Christophe Leroyer

Diagnostic strategy for patients with suspected pulmonary embolism: a prospective multicentre outcome study

BACKGROUND We designed a prospective multicentre outcome study to evaluate a diagnostic strategy based on clinical probability, spiral CT, and venous compression ultrasonography of the legs in patients with suspected pulmonary embolism (PE). The main aim was to assess the safety of withholding anticoagulant treatment in patients with low or intermediate clinical probability of PE and negative findings on spiral CT and ultrasonography. METHODS 1041 consecutive inpatients and outpatients with suspected PE were included. Patients with negative spiral CT and ultrasonography and clinically assessed as having a low or intermediate clinical probability were left untreated. Those with high clinical probability underwent lung scanning, pulmonary angiography, or both. All patients were followed up for 3 months. FINDINGS PE was diagnosed in 360 (34.6%) patients; 55 had positive ultrasonography despite negative spiral CT. Of 601 patients with negative spiral CT and ultrasonography, 76 were clinically assessed as having a high probability of PE; lung scanning or angiography showed PE in four (5.3% [95% CI 1.5-13.1]). The remaining 525 patients were assessed as having low or intermediate clinical probability, and 507 of them were not treated. Of these patients, nine experienced venous thromboembolism during follow-up (1.8% [0.8-3.3]). The diagnostic strategy proved inconclusive in 95 (9.1%) patients, and pulmonary angiography was done in 74 (7.1%). INTERPRETATION Withholding of anticoagulant therapy is safe when the clinical probability of PE is assessed as low or intermediate and spiral CT and ultrasonography are negative.

High prevalence of asymptomatic deep vein thrombosis on admission in a medical unit among elderly patients.

The prevention of venous thromboembolism in medical patients remains questioned. All consecutive outpatients admitted in our medical unit were considered for inclusion in this study which aimed to estimate the prevalence of asymptomatic venous thrombosis on admission and the incidence during hospital stay. Exclusion criteria were: age <18 years, suspicion of venous thromboembolism, stay <4 days, ongoing anticoagulant therapy. Venous compression ultrasonography of the lower limbs was performed within 48 h. 234 patients were included. The prevalence of asymptomatic deep vein thrombosis on admission and the incidence during hospital follow-up were respectively 5.5% (95% confidence interval, 3.1 to 9.5%) and 2.6 per 1,000 person-days (95% confidence interval, 0.0 to 5.2). The prevalence and the incidence reached respectively 17.8% (95% confidence interval, 8.5 to 32.6%) and 6.0 per 1,000 person-days (95% confidence interval, 0.0 to 12.7) among patients over 80 years. A high prevalence of asymptomatic deep vein thrombosis on admission was suggested particularly among elderly medical patients.

Masitinib, a c‐kit/PDGF receptor tyrosine kinase inhibitor, improves disease control in severe corticosteroid‐dependent asthmatics

Background:  Masitinib is a tyrosine kinase inhibitor targeting stem cell factor receptor (c‐kit) and platelet‐derived growth factor (PDGF) receptor, which are expressed on several cell types including mast cells and bronchial structural cells, respectively. We hypothesized that c‐kit and PDGF receptor inhibition may decrease bronchial inflammation and interfere with airway remodeling, which are crucial features of severe asthma.

Family history as a risk factor for venous thromboembolism

INTRODUCTION There are very few data assessing a family history of venous thromboembolism (VTE) as a risk factor for VTE. This question is nonetheless of interest as inherited risk factors are involved but at least partly unknown. METHODS The E.D.I.TH. study is a prospective hospital-based case-control study. The family history was assessed by using a standard questionnaire, considering the total number of the first-degree relatives and the number of these relatives who had suffered from VTE. We analysed 698 first VTE cases and their matched controls, 507 pairs without and 191 pairs with a major acquired risk factor (active malignancy, surgery or plaster cast in the past three months, pregnancy or delivery in the past three months). RESULTS A family history of VTE was associated with VTE occurrence, irrespective of carrying or not factor V Leiden mutation or G20210A prothrombin gene mutation and irrespective of the presence or absence of major acquired risk factors; adjusted conditional odds ratio: 2.7 (95%CI, 1.8-3.8). CONCLUSION A family history might well be considered when estimating type and duration of prophylaxis for VTE specifically in patients with active cancer or who experienced surgery. Family history of VTE could be added to a prior VTE history to define a concept of clinical thrombophilia which is not necessarily related to carrying a known inherited risk factor.

Statins but not fibrates are associated with a reduced risk of venous thromboembolism: a hospital-based case-control study.

Previous studies of selected patients have suggested a reduction in the risk of venous thromboembolism with the use of statins. The objective of this study is to evaluate the influence of statin use on the risk of venous thromboembolic (VTE) events. The study is a case–control study (EDITH: Etude des Déterminants et Interactions de la Thrombose Veineuse), designed to investigate the genetic and environmental risk factors of VTE. A total of 377 patients consecutively hospitalized in the Brest University Hospital for a documented VTE event, between May 2000 and May 2002, and 377 age‐ and sex‐matched controls were studied. Statin use was associated with a 58% decreased risk of VTE [odds ratio (OR) 0.42; 95% confidence interval (CI) 0.23–0.76; P = 0.002]. Adjustment for age, gender, coronary heart disease, atherosclerothrombotic disease or current use of aspirin did not alter the result. Neither fibrates (OR 1.38; 95% CI 0.76–2.52; P = 0.26), nor thienopyridines (OR 1.07; 95% CI 0.48–2.41; P = 0.85) were associated with a reduced risk of VTE. Aspirin use tended to decrease the risk of VTE, but this result was not significant (OR, 0.66; 95% CI, 0.42–1.05). The use of statins is associated with a significant reduction in the risk of VTE, irrespective of age, gender, and past history of atherosclerothrombotic disease, as well as the use of aspirin. This possible protective effect of statins warrants further investigations.

Benfluorex and Unexplained Valvular Heart Disease: A Case-Control Study

Background Recent case reports suggest that benfluorex, a fenfluramine derivative used in the management of overweight diabetic patients and dyslipidemia, is associated with cardiac valve regurgitation. Methods We conducted a case-control study. Eligible patients were those admitted in the cardiology or the cardiac surgery units of our hospital between January, 1st 2003 and June 30th 2009, with mitral insufficiency diagnostic codes (ICD-10 I340 and I051). Patients with either a primary cause (degenerative, known rheumatic heart disease, infectious endocarditis, congenital, radiation-induced valvular disease, associated connective and/or vasculitis disease, trauma, tumor) or a secondary (functional) cause were considered as having an “explained” mitral regurgitation. Other patients were considered as having an “unexplained” mitral regurgitation and were included as cases. For each case, two controls were matched for gender and for the closest date of birth, among a list of patients with an “explained” mitral regurgitation. Drug exposures were assessed blindly regarding the case or control status, through contacts with patients, their family and/or their physicians. Results Out of the 682 eligible patients, 27 cases and 54 matched controls were identified. The use of benfluorex was reported in 22 patients: 19 of the 27 cases, versus 3 of the 54 controls, odds-ratio 17.1 (3.5 to 83), adjusted for body mass index, diabetes and dexfenfluramine use. Conclusion The use of benfluorex is associated with unexplained mitral regurgitation.

Fenfluramine-like cardiovascular side-effects of benfluorex.

Since 1976, benfluorex has been approved in Europe as a hypolipidemic and hypoglycemic drug, and is commonly used in the treatment of the metabolic syndrome. As a derivative of fenfluramine with an appetite suppressant action, benfluorex is preferentially used in overweight patients. In contrast to fenfluramine and dexfenfluramine, to date, benfluorex has not been reported to be associated with frequent cardiovascular side-effects. The present study reports five cases of severe pulmonary arterial hypertension and one case of valvular heart disease occurring in patients exposed to benfluorex. These individuals were middle age, diabetic females with a body mass index ranging 24.2–49 kg·m−2. No definite causal effect for cardiovascular disease with benfluorex can be drawn from such case reports. However, as benfluorex, like dexfenfluramine and fenfluramine, is metabolised into active metabolite norfenfluramine, further extensive assessment of drug exposure in newly diagnosed pulmonary arterial hypertension or valvular heart disease patients is warranted.

Noninvasive Diagnosis of Pulmonary Embolism

BACKGROUND We designed a simple and integrated diagnostic algorithm for acute pulmonary embolism (PE). Diagnosis was based on clinical probability assessment, plasma D-dimer testing, then sequential testing to include lower limb venous compression ultrasonography, ventilation perfusion lung scan, and chest multidetector CT (MDCT) imaging. METHODS We included 321 consecutive patients presenting at Brest University Hospital in Brest, France, with clinically suspected PE and positive d-dimer or high clinical probability. Patients in whom VTE was deemed absent were not given anticoagulants and were followed up for 3 months. RESULTS Detection of DVT by ultrasonography established the diagnosis of PE in 43 (13%). Lung scan associated with clinical probability was diagnostic in 243 (76%) of the remaining patients. MDCT scan was required in only 35 (11%) of the patients. The 3-month thromboembolic risk in patients not given anticoagulants, based on the results of the diagnostic protocol, was 0.53% (95% CI, 0.09-2.94). CONCLUSIONS A diagnostic strategy combining clinical assessment, d-dimer, ultrasonography, and lung scan gave a noninvasive diagnosis in the majority of outpatients with suspected PE and appeared to be safe.

Mild asthma: an expert review on epidemiology, clinical characteristics and treatment recommendations

This review is the synthesis of a working group on mild asthma. Mild asthma includes intermittent and persistent mild asthma according to the Global Initiative for Asthma (GINA) classification, and affects between 50% and 75% of asthmatic patients. Mild asthma is more frequent, more symptomatic, and less well controlled in children than in adults. Cohort studies from childhood to adulthood show that asthma severity usually remains stable over time. Nevertheless, mild asthma can lead to severe exacerbations, with a frequency ranging from 0.12 to 0.77 per patient‐year. Severe exacerbations in mild asthma represent 30–40% of asthma exacerbations requiring emergency consultation. In mild asthma, inflammation and structural remodelling are constant, of varying intensity, but nonspecific. Therapy with inhaled corticosteroids (ICS) decreases bronchial inflammation, but has only a slight effect on structural remodelling, and, when stopped, inflammation immediately recurs. Permanent low‐dose ICS therapy is the reference treatment for persistent mild asthma. Effectiveness is to be reassessed at 3 months, and if it is insufficient the patient is no longer considered mildly asthmatic, and treatment has to be stepped up. As mild asthma is the most frequent form of the disease, diagnosis and management require physicians’ particular attention.

Diagnostic Accuracy of Single-Photon Emission Tomography Ventilation/Perfusion Lung Scan in the Diagnosis of Pulmonary Embolism

BACKGROUND Planar ventilation/perfusion (V/Q) lung scintigraphy is a validated tool for the diagnosis of pulmonary embolism (PE). Nevertheless, given the high rate of nonconclusive V/Q, further investigation is often necessary. V/Q single-photon emission CT (SPECT) scan could improve V/Q performance, but sparse data are available on its accuracy. This study assessed the diagnostic performance of V/Q SPECT scan in a cohort of consecutive patients with suspected PE. METHODS Three hundred twenty-one consecutive patients with a clinical suspicion of PE were prospectively included. Patients suspected of having PE were managed according to a reference diagnostic strategy validated by a 3-month follow-up. In addition to the reference strategy, patients had a V/Q SPECT scan, the results of which were compared with the initial work-up results. RESULTS Prevalence of PE was 0 of 41 (0%; 95% CI, 0%-9%), six of 134 (4%; 95% CI, 2%-9%),15 of 36 (42%; 95% CI, 27%-58%), and 28 of 32 (88%; 95% CI, 72%-95%) in the normal, low,intermediate, and high V/Q SPECT scan probability groups, respectively. The combination of V/Q SPECT scan with clinical probability was diagnostic in 88% of patients. CONCLUSIONS V/Q SPECT scan results show satisfactory accuracy for PE diagnosis. Validation of dedicated interpretation criteria is required, followed by outcome studies that use V/Q SPECT scan as part of a diagnostic strategy to rule out PE. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT01183026; URL: www.clinicaltrials.gov