Paul Frappé

From randomized trials to the clinic: is it time to implement individual lung-cancer screening in clinical practice? A multidisciplinary statement from French experts on behalf of the french intergroup (IFCT) and the groupe d'Oncologie de langue française (GOLF)

Background Despite advances in cancer therapy, mortality is still high except in early-stage tumors, and screening remains a challenge. The randomized National Lung Screening Trial (NLST), comparing annual low-dose computed tomography (LDCT) and chest X-rays, revealed a 20% decrease in lung-cancer-specific mortality. These results raised numerous questions. The French intergroup for thoracic oncology and the French-speaking oncology group convened an expert group to provide a coherent outlook on screening modalities in France. Methods A literature review was carried out and transmitted to the expert group, which was divided into three workshops to tackle specific questions, with responses presented in a plenary session. A writing committee drafted this article. Results The multidisciplinary group favored individual screening in France, when carried out as outlined in this article and after informing subjects of the benefits and risks. The target population involves subjects aged 55–74 years, who are smokers or have a 30 pack-year smoking history. Subjects should be informed about the benefits of quitting. Screening should involve LDCT scanning with specific modalities. Criteria for CT positivity and management algorithms for positive examinations are given. Conclusions Individual screening requires rigorous assessment and precise research in order to potentially develop a lung-cancer screening policy.

Annual diagnosis rate of superficial vein thrombosis of the lower limbs: the STEPH community‐based study

The incidence of superficial vein thrombosis (SVT) in the general adult population remains unknown.

Recent findings in the epidemiology, diagnosis and treatment of superficial-vein thrombosis

Recent data on lower-limb superficial-vein thrombosis (SVT) may substantially impact its clinical management. Thus, the clear confirmation that SVT is closely linked to deep-vein thrombosis (DVT) or pulmonary embolism (PE) highlights the potential severity of the disease. DVT or PE are diagnosed in 20-30% of SVT patients. Moreover, clinically relevant symptomatic thromboembolic events complicate isolated SVT (without concomitant DVT or PE at diagnosis) in 4-8% of patients. For the first time, an anticoagulant treatment, once-daily 2.5 mg fondaparinux for 45 days, was demonstrated to be effective and safe for preventing these symptomatic thromboembolic events in patients with lower-limb isolated SVT in the randomized placebo-controlled CALISTO study. Based on these recent findings, new recommendations on the management of SVT patients, including complete ultrasonography examination of the legs, and in patients with isolated SVT, prescription of once-daily 2.5 mg fondaparinux subcutaneously for 45 days on top of symptomatic treatments, may be proposed.

In-patient versus out-patient withdrawal programmes for medication overuse headache: A 2-year randomized trial

Background: Medication-overuse headache (MOH) management usually includes a medication withdrawal. The choice of withdrawal modalities remains a matter of debate. Methods: We compared the efficacy of in-patient versus out-patient withdrawal programmes in 82 consecutive patients with MOH in an open-label prospective randomized trial. The main outcome measure was the reduction in number of headache days after 2 months and after 2 years. The responders were defined as patients who had reverted to episodic headaches and to an intake of acute treatments for headache less than 10 days per month. Results: Seventy-one patients had a complete drug withdrawal (n = 36 in the out-patient group; n = 35 in the in-patient group). The reduction of headache frequency and subjective improvement did not differ between groups. The long-term responder rate was similar in the out- and in- patient groups (44% and 44%; p = 0.810). The only predictive factor of a bad outcome 2 years after withdrawal was an initial consumption of more than 150 units of acute treatments for headache per month (OR = 3.1; 95% confidence interval 1.1–9.3; p = 0.044). Conclusion: Given that we did not observe any difference in efficacy between the in- and out-patient withdrawals, we would recommend out-patient withdrawal in the first instance for patients with uncomplicated MOH.

Spontaneous acute superficial vein thrombosis of the legs: do we really need to treat?

Spontaneous acute superficial vein thrombosis (SVT) of the leg is now generally recognized as an integral component of venous thromboembolic disease with potentially severe consequences. However, the relatively low grades of some current international recommendations and uncertainty regarding the cost‐effectiveness of available therapies may prompt questioning of the real need to treat patients with SVT and explain the persisting heterogeneity of their management in practise. Yet several studies have consistently shown high rates of thromboembolic complications associated with SVT, whether at first presentation or during follow‐up. The CALISTO trial established for the first time the clinical benefit of a well‐defined anticoagulant regimen for the prevention of serious thromboembolic complications in SVT patients, and we believe that patients such as those included in this trial should receive this regimen as tested. However, several areas of uncertainty remain for categories of SVT patients not evaluated in CALISTO.

PK evaluation of fondaparinux sodium for the treatment of thrombosis

Introduction: Fondaparinux sodium (pentasaccharide) was the first of a new class of antithrombotic agents developed for the prevention and treatment of venous thromboembolism (VTE), blocking thrombin generation by selectively inhibiting factor Xa. Areas covered: This review focuses on the currently available information evaluating the pharmacokinetics, pharmacodynamics, clinical efficacy and safety of fondaparinux in the prevention and treatment of VTE and treatment of acute coronary syndromes (ACS). Expert opinion: Fondaparinux is an alternative to low-molecular-weight heparins (LMWH) for thromboprophylaxis in various clinical settings (major orthopedic surgery of the lower limbs, major abdominal surgery, immobilized medical patients at high risk of VTE), as well as for the treatment of VTE (deep venous thrombosis, pulmonary embolism). It is currently challenged, in the context of both surgical thromboprophylaxis and acute VTE treatment, by the new oral anticoagulants. Fondaparinux remains the sole drug validated in patients with isolated superficial vein thrombosis of the lower limbs, and at prophylactic doses is a good alternative to LMWH at anticoagulant doses for patients with ACS, especially those ineligible for percutaneous coronary intervention.

Areas of improvement in anticoagulant safety. Data from the CACAO study, a cohort in general practice

Background Real-world studies on anticoagulants are mostly performed on health insurance databases, limited to reported events, and sometimes far from every-day issues in family practice. We assess the presence of data for safe monitoring of oral anticoagulants in general practice, and compare patients’ knowledge of taking an anticoagulant between vitamin K antagonists (VKA) and direct anticoagulants (DOAC), and the general practitioner’s perception of their adherence to anticoagulation. Methods The CACAO study is a national cohort study, conducted by general practitioners on ambulatory patients under oral anticoagulant. In the first phase, investigators provided safety data available from medical records at inclusion. They also evaluated patients’ knowledge about anticoagulation and graded their perception of patients’ adherence. Results Between April and December 2014, 463 general practitioners included 7154 patients. Renal and hepatic function tests were respectively unavailable in 109 (7.5%) and 359 (24.7%) DOAC patients. Among patients with atrial fibrillation, 345 patients (6.9%) had a questionable indication of anticoagulant (CHA2DS2-Vasc<2). One hundred and thirty-three VKA patients (2.3%) and 70 DOAC patients (4.9%) answered they took no anticoagulant (p<0.0001). According to general practitioners’ perception, 430 patients (6.1%) were classified as “not very” or “not adherent”, with no difference between groups. Conclusions Our results highlight the efforts needed to improve anticoagulant safety in daily practice: decreasing the rate of unknown biological data in patients with DOACs or the rate of patients with VKA with no strong indication of anticoagulation, and improving patient knowledge with regard to their anticoagulant. Patients’ adherence seems highly over-estimated by the general practitioners. Clinical trial registration ClinicalTrials.gov NCT02376777

Ruling out deep vein thrombosis in patients with superficial vein thrombosis: external validation of the ICARO score

A clinical score was recently proposed to rule out concomitant DVT in patients with a clinical suspicion of SVT. This study aimed to assess the external validity of this score in patients from the STEPH study. We performed a post-hoc analysis of data from the STEPH study. The STEPH study was a prospective multicenter community-based study conducted during a 1-year period in the resident adult population of the Greater Saint-Etienne urban area (France). Every patient with a clinical suspicion of SVT underwent a venous compression ultrasonography, to confirm SVT and to assess the presence of a concomitant DVT or not. Odds ratios for concomitant DVT were calculated for each item of the ICARO score. We then computed the score for each patient, and performed a receiver operating characteristic (ROC) curve analysis. In univariate analysis, none of the ICARO items were significantly different given the presence of a concomitant DVT. Given computed scores, 55 patients (45.1%) had a low risk, 17 (13.9%) had an intermediate risk and 50 (41.0%) had a high risk of a concomitant DVT. The area under the ROC curve was 0.386 [95% CI, 0.268–0.504]. When risk levels were dichotomized as low vs intermediate-high risk, the ICARO score had a sensitivity of 36.0%, a specificity of 40.2%, a positive predictive value of 13.4% and a negative predictive value of 70.9%. Our study does not confirm the utility of the ICARO clinical score to rule out concomitant DVT in case of SVT.

Cross-sectional multicentre study on the cohort of all the French junior lecturers in general practice

Abstract Background: General practice became an academic discipline quite recently in many western countries. In France, junior lecturer work is specified in a three-part mandate: medical work in general practice, teaching in the university, and research. Since 2007, 130 junior lecturers have been appointed in general practice. The aim of the creation of junior lecturer status was to align general practice with other specialties and to develop research and education in primary care. Objectives: To describe the healthcare, teaching and research undertaken by junior lecturers in general practice, practising in October 2014. Methods: A cross-sectional multicentre study using an online self-administered questionnaire on the cohort composed of all the junior lecturers in general practice with open questions and the qualitative analysis of written verbatim accounts. Results: Of the 95 junior lecturers practising at the date of the study, 75 (79%) responded; average age 32 years; gender ratio (F/M) 2.4:1. They spent five, two and three half-days per week respectively in healthcare, teaching and research. The healthcare activity was predominantly carried out in the community (73%). Thirty-nine per cent worked as part of a multi-professional team taking on 50 consultations per week. Most of the educational work involved lecturing and mentoring students specializing in general practice (median 86 hours per year). Research output increased during the fellowship. Research topics were varied and relevant to the disciplinary field. Conclusion: During the fellowship, the balancing, and even the reinforcement, of healthcare and research contributions were accompanied by a significant investment in educational provision.

Seasonal variation in the superficial vein thrombosis frequency.

INTRODUCTION A seasonal variation of venous thromboembolic disease frequency is subject to discussion, and has been recently suggested for superficial vein thrombosis (SVT) in a small retrospective study. Our aim was to search for a seasonal variation of SVT frequency according to the data of larger studies. MATERIALS AND METHODS We analyzed the data of three French prospective multicenter studies with different designs which have included patients with SVT (STENOX, POST, and STEPH studies). Seasonal variation of SVT frequency was evaluated by comparing the observed seasonal frequency of SVT to a theoretical frequency of 25% for each season. RESULTS The analysis included 1395 patients and 4.75 seasonal cycles. The difference to a theoretical frequency of 25% was statistically significant in one study (POST, p = 0.044). The higher risk difference was -6.1% (95% CI -11.7–−0.5) in summer in STENOX, +7.1% (95% CI +2.7-+11.5) in winter in POST and 4.2% (95% CI -5.2-+13.7) in spring in STEPH, corresponding to a relative risk of 0.80, 1.40 and 1.20, respectively. CONCLUSIONS A seasonal variation was found in only one study which has the weakest methodology to warrant completeness. Variation pattern was