Cluster Detection Tests in Spatial Epidemiology: A Global Indicator for Performance Assessment

International audienceIn cluster detection of disease, the use of local cluster detection tests (CDTs) is current. These methods aim both at locating likely clusters and testing for their statistical significance. New or improved CDTs are regularly proposed to epidemiologists and must be subjected to performance assessment. Because location accuracy has to be considered, performance assessment goes beyond the raw estimation of type I or II errors. As no consensus exists for performance evaluations, heterogeneous methods are used, and therefore studies are rarely comparable. A global indicator of performance, which assesses both spatial accuracy and usual power, would facilitate the exploration of CDTs behaviour and help between-studies comparisons. The Tanimoto coefficient (TC) is a well-known measure of similarity that can assess location accuracy but only for one detected cluster. In a simulation study, performance is measured for many tests. From the TC, we here propose two statistics, the averaged TC and the cumulated TC, as indicators able to provide a global overview of CDTs performance for both usual power and location accuracy. We evidence the properties of these two indicators and the superiority of the cumulated TC to assess performance. We tested these indicators to conduct a systematic spatial assessment displayed through performance maps

Performance map of a cluster detection test using extended power.

International audienceBACKGROUND: Conventional power studies possess limited ability to assess the performance of cluster detection tests. In particular, they cannot evaluate the accuracy of the cluster location, which is essential in such assessments. Furthermore, they usually estimate power for one or a few particular alternative hypotheses and thus cannot assess performance over an entire region. Takahashi and Tango developed the concept of extended power that indicates both the rate of null hypothesis rejection and the accuracy of the cluster location. We propose a systematic assessment method, using here extended power, to produce a map showing the performance of cluster detection tests over an entire region. METHODS: To explore the behavior of a cluster detection test on identical cluster types at any possible location, we successively applied four different spatial and epidemiological parameters. These parameters determined four cluster collections, each covering the entire study region. We simulated 1,000 datasets for each cluster and analyzed them with Kulldorff's spatial scan statistic. From the area under the extended power curve, we constructed a map for each parameter set showing the performance of the test across the entire region. RESULTS: Consistent with previous studies, the performance of the spatial scan statistic increased with the baseline incidence of disease, the size of the at-risk population and the strength of the cluster (i.e., the relative risk). Performance was heterogeneous, however, even for very similar clusters (i.e., similar with respect to the aforementioned factors), suggesting the influence of other factors. CONCLUSIONS: The area under the extended power curve is a single measure of performance and, although needing further exploration, it is suitable to conduct a systematic spatial evaluation of performance. The performance map we propose enables epidemiologists to assess cluster detection tests across an entire study region

Spatial heterogeneity of type I error for local cluster detection tests.

International audienceBACKGROUND: Just as power, type I error of cluster detection tests (CDTs) should be spatially assessed. Indeed, CDTs' type I error and power have both a spatial component as CDTs both detect and locate clusters. In the case of type I error, the spatial distribution of wrongly detected clusters (WDCs) can be particularly affected by edge effect. This simulation study aims to describe the spatial distribution of WDCs and to confirm and quantify the presence of edge effect. METHODS: A simulation of 40 000 datasets has been performed under the null hypothesis of risk homogeneity. The simulation design used realistic parameters from survey data on birth defects, and in particular, two baseline risks. The simulated datasets were analyzed using the Kulldorff's spatial scan as a commonly used test whose behavior is otherwise well known. To describe the spatial distribution of type I error, we defined the participation rate for each spatial unit of the region. We used this indicator in a new statistical test proposed to confirm, as well as quantify, the edge effect. RESULTS: The predefined type I error of 5% was respected for both baseline risks. Results showed strong edge effect in participation rates, with a descending gradient from center to edge, and WDCs more often centrally situated. CONCLUSIONS: In routine analysis of real data, clusters on the edge of the region should be carefully considered as they rarely occur when there is no cluster. Further work is needed to combine results from power studies with this work in order to optimize CDTs performance

Eukaryotic Initiation Factor 2B (eIF2B) GEF Activity as a Diagnostic Tool for EIF2B-Related Disorders

BACKGROUND:In recent years, the phenotypes of leukodystrophies linked to mutations in the eukaryotic initiation factor 2B genes have been extended, classically called CACH/VWM (Childhood ataxia with cntral hypomyélination/vanishing white matter disorder). The large clinical spectrum observed from the more severe antenatal forms responsible for fetal death to milder adult forms with an onset after 16 years old and restricted to slow cognitive impairment have lead to the concept of eIF2B-related disorders. The typical MRI pattern with a diffuse CSF-like aspect of the cerebral white matter can lack particularly in the adult forms whereas an increasing number of patients with clinical and MRI criteria for CACH/VWM disease but without eIF2B mutations are found. Then we propose the use of biochemical markers to help in this difficult diagnosis. The biochemical diagnosis of eIF2B-related disorder is difficult as no marker, except the recently described asialotransferrin/transferrin ratio measured in cerebrospinal fluid, has been proposed and validated until now. Decreased eIF2B GEF activity has been previously reported in lymphoblastoid cell lines from 30 eIF2B-mutated patients. Our objective was to evaluate further the utility of this marker and to validate eIF2B GEF activity in a larger cohort as a specific diagnostic test for eIF2B-related disorders. METHODOLOGY/PRINCIPAL FINDINGS:We performed eIF2B GEF activity assays in cells from 63 patients presenting with different clinical forms and eIF2B mutations in comparison to controls but also to patients with defined leukodystrophies or CACH/VWM-like diseases without eIF2B mutations. We found a significant decrease of GEF activity in cells from eIF2B-mutated patients with 100% specificity and 89% sensitivity when the activity threshold was set at < or =77.5%. CONCLUSION:These results validate the measurement of eIF2B GEF activity in patients' transformed-lymphocytes as an important tool for the diagnosis of eIF2B-related disorders

Détection d'agrégats spatio-temporels de malformations congénitales (mise en place d'un système de surveillance et d'alerte en Auvergne)

La recherche d'agrégats de maladie est une question centrale de la veille sanitaire. Le choix d'une ou plusieurs méthodes statistiques parmi la centaine existant aujourd'hui dépend des données disponibles, de l'objectif de l'analyse et des éventuelles contraintes matérielles. La mise en place d'un système de surveillance-alerte, et en particulier dès que la dimension spatiale de la détection d'agrégat est concernée, ne peut s'affranchir de l'étape de l'étude du comportement des méthodes statistiques utilisées qui dépendent pour grande part des caractéristiques de la région d'étude. C'est l'étude de puissance qui fournira des arguments précis et fiables pour consolider les résultats des analyses et donnera des éléments d'interprétation indispensables lors de la surveillance de routine. Plus largement, la qualité globale du système est conditionnée par les performances de chacune de ses composantes, les méthodes statistiques utilisées n'en sont qu'une parmi d'autres. Notre travail avait pour but d'une part de sélectionner les méthodes statistiques les plus appropriées à la détection d'agrégats dans le cadre d'une surveillance spatio-temporelle prospective et d'en étudier les performances dans le contexte des malformations congénitales en Auvergne, et d'autre part d'assurer l'ensemble des étapes nécessaires à la mise en place effective de ces méthodes au sein du système de surveillance. Ainsi, ce travail s'est d'abord intéressé à la qualité des données en réévaluant et en mettant à jour la base de données du CEMC-Auvergne, puis l'étude de puissance et la construction du protocole de surveillance ont été effectuées en parallèle, enfin, l'implémentation du logiciel destiné à la réalisation des analyses a été réalisée. La mise en place du système et son utilisation feront l'objet d'une formation à destination de l'ensemble des acteurs concernés.CLERMONT FD-BCIU-Santé (631132104) / SudocSudocFranceF

Modélisation de l'attraction hospitalière

CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Does legislative framework favors prescription of physical activity in primary care ? The French experience

International audienc

Risk factors for recurrence of venous thromboembolism associated with the use of oral contraceptives

International audienc

PRZEDRUK POLSKIEGO TŁUMACZENIA ARTYKUŁU ZA ZGODĄ INTERNATIONAL ASSOCIATION FOR THE STUDY OF PAIN (IASP) - PAIN 154 (2013) 2691-2699 Migrenowe bóle głowy i ból o cechach neuropatycznych: schorzenia współistniejące u chorych na stwardnienie rozsiane

We conducted a postal survey to assess the prevalence and characteristics of neuropathic pain and migraine in a cohort of multiple sclerosis (MS) patients. Of the 1300 questionnaires sent, 673 could be used for statistical analysis. Among the respondents, the overall pain prevalence in the previous month was 79%, with 51% experiencing pain with neuropathic characteristics (NCs) and 46% migraine. MS patients with both migraine and NC pain (32% of the respondents) reported more severe pain and had lower health-related quality of life than MS patients with either migraine or NC pain. Pain intensity in MS patients with migraine was moderate (6.0±0.1). Migraine was mostly episodic, but headaches were occurring on P15 days per month in 15% of those with migraine. MS patients with migraine were younger and had shorter disease durations than those with NC pain. NC pain was most often located in the extremities, back and head, and was frequently described as tingling and pins-and-needles. The intensity of NC pain was low to moderate (4.9±0.1), but positively correlated with the number of painful body sites. Nonetheless, patients with NC pain were more disabled (with a higher Expanded Disability Status Scale and pain interference index) than patients with migraine. Migraine, but not NC pain, was associated with age, disease duration, relapsing-remitting course, and interferon-beta treatment. This suggests that NC pain and migraine are mediated by different mechanisms. Therefore, pain mechanisms that specifically operate in MS patients need to be characterized to design optimal treatments for these individuals.Przeprowadziliśmy listowne badanie kwestionariuszowe w celu oceny częstości występowania i charakterystyki bólu neuropatycznego i migreny w kohorcie chorych na stwardnienie rozsiane (SR). Spośród wysłanych 1300 kwestionariuszy 673 nadawało się do analizy statystycznej. Ogólna częstość występowania bólu u respondentów w ciągu miesiąca poprzedzającego badanie wyniosła 79%; 51% badanych odczuwało ból o cechach neuropatycznych (BN), a 46% - ból migrenowy. Chorzy odczuwający zarówno ból migrenowy jak i BN (32% respondentów) zgłaszali większe natężenie bólu i gorszą jakość życia związaną ze stanem zdrowia niż pacjenci ze SR odczuwający tylko jeden z tych bólów. Natężenie bólu u chorych na SR i migrenę było umiarkowane (6,0±0,1). Migrena w większości przypadków miała charakter epizodyczny, ale u 15% osób z migreną bóle głowy występowały ≥15 dni w miesiącu. Chorzy na SR i na migrenę byli młodsi i chorowali krócej niż pacjenci z BN. Ból o charakterze neuropatycznym najczęściej umiejscowiony był w kończynach, plecach i głowie; często opisywany był jako mrowienie lub kłucie. Nasilenie BN było małe lub umiarkowane (4,9±0,1) ale korelowało z liczbą objętych bólem części ciała. Niemniej jednak pacjenci z BN byli bardziej niesprawni (mieli większą punktację w Expanded Disability Status Scale i w Pain Interference Index) niż pacjenci z migreną. W przeciwieństwie do BN, migrena była powiązana z wiekiem, czasem trwania choroby, postacią nawracająco-zwalniającą choroby oraz z leczeniem interferonem beta. Wskazuje to na odrębne mechanizmy BN i migreny. W związku z tym wydaje się konieczne scharakteryzowanie mechanizmów bólu, które działają swoiście u chorych na SR w celu opracowania optymalnego leczenia tych pacjentów