Sylvie Escolano

• French Institute of Health and Medical Research

Background: Statins represent candidates for drug repurposing in Parkinson's disease (PD). Few studies examined the role of reverse causation, statin subgroups, and dose-response relations based on time-varying exposures. Objectives: We examined whether statin use is associated with PD incidence while attempting to overcome the limitations descr...

Background: Available treatments for Parkinson's disease (PD) are only partially or transiently effective. Identifying existing molecules that may present a therapeutic or preventive benefit for PD (drug repositioning) is thus of utmost interest. Objective: We aimed at detecting potentially protective associations between marketed drugs and PD t...

Introduction La maladie de Parkinson (MP) est celle dont la prévalence augmente le plus rapidement parmi les maladies neurologiques alors que les traitements disponibles ne sont que partiellement ou transitoirement efficaces. Une stratégie prometteuse consiste à identifier des molécules existantes pouvant présenter un avantage thérapeutique voire p...

Introduction: Increasing availability of medico-administrative databases has prompted the development of automated pharmacovigilance signal detection methodologies. Self-controlled approaches have recently been proposed. They account for time-independent confounding factors that may not be recorded. So far, large numbers of drugs have been screene...

Background The burden of human papillomavirus (HPV) infection can be substantially reduced through vaccination of girls, and gender-neutral policies are being adopted in many countries to accelerate disease control among women and expand direct benefits to men. Clinical direct benefit of boys HPV vaccination has been established for ano-genital war...

Objective: To assess the risk of preterm birth associated with nonsteroidal anti-inflammatory drugs (NSAIDs), focusing on early exposure in the period from conception to 22 weeks of gestation (WG). Design: National population-based retrospective cohort study SETTING: The French National Health Insurance Database that includes hospital discharge...

Background Rotavirus is a major cause of severe gastroenteritis in children worldwide. The disease burden has been substantially reduced in countries where rotavirus vaccines are used. Given the risk of vaccine-induced intussusception, the benefit-risk balance of rotavirus vaccination has been assessed in several countries, however mostly without c...

Background Pregnant women are largely exposed to medications. However, knowledge is lacking about their effects on pregnancy and the fetus.Objective This study sought to evaluate the potential of high-dimensional propensity scores and high-dimensional disease risk scores for automated signal detection in pregnant women from medico-administrative da...

Introduction Peu d’études ont exploré le risque de prématurité induit par les anti-inflammatoires non stéroïdiens (AINS), alors que la prématurité constitue un facteur de risque majeur de morbidité et de mortalité post-natales. Le but de cette étude était d’évaluer le risque de naissance prématurée associé aux AINS, en mettant l’accent sur l’exposi...

Objective To evaluate the risk of Guillain-Barré syndrome (GBS) following seasonal influenza vaccination based on French nationwide data. Methods All cases of GBS occurring in metropolitan France between September 1 and March 31 from 2010 to 2014 were identified from the French national health data system. Data were analyzed according to the self-...

Background:Pregnant women are often excluded from clinical tri-als despite their need to use drugs. So, there is a lack of informa-tion of drugs adverse effects during pregnancy. Administrativedatabases are a promising tool for post‐market surveillance in thispopulation and confounder summary scores can improve signaldetection.Objectives:To evaluat...

Introduction Chaque année en France, plus de 5 millions de personnes sont vaccinées contre la grippe dans le cadre de la campagne de vaccination de l’Assurance maladie. Certaines études ont rapporté une association entre la vaccination antigrippale et le syndrome de Guillain-Barré (SGB), mais cette association demeure incertaine. L’objectif de cett...

Background In pharmacoepidemiology, the prescription preference-based instrumental variables (IV) are often used with linear models to solve the endogeneity due to unobserved confounders even when the outcome and the endogenous treatment are dichotomous variables. Using this instrumental variable, we proceed by Monte-Carlo simulations to compare th...

Introduction Two vaccines available for protection against rotavirus gastroenteritis (RVGE), Rotarix and RotaTeq, have contributed to a large decrease in the incidence of paediatric diarrhoea in countries where they have been used. However, they have also led to a small increase in the risk of intussusception. Methods: We compare the number of prev...

Purpose: To provide an up-to-date account of drug prescription during pregnancy in France from 2011 to 2014 using the permanent sample of the French national computerized healthcare database and with a focus on recommended supplementations, fetotoxic drugs and teratogenic drugs. Methods: All pregnancies identified by the International Classifica...

Background: Executive function (EF) impairment is a major predictor of overall outcome after traumatic brain injury (TBI). TBI severity is a factor of poor outcome, but most studies include a majority of children with mild and moderate TBI. The aims of this study were to estimate EF impairment after severe childhood TBI and to explore factors pred...

Introduction La grossesse est une periode a risque concernant l’utilisation des medicaments du fait d’effets potentiellement graves sur l’enfant a naitre. Les recommandations concernant la prescription chez la femme enceinte evoluent rapidement. L’objectif de cette etude est d’offrir un etat des lieux de la prescription medicamenteuse pendant la gr...

Since there is no ideal candidate to replace sulfadoxine-pyrimethamine (SP) for intermittent preventive treatment (IPTp), alternatives need to be evaluated on basis of their benefit-risk ratio. We reanalyzed the first Beninese trial on mefloquine (MQ) versus SP for IPTp using a multiple outcome approach, which allowed the joint assessment of effica...

Environmental parameters have been reported to be triggers of acute myocardial infarction (MI). However, the individual role of each parameter is unknown. We quantified the respective association of climate parameters, influenza epidemics and air pollutants with the onset of ST elevation MI (STEMI) in Paris and the surrounding small ring. Data from...

Introduction Les bases de données médico-administratives sont de plus en plus utilisées pour évaluer le risque vaccinal. L’échantillon généraliste des bénéficiaires (EGB) a été créé à partir de celle de l’Assurance-maladie par échantillonnage au 1/97e de la population française. L’objectif de l’étude est de calculer pour différentes associations ef...

Multidrug resistant leprosy, defined as resistance to rifampin, dapsone and fluoroquinolones (FQ), has been described in Mycobacterium leprae. However, the in vivo impact of fluoroquinolone resistance, mainly mediated by mutations in DNA gyrase (GyrA2GyrB2), has not been precisely assessed. Our objective was to measure the impact of a DNA gyrase mu...

In the French national health insurance information system (SNIIR-AM), routine records of health claimed reimbursements are linked to hospital admissions for the whole French population. The main focus of this work is the usability of this system for vaccine safety assessment programme. Self-controlled case series analyses were performed using an e...

In this paper, we propose new methods for analyzing cases of vaccine adverse events spontaneously reported to a surveillance database. The methods use the self-controlled case series approach, extended in several ways with parametric and nonparametric assumptions to account for the specific features of the data (large amount of underreporting and v...

When fitting marginal models to correlated outcomes, the so-called sandwich variance is commonly used. However, this is not the case when fitting mixed models. Using two data sets, we illustrate the problems that can be encountered. We show that the differences or the ratios between the naive and sandwich standard deviations of the fixed effects es...

Short-term exposure to high levels of air pollution may trigger myocardial infarction (MI), but this association remains unclear. To assess and quantify the association between short-term exposure to major air pollutants (ozone, carbon monoxide, nitrogen dioxide, sulfur dioxide, and particulate matter ≤10 μm [PM(10)] and ≤2.5 μm [PM(2.5)] in diamet...

To the Editor: Patel et al. report an increased risk of intussusception after rotavirus vaccination.1 We conducted a case-series analysis2 of 151 spontaneous reports of intussusception worldwide after administration of the rotavirus vaccine RV1 (Rotarix, GlaxoSmithKline Biologicals). On the basis of a report citing the incidence of intussusception...

In cognitively impaired or young children with epilepsy, only proxy-report can be used for the assessment of Quality of Life (QOL) and behavior. The present study aims to propose proxy QOL tools applicable in all children with epilepsy and to examine the impact of epilepsy characteristics (e.g., age of onset of epilepsy, epilepsy syndrome) and chil...

Data from several previous studies examining heart-rate and cardiovascular risk have hinted at a possible relationship between heart-rate and non-cardiac mortality. We thus systematically examined the predictive value of heart-rate variables on the subsequent risk of death from cancer. In the Paris Prospective Study I, 6101 asymptomatic French work...

We aimed to develop and validate a simple coronary heart disease (CHD) risk algorithm applicable to asymptomatic men and women in France, and to compare its accuracy with that of the last published version of the Framingham risk function for cardiovascular disease. A pooled analysis of four French prospective general-population studies. The baselin...

To determine if female gender is an independent predictor of in-hospital mortality after percutaneous coronary intervention (PCI) for ST segment elevation myocardial infarction (STEMI). A higher early mortality rate after STEMI has been reported in women before the widespread use of PCI in STEMI. PCI improves the prognosis of STEMI, however, the ef...

Background: We aimed to develop and validate a simple coronary heart disease (CHD) risk algorithm applicable to asymptomatic men and women in France, and to compare its accuracy with that of the last published version of the Framingham risk function for cardiovascular disease. Design: A pooled analysis of four French prospective general-population...

To report daily practice of scene emergency tracheal intubation performed by physicians and changes induced by implementation of national guidelines, with special attention to rapid sequence induction (RSI) and control of assisted ventilation. Observational study. Pediatric intensive care unit of a university hospital. A total of 296 children (age,...

The science of engineering materials and the development of materials science during human history have strongly evolved over the past two centuries 1,2 . Other new technological fields such as particle physics, computer science, nanoscience also flourished 3 , all leading to innovations that impacted sport. Polymers and metal alloys such as carbon...

Anticoagulation therapy is recommended for patients with Budd-Chiari syndrome (BCS). This study aimed to assess the incidence, severity, and risk factors of major bleeding in patients with Budd-Chiari syndrome (BCS) receiving anticoagulation therapy. We evaluated 94 consecutive BCS patients. Major bleeding required hospitalization, and/or transfusi...

Vagal hyperreactivity (VHR) is a frequent etiology of infant fainting spells; but it is sometimes difficult to diagnose. A biochemical test would therefore be useful, especially as the oculocardiac reflex (OCR) test innocuity is not absolute. To evaluate urinary excretions of norepinephrine, epinephrine and dopamine as markers for vagal hyperreacti...

Sex is a major factor influencing best performances and world records. Here the evolution of the difference between men and women's best performances is characterized through the analysis of 82 quantifiable events since the beginning of the Olympic era. For each event in swimming, athletics, track cycling, weightlifting and speed skating the gender...

Little is known on the morphological changes in the kidneys of cirrhotic patients with abnormal urinalysis and/or high serum creatinine levels. This retrospective, one-point-in-time study aimed to report the results of the analysis of renal biopsy specimens obtained in patients with cirrhosis. We retrieved information on 65 patients who underwent t...

The use of structural equation modeling and latent variables remains uncommon in epidemiology despite its potential usefulness. The latter was illustrated by studying cross-sectional and longitudinal relationships between eating behavior and adiposity, using four different indicators of fat mass. Using data from a longitudinal community-based study...

Secular evolution of the yearly average distance of residuals (YADR). A. Secular evolution of YADR in T&F (gray bars, left ordinate) with the number of changes of inclines (red bars, right ordinate). B. Secular evolution of YADR in swimming (gray bars, left ordinate) with the number of MRCOI detected each year (red bars, right ordinate). The analys...

Model and descriptors (d1-d3) description. Description of the model and the Gompertz function. Description of the three statistical descriptors d1-d3. (0.08 MB DOC)

Evolution of cv(t) factor in T&F and swimming. cv(t) values are decreasing over time in T&F (black dots); cv(t) values show no trend in swimming (red squares) on a shorter follow-up period. T&F cv(t) evolution is linked to historic events: after World War II values are getting tighter (<0.015) suggesting all performances are progressing in the same...

Evolution of the 10 best performers in all 70 events. Women events (W) and Men events (M) are sorted by disciplines (T&F vs. swimming), and distances/type of efforts for T&F. All swimming events show progression after the MRCOI. (0.10 MB DOC)

Model fitting on 6 T&F. A. Men discus throw (T&F) (R2i = 0.85; R2ii = 0.83; R2iii = 0.94), “halted” in 1984.2. B. Women discus throw (T&F) (R2i = 0.88; R2ii = 0.92), “halted” in 1988.4. C. Women long jump (R2i = 0.70; R2ii = 0.90), “halted” in 1996.8. D. Women high jump (R2i = 0.78; R2ii = 0.95), “halted” in 1995.2. E. Men shot put (R2i = 0.43; R2i...

Secular evolution of descriptors. Evolution is given in T&F (A, B, C, black dots) and swimming (D, E, F, red squares). Descriptor d2 presents a decreasing evolution from 2003 to 2008, which is related to time. It is assessed by T, measuring the number of performances still unbeaten (green squares) in both disciplines. High average values of T&F des...

Spatial repartition and distributions of the 3 uniformized descriptors d1, d2, d3. Spatial repartition and distributions of the 3 uniformized descriptors d1, d2, d3 for T&F (A, black dots and bars) and swimming (B, red dots and bars). All distributions are unimodal with positive skew. For T&F: d'1 skew = 2.9; d'2 skew = 3.8; d'3 skew = 4.5; for swi...

The growth law for the development of top athletes performances remains unknown in quantifiable sport events. Here we present a growth model for 41351 best performers from 70 track and field (T&F) and swimming events and detail their characteristics over the modern Olympic era. We show that 64% of T&F events no longer improved since 1993, while 47%...

To examine the impact of malignancy and location of the cerebellar tumor on motor, cognitive, and psychologic outcome. Although many studies focus on long-term outcome after cerebellar tumor treatment in childhood, the impact of its precise location remains unclear. Children, aged from 6 to 13 years, with a cerebellar malignant tumor (MT; MT group,...

Patients with Budd-Chiari syndrome can present with acute, subacute, or chronic disease; the definitions and significance of these variants have been disputed. An increased level of serum alanine aminotransferase (ALT) is an objective marker for acute liver injury. We analyzed the significance of changes in ALT levels in Budd-Chiari syndrome patien...

The aim of this study involves the early identification, among apparently healthy individuals, of those at high risk for sudden cardiac death. We tested the hypothesis that individuals who respond to mild mental stress in preparation for exercise test with the largest heart rate increases might be at highest risk. Data from 7746 civil servants part...

Several prognostic indices (PIs) have been proposed for Budd-Chiari syndrome (BCS). However, patient characteristics, causal factors, and treatment outcomes have changed since these indices have been elaborated. Validation in a recent patient population and comparison of predictive accuracy between these PIs are needed. A database of 96 BCS patient...

The prognostic implications of heart rate (HR) change over years have never been assessed. It was hypothesized that an increase in HR in apparently healthy persons observed over years could be associated with an increase in mortality risk and conversely. A total of 5,139 asymptomatic working men (aged 42 to 53 years) free of clinically detectable c...

We have investigated the relation between haptico-visual recognition of objects and cognitive tasks in two large samples of preschoolers (n = 534; n = 750). Children aged 6 years completed a cross-modal task in which they have first to haptically explore an object and second to visually recognize it; they also performed phonological, verbal semanti...

The behavioural and academic performance of young children with teachers' reported hyperactivity, conduct problems or inattention is under debate. This study investigates the associations between teachers' reported behavioural difficulties and academic and cognitive performances in two large samples of preschool and school children in France. SAMPL...

World records (WR) in sports illustrate the ultimate expression of human integrated muscle biology, through speed or strength performances. Analysis and prediction of man's physiological boundaries in sports and impact of external (historical or environmental) conditions on WR occurrence are subject to scientific controversy. Based on the analysis...

Various methods have recently been proposed to assess the physical, psychological or social dimensions of quality of life (QoL) in children with epilepsy (CwE) and their families. Some methods are based exclusively on parental report and others emphasize the importance of an interview with the patient himself. In children with epilepsy and severe c...

Children with epilepsy are known to be prone to educational underachievement as a result of learning and behavioral problems. This cross-sectional study evaluated the effects of the characteristics of epilepsy and behavioral problems on school placement. One hundred eighty-five children aged between 3 and 16 years with nonoccasional epileptic seizu...

Reliable estimation methods for non-linear mixed-effects models are now available and, although these models are increasingly used, only a limited number of statistical developments for their evaluation have been reported. We develop a criterion and a test to evaluate nonlinear mixed-effects models based on the whole predictive distribution. For ea...

Phonological awareness is strongly related to reading ability, but reports are more conflicting concerning the association of high level oculomotor skills with reading. Here, we show that phonological awareness is specifically associated with the ability to perform smooth pursuit eye movements in preschool children. Two large independent samples of...

It is now widely accepted that haplotypic information can be of great interest for investigating the role of a candidate gene in the etiology of complex diseases. In the absence of family data, haplotypes cannot be deduced from genotypes, except for individuals who are homozygous at all loci or heterozygous at only one site. Statistical methodologi...

P-selectin and P-selectin glycoprotein ligand (SELPLG, selectin P ligand) constitute a receptor/ligand complex that is likely to be involved in the development of atherosclerosis and its complications. While the genetic variability of P-selectin has already been investigated in depth, that of the SELPLG gene has not yet been extensively explored. T...

A recent study in patients with Budd-Chiari syndrome showed the value of a prognostic index including age, Pugh score, ascites and serum creatinine. Surgical portosystemic shunt did not appear to improve survival. To validate these findings in an independent sample; to evaluate a classification into three forms according to the presence of features...

P-selectin is a cellular adhesion molecule that may be involved in the development of atherosclerosis and its complications. We have previously identified thirteen polymorphisms of the P-selectin gene among which five were located in the coding region of the gene (S290N, N562D, V599L, T715P, T741T (A/G)). These polymorphisms were tested individuall...

Background: beta-Blockade-induced benefit in heart failure (HF) could be related to baseline heart rate and treatment-induced heart rate reduction, but no such relationships have been demonstrated. Methods and results: In CIBIS II, we studied the relationships between baseline heart rate (BHR), heart rate changes at 2 months (HRC), nature of car...

Nosocomial (hospital-acquired) infections are very frequent in intensive care units (ICU). The risk of death after severe infection is high, but the precise rate of death in ICU attributable to nosocomial infection is not known. The goal of this project was to build a statistical model to predict the occurrence of nosocomial infections in ICU and t...

In vitro activities of 17 antibiotics against 53 clinical strains of Mycobacterium marinum, an atypical mycobacterium responsible for cutaneous infections, were determined using the reference agar dilution method. Rifampin and rifabutin were the most active drugs (MICs at which 90% of the isolates tested were inhibited [MIC90s], 0.5 and 0.6 μg/ml,...

The aim of this study was to assess the factors, including surgical portosystemic shunts, which affect survival in adults with Budd-Chiari syndrome. Multivariate retrospective analysis was performed using characteristics recorded at the time of diagnosis in 120 patients admitted from 1970 to 1992, of whom 82 were treated with surgical portosystemic...

To further evaluate the mechanism of beta-blocker-induced benefits in heart failure, the relationships between bisoprolol-induced hemodynamic effects and survival were studied during the Cardiac Insufficiency BIsoprolol Study (CIBIS). In 557 patients studied, bisoprolol significantly reduced heart rate (-16.3+/-15.3 versus -1.6+/-13.4 bpm, respecti...

Endothelin-1 is a potent vasoconstrictive and multifunctional peptide. Elevated concentrations have been reported in congestive heart failure. We hypothesized that the level of endothelin-1 in plasma is a prognostic marker in congestive heart failure. Plasma levels of endothelin-1 were measured by radioimmunoassay in 120 congestive heart failure pa...

Elastic arteries were found to be less prone to intimal hyperplasia than muscular arteries. The internal mammary artery (IMA), which is elastic in its proximal segment, presents a gradual decrease of media elastic fibers along its downstream course. Metabolic and morphometric studies of the distal end of the IMA with regard to its local susceptibil...

The feasibility of spirometry or respiratory impedance measurements for assessing lung function in the elderly was compared in 208 institutionalized patients with various degrees of cognitive function impairment. Respiratory impedance was determined by the forced oscillation technique. Cognitive function was assessed by the score for the mini-menta...

In cirrhotic patients, bacterial infection is frequently associated with gastrointestinal bleeding and seems to increase mortality. The aims of this study were to determine the incidence of bacterial infections in bleeding cirrhotic patients and the influence of infections on the risk of rebleeding and death. Cirrhotic patients admitted for gastroi...

To identify a physico-chemical criterion, or set of criteria, explaining and possibly predicting the nephrotoxic behaviour of Bence-Jones proteins (BJP). The electrophoretic mobility and isoelectric point (pI) of 92 BJP isolates were determined using various electrophoresis procedures on polyacrylamide gel. The proportions of monomers and dimers we...

The most widely used model for multidimensional survival analysis is the Cox model. This model is semi-parametric, since its hazard function is the product of an unspecified baseline hazard, and a parametric functional form relating the hazard and the covariates. We consider a more flexible and fully nonparametric proportional hazards model, where...

The purpose of this study is to evaluate the use of antiemetics in a hospital setting. The principal issues addressed in this study are first the usual antiemetic therapy prescribed for chemotherapy-induced nausea and vomiting, and then assessing the efficacy of various antiemetic using evaluations from patients and hospital staff (satisfaction sca...

The variability of the pharmacokinetics of zidovudine after its oral administration to 36 AIDS patients has been investigated by measuring the plasma and urine levels of zidovudine and its metabolite on Days 1 and 35 of continuous treatment. A two-phase absorption model was first defined from well-documented data in 12 subjects. The population char...

To the Editor: In a letter in the April 4, 1991, issue of the Journal,* we provided data on a relation between the mean plasma concentration of zidovudine and the occurrence of opportunistic infections. We have discovered a computational error in the program used in our analysis. The results should have been as follows. The estimated mean concentra...

Les records du monde (RM) illustrent l'ultime expression de la biologie musculaire humaine. Les prédictions des limites physiologiques de l'homme et l'impact des conditions extérieures (historiques ou environnementales) sur l'établissement d'un RM sont sujets à controverse. Après l'analyse de 3 263 RM établis dans toutes les disciplines officielles...