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Managed care plans often attempt to control health care costs through strategies designed to decrease health care utilization. However, the extent to which the resulting patterns of utilization represent high-quality care (compared to fee-for-service products) remains controversial. The authors sought to compare patterns of ambulatory care (including how diffuse or fragmented the care patterns were) for Medicaid fee-for-service beneficiaries vs. Medicaid managed care beneficiaries. A serial cross-sectional study of adults (≥18 years old) was conducted using statewide Medicaid claims from New York State for calendar years 2010-2013. Beneficiaries were required to be continuously enrolled and have ≥4 ambulatory visits for each year they contributed data, yielding a sample of more than 1 million beneficiaries per year. Beneficiaries were characterized by age, sex, and case mix. For each year, ambulatory care patterns were compared across subgroups of beneficiaries using Poisson models (for numbers of visits and providers) and bounded Tobit models (for fragmentation scores). In 2010, among those who were not dual eligible, managed care beneficiaries had on average fewer visits (10.9 visits vs. 11.4 visits [

Health care fragmentation occurs when patients see multiple ambulatory providers, but no single provider accounts for a substantial proportion of visits. Most previous studies have measured fragmentation in Medicare, which may not be generalizable. The study objective was to compare the extent of fragmented ambulatory care across commercially insured, Medicare, and Medicaid populations. The authors conducted a cross-sectional study of adults (N = 256,047) in the Hudson Valley region of New York, who were continuously insured (through 5 commercial payers, Medicare, or Medicaid), were attributed to a primary care physician, and had ≥4 ambulatory visits in the study year. Fragmentation was calculated using a reversed Bice-Boxerman Index, which captures both dispersion of care across providers and the relative share of visits by each provider. Chi-square tests, t tests, and correlation were used to compare patient characteristics and patterns of care across payers. Patients with Medicare had more chronic conditions (45% had ≥5 chronic conditions) than patients with commercial insurance (20%) or Medicaid (23%) (P 0.01). However, mean fragmentation scores were comparable across all 3 payer populations: 0.73 (commercial insurance), 0.74 (Medicare), 0.72 (Medicaid). The correlation between number of chronic conditions and fragmentation was weak across payers, ranging from r = 0.004 to r = 0.12. If the extent of fragmentation does not vary with payer type or with the number of chronic conditions, it suggests that the causes of fragmentation may be more numerous and more complex than medical need alone.

INTRODUCTION: Long-term inappropriate proton pump inhibitors use (PPIs) is a matter of concern because of the risks associated with their long-term use in older patients with chronic conditions. The risk of PPI treatment in hemodialysis patients remains unexplored. METHODS: We assessed the relationship between the use of PPIs and the risk of death in hemodialysis patients throughout a retrospective multicenter propensity score-matched study. Information about demographic, hemodialysis treatment, laboratory data, and concomitant medication was obtained from the EuCliD database (Fresenius Medical Care). We studied 1776 hemodialysis patients on PPI therapy compared to 466 patients not receiving PPIs. The resulting population comprising 2 groups of 410 matched patients was studied. RESULTS: PPI use was associated with hypomagnesemia (Mg

To observe any change in ambulatory care utilization after switching from Medicaid fee-for-service (FFS) to Medicaid managed care (MC).We conducted a statewide longitudinal study of 21,048 adult Medicaid beneficiaries in New York State who switched from FFS to MC in 2011 or 2012, with 2 sets of controls (n = 21,048 with continuous FFS; n = 21,048 with continuous MC) who were matched on age, gender, dual-eligible status, and number of chronic conditions.We measured ambulatory care utilization in the 12 months before and 12 months after the switch date, using regression to adjust for case mix and account for matching.Overall, switching from Medicaid FFS to Medicaid MC was associated with greater absolute decreases over time in ambulatory visits and providers compared with controls (-1.49 visits vs continuous FFS and -1.60 visits vs continuous MC; each P.0001; -0.10 providers vs continuous FFS and -0.12 providers vs continuous MC; each P.0001). The subset of switchers with 5 or more chronic conditions had the greatest absolute decreases in visits (-5.88 visits vs continuous FFS and -5.98 visits vs continuous MC; each P.0001) and providers (-1.37 providers vs continuous FFS and -1.39 providers vs continuous MC; each P.0001). Significant decreases in visits and providers were also observed for switchers with 3 to 4 chronic conditions but not for those with 0 to 2 chronic conditions.Switching from Medicaid FFS to Medicaid MC was associated with a decrease in ambulatory utilization, especially for the sickest patients.

Results of previous studies of Medicare beneficiaries have shown that more fragmented ambulatory care is associated with more emergency department (ED) visits and hospital admissions. Whether this observation is generalizable to Medicaid beneficiaries is unknown.We conducted a 3-year retrospective cohort study in the 7-county Hudson Valley region of New York. We included 19,330 adult Medicaid beneficiaries who were continuously enrolled, were attributed to a primary care provider, and had 4 or more ambulatory visits in the baseline year.We measured fragmentation using a modified Bice-Boxerman Index. Cox proportional hazards models were used to determine associations between fragmentation score and ED visits or, separately, hospital admissions, adjusting for age, gender, and chronic conditions.The average beneficiary had 15 ambulatory visits in the baseline year, spread across 5 providers, with the most frequently seen provider accounting for 48% of the visits. One-fourth of the sample had more than 20 ambulatory visits and more than 7 providers, with the most frequently seen provider accounting for fewer than 33% of visits. For every 0.1-point increase in fragmentation score, the adjusted hazard of an ED visit over 2 years of follow-up increased by 1.7% (95% CI, 0.5%-2.9%). Having more fragmented care was not associated with a change in the hazard of a hospital admission.Among Medicaid beneficiaries, having more fragmented care was associated with a modest increase in the hazard of an ED visit, independent of chronic conditions. Fragmented ambulatory care may be modifiable and may represent a novel target for improvement.

Table S3. Cumulative numbers of deaths, competing events and censored events in prevalent and incident patients every 6â months throughout the study period. This table provides additional information to Table 5 and Fig. 1. (PDF 24 kb)

Figure S1. Study design and definition of prevalent and incident patients. This figure illustrates the design of the study and visualizes how prevalent and incident patients were defined. The renal-replacement therapy initiation date was before 1 October, 2011 for prevalent patients and between 1 October, 2011 and 31 December, 2016 for incident patients. The study index date was the study start date (1 January, 2012) for prevalent patients and the date of first treatment in the Seriate dialysis unit (i.e., any time between 1 January, 2012 and 31 December, 2016) for incident patients. (PDF 8 kb)

Table S1. Cause of renal disease of the study patients. This table provides information about the number and percentages of underling renal disease of the study participants. (PDF 17 kb)

Table S2. Use of medication at least once during the study period. This table provides information about the medication use in our study population during the study period. (PDF 18 kb)

We sought to determine the associations between fragmented ambulatory care and subsequent emergency department (ED) visits and hospital admissions, while considering possible interactions between fragmentation and number of chronic conditions.We conducted a cohort study over 3 years among 117,977 fee-for-service Medicare beneficiaries who were attributed to primary care physicians in a 7-county region of New York and had 4 or more ambulatory visits in the baseline year.We calculated fragmentation scores using a modified Bice-Boxerman Index and, because scores were skewed, divided them into quintiles. We used Cox regression models to determine associations between fragmentation and ED visits and, separately, hospital admissions, stratifying by number of chronic conditions and adjusting for age, gender, number of ambulatory visits, and case mix.Among those with 1 to 2 or 3 to 4 chronic conditions, having the most (vs the least) fragmented care significantly increased the hazard of an ED visit and, separately, increased the hazard of an admission (adjusted P.05 for each comparison). Among those with 5 or more chronic conditions, having the most fragmented care significantly increased the hazard of an ED visit but decreased the hazard of an admission (adjusted P .05 for each comparison). Among those with 0 chronic conditions, having fragmented care was not associated with either outcome.The relationship between fragmented ambulatory care and subsequent utilization varies with the number of chronic conditions. Beneficiaries with a moderate burden of chronic conditions (1-2 or 3-4) appear to be at highest risk of excess ED visits and admissions due to fragmented care.

The study compared, by a prospective, randomized method, 6 treatment options: A: Sclero therapy ; B: High-dose sclerotherapy; C: Multiple ligations; D: Stab avulsion; E: Foam-sclero therapy ; 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 occur rence 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.

AIM:he aim of this pilot, single-blinded study was to evaluate the efficacy of a proprietary, dietary supplement Lady Prelox® for supporting and improving sexual function in generally healthy, post-menopausal women. METHODS: The Lady Prelox® and placebo control groups were comparable at inclusion with regard to the total Female Sexual Function Index (FSFI) score, as well as for the six individual FSFI domains, with 40 women (50.1±3.1 years) and 43 women (51.2±2.3 years), respectively. RESULTS:At baseline the women in the verum group presented with a mean total FSFI score of 44.6±24.1 which increased significantly already after four weeks treatment with Lady Prelox® to 70.9±18.5 and further increased to 71.7±23.9 after completion of the eight-week trial period. In the control group the mean total FSFI was 44.1±22.8 at inclusion and non-significantly increased to 45±21.4 after four weeks and 47.4±21.8 after eight weeks, respectively. The treatment with Lady Prelox® was comparatively significantly more effective than placebo after both four and eight weeks of treatment (P0.05). The individual six FSFI domains related to desire, arousal, lubrication, orgasm, satisfaction and pain did all respond favourably to treatment with Lady Prelox®; however, with only marginable higher scores in the placebo group. Four women in each group dropped out because of inabilities to attend scheduled check-ups. No adverse effects were reported. CONCLUSION: This study opens an interesting perspective for women experiencing moderate sexual function impairment and suggests a promising new treatment option. Further studies with larger numbers of women, including also premenopausal and perimenopausal women are warranted.

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).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.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 (P0.022) at 3 months. The increase in GSM in these patients was significantly higher (P0.05) in comparison with control patient with osteoporosis. The Tolerability of the product was very good and the compliance corresponded to 98%.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.

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.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.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 (P0.05) 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 (P0.05) and a corresponding improvement in the venoarteriolar response (P0.05) were observed. The PO2 increased at four weeks (P0.05), 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.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.

Current efforts to reform health care have put pressure on provider organizations to become more coordinated and accountable; to improve quality while controlling costs; and to begin sharing financial risk. Success in taking on these types of activities requires a relatively sophisticated infrastructure and many policy experts believe that integrated delivery networks (IDNs), such as Geisinger Health System and Intermountain Healthcare, are the type of organizations best equipped to handle the job. However, the vast majority of Americans do not receive their health care within an IDN. In 2006, more than 60% of the nation’s 956 million annual office visits were made to primary care physicians, and 78% of these practices had five or fewer providers.1These statistics indicate that current efforts to overhaul the system, if they are only viable within IDNs, may fall far short of transforming health care for all Americans. The Hudson Valley region in New York, however, provides one example of how many of the tasks seen as essential for health care reform can be accomplished in an open community comprised of smaller, unaffiliated practices, without a formal mechanism for integration.

The aim of this study was to evaluate the efficacy of colostrum (ARD Colostrum) in association with the immunomodulator Bifivir in the prevention of flu episodes compared with anti-flu vaccination. The registry groups included no prevention, vaccination, vaccination+immunomodulators, and immunomodulators only. Groups were comparable for age and sex distribution. In the group without prevention there were 8 major episodes and 12 minor episodes out of 34 subjects (8-12/34); in the vaccination group the respective figures were 8-13/38; in the group treated with a combination of vaccination and immunomodulators (ARD Colostrum + Bifivir) the figures were 4-9/33; and in the group treated with immunomodulators only there were 11 viral episodes (3-8) in 36 subjects. The episodes in the vaccination+immunomodulators and immunomodulators only groups were significantly lower compared with the other two groups (P0.05). The number of episodes registered with the immunnomodulators was significantly lower than those observed in patients using vaccination or no prevention (P0.05). The number of days of disease was higher in untreated controls compared to the groups treated with immunomodulators (P0.05) and 2 times higher in the vaccination group compared to the same groups (P0.05). The average relative costs were significantly lower (2.3 times) in the immunomodulators groups in comparison with the other groups (P0.05). No problems concerning tolerability or side effects were observed during the study. Compliance was very good. In conclusion, the administration of immunomodulators is very cost effective and appears to be more effective than vaccination to prevent flu.

This study evaluated the clinical efficacy of Venoruton (O-(beta-hydroxyethyl)-rutosides) (HR) (Novartis Consumer Healthcare) in subjects with severe chronic venous insufficiency (CVI).Patients were included in an average 8-month follow-up registry. At the end of the study 3 spontaneous groups emerged: a group treated with HR 2 g/day, a second group with HR 1 g/day and elastic stockings, and another group with stockings only. The age range was between 45 and 55. The 3 resulting groups were comparable clinically and for age/sex distribution. There were no differences in ambulatory venous pressure (AVP) at inclusion; microcirculatory and clinical evaluations were comparable.At 8 months there was a decrease in skin resting flux in all groups. Better results (P0.05) were obtained in the group using the higher dosage and the associated treatment. Stockings alone were less effective (P0.05). There was significant decrease (P0.05) in capillary filtration (RAS) in all groups with an advantage in the combination group (P0.021). HR alone was more effective (P0.05) than compression alone. There was an improvement in the symptomatic score in all groups with better results (P0.5) in the combined group; HR alone was more effective (P0.025) than compression alone. The clinical severity score was reduced (P0.05) in all groups with better results in the combined group. HR alone was more effective (P0.05) than compression alone. The venous disability score indicated that HR alone was more effective (P0.025) than compression. No side effects or tolerability problems were observed with HR. Compliance of HR was also very good. A cost comparison was made considering a comparable control groups (cost of best standard management=100%). Cost in group A was 44% of standard costs; cost in group B (HR+stockings) was 48% of standard costs, and cost in group C (stockings only) was 67% (P0.05).The study confirms the long-term efficacy of HR in CVI patients. Controlling signs/symptoms and edema in CVI with HR also prevents the most severe complications of CVI.

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.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).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.Considering these results, it appears that topically applied heparin may sustain AVF patency and suitability for dialysis.

The aim of the paper was to describe a new formula (Antilip®) consisting of very low dosages of polyglucosamine, phytosterols and Monascus purpureus. It was given to subjects affected by high cholesterol levels.The formula was used in combination with mild physical exercise (8 MET/h/week) and mild diet (reduction of cholesterol intake through foods containing80 mg/100 g). The product combination was tested in an 8-week registry study, comparing those subjects to 33 subjects with no Antilip® treatment but following the same mild exercise training and diet.Results showed that Antilip® was effective in significantly reducing the total cholesterol levels from 268+/-23.2 to 201+/-11.4, whereas in the control group the reduction was almost absent (from 273+/-27 to 267+/-28).Data shows that Antilip® is a safe and effective treatment for hypercholesterolemia.

We investigated benefits of Pycnogenol(R) as an adjunct to hypotensive medication in metabolic syndrome patients with micro-albuminurea.Fifty eight patients were treated with Ramipril and a subgroup received Pycnogenol in addition for six months. Colour Doppler duplex ultrasound was employed for cortical flow measurements.Blood pressure decreased with Ramipril from 188.8/95.2 to 128.2/90.2, with additional Pycnogenol from 189.3/97.2 to 122.2/85.3 (P0.05). Kidney function improved in both groups, with 24 hour urinary albumin decreasing from 88.8 to 68.9 mg with Ramipril and from 89.3 to 42.2 mg with additional Pycnogenol (P0.05). In both groups treatment lowered serum creatinine, with combination treatment being significantly more effective. Cortical flow velocities significantly increased with Ramipril from systolic 17.2 +/- 3.1 to 23.8 +/- 2.0 cms-1 and diastolic 4.2+/-2.8 to 2.0+/-3.1 cms-1. The addition of Pycnogenol was more effective, improving cortical flow from systolic 18.2+/-2.2 to 27.2+/-2.9 cms-1 and diastolic 4.1+/-2.2 to 9.8+/-2.1 cms-1 (P0.05). C-reactive protein (CRP) levels decreased marginally with Ramipril, but significantly with Pycnogenol from 2.17 to 1.62 mg/dL. Pycnogenol significantly lowered fasting blood glucose to 102.3 +/- 11.2 mg/mL and HbA1c to 6.9 +/- 0.3 %. The Pycnogenol group showed a significantly lowered BMI, from baseline 26.5+/-0.9 to 25.0+/-1.2 kgm-2, without reaching statistical significance versus control. Only a limited improvement of blood lipid profile was found in both groups.Pycnogenol should be further investigated for kidney function.

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.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.

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.

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 (P0.05). 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 (P0.05) 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 (P0.05) between the Pycnogenol and control groups. In conlusion, Pycnogenol was useful to control jet-lag and minimal brain edema.

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.

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.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.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.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.

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.

Platelet interaction with neutrophils may occur to a significant degree during hemodialysis (HD). We have recently shown that the enhanced neutrophil reactive oxygen species (ROS) production during the early phase of HD with cuprophan (CUP) is sustained by neutrophils which have bound platelets through P-selectin (CD62P). The evaluation of platelet-neutrophil interactions during dialysis offers the novel aspect of cell-cell interactions as a new parameter for studying the biocompatibility of dialyzer membranes. By the use of flow cytometry techniques, the present study was set up to analyze intradialytic platelet-neutrophil coaggregate formation and neutrophil ROS (hydrogen peroxide) production from 6 HD patients each dialysed with CUP, cellulose diacetate (CDA), polymethylmethacrylate (PMMA), and polyacrylonitrile (PAN) in a cross-over clinical trial. Platelet-neutrophil coaggregate formation (percentage of neutrophil cells positive for CD62P) and ROS production by neutrophils (total population; CD62P+ cells; CD62P- cells) were determined before HD and after 10', 20'and 40'. CD62P+ neutrophils significantly increased during HD with CUP (10', 20', 40'), PMMA (20') and CDA (20), while no change was observed with PAN. The difference between CUP and the other membranes was significant at 10', 20' and 40'; at 20', PMMA vs PAN p0.005. ROS production by total neutrophil population significantly increased with CUP (10', 20), PMMA (20) and CDA (20'). The increase with CUP was higher at 10' when compared to CDA (p0.020) or PAN (p0.005), and at 20' versus the other three membranes; at 20' PMMA vs PAN p0.005. Only neutrophils gated in neutrophil-platelet coaggregate areas (CD26P+ neutrophils) produced hydrogen peroxide. ROS production by CD62P+ neutrophils significantly increased with CUP (10', 20), PMMA (20') and CDA (20'). The increase with CUP was significantly (p0.0002) higher than the other three membranes at 10' and 20'; at 20', PMMA vs PAN p0.02. With each membrane, ROS production by CD62P- neutrophils showed no significant change at any time point during HD. The results of the present study indicate that interactions between platelets and neutrophils can mediate some pathophysiological abnormalities associated with hemodialysis treatment. Our data show that cellulose diacetate, a modified cellulosic membrane, exhibits a biocompatibility profile in terms of platelet-neutrophil interactions improved as compared to the parent cellulose membrane and comparable to that of some synthetic membranes. Our data also show that there is considerable variability in the biocompatibility of synthetic membranes. Though cellulosic membranes are generally considered as being less biocompatible than synthetic membranes, our results indicate that classification of membranes by biocompatibility is more complex than a simple division into cellulosic and synthetic membranes, especially with the advent of modified cellulosic membranes.

Chronic renal failure (CRF) may be accelerated by secondary lipid and immune abnormalities which could be antagonized by polyunsaturated fatty acid (PUFA). We examined 20 CRF patients on conservative treatment, randomized in two groups: G1 consisted of 10 control patients and G2 10 patients supplemented for 12 months with a 3.4 g daily dose of PUFA. In basal conditions and after 12 months the following parameters were checked: creatinine clearance (CCr), daily urinary protein excretion per unit of residual renal function (UProt/CCr), rate of progression of renal insufficiency (delta CCr); triglycerides (TG), total (TC), HDL (HDALC) and LDL (LDLC) cholesterol, apolipoproteins Apo Al, Apo B, lipoprotein(a) Lp(a); lymphocyte subpopulations; spontaneous (c) and stimulated (s) cytokines IL-1 beta, IL-2, tumor necrosis factors TNF-alpha secretion by peripheral mononuclear cells. The groups did not differ in their basal parameters, which did not change in G1 during follow-up. In G2 the following parameters, initially higher than normal significantly decreased after 12 months: TG (2.9 +/- 0.45 to 2.6 +/- 0.3 mmol/l p0.005), Apo B (1.40 +/- 0.37 to 1.22 +/- 0.36 g/l, p0.05), c TNF-alpha (1008.1 +/- 534.9 to 726.8 +/- 458.7 pg/ml, p0.05). Spontaneous (c) IL-1 beta (216.7 +/- 116.2 to 150.5 +/- 107.8 pg/ml, p0.05), c IL-2 (124.5 +/- 43.8 to 101.6 +/- 25.8 pg/ml, p0.05), and s TNF-alpha (2456.4 +/- 908.3 to 1632.2 +/- 497.1 pg/ml, p0.005) also decreased, although already within the normal range at baseline. G2 patients experienced a steady monthly reduction of CCr whereas it rose progressively in G1 (p0.05), with a simultaneous increase in UProt/CCr (p0.05). PUFA are beneficial on the lipid and immune abnormalities secondary to CRF and may also have a useful effect on the progression of chronic renal damage.

Transient nature of adhesive interactions occurring during cell margination is mainly dependent on expression of selectins which are shed by activated cells. This shedding in the circulation may play an important role as anti-inflammatory mediator. Haemodialysis is also associated with P-selectin (CD62P)/sialyl-Lewis(x) (CD15s) interactions which mediate platelet-leukocyte coaggregation. We further investigated the mechanisms underlying leukocyte margination during haemodialysis.CD15s, CD11b and CD61 expression on circulating leukocytes from patients dialysed on synthetic membranes (modified polyacrylonitrile (SPAN), polysulphone (PS), and polyacrylonitrile (AN69) was assessed by cytofluorometry in a prospective crossover trial. We measured plasma levels C3a/C3a desArg, soluble CD62P, and CD62E molecules obtained from patients and healthy individuals.Expression of CD11b and CD15s was upregulated on neutrophils from patients dialysed with SPAN and PS membranes during the dialysis session. A significant negative correlation was found between the expression of CD11b or CD15s molecules and neutrophil counts as well as between CD15s expression and monocyte counts during haemodialysis. As assessed by CD61 expression on leukocytes, we observed that platelets bound significantly onto both neutrophils and monocytes during dialysis with both membranes. A significant positive correlation was found between the expression of CD11b molecules and the percentage of CD61+ monocytes counts during SPAN and PS dialysis. We found a significant increase of soluble CD62P in plasma samples obtained from haemodialysed patients before the dialysis session as compared to the levels detected in plasma from healthy individuals.This study documents a major role of CD15s, CD11b, CD61, CD62P molecules in the transient leukocytes activation and margination during haemodialysis on synthetic membranes despite their low complement-activating properties.

The use of recombinant human erythropoietin (rHuEPO) has revolutionized the treatment of renal anemia, but the dose regimens, the optimal frequency, and the effects on other target organs like the central nervous systems (CNS) are still under discussion. We designed a prospective, ongoing study with 10 stable continuous ambulatory peritoneal dialysis (CAPD) patients (6 males, 4 females; mean age 64.4 +/- 7.8 years), with a pretreatment hemoglobin (Hb)7.0 g% and requiring regular blood transfusions. Seven patients were treated with 4000 U rHuEPO once weekly (Eritrogen, Boehringer Mannheim), 2 patients received 4000 U every 5 and 8 days, and the last one 4000 U every 10 days. The target hematocrit was 33% and Hb 10.0 g%. The CNS activity was recorded as visual (VEP), brainstem (BAER), and somatosensory (SEP)-evoked potentials. The mean Hb concentration increased from 6.9 +/- 1.2 g% to 10.3 +/- 1.6 g% (p0.001) over 8 weeks. There were no significant changes in urea, creatinine, and potassium levels, and urine output. rHuEPO induced a decrease in latency of P100 VEP, in the four main components of BAER, and in the P27-N35 intertime of SEP. Parallel to the improvement of red cell indices, patients experienced a dramatic improvement in well-being. The subcutaneous administration of a single vial of rHuEPO is safe, convenient, and inexpensive in CAPD. The role of rHuEPO treatment in improving the electrophysiological brain function in uremic and anemic patients remains to be studied and may not necessarily be based on improved cerebral oxygenation.