Chronic venous insufficiency: worldwide results of the RELIEF study. Reflux assEssment and quaLity of lIfe improvEment with micronized Flavonoids

Chronic venous insufficiency (CVI) results in considerable morbidity and may seriously affect patients' quality of life. The RELIEF (Reflux assEssment and quaLity of life improvEment with micronized Flavonoids) Study was a prospective controlled study designed to assess differences in the severity and in the evolution of symptoms and signs of CVI according to presence or not of venous reflux. Patients were thus separated into 2 comparative groups: those presenting venous reflux and those without venous reflux. The design of the study was multicentric and international, carried out in 23 countries over 2 years, in which 5,052 symptomatic patients assigned to classes C0 to C4 (on the basis of CEAP clinical classification) were enrolled. Patients were treated with micronized purified flavonoid fraction (MPFF), consisting of 450 mg of micronized diosmin and 50 mg of flavonoids expressed in hesperidin over 6 months. In order to document changes in the quality of life of these patients during MPFF treatment, a new validated Quality of Life Questionnaire specific to CVI (CIVIQ) was used. The study also set out to gather epidemiologic data including the prevalence of venous reflux in symptomatic patients. The RELIEF study provided important information about the epidemiology and clinical manifestations of CVI. Of particular interest was the observation that venous reflux was found to be absent in 57% of patients diagnosed as suffering from CVI belonging to CEAP classes C0 to C4. A positive relationship between symptoms of CVI (pain, leg heaviness, sensation of swelling, and cramps) and presence of venous reflux was found in the RELIEF study: symptoms were more frequent and more severe at presentation in patients with venous reflux. Moreover, during MPFF treatment, all symptoms showed a greater decrease in the group without venous reflux compared with the other group. This difference in the evolution of symptoms between the 2 groups was significant for pain, sensation of swelling, and cramps. Regarding leg heaviness and signs such as edema (assessed by leg circumference), patients improved equally independently of the presence or not of venous reflux. The significant and progressive improvement in the signs of CVI was reflected in significant changes in the clinical class of the CEAP classification, ie, from more severe to less severe stages. Continuous clinical improvement was found throughout the study and after treatment with MPFF for 6 months, the clinical scores of all symptoms and signs had significantly decreased (p=0.0001 versus DO) in both groups. This improvement was also associated with a significant and continuous progression in the quality of life scores of all patients. Age of patients, average time since diagnosis, and presence of venous reflux increased with the severity of the disease. The relationship shown in this study between these parameters and clinical CEAP classification reflects the progressive nature of CVI. Despite obvious symptoms of CVI, a very low percentage (21.8%) of the "intention-to-treat" (ITT) population had previously been treated. This was the case whether venous reflux was present or not.     

HIV reporting in western Europe : national systems and first European data

AIDS case reporting has been an essential tool for monitoring HIV infection in western Europe. Recent trends in AIDS have been affected by improved antiretroviral treatments that delay HIV disease progression, however, and no longer serve as indicators of     

Reflux esophagitis in children: histological and morphometric study

BACKGROUND: Gastroesophageal reflux disease is a frequent cause of morbidity in childhood, including esophagitis and recurrent respiratory symptoms; however histological and morphometric studies in esophageal biopsies of children are scarce. AIM: To study histological and morphometric findings in children with reflux esophagitis. PATIENTS AND METHODS: We studied 26 esophageal biopsies of children (mean age: 4.1 years +/- 3.4) with reflux esophagitis, which prevailed in boys (84.6%); post-prandial vomiting (76.9%) and repetitive bronchopneumonia (38.5%) were the most frequent symptoms. The diagnosis was made by X-ray in 18, by pH evaluation in 5 and by scintilography in 3 patients. The control group was formed by seven children without reflux symptoms who died from meningococcemia or congenital heart malformation (mean age: 2.5 years +/- 2.3). Histological variables were studied by hematoxylin-eosin and periodic acid of Schiff stain, inflammatory infiltrate, epithelial and basal layer thickness, papillary length and its ratio with the thickness of the epithelium. Morphometry was performed at a digital system connected to pro-image software. Student's t test, Mann-Whitney test, Fisher and Pearson's correlation methods were used for the statistical analysis. RESULTS: Epithelial and basal zone thickness, papillary length and its rate with thickness of epithelium, among the reflux group patients were higher than the control group. Eosinophils, neutrophils and "balloon cells" were not observed in the control group. Intraepithelial capillaries occurred in 11 cases in the reflux group (mean diameter: 59 mum). CONCLUSION: Epithelial and basal zone thickness, papillary length and its ratio with thickness of epithelium, resulted greater in the gastroesophageal reflux group than in the control group. There was a direct correlation between thickness of epithelium, basal zone thickness and papillary length, showing increased epithelial cell turnover. Eosinophils, neutrophils and "balloon cells" were observed only in patients with gastroesophageal reflux, thus serving as specific markers of this disease.     

Safety of bepridil: from review of the European data.

In France, bepridil has been available since 1981 for treatment of angina. Reports of arrhythmogenic effects (torsades de pointes) related to bepridil led to the assembly of a task force of physicians from France and the Netherlands. The task force found that the risk of torsades de pointes was indeed increased in elderly patients, especially women greater than 70 years old, as well as in those taking diuretics, which can precipitate hypokalemia. Postmarketing surveillance data developed from 1981 to 1989 have revealed 108 validated episodes of torsades de pointes in patients treated with bepridil. Improved patient selection has dramatically decreased the incidence of this complication. Several comparative clinical trials assessing the safety of bepridil have concluded that the drug may prolong the QT interval in certain patients; however, no occurrence of torsades de pointes was documented in these safety studies. The 9-year French experience suggests that bepridil is a safe and effective agent for treatment of angina pectoris in properly selected patients.     

Efficacy and safety of leflunomide and predisposing factors for treatment response in patients with active rheumatoid arthritis: RELIEF 6-month data

OBJECTIVE: The RELIEF investigation was a 48-week, multicenter, international study comprising 2 phases. Results from the first phase, a 24-week open-label cohort study that evaluated the safety and efficacy of leflunomide, as well as predisposing factors to treatment response, are reported here. METHODS: Patients received leflunomide 100 mg once daily for 3 days, followed by 20 mg once daily thereafter. All adverse events were documented. Efficacy variables were the European League Against Rheumatism (EULAR) response criteria using the Disease Activity Score (DAS 28) responder rate and the response rate according to American College of Rheumatology (ACR) criteria. At Week 24, baseline data were analyzed to determine predictive factors for treatment response. RESULTS: A total of 969 patients were entered in the trial. No adverse events that have not previously been seen with leflunomide were reported. Among 968 evaluable patients, 673 (69.6%) completed 24 weeks of treatment and were responders according to DAS 28 response rate, and 587 (60.6%) completed 24 weeks of treatment and were responders according to ACR 20%. Thus, there was a high correlation between the EULAR and ACR criteria in determining treatment response. In addition, 240 (24.8%) patients had a low DAS 28 (< or = 3.2) and 123 (12.7%) patients fulfilled the disease remission criteria (DAS 28 < 2.6) at the end of the study. CONCLUSION: This study demonstrates that leflunomide is well tolerated, with a safety profile similar to that seen previously in Phase III studies, and confirms the efficacy of leflunomide across a range of patient categories.     

European survey of fertility and pregnancy in women with Crohn's disease: a case control study by European collaborative group.

Two hundred and seventy five patients with Crohn's disease from five countries were interviewed. Each patient was matched with a control of the same age. Of the 275 women with Crohn's disease 224 had been married at some time compared with 208 controls. The mean age at marriage was 23 years. Diagnosis of Crohn's disease was made five years later and the survey was conducted on average 16 years after marriage. Cases and controls had a similar obstetric study before diagnosis. After diagnosis there was a significant reduction in the number of children born to patients (0.4) compared with controls (0.7). Crohn's disease did not increase the rate of miscarriage or Caesarean section but prematurity was more common in patients (16%) than controls (7%). The site of disease at diagnosis did not affect these findings. Medical advice against pregnancy may be partly responsible for this reduction in fertility, but patients practised contraception less than controls and a significantly greater proportion of these (42%) failed to become pregnant compared with controls (28%). Crohn's disease results in subfertility.     

Multi-center study on the characteristics and treatment strategies of patients with Graves' orbitopathy: the first European Group on Graves' Orbitopathy experience

To improve management of patients with Graves' orbitopathy, a multi-center collaborative approach is necessary in order to have large enough sample sizes for meaningful randomized clinical trials. This is hampered by a lack of consensus on how to investigate the eye condition. The European Group on Graves' Orbitopathy aims to overcome this and has designed a preliminary case record form (CRF) to assess Graves' orbitopathy patients. This form was used in this first multi-center study. AIM: To investigate patient characteristics and treatment strategies in 152 new consecutively referred patients with thyroid eye disease seen in nine large European referral centers. METHODS: Newly referred patients with Graves' orbitopathy were included who were seen between September and December 2000. Demographic data and a complete ophthalmological assessment were recorded. RESULTS: One-hundred and fifty-two patients (77% females) were included. Diabetes was present in 9%, and glaucoma or cataract in 14% of patients. Forty percent were current smokers, 9% also had dermopathy, and only 33% reported a positive family history of thyroid disease. Mild eye disease was seen in 40%, moderately severe eye disease was seen in 33% and severe eye disease was seen in 28% of patients. Soft tissue involvement was the most frequent abnormality (seen in 75%), proptosis > or =21 mm was found in 63%, eye motility dysfunction in 49%, keratopathy in 16% and optic nerve involvement was found in 21% of patients. According to the clinical impression, 60% had active eye disease. Immunosuppressive treatment was planned more frequently in active patients (57/86; 66%) than in inactive patients (5/57, 9%; Chi-square 46.16; P<0.02). There were no important differences among the eight centers regarding the severity and the activity of their patients. CONCLUSIONS: In view of the large number of patients recruited in only 4 months, multi-center studies in the eight EUGOGO centers appear to be feasible.     

A new questionnaire for the repeat of the first stage of the European Community Respiratory Health Survey: a pilot study.

In the early 1990s a multicentre survey on asthma was performed on the young adult population (European Community Respiratory Health Survey - ECRHS). This study is to be repeated in order to estimate changes in the prevalence of asthma-like symptoms during the last decade and to assess the social and economic costs of the disease and their variations among countries. The self-administered questionnaire devised for this purpose is a two-page questionnaire. The first page contains the same items as those used in the first survey with four additional questions related to: 1) the frequency and severity of asthma attacks; 2) the presence of chronic bronchitis; 3) smoking habits; and 4) a visual analogue scale assessing perception of outdoor pollution. The second page aims to collect information regarding the direct and indirect costs of asthma. The influence of the length of the questionnaire on the response rate was assessed in a pilot study in Italy. Two random samples of 150 subjects received either the one-page questionnaire (first page) or the two-page questionnaire. The response rate was compared with that obtained from the first postal wave in the 1991-1992 survey. Although the response rate was unchanged when using the one-page questionnaire (45% versus 45%), it decreased by 7% when the two-page questionnaire was used (38% versus 45%). On the basis of these results, no problem should arise if four more questions are added to the one-page questionnaire. The slight reduction in the response rate of the two-page questionnaire is worrying but could be corrected by the use of telephone interviews.     

Coronary restenosis elimination with a sirolimus eluting stent: first European human experience with 6-month angiographic and intravascular ultrasonic follow-up.

AIMS: Coronary stenting is limited by a 10%-60% restenosis rate due to neointimal hyperplasia. Sirolimus is a macrocyclic lactone agent that interacts with cell-cycle regulating proteins and inhibits cell division between phases G1 and S1. The hypothesis tested in this study is that local delivery of sirolimus with an eluting stent can prevent restenosis. METHODS AND RESULTS: Fifteen patients were treated with 18 mm sirolimus eluting BX VELOCITY stents. Quantitative angiography and three-dimensional quantitative intravascular ultrasound were performed at implantation and at the 6 months follow-up. All stent implantations were successful. One patient died on day 2, of cerebral haemorrhage and one patient suffered a subacute stent occlusion due to edge dissection (re-PTCA, CKMB 42). At 9 months no further adverse events had occurred and all patients were angina free. Quantitative coronary angiography revealed no change in minimal lumen diameter and percent diameter stenosis and hence no in-lesion or in-stent restenosis. Quantitative intravascular ultrasound showed that intimal hyperplasia volume and percent obstruction volume at follow-up were negligible at 5.3 mm(3)and 1.8%, respectively. No edge effect was observed in the segments proximal and distal to the stents. CONCLUSION: Implantation of a sirolimus-eluting stent seems to effectively prevent intimal hyperplasia.     

Effective compliance during the first 3 months of continuous positive airway pressure. A European prospective study of 121 patients.

Effective compliance (time spent at the effective pressure) with nasal CPAP in obstructive sleep apnea has been reported to be poor. The aim of our study was to evaluate effective compliance in a large European multicenter study. One hundred twenty-one consecutive newly treated patients (initial apnea-hypopnea index [AHI] = 62.0 +/- 29. 5/h, AHI under CPAP = 6.4 +/- 8.1/h, CPAP pressure = 8.7 +/- 2.6 cm H(2)O, BMI = 33.1 +/- 6.8 kg/m(2)) were randomly allocated to a group with (MC(+)) (n = 58) or without (MC(-)) (n = 63) a control unit measuring effective compliance at 1, 2, and 3 mo, which was compared with the built-in time counter data. MC(+) data were 94 +/- 10, 98 +/- 5, and 96 +/- 9% of counter data at 1, 2, and 3 mo, respectively. Using criteria of regular use already reported in the literature (at least 4 h of nCPAP per day of use and nCPAP administered more than 70% of the days) we found 77, 82, and 79% compliant patients at 1, 2, and 3 mo, respectively, 79% of the patients meeting these criteria each month. Although there were no pulmonary functions or polysomnographic differences between the two subgroups, the compliant patients did report a greater improvement in minor symptoms. We found a close correlation between effective use of CPAP and the machine run time. The main result of our study was a higher effective compliance than previously reported, approximately 80% of the patients being regular users versus 46% in a previously published study. This may result from different technical and medical follow-up.     

Predictors of improvement in disease activity in first hospitalized patients with systemic lupus erythematosus: a multicenter retrospective study of a Chinese cohort

Clinical Rheumatology - To analyze the relative factors of improvement in disease activity (IDA) after first hospitalized treatment based on the systemic lupus erythematosus disease activity index...     

The first attack of acute pancreatitis: a clinical study.

Acute pancreatitis of biliary tract origin and that of alcoholic origin may be difficult to separate on clinical grounds alone. Such separation is important since operation prevents recurrent attacks in gallstone pancreatitis. We examined the records of 78 patients in the first attack of pancreatitis from gallstones or alcohol. The gallstone group were usually women, older, and had a shorter period of abdominal pain. Pancreatic complications occurred more frequently in the alcoholic group and led to two deaths. Amylase values were diagnostically helpful in that a level greater than 1000 units in patients of the proper age and sex, and a level greater than 2000 units by itself indicated gallstone pancreatitis.     

Factors associated with poor pulmonary function: cross-sectional analysis of data from the ERCF. European Epidemiologic Registry of Cystic Fibrosis.

The European Epidemiologic Registry of Cystic Fibrosis began collecting longitudinal data on European cystic fibrosis patients in 1994. A cross-sectional analysis was performed to identify the factors associated with low values of % predicted forced expiratory volume in one second (FEV1) upon patient enrollment. Data from 7,010 patients aged > or =6 yrs were included. Clinical conditions, microbiological isolates and medications reported at enrollment or within the following 180 days were analysed for age-specific associations. Factors associated with FEV1 that were lower by >10% of pred values were: lower weight for age percentiles, haemoptysis, pneumothorax, pulmonary symptoms at presentation, Pseudomonas aeruginosa, Burkholderia cepacia, oral corticosteroids, nonsteroid anti-inflammatory drugs, dornase alfa, oxygen and assisted ventilation and, in patients >12 yrs old only, use of airway clearance techniques, inhaled bronchodilators, oral nutritional supplements, pancreatic enzymes and insulin or oral hypoglycaemics. Slightly impaired lung function (5-10%) was associated with: diabetes (> or = 18-yrs-old), gastro-oesophageal reflux, allergic bronchopulmonary aspergillosis, asthma-like symptoms, portal hypertension, Aspergillus spp. and Candida spp. Sex, Haemophilus influenzae and Staphylococcus aureus were not associated with impaired pulmonary status. Regular exercise (especially in older patients) and nasal polyposis were associated with slightly better FEV1. The results confirm those of previous studies and suggest selective prescribing in sicker patients.     

Huntington's disease: improvement with an anticoagulant-psychotherapy regimen.

A 45-year old women with Huntington's disease (HD) was followed for three years while under an anticoagulant-psychotherapy regimen. The chorea disappeared and the patient improved rather than deteriorating as predicted. All psychotropic drugs were discontinued. This case of reversal of the disease may help to confirm the hypothesis that HD is probably due to circulatory insufficiency in the substantia nigra.     

Prospective Acid Reflux Study of Iran (PARSI): Methodology and study design

Background

Gastroesophageal reflux disease is a common and chronic disorder but long term, prospective studies of the fate of patients seeking medical advice are scarce. This is especially prominent when looking at non-erosive reflux disease (NERD) patients.

Methods

We designed a prospective cohort to assess the long term outcome of GERD patients referring to gastroenterologists. Consecutive consenting patients, 15 years of age and older, presenting with symptoms suggestive of GERD referring to our outpatient clinics undergo a 30 minute interview. Upper gastrointestinal endoscopy is performed for them with protocol biopsies and blood samples are drawn. Patients are then treated according to a set protocol and followed regularly either in person or by telephone for at least 10 years.

Discussion

Our data show that such a study is feasible and follow-ups, which are the main concern, can be done in a fairly reliable way to collect data. The results of this study will help to clarify the course of various subgroups of GERD patients after coming to medical attention and their response to treatment considering different variables. In addition, the basic symptoms and biological database will fuel further molecular epidemiologic studies.