A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial)

To assess the efficacy of the interleukin 1 receptor antagonist anakinra in systemic-onset juvenile idiopathic arthritis (SJIA).status: publishe

10 years of CEMARA database in the AnDDI-Rares network: a unique resource facilitating research and epidemiology in developmental disorders in France

Background : In France, the Ministry of Health has implemented a comprehensive program for rare diseases (RD) that includes an epidemiological program as well as the establishment of expert centers for the clinical care of patients with RD. Since 2007, most of these centers have entered the data for patients with developmental disorders into the CEMARA population-based registry, a national online data repository for all rare diseases. Through the CEMARA web portal, descriptive demographic data, clinical data, and the chronology of medical follow-up can be obtained for each center. We address the interest and ongoing challenges of this national data collection system 10 years after its implementation. Methods : Since 2007, clinicians and researchers have reported the “minimum dataset (MDS)” for each patient presenting to their expert center. We retrospectively analyzed administrative data, demographic data, care organization and diagnoses. Results : Over 10 years, 228,243 RD patients (including healthy carriers and family members for whom experts denied any suspicion of RD) have visited an expert center. Among them, 167,361 were patients affected by a RD (median age 11 years, 54% children, 46% adults, with a balanced sex ratio), and 60,882 were unaffected relatives (median age 37 years). The majority of patients (87%) were seen no more than once a year, and 52% of visits were for a diagnostic procedure. Among the 2,869 recorded rare disorders, 1,907 (66.5%) were recorded in less than 10 patients, 802 (28%) in 10 to 100 patients, 149 (5.2%) in 100 to 1,000 patients, and 11 (0.4%) in > 1,000 patients. Overall, 45.6% of individuals had no diagnosis and 6.7% had an uncertain diagnosis. Children were mainly referred by their pediatrician (46%; n = 55,755 among the 121,136 total children referrals) and adults by a medical specialist (34%; n = 14,053 among the 41,564 total adult referrals). Given the geographical coverage of the centers, the median distance from the patient’s home was 25.1 km (IQR = 6.3 km-64.2 km). Conclusions : CEMARA provides unprecedented support for epidemiological, clinical and therapeutic studies in the field of RD. Researchers can benefit from the national scope of CEMARA data, but also focus on specific diseases or patient subgroups. While this endeavor has been a major collective effort among French RD experts to gather large-scale data into a single database, it provides tremendous potential to improve patient care

Znanje, ključni dejavnik v globalnih podjetjih

Time series of physico-chemical data and concentrations (cell L-1) of the toxic dinoflagellate Alexandrium minutum collected in the Rance macrotidal estuary (Brittany, France) were analyzed to understand the physico-chemical processes of the estuary and their relation to changes in bloom development from 1996 to 2009. The construction of the tidal power plant in the north and the presence of a lock in the south have greatly altered hydrodynamics, blocking the zone of maximum turbidity upstream, in the narrowest part of the estuary. Alexandrium minutum occurs in the middle part of the estuary. Most physical and chemical parameters of the Rance estuary are similar to those observed elsewhere in Brittany with water temperatures between 15–18 °C, slightly lowered salinities (31.8–33.1 PSU), low river flow rates upstream and significant solar radiation (8 h day-1). A notable exception is phosphate input from the drainage basin which seems to limit bloom development: in recent years, bloom decline can be significantly correlated with the decrease in phosphate input. On the other hand, the chemical processes occurring in the freshwater-saltwater interface do not seem to have an influence on these occurrences. The other hypotheses for bloom declines are discussed, including the prevalence of parasitism, but remain to be verified in further studies

Federating patients identities: the case of rare diseases

Abstract Background Patient information in rare disease registries is generally collected from numerous data sources, necessitating the data to be federated. In addition, data for research purposes must be de-identified. Transforming nominative data into de-identified data is thus a key issue, while minimizing the number of identity duplicates. We propose a method enabling patient identity federation and rare disease data de-identification while preserving the pertinence of the provided data. Results We developed a rare disease patient identifier. The IdMR generation process is a three-phased algorithm involving a hash function to irreversibly de-identify nominative patient data, including those of foetuses. This process minimizes collision risks and reduces variability for the purpose of identity federation. The IdMR was generated for 360,000 patients of the CEMARA database. It allowed identity federation of 1771 duplicated files. No collisions were introduced. Conclusion We examined and discussed the risks of collisions and the creation of duplicates as well as the risks of patient re-identification. We discussed our choice of nominative input information in light of that used by other patient identification solutions. The IdMR is a patient identifier that enables identity federation and file linkage. The simplicity of the algorithm and the universality and stability of the input data make it a good candidate for European cross-border rare disease projects

The ongoing French BaMaRa-BNDMR cohort: implementation and deployment of a nationwide information system on rare disease

International audienceAbstract Background BaMaRa allows the secure collection and deidentified centralization of medical data from all patients followed-up in a rare disease expert network in France, based on a minimum data set (SDM-MR). The present article describes BaMaRa information system implementation and development across the whole national territory as well as data access requests through BNDMR, the data warehouse which centralizes all BaMaRa data, during the 2015–2020 period. Materials and Methods SDM-MR is made up of 60 interoperable items and is routinely collected through BaMaRa in rare disease centers as part of care and discharged into BNDMR after deidentification and data reconciliation. Data access is regulated by a scientific committee. Results In total, 668 002 affected patients had an SDM-MR recorded in BNDMR by the end of 2020 with a mean value of 3.4 activities per patients. Data access was provided for 66 projects. Conclusion The BaMaRa-BNDMR infrastructure provides an administrative and epidemiological resources for rare diseases in France

Gagaku, de Olivier Messiaen Messiaen's Gagaku

A tensão entre nostalgia e inovação se manifesta de maneira única em Gagaku, o quarto movimento de Sept Haikai, de Olivier Messiaen. A religiosidade de Messiaen representa uma forma de nostalgia para a vanguarda intelectual francesa. Messiaen considera o senso de ritual e de estase como expressões musicais do sagrado. Através da comparação da estrutura do Gagaku de Messiaen (analisado à luz de seus próprios escritos sobre os seus métodos composicionais) e da estrutura da música tradicional japonesa gagaku, este artigo mostra de que modo o senso de ritual e de estase constitui o elemento estético comum existente independentemente em ambas as formas musicais. A existência de um elemento comum entre a "fonte" não-ocidental e a composição ocidental inspirada por esta fonte provê a condição necessária para a transformação de nostalgia em inovação. O conceito de écriture tem um papel importante na dialética de passado/futuro desta transformação, causando estrutura e estilo a se diferenciarem baseados no princípio da não-imitação, e afirmando-se como o elemento formativo que faz de Gagaku uma peça distintamente francesa.<br>The tension between nostalgia and innovation is uniquely manifested in Olivier Messiaen's Gagaku, the fourth movement of his 1962 composition Sept Haikai. Messiaen's religiosity represented a form of nostalgia to the intellectual French Avant-Garde. Messiaen considers the sense of ritual and stasis as musical expressions of sacredness. By comparing the structure of Messiaen's Gagaku (analyzed in the light of his writings about his compositional methods) and that of ancient Japanese gagaku court music, this paper will show how this sense of ritual and stasis constitutes the aesthetic common ground existing independently in both forms. The existence of common elements between a non-western "source" and the western composition inspired by that source provides the necessary condition for the transformation of nostalgia into innovation. The concept of écriture plays an important role in the past/future dialectic of this transformation, causing structure and style to differ based on the principle of non-imitation and asserting itself as the shaping element that makes Gagaku a piece of distinctly French music

A methodology for a minimum data set for rare diseases to support national centers of excellence for healthcare and research

International audienceBACKGROUND:Although rare disease patients make up approximately 6-8% of all patients in Europe, it is often difficult to find the necessary expertise for diagnosis and care and the patient numbers needed for rare disease research. The second French National Plan for Rare Diseases highlighted the necessity for better care coordination and epidemiology for rare diseases. A clinical data standard for normalization and exchange of rare disease patient data was proposed. The original methodology used to build the French national minimum data set (F-MDS-RD) common to the 131 expert rare disease centers is presented.METHODS:To encourage consensus at a national level for homogeneous data collection at the point of care for rare disease patients, we first identified four national expert groups. We reviewed the scientific literature for rare disease common data elements (CDEs) in order to build the first version of the F-MDS-RD. The French rare disease expert centers validated the data elements (DEs). The resulting F-MDS-RD was reviewed and approved by the National Plan Strategic Committee. It was then represented in an HL7 electronic format to maximize interoperability with electronic health records.RESULTS:The F-MDS-RD is composed of 58 DEs in six categories: patient, family history, encounter, condition, medication, and questionnaire. It is HL7 compatible and can use various ontologies for diagnosis or sign encoding. The F-MDS-RD was aligned with other CDE initiatives for rare diseases, thus facilitating potential interconnections between rare disease registries.CONCLUSIONS:The French F-MDS-RD was defined through national consensus. It can foster better care coordination and facilitate determining rare disease patients' eligibility for research studies, trials, or cohorts. Since other countries will need to develop their own standards for rare disease data collection, they might benefit from the methods presented here

Impact of the COVID-19 pandemic on the care of rare and undiagnosed diseases patients in France: a longitudinal population-based study

International audienceBackground Preliminary data suggest that COVID-19 pandemic has generated a switch from face-to-face to remote care for individuals with chronic diseases. However, few data are available for rare and undiagnosed diseases (RUDs). We aimed to assess the impact of the COVID-19 pandemic on the activities of the French reference network for RUDs in 2020. Results In this longitudinal retrospective study, we extracted and analyzed the data of the French national registry for RUDs collected between Jan 1, 2019 and Dec 31, 2020. We compared the annual longitudinal evolution of face-to-face and remote care activities between 2019 and 2020 focusing on adult and pediatric patients. Compared to 2019, rare diseases (RD) care activities showed a decrease in 2020 (− 12%) which occurred mostly during the first lockdown (− 45%) but did not catch up completely. This decrease was mainly in face-to-face care activities. Telehealth activities showed a 9-fold increase during the first lockdown and was able to cover for one third of the decrease in RD activities. Finally, the total number of patients receiving care was lower in 2020(− 9%) with a drastic decrease of cases with newly confirmed diagnosis (− 47%).Conclusion Although telehealth was quickly introduced during the COVID-19 pandemic, RUD patient care was strongly affected in France with a decline in the number of patients treated and new patients recruited. This is likely to result in delays in patient diagnosis and care over the next few years

Overview of patients’ cohorts in the French National rare disease registry

International audienceIn France, all patients followed by Rare Disease (RD) expert centers have to be registered in the National Rare Disease Registry (BNDMR). This database collects a minimum data set including diagnosis coded using the Orphanet nomenclature. Overall, 753,660 patients were recorded from 2007 to March 2022 including 493,740 with at least one rare disease diagnosis. Among these rare disease diagnoses, 1,300 diagnoses gathered between 10 and 70 patients and 792 gathered more than 70 patients, corresponding to more than one patient per million inhabitants. A total of 47 rare disease diagnoses with point prevalence or incidence reported in the literature below 1/1,000,000 have more than 70 patients in the BNDMR, suggesting larger BNDMR cohorts than expected from reported literature. As a conclusion, our national RD registry is a great resource to facilitate patients’ recruitment in clinical research and a better understanding of RD natural history and epidemiology

Dora Iveković, klavir : diplomski ispit

Diplomski ispit Dore Iveković (klavir), studentice MA. Ispit je održan na MA u dvorani "Stančić" 27.1.2021. Program: 1. J. S. Bach: Talijanski koncert, BWV 971 (I. Allegro, II. Andante, III. Presto); 2. T. Oliver: Reincarnation Suite for piano (II. Lento); 3. L. van Beethoven: Sonata br. 31 u As-duru, op.110 (I. Moderato cantabile molto espressivo, II. Allegro molto, III. Adagio ma non troppo - Arioso dolente - Fuga. Allegro ma non troppo); 4. O. Messiaen: Dvadeset pogleda na dijete Isusa (IV. Pogled Djevice); 5. C. Debussy: 12 Études, L. 136 (2. Pour les Tierces); 6. S. Rahmanjinov: Etida - slika u a-molu, op. 39 br. 6; 7. R. Schumann: Fantasiestücke, op.12 (I. Des Abends, II. Aufschwung, III. Warum?, IV. Grillen, V. In der Nacht, VI. Fabel, VII. Traumes Wirren, VIII. Ende vom Lied). Mentor: Danijel Detoni