Reliability of Drug-Drug Interaction Measurement on Real-Word Data: The ReMIAMes Project.

The ReMIAMes project proposes a methodological framework to provide a reliable and reproducible measurement of the frequency of drug-drug interactions (DDI) when performed on real-world data. This framework relies on (i) a fine-grained and contextualized definition of DDIs, (ii) a shared minimum information model to select the appropriate data for the correct interpretation of potential DDIs, (iii) an ontology-based inference module able to handle missing data to classify prescription lines with potential DDIs, (iv) a report generator giving the value of the measurement and explanations when potential false positive are detected due to a lack of available data. All the tools developed are intended to be publicly shared under open license.

Increased Collagen Turnover Is a Feature of Fibromuscular Dysplasia and Associated With Hypertrophic Radial Remodeling: A Pilot, Urine Proteomic Study.

Fibromuscular dysplasia (FMD), a nonatherosclerotic, noninflammatory disease of medium-sized arteries, is an underdiagnosed disease. We investigated the urinary proteome and developed a classifier for discrimination of FMD from healthy controls and other diseases. We further hypothesized that urinary proteomics biomarkers may be associated with alterations in medium-sized, but not large artery geometry and mechanics. The study included 33 patients with mostly multifocal, renal FMD who underwent in depth arterial exploration using ultra-high frequency ultrasound. The cohort was separated in a training set of 23 patients with FMD from Belgium and an independent test set of 10 patients with FMD from Italy. For each set, controls matched 2:1 were selected from the Human Urinary Proteome Database. The specificity of the classifier was tested in 700 additional controls from general population studies, patients with chronic kidney disease (n=66) and coronary artery disease (n=31). Three hundred thirty-five urinary peptides, mostly related to collagen turnover, were identified in the training cohort and combined into a classifier. When applying in the test cohort, the area under the receiver operating characteristic curve was 1.00, 100% specificity at 100% sensitivity. The classifier maintained a high specificity in additional controls (98.3%), patients with chronic kidney (90.9%) and coronary artery (96.8%) diseases. Furthermore, in patients with FMD, the proteomic score was positively associated with radial wall thickness and wall cross-sectional area. In conclusion, a proteomic score has the potential to discriminate between patients with FMD and controls. If confirmed in a wider and more diverse cohort, these findings may pave the way for a noninvasive diagnostic test of FMD.

Sociodemographic and Clinical Characteristics of Vapers Using E-Cigarettes Exclusively: The French Vapoquid Study.

BACKGROUND: Electronic cigarettes are increasingly being used as smoking cessation aids. Most studies assess the dual use of e-cigarettes and traditional cigarettes, but there remains a paucity of literature concerning individuals who use e-cigarettes exclusively. Objective: The aim of this study is to examine the sociodemographic and clinical characteristics of exclusive e-cigarette users, and consider their willingness to quit e-cigarette use. Methods: A French online survey was conducted from March to December 2017. We assessed the following factors: sociodemographic factors; the clinical characteristics of e-cigarette use and its social acceptability; and the self-perceived effectiveness of nicotine replacement therapy (NRT). Associations between the listed factors and a willingness to quit e-cigarette use were examined. Results: A total of 386 exclusive e-cigarette users (70% men) participated in the study and were included in the analysis. Most respondents were not planning to quit e-cigarette use (75%). Compared to those who did not want to quit, a desire to quit was associated with using smoking cessation services (OR [95%CI]: 3.45 [1.82-6.56]), e-cigarette craving (OR [95%CI]: 2.63 [1.44-4.80]) and NRT past-use (1.78 [1.12-2.87]). Users who planned to quit expressed more concerns about smoking initiation among youths using e-cigarettes (OR [95%CI]: 3.62 [1.90-6.93]). In multivariate analysis, these associations remained significant for the use of smoking cessation services, e-cigarette cravings, and concerns about youth tobacco initiation. Conclusion: Most exclusive e-cigarette users were not likely to quit. Planned cessation was associated with using smoking cessation services, experiencing e-cigarette dependence symptoms, and being concerned about smoking initiation among teenager e-cigarette users.

The European/International Fibromuscular Dysplasia Registry and Initiative (FEIRI)-clinical phenotypes and their predictors based on a cohort of 1000 patients.

AIMS: Since December 2015, the European/International Fibromuscular Dysplasia (FMD) Registry enrolled 1022 patients from 22 countries. We present their characteristics according to disease subtype, age and gender, as well as predictors of widespread disease, aneurysms and dissections. METHODS AND RESULTS: All patients diagnosed with FMD (string-of-beads or focal stenosis in at least one vascular bed) based on computed tomography angiography, magnetic resonance angiography, and/or catheter-based angiography were eligible. Patients were predominantly women (82%) and Caucasians (88%). Age at diagnosis was 46 ± 16 years (12% ≥65 years old), 86% were hypertensive, 72% had multifocal, and 57% multivessel FMD. Compared to patients with multifocal FMD, patients with focal FMD were younger, more often men, had less often multivessel FMD but more revascularizations. Compared to women with FMD, men were younger, had more often focal FMD and arterial dissections. Compared to younger patients with FMD, patients ≥65 years old had more often multifocal FMD, lower estimated glomerular filtration rate and more atherosclerotic lesions. Independent predictors of multivessel FMD were age at FMD diagnosis, stroke, multifocal subtype, presence of aneurysm or dissection, and family history of FMD. Predictors of aneurysms were multivessel and multifocal FMD. Predictors of dissections were age at FMD diagnosis, male gender, stroke, and multivessel FMD. CONCLUSIONS: The European/International FMD Registry allowed large-scale characterization of distinct profiles of patients with FMD and, more importantly, identification of a unique set of independent predictors of widespread disease, aneurysms and dissections, paving the way for targeted screening, management, and follow-up of FMD.

Pregnancy-Related Complications in Patients With Fibromuscular Dysplasia: A Report From the European/International Fibromuscular Dysplasia Registry.

Current literature suggests a higher risk of pregnancy-related complications in patients with renal fibromuscular dysplasia (FMD). The aim of our study was to assess the nature and prevalence of pregnancy-related complications in patients subsequently diagnosed with FMD. A call for participation was sent to centers contributing to the European/International FMD Registry. Patients with at least 1 pregnancy were included. Data on pregnancy were collected through medical files and FMD characteristics through the European/International FMD Registry. Data from 534 pregnancies were obtained in 237 patients. Despite the fact that, in 96% of cases, FMD was not diagnosed before pregnancy, 40% of women (n=93) experienced pregnancy-related complications, mostly gestational hypertension (25%) and preterm birth (20%), while preeclampsia was reported in only 7.5%. Only 1 patient experienced arterial dissection and another patient an aneurysm rupture. When compared with patients without pregnancy-related complications, patients with complicated pregnancies were younger at FMD diagnosis (43 versus 51 years old; P<0.001) and had a lower prevalence of cerebrovascular FMD (30% versus 52%; P=0.003) but underwent more often renal revascularization (63% versus 40%, P<0.001). In conclusion, the prevalence of pregnancy-related complications such as gestational hypertension and preterm birth was high in patients with FMD, probably related to the severity of renal FMD. However, the prevalence of preeclampsia and arterial complications was low/moderate. These findings emphasize the need to screen hypertensive women for FMD to ensure revascularization before pregnancy if indicated and appropriate follow-up during pregnancy, without discouraging patients with FMD from considering pregnancy.

Prevalence and characteristics of renal artery fibromuscular dysplasia in hypertensive women below 50 years old.

BACKGROUND: Renal fibromuscular dysplasia (FMD) is typically diagnosed in young hypertensive women. The 2014 European FMD Consensus recommended screening in all hypertensive women <30 yo. However, the prevalence of renal FMD in young/middle-aged hypertensive women remains unclear. The aim of this work was to assess the prevalence and characteristics of renal FMD in hypertensive women ≤50 yo. METHODS: We retrospectively included all consecutive women aged ≤50 years referred to our Hypertension Unit from 2014 to 2017 and collected standardized information on patient characteristics and screening modalities. RESULTS: Of 1083 incident hypertensive patients, 157 patients fitted with inclusion criteria. The prevalence of renal FMD varied between 3.2% in the whole sample and 7.5% in patients explored by CTA and/or MRA (n = 67). In the subgroup of patients ≤30 yo (n = 32), the corresponding figures were 3.1% and 5.6%. The yearly prevalence of FMD tended to increase over time, in parallel with increased use of CTA/MRA as a first-line imaging modality. Out of 5 patients with renal FMD, 2 were revascularized and 1 had extra-renal FMD. CONCLUSIONS: The prevalence of renal FMD in young/middle-aged hypertensive women is probably one order of magnitude higher than previously assumed, in the range of 3%-8%, depending on imaging modalities. While the diagnosis of FMD does not influence short-term management in all patients, it may allow close monitoring and prevention of complications of the disease over time. This analysis provides the rationale for a prospective, multicentre study aiming at determining the cost-effectiveness of systematic screening for renal FMD.

[Fibromuscular dysplasia and hypertension : beyond renal arteries]. / Hypertension et dysplasie fibromusculaire :au-delà des artères rénales.

Fibromuscular dysplasia (FMD) is a disease associated with abnormalities of the arterial wall of medium-sized arteries. These abnormalities can lead to stenosis or less frequently to dissections or aneurysms. FMD is probably more frequent than initially thought. Nowadays, it is often a chance finding during a radiologic exam. In symptomatic cases, poor organ perfusion due to stenosis, dissection or aneurysm rupture may lead to the diagnosis. The aim of this non-systematic review illustrated with a clinical case is to present our current knowledge of FMD and to highlight the necessity of a standardized and multidisciplinary work-up to improve management of affected patients and understanding of the disease.

La dysplasie fibromusculaire (DFM) est une maladie associée à des anomalies de la paroi des artères de moyen calibre pouvant entraîner des sténoses et plus rarement des anévrismes ou des dissections. Moins rare qu'on ne le pensait initialement, la DFM est parfois découverte fortuitement lors d'un bilan de santé lorsque la maladie est asymptomatique ou lors des manifestations secondaires à l'ischémie de l'organe atteint, conséquence d'une sténose, d'une dissection ou d'une rupture de la paroi artérielle. A partir d'un cas clinique, cette revue non systématique illustre nos connaissances actuelles de la DFM et souligne l'importance d'une prise en charge multidisciplinaire et standardisée pour de meilleurs soins aux patients et une meilleure compréhension de la maladie.

Building a Semantic Interoperability Framework for Care and Research in Fibromuscular Dysplasia.

UNLABELLED: Identifying patients with Fibromuscular Dysplasia (FMD) at the international level will have considerable value for understanding the epidemiology, clinical manifestations and susceptible genes in this arterial disease, but also for identifying eligible patients in clinical trials or cohorts. We present a two-step methodology to create a general semantic interoperability framework allowing access and comparison of distributed data over various nations, languages, formats and databases. METHODS: The first step is to develop a pivot multidimensional model based on a core dataset to harmonize existing heterogeneous data sources. The second step is to align the model to additional data, semantically related to FMD and collected currently in various registries. We present the results of the first step that has been fully completed with the validation and implementation of the model in a dedicated information system (SIR-FMD). We discuss the current achievements for step 2 and the extensibility of the methodology in the context of other rare diseases.

A new approach for cleansing geographical dataset using Levenshtein distance, prior knowledge and contextual information.

Epidemiological studies are necessary to take public health decisions. Their relevance depends on the quality of data. Doctors in continuous care collect a big amount of data that can be used for epidemiological purpose, but spatial data may be dirty; based on city names, the localization is imprecise, even more if it is misspelled. The only way to identify a city without ambiguity is to use its identifier, which can be retrieved by cleansing geographical textual data. In France, cities are organized in administrative zones called departments and some city names are shared by several cities in several departments. The clear identification of the department and the city name allows to deduce the city unique identifier and to make some spatial analysis such as epidemiological studies. In this paper, we propose a method to cleanse such data, using several steps. After having standardized the text to cleanse, we use the Levenshtein distance to generate a first set of propositions. Finally, the propositions are filtered, by removing the less likely candidates, so that it remains only one, which becomes the chosen city. Tested on a dataset of 9818 entries, we obtained 89.1% of concordance, whereas the standard Levenshtein distance obtained 70.5%. This demonstrates that our method has better results.

ADVISE: First Results of a European Interoperative Information System Network Developed for the ADenoVirus Initiative Study in Epidemiology.

Adenoviral conjunctivitis is extremely contagious, causes a form of conjunctivitis. Therefore, it is important to identify patients who suffer from adenoviral conjunctivitis, as early as possible, in order to contain the disease. We present the 6 independent but interoperable platforms developed for the purpose of a large European epidemiologic study (ADVISE), which has been implemented independently in France, Germany, Spain, Italy and the UK. ADVISE is a non-interventional, observational epidemiology study with the objectives of assessing clinical characteristics and incidence of adenovirus conjunctivitis. One of the challenges faced in developing this network of European epidemiology platforms has been the multilingual context. Actually, we have established independent platforms fully dedicated to each of the participating countries. Similar protocols have been submitted across these countries, allowing individual and pooled analyses of the data. A standardized questionnaire is used to collect patient ocular medical history. The electronic questionnaire contains 151 items with automatic coherence control. The first platform ADVISE was set up in France. Development, evaluation and validation of this platform were carried out between January and July 2013. The Medical Informatics and Knowledge Engineering Laboratory (LIMICS), proposes through this project, a tool that allows the installation and application of epidemiologic monitoring in any part of the world.

A "pivot" Model to set up Large Scale Rare Diseases Information Systems: Application to the Fibromuscular Dysplasia Registry.

The SIR-FMD project is a partnership between the Department of Genetics and Reference Centre for Rare Vascular Diseases at the Georges Pompidou European Hospital in Paris and the Medical Informatics and Knowledge Engineering Laboratory of Inserm. Its aim is to use an ontological approach to implement an information system for the French Fibromuscular Dysplasia Registry. The existing data was dispersed in numerous databases, which had been created independently. These databases have different structures and contain data of diverse quality. The project aims to provide generic solutions for the management of the communication of medical data. The secondary objective is to demonstrate the applicability of these generic solutions in the field of rare diseases (RD) in an operational context. The construction of the French FMD registry was a multistep process. A secure platform has been available since the beginning of November 2013. The medical records of 471 patients from the initial dataset provided by the HEGP-Paris, France have been included, and are accessible from a secure user account. Users are organized into a collaborative group, and can access patient groups. Each electronic patient record contains more than 2,200 items. The problem of semantic interoperability has become one of the major challenges for the development of applications requiring the sharing and reuse of data. The information system component of the SIR-FMD project has a direct impact on the standardisation of coding of rare diseases and thereby contributes to the development of e-Health.

Suspected community-acquired pneumonia in an ambulatory setting (CAPA): a French prospective observational cohort study in general practice.

BACKGROUND: Few studies have addressed the pragmatic management of ambulatory patients with suspected community-acquired pneumonia (CAP) using a precise description of the disease with or without chest X-ray (X-ray) evidence. AIMS: To describe the characteristics, clinical findings, additional investigations and disease progression in patients with suspected CAP managed by French General Practitioners (GPs). METHODS: The patients included were older than 18 years, with signs or symptoms suggestive of CAP associated with recent-onset unilateral crackles on auscultation or a new opacity on X-ray. They were followed for up to 6 weeks. Descriptive analyses of all patients and according to their management with X-rays were carried out. RESULTS: From September 2011 to July 2012, 886 patients have been consulted by 267 GPs. Among them, 278 (31%) were older than 65 years and 337 (38%) were at increased risk for invasive pneumococcal disease. At presentation, the three most common symptoms, cough (94%), fever (93%), and weakness or myalgia (81%), were all observed in 70% of patients. Unilateral crackles were observed in 77% of patients. Among patients with positive radiography (64%), 36% had no unilateral crackles. A null CRB-65 score was obtained in 62% of patients. Most patients (94%) initially received antibiotics and experienced uncomplicated disease progression regardless of their management with X-rays. Finally, 7% of patients were hospitalised and 0.3% died. CONCLUSIONS: Most patients consulting GPs for suspected CAP had the three following most common symptoms: cough, fever, and weakness or myalgia. More than a third of them were at increased risk for invasive pneumococcal disease. With or without X-rays, most patients received antibiotics and experienced uncomplicated disease progression.

Venous thromboembolism prophylaxis in patients undergoing abdominal or pelvic surgery for cancer--a real-world, prospective, observational French study: PRéOBS.

INTRODUCTION: Data on the epidemiology and prevention of venous thromboembolism in patients undergoing abdominal or pelvic cancer surgery in real practice are limited. The primary objective of this observational study was to describe the thromboprophylactic strategy implemented in routine practice. The main secondary objective was to assess the incidence of outcomes. MATERIALS AND METHODS: Patients admitted to public or private hospitals for abdominal or pelvic cancer surgery were included between November 2009 and November 2010; endoscopic route for surgery was the only exclusion criterion. Study outcomes were recorded at hospital discharge and at routine follow-up (generally 9±3weeks). RESULTS: 2380 patients (mean±SD age: 66.4±11.6years, women: 36.8%) admitted to hospital for abdominal (47.8%), urological (41%), or gynaecological (11.2%) cancer surgery were included in the analysis. Of these, 2179 had data available at study end. Perioperative antithrombotic prophylaxis, consisting mainly of low-molecular-weight heparin, was given to 99.5% of patients. At hospital discharge, thromboprophylaxis was continued in 91.7% of patients, 57.4% receiving a 4-6week prophylaxis. This management strategy was associated with an overall venous thromboembolic event rate of 1.9%, 34.7% of events occurring after discharge. Incidences of fatal bleeding, bleeding in a critical organ and bleeding necessitating re-intervention were 0.1%, 0.3% and 1.7%, respectively. Overall mortality was 1.5%. CONCLUSIONS: Thromboprophylaxis is routinely used in French patients undergoing major cancer surgery. For more than a third of patients, however, treatment duration did not comply with best-practice recommendations, which might explain the non-negligible rate of thromboembolic complications still observed in this patient population.

CEMARA an information system for rare diseases.

Rare diseases cover a group of conditions characterized by a low prevalence, affecting less than 1 in 2,000 people; 5000 to 7000 rare diseases have been currently identified in Europe. Most diseases do not have any curative treatment. They represent thus an important public health concern. CEMARA is based on a n-tier architecture. Its main objective is to collect continuous and complete records of patients with rare diseases, and their follow-up through a web-based Information System, and to analyse the epidemiological patterns. In France, 41 out of 131 labelled Reference Centres (RC) are sharing CEMARA. Presently 56,593 cases have been registered by more than 850 health care professionals belonging to 171 clinical sites. The national demand of care was explored in relation with the offer of care in order to reach an improved match. Within 2 years, CEMARA stimulated sharing a common platform, a common ontology with Orphanet and initiating new cohorts of rare diseases for improving patient care and research.

Dynamical modeling of viral spread in spatially distributed populations: stochastic origins of oscillations and density dependence.

In order to understand the spatio-temporal structure of epidemics beyond that permitted with classical SIR (susceptible-infective-recovered)-type models, a new mathematical model for the spread of a viral disease in a population of spatially distributed hosts is described. The positions of the hosts are randomly generated in a rectangular habitat. Encounters between any pair of individuals are according to a Poisson process with a mean rate that declines exponentially as the distance between them increases. The contact rate allows the mean rates to be set at a certain number of encounters per day on average. The relevant state variables for each individual at any time are given by the solution of a pair of coupled differential equations for the viral load and the quantity of general immune system effectors which reduce the viral load. The parameters describing within-host viral-immune system dynamics are generated randomly to reflect variability across a population. Transmission is assumed to depend on the viral loads in donors and occurs with a probability ptrans. The initial conditions are such that one randomly chosen individual carries a randomly chosen amount of the virus, whereas the rest of the population is uninfected. Simulations reveal local or whole-population responses. Whole-population disease spread may be in the form of isolated or multiple occurrences, the latter often being approximately periodic. The mechanisms of this oscillatory behaviour are analyzed in terms of several parameters and the distribution of critical points in the host dynamical systems. Increased contact rate, increased probability of transmission and decreased threshold for viral transmission, decreased immune strength and increased viral growth rate all increase the probability of multiple outbreaks and the distribution of the critical points also plays a role.

Log files analysis to assess the use and workload of a dynamic web server dedicated to end-stage renal disease.

A Multi-Source Information System (MSIS), has been designed for the Renal Epidemiology and Information Network (REIN) dedicated to End-Stage Renal Disease (ESRD). MSIS aims at providing reliable follow-up data for ESRD patients. It is based on an n-tier architecture, made out of a universal client, a dynamic Web server connected to a production database and to a data warehouse. MSIS is operational since 2002 and progressively deployed in 9 regions in France. It includes 16,677 patients. We show that the analysis of MSIS web log files allows evaluating the use of the system and the workload in a public-health perspective.

ICPCview: visualizing the International Classification of Primary Care.

This paper proposes a method to visualize the semantic content of data bases where the medical information is coded with the International Classification of Primary Care. The main idea is the identification of a pixel with a code and the conversion of all the data associated with these into an image the ICPCview. The method proceeds in two step, defining the reference frame and using this reference frame to visualize data. The reference frame is built by using a sign/diagnosis binary criterion, a seventeen category nosological criterion and an age ordinal criterion. The results are visualization of the signs and diagnosis of the ICPC according to gender, age and time period of the year. A limitation of the method lies in the fact that the result depends on the chosen reference frame. Further work has to be done with various reference frames and data. However the main point is that, when both the reference set of the image and of the mind of the user are built, the method is powerful at extracting the hidden content of a very large amount of data.

SIGNe: A Geographic Information System on the Web for End-Stage Renal Disease.

A Web-based Geographic Information System (Web-GIS), the SIGNe (Système d'Information Géographique pour la Néphrologie), was designed for the Renal Epidemiology and Information Network (REIN) dedicated to End-Stage Renal Disease (ESRD). This Web-GIS was coupled to a data warehouse and embedded in an n-tier architecture designed as the Multi-Source Information System (MSIS). It allows to access views of ESRD concerning the epidemiology of the demand and the supply of care. It also provides maps matching the offer of care to the demand. It is presented with insights on the design and underlying technologies. It is dedicated to professionals and to public health care decision-makers in the domain of ESRD.