospective studies with larger number of patients to validate benefits more specifically with regard to type of malignancy and treatment regimen.

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.

Jet-lag: prevention with Pycnogenol. Preliminary report: evaluation in healthy individuals and in hypertensive patients.

This study was conducted with the aim of showing the effects of Pycnogenol on controlling jet-lag symptoms. Oral Pycnogenol, 50 mg tablets 3 times/die, for 7 days starting 2 days prior to the flight was used. The study was divided into two separate parts. In study 1 the most common complaints of patients with jet-lag were evaluated with a rating scale consisting in of a scoring system. In study 2 a brain CT scan was performed after the flight in order to assess minimal brain edema (MBE) in association with typical signs and symptoms, observed in previous published flight studies. Study one included 38 subjects treated with Pycnogenol and 30 controls. The symptomatic jet-lag related total score was significantly lower (indicating a lower level of jet-lag) in the Pycnogenol group. The average duration of any jet lag symptom following the flight was significantly reduced from 39.3 (SD=0.8) hours in controls to an average of 18.2 (SD=3.3) hours in the Pycnogenol group (P<0.05). Study 2 included 34 subjects treated with Pycnogenol and 31 controls. The main observation was the brain CT scan performed within 28 hours after the end of the flight. The difference between the Pycnogenol and the control groups was statistically significant (P<0.05) for all items assessed including the cerebral edema score obtained by CT scan. The short-term memory was significantly altered in the control group and associated to edema and swelling of the lower limbs. The score (and the level of edema) was comparatively higher in a subgroup of hypertensive subjects in the control group. Minor alterations of cardiac function were observed in association with de-stabilisation of blood pressure. Fatigue was also significantly higher in the control group in comparison with the Pycnogenol group. A number of spontaneously reported symptoms was also scored and there was a statistically significant difference (P<0.05) between the Pycnogenol and control groups. In conlusion, Pycnogenol was useful to control jet-lag and minimal brain edema.

Fingerprints and cardiovascular risk. The San Valentino fingerprint vascular screening project (SanVal/FP).

UNLABELLED: Fingerprints (FP), characteristic of humans, are impressions due to skin marks (ridges) on fingertips. Ridges are present on fingers/hands forming curved lines of different sizes/patterns. The point where a line stops or splits is defined typica' (their number/amount constitute identification patterns). FP are permanent and unique. This study compared FP patterns with cardiovascular risk factors: 7 main types of FP were used: 1. Arch: lines form waves from one site to the other side. 2. Tentarch: like arches but with a rising stick in the middle. 3. Loop: lines coming from one site returning in the middle to the same site. 4. Double loop: like loops but with two loops inside: one standing, one hanging. 5. Pocked loop: like the loop but with a small circle in the turning point. 6. Whorl: lines make circles. 7. Mixed figure: composed of different figures. There are two kinds of real typica: A. Ending line; B. Splitting lines (bifurcations). Several combinations may result. Ultrasound evaluation of carotid/femoral arteries in asymptomatic subjects. Arteries were evaluated with high-resolution ultrasound at the bifurcations. Four classes were defined: 1: normal intima-media (IMT) complex; 2: IMT thickening; 3: non-stenosing plaques (<50% stenosis); 4: stenosing plaque (>50%). Subjects in classes 1, 2, 3 were included into the analysis made comparing FP patterns and ultrasound. RESULTS: For each FP pattern: A. the main proportion of subjects with cardiovacular risk factors (91%) had arches (41.2%) and loops (either single, 38.2% or double 11.7% for a total of 49.9%). B. The remaining classes were statistically less important. C. The number of ridges per square mm was comparable in all pattern classes. D. The analysis of typica and other ridges characteristics requires a more elaborated system. Future research must define simple, low cost screening methods for preselection of subjects at higher cardiovascular risk or for exclusion of low risk subjects. The evaluation of fingerprint pattern may be useful to define risk groups.

[NPT (near patient test) in the pharmacy: document and practice guidelines 2008]. / Screening nelle farmacia: documento e linee guida 2008.

NPT tests in the pharmacy. Blood testing can be made with NPT (near patient testing) directly in the pharmacy. Most tests can be made with a single drop of blood (i.e. from a finger) and results are comparable with results from blood test obtained with standard vein blood samples. NPT is basically used for: 1 - evaluating the risk of a disease. 2 evaluating or confirming the presence of a disease. 3 to manage and monitor treatments. The social role of the pharmacy in NPT (particularly in cardiovascular screening) is very important as the pharmacy is an institution with capillary diffusion in the territory. The pharmacy often constitutes an important, first-level consultancy point for the population, particularly where health institutions are far away (small villages) or not easily accessible. Rules for NPT. Guidelines for NPT testing in the pharmacy have been proposed and discussed in a consensus meeting (Spoleto, 2007). NPT guidelines suggest operating management and technical procedures and indicate prospective lines of action defining new roles for the pharmacy. Coagulation tests can be now made in the pharmacy at a very low cost and with an efficacy comparable to blood tests obtained with a vein sample. Results can be read in seconds. This test is also available for personal use and home testing. NPT: The Clinical Study. The evaluation of the results of a clinical study (patients with venous thrombosis/pulmonary embolisation, patients with fibrillation and patients with artificial cardiac valves) indicates that costing is very favourable for NPT which may reduce costs and improve management of many clinical conditions and their monitoring. Training and control systems help NPT testing to be reliable and useful to screen and manage most clinical and risk conditions. The clinical study also shows the positive correlation between NPT tests and standard' tests. In conclusion NPT tests are now very reliable and cost-effective and can be used for screening, diagnosis and to monitor treatments.

Treatment of ankle sprain in patients with vascular diseases of the lower limbs.

Patients (with venous or arterial disease) are particularly affected by even minor sprains as edema, swelling are more disabling and cause a more severe clinical picture. In such vulnerable population, it is imperative to rehabilitate the patient in shortest possible time to regain the functionality of the injured joint and thus assure ambulation. The aim of the present study was to compare the efficacy of locally applied and orally administered ketoprofen in a group of 41 patients with vascular diseases of lower limbs with accidental grade I ankle sprain. Forty one patients were included in this study and divided into in three treatment groups: ketoprofen 10% spray gel* (360 mg/die), oral ketoprofen (tablets, 25 mg t.i.d. and control group (no pharmacological treatment). The duration of treatment was one week. The three groups of patients were comparable for age and sex distribution and for the clinical characteristics at inclusion. After seven days of treatment all patients experienced reduction of symptoms (pain at rest and on active movement, swelling) which was significant only in patients treated by topical, local application of ketoprofen. The effects of oral treatment were not significantly different from those observed in untreated controls. The minimal effort treadmill testing showed significant increase in pain-free walking distance in patients who applied the medication locally in comparison to the other groups. The tolerability of locally applied ketoprofen was good and no side effects were noted. The observed clinical outcomes of the patients included in this small, pilot study indicated that locally applied ketoprofen 10% spray gel is effective in relieving the pain and other symptoms of ankle sprain in vascular patients.

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.

Topical heparin: new observations.

Topical effects of heparins on the skin need deeper investigations. The lack of evidence is mainly due to the lack of large investments in this field. Three main local actions of heparin on the skin can be defined: (a) the anticoagulant action, (b) the microcirculatory-modulatory action determining important control of the microcirculation in case of excessive vasoconstriction or vasodilatation, and (c) the 'facilitatory action' on skin permeability allowing other drugs to diffuse better and faster into the skin (producing a therapeutic effect). These aspects have to be evaluated more extensively in both experimental and clinical conditions. Recent experimental studies demonstrate these effects of locally applied heparin. Therefore, key questions on local heparin administration such as skin penetration and the action on the local thrombi have promising answers. These observations suggest important clinical applications for local liposomal heparin. Both the potentials of local applications of heparin, particularly with new formulations, and some new aspects in the management of superficial vein thrombosis (SVT) can focus on locally applied heparin. SVT is an important clinical condition considering its frequency and the potentially heavy use of local heparin in this clinical problem. Results from new studies and observations presented in this issue of Angiology could be a window for suggesting new significant clinical applications and therapeutic solutions.

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.

Comparison of Pycnogenol and Daflon in treating chronic venous insufficiency: a prospective, controlled study.

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 (CVI) in comparison to the combination of diosmin and hesperidin (Daflon, Servier, France). A group of 86 patients with severe chronic venous insufficiency (CVI), venous hypertension, ankle swelling) and previous history of venous ulcerations received either oral Pycnogenol (capsules) 150 mg or 300 mg daily for 8 weeks or Daflon, 1,000 mg/day. All patients completed the study without dropouts. At the end of the study, microcirculatory results indicated: a progressive decrease of skin flux at rest (RF); a significant decrease in capillary filtration (RAS); an improvement in the symptomatic venous score (ASLS); a reduction in edema; a significant improvement (increase) in pO(2) and a decrease in pCO(2) in the Pycnogenol group. A significant level of improvement was reached after 4 weeks of treatment in most patients (p < .05) of the Pycnogenol group while clinical improvement was significant only in 6 subjects in the Daflon group. The positive effects of treatment with Pycnogenol after 8 weeks were significantly larger in comparison with the Daflon group. In conclusion, this study confirms the fast clinical efficacy of Pycnogenol in patients with chronic venous insufficiency and venous microangiopathy and its superiority-considering the evaluated parameters-to the combination of diosmin and hesperidin.

Diabetic ulcers: microcirculatory improvement and faster healing with pycnogenol.

Diabetic microangiopathy leads to lower limb ulcers that are very slow to heal. Pycnogenol was evaluated on diabetic ulcers in a controlled trial. Ulcer medications were used in 4 groups (30 patients): (1) systemic Pycnogenol and local application; (2) local Pycnogenol only; (3) oral Pycnogenol; and (4) medications only (control group). Ulcerated areas and symptom scores were more reduced with the combined oral and local treatment (P < .05). Oral and local treatment were less effective, but still improved compared with the controls. Combined treatment produced 89% complete healing at 6 weeks versus 84% with local treatment and 85% with oral treatment; healing in controls was 61%. The combined treatment group and oral only group had better microcirculation after the combined treatment. Combined local and systemic application of Pycnogenol may offer a new treatment of diabetic ulcers. Local treatment also speeds ulcer healing.

Rapid relief of signs/symptoms in chronic venous microangiopathy with pycnogenol: a prospective, controlled study.

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.

Cramps and muscular pain: prevention with pycnogenol in normal subjects, venous patients, athletes, claudicants and in diabetic microangiopathy.

The aim of this study was to assess the preventive action of Pycnogenol (Horphag Research Ltd, UK) on cramps and muscular pain in different groups of subjects and patients. The study included a 5-week observation period (4 weeks treatment and one follow-up week after the suspension of treatment) to evaluate the efficacy of Pycnogenol after its withdrawal. Four 50 mg capsules (total dose 200 mg/day) were prescribed with suggestion to drink at least 1.5 liters of water every day. In the first part of the study 66 healthy subjects completed a 5-week follow-up period. The difference between number of cramps attacks recorded within the 2 weeks before inclusion and the number of episodes during the fourth (p <0.05) and fifth (p <0.05) week were statistically significant. In normal subjects the average number of episodes was reduced from 4.8 (1.2) events per week to 1.3 (1.1) at 4 weeks (p <0.05). In venous patients the decrease in events was from 6.3 (1.1) to 2.6 (0.4) per week (p <0.05). In athletes the number of episodes decreased from 8.6 (2) to 2.4 (0.5) (p <0.05). The decrease was still present at 5 weeks in the 3 groups, to levels significantly lower than inclusion values (p <0.05). In the second part of the study, patients with intermittent claudication and diabetic microangiopathy were evaluated and treated (4 weeks). The groups treated with Pycnogenol and the control, placebo groups were comparable. There was a significant decrease in the number of cramps episodes (p <0.05) and in the score concerning muscular pain (p <0.05) in claudicants and diabetics. No significant effects were observed in the placebo groups. In conclusion, cramps and muscular pain, common in these 2 types of patients, were decreased by the use of Pycnogenol. Globally, these results suggest that the use of Pycnogenol prevents cramps, muscular pain at rest, and pain after/during exercise in normals, in athletes prone to cramps, in patients with venous disease, in claudicants, and in diabetics with microangiopathy. The difference is statistically significant considering objective observations (cramps episodes) and evaluating more subjective aspects (score). This indicates that Pycnogenol is effective in reducing pain and cramps during retraining and rehabilitation increasing its efficiency. In starting any physical rehabilitation program, particularly in vascular subjects, the limitation in mobility associated with muscular pain and with cramps tends to be relevant, and controlling these symptoms is useful to speed up the retraining process.

Venoruton vs Daflon: evaluation of effects on quality of life in chronic venous insufficiency.

The aim of this independent study was to investigate differences in efficacy between oxerutins (Venoruton) and 500 mg micronized diosmin + hesperidin (D+H) (Daflon) in patients with chronic venous insufficiency (CVI), evaluating venous-related quality of life (Ve-QOL). A first group of 90 patients with severe venous hypertension (CVI, ankle swelling) was randomized to treatment with oxerutins or D+H. The oxerutins group received oral oxerutins (2 g/day); the D+H group received 3 (500 mg) tablets daily every 8 hours for 8 weeks. A second group of 122 comparable patients was included in a registry following the same study format. The 2 treatments were administered with the same methods and procedures. Clinical conditions were comparable. All patients completing 8 weeks of treatment were included in a registry. Specialists or general practitioners included patients when they considered that clinical conditions were compatible with treatment indications using 1 of the 2 treatments on the basis of their evaluation and experience. When cases were compatible with the registry, the prescribing physician communicated the case to our monitoring center. Patients were evaluated without interfering with their treatment. The main target of evaluation for this study was the change in Ve-QOL (range, 0-100) induced by treatment. A specific Ve-QOL questionnaire was used for this study. Ve-QOL score is a specific expression of the changes in QOL induced by CVI in patients between 35 and 75 years old (defined in our population studies) in which no other significant clinical disease is present (as a confounding factor affecting QOL). Two hundred twelve patients completed the 2 parts of the study. The 2 treatment groups were comparable for age and gender distribution. The mean age was 42 years (SD +/-5.5) in the oxerutins group and 41.5 (SD +/-6) in the D+H group. There were no differences in the severity of CVI between the treatment groups at inclusion. A significant decrease (46.8%, p <0.05) in Ve-QOL score; that is, improvement, was observed in the oxerutins group. The change in Ve-QOL was significantly less in the D+H group (15.5%). In conclusion, CVI, venous microangiopathy, and edema were significantly improved by the treatment with oxerutins; the improvement in QOL was significantly greater in the oxerutins group. The comparison with D+H indicates that oxerutins is comparatively more effective on Ve-QOL and on signs/symptoms of CVI.

Improvement of diabetic microangiopathy with pycnogenol: A prospective, controlled study.

The aim of this study was to investigate the clinical efficacy of oral Pycnogenol (Horphag Research Ltd, United Kingdom) in patients with diabetic microangiopathy. Patients without a history of diabetic ulcerations were treated with Pycnogenol. Patients received oral Pycnogenol (50 mg capsules, 3 times daily for a total of 150 mg daily for 4 weeks). A group of 30 patients was included (severe microangiopathy); 30 comparable patients were observed as controls (no treatment during the observation period). All patients (age, 59 years; range, 55-68 years; male:female = 18:12) included in the treatment group completed the 4-week study. Also, all controls completed the follow-up period. There were no drop-outs. All included subjects had signs and symptoms of diabetic microangiopathy. The duration of diabetes-from the first signs/symptoms--was on average 7.5 years (SD = 3). After 4 weeks, microcirculatory and clinical evaluations showed a progressive decrease in skin flux at rest in the foot (indicating an improvement in the level of microangiopathy), a significant decrease in capillary filtration, and a significant improvement in the venoarteriolar response in all treated subjects. There were no visible effects in controls except a slight reduction in skin flux at rest in the foot. Treatment was well tolerated in both groups. In conclusion, this study confirms the clinical efficacy of Pycnogenol in patients with diabetic microangiopathy. The study indicates the clinical role of Pycnogenol in the management, treatment, and control of this common clinical problem. The treatment may be also useful to prevent diabetic ulcerations by controlling the level of microangiopathy.

Prevention of edema in long flights with Pycnogenol.

The aim of this study was to evaluate the prevention of edema during long-haul flights with an oral, anti-edema and antithrombotic agent (Pycnogenol, Horphag, Research Management SA, Geneva, Switzerland) in asymptomatic subjects. The assessment of edema was performed by evaluating an analogue scale, the rate of ankle swelling by strain-gauge derived rate of ankle swelling (RAS), and by assessing the ankle circumference variation. The study included 211 subjects; 169 completed the study (88 in the control group and 81 in the Pycnogenol group). There were no important differences between the two groups (comparable for age, gender, weight, body mass index, and pattern distribution). The edema score, the RAS, and the circumference at inclusion were also comparable. After the flight in those treated with Pycnogenol, the edema score was increased only by 17.9% (vs. an increase of 58.3% in the control group) (p<0.05). The RAS, evaluated in 22 subjects in the Pycnogenol group (age 44.5; SD 8) and in 23 in the control group (age 45; SD 9) was increased on average by 91% in the control group and 36% in the Pycnogenol group (p<0.05). The variation on circumference at the ankle was 6% in the Pycnogenol group (11% in the control group; p<0.05). These results indicate a positive effect of Pycnogenol on edema during long flights when considering subjective and objective data. No unwanted effects were observed.

HR, 0-(beta-hydroxyethyl)-rutosides, in comparison with diosmin+hesperidin in chronic venous insufficiency and venous microangiopathy: an independent, prospective, comparative registry study.

The aim of this independent study was to investigate differences in efficacy between HR, (0-[beta-hydroxyethyl]-rutosides) and D+H (500 mg, diosmin+hesperidin) in patients with chronic venous insufficiency (CVI). A first group of 90 patients with severe venous hypertension (CVI, ankle swelling) were randomized into an HR or a D+H group. The HR group received oral HR (2 g/day, 8 weeks); the D+H group received a 500 mg tablet 3 times daily for 8 weeks. A second group of comparable patients was included in a registry following the same study format. Patients were openly included; the 2 treatments were administered with the same methods and procedures. Clinical conditions were comparable to those described in the randomized study. Patients treated for at least 8 weeks were included in the registry. A number of physicians (specialists or general practitioners) included patients when they considered that clinical conditions were compatible with using 1 of the 2 treatments on the basis of their personal evaluation and experience. When cases were compatible with the registry, the prescribing physician communicated the case. Patients were evaluated without interfering with the treatment. Main targets of evaluation were skin flux at rest (RF), strain-gauge-derived rate of ankle swelling (RAS), and analogue symptoms score (ASLS). Ninety subjects completed the study in the first group; 122 in the second, registry group (total of 212 patients). The first and second (registry) groups and the 2 treatment groups were comparable for age and sex distribution. The pooled mean age was 42 years (SD +/-5.5) in the HR group (46+62 patients) and 41.5 (SD +/-6) in the D+H group (44+60 patients). Considering pooled data there were no differences in microcirculatory parameters between the pooled treatment groups at inclusion. A significant decrease (p<0.05) in RF and RAS was observed in the HR group at 8 weeks. The decrease in resting skin flux and in capillary filtration was associated with a significant improvement in signs/symptoms (analogue scale line) from an average of 9.4 (range 3-10) to 3.3 (4-6) (p<0.05). Significantly smaller variations were observed in the D+H group. The decrease in RF was 47.6% in the HR group vs 15.7% in the D+H group. The decrease in RAS was 40.9% in the HR group vs 12.8% in the D+H group. The decrease in ASLS was 64.8% in the HR group vs 12.9% in the comparative group. In conclusion venous microangiopathy and edema were improved by the treatment with HR both in the randomized study and in the pooled analysis. The comparison with D+H indicates that HR is comparatively more effective both on microcirculatory parameters and on signs/symptoms of CVI.

Venous ulcers: microcirculatory improvement and faster healing with local use of Pycnogenol.

Chronic venous insufficiency (CVI) causes a well-defined microangiopathy described as venous hypertensive microangiopathy (VHM) leading to venous ulcerations. VHM is mainly observed in the distal part of the leg, in the perimalleolar region. In VHM edema is the consequence of increased capillary pressure and reduced local clearance, and this affects local perfusion. The healing of venous ulcers is usually very slow. Many treatments are available, but there is still no standard. Oral Pycnogenol is effective in venous disease and particularly in controlling edema. The aim of this study was the evaluation of the local effects of Pycnogenol on ulcers healing associated with venous hypertension. The study lasted 6 weeks including 18 patients (16 completed the study) with venous ulcerations. The oral treatment with Pycnogenol was compared with a combination treatment including oral and local treatment. In subjects treated with the combination treatment (oral and local), venous ulcers healed better (there was a faster reduction in ulcerated area) in comparison with oral treatment only. According to this pilot study Pycnogenol appears to have an important role in local treatment of venous ulcers improving healing and signs/symptoms.