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

In 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.

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

BACKGROUND: 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.

An empiric weight computation for record linkage using linearly combined fields' similarity scores.

Record linkage is the task of identifying which records from one or more data sources refer to the same entity. Many record linkage methods were introduced and applied over the last decades. In general, the principle is to compare a range of available identifier fields in record pairs among different data sources, in order to make a linkage decision. The Fellegi-Sunter probabilistic record linkage (PRL-FS) is one of the most commonly used methods. To obtain a better performance, Winkler proposed an enhanced PRL-FS method (PRL-W) that takes into account field similarity, but its implementation requires the estimation of much more parameters which complicates the task. Consequently, we propose to develop a method that contains the best features in the PRL-FS and the PRL-W methods: simplicity of parameters estimation and consideration of fields' similarities. We hypothesize that our record linkage method outperforms the PRL-FS, and can achieve a similar performance of the PRL-W. This paper presents briefly the PRL-FS and PRL-W methods, and describes in details how to combine fields' similarity scores to create a novel record pair weight. Simulated data sets were used to assess and to compare these three methods regarding their ability to reduce the rates of false matches and false non-matches.

Performance map of a cluster detection test using extended power.

BACKGROUND: 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.

Sentinel e-health network on grid: developments and challenges.

Grid technologies have proven their capabilities to settle challenging problems of medical data access. The grid ability to access distributed databases in a secure and reliable way while preserving data ownership opened new perspectives in medical data sharing and disease surveillance. This paper focuses on the implementation challenges of grid-powered sentinel networks within the e-sentinelle project. This initiative aims to create a lightweight grid dedicated to cancer data exchange and enable automatic disease surveillance according to definition of epidemiological alarms. Particularly, issues related to security, patient identification, databases integration, data representation and medical record linkage are discussed.

Evaluating OPTISAS, a visual method to analyse sleep apnea syndromes.

The sleep apnea syndrome is a real public health problem. Improving its diagnosis using the polysomnography is of huge importance. Optisas was a visual method allowing translating the polysomnographic data into a meaningful image. In a previous paper, it was shown to bring extra information in 62% of cases. Here its capacity for displaying information of the same relevance as the one got using the classical report of the polysomnography is studied. The main result is that this capacity is weak and seems to be present only to identify the obstructive sleep apnea syndrome. Moreover this study suggests to improve the standardization of the classical report in the framework of a quality insurance process.

Centralised versus decentralised management of patients' medical records.

For more than 20 years, many countries have been trying to set up a standardised medical record at the regional or at the national level. Most of them have not reached this goal, essentially due to two main difficulties related to patient identification and medical records standardisation. Moreover, the issues raised by the centralisation of all gathered medical data have to be tackled particularly in terms of security and privacy. We discuss here the interest of a non-centralised management of medical records which would require a specific procedure that gives to the patient access to his/her distributed medical data, wherever he/she is located.

New advanced technologies to provide decentralised and secure access to medical records: case studies in oncology.

The main problem for health professionals and patients in accessing information is that this information is very often distributed over many medical records and locations. This problem is particularly acute in cancerology because patients may be treated for many years and undergo a variety of examinations. Recent advances in technology make it feasible to gain access to medical records anywhere and anytime, allowing the physician or the patient to gather information from an "ephemeral electronic patient record". However, this easy access to data is accompanied by the requirement for improved security (confidentiality, traceability, integrity, ...) and this issue needs to be addressed. In this paper we propose and discuss a decentralised approach based on recent advances in information sharing and protection: Grid technologies and watermarking methodologies. The potential impact of these technologies for oncology is illustrated by the examples of two experimental cases: a cancer surveillance network and a radiotherapy treatment plan. It is expected that the proposed approach will constitute the basis of a future secure "google-like" access to medical records.

Grid-enabled sentinel network for cancer surveillance.

Recent developments of grid services for secured distributed data management open new perspectives for disease surveillance. In this paper, we report on our initiative to develop a surveillance network for breast cancer in the Auvergne region. The network gathers cytopathology laboratories, structures in charge of cancer screening and institutes in charge of cancer epidemiology. Data stored in cytopathology laboratories are queried through the grid for the purpose of second diagnosis and to produce statistical indicators. The paper describes the network goal and design and discusses specific issues related to patient identification and security.

Giving patients secure << Google-like >> access to their medical record.

The main problem for the patient who wants to have access to all of the information about his health is that this information is very often spread over many medical records. Therefore, it would be convenient for the patient, after being identified and authenticated, to use a kind of specific medical search engine as one part of the solution to this main problem. The principal objective is for the patient to have access to his or her medical information at anytime and wherever it has been stored. This proposal for secure "Google Like" access requires the addition of different conditions: very strict identity checks using cryptographic techniques such as those planned for the electronic signature, which will not only ensure authentication of the patient and integrity of the file, but also protection of the confidentiality and access follow-up. The electronic medical record must also be electronically signed by the practitioner in order to provide evidence that he has given his agreement and accepted responsibility for the content. This electronic signature also prevents any kind of post-transmission falsification. New advances in technology make it possible to envisage access to medical records anywhere and anytime, thanks to Grid and watermarking methodologies.

Three-dimensional mapping of the lateral ventricles in autism.

In this study, a computational mapping technique was used to examine the three-dimensional profile of the lateral ventricles in autism. T1-weighted three-dimensional magnetic resonance images of the brain were acquired from 20 males with autism (age: 10.1+/-3.5 years) and 22 male control subjects (age: 10.7+/-2.5 years). The lateral ventricles were delineated manually and ventricular volumes were compared between the two groups. Ventricular traces were also converted into statistical three-dimensional maps, based on anatomical surface meshes. These maps were used to visualize regional morphological differences in the thickness of the lateral ventricles between patients and controls. Although ventricular volumes measured using traditional methods did not differ significantly between groups, statistical surface maps revealed subtle, highly localized reductions in ventricular size in patients with autism in the left frontal and occipital horns. These localized reductions in the lateral ventricles may result from exaggerated brain growth early in life.

MDRView: a visualization of the polymorphisms of MDR1(ABCB1) GENE in breast cancer.

This paper presents the Generalized CaseView method applied to the study of polymorphisms of MDR1 (Multi Drug Resistant), a gene coding for a trans-membrane transporting protein. The data base contains Single nucleotide polymorphisms, their positions in cDNA, and the Area Under the Curve of drugs concentrations. The generalized CaseView method permits a compact visualization of these data. The main result is that pharmacokinetics of some anticancer drugs depends on the genotype.

Comparison of transthoracic echocardiography using second harmonic imaging, transcranial Doppler and transesophageal echocardiography for the detection of patent foramen ovale in stroke patients.

AIMS: The comparison of three imaging methods to determine which is the most accurate and reliable for the detection of right-to-left shunt. METHODS AND RESULTS: One hundred and seven patients who were hospitalized for stroke underwent: a transthoracic echocardiography (TTE) using second harmonic, a transcranial Doppler (TCD) and a transesophageal echocardiography (TEE) from August 2003 to April 2004. All studies were recorded on a videotape and were studied by a physician blinded to the study. With TTE and TEE, we found 44 (41%) patent foramen ovales. All contrast tests were positive with TCD for these 44 patients. For two patients, the contrast test was positive only with TTE and TCD. We found four false negative contrast tests with TTE. Among the 63 patients who had a negative contrast test with TEE and TTE, the results were the same with TCD for 59 of them; we were not able to determine a cause for the four positive tests. CONCLUSION: This study confirms that transesophageal echocardiography has limitations in the diagnosis of patent foramen ovale. In this study, the negative predictive value of transcranial Doppler was excellent. Therefore, this examination is able to exclude a patent foramen ovale with a high level of confidence.

Assistance to planning in deep brain stimulation: data fusion method for locating anatomical targets in MRI.

Symptoms of Parkinson's disease can be relieved through deep brain stimulation. This neurosurgical technique relies on high precision positioning of electrodes in specific areas of the basal ganglia and the thalamus. In order to identify these anatomical targets, which are located deep within the brain, we developed a semi-automated method of image analysis, based on data fusion. Information provided by both anatomical magnetic resonance images and expert knowledge is managed in a common possibilistic frame, using a fuzzy logic approach. More specifically, a graph-based virtual atlas modeling theoretical anatomical knowledge is matched to the image data from each patient, through a research algorithm (or strategy) which simultaneously computes an estimation of the location of every structures, thus assisting the neurosurgeon in defining the optimal target. The method was tested on 10 images, with promising results. Location and segmentation results were statistically assessed, opening perspectives for enhancements.

Radiographic stereometry for non-metal-backed acetubular cups: 3D wear estimation and related uncertainty.

The aim of this work was to assess the 3D wear of non-metal-backed acetubular cups from two conventional digitized radiographs. The centers of the femoral head and the metal ring in the equatorial plane of the cup are located using 3D pose techniques for spheres and circles from sampled points in the images. The method used to locate these points of interest and also estimate their covariance is fully described in previous work. The covariance is used to decrease the bias of the pose estimation, while bootstrapping decreases its variance and gives access to the directions of minimal variability between the two centers for each image. These directions are used to produce the final distance after reconstruction. Results are compared with the 2D technique working on a single anteroposterior (AP) radiograph and assuming null lateral wear. Validation is performed on acetubular cups: (a) simulated by Monte-Carlo, (b) implanted on a pelvic model, and (c) acquired on patients just after arthroplasty. The accuracy in wear for simulation increases from about one to four hundredths of a millimeter as caudal and cranial absolute angulations decreases from 45 degrees to 30 degrees . It is more difficult to assess for real prostheses, but results are shown to lie within the manufacturer's dimensional tolerances. Globally, the access to the lateral wear is obtained at the expense of confidence in the global linear wear (0.06 mm), which is doubled with regard to 2D technique but still satisfying for clinical use, whereas the bias of the measurement is decreased.

Percutaneous transluminal angioplasty of dysplastic stenoses of the renal artery: results on 70 adults.

PURPOSE: Retrospective analysis of the dilatation (PTRA) of renal arterial dysplastic stenosis (RADS). METHODS: Seventy patients suffering from hypertension (87 RADS) were treated at our institution for medial (83%) or non-classified fibrodysplasias (17%). Four patients suffered from renal insufficiency. Two endoprostheses were implanted. We evaluated blood pressure with the USCSRH criteria and renal insufficiency with the Martin criteria. RESULTS: Ninety-five percent technical success and 87.9% clinical success for blood pressure were obtained, with worse results for patients older than 57 years or with a history of hypertension greater than 9 years. Results were better when the RADS was responsible for an ipsilateral renal atrophy or for poorly controlled hypertension. No renal insufficiency worsened during the follow-up. CONCLUSION: PTRA is a first-line treatment for renovascular hypertension caused by RADS. The results were encouraging despite a high average age of the subjects and frequent associated extrarenal vascular lesions.

Segmentation of fat and muscle from MR images of the thigh by a possibilistic clustering algorithm.

Physical training is proved to induce changes in physical capacity and body composition. We propose in this article a fast, unsupervised and fully three-dimensional automatic method to extract muscle and fat volumes from magnetic resonance images of thighs in order to assess these changes. The technique relies on the use of a fuzzy clustering algorithm and post-processings to accurately process the body composition of thighs. Results are compared on 11 healthy voluntary elderly people with those provided on the same data by a validated method already published, and its reliability is assessed on repeated measures on three subjects. The two methods statistically agree when computing muscle and fat volumes, and clinical implications of this fully automatic method are important for medicine, physical conditioning, weight-loss programs and predictions of optimal body weight.

Automatic volumetric measurement of lateral ventricles on magnetic resonance images with correction of partial volume effects.

PURPOSE: To propose a method for the quantification of lateral ventricle (LV) volumes on a single sequence of 3D magnetic resonance (MR) images. MATERIALS AND METHODS: This algorithm, following a preliminary fuzzy tissue classification step, is based on the development of mathematical morphology processes allowing both the extraction of the LVs and the correction of partial volume effects on their boundaries. The procedure is fast and totally unsupervised. The method is tested on a phantom image, then applied to five patients diagnosed as potentially suffering from Alzheimer's disease, and finally applied on several MR acquisitions to show the genericness of the algorithm. RESULTS AND CONCLUSION: This technique yielded both an accurate estimation of ventricular volumes intra- and intersubject with respect to published data and a relevant management of partial volume effects. Numerous clinical applications are now expected, from the study of schizophrenia to the longitudinal follow-up of Alzheimer's patients.