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International audience; OBJECTIVES: Comfort care for a dying patient increases the quality of the end of life. End-of-life situations are frequently managed in acute geriatric units (AGUs), and transition to comfort care only is often necessary. However, the frequency of transition to comfort care and the latter's putative link with the end-of-life trajectory (sudden death, cancer, organ failure, and frailty with or without dementia) have not previously been studied in acute geriatric units. We sought to (1) describe end-of-life trajectories and the transition to comfort care only, and (2) analyse the relationship between the two, prior to death in an AGU. DESIGN: A secondary analysis of a subgroup of the DAMAGE cohort (a prospective multicentre cohort of 3509 patients aged 75~years and over and admitted consecutively to an AGU). SETTING/PARTICIPANTS: DAMAGE patients who died in an AGU after a stay of at least 48~hours. METHODS: Data on the end-of-life trajectory and the transition to comfort care only were extracted from medical records. RESULTS: Of the 177 included patients, 123 (69.5%) transitioned to comfort care only in the AGU. A frailty trajectory (in patients living with dementia or not) accounted for nearly 70% of deaths. Paradoxically, only frailty among people living without dementia was not significantly associated with a more frequent transition to comfort care [odds ratio (95% confidence interval): 1.44 (0.44-4.76), relative to a patient dying suddenly]. CONCLUSIONS AND IMPLICATIONS: Transition to comfort care only is frequent in AGUs and is linked to the end-of-life trajectory (except for frail patients living without dementia). The frailty trajectory is one of the most frequent, and, therefore, physicians must be aware of the need to improve practice in this context.

BackgroundSince 2005, the international guidelines for out-of-hospital cardiac arrest (OHCA) use puberty to differentiate paediatric and adult care. This threshold is mainly relied on the more frequent respiratory aetiologies in children. Hitherto, to the best of our knowledge, no study has compared the characteristics and outcomes of non-pubescent children, adolescents and adult patients with OHCA. In this study, we intended to describe the characteristics, outcome and factors associated with survival of patients who experienced OHCA in the three groups: children, adolescents (pubescentMethodsData from the French national cardiac arrest registry (2012–2017) were used in this nationwide observational study. Victims of OHCA who were ResultsWe included 934 children, 433 adolescents and 26 952 adults. Respiratory aetiology was more frequent and shockable rhythm less frequent in children compared with adolescents (25.5% vs 17.2%, p=0.025 and 2.4% vs 6.8%, pConclusionFrequency of respiratory aetiologies and shockable rhythm were common in adolescents and adults and different between children and adolescents. These results indicate that puberty as a threshold in international guidelines seems to be relevant.

International audience; Objective: The aim of this study was to build a predictive model of operative difficulty in open liver resections (LRs). Summary Background Data: Recent attempts at classifying open-LR have been focused on postoperative outcomes and were based on predefined anatomical schemes without taking into account other anatomical/technical factors. Methods: Four intraoperative variables were perceived by the authors as to reflect operative difficulty: operation and transection times, blood loss, and number of Pringle maneuvers. A hierarchical ascendant classification (HAC) was used to identify homogeneous groups of operative difficulty, based on these variables. Predefined technical/anatomical factors were then selected to build a multivariable logistic regression model (DIFF-scOR), to predict the probability of pertaining to the highest difficulty group. Its discrimination/calibration was assessed. Missing data were handled using multiple imputation. Results: HAC identified 2 clusters of operative difficulty. In the ``Difficult LR'' group (20.8% of the procedures), operation time (401 min vs 243 min), transection time (150 vs.63 minute), blood loss (900 vs 400 mL), and number of Pringle maneuvers (3 vs 1) were higher than in the ``Standard LR'' group. Determinants of operative difficulty were body weight, number and size of nodules, biliary drainage, anatomical or combined LR, transection planes between segments 2 and 4, 4, and 8 or 7 and 8, nonanatomical resections in segments 2, 7, or 8, caval resection, bilioentric anastomosis and number of specimens. The c-statistic of the DIFF-scOR was 0.822. By contrast, the discrimination of the DIFF-scOR to predict 90-day mortality and severe morbidity was poor (c-statistic: 0.616 and 0.634, respectively). Conclusion: The DIFF-scOR accurately predicts open-LR difficulty and may be used for various purposes in clinical practice and research.

BACKGROUND The institutionalization of a patient with Alzheimer's disease or other dementia (ADOD) is the last resort for the latter's family and/or caregivers. We hypothesized that the degree of kinship between the patient and his/her caregiver would influence the likelihood of institutionalization. OBJECTIVE To assess the association between institutionalization of patients with ADOD and the degree of kinship with the family caregiver. METHODS A cross-sectional study of patients with ADOD aged 75 or over attending a memory center in France for the first time between 2011 and 2014, as recorded in the French National Alzheimer Database. Multivariable logistic regression was used to assess factors associated with institutionalization after adjustment for age, sex, the Mini-Mental State Examination score, educational level, and type of dementia. RESULTS A total of 52,874 patients were included. The primary caregiver was most often a child (54.8%) or the spouse (36.7%). Compared with the "spouse" reference category, all the other caregiver categories were associated with a significantly greater likelihood of institutionalization; the odds ratio [95% confidence interval] was 4.68 [3.67-5.92] when the carer was a grandchild, 5.48 [4.93-6.09] for a child, 4.93 [4.11-5.91] for a daughter-/son-in-law, 8.76 [7.15-10.70] for a sibling, and 8.93 [7.48-10.65] for a niece/nephew. CONCLUSION The likelihood of institutionalization of older patients with ADOD varied with the degree of kinship. Compared with the "spouse" reference category, the likelihood was higher for all other types of caregivers but was especially high when the caregiver was not a direct descendant of the patient.

International audience; Book music is extensively used in street organs. It consists of thick cardboard, containing perforated holes specifying the musical notes. We propose to represent clinical time-dependent data in a tabular form inspired from this principle. The sheet represents a statistical individual, each row represents a binary time-dependent variable, and each hole denotes the "true" value. Data from electronic health records or nationwide medical-administrative databases can then be represented: demographics, patient flow, drugs, laboratory results, diagnoses, and procedures. This data representation is suitable for survival analysis (e.g., Cox model with repeated outcomes and changing covariates) and different types of temporal association rules. Quantitative continuous variables can be discretized, as in clinical studies. The "book music" approach could become an intermediary step in feature extraction from structured data. It would enable to better account for time in analyses, notably for historical cohort analyses based on healthcare data reuse.

ACL; OBJECTIVE:The aim of the study was to compare outcomes after out-of-hospital cardiac arrest (OHCA) between comparable female and male OHCA cohorts in a large nationwide registry. METHODS:This was a national multicentre retrospective, case-control propensity score-matched study based on French National Cardiac Arrest Registry data from 1 July 2011 to 21 September 2017. Female and male survival rates at D30 were compared. RESULTS:At baseline 66 395 OHCA victims were included, of which 34.3% were women. At hospital admission, survival was 18.2% for female patients and 20.2% for male patients [odds ratio (OR), 1.138 (1.092-1.185)]; at 30 days, survival was 4.3 and 5.9%, respectively [OR, 1.290 (1.191-1.500)]. After matching (14 051 patients within each group), female patients received less advanced life support by mobile medical team (MMT), they also had a longer no-flow duration and shorter resuscitation effort by MMT than male patients. However, 15.3% of female patients vs. 9.1% of male patients were alive at hospital admission [OR, 0.557 (0.517-0.599)] and 3.2 vs. 2.6% at D30 [OR, 0.801 (0.697-0.921)], with no statistically significant difference in neurological outcome [OR, 0.966 (0.664-1.407)]. CONCLUSIONS:In this large nationwide matched OHCA study, female patients had a better chance of survival with no significant difference in neurological outcome. We also noticed that female patients received delayed care with a shorter resuscitation effort compared to men; these complex issues warrant further specific investigation. Encouraging bystanders to act as quickly as possible and medical teams to care for female patients in the same way as male patients should increase survival rates.

Background consideration of the first hospital re-admission only and failure to take account of previous hospital stays, which are the two significant limitations when studying risk factors for hospital re-admission. The objective of the study was to use appropriate statistical models to analyse the impact of previous hospital stays on the risk of hospital re-admission among older patients. Methods an exhaustive analysis of hospital discharge and health insurance data for a cohort of patients participating in the PAERPA (‘Care Pathways for Elderly People at Risk of Loss of Personal Independence’) project in the Hauts de France region of France. All patients aged 75 or over were included. All data on hospital re-admissions via the emergency department were extracted. The risk of unplanned hospital re-admission was estimated by applying a semiparametric frailty model, the risk of death by applying a time-dependent semiparametric Cox regression model. Results a total of 24,500 patients (median [interquartile range] age: 81 [77–85]) were included between 1 January 2015 and 31 December 2017. In a multivariate analysis, the relative risk (95% confidence interval [CI]) of hospital re-admission rose progressively from 1.8 (1.7–1.9) after one previous hospital stay to 3.0 (2.6–3.5) after five previous hospital stays. The relative risk [95%CI] of death rose slowly from 1.1 (1.07–1.11) after one previous hospital stay to 1.3 (1.1–1.5) after five previous hospital stays. Conclusion analyses of the risk of hospital re-admission in older adults must take account of the number of previous hospital stays. The risk of death should also be analysed.

RATIONALE, AIMS, AND OBJECTIVES The human body is regulated by intrinsic factors which follow a 24-hour biological clock. Implications of a circadian rhythm in the out-of-hospital cardiac arrest (OHCA) are studied but the literature is not consistent. The main objective of our study was to identify temporal cluster of high or low incidence of OHCA occurrence during a day. METHODS Multicentre comparative study based on the French national OHCA registry data between 2013 and 2017. After describing the population, the detection of significant temporal clusters of OHCA incidence was achieved using temporal scan statistics based on a Poisson model adjusted for age and gender. Then, comparisons between identified patients clusters and the rest of the population were performed. RESULTS During the study, 37 163 medical OHCA victims were included. The temporal scan revealed a significant 3-hour high incidence temporal cluster between 8:00 am and 10:59 am (Relative R = 1.76, P

This paper introduces new scan statistics for multivariate functional data indexed in space. The new methods are derivated from a MANOVA test statistic for functional data, an adaptation of the Hotelling T2-test statistic, and a multivariate extension of the Wilcoxon rank-sum test statistic. In a simulation study, the latter two methods present very good performances and the adaptation of the functional MANOVA also shows good performances for a normal distribution. Our methods detect more accurate spatial clusters than an existing nonparametric functional scan statistic. Lastly we applied the methods on multivariate functional data to search for spatial clusters of abnormal daily concentrations of air pollutants in the north of France in May and June 2020., Comment: arXiv admin note: text overlap with arXiv:2011.03482

Spatial scan statistics are well-known methods for cluster detection and are widely used in epidemiology and medical studies for detecting and evaluating the statistical significance of disease hotspots. For the sake of simplicity, the classical spatial scan statistic assumes that the observations of the outcome variable in different locations are independent, while in practice the data may exhibit a spatial correlation. In this article, we use spatial autoregressive (SAR) models to account the spatial correlation in parametric/non-parametric scan statistic. Firstly, the correlation parameter is estimated in the SAR model to transform the outcome into a new independent outcome over all locations. Secondly, we propose an adapted spatial scan statistic based on this independent outcome for cluster detection. A simulation study highlights the better performance of the proposed methods than the classical one in presence of spatial correlation in the data. The latter shows a sharp increase in Type I error and false-positive rate but also decreases the true-positive rate when spatial correlation increases. Besides, our methods retain the Type I error and have stable true and false positive rates with respect to the spatial correlation. The proposed methods are illustrated using a spatial economic dataset of the median income in Paris city. In this application, we show that taking spatial correlation into account leads to the identification of more concentrated clusters than those identified by the classical spatial scan statistic.

Background Non-Hodgkin's lymphomas (NHL) are the seventh most commonly diagnosed cancer in France. Nord-Pas-de-Calais is ranked as the region with the highest incidence of cancers and deaths by cancer in France. With its rich industrial past and its contrasted population densities between urban and rural territories, Nord-Pas-de-Calais represents a geographic area of interest to study the overall incidence of NHL and examine spatial variation of NHL incidence between the 170 cantons of the region. Methods LYMPHONOR was a population-based multicentre retrospective study of patients residing in the Nord-Pas-de-Calais region and diagnosed with NHL between January 2001 and December 2005. Spatial distribution of NHL incidence in Nord-Pas-de-Calais was explored using two complementary approaches: adjusted smoothed standardised incidence ratio (SIR) and spatial scan statistics (detection of atypical clusters). Results Between 2001 and 2005, 2132 new cases of NHL were diagnosed in the Nord-Pas-de-Calais region. In 2005, age-standardised NHL incidence rates were 10.2 and 7.0 cases per 100,000 person-years in male and female residents, respectively. No significant spatial disparities in NHL incidence were found within the Nord-Pas-de-Calais region. The age-adjusted smoothed SIR varied from 0.82 to 1.25 between cantons. Consistently, spatial scan statistics did not detect any significant atypical cluster of high NHL incidence. Conclusion Comparison with national data collected during the same period does not show an overincidence of NHL in the Nord-Pas-de-Calais region. In addition, no evidence for spatial heterogeneity and clustering of NHL incidence was found within this region. Future epidemiological research using large-scale registries is needed to better appraise spatial variation of NHL incidence in France and to investigate possible reasons for significant clusters.

Background Somatic mutations in the KRAS gene are the most common oncogenic mutations found in human cancers. However, no clinical features have been linked to KRAS mutations in colorectal cancer [CRC]. Purpose In this study, we attempted to identify the potential geographical population clusters of KRAS mutations in CRC patients in northern France. Patients and methods All patients with CRC who were identified to have KRAS mutations between 2008 and 2014 at the Regional Molecular Biology Platform at Lille University Hospital were included. 2,486 patients underwent a KRAS status available, with 40.9% of CRC with KRAS mutations in northern France. We retrospectively collected demographic and geographic data from these patients. The proportions of KRAS mutation were smoothed to take into account the variability related to low frequencies and spatial autocorrelation. Geographical clusters were searched using spatial scan statistical models. Results A mutation at KRAS codon 12 or 13 was found in 1,018 patients [40.9%]. We report 5 clusters of over-incidence but only one elongated cluster that was statistically significant [Cluster 1; proportion of KRAS mutation among CRC: 0.4570; RR=1.29; P=0.0314]. We made an ecological study which did not highlight a significant association between KRAS mutations and the distance to the Closest Waste Incineration Plant, and between KRAS mutations and The French Ecological Deprivation Index but few socio-economic and environmental data were available. Conclusion There was a spatial heterogeneity and a greater frequency of KRAS mutations in some areas close to major highways and big cities in northern France. These data demand deeper epidemiological investigations to identify environmental factors such as air pollution as key factors in the occurrence of KRAS mutations.

Objective Cardiac arrest (CA) is considered a major public health issue. Few studies have focused on geographic variations in incidence and socioeconomic characteristics. The aim of this study is to identify clusters of municipalities with high or low CA incidence, and find socioeconomic factors associated with them. Patients and methods CA data from three Parisian counties, representing 123 municipalities, were extracted from the French CA registry. Socioeconomic data for each municipality were collected from the French national institute of statistics. We used a statistical approach combining Bayesian methods to study geographical CA incidence variations, and scan statistics, to identify CA incidence clusters of municipalities. Finally, we compared clusters of municipalities in terms of socioeconomic factors. Results Strong geographical variations were found among 123 municipalities: 34 presented a significantly increased risk of incidence and 37 presented a significantly low risk. Scan statistics identified seven significant spatial clusters of CA incidence, including three clusters with low incidence (the relative risk varied from 0.23 to 0.54) and four clusters with high incidence (the relative risk varied from 1.43 to 2). Clusters of municipalities with a high CA incidence are characterized by a lower socioeconomic status than the others (low and normal CA incidence clusters). Analysis showed a statistically significant relationship between social deprivation factors and high incidence. Conclusion This study shows strong geographical variations in CA incidence and a statistically significant relationship between over-incidence and social deprivation variables.

Background The fetal heart rate (FHR) serves as a guide to fetal well-being during the first stage of delivery. The visual morphological analysis of the FHR during labor is subject to inter- and intra-observer variability – particularly when the FHR is abnormal. It has been suggested that automatic analysis of the FHR can reduce this variability. Objectives To compare 11 morphological FHR analyses (baseline computation, and detection of FHR decelerations and accelerations) produced by automatic analysis methods (AAMs) with an expert consensus. Materials and methods Eleven AAMs were reprogrammed (using the description published in the literature) and applied to 90 FHR recordings collected during the early phase of labor. Furthermore, the recordings were divided into three tertiles, according to the difficulty of analysis. The results of the morphological FHR analyses produced by the AAMs were compared with a consensus morphological analysis performed by four experts. In addition to standard discriminant criteria, a new morphological analysis discriminant index (MADI) was introduced; it provides an overall evaluation that collates all the individual criteria. Results The AAM developed by Lu and Wei's gave better results than the other AAMs for baseline computation. Regarding this method's detection of FHR decelerations and accelerations, the F-measure [95% confidence interval] was respectively 0.73 [0.67; 0.76] and 0.70 [0.64; 0.76]. The MADI indicated that Lu and Wei's AAM agreed best with the expert consensus (discordance: 7.3% [6.10; 8.60]). Conclusion Our study demonstrated the superiority of Lu and Wei's method for baseline computation and deceleration/acceleration detection, although there was still a significant degree of discordance versus expert consensus. The MADI appears to be a good overall index for evaluating AAMs with regard to the quality of baseline computation and acceleration/deceleration detection. The application of precise criteria and the methodology and software tools developed here should facilitate the evaluation of new AAMs and their comparison with other methods.

ACL; La mobilisation de toutes les politiques publiques est indispensable pour agir sur les inégalités environnementales et sociales de santé (IESS). Le paradigme actuel décrit ces inégalités territoriales comme une accumulation de déterminants de santé défavorables dans une zone géographique donnée, généralement entendue comme la vulnérabilité d’un territoire. L’absence quasi-systématique des déterminants ayant un impact positif sur la santé dans les modèles ne permet pas d’obtenir une vision réaliste de l’impact global de l’environnement sur la santé des populations. L’intégration de la résilience, comme la capacité des territoires à gérer les IESS, devient alors indispensable pour inclure les efforts déployés pour améliorer le cadre de vie des habitants. Validée dans la région des Hauts-de-France, l’analyse conjointe d’un indice composite spatialisé de vulnérabilité et d’un indice composite spatialisé de résilience permet de décrire la balance résilience/vulnérabilité à l’échelle des communes. Cette démarche permettra in fine de mieux caractériser les IESS, d’affiner les connaissances sur les dynamiques territoriales en jeu et d’orienter de nouvelles réflexions en termes de gestion politique et territoriale des risques sanitaires.

We have developed two scan statistics for detecting clusters of functional data indexed in space. The first method is based on an adaptation of a functional analysis of variance and the second one is based on a distribution-free spatial scan statistic for univariate data. In a simulation study, the distribution-free method always performed better than a nonparametric functional scan statistic, and the adaptation of the anova also performed better for data with a normal or a quasi-normal distribution. Our methods can detect smaller spatial clusters than the nonparametric method. Lastly, we used our scan statistics for functional data to search for spatial clusters of abnormal unemployment rates in France over the period 1998-2013 (divided into quarters)., Comment: 15 pages, 5 figures

BACKGROUND: Geographical variations in Crohn's disease (CD) suggest that the environment has a role in the pathogenesis of this condition. OBJECTIVE: To describe the spatial distribution and the clustering of CD cases in France, and to assess the relationship between the prevalence of CD and environmental risk factors. METHODS: We identified all patients with CD included in the French hospital discharge database from 2007 to 2014. Age- and gender-smoothed standardised prevalence ratios over this period were computed for 5610 spatial units. An ecological regression analysis was used to assess the relationship between the risk of CD and ecological variables (health care, latitude, socio-economic deprivation, urbanisation, proportion of agricultural surfaces and density of industries). Local spatial clusters of high-CD prevalence were searched for using elliptic spatial scan statistics and characterised in a hierarchical ascendant classification based on the same ecological variables. RESULTS: About 129 089 patients with CD were identified, yielding a crude prevalence of 203 per 100 000 inhabitants. The overall spatial heterogeneity was statistically significant (P

The wide range of factors involved in environmental health and the complexity of interactions between all environmental determinants require the validation of multidimensional approaches. While the development of composite indices is receiving growing attention by scientists and public authorities, the concept continues to lack transposability and robustness partly due to varying conceptualizations and/or methodologies. This review aims to promote harmonizing practices governing the first step of development of composite index, namely identification and characterization of the dimensions and variables that are included in environmental health indices. A review of available literature (more than 1500 studies) was conducted to identify the composite indices developed to assess territorial determinants from an environmental health perspective. This process made it possible to identify 23 spatialized composite indices and to assess a total of 329 variables. This diversity highlights that the absence of a common framework can lead to a strong subjectivity and limit comparisons between different environmental health indices. The specificity and the availability of certain variables would limit the transposability of indices. In light of current knowledge, this review proposes a consolidated methodological framework based on a categorization of variables into dimensions and sub-dimensions related to heath, environment, social, economics, services and policy. To characterize the sub-dimensions, several variables are possible and can be chosen according to the availability and/or accessibility of the data. The adaptation of a composite index to a specific territory or to a specific issue would then be effective through the included variables. This also aims to be transposable to any spatial unit (country, region, census tract). This work is a first step towards a proposal of guidelines designed to provide a consensual framework that could facilitate the exploitation of environmental health indices. This transparency could also increase the understanding and adoption of these tools by public authorities and general public.

Geographical variations in cardiovascular disease rates have been linked to individual air pollutants. Investigating the relation between cardiovascular disease and exposure to a complex mixture of air pollutants requires holistic approaches. We assessed the relationship between exposure to multiple air pollutants and the incidence of coronary heart disease (CHD) in a general population sample. We collected data in the Lille MONICA registry (2008–2011) on 3268 incident cases (age range: 35–74). Based on 20 indicators, we derived a composite environmental score (SEnv) for cumulative exposure to air pollution. Poisson regression models were used to analyse associations between CHD rates on one hand and SEnv and each single indicator on the other (considered in tertiles, where T3 is the most contaminated). We adjusted models for age, sex, area-level social deprivation, and neighbourhood spatial structure. The incidence of CHD was a spatially heterogeneous (p=0.006). There was a significant positive association between SEnv and CHD incidence (trend p=0.0151). The relative risks [95%CI] of CHD were 1.08 [0.98–1.18] and 1.16 [1.04–1.29] for the 2nd and 3rd tertile of SEnv exposure. In the single pollutant analysis, PM10, NO2, cadmium, copper, nickel, and palladium were significantly associated with CHD rates. Multiple air pollution was associated with an increased risk of CHD. Single pollutants reflecting road traffic pollution were the most strongly associated with CHD. Our present results are consistent with the literature data on the impact of road traffic on the CHD risk in urban areas., Graphical abstract Unlabelled Image, Highlights • A small area level geographic analysis from a coronary heart disease (CHD) registry • Long-term exposure to heavy metals assessed by lichen biomonitoring • Proposed a composite air pollution index (SENV) for multiple exposure • Found associations between SENV and CHD incidence • Exposure to multiple low-dose air pollutants may increase cardiovascular risks

Résumé : Nous avons étudié l'association entre l'incidence des fractures de la hanche et les caractéristiques du lieu de vie en France. La répartition spatiale de l'incidence des fractures de la hanche était hétérogène et il existait une relation significative entre la privation sociale, l'urbanisation, l'accès à la santé et le risque de fracture de la hanche. Objectif : Plusieurs études ont montré de grandes disparités dans la répartition spatiale des fractures de hanche (FH). L'objectif de l'étude était d'analyser l'association entre l'incidence des FH et les caractéristiques du lieu de vie. Méthodes : Tous les patients âgés de 50 ans ou plus, résidant en France, qui ont été hospitalisés pour une HF entre 2012 et 2014 ont été inclus, en utilisant la base de données nationale française des sorties d'hôpital. Les ratios d'incidence standardisés (SIR) ont été calculés pour chaque unité spatiale et ajustés sur l'âge et le sexe. Une régression écologique a été réalisée pour analyser l'association entre l'incidence standardisée de l'HF et les variables écologiques. Nous avons ajusté le modèle pour la structure spatiale du quartier. Nous avons utilisé trois variables pour caractériser les zones de vie : un indice de privation (French-EDI) ; l'accès aux soins (indice standardisé français) ; l'utilisation du sol (pourcentage de surfaces artificialisées). Résultats : 236 328 HF ont été enregistrées dans la base de données nationale des hôpitaux français, conduisant à une incidence annuelle d'HF de 333/100 000. L'analyse spatiale a révélé des variations géographiques de l'incidence de l'HF avec un SIR variant de 0,67 [0,52 ; 0,85] à 1,45 [1,23 ; 1,70]. Il y avait une association significative entre les taux d'incidence de l'HF et : (1) l'indice French-EDI (tendance p=0,0023) ; (2) l'accessibilité des médecins généralistes et des infirmières (tendance p=0,0232 et p=0,0129, respectivement) ; (3) le pourcentage de surfaces artificialisées (p

This paper introduces a nonparametric scan method for multivariate data indexed in space. Contrary to many other scan methods, it does not rely on a generalized likelihood ratio but is completely distribution-free as it is based on so-called multivariate ranks. This spatial scan test seems to be more reliable for analysing data that are not Gaussian, such as environmental measurements. We apply this method to a dataset recording the levels of metallic pollutants for two areas in the North of France.

International audience; Aim: Cardiac arrest (CA) was considered irreversible until 1960, when basic cardiopulmonary resuscitation (CPR) was defined. CPR guidelines include early recognition of CA, rapid and effective CPR, effective defibrillation strategies and organized post-resuscitation to ensure a strengthening of the survival chain. Bystanders are the key to extremely early management, which is associated with the early medical care provided by EMS. This study aims to assess the prognosis of a bystander's cardiac CPR when it is initiated by the Dispatch Centre (DC).Methods: We included patients in 3 groups according to who initiated the CPR. The groups were matched according to multiple propensity partition methods. We presented our results in terms of 30-day survival and neurological prognosis.Results: 85,634 patients were included. Statistical study focused on 18,185 patients once the exclusion criteria were applied. 12,743 (70.1%) are men and the average age is 70.1 years. Survival at D30 was 5.11% in the absence of CPR, 8.86% with bystander initiation and 7.35% with DC initiation (p < 0.001). Survival at D30 with favourable neurologic prognosis (CPC 1-2) was 76.30%, 83.69% and 82.82%, respectively. Our results show a 3.75% increase in the chance of survival at D30 if CPR was initiated by bystanders compared to patients for whom CPR was not initiated, a 2.25% increase in survival in the group that received from CPR initiated by the DC compared to the group that did not receive CPR.Conclusions: Bystander CPR initiated by the DC represents a suitable option following out-of-hospital cardiac arrest.

In environmental health, vulnerability reflecting the cumulative harmful constraints and nuisances to which populations are subjected and resilience defined as the capacity of a territory to cope with health inequalities have been little extensively investigated together with the same importance. Besides the diversity of factors involved, there is no consensual framework to develop composite indices, one recognized methodology to deal with a multifaceted issue. Therefore, this research aims to establish a new transferable approach to assess the spatial heterogeneity of territorial inequalities. This new strategy relies on the simultaneous evaluation of resilience and vulnerability and the joint analysis based on the cross-interpretation of the spatialized composite indices of resilience and vulnerability. A case study was conducted to demonstrate the feasibility of this methodology, using the municipality as a spatial unit of analysis within a region in the north of France. To provide the most holistic description possible of the 3817 studied municipalities, 50 variables related to the economic, environment, policy, health, services and social dimensions were used to develop the composite indices. The vulnerability Index has a median value of 0.151 with an IQR of [0.126–0.180] and the Resilience Index has a median value of 0.341 with an IQR of [0.273–0.401]. The joint analysis was conducted to classify each municipality among four defined typologies: 1687 municipalities (44.2%) belong to the “To monitor” category, 1646 (43.1%) to the “Resilient” category, 329 (8.6%) to the “Have resources” category and 155 (4.1%) to the “Territorial blackspot” category. The methodology herein may be a diagnostic tool to identify and prioritize municipalities that could benefit from the implementation of specifically tailored public health policies.

International audience; ScopeNɛ-Carboxymethyl-lysine (CML) is a prominent advanced glycation end-product which is not only found in vivo but also in food. It is known that a percentage of the dietary CML (dCML) is absorbed into the circulation and only partly excreted in the urine. Several studies have tried to measure how much dCML remains in tissues. However obstacles to interpreting the data have been found.Methods and resultsA new protocol which discriminates dCML from native CML (nCML) has been developed. Three CML isotopes with different mass-to-charge ratios were used: nCML Nε-carboxymethyl-L-lysine, dCML Nε-[13C]carboxy[13C]methyl-L-lysine and internal standard Nε-carboxymethyl-L-[4,4,5,5-2H4]lysine. Wild-type (n = 7) and RAGE−/− (n = 8) mice were fed for 30 days with either a control, or a BSA-bound dCML-enriched diet. Organs were analyzed for nCML and dCML using liquid chromatography–tandem mass spectrometry. Mice exposed to dCML showed an accumulation in all tissues tested except fat. The rate of deposition was high (81–320 μgdCML/g dry matter) in kidneys, intestine, and lungs and low (

The farnesoid X receptor (FXR) is a member of the "metabolic" subfamily of nuclear receptors. Several FXR agonists have been reported in the literature to have profound effects on plasma lipids in animal models. To discover novel and effective therapies for dyslipidemia and atherosclerosis, we have developed a series of potent FXR agonists that robustly lower plasma LDL and vLDL in LDLr-/- mice. To this end the novel piperidinylisoxazole system LY2562175 was discovered. This molecule is a potent and selective FXR agonist in vitro and has robust lipid modulating properties, lowering LDL and triglycerides while raising HDL in preclinical species. The preclinical ADME properties of LY2562175 were consistent with enabling once daily dosing in humans, and it was ultimately advanced to the clinic for evaluation in humans. The synthesis and biological profile of this molecule is discussed.

Objective To identify clinical parameters and intrapartum fetal heart rate parameters associated with a risk of umbilical cord acidosis at birth, using an automated analysis method based on empirical mode decomposition. Methods Our single-center study included 381 cases (arterial cord blood pH at birth pHa ≤7.15) and 1860 controls (pHa ≥7.25) extracted from a database comprising 8,383 full datasets for over-18 mothers after vaginal or caesarean non-twin, non-breech deliveries at term (>37 weeks of amenorrhea). The analysis of a 120-min period of the FHR recording (before maternal pushing or the decision to perform a caesarean section during labor) led to the extraction of morphological, frequency-related, and long- and short-term heart rate variability variables. After univariate analyses, sparse partial least square selection and logistic regression were applied. Results Several clinical factors were predictive of fetal acidosis in a multivariate analysis: nulliparity (odds ratio (OR) 95% confidence interval (CI)]: 1.769 [1.362–2.300]), a male fetus (1.408 [1.097–1.811]), and the term of the pregnancy (1.333 [1.189–1.497]). The risk of acidosis increased with the time interval between the end of the FHR recording and the delivery (OR [95%CI] for a 1-min increment: 1.022 [1.012–1.031]). The risk factors related to the FHR signal were mainly the difference between the mean baseline and the mean FHR (OR [95%CI]: 1.292 [1.174–1.424]), the baseline range (1.027 [1.014–1.040]), fetal bradycardia (1.038 [1.003–1.075]) and the late deceleration area (1.002 [1.000–1.005]). The area under the curve for the multivariate model was 0.79 [0.76; 0.81]. Conclusion In addition to clinical predictors, the automated FHR analysis highlighted other significant predictors, such as the baseline range, the instability of the FHR signal and the late deceleration area. This study further extends the routine application of automated FHR analysis during labor and, ultimately, contributes to the development of predictive scores for fetal acidosis.

Introduction The survival from traumatic vs. medical out-of-hospital cardiac arrest (OHCA) are not yet well described. The objective of this study was to compare survival to hospital discharge and 30-day survival of non-matched and matched traumatic and medical OHCA cohorts. Material & methods National case-control, multicentre study based on the French national cardiac arrest registry. Following descriptive analysis, we compared survival rates of traumatic and medical cardiac arrest patients after propensity score matching. Results Compared with medical OHCA (n = 40,878) trauma victims (n = 3209) were younger, more likely to be male and away from home at the time and less likely to be resuscitated. At hospital admission and at 30 days their survival odds were lower (OR: respectively 0.456 [0.353;0.558] and 0.240 [0.186;0.329]). After adjustment the survival odds for traumatic OHCA were 2.4 times lower at admission (OR: 0.416 [0.359;0.482]) and 6 times lower at day 30 (OR: 0.168 [0.117;0.241]). Conclusions The survival rates for traumatic OHCA were lower than for medical OHCA, with wider difference in matched vs. non-matched cohorts. Although the probability of survival is lower for trauma victims, the efforts are not futile and pre-hospital resuscitation efforts seem worthwhile.

Activation of free fatty acid receptor 1 (GPR40) by synthetic partial and full agonists occur via distinct allosteric sites. A crystal structure of GPR40-TAK-875 complex revealed the allosteric site for the partial agonist. Here we report the 2.76-Å crystal structure of human GPR40 in complex with a synthetic full agonist, compound 1, bound to the second allosteric site. Unlike TAK-875, which acts as a Gαq-coupled partial agonist, compound 1 is a dual Gαq and Gαs-coupled full agonist. compound 1 binds in the lipid-rich region of the receptor near intracellular loop 2 (ICL2), in which the stabilization of ICL2 by the ligand is likely the primary mechanism for the enhanced G protein activities. The endogenous free fatty acid (FFA), γ-linolenic acid, can be computationally modeled in this site. Both γ-linolenic acid and compound 1 exhibit positive cooperativity with TAK-875, suggesting that this site could also serve as a FFA binding site., GPR40 is a G-protein coupled receptor that binds to free fatty acids, mediating insulin and incretin secretion. Here, the authors present the crystal structure of human GPR40 with an agonist bound to an allosteric site located near the lipid-rich region that suggests a mechanism for biased agonism.

International audience; This paper presents a web viewer of Fetal Heart Rate (FHR) signals developed on HTML5/JavaScript. It provides an easy solution to remotely consult an FHR signal on a web browser without installing any specific software and it can be used either on a computer or on mobile device. There are three major applications of this tool. First, it is used to build up our FHR database used for research on signal processing and analysis. Secondly, it is used on our E-learning website e.RCF in order to train midwives and obstetricians to interpret FHR signals. At last, it could be used on telemedicine either on tele-monitoring to remotely check the fetal welfare, or on tele-expertise to enable practitioners to ask for specialists’ opinion. This viewer is designed to correspond to practitioners’ habits while including tools to ease the interpretation the FHR signal.

International audience; The fetal heart rate (FHR) is a marker of fetal well-being in utero (when monitoring maternal and/or fetal pathologies) and during labor. Here, we developed a smart mobile data module for the remote acquisition and transmission (via a Wi-Fi or 4G connection) of FHR recordings, together with a web-based viewer for displaying the FHR datasets on a computer, smartphone or tablet. In order to define the features required by users, we modelled the fetal monitoring procedure (in home and hospital settings) via semi-structured interviews with midwives and obstetricians. Using this information, we developed a mobile data transfer module based on a Raspberry Pi. When connected to a standalone fetal monitor, the module acquires the FHR signal and sends it (via a Wi-Fi or a 3G/4G mobile internet connection) to a secure server within our hospital information system. The archived, digitized signal data are linked to the patient’s electronic medical records. An HTML5/JavaScript web viewer converts the digitized FHR data into easily readable and interpretable graphs for viewing on a computer (running Windows, Linux or MacOS) or a mobile device (running Android, iOS or Windows Phone OS). The data can be viewed in real time or offline. The application includes tools required for correct interpretation of the data (signal loss calculation, scale adjustment, and precise measurements of the signal’s characteristics). We performed a proof-of-concept case study of the transmission, reception and visualization of FHR data for a pregnant woman at 30 weeks of amenorrhea. She was hospitalized in the pregnancy assessment unit and FHR data were acquired three times a day with a Philips Avalon® FM30 fetal monitor. The prototype (Raspberry Pi) was connected to the fetal monitor’s RS232 port. The emission and reception of prerecorded signals were tested and the web server correctly received the signals, and the FHR recording was visualized in real time on a computer, a tablet and smartphones (running Android and iOS) via the web viewer. This process did not perturb the hospital’s computer network. There was no data delay or loss during a 60-min test. The web viewer was tested successfully in the various usage situations. The system was as user-friendly as expected, and enabled rapid, secure archiving. We have developed a system for the acquisition, transmission, recording and visualization of RCF data. Healthcare professionals can view the FHR data remotely on their computer, tablet or smartphone. Integration of FHR data into a hospital information system enables optimal, secure, long-term data archiving.

Out-of-hospital cardiac arrest (OHCA) is considered an important public health issue but its incidence has not been examined in France. The aim of this study is to define the incidence of OHCA in France and to compare this to other neighbouring countries. Data were extracted from the French OHCA registry. Only exhaustive centres during the period from January 1, 2013, to September 30, 2014 were included. All patients were included, regardless of their age and cause of OHCA. The participating centres covered about 10% of the French population. The study involved 6918 OHCA. The median age was 68 years, with 63% of males. Paediatric population (< 15 years) represented 1.8%. The global incidence of OHCA was 61.5 per 100,000 inhabitants per year in the total population corresponding to approximately 46,000 OHCA per year. In the adult population, we found an incidence of 75.3 cases per 100,000 inhabitants per year. In adults, the incidences were 100.3 and 52.7 in males and females, respectively. Most (75%) OHCA occurred at home and were due to medical causes (88%). Half of medical OHCA had cardiovascular causes. Survival rates at 30 days was 4.9% [4.4; 5.4] and increased to 10.4% [9.1; 11.7] when resuscitation was immediately performed by bystander at patient's collapse. The incidence and survival at 30 days of OHCA in France appeared similar to that reported in other European countries. Compared to other causes of deaths in France, OHCA is one of the most frequent causes, regardless of the initial pathology.

Primary alveolar cleft repair has two main purposes: to restore normal morphology and normal function. Gingivoperiosteoplasty with bone grafting in mixed dentition has been a well-established procedure. We hypothesized that 1) performance of this surgery in deciduous dentition would provide favorable bone graft osseointegration, and 2) would improve the support of incisor teeth eruption, thereby avoiding maxillary growth disturbances. We conducted a retrospective study of clinical and tridimensional radiological data for 73 patients with alveolar clefts (with or without lip and palate clefts) who underwent gingivoperiosteoplasty with iliac bone graft in deciduous dentition. Pre- and post-operative Cone Beam Computed Tomography (CBCT) comparison allowed evaluation of the ratio between bone graft volume and initial cleft volume (BGV/ICV ratio), and measurement of central incisor teeth movements. This series of 73 patients included 44 males and 29 females, with a mean age of 5.5 years. Few complications were observed. Post-operative CBCT was performed at 7.4 months. The mean BGV/ICV ratio was 0.62. Axial rotation was significantly improved post-operatively (p = 0.004). Gingivoperiosteoplasty with iliac bone graft is safe when performed in deciduous dentition and results in a sufficient bone graft volume to support lateral incisor eruption and upper central incisor tooth position improvement.

A new spatial scan statistic is proposed for multivariate data indexed in space. Such as many other scan methods, it relies on a generalized likelihood ratio but it also takes into account the correlations between variables. This spatial scan test seems to be more powerful than the independent version, whatever the level of correlation between variables. We apply this method to a data set recording the levels of pollutant metals in the area of Lille, France.

Introduction De fortes disparites d’incidence de l’IRCT ont recemment ete observees entre les departements de France metropolitaine avec une influence notable du diabete et de la precarite sociale des populations. La litterature recente suggere egalement une part attribuable a l’environnement. Une analyse spatiale a fine echelle de l’incidence d’IRCT a ete effectuee au sein d’une des regions les plus touchees, afin de rechercher des facteurs de risque. Patients/Materiels et methodes Une etude ecologique geographique a ete menee a partir de l’ensemble des cas incidents d’IRCT recenses dans cette region a partir du registre REIN entre 2005 et 2014. Des methodes de cartographie de ratios d’incidence standardises (SIR lisses) et de detection de clusters atypiques d’evenements (statistique de scan), ajustees sur l’âge, le sexe et la prevalence de diabete ont ete menees pour mettre en evidence des disparites d’incidence a l’echelle cantonale. Les clusters de sur-incidence (C + ) et de sous-incidence (C − ) detectes ont ete decrits et compares a l’aide (i) des donnees cliniques des patients (caracteristiques nephropatiques et comorbidites) afin d’evaluer l’influence de pratiques medicales ; (ii) de donnees ecologiques (demographie medicale, precarite des populations, occupation du sol et pollution atmospherique) afin d’evaluer l’influence de l’offre de soins et de facteurs de risques dans la genese de ces disparites spatiales. Observation/Resultats La cartographie des SIR lisses montre de fortes disparites infraregionales d’incidence d’IRCT, avec la presence de deux clusters de sur-incidence (Risque relatif de 1,24 pour C + 1 et 1,18 pour C + 2), et trois clusters de sous-incidence (Risque relatif de 0,74 pour C − 1 ; 0,78 pour C − 2 ; 0,83 pour C − 3). Les clusters de sous-incidence sont plutot retrouves au niveau des zones rurales, suggerant l’influence de deserts medicaux. Il n’existe pas de differences de pratiques de prise en charge entre les clusters. Les clusters de sur-incidence hebergent des populations plus defavorisees que les clusters de sous-incidence. Cela confirme la forte influence de la precarite socio–economique dans la maladie renale chronique. Il existe egalement des differences de niveau de pollution entre les clusters, avec des niveaux tres eleves sur C + 2, tres faibles sur C − 1 et moyens sur C − 2, C − 3 et C + 1. Discussion/Conclusion L’ajustement sur la prevalence de diabete permet de mettre en avant d’autres facteurs de risque et devrait etre mis en oeuvre en routine dans ce type d’analyse. Le poids de la precarite par rapport a celui de l’environnement ne semble pas identique quel que soit le cluster detecte. Une analyse multivariee est desormais necessaire.

e15101 Background: Somatic mutations in the KRAS gene are present in about 40% of tumors from colorectal cancer (CRC) patients and are associated with a resistance to anti-EGFR therapies. However, no clinical features have been linked to KRAS mutations in CRC. In this study, we attempted to identify the potential geographical population clusters of KRAS mutations in CRC patients in northern France. Methods: All patients with CRC who were identified to have KRAS mutations performed by pyrosequencing between 2008 and 2014 at the Regional Molecular Biology Platform at Lille University Hospital were included. We retrospectively collected demographic and geographic data from these patients. The proportions of KRAS mutation were smoothed to take into account the variability related to low frequencies and spatial autocorrelation. Geographical clusters were searched using spatial scan statistical models. Then, we made an ecological study. Results: 2,486 patients underwent a KRAS status available. A mutation of KRAS codon 12 or 13 performed by pyrosequencing was found in 1,018 patients (40.9%). We report 5 clusters of over-incidence but only one elongated cluster that was statistically significant ranging from the city of Tourcoing to the city of Marquion (Cluster 1; smoothed proportion of KRAS mutation: 0.4570; RR = 1.29; p = 0.0314). The ecological study did not highlight a significant association between KRAS mutations and the distance to the Closest Waste Incineration Plant , and between KRAS mutations and The French Ecological Deprivation Index. There was a greater frequency of KRAS mutations in some areas close to major highways and big cities in northern France. Conclusions: There is a spatial heterogeneity of KRAS codon 12 or 13 mutations in CRC in northern France. These data demand deeper epidemiological investigations to identify environmental factors such as air pollution as key factors in the occurrence of KRAS mutations.

Introduction La reutilisation de donnees structurees de sante est particulierement prometteuse en recherche. Elle fut d’abord decrite par Fayyad sous le terme de “knowledge discovery in databases”, puis le terme “data reuse” est apparu. L’extraction de caracteristiques en est une phase primordiale mais peu commentee dans la litterature. Les objectifs sont :. – de proposer une representation a jour du processus de reutilisation de donnees structurees de sante ; – d’illustrer les methodes et objectifs de l’extraction de caracteristiques et ; – de discuter la place des connaissances metier. Methodes 1) Un consensus entre auteurs permet de proposer un schema a jour ; 2) Un cas d’etude (projet europeen FP7) consistant a identifier automatiquement les episodes d’insuffisance renale aigue et decouvrir automatiquement les facteurs de risque par reutilisation de donnees est analyse et presente ; 3) Une revue de la litterature publiee par Meystre et al. en 2017 est analysee. Resultats 1) Nous proposons une schematisation du processus de reutilisation de donnees en cinq phases. Phase 1 : preparation des donnees (nettoyage, jointure, alignement terminologique, conversions d’unites, de-identification). Elle permet de construire un entrepot de donnees. Phase 2 : extraction de caracteristiques. Phase 3 : fouille de donnees statistique et graphique. Phase 4 : filtrage expert et reorganisation des resultats. Phase 5 : prise de decision. – Le cas d’etude illustre comment des caracteristiques temps-dependantes peuvent etre extraites de resultats de biologie medicale et d’administrations de medicaments, a l’aide de connaissances expertes specifiques au domaine. – Parmi les 200 articles cites par Meystre et al., le premier et le dernier auteur sont affilies a une institution de sante dans 74 % des articles (68 % pour les articles methodologiques, 79 % pour les appliques). Discussion/Conclusion L’extraction de caracteristiques a un impact majeur sur le succes d’une operation de reutilisation de donnees. Les raisonnements bases sur une expertise du domaine etudie y prennent une part importante, ce qui requiert une collaboration etroite entre informaticiens, statisticiens et professionnels de sante.

NA new protocol which discriminates dCML from native CML (nCML) has been developed. Three CML isotopes with different mass-to-charge ratios were used: nCML NThe kidney is not the only organ affected by the accumulation of dCML. Its high accumulation in other tissues and organs may also, however, have important physiological consequences.