ERN EuroBloodNet

PURPOSE OF REVIEW: The aim of this study was to highlight the diagnostic and management challenges of primary vitreoretinal lymphoma (PVRL) through a review of the literature and a European survey on real-life practices for PVRL. RECENT FINDINGS: The care of PVRL patients is heterogeneous between specialists and countries. Upfront systemic treatment based on high-dose methotrexate chemotherapy, with or without local treatment, might reduce or delay the risk of brain relapse.Ibrutinib, lenalidomide with or without rituximab, and temozolomide are effective for patients with relapsed/refractory PVRL and should be tested as first-line treatments. SUMMARY: The prognosis of PVRL remains dismal. No firm conclusion regarding optimal treatment can yet be drawn. The risk of brain relapse remains high. Diagnostic procedures and assessment of therapeutic responses need to be homogenized. Collaboration between specialists involved in PVRL and multicentric prospective therapeutic studies are strongly needed. The recommendations of the French group for primary oculocerebral lymphoma (LOC network) are provided, as a basis for further European collaborative work.

Since developments are global in the healthcare arena, more should be done to align EU and other big markets' regulatory practices for rare disease patients. Notwithstanding efforts and cooperation between the US and EU aimed to harmonize their strategic plans in the field of orphan drugs, regulatory criteria and procedures to gain the designation, terms and classifications should be still harmonised. Aligning the criteria of prevalence and support to orphan medicines in the various jurisdictions internationally, would facilitate patient recruitment eventually at global level, so as to gain the data and the biological insights required to identify biomarkers and appropriate endpoints needed for progressing clinical development. A conducive regulatory environment can further support the development of medicines to treat rare diseases. Overall there is a need for joined-up regulatory process coordination. Better integration of regulatory pathways and better integration of regulatory systems, such as scientific tools and methods to generate evidence, would be helpful. There is a need to revise and agree the current frameworks to be improved which will take into account the considerations and challenges to diagnose and treat different rare diseases and improve quality of life. Deliberative processes with multi-stakeholders' involvement for reimbursement should be considered. This paper explores the successes and limitation of both the regulation and its implementation mechanisms in the current regulatory context, and suggests some improvements that could maximise its benefits and boost rare disease research even further.

BACKGROUND: Sickle cell disease (SCD) is an inherited chronic life-threatening disorder with increasing prevalence in Europe. People living with SCD in Europe mainly belong to vulnerable minorities, have a lower level of health education and suffer from isolation compared to those living with other chronic conditions. As a result, SCD patients are much less likely to partner in the design of research related to their condition and are limited in their ability to influence the research agenda. Aiming to increase the influence of patient voice in the development of SCD-related research, we set out to develop patient centered actions in the frame of International Scientific Conferences in collaboration with the ERN-EuroBloodNet, Oxford Blood Group, Annual Sickle Cell Disease and Thalassaemia Conference (ASCAT), the European Hematology Association and the British Society of Hematology. RESULTS: Two events were organized: a one-day research prioritization workshop and a series of education sessions based on topics chosen by SCD patients and their families. Methodology and outcomes were analyzed in terms of influence on scientific, medical and patient communities. CONCLUSION: The ERN-EuroBloodNet workshops with patients at annual ASCAT conferences have provided an opportunity to enhance patient experience and empowerment in SCD in Europe, producing benefits for patients, caregivers, patient associations and health professionals. Future work should focus on delivering the research questions identified at this workshop and the opportunities to share information for patient education.

Background: The European Rare Disease Research Coordination and Support Action (ERICA) consortium aims at promoting and disseminating the adoption of standardized PROMs for rare diseases.The dedicated working team (the WP3 group) facilitates the creation of a PROMs repository for use in clinical practice, evaluation of care and clinical research.Material and methods: First, among the 4.000 questionnaires described in the Mapi Research Trust PROMs database, PROQOLID, we have selected PROMs developed and validated for rare diseasesand PROMs measuring specific functional impacts (such as mobility, self-care or communication).Second, we conducted a survey among European Reference Networks and patient organisations to collect additional PROMs of interest.Third, we developed coding rules for PROMs, based on the International Classification of Functioning, Disability and Health (ICF) code.The resulting ICF-coded PROMs had to match the ICF-coded functional impacts of rare diseases, generated by semi-structured interviews with the Orphanet Disability Questionnaire.Results: The search in PROQOLID identified 279 PROMs developed in rare diseases and 200 PROMs measuring functional impacts.The survey identified 31 additional PROMs.A preliminary coding was conducted on a convenient sample of 10 PROMs including generic (EQ-5D, SF-36), disease specific (Myasthenia Gravis-Quality of Life (MG-QOL) and Myasthenia Gravis-Activity of Daily Living (MG-ADL)) and function specific (Health Assessment Questionnaire (HAQ), National Eye Institute Visual Function Questionnaire -25 (NEI-VFQ-25)) PROMs. Conclusion:We have selected a first set of more than 500 PROMs eligible for inclusion in the repository.We have defined and tested PROMs coding rules, which will allow 600 rare diseases described through the Orphanet Disability Questionnaire to be matched with the relevant PROMs.The next steps are to implement the coding model to the full set of PROMs, to operationalize the repository platform for both researchers and clinicians and to routinely code new eligible PROMs.

In an editorial published in the Journal Thrombosis and Haemostasis in 2005, two renowned pioneers in the field, Professor Pier Mannucci and Professor Harold Roberts, raised a significant concern about the declining interest of young physicians in pursuing clinical and research careers in bleeding disorders. They emphasized that many young haematologists perceive the field of bleeding disorders as being too narrow. To address this issue, they proposed the establishment of training programs in Thrombosis and Haemostasis (T&H) at various haemophilia centers.1 Regrettably, their proposal did not lead to the implementation of dedicated and uniform educational programs for post-graduate specialization in T&H. A few years later, in 2009, a group of internationally renowned hematologists2 underscored the necessity for training programs in Europe. Recognizing the lack of consensus regarding the criteria to define a specialist in T&H, they put forth a comprehensive European curriculum to serve as a foundation for teaching and training initiatives. Fourteen years later, in 2023, the situation remains largely unchanged and very similar to that of 2009. Numerous educational activities, predominantly sponsored by the pharmaceutical industry, have flourished across Europe over the past 20 years, positively impacting the community. However, no standardized official European educational programs specifically focused on clinical T&H have been established. The field lacks an official definition and recognition of specialized expertise in haemophilia and other inherited bleeding disorders, which could be a requirement at Haemophilia Treatment Centres. Most young haematologists now concentrate on malignant haematology, both in terms of clinical expertise and research interests.3 Consequently, attracting new physicians to the field of T&H to meet the present and future human resource demands has become increasingly challenging. In this context, we undertook an investigation into the current educational background of physicians involved in the diagnosis and management of T&H disorders across Europe. We also gathered data on the available teaching programs during medical studies, residency (internship), and post-graduation. The survey involved 21 experienced T&H specialists from 12 European countries (supporting information). Half of the participants were certified haematologists, while others held board certifications in internal medicine or vascular medicine. Additionally, three participants identified themselves as ‘specialists in T&H’ without specifying their background. Our findings revealed highly heterogeneous training programs across countries and even within the same country, varying based on different regions. During medical studies, students receive limited instruction dedicated to T&H disorders. A significant 71% of participants reported receiving less than 10 h of teaching on T&H during their medical education. Teaching on T&H disorders is primarily provided after obtaining the medical degree, with 80% of participants reporting the existence of teaching programs for the ‘diagnosis and clinical management of T&H disorders’ as part of specialization programs in haematology or internal medicine. However, the duration of this training appears highly variable, ranging from 5 h of lectures to 6 months of clinical practice. While 57% of participants from France, the United Kingdom, Switzerland, Germany, Spain, Finland, and the Netherlands reported the availability of structured educational programs in their respective countries, access to these programs seems to be potentially restricted based on various criteria, such as geographical origin or affiliation with public versus private hospitals. Most training activities consist of post-graduate short courses or industry-sponsored educational initiatives, with only a few delivered by universities leading to a diploma or certificate. In some countries, national haematology or internal medicine societies organize training courses on antithrombotic agents or T&H disorders. In addition to the above-mentioned training courses and in the absence of a strong European approach to develop the discipline, several academics help and mentor PhD students and junior physicians interested with T&H, supported by few educational grants and programs organized by scientific societies like International Society on Thrombosis and Haemostasis and European Haematology Association. In an effort to address this unmet need, three French-speaking European Universities—University of Lyon 1 in France, Catholic University of Louvain in Belgium, and University of Geneva in Switzerland—have recently collaborated to establish a unique joint university certificate program in Clinical Thrombosis and Haemostasis (T&H). These universities are also home to European Haemophilia Comprehensive Care Centres and are active members of the ERN EuroBloodNet (https://eurobloodnet.eu). The training program is organized, overseen by an educational committee approved by all three partner universities and is supported by European Reference Network on Rare Haematological Diseases (ERN-EuroBloodNet)-Project ID No 101085717. ERN-EuroBloodNet is partly co-funded by the European Union within the framework of the Fourth EU Health Programme. The program itself consists of 116 h of online teaching, covering both thrombotic and bleeding disorders, and is delivered by experts from the three countries. This online component is followed by a week of face-to-face practical teaching and clinical case-based workshops. The final part of the program involves a training period of at least one week at a European Haemophilia Comprehensive Care Centre. Upon completion of these activities and a successful examination, participants are granted certification by the three universities. Although still in its early stages, we firmly believe that such academic initiatives have the potential to significantly enhance and standardize the specialized training of healthcare professionals working in clinical T&H. Furthermore, this program could serve as a foundation for a broader European training program, leading to a board certification in collaboration with multiple European universities, the ERN-EuroBloodNet, and the support of national and pan-European scientific societies in the field (such as EAHAD, EHA, and others). Given the recent advancements in the field of T&H, the increasing collaborations among specialists and centres across Europe, the growing role of the ERNs, and the recognition of the need to establish T&H as a distinct discipline requiring specific expertise, all these factors contribute to the structure and provision of educational and training initiatives supported and endorsed by academic institutions throughout Europe. Therefore, we strongly encourage all initiatives that pave the way for an official pan-European training program in the field of T&H. The authors thank the European T&H specialists who participated in the survey. The authors declare no conflicts of interest. This study was based on a voluntary online survey, did not include data pertaining to human subjects, and was performed in accordance with local regulations. Informed consent was obtained from all participants. The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

ABSTRACT Introduction Adult patients with sickle cell anemia (SCA) are at high risk for atrial arrhythmias; however, data on the outcomes of atrial fibrillation (AF) ablation in this population are scarce. Methods and Results Eight consecutive SCA patients undergoing AF ablation in three tertiary ablation centers were retrospectively included (6 males, mean age 46 ± 9 years). Patients exhibited severe left atrial (LA) remodeling (mean indexed LA volume 71 ± 14 mL/m 2 ) and six presented with persistent AF. Ablation techniques included radiofrequency (RF, n = 6), cryoballoon ( n = 1), and pulsed‐field ablation (PFA, n = 1). Three patients received additional LA lesions beyond pulmonary vein isolation. At 12 months, seven patients (88%) were free from any atrial arrhythmia, with 88% off antiarrhythmic therapy, and NYHA class significantly improved from 2.00 ± 0.93 to 1.38 ± 0.52 ( p = 0.049). No major complications were reported following RF ablations. The cryoballoon case was complicated by an acute chest syndrome, while moderate hemolysis occurred following PFA, without clinical consequence. Conclusion AF catheter ablation appears effective in SCA patients. While RF ablation showed a reassuring safety profile, specific risks associated with cryoballoon and PFA warrant further investigation.

The ERICA Patient Reported Outcome Measures (PROMs) Repository is the first attempt to identify and centralize Clinical Assessment Outcomes questionnaires of relevance for rare diseases and constitutes a milestone in the Europe-wide standardization of Patient-Centered Outcome Measures (PCOMs) and PROMs for rare diseases. It has been made possible through the joint collaboration between Orphanet, Mapi Research Trust/ICON and ERN EuroBloodNet (VHIR, APHP), and the active contribution of ERNs and ePAGs. Available at ERICA website: ERICA PROMs Repository

The ERICA Patient Reported Outcome Measures (PROMs) Repository is the first attempt to identify and centralize Clinical Assessment Outcomes questionnaires of relevance for rare diseases and constitutes a milestone in the Europe-wide standardization of Patient-Centered Outcome Measures (PCOMs) and PROMs for rare diseases. It has been made possible through the joint collaboration between Orphanet, Mapi Research Trust/ICON and ERN EuroBloodNet (VHIR, APHP), and the active contribution of ERNs and ePAGs. Available at ERICA website: ERICA PROMs Repository