Morbidity and mortality from ataxia-telangiectasia are associated with ATM genotype.

BACKGROUND: Ataxia-telangiectasia (A-T) is a rare genetic disease caused by germline biallelic mutations in the ataxia-telangiectasia mutated gene (ATM) that result in partial or complete loss of ATM expression or activity. The course of the disease is characterized by neurologic manifestations, infections, and cancers. OBJECTIVE: We studied A-T progression and investigated whether manifestations were associated with the ATM genotype. METHODS: We performed a retrospective cohort study in France of 240 patients with A-T born from 1954 to 2005 and analyzed ATM mutations in 184 patients, along with neurologic manifestations, infections, and cancers. RESULTS: Among patients with A-T, the Kaplan-Meier 20-year survival rate was 53.4%; the prognosis for these patients has not changed since 1954. Life expectancy was lower among patients with mutations in ATM that caused total loss of expression or function of the gene product (null mutations) compared with that seen in patients with hypomorphic mutations because of earlier onset of cancer (mainly hematologic malignancies). Cancer (hazard ratio, 2.7; 95% CI, 1.6-4.5) and respiratory tract infections (hazard ratio, 2.3; 95% CI, 1.4-3.8) were independently associated with mortality. Cancer (hazard ratio, 5.8; 95% CI, 2.9-11.6) was a major risk factor for mortality among patients with null mutations, whereas respiratory tract infections (hazard ratio, 4.1; 95% CI, 1.8-9.1) were the leading cause of death among patients with hypomorphic mutations. CONCLUSION: Morbidity and mortality among patients with A-T are associated with ATM genotype. This information could improve our prognostic ability and lead to adapted therapeutic strategies.

Epidemiology and outcome of invasive fungal diseases in patients with chronic granulomatous disease: a multicenter study in France.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare inherited phagocytic disorder resulting in an increased susceptibility to infections including invasive fungal diseases (IFDs) and inflammatory complications. This study is aimed at assessing the incidence, prevalence, and outcome of IFDs among CGD patients followed in France. METHODS: CGD patients were identified through the French national registry for primary immunodeficiencies (PID) held by the French national reference Centre of PID (Centre de Référence Déficits Immunitaires Héréditaires), which comprises a total of 3083 patients including 155 with CGD followed between 1976 and 2008. A questionnaire was filled out for each episode of IFD. Information retrieved included a description of the IFD using the 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group IFD definition criteria. RESULTS: Of CGD patients, 42.6% (66/155) developed at least 1 episode of IFD. Overall incidence of IFD was 0.040/patient-years (1862 patient-years of total follow-up). IFD incidence was found to be significant while receiving itraconazole prophylaxis compared with no prophylaxis (0.027 vs. 0.053 IFD/patient-years; P < 0.01). Median age at IFD diagnosis was 6.5 years (3.3-11.3). The most common fungal genus was Aspergillus sp. accounting for 40% of all IFDs. Of the IFDs, 42.5% were proven, 30.0% probable, and 27.5% possible. Of all IFD episodes, 52.5% were treated by antifungal monotherapy, mostly by amphotericin B. Survival was reduced in IFD patients compared with those without it (log-rank 0.04). CONCLUSIONS: IFDs are a frequent and life-threatening complication in CGD patients. Itraconazole significantly reduces its incidence and should be recommended in absence of better alternatives.

CEMARA an information system for rare diseases.

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

An XML schema for automated data integration in a Multi-Source Information System dedicated to end-stage renal disease.

Data exchange and interoperability between clinical information systems represent a crucial issue in the context of patient record data collection. An XML representation schema adapted to end-stage renal disease (ESRD) patients was developed and successfully tested against patient data in the dedicated Multi-Source Information System (MSIS) active file (more than 16,000 patient records). The ESRD-XML-Schema is organized into Schema subsets respecting the coherence of the clinical information and enriched with coherent data types. Tests are realized against XML-data files generated in conformity with the ESRD-XML Schema. Manual tests allowed the XML schema validation of the data format and content. Programmatic tests allowed the design of generic XML parsing routines, a portable object data model representation and the implementation of automatic data-exchange flows with the MSIS database system. The ESRD-XML-Schema represents a valid framework for data exchange and supports interoperability. Its modular design offers opportunity to simplify physicians' multiple tasks in order to privilege their clinical work.

Equity of accessibility to dialysis facilities.

Patients' end-stage renal disease (ESRD) characteristics are changing. Improving the quality of care requires a steady adaptation of treatment modalities together with equity of access to dialysis facilities. We explored the ability of the health system to cope with the demand of ESRD care. An analysis of a 5-year follow-up cohort of ESRD patients in the Limousin region, France, was performed. Data were entered in the Multi-Source Information System of the Renal Epidemiology and Information Network (REIN). The participation rate of centres was complete. We analysed patient characteristics, therapeutic options and driving time to reach dialysis facilities. We investigated geographic accessibility by defining areas within 45 minutes from dialysis units. We constructed scenarios to assess the impact of health care reorganization. In-centre haemodialysis units represented 73% of treatment modalities. One quarter of patients lived at more than 45 minutes of their dialysis unit. Based on a scenario of creating an additional In-centre unit, the number of patients living far from their centre would decrease by 31%. This study emphasizes important issues related to ESRD epidemiology, comorbidity and health care planning. It stimulates the development of new scenarios allowing the assessment of equity in accessing health care facilities.

CEMARA: a Web dynamic application within a N-tier architecture for rare diseases.

Rare diseases include a group of conditions characterized by a prevalence lower than 5 per 10,000 in the community. In France, any rare disease affects less than 30,000 patients and often much less. Three to 4% of children and 6% of the population in Europe are affected. It is a true public health stake since most diseases do not have any curative treatment. In France, the Ministry of Health has initiated a National Rare Diseases Plan. Twenty five out of 132 labelled Reference Centres (RC) decided to share a common Information System named CEMARA. It is dedicated to collect continuous and complete records of all patients presenting with a rare disease, and their follow-up. The main objective of CEMARA is to contribute to the missions of the RC regarding the registration and description of their activities, coordination of the network of their correspondents, organization of the follow-up of rare diseases, and analysis of the epidemiological patterns. A description of CEMARA is provided as well as its cooperation with Orphanet and Genatlas, and a presentation of 11803 current records collected by more than 300 health care professionals belonging to more than 70 sites.

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

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

Avoiding doubles in distributed nominative medical databases: optimization of the needleman and wunsch algorithm.

Difficulties in reconstituting patients' trajectory in the public health information systems are raised by errors in patients' identification processes. A crucial issue to achieve is avoiding doubles in distributed web databases. We explored Needleman and Wunsch (N&W) algorithm in order to optimize the properties of string matching. Five variants of the N&W algorithm were developed. The algorithms were implemented for a web Multi-Source Information System. This system was dedicated to tracking patients with End-Stage Renal Disease at both regional and national level. A simulated study database of 73,210 records was created. An insertion or suppression of each character of the original string was simulated. The rate of double entries was 2% given an acceptable distance set to 5 modifications. The search was sensitive and specific with an acceptable detection time. It detected up to 10% of modifications that is above the estimated error rate. A variant of the N&W algorithm designed as "cut-off heuristic", proved to be efficient for the search of double entries occurring in nominative distributed databases.

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

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

A Multi-Source Information System via the Internet for End-Stage Renal Disease: Scalability and Data Quality.

A Multi-Source Information System (MSIS), has been designed for the Renal Epidemiology and Information Network (REIN) dedicated to End-Stage Renal Disease (ESRD). MSIS aims at providing reliable follow-up data for ESRD patients. It is based on an n-tier architecture, made out of a universal client, a dynamic Web server connected to a production database and to a data warehouse. MSIS is operational since 2002 and progressively deployed in 9 regions in France. It includes 11,500 patients. MSIS facilitates documenting medical events which occur during the course of ESRD patient' health care and provides means to control the quality of each patient's record and reconstruct the patient trajectory of care. Consolidated data are made available to a data warehouse and to a geographic information system for analysis and data representation in support of public-health decision making.

A Web-based GIS for health care decision-support.

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