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SummaryAcute deep venous thrombosis (DVT) causes leg pain. Elastic compression stockings (ECS) have potential to relieve DVT-related leg pain by diminishing the diameter of distended veins and increasing venous blood flow. It was our objective to determine whether ECS reduce leg pain in patients with acute DVT. We performed a secondary analysis of the SOX Trial, a multicentre randomised placebo controlled trial of active ECS versus placebo ECS to prevent the post-thrombotic syndrome.The study was performed in 24 hospital centres in Canada and the U.S. and included 803 patients with a first episode of acute proximal DVT. Patients were randomised to receive active ECS (knee length, 30–40 mm Hg graduated pressure) or placebo ECS (manufactured to look identical to active ECS, but lacking therapeutic compression). Study outcome was leg pain severity assessed on an 11-point numerical pain rating scale (0, no pain; 10, worst possible pain) at baseline, 14, 30 and 60 days after randomisation. Mean age was 55 years and 60% were male. In active ECS patients (n=409), mean (SD) pain severity at baseline and at 60 days were 5.18 (3.29) and 1.39 (2.19), respectively, and in placebo ECS patients (n=394) were 5.38 (3.29) and 1.13 (1.86), respectively. There were no significant differences in pain scores between groups at any assessment point, and no evidence for subgroup interaction by age, sex or anatomical extent of DVT. Results were similar in an analysis restricted to patients who reported wearing stockings every day. In conclusion, ECS do not reduce leg pain in patients with acute proximal DVT.

Introduction En cas de thrombose veineuse profonde des membres inferieurs (TVP) l’efficacite de la compression elastique (CE) pour prevenir le syndrome post thrombotique est desormais debattue en particulier pour la prevention du syndrome post thrombotique (SPT). En revanche, les recommandations suggerent l’application d’une CE a la phase aigue de la TVP pour soulager le patient des symptomes de la TVP. Nous presentons ici les resultats de l’etude Celest (Promoteur Innothera) sur l’evolution a court terme des symptomes de TVP. Materiel et methode Essai therapeutique multicentrique en double aveugle comparant la CE appliquant 25 mmHg a la cheville vs. CE appliquant 35 mmHg a la cheville en cas de premiere TVP proximale des membres inferieurs. Nous avons compare l’evolution des symptomes (douleur et œdeme evalues par le patient sur une echelle analogique de 1–100) au cours des 3 premiers mois. Resultats Les resultats presentes dans ce resume sont des resultats preliminaires avant gel de base et en l’absence de levee d’aveugle. Trois cent cinquante patients ont ete randomises (75 % a l’hopital et 25 % en liberal). Leur âge moyen etait de 57,5 ans, 68 % (n = 238) etaient des hommes. Cinquante-huit pour cent (n = 202) presentaient une TVP du membre inferieur gauche et 15 % une extension iliaque. L’evolution, significative, de la diminution des symptomes a 1 semaine (s1), 1 mois (m1) et 3 mois (m3) etait comparable entre les 2 groupes (NS) : pour la douleur, la mediane etait de 28 avec un interquartile de [10–62] a s1, 13 [8–33] a m1 et 9,5 [4–17] a m3 dans le groupe A et de 19 [9–56] a s1, 12 [7–28] a m1 et 8,5 [4–13] a m3 dans le groupe B ; pour l’œdeme, la mediane etait de 24 [10–57] a s1, 14 [6–35] a m1 et 9 [4–16] a m3 dans le groupe A et 14 [7–53] a s1, 10 [5–19] a m1 et 8 [4–13] a m3 dans le groupe B. Discussion Nos resultats montrent la rapide amelioration sous traitement anticoagulant et compression elastique des symptomes aigus de TVP meme si environ 25 % des patients gardent des symptomes cliniquement significatifs (EVA ≥ 15/100) a trois mois. On n’observe pas de difference statistique selon le type de compression. Conclusion La CE 25 mmHg et la CE 35 mmHg sont similairement efficaces pour traiter la douleur et faire regresser l’œdeme a la phase aigue en cas de TVP proximale des membres inferieurs. Ces donnees suggerent que, compte tenu de la plus grande facilite d’enfilage de la CE 25 mmHg, la CE 25 mmHg peut etre egalement utilisee dans cette indication.

International audience; BACKGROUND:The efficacy and safety of anticoagulant treatment is not established for patients with acute symptomatic deep vein thrombosis (DVT) of the calf. We aimed to assess whether therapeutic anticoagulation is superior to placebo in patients with symptomatic calf DVT.METHODS:In this randomised, double-blind, placebo-controlled trial, we enrolled low-risk outpatients (without active cancer or previous venous thromboembolic disease) with a first acute symptomatic DVT in the calf from 23 university medical centres or community medical clinics in Canada, France, and Switzerland. We randomly assigned (1:1) patients to receive either the low-molecular-weight heparin nadroparin (171 UI/kg, subcutaneously, once a day) or placebo (saline 0·9%, subcutaneously, once a day) for 6 weeks (42 days). Central randomisation was done using a computer-generated randomisation list, stratified by study centre. Random allocation sequences of variable block size were centrally determined by an independent research clinical centre. Study staff, patients, and outcome assessors (central adjudication committee) were masked to group assignment. Numbered boxes of active drug or placebo were provided to pharmacies in identical packaging. All patients were prescribed compression stockings and followed up for 90 days. The primary efficacy outcome was a composite measure of extension of calf DVT to proximal veins, contralateral proximal DVT, and symptomatic pulmonary embolism at day 42 in the modified intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding at day 42. The trial was registered with ClinicalTrials.gov, number NCT00421538.FINDINGS:Between Feb 1, 2008, and Nov 30, 2014, we screened 746 patients, enrolling 259 patients (50% of the prespecified sample size), before the trial steering committee terminated the trial because of expiry of study drug and slow recruitment. The intention-to-treat analysis population comprised 122 patients in the nadroparin group and 130 in the placebo group. There was no significant difference between the groups in the composite primary outcome, which occurred in four patients (3%) in the nadroparin group and in seven (5%) in the placebo group (risk difference -2·1%, 95% CI -7·8 to 3·5; p=0·54). Bleeding occurred in five patients (4%) in the nadroparin group and no patients in the placebo group (risk difference 4·1, 95% CI 0·4 to 9·2; p=0·0255). In the nadroparin group one patient died from metastatic pancreatic cancer and one patient was diagnosed with heparin-induced thrombocytopenia type 2.INTERPRETATION:Nadroparin was not superior to placebo in reducing the risk of proximal extension or venous thromboembolic events in low-risk outpatients with symptomatic calf DVT, but did increase the risk of bleeding. Avoidance of systematic anticoagulation for calf DVT could have a substantial impact on individual patients and from a public health perspective.FUNDING:Swiss National Science Foundation, the Programme Hospitalier de Recherche Clinique in France, and the Canadian Institutes of Health Research.

International audience; The post-thrombotic syndrome (PTS), which refers to chronic clinical manifestations of venous insufficiency after a deep vein thrombosis (DVT), is a frequent occurrence. Because treatment options for PTS are limited, its management mainly relies on the prevention of its occurrence after DVT. Among identified predictors of PTS, extensive proximal location of DVT directly modifies the treatment of DVT because of the possibility of performance of complementary endovascular techniques. The association between poor international normalized ratio control and subsequent PTS should encourage physicians to perform frequent and regular international normalized ratio monitoring of patients receiving vitamin K antagonists. Other identified PTS risk factors are ipsilateral DVT recurrence, older age, pre-existing primary venous insufficiency, obesity, and residual venous obstruction, but these are less amenable to therapy. Because of their potential therapeutic implications, identification of biomarkers that are predictive of PTS such as markers of inflammation is crucial and such research is ongoing.

International guidelines recommend extended duration secondary prophylaxis in cancer patients who develop primary venous thromboembolism (VTE). Agent selection is guided in part by one large randomized trial (i.e., CLOT; Lee et al., N Engl J Med 349:146–53, 2003) which demonstrated that dalteparin reduced the relative risk of recurrence by 52% compared with oral vitamin K antagonists (VKA; HR = 0.48, 95% CI, 0.30 to 0.77). In a subgroup analysis from that same trial, patients with renal impairment also derived benefit with dalteparin (VTE rates = 3% vs. 17%; p = 0.011). To measure the economic value of secondary VTE prophylaxis with dalteparin, a patient-level pharmacoeconomic analysis was conducted from the Austrian and French healthcare system perspectives. Chapter 1 Healthcare resource use collected during the CLOT trial was extracted and converted into direct cost estimates. Incremental cost differences between the dalteparin and VKA groups were then combined with health state utilities to measure the cost per quality-adjusted life year (QALY) gained. The dalteparin group had significantly higher costs than the VKA group in both countries (Austria: dalteparin = €2687 vs. VKA = €2012; France: dalteparin = €2053 vs. VKA = €1352: p

Essentials Long-term risk of recurrence of isolated superficial vein thrombosis (SVT) is under-studied. We analyzed data from a cohort of first SVT and proximal deep vein thrombosis (DVT) without cancer. The risk of recurrence as DVT or pulmonary embolism is twice lower in SVT patients. However, overall risk of recurrence is similar between SVT and proximal DVT patients. Click to hear Dr Decousus' perspective on superficial vein thrombosis SUMMARY: Background Isolated superficial vein thrombosis (iSVT) (without concomitant deep vein thrombosis [DVT] or pulmonary embolism [PE]) is a frequent event, but available data on long-term outcomes are scarce and retrospective. Therefore, we aimed to determine prospectively the risk and type of venous thromboembolism (VTE) recurrence after iSVT and compare them with those of proximal DVT. Methods Using data from the prospective, multicenter, observational, OPTIMEV study, we assessed, at 3 years and after anticoagulants were stopped, the incidence and the type of VTE recurrence (iSVT/DVT/PE) of patients with a first objectively confirmed iSVT without cancer (n = 285), and compared these with those of patients with a first proximal DVT without cancer (n = 262). Results As compared with proximal DVT patients, iSVT patients had a similar overall incidence of VTE recurrence (5.4% per patient-year [PY] versus 6.5% per PY, adjusted hazard ratio [aHR] 0.9, 95% confidence interval [CI] 0.5-1.6), but iSVT recurred six times more often as iSVT (2.7% versus 0.6%, aHR 5.9, 95% CI 1.3-27.1) and 2.5 times less often as deep-VTE events (2.5% versus 5.9%, aHR 0.4, 95% CI 0.2-0.9). Varicose vein status did not influence the risk or the type of VTE recurrence. Saphenian junction involvement by iSVT was not associated with a higher risk of recurrence (5.2% per PY versus 5.4% per PY), but was associated with recurrence exclusively as deep-VTE events. Conclusion In patients with a first iSVT without cancer, after stopping anticoagulants, the incidence of deep-VTE recurrence is half that of DVT patients, but the overall risk of recurrence is similar. Ssaphenian junction involvement seems to influence the risk of deep-VTE recurrence, whereas varicose vein status has no impact or a low impact on VTE recurrence.

International audience; The post-thrombotic syndrome (PTS) is a frequent, potentially disabling complication of deep vein thrombosis (DVT) that reduces quality of life and is costly. Clinical manifestations include symptoms and signs such as leg pain and heaviness, edema, redness, telangiectasia, new varicose veins, hyperpigmentation, skin thickening and in severe cases, leg ulcers. The best way to prevent PTS is to prevent DVT with pharmacologic or mechanical thromboprophylaxis used in high risk patients and settings. In patients whose DVT is treated with a vitamin K antagonist, subtherapeutic INRs should be avoided. We do not suggest routine use of elastic compression stockings (ECS) after DVT to prevent PTS, but in patients with acute DVT-related leg swelling that is bothersome, a trial of ECS is reasonable. We suggest that selecting patients for catheter-directed thrombolytic techniques be done on a case-by-case basis, with a focus on patients with extensive thrombosis, recent symptoms onset, and low bleeding risk, who are seen at experienced hospital centers. For patients with established PTS, we suggest prescribing 20-30 mm Hg knee-length ECS to be worn daily. If ineffective, a stronger pressure stocking can be tried. We suggest that intermittent compression devices or pneumatic compression sleeve units be tried in patients with moderate-to-severe PTS whose symptoms are inadequately controlled with ECS alone. We suggest that a supervised exercise training program for 6 months or more is reasonable for PTS patients who can tolerate it. We suggest that management of post-thrombotic ulcers should involve a multidisciplinary approach. We briefly discuss upper extremity PTS and PTS in children.

Isolated distal deep-vein thrombosis (iDDVT) is a distal deep-vein thrombosis (DVT) without proximal DVT or pulmonary embolism. Although its clinical significance is uncertain, its prevalence is increasing with the use of whole leg compression ultrasonography. Epidemiological data giving reported rates of venous thromboembolism (VTE) are scarce, and there is potential conflict regarding the need to treat with anticoagulant drugs. Therefore, iDDVT management varies widely from one country/physician to another.Data are available from two large multicenter observational studies of iDDVT and proximal DVT without pulmonary embolism (iPDVT), comparing risk factor profiles and early prognosis, and also from clinical trials on iDDVT.iDDVT and iPDVT differ in terms of risk factor profile, iPDVT being more associated with chronic risk factors and iDDVT with transient ones. In the short term, case fatality rates associated with iDDVT suggest that it is a clinically relevant entity and should at least be diagnosed. From a therapeutic point of view, differences in population profile and outcomes between iPDVT and iDDVT, and results from recent clinical trials in favor of a modest VTE potential of iDDVT indicate that specific randomized double-blind trials are necessary to determine an appropriate and accepted mode of care for iDDVT.

The Sapporo criteria-related definition commonly used for diagnosis of the antiphospholipid syndrome (APS) associates the occurrence of thrombotic and/or obstetrical events with persistently positive antiphospholipid antibodies (aPL-Ab), including lupus anticoagulant (LAC), anticardiolipin IgG (aCL-G) or IgM, and/or anti-b2-glycoprotein I IgG or IgM antibodies. Criteria used to define the purely obstetrical clinical subtype of the APS syndrome include the aPLs listed above plus a fetal loss later than 10-weeks gestation, 3 or more unexplained consecutive embryonic losses before the 10th week gestation, or eclampsia or features of placental insufficiency requiring the preterm birth before 34 weeks of a morphologically normal child. Some investigators have questioned the serological criteria associated with this form of APS and have suggested that the aCL-G, anticardiolipin IgM, and anti-b2-glycoprotein I IgM measurements should be excluded. To determine the effects of the various aPL-Ab subtypes on pregnancy outcome, the investigators prospectively monitored women who had had an unexplained embryonic loss during their first pregnancy and were undergoing their untreated second pregnancy. They selected women who did not have APS; any hormonal abnormalities; or inflammatory, infectious, or malignant diseases; and who had normal parental karyotypes; the pregnancy outcomes of 142 women who tested positive for at least 1 of the 5 classical aPL-Abs were compared with those of 142 control women who were confirmed to be aPL-Abs negative. Compared with the women without aPL-Abs, the aPL-Ab-positive women experienced more clinical complications during their second pregnancy, including pregnancy loss (of which the majority were embryonic losses), preeclampsia, placental abruption, and intrauterine fetal growth restriction. The presence of LAC alone (type IIa aPL-Ab positivity) was associated with the highest risk of recurrent embryonic loss and intrauterine growth restriction. Positive tests for combinations of aPL-Ab (type I aPL-Ab positivity) were associated with the highest risk of late complications, placental abruption, and preeclampsia. A finding of anti-b2-glycoprotein I IgM positivity had no apparent diagnostic clinical relevance. These findings demonstrate that among women with a first unexplained pregnancy loss before the 10th week of gestation, those who are aPL-Abs positive have a higher risk of complications in their next pregnancy, including embryonic loss, preeclampsia, placental abruption, and intrauterine growth restriction, than women who are aPL-Abs negative. These findings suggest that the aPL-Ab LAC, aCL-G or IgM, and anti-b2-glycoprotein I IgG are helpful in identifying patients at increased risk of an adverse outcome, whereas anti-b2-glycoprotein I IgM has questionable diagnostic value.

Summary. Background: The clinical significance of symptomatic isolated distal deep vein thrombosis (DVT) is uncertain. Consequently, this leads to important disparities in its management. Objective: To examine the clinical history of isolated distal DVT and to compare it with that of proximal DVT. Methods: Using data from the international, prospective, RIETE registry on patients with confirmed symptomatic venous thromboembolism (VTE), we compared the risk factors and 3-month outcome in patients with isolated distal DVT vs. proximal DVT. Results: Eleven thousand and eighty-six patients with symptomatic DVT, but without pulmonary embolism, were included between 2001 and 2008; 1921 (17.3%) exhibited isolated distal DVT. Anticoagulant treatment was received by 89.1% (1680/1885) of isolated distal DVT and 91.8% (7911/8613) of proximal DVT patients for the entire follow-up period. Isolated distal DVTs were more associated with transient risk factors (i.e. recent travel, hospitalization, recent surgery), whereas proximal DVTs were more associated with chronic states (i.e. ≥75 years or with active cancer). At 3 months, major bleeding rate was lower in patients with isolated distal DVT (1.0% vs. 2.2%, P

Objective We studied the relation between Parkinson disease (PD) and professional exposure to pesticides in a community-based case-control study conducted in a population characterized by a high prevalence of exposure. Our objective was to investigate the role of specific pesticide families and to perform dose-effect analyses. Methods PD cases (n = 224) from the Mutualite Sociale Agricole (France) were matched to 557 controls free of PD affiliated with the same health insurance. Pesticide exposure was assessed using a 2-phase procedure, including a case-by-case expert evaluation. Analyses of the relation between PD and professional exposure to pesticides were first performed overall and by broad category (insecticides, fungicides, herbicides). Analyses of 29 pesticide families defined based on a chemical classification were restricted to men. Multiple imputation was used to impute missing values of pesticide families. Data were analyzed using conditional logistic regression, both using a complete-case and an imputed dataset. Results We found a positive association between PD and overall professional pesticide use (odds ratio [OR] = 1.8, 95% confidence interval [CI] = 1.1–3.1), with a dose-effect relation for the number of years of use (p = 0.01). In men, insecticides were associated with PD (OR = 2.2, 95% CI = 1.1–4.3), in particular organochlorine insecticides (OR = 2.4, 95% CI = 1.2–5.0). These associations were stronger in men with older onset PD than in those with younger onset PD, and were characterized by a dose-effect relation in the former group. Interpretation Our results support an association between PD and professional pesticide exposure, and show that some pesticides (ie, organochlorine insecticides) may be more particularly involved. Ann Neurol 2009;66:494–504

Objective: To analyse the determinants of anti-haemophilic drug costs in hospitalised patients with haemophilia and to estimate the impact of recombinant activated factor VII (rFVIIa) therapy on this expenditure. Perspective: The perspective of the study was from the viewpoint of the hospital. Design and setting: A prospective study was carried out. All patients with haemophilia who were hospitalised in 1999 in Bicetre public hospital, Paris, France were included in the cohort. Main outcome measures and results: For each of the 96 patients (154 hospital stays), we estimated the costs of anti-haemophilic drugs (coagulation concentrates) used. Costs were then stratified by different variables (severity of the disease, presence of a circulating inhibitor to coagulation factors, etc.) and a multivariate model was developed to determine the relationship between these variables and total anti-haemophilic drug costs, while controlling for potential confounders. Our study revealed: (i) the independent role of the five following variables in contributing to high anti-haemophilic drug expenditure: presence of a circulating inhibitor to coagulation factors, odds ratio (OR) = 16.9 (95% CI: 4.3–66); severity of the disease (factor VIII or factor IX≤0.01 IU/mL), OR = 3.7 (95% CI: 1.6–8.6); length of hospital stay >4 days, OR = 8 (95% CI: 2.2–29.4); age >18 years old, OR = 6.2 (95% CI: 1.6–24.5); and surgical reasons for hospitalisation (whether surgery was haemophilia related [OR = 35.7 (95% CI: 7.3–175)] or not [OR = 5.4 (95% CI: 1.3–22.5)]); (ii) the large share that rFVIIa represented in this expenditure on medicines: rFVIIa was used in 20.1% of hospital stays and accounted for 56.2% of the total anti-haemophilic drug costs, which were estimated at €4 384 732 (2000 values). Conclusions: Our data underline the heavy cost of the treatment of haemophilic patients with an inhibitor to coagulation factors. But, to the question of whether the high expenditure linked to rFVIIa utilisation will be balanced out by later benefits, it is not yet possible to reply with any certainty; further cost-benefit evaluation should be carried out.

Purpose of review Postthrombotic syndrome (PTS) is the most frequent complication of deep vein thrombosis. Its pathophysiology is incompletely understood and therapeutic options are limited. This review aims to present and discuss recently published studies that have improved our knowledge related to PTS. Recent findings From a prognostic point of view, some polymorphisms of plasminogen activator inhibitor-1 and platelet endothelial cell adhesion molecule 1 influence the degree of thrombus resolution after deep vein thrombosis and the subsequent rate of PTS, and could help in predicting the risk of PTS. From a therapeutic point of view, the results of a large multicenter placebo-controlled trial suggest an absence of effectiveness of elastic compression stockings to prevent PTS. In addition, although the Cavent trial of catheter-directed thrombolysis to treat ilio-femoral deep vein thrombosis showed significant reduction in the incidence of PTS that was cost-effective, secondary analyses did not show dramatic improvements in quality of life associated with use of catheter-directed thrombolysis. Summary Choice of anticoagulant to treat deep vein thrombosis may represent a new cornerstone of PTS therapeutic management. Studies are needed to assess the impact of new oral anticoagulants and the benefit of extended courses of low molecular weight heparins on the risk of PTS.

www.thelancet.com Vol 384 July 12, 2014 129 left to the discretion of the observer with no quantitative measurement or use of CEAP (Clinical, Etiological, Anatomical, and Pathophysiological) classification. The results were not reported at 2 years as planned, but rather were a cumulative incidence of post-thrombotic syndrome from 6 to 24 months. There was no diff erence for both endpoints, with 2-year data for the primary outcome available in only 45·5% of patients, and for the secondary endpoint in 27% of patients. This study contradicts previous fi ndings. The design and execution of this trial, including the timing of application of elastic compression stockings, the application itself, and defi nition and evaluation of compliance, seem inappropriate. Patients were randomised at a mean of 4·7 days from the time of deep venous thrombosis, and elastic compression stockings were applied within the first 2 weeks of diagnosis. What was the mean time from diagnosis to elastic compression stockings application? Optimum management in this acute phase is crucial for early symptom relief, recurrence, and late outcome. This has clearly been shown for adequate anticoagulation treatment, but also for compression and immediate mobilisation. Compression and walking exercises reduce pain and swelling immediately, and symptoms diminish after 1 week. The aim of continuing wearing elastic compression stockings is to maintain this effect—this could be crucial because the patient might recognise the immediate benefit from using elastic compression stockings and therefore overall compliance would be improved. Sizing was based on leg measurements and elastic compression stockings were sent to patients without provision of proper training. Most patients are unable to apply stockings without specific instruments or training, especially post-thrombotic syndrome: heparin, a drug discovered a century ago by Jay McLean (in 1916), which revolutionised deep-vein thrombosis prognosis. Moreover, a well-conducted anticoagulation treatment has also been associated with a decreased rate of post-thrombotic syndrome. Therefore, the results of the SOX trial should not be “leaving doctors empty handed”, but should rather reinforce their role in off ering a high-quality anticoagulant treatment to their patients. An ongoing international placebocontrolled trial should assess more precisely the eff ect of heparin on the natural history of post-thrombotic syndrome after a distal deep-vein thrombosis (NCT00539058). The eff ect of new oral anticoagulants on the prevention of post-thrombotic syndrome is another important issue.

Post-thrombotic syndrome (PTS) refers to chronic manifestations of venous insufficiency following a deep-vein thrombosis (DVT). It is a frequent, chronic, burdensome and costly disease for which therapeutic options are limited. Above all, the optimal management of PTS consists of preventing its occurrence: first, by preventing DVT, and second, by preventing development of PTS after a DVT. Prevention of DVT is challenging, particularly in the case of nonsurgical hospital inpatients, where physician’s adherence to recommended thromboprophylaxis is often low. In our opinion, this adherence should be improved by generalizing the use of multi-component approaches, including that of automatic reminders. For prevention of PTS after an acute DVT, our recommendations are as follows. After a proximal (popliteal and above) DVT we recommend early ambulation with daily use of 30–40 mmHg graduated elastic compression stockings (ECS) for two years, in addition to careful monitoring of anticoagulant therapy. Below-knee ECS are preferred to thigh-length ECS, as they have similar efficacy in preventing PTS and are better tolerated. To improve compliance with ECS, patient education is important, and use of lighter strengths of compression in patients not tolerating traditional strengths should be considered. Catheter-directed thrombolysis of acute DVT was recently shown to be effective in preventing PTS, but we believe that confirmatory studies are needed before recommending its general use. The cornerstone of management of established PTS relies on patient education and use of compression therapy. We encourage ambulation, use of ECS to manage symptoms, and participation in an exercise training program, which has the potential to improve patients’ quality of life (QOL) and PTS scores. In the absence of symptom relief, ECS that provide a higher strength (40–50 mmHg) should be tried. In case of moderate to severe PTS, intermittent compressive devices can be used to improve PTS symptoms. Surgery and endovascular procedures, including balloon angioplasty, stent placement, endovenectomy or valve reconstruction should be considered only in specialized centers, and only for patients with severe PTS for whom previous conservative treatment has failed. These techniques are still under evaluation and the level of evidence supporting their use is low.

International audience; BACKGROUND: Post-thrombotic syndrome (PTS) is the most frequent complication of deep vein thrombosis (DVT). Its diagnosis is based on clinical characteristics. However, symptoms and signs of PTS are non-specific, and could result from concomitant primary venous insufficiency (PVI) rather than DVT. This could bias evaluation of PTS. METHODS: Using data from the REVERSE multicenter study, we assessed risk factors for PTS in patients with a first unprovoked unilateral proximal DVT 5-7 months earlier who were free of clinically significant PVI (defined as absence of moderate or severe venous ectasia in the contralateral leg). RESULTS: Among the 328 patients considered, the prevalence of PTS was 27.1%. Obesity (odds ratio [OR] 2.6 [95% confidence interval (CI) 1.5-4.7]), mild contralateral venous ectasia (OR 2.2 [95% CI 1.1-4.3]), poor International Normalized Ratio (INR) control (OR per additional 1% of time with INR < 2 during anticoagulant treatment of 1.018 [95% CI 1.003-1.034]) and the presence of residual venous obstruction on ultrasound (OR 2.1 [95% CI 1.1-3.7]) significantly increased the risk for PTS in multivariable analyses. When we restricted our analysis to patients without any signs, even mild, of contralateral venous insufficiency (n = 244), the prevalence of PTS decreased slightly to 24.6%. Only obesity remained an independent predictor of PTS (OR 2.6 [95% CI 1.3-5.0]). Poor INR control and residual venous obstruction also increased the risk, but the results were no longer statistically significant (OR 1.017 [95% CI 0.999-1.035] and OR 1.7 [95% CI 0.9-3.3], respectively). CONCLUSIONS: After a first unprovoked proximal DVT, obese patients and patients with even mild PVI constitute a group at increased risk of developing PTS for whom particular attention should be paid with respect to PTS prevention. Careful monitoring of anticoagulant treatment may prevent PTS.

Gris, Jean-Christophe Bouvier, Sylvie Molinari, Nicolas Galanaud, Jean-Philippe Cochery-Nouvellon, Eva Mercier, Erik Fabbro-Peray, Pascale Balducchi, Jean-Pierre Mares, Pierre Quere, Isabelle Dauzat, Michel; The incidence of thrombosis in the purely obstetric form of antiphospholipid syndrome is uncertain. We performed a 10-year observational study of 1592 nonthrombotic women who had experienced 3 consecutive spontaneous abortions before the 10th week of gestation or 1 fetal death at or beyond the 10th week of gestation. We compared the frequencies of thrombotic events among women positive for antiphospholipid Abs (n = 517), women carrying the F5 6025 or F2 rs1799963 polymorphism (n = 279), and women with negative thrombophilia screening results (n = 796). The annual rates of deep vein thrombosis (1.46%; range, 1.15%-1.82%), pulmonary embolism (0.43%; range, 0.26%-0.66%), superficial vein thrombosis (0.44%; range, 0.28%0.68%), and cerebrovascular events (0.32%; range, 0.18%-0.53%) were significantly higher in aPLAbs women than in the other groups despite low-dose aspirin primary prophylaxis. Women carrying 1 of the 2 polymorphisms did not experience more thrombotic events than women who screened negative for thrombophilia. Lupus anticoagulant was a risk factor for unprovoked proximal and distal deep and superficial vein thrombosis and women in the upper quartile of lupus anticoagulant activity had the highest risk. Despite data suggesting that aPLAbs may induce pregnancy loss through nonthrombotic mechanisms, women with purely obstetric antiphospholipid syndrome are at risk for thrombotic complications

SummarySuperficial venous thrombosis (SVT) prognosis is debated and its management is highly variable. It was the objective of this study to assess predictive risk factors for concurrent deep-vein thrombosis (DVT) at presentation and for three-month adverse outcome. Using data from the prospective multicentre OPTIMEV study, we analysed SVT predictive factors associated with concurrent DVT and three-month adverse outcome. Out of 788 SVT included, 227 (28.8%) exhibited a concurrent DVT at presentation. Age >75years (odds ratio [OR]=2.9 [1.5–5.9]), active cancer (OR=2.6 [1.3–5.2]), inpatient status (OR=2.3 [1.2–4.4]) and SVT on non-varicose veins (OR=1.8 [1.1–2.7]) were significantly and independently associated with an increased risk of concurrent DVT. 39.4% of SVT on non-varicose veins presented a concurrent DVT. However, varicose vein status did not influence the three-month prognosis as rates of death, symptomatic venous thromboembolic (VTE) recurrence and major bleeding were equivalent in both non-varicose and varicose SVTs (1.4% vs. 1.1%; 3.4% vs. 2.8%; 0.7% vs. 0.3%). Only male gender (OR=3.5 [1.1–11.3]) and inpatient status (OR=4.5 [1.3–15.3]) were independent predictive factors for symptomatic VTE recurrence but the number of events was low (n=15, 3.0%). Three-month numbers of deaths (n=6, 1.2%) and of major bleedings (n=2, 0.4%) were even lower, precluding any relevant interpretation. In conclusion, SVT on non-varicose veins and some classical risk factors for DVT were predictive factors for concurrent DVT at presentation. As SVT remains mostly a clinical diagnosis, these data may help selecting patients deserving an ultrasound examination or needing anticoagulation while waiting for diagnostic tests. Larger studies are needed to evaluate predictive factors for adverse outcome.

We studied the relation between Parkinson disease (PD) and professional exposure to pesticides in a community-based case-control study conducted in a population characterized by a high prevalence of exposure. Our objective was to investigate the role of specific pesticide families and to perform dose-effect analyses.PD cases (n = 224) from the Mutualité Sociale Agricole (France) were matched to 557 controls free of PD affiliated with the same health insurance. Pesticide exposure was assessed using a 2-phase procedure, including a case-by-case expert evaluation. Analyses of the relation between PD and professional exposure to pesticides were first performed overall and by broad category (insecticides, fungicides, herbicides). Analyses of 29 pesticide families defined based on a chemical classification were restricted to men. Multiple imputation was used to impute missing values of pesticide families. Data were analyzed using conditional logistic regression, both using a complete-case and an imputed dataset.We found a positive association between PD and overall professional pesticide use (odds ratio [OR] = 1.8, 95% confidence interval [CI] = 1.1-3.1), with a dose-effect relation for the number of years of use (p = 0.01). In men, insecticides were associated with PD (OR = 2.2, 95% CI = 1.1-4.3), in particular organochlorine insecticides (OR = 2.4, 95% CI = 1.2-5.0). These associations were stronger in men with older onset PD than in those with younger onset PD, and were characterized by a dose-effect relation in the former group.Our results support an association between PD and professional pesticide exposure, and show that some pesticides (ie, organochlorine insecticides) may be more particularly involved.

SummaryThere is a lack of consensus on the value of detecting and treating symptomatic isolated distal deep-vein thrombosis (DVT) of the lower limbs. In our study, we compared the risk factors and outcomes in patients with isolated symptomatic distal DVT with those with proximal symptomatic DVT. We analysed the data of patients with objectively confirmed symptomatic isolated DVT enrolled in the national (France), multicenter, prospective OPTIMEV study.This sub-study outcomes were recurrent venous thromboembolism, major bleeding and death at three months. Among the 6141 patients with suspicion of isolated DVT included between November 2004 and January 2006, DVT was confirmed in 1643 patients (26.8%). Isolated distal DVT was more frequent than proximal DVT (56.8% vs. 43.2%, respectively; p=0.01). Isolated distal DVT was significantly more often associated with transient risk factors (recent surgery, recent plaster immobilisation, recent travel), whereas proximal DVT was significantly more associated with more chronic states (active cancer, congestive heart failure or respiratory insufficiency, age >75 years). Most patients (96.8%) with isolated distal DVT received anticoagulant therapies.There was no difference in the percentage of recurrent venous thromboembolism and major bleeding in patients with proximal DVT and isolated distal DVT. However, the mortality rate was significantly higher (p

Background: Isolated superficial vein thrombosis (iSVT) (i.e. without concurrent deep-vein thrombosis or pulmonary embolism) is a frequent event. Its clinical significance and management are controversial. Data on long-term follow-up are scarce and the impact of anatomical characteristics of iSVT on the risk of venous thromboembolism (VTE) (DVT and/or PE) recurrence has not been assessed. Objective: To determine the impact of anatomical characteristics of iSVT on the long-term risk of VTE recurrence. Methods: Using data from the The OPTIMEV (OPTimisation de l'Interrogatoire dans l'_evaluation du risque throMbo-Embolique Veineux) study, a prospective, observational, multicenter study, we assessed at 3 years in patients recruited for an objectively confirmed iSVT i) cumulative rates of DVT, PE and SVT recurrences using the Kaplan-Meier method; and ii) anatomical predictors of VTE recurrence (SVT involving the sapheno-femoral junction (i.e. ≤3 cm), SVT of the trunk of the great saphenous vein, bilateral SVT, SVT occurring in a varicose vein (i.e. C≥2 according to CEAP classification) using a Cox multivariable model adjusted for age, sex, cancer and personal history of VTE. At baseline, all patients with SVT underwent a complete bilateral swhole leg ultrasound to exclude concurrent DVT and during follow-up, all suspected VTE recurrences were confirmed/ruled out with objective tests. All recurrences were centrally adjudicated by the study's expert committee. Results: Among the 479 recruited patients with iSVT, 12.5% (n=60) had a thrombotic recurrence during the 3 years of follow-up. Cumulative rates of recurrence as a PE, DVT and iSVT were 1.9%, 4.8% and 5.8%, respectively. In multivariate analysis, a thrombus involving the sapheno-femoral junction at baseline independently increased the risk of VTE recurrence (HR=3.34 [1.5-7.2]). Presence of varicose veins also increased the risk but this result did not reach statistical significance (HR=1.8 [0.9 - 3.9], p=0.11). Conclusion: In an unselected population of patients with iSVT, long-term risk of VTE recurrence is substantial. Involvement of the sapheno-femoral junction is a strong independent predictor of VTE during the subsequent 3 years. Our results suggest the need for more aggressive management and follow-up of patients with iSVT exhibiting this anatomical characteristic. Disclosures Galanaud: Daichi: Membership on an entity's Board of Directors or advisory committees, Research Funding; bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding. Sevestre:bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Daichi: Membership on an entity's Board of Directors or advisory committees, Research Funding. Pernod:pfizer: Consultancy; leo: Consultancy; bristol meyers: Consultancy; Daichi: Consultancy; bayer: Consultancy. Brisot:bayer: Membership on an entity's Board of Directors or advisory committees; daichi: Membership on an entity's Board of Directors or advisory committees. Quéré:3-M: Research Funding; thuasne: Research Funding; aspen: Research Funding; daichi: Membership on an entity's Board of Directors or advisory committees; bayer: Membership on an entity's Board of Directors or advisory committees; leo: Membership on an entity's Board of Directors or advisory committees.

Background: Venous ulcer, the most serious consequence of chronic venous insufficiency (CVI), is associated with a high morbidity, impaired quality of life and high costs. To date, risk factors for venous ulcer after acute VTE have not been characterized. Objective: To identify independent predictors of venous ulcer development one year after an acute VTE event. Methods: Using data from the RIETE international registry, we analysed risk factors for venous ulcers in patients with an objectively confirmed symptomatic acute VTE (DVT and/or pulmonary embolism (PE)) and followed up for at least one year. During follow-up, signs and symptoms of CVI, occurrence of a venous ulcer in the leg ipsilateral to DVT or, in the absence of reported DVT, in any leg were reported by local investigators. Independent predictors of venous ulcers were assessed using a stepwise multivariable model. Results: Of the 34,144 patients included in the RIETE registry, 4,305 were recruited in centres participating in long-term (1 to 3 years) follow-up. Of these, 54% (n=2,337) underwent an assessment for CVI. After a mean (SD) follow-up of 383 (+/-575) days, 55% (n=1297) had signs or symptoms of CVI and 2.5% (n=59) had developed a venous ulcer. History of previous VTE (OR=4.4 [2.6 - 7.7], signs of venous insufficiency (i.e. leg varicosities) at time of VTE event (OR=2.3 [1.3 - 4.0]), diabetes (OR=2.0 [1.0 - 3.8]), obesity (OR=1.8 [1.1 - 3.2]) and male sex (OR=2.7 [1.5 - 4.9]) were independent predictors of an increased risk of venous ulcer. Conversely, older age, presence of an objectively confirmed DVT at study enrolment, anticoagulant duration (1 year), anticoagulant type (extended low molecular weight heparin vs. vitamin K antagonist), or presence of vena cava filter had no significant impact on risk of venous ulcer. When restricting our analysis to the 1790 patients with objectively confirmed DVT only, results remained similar in magnitude. Proximal character of DVT was associated with a 30% non-significant increased risk of - unquestionable - post-thrombotic ulcer but the proportion of distal DVT was low in our population (11%). Conclusions: After an acute VTE event, history of VTE, pre-existing signs of CVI, male sex, diabetes and obesity independently influenced the risk of venous ulcer. VTE therapeutic management (neither duration nor drugs) did not appear to modify this risk. Our results suggest that clinicians should consider strategies aimed to prevent ulcers in high risk patients, such as preventing VTE recurrence, use of compression stockings in those with CVI and encouraging weight loss in obese patients. Disclosures Galanaud: bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Daichi: Membership on an entity's Board of Directors or advisory committees, Research Funding. Bertoletti:Daichi: Honoraria; bayer: Honoraria; BMS-Pfizer: Consultancy, Honoraria. Monreal:Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; boehringer: Consultancy, Membership on an entity's Board of Directors or advisory committees; daichii: Consultancy, Membership on an entity's Board of Directors or advisory committees.

International audience; Epidemiological studies have been consistent in showing that cigarette smoking is inversely associated with Parkinson's disease (PD), whereas pesticide use is positively associated with PD. However, the relationship between PD and cigarette smoking remains poorly understood. Our objective was to study the relationship between cigarette smoking and PD in a population characterized by a high prevalence of pesticide exposure. This case-control study was carried out among subjects enrolled in the Mutualite Sociale Agricole, the French health insurance organization for workers connected to the agricultural world. We included 247 cases and 676 controls matched on age, sex, and region of residency. Information on smoking was obtained through in-person interviews. Pesticide exposure was assessed using a case-by-case expert evaluation procedure. We found an inverse relationship between ever cigarette smoking and PD (odds ratio [OR] = 0.6; 95% confidence interval [CI] = 0.4-0.9). The strength of this association increased with the number of pack-years. This relationship was present even when smoking was considered as long as 40 years before PD onset. An inverse association was also present among subjects professionally exposed to pesticides (OR = 0.5; 95% CI = 0.3-0.8) and was independent of the duration of exposure among men. We confirm the inverse association between cigarette smoking and PD in a population characterized by a high prevalence of professional pesticide exposure. The relationship between PD and cigarette smoking was not significantly modified or confounded by exposure to pesticides.

Background: One of the major complications of angioplasty is the early occurrence of restenosis requiring a repeat procedure. When bare-metal stents are used, clinical restenosis results in a repeat procedure in 10% to 15% of cases. Based on the results of an international, randomized clinical trial, the use of sirolimus-eluting stents reduces this risk. Objectives: The aims of this study were to calculate the theoretical break-even price for sirolimus-eluting stents in France, the Netherlands, and the United States, and to determine the additional health care cost per patient. Methods: The break-even price was calculated by adding the savings resulting from a 15% decrease in the rate of clinical restenosis to the price of bare-metal stents. Costs were computed from the viewpoint of the health care system, exclusive of the other societal costs. Results: The break-even prices were €1291 to €1489 in France, €2028 in the Netherlands, and €2708 in the United States (€1.00 = US $1.00 in purchasing power parity). These results indicate that the commercial price of sirolimus-eluting stents will increase hospital spending for patients undergoing angioplasty by 17% to 55% per patient. Conclusion: This additional cost to the health care system should be discussed in view of possible productivity savings and improved quality of life for patients.

Introduction: Recent studies have shown lower rates of cancer (2 – 3%) following a single episode of venous thromboembolism (VTE) than previously described. The absence of any proven impact of early diagnosis has revived the debate about systematic screening for cancer in these patients. The aim of this study was to identify whether any sub-groups of patients were at excessive risk of cancer. Methods: Based on available data at baseline and during a 3 years longitudinal follow-up of the OPTIMEV cohort, a French multicenter prospective epidemiological study (N° NCT00670540), we performed a comparative prospective epidemiological study, whose main objective was to reassess the occurrence of cancer after an episode of VTE. We sought to determine whether among the VTE positive (VTE+) patients there was any sub-group of patients at greater risk of cancer and to define classification criteria that would allow them to be identified. Results: Among 1565 VTE+ patients, 2.7% and 4.7% developed cancer during the 1stand 3 years of follow-up respectively. The probability of cancer before 3 years was similar whether the DVT was proximal or distal. In contrast, the probability of cancer before 3 years depended on the number of sites affected by VTE, 4.2 % [3.1 - 5.6] for those who had presented with unilateral DVT without PE, and 8.5% [4.6 - 15.2] for those with bilateral DVT with or without PE. The probability also depended on whether the thrombosis was idiopathic 7.1% [5.1 - 9.9] vsa probability of 4.1% [3.1- 5.5] for those who had non-idiopathic DVT. The probability of cancer was also linked to whether or not the patient was on anticoagulant treatment at the time of VTE recurrence. This was 24.8 % [13.7 - 42.5] for those who had relapsed whilst on anticoagulant treatment, 13.1% [7.4 -22.5 ] for those who have relapsed when not on anticoagulants, compared with 4.0% [3.1 - 5.2] for those who did not relapse (p < 0.01). After adjustment, in VTE+ patients, there was a significantly higher adjusted HR for patients over 50 years of age (HR 11.1 [2.7 - 45.5] (p < 0.01), those with idiopathic VTE (HR 1.8 [1.1-2.8] (p = 0.02), bilateral DVT with or without PE (HR 1.9 [1.01 - 3.7] (p = 0.05), those who had a recurrence during follow-up whilst on anticoagulant treatment (HR 6.5 [3.2 - 13.4] (p For VTE+ patients over 50 (n = 1169), we sought to classify these patients according to their risk of cancer by weighting risk factors according to adjusted HR from the multivariate model. Three points were given for recurrence while on anticoagulants, one point for a recurrence when not on anticoagulant treatment, one point for cases of idiopathic VTE and one point for cases of bilateral DVT. According to the scoring, the probability of developing cancer during follow-up was depicted table 1. Discussion The utility of systematically screening for cancer during an episode of VTE is debatable. The issue of the cost of screening in relation to its benefit in terms of reducing mortality and the problem of the physical and psycho-social consequences caused by such screening are also increasingly questioned. Based on the lower incidence of cancer observed in this prospective cohort, it might be more accurate to focus further studies regarding cancer screening on high risk population. Conclusion: Bilateral DVT, idiopathic but especially recurrent VTE appear to be good criteria for selecting patients over 50 years of age for whom the issue of cancer testing should be posed. Table 1 Class Risk N (% of VTE+ patients) Probability of cancer at 3y Low risk (score 0) 597 (51%) 3.6% [2.4 – 5.6] Intermediate risk (score 1 – 2) 525 (45%) 9.1% [6.8 – 12.2] High risk (score ≥ 3) 47 (4%) 27.3% [15.6 – 45.1] Disclosures Bosson: Sanofi-Aventis: Research Funding.

Background Acute deep venous thrombosis (DVT) is associated with leg pain and discomfort. Elastic compression stockings (ECS) have the potential to improve DVT-related leg pain by reducing the diameter of distended veins, increasing venous blood flow and reducing venous hypertension. To date, however, the effect of ECS on DVT-related leg pain has not been studied. In the SOX Trial, a randomized trial of active ECS vs. placebo ECS to prevent the post-thrombotic syndrome, we measured leg pain intensity at baseline and at several time-points during follow-up. Objective In a secondary, non-prespecified analysis of the SOX Trial, to determine whether active ECS, compared with placebo (sham) stockings, are effective to reduce leg pain associated with acute proximal DVT. Methods We did a multicenter (24 centres in Canada and U.S.) randomized placebo controlled trial of active ECS vs. placebo ECS after a first, symptomatic proximal DVT. Active ECS were knee length, 30-40 mm Hg (Class II) graduated ECS. Placebo ECS were manufactured to appear identical to active ECS but lacked therapeutic compression. Study stockings were worn on the DVT-affected leg daily and continued for up to 2 years. Exclusion criteria were >10 days since DVT diagnosis, not planned to be treated with anticoagulants, known peripheral arterial disease or limb phlegmasia, anticipated lifespan < 6 months, inability of patient or caregiver to apply ECS, thrombolysis to treat DVT, geographically inaccessible for follow-up visits or unable to give informed consent. Leg pain intensity was assessed on a 10-point Visual Analog Scale (0, no pain; 10, worst possible pain) via patient self-report at baseline, 14 days, 1 month and 60 days after randomization. We compared mean pain scores at each time point in the active ECS vs. placebo ECS groups using t-tests. We repeated this analysis, restricted to patients who reported daily stockings use at the 1 month visit (the first visit at which frequency of stocking use was assessed). We conducted pre-specified subgroup analyses by age, sex, and extent of DVT. Results are presented as mean difference (95% confidence interval [CI]) in pain intensity score between groups. All statistical tests were 2-sided and significance was set at P Results 410 patients were randomized to active ECS and 396 to placebo ECS. One and 2 patients, respectively, were found to be ineligible soon after randomization and excluded from the analysis. Mean time from DVT diagnosis to randomization was 4.7 days. Baseline characteristics were similar in the 2 groups (60% male, mean age 55.1 years, highest proximal extent of DVT was iliac or femoral vein in 70% and popliteal vein in 30%, 87% were out-patients). Pain scores diminished over time in both groups. There were no differences between groups in pain scores at any time-point (Table), and no evidence for subgroup interaction by age category, sex or anatomical extent of DVT (not shown). Conclusions In a large randomized placebo-controlled trial in patients with symptomatic proximal DVT, leg pain improved at each follow-up visit to a similar degree in patients randomized to active ECS and placebo ECS, and we did not find evidence for benefit of active ECS to reduce pain associated with acute proximal DVT. As our first follow-up assessment was 14 days after DVT, we were unable to evaluate if active ECS had a beneficial or detrimental effect on pain scores during the first 2 weeks after DVT. Disclosures: No relevant conflicts of interest to declare.

Abstract 630 Background: Cancer constitutes a strong risk factor for proximal deep-vein thrombosis (DVT). After a proximal DVT, the risk of being diagnosed a previously undiagnosed cancer in the following years is high. This has justified a cancer screening in this situation, the optimal modalities of which (extensive vs. limited screening) are currently under evaluation. However, little is known on the risk of subsequent cancer in case of symptomatic isolated distal DVT (e.g. infra-popliteal DVT without PE) and symptomatic isolated superficial vein thrombosis (SVT) (e.g. without concomitant DVT and PE). The value of cancer screening is therefore debated in these situations. Yet, each of those two other clinical expressions of venous thromboembolic disease (VTE) in the lower limbs is at least as frequent as proximal DVT. Objective: As compared with patients with a first episode of symptomatic isolated proximal DVT (e.g. without PE), we aim assessing the risk of subsequent cancer in patients with a first isolated distal DVT or with a first isolated SVT. A secondary objective was to assess the influence of anatomical characteristics of distal DVT and SVT (deep calf DVT vs. muscular DVT and SVT on varicose vein vs. SVT on non-varicose vein) on the risk of subsequent cancer. Methods: We analysed the data from the OPTIMEV prospective, observational, multicenter study of consecutive in and outpatients recruited after an objectively confirmed symptomatic VTE and followed up three years. All VTE events were diagnosed via a standardized bilateral whole leg compression ultrasonographic protocol screening the entire deep and superficial venous networks. Results: 327 patients with a proximal DVT, 536 with a distal DVT, and 329 with an SVT fulfilled our study's inclusion criteria. 2.9% (n=35) of patients were lost to follow-up before 3 years. At 3 years cumulative rates of cancer were similar whatever the kind of VTE considered (Figure 1). Incidence of subsequent cancer was respectively of 3.9% [2.2 – 6.1] in case of proximal DVT, 4.1% (95% CI [2.7 – 6.1]) in case of distal DVT and 3.1% [1.7 – 5.7] in case of isolated SVT. Neither anatomical characteristics of distal DVT (cumulative rates of subsequent cancer 4.2% [2.3 – 7.4] in case of muscular DVT, 3.7% [1.6 – 8.6] in case of deep calf DVT and 4.3% [1.8 – 9.9] in case of combined muscular and deep calf DVT, p=0.98) nor anatomical characteristics of SVT (cumulative rates of subsequent cancer 1.9% [0.5 – 7.2] in case of SVT on non-varicose vein and 3.4% [1.9 – 7.4] in case of SVT on varicose vein, p=0.4) significantly influenced the risk of subsequent cancer. Main strengths/limitations: This is the largest prospective observational cohort of in and out patients with an objectively confirmed isolated SVT or isolated distal DVT, managed in routine practice, and with a long-term follow-up. Our results only apply to first episodes of isolated SVT or distal DVT. As compared with previous reports on the risk of subsequent cancer in case of VTE, our population of DVT/SVT patients was at low risk of cancer a priori. Indeed, we only included first episodes of VTE, most of which were diagnosed and managed in an outpatient setting and/or were associated with a transient risk factor. Therefore the number of newly diagnosed cancer was limited and we may have lacked statistical power for some sub-group analyses. However our rate of subsequent cancer in proximal DVT patients was in the range of that from recent studies and significantly higher than the expected rate of cancer in the French general population of the same age. Conclusion: In patients managed in routine practice without previous history of cancer or VTE, every clinical expression of lower limb VTE (proximal DVT, distal DVT and SVT) is associated with a similar risk of subsequent cancer. Anatomical characteristics of distal DVT and SVT do not seem to have a strong impact on this risk. These results suggest that cancer screening should not be modulated according to the deep-proximal, deep-distal or superficial location of lower limb thrombosis. Cumulative rates of subsequent cancer according to the proximal, distal or superficial location of VTE were estimated with the Kaplan-Meier method and compared with logrank test. Disclosures: No relevant conflicts of interest to declare.

Abstract 3332 Background: Post thrombotic syndrome (PTS) is the most common complication of deep vein thrombosis (DVT). Symptoms and signs assessed by the Villalta PTS scale are non-specific and may have causes other than PTS, especially primary venous insufficiency. This may lead to an overestimate of patients categorized as having PTS. To date, the frequency and predictors of PTS in patients with DVT who are free of primary venous insufficiency have not been evaluated. Methods: Using data from the REVERSE prospective multicentre cohort study, we analyzed the prevalence and risk factors for PTS in patients who had a first, unprovoked, unilateral proximal DVT 5–7 months previously and did not have clinically significant primary venous insufficiency (defined as the absence of moderate or severe venous ectasia in the contralateral leg). At the time of enrolment in the REVERSE study, PTS was evaluated in the DVT-affected leg using the Villalta scale and was considered to be present if Villalta score >4. Independent predictors of PTS were assessed using a multivariable logistic regression model adjusting for age, sex, and use of compression stockings and included all variables achieving a p value ≤ 0.10 in univariate analysis. Results: Between October 2001 and March 2006, 664 patients were enrolled in the REVERSE study after having received a 5–7 month course of anticoagulant therapy. Of these, 452 had DVT with or without concomitant pulmonary embolism (PE) as the index event. Of these, 131 patients were excluded from this sub-study for the following reasons: previous secondary DVT/PE (n=24), presence of moderate or severe venous insufficiency in the contralateral leg (n=54), no PTS assessment (n=53). Among the remaining 321 sub-study patients, 48% (n=155) reported using compression stockings. The overall prevalence of PTS 5–7 months after DVT was 27.4% (n=88). The distribution of PTS severity category was as follows: mild PTS (Villalta score, 5–9) in 80% (n=70) of cases, moderate PTS (Villalta score, 10–14) in 17% (n=15) of cases and severe PTS (Villalta score ≥15 or ipsilateral leg ulcer) in 3.4% (n=3) of cases. In univariate analysis, age, sex, concomitant PE at presentation, thrombophilia (mutation of factor II or V, elevated factor VIII or hyperhomocysteinemia, presence of a lupus anticoagulant) and levels of the inflammatory marker C reactive protein or elevated ddimer before stopping anticoagulant therapy did not influence the risk of developing a PTS at 5–7 months (all p>0.10). Obesity (OR=2.3 [1.3 – 4.0]), household income When restricting our analysis to the 226 patients without any signs, even mild, of contralateral venous insufficiency, the prevalence of PTS decreased slightly to 24.8% (n=56). Only obesity remained an independent predictor of PTS (OR=2.3 [1.2 – 4.4]). Poor INR control, ultrasonographic features described above and household income Conclusions: In a population of patients with a first unprovoked proximal DVT and without significant primary venous insufficiency, obesity and ultrasonographic evidence of DVT sequelae at 5–7 months after DVT independently influenced the risk of PTS. Mild clinical expression of primary venous insufficiency was also found to be a predictor of PTS and could therefore play a role in PTS pathophysiology. Nevertheless, it had a limited impact on the assessment of the overall prevalence of ipsilateral PTS according to the Villalta scale. Disclosures: Crowther: Pfizer: Consultancy, Honoraria; Leo Pharma: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; BI: Honoraria; CSL Behring: Consultancy; Octaphram: Consultancy; Artisan: Consultancy.

BackgroundHalf of all lower limb deep vein thromboses (DVT) are distal DVT that are equally distributed between muscular calf vein thromboses (MCVT) and deep calf vein thromboses (DCVT). Despite their high prevalence, MCVT and DCVT have never been compared so far, which prevents possible modulation of distal DVT management according to the kind of distal DVT (MCVT or DCVT).MethodsUsing data from the French, multicenter, prospective observational OPTimisation de l'Interrogatoire dans l'évaluation du risque throMbo-Embolique Veineux (OPTIMEV) study, we compared the clinical presentation and risk factors of 268 symptomatic isolated DCVT and 457 symptomatic isolated MCVT and the 3-month outcomes of the 222 DCVT and 390 MCVT that were followed-up.ResultsDuring the entire follow-up, 86.5% of DCVT patients and 76.7% of MCVT patients were treated with anticoagulant drugs (P = .003). MCVT was significantly more associated with localized pain than DCVT (30.4% vs 22.4%, P = .02) and less associated with swelling (47.9% vs 62.7%, P < .001). MCVT and DCVT patients exhibited the same risk factors profile, except that recent surgery was slightly more associated with DCVT (odds ratio, 1.70%; confidence interval, 1.06-2.75), and had equivalent comorbidities as evaluated by the Charlson index. At 3 months, no statistically significant difference was noted between MCVT and DCVT in death (3.8% vs 4.1%), venous thromboembolism recurrence (1.5% vs 1.4%), and major bleeding (0% vs 0.5%).ConclusionIsolated symptomatic MCVT and DCVT exhibit different clinical symptoms at presentation but affect the same patient population. Under anticoagulant treatment and in the short-term, isolated distal DVT constitutes a homogeneous entity. Therapeutic trials are needed to determine a consensual mode of care of MCVT and DCVT.

Background A current debate concerning suspected superficial vein thrombosis (SVT) focuses on the need of performing a compression ultrasound (CUS) exploration for confirming the diagnosis of SVT. This study was conducted to determine the clinical relevance and optimal CUS exploration in patients with symptomatic SVT. Methods We analyzed the characteristics of SVT and concomitant deep vein thrombosis (DVT) in patients included in the Prospective Observational Superficial Thrombophlebitis (POST) multicenter, observational prospective study. All patients underwent complete bilateral lower limb CUS, exploring both the superficial and deep venous systems. Results A total of 844 patients with clinical symptoms of SVT were recruited, of which 99 isolated SVTs (21.4%) had saphenofemoral/popliteal junction involvement, and 198 (23.5%) had a concomitant DVT, with 41.8% of them proximal DVTs. In 83 patients (41.9%), DVT and SVT were not contiguous. Five of 639 patients (1%) had an isolated contralateral DVT (ie, not bilateral). Age ≥75 years (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.6-3.4), inpatient status (OR, 5.4; 95% CI, 3.4-8.7), a personal history of DVT or pulmonary embolism (OR, 1.8; 95% CI, 1.2-2.8), and SVT on nonvaricose veins (OR, 3.3; 95% CI, 2.1-5.0) were significantly and independently associated with an increased risk of concomitant DVT. Half of the patients exhibited none of these risk factors, and the prevalence of concomitant DVT dropped to 11%. Conclusions In patients with symptomatic SVT, a CUS exploration screening the whole venous system of the affected limb is useful because it provides information that has important consequences for the management of these patients.

International audience; BACKGROUND: The Saitohin gene has recently been identified in intron 9 of the Tau gene. Because an association between Parkinson's disease and Tau has been described, Saitohin represents a candidate gene for Parkinson's disease. OBJECTIVE: To test these two genes for their association with Parkinson's disease in a large community based case-control study. RESULTS: Cases (n = 208) were more often homozygotes for the Tau H1 haplotype than controls (n = 483; odds ratio (OR) = 1.71 (95% confidence interval, 1.20 to 2.43); p = 0.003), and the saitohin Q allele was in complete linkage disequilibrium with the H1 haplotype. This association was stronger among cases with Parkinson's disease onset below 65 years (< or =65 years: OR = 2.52 (1.49 to 4.25); p65 years: OR = 1.20 (0.73 to 1.98); p

International audience; Excess of nitric oxide (NO) has been shown to exert neurotoxic impacts in the brain. Moreover, inhibition of two NO-synthesizing enzymes, neuronal NOS (nNOS) and inducible NOS (iNOS), displays neuroprotective effects in the MPTP model of Parkinson's disease (PD). These data suggest a possible involvement of NOS as factors controlling the resistance of the nigral dopaminergic neurons to environmental insults. Therefore, we investigated whether polymorphisms present in these genes could contribute to the risk of developing PD. We carried out a community-based case-control study among subjects enrolled in the Mutualit?ociale Agricole, the French health insurance organization for workers connected to agriculture. Two-hundred and nine PD patients and 488 controls of European (mostly French) ancestry and matched for age, sex and region of residency were included in this study. Associations were observed with polymorphisms present in exon 22 of iNOS (OR for AA carriers=0.50, 95% CI=0.29-0.86, P=0.01) and in exon 29 of nNOS (OR for carriers of the T allele=1.53, 95% CI=1.08-2.16, P=0.02); no association was observed with a polymorphism in exon 18 of nNOS (OR for carriers of the T allele=1.20, 95% CI=0.85-1.69, P=0.30). Moreover, a significant interaction of the nNOS polymorphisms with current and ever cigarette smoking was found (nNOS 18, P=0.05; nNOS 29, P=0.04). All together, these data favour an involvement of these two genes as new modifier genes in PD.