Overview of patients' cohorts in the French National rare disease registry.

In 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.

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

BACKGROUND: 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.

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

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.

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.

Healthcare trajectory of children with rare bone disease attending pediatric emergency departments.

BACKGROUND: Children with rare bone diseases (RBDs), whether medically complex or not, raise multiple issues in emergency situations. The healthcare burden of children with RBD in emergency structures remains unknown. The objective of this study was to describe the place of the pediatric emergency department (PED) in the healthcare of children with RBD. METHODS: We performed a retrospective single-center cohort study at a French university hospital. We included all children under the age of 18 years with RBD who visited the PED in 2017. By cross-checking data from the hospital clinical data warehouse, we were able to trace the healthcare trajectories of the patients. The main outcome of interest was the incidence (IR) of a second healthcare visit (HCV) within 30 days of the index visit to the PED. The secondary outcomes were the IR of planned and unplanned second HCVs and the proportion of patients classified as having chronic medically complex (CMC) disease at the PED visit. RESULTS: The 141 visits to the PED were followed by 84 s HCVs, giving an IR of 0.60 [95% CI: 0.48-0.74]. These second HCVs were planned in 60 cases (IR = 0.43 [95% CI: 0.33-0.55]) and unplanned in 24 (IR = 0.17 [95% CI: 0.11-0.25]). Patients with CMC diseases accounted for 59 index visits (42%) and 43 s HCVs (51%). Multivariate analysis including CMC status as an independent variable, with adjustment for age, yielded an incidence rate ratio (IRR) of second HCVs of 1.51 [95% CI: 0.98-2.32]. The IRR of planned second HCVs was 1.20 [95% CI: 0.76-1.90] and that of unplanned second HCVs was 2.81 [95% CI: 1.20-6.58]. CONCLUSION: An index PED visit is often associated with further HCVs in patients with RBD. The IRR of unplanned second HCVs was high, highlighting the major burden of HCVs for patients with chronic and severe disease.