Plan For Rare Diseases Research Articles

Framing the European Rare Diseases field through a structured movement of patient organisations

EURORDIS-Rare Diseases Europe is an alliance of patient organisations, working across countries, empowering patients with trainings, and generating evidence through surveys. It advocates for the needs of people living with rare diseases in Europe, influencing policy, legislation, research, healthcare services, social inclusion, medicines development and access. Since its creation, EURORDIS has maintained a global perspective. By nature of the rarity of these conditions, knowledge and expertise are scattered, so collaboration on a global level is required to have an understanding of disease progression. Thus, every rare disease patient group must be equipped to collaborate beyond its own borders. EURORDIS impacts global activities with a focus on raising awareness; empowering a global alliance; supporting international, national and regional initiatives; and recognising rare diseases within the international community while fostering collaboration among stakeholders. For these reasons, the organisation’s impact extends beyond Europe, as demonstrated by its international partnerships. This perspective paper explores EURORDIS’ achievements over two decades, examining its role in shaping policies and regulations, to demonstrate the vital importance of global collaboration in the rare disease field. Looking ahead, EURORDIS’ Strategic Goals, to be achieved by 2030, align with the United Nations Sustainable Development Goals Agenda 2030 and advocate for a European Action Plan for Rare Diseases. This illustrates EURORDIS’ continued commitment to transforming policies into tangible outcomes. With its ongoing dedication, collaborative efforts, and enduring impact on the rare disease community, EURORDIS remains a driving force for positive change in the lives of people living with rare diseases.

The experience of diagnosis announcement in rare endocrine diseases: A survey of the French FIRENDO network

ContextDiagnosis announcement of a chronic disease is a crucial moment for patients as well as for their families and an important step in the management of severe conditions such as rare endocrine diseases. Little is known of how diagnosis is communicated to patients and families. The FIRENDO network was created by the third French Plan for Rare Diseases, to promote autonomy, care and research on rare endocrine diseases. ObjectivesThe aim of this study was to characterize, for the first time, the experience and needs of patients and/or their parents around the announcement of diagnosis to ensure optimal quality of care. MethodsA quantitative self-administered survey on diagnosis announcement procedures in rare endocrine diseases was launched in April 2017 by the ad hoc FIRENDO thematic working group in collaboration with its 11 partnering patient associations and support groups. The questionnaire was designed and revised by patient support group representatives, adult and pediatric endocrinologists, psychologists and biologists, all expert in rare endocrine diseases. It was made available on the FIRENDO network website and distributed mainly by email with electronic links on their respective websites to members of all affiliated patient support groups. ResultsQuestionnaires were filled out by 391 patients and 223 parents (median age of patients: 39 years). The following conditions were associated with at least 30 answers: Addison's disease, classical forms of congenital adrenal hyperplasia (CAH), Russell-Silver syndrome, Cushing's syndrome, acromegaly and craniopharyngioma. Overall, some announcement modalities were judged favorably by patients: physician's empathy, availability and use of clear terms, and presence of family at the time of announcement. However, a lack of psychological care and information documents was reported, as well as some inadequate procedures such as postal mail announcements. ConclusionThis work suggests that better knowledge of the patient's experience is useful for improving the diagnosis announcement of rare endocrine disorders. The main recommendations derived from the survey were the need for several announcement visits, information on patient support groups and reference centers, imperatively avoiding impersonal announcement, and the usefulness of a written accompanying document.

Access to orphan drugs for the treatment of spinal muscular atrophy in Spain

Spinal muscular atrophy (SMA) is a rare disease whose diagnosis and treatment are complex. In Spain, there are two orphan medicines that are currently financed by the state, nusinersen and onasemnogene abeparvovec and, a third in process, risdiplam. The objective was to detect possible causes of inequity in the diagnosis and treatment of SMA in Spain. Descriptive study realized in two phases: a first phase of bibliographic revision and a second phase of semi-structured interviews with clinical experts in SMA in Andalusia, Castilla-La Mancha, Catalonia and Murcia. The number of centers, services or units of reference, the availability of regional autonomous plans for rare diseases and pilot programs of neonatal screenings can regulate access to treatments. The number of new patients diagnosed per year is estimated between one and six in the four autonomous communities (ACs) of Spain studied. Differences were not found in logistical resources. Two of the four ACs studied have regional autonomous plans for rare diseases, however, their utility has only had relevance in one of two of the ACs. Important differences in access to nusinersen were not identified in the studied ACs The diagnosis of SMA requires clinical specialized experts and specialized centers for early intervention of disease-modifying therapies.

Rare diseases research and policy in Australia: On the journey to equitable care.

Almost exactly 10 years after the publication of 'Call for a national plan for rare diseases' in this journal, the Federal Government launched the National Strategic Action Plan for Rare Diseases (the Action Plan) on the 26th of February 2020, in the lead up to Rare Disease Day on the 29th of February - a rare day for rare diseases. The Action Plan is the culmination of effective advocacy by Rare Voices Australia (RVA) and other stakeholders in the rare disease (RD) sector. RVA is the peak body for Australians living with a RD. The organisation works collaboratively with RD organisations, researchers and clinicians. Since the initial call for a RD plan, a number of health-care initiatives and policy changes have gathered apace including expanded antenatal and newborn screening, the increasing application of next generation sequencing and advances in gene and cell therapeutics. The development of new models of care, diagnostic and treatment pathways, and communities of practice have started to ease the considerable burden and inequitable access to care experienced by RD patients and their families. However, much work remains to be done. The Action Plan outlines the actions to bring about the best possible health and well-being outcomes for Australians living with RD. It is centred around three pillars - awareness and education, care and support, research and data - and will be delivered against the principles of person centredness, equity, and sustainable systems and workforce.

The need for widely available genomic testing in rare eye diseases: an ERN-EYE position statement

BackgroundRare Eye Diseases (RED) are the leading cause of visual impairment and blindness for children and young adults in Europe. This heterogeneous group of conditions includes over 900 disorders ranging from relatively prevalent disorders such as retinitis pigmentosa to very rare entities such as developmental eye anomalies. A significant number of patients with RED have an underlying genetic etiology. One of the aims of the European Reference Network for Rare Eye Diseases (ERN–EYE) is to facilitate improvement in diagnosis of RED in European member states.Main bodyTechnological advances have allowed genetic and genomic testing for RED. The outcome of genetic testing allows better understanding of the condition and allows reproductive and therapeutic options. The increase of the number of clinical trials for RED has provided urgency for genetic testing in RED. A survey of countries participating in ERN-EYE demonstrated that the majority are able to access some forms of genomic testing. However, there is significant variability, particularly regarding testing as part of clinical service. Some countries have a well-delineated rare disease pathway and have a national plan for rare diseases combined or not with a national plan for genomics in medicine. In other countries, there is a well-established organization of genetic centres that offer reimbursed genomic testing of RED and other rare diseases. Clinicians often rely upon research-funded laboratories or private companies. Notably, some member states rely on cross-border testing by way of an academic research project. Consequently, many clinicians are either unable to access testing or are confronted with long turnaround times. Overall, while the cost of sequencing has dropped, the cumulative cost of a genomic testing service for populations remains considerable. Importantly, the majority of countries reported healthcare budgets that limit testing.Short conclusionDespite technological advances, critical gaps in genomic testing remain in Europe, especially in smaller countries where no formal genomic testing pathways exist. Even within larger countries, the existing arrangements are insufficient to meet the demand and to ensure access. ERN-EYE promotes access to genetic testing in RED and emphasizes the clinical need and relevance of genetic testing in RED.

Belgian rare diseases plan in clinical pathology: identification of key biochemical diagnostic tests and establishment of reference laboratories and financing conditions

BackgroundOne objective of the Belgian Rare Diseases plan is to improve patients’ management using phenotypic tests and, more specifically, the access to those tests by identifying the biochemical analyses used for rare diseases, developing new financing conditions and establishing reference laboratories.MethodsA feasibility study was performed from May 2015 until August 2016 in order to select the financeable biochemical analyses, and, among them, those that should be performed by reference laboratories. This selection was based on an inventory of analyses used for rare diseases and a survey addressed to the Belgian laboratories of clinical pathology (investigating the annual analytical costs, volumes, turnaround times and the tests unavailable in Belgium and outsourced abroad). A proposal of financeable analyses, financing modalities, reference laboratories’ scope and budget estimation was developed and submitted to the Belgian healthcare authorities. After its approval in December 2016, the implementation phase took place from January 2017 until December 2019.ResultsIn 2019, new reimbursement conditions have been published for 46 analyses and eighteen reference laboratories have been recognized. Collaborations have also been developed with 5 foreign laboratories in order to organize the outsourcing and financing of 9 analyses unavailable in Belgium.ConclusionsIn the context of clinical pathology and rare diseases, this initiative enabled to identify unreimbursed analyses and to meet the most crucial financial needs. It also contributed to improve patients’ management by establishing Belgian reference laboratories and foreign referral laboratories for highly-specific analyses and a permanent surveillance, quality and financing framework for those tests.

Educational and knowledge gaps within the European reference network on rare endocrine conditions.

ObjectiveThe European Reference Network on Rare Endocrine Conditions (Endo-ERN), operational since 2017, consists of 71 health care providers (HCPs) in 19 EU member states. Our objective was to assess education and knowledge on rare endocrine conditions.Design and methodsA survey was developed and sent through the DIGIT-EUROSURVEY system to all Endo-ERN HCPs.ResultsResponse rate was 55% (n = 146), 95% physicians, 58% >20 years of experience, 96% academics. Largest knowledge gaps were reported for the transition and neonatal ages, and for the GPs. Less than 50% of HCPs had structured educational rare diseases (RD) plans, while 86% used RD specific guidelines. HCPs would share educational materials within Endo-ERN (74%), and participate in an accreditation model (85%). E-learning portals of the endocrine scientific societies used 58% (ESPE) and 64% (ESE). Most participants (90%) regarded Endo-ERN coordinated educational activities (annual meetings slots, webinars, etc.) as highly important and supported a common educational platform. Social media was perceived as important for educating patients (86%) but not for physicians (36%). Seventy-five % had developed patient education materials; only 31% had specific children’s materials, and by-country availability varied from 0 to 100%. Respondents provided newly diagnosed patients with their own material in the national language (81%); referred to advocacy groups (68%), and relevant online sources (50%). Respondents believed the European Commission should fund education through Endo-ERN.ConclusionIdentified knowledge gaps in rare endocrine disorders set the basis for fast catch-up through collaboration, alignment with patients’ needs, and further development of existing and newly developed educational resources.

Neurofibromatosis 1 French national guidelines based on an extensive literature review since 1966

Neurofibromatosis type 1 is a relatively common genetic disease, with a prevalence ranging between 1/3000 and 1/6000 people worldwide. The disease affects multiple systems with cutaneous, neurologic, and orthopedic as major manifestations which lead to significant morbidity or mortality. Indeed, NF1 patients are at an increased risk of malignancy and have a life expectancy about 10–15 years shorter than the general population. The mainstay of management of NF1 is a patient-centered longitudinal care with age-specific monitoring of clinical manifestations, aiming at the early recognition and symptomatic treatment of complications as they occur. Protocole national de diagnostic et de soins (PNDS) are mandatory French clinical practice guidelines for rare diseases required by the French national plan for rare diseases. Their purpose is to provide health care professionals with guidance regarding the optimal diagnostic and therapeutic management of patients affected with a rare disease; and thus, harmonizing their management nationwide. PNDS are usually developed through a critical literature review and a multidisciplinary expert consensus. The purpose of this article is to present the French guidelines on NF1, making them even more available to the international medical community. We further dwelled on the emerging new evidence that might have therapeutic potential or a strong impact on NF1 management in the coming feature. Given the complexity of the disease, the management of children and adults with NF1 entails the full complement healthcare providers and communication among the various specialties.

The needs of patients with rare disease in Serbia. Why do we need National Strategy for rare disease?

The patients with rare diseases in Serbia face the difficulties in procurement of medications as the Health insurance fund does not cover reimbursement for some medications, they face difficulties in receiving proper diagnosis which makes their position specific and complex. In an attempt to provide more support for the patients with rare diseases, their families and caregivers the helpline for rare diseases was established in October 2015. The aim of this research was to identify, examine and systematise needs of helpline users and forms of assistance provided by the team from the free helpline. The research was designed as a cross-sectional study and was conducted between October 2015 and December 2016. The electronic database of National Organization for rare disease in Serbia helpline users was used as a data source. The user was the person who contacted helpline (patient, relative, friend, physician, etc). The "need" refers to the reasons for addressing the helpline. Helpline users had 549 needs in total; about healthcare-236 (42.98%), social care-113 (20.58%), psychological support-56 (10.20%) and other-144 (26.22%). Services were provided by the lawyer-130 (23.70%), social worker-71 (12.93%), Psychologist-56 (10.20%) and by all employees-292 (53.19%). The most common need for legal assistance among needs on healthcare was on legal aspects of access to and reimbursement of expenses for medications (32/74%-43.24%) and procedures for reimbursement of treatment abroad (11/74%-14.86%). The problems of patients with rare diseases and their families result primarily from the lack of relevant information and knowledge, as well as the non-recognition of rare diseases in the laws and regulations of health and social care. Some problems can simply be solved by legal changes and by a better organisation and do not require additional funding. Only by adopting and implementing the National Strategy and Action Plan for Rare Diseases, the greatest number of problems and needs of people with rare diseases can be systematised and solved.

Health and socio-educational needs of the families and children with rare metabolic diseases: Qualitative study in a tertiary hospital

IntroductionRare diseases are a challenge for public health due to the lack of information on their magnitude. These include inborn errors of metabolism. The objective of this study was to assess the quality of life and social, health, economic, and educational needs of a group of paediatric patients with inborn errors of metabolism attended to in a hospital. Material and methodA questionnaire was developed based on the needs and expectations, based mainly on the Andalusian Plan for Rare Diseases. An analysis was performed on the variables of health, socioeconomic, and educational needs of 65 paediatric patients with inborn errors of metabolism. ResultsThe respondents showed few possibilities to cope with medication (61%), special diet (86%), and other health benefits (79%). Just under half of them (43%) believed that the quality of family life had been greatly reduced since the onset of the disease. The main caregiver was the mother in 61.5% of cases, compared to 1.5% of cases in which it was the father. The primary caregivers had to reduce their working hours or give up their job in 77% of cases. ConclusionsThe multidisciplinary treatment is affected by the inability of families to cope with a high cost, as well as with difficult access to these resources. In addition, there is great impact on the quality of life of patients, and their caregivers. Therefore, there is a need to evaluate the results of government health and socio-economic support plans for patients with rare diseases, and make a real response to their needs.

Conceptualization and Implementation of the Central Information Portal on Rare Diseases: Protocol for a Qualitative Study.

BackgroundRecently, public and political interest has focused on people living with rare diseases and their health concerns. Due to the large number of different types of rare diseases and the sizable number of patients, taking action to improve the life of those affected is gaining importance. In 2013, the federal government of Germany adopted a national action plan for rare diseases, including the call to establish a central information portal on rare diseases (Zentrales Informationsportal über seltene Erkrankungen, ZIPSE).ObjectiveThe objective of this study, therefore, was to conduct scientific research on how such a portal must be designed to meet the needs of patients, their families, and medical professionals, and to provide high-quality information for information seekers.MethodsWe chose a 3-step procedure to develop a needs-based prototype of a central information portal. In the first step, we determined the information needs of patients with rare diseases, their relatives, and health care professionals by means of qualitative interviews and their content-analytical evaluation. On the basis of this, we developed the basic structure of the portal. In the second step, we identified quality criteria for websites on rare diseases to ensure that the information linked with ZIPSE meets the quality demands. Therefore, we gathered existing criteria catalogs and discussed them in an expert workshop. In the third step, we implemented and tested the developed prototypical information portal.ResultsA portal page was configured and made accessible on the Web. The structure of ZIPSE was based on the findings from 108 qualitative interviews with patients, their relatives, and health care professionals, through which numerous information needs were identified. We placed particularly important areas of information, such as symptoms, therapy, research, and advisory services, on the start page. Moreover, we defined 13 quality criteria, referring to factors such as author information, creation date, and privacy, enabling links with high-quality information. Moreover, 19 users tested all the developed routines based on usability and comprehensibility. Subsequently, we improved the visual presentation of search results and other important search functions.ConclusionsThe implemented information portal, ZIPSE, provides high-quality information on rare diseases from a central point of access. By integrating the targeted groups as well as different experts on medical information during the construction, the website can assure an improved search for information for users. ZIPSE can also serve as a model for other Web-based information systems in the field of rare diseases.Registered Report IdentifierRR1-10.2196/7425

Telephone health services in the field of rare diseases: a qualitative interview study examining the needs of patients, relatives, and health care professionals in Germany

BackgroundRare diseases are, by definition, very serious and chronic diseases with a high negative impact on quality of life. Approximately 350 million people worldwide live with rare diseases. The resulting high disease burden triggers health information search, but helpful, high-quality, and up-to-date information is often hard to find. Therefore, the improvement of health information provision has been integrated in many national plans for rare diseases, discussing the telephone as one access option. In this context, this study examines the need for a telephone service offering information for people affected by rare diseases, their relatives, and physicians.MethodsIn total, 107 individuals participated in a qualitative interview study conducted in Germany. Sixty-eight individuals suffering from a rare disease or related to somebody with rare diseases and 39 health care professionals took part. Individual interviews were conducted using a standardized semi-structured questionnaire. Interviews were analysed using the qualitative content analysis, triangulating patients, relatives, and health care professionals. The fulfilment of qualitative data processing standards has been controlled for.ResultsOut of 68 patients and relatives and 39 physicians, 52 and 18, respectively, advocated for the establishment of a rare diseases telephone service. Interviewees expected a helpline to include expert staffing, personal contact, good availability, low technical barriers, medical and psychosocial topics of counselling, guidance in reducing information chaos, and referrals. Health care professionals highlighted the importance of medical topics of counselling—in particular, differential diagnostics—and referrals.ConclusionsTherefore, the need for a national rare diseases helpline was confirmed in this study. Due to limited financial resources, existing offers should be adapted in a stepwise procedure in accordance with the identified attributes.

The actual questions of the care of rare diseases

The aim was to present the actual situation of rare diseases, especially to characterize the circumstances in Hungary. The most important developments were summarized which could help the care of rare disease patients in the everyday practice. There are around 800 000 patients with rare diseases in Hungary. The lack of information leads to "invisibility" for the health and social care system (most of them without ICD code). Therefore, these patients still have a huge disadvantage even when compared to the patients of common diseases. Important national and international measures took place in the last years to decrease these disadvantages. The Hungarian Centres of Expertise were officially approved, thus several health care providers were able to get membership in the forming European Reference Networks. The rare disease specific "Lifebelt" Information Centre and Help Line was established by HUFERDIS. These steps assist the implementation of the National Rare Disease Plan, although its formal approval process has temporarily stopped because of the reorganization of the health care system. The summarized developments can contribute to define better patient directions, and thus decrease the family knocks about the maze of health, social and educational systems. The realization of Rare Disease National Strategy is needed to improve the current fragmentation of services and enable patients and health, social and educational professionals to provide and use best practice care. This will ensure that all patients with rare disease cannot only be diagnosed quickly, but also have timely access to the care and support that they need, resulting in a decreasing burden of families and society. Orv Hetil. 2017; 158(47): 1851-1856.

Hypophosphatasia: the patient’s and patient’s family’s point of view

Today, public opinion and the French authorities are more aware of rare diseases, in particular due to the implementation of national plans for rare diseases (PNMR I: 2005-2008 and PNMR II: 2011-2016), the existence of national networks and the current organization of the reference expert centers for rare diseases. While the management of rare diseases is now better structured, it remains long for the patients to be diagnosed. It is not always easy for physicians to clearly identify one of the 7,000 rare diseases even though they increasingly ask themselves the question: is this a rare disease? A person diagnosed with a rare disease lives in a familial, social and professional environment that has not prepared him or her, suddenly or after years of uncertainty, for such an experience. It may be temptng to take refuge in isolation. The patient's pathway is a real challenge and include the recognition to his/her 'difference' and the right to benefit from the expert medical and social care. Patients affected with hypophosphatasia, a very rare bone and dental disease, are not exceptions to the rule, despite the dynamic support of Hypophosphatasie Europe, the first patient association, created in 2004. In twelve years, the overall understanding of hypophosphatasia has dramatically improved, including through the discovery of novel therapies. Yet, diagnostic errance, transition between childhood and adulthood and management and care of affected adults remain unsolved issues.

Negotiating prices of drugs for rare diseases.

Rare diseases are often serious, chronic and life-threatening. The European Union (EU) definition of a rare disease is one that affects fewer than 5 in 10 000 people. (1) At present, more than 6000 rare diseases are known; around 80% of them are genetic disorders and half of them occur during childhood. Grouped together, rare diseases affect 6-8% (or about 30 million people) out of the 508 million population of EU countries. (2) This roughly equals the estimated prevalence of diabetes in the World Health Organization European Region, which in 2013 was 6.8% of 658.7 million adults in the 20-79 year age group. (3) This illustrates the paradox of rarity: each disease is rare but collectively, rare diseases affect many people. (4) In 2009, responding to increasing concerns about the issue, the European Council published a recommendation (2009/C 151/02) on action in the field of rare diseases, recommending Member States to adopt and establish national plans for rare diseases by the end of 2013. (2) Rare diseases are associated with a high psychological burden for the patient but they can also have a major impact on a patient's family. (5) In addition to the health burden on patients, few of these diseases have an effective drug treatment available. This is because the drugs to treat rare diseases (called orphan drugs) are not commercially viable for pharmaceutical companies, due to the small number of patients per disease. To encourage pharmaceutical companies to develop and market orphan drugs, the European Parliament and the European Council published the regulation (EC) No 141/2000 on orphan medicinal products in 1999. (1) Orphan designation for a medicine is granted at the European level by the European Medicines Agency (EMA). Three criteria must be met, as stated in the regulation: (i) the medicine must be intended for the treatment, prevention or diagnosis of a disease that is life-threatening or chronically debilitating; (ii) the prevalence of the condition in the European Union must be no more than 5 in 10 000 or it must be unlikely that the marketing of the medicine would generate sufficient returns to justify the investment needed for its development; and (iii) no satisfactory method of diagnosis, prevention or treatment of the condition concerned can be authorized, or, if such a method exists, the medicine must be of significant benefit to those affected by the condition. (1) The application for orphan designation, which can be submitted by the sponsor of the medicinal product at any stage of drug development, is then examined within 90 days by the Committee for Orphan Medicinal Products of the EMA. When a medicine is granted orphan designation, several incentives are provided to the sponsor of a clinical trial, as stated in regulation (EC) No 141/2000. (1) These incentives include protocol assistance, scientific advice from EMA before the submission for marketing authorization and market exclusivity of 10 years once the medicine is marketed. This period of market exclusivity can be extended by two years for medicines that comply with an agreed investigation plan for medicines for paediatric care. Finally, depending on the status of the sponsor and the type of service required, reductions in fees to be paid for regulatory activities related to the evaluation of orphan medicinal products by EMA (e.g. protocol assistance, application for marketing authorization) can also be available for the sponsor. By the end of 2015, 89 different orphan medicinal products had received authorization to enter the market from the EMA's Committee for Medicinal Products for Human Use, and 123 other medicinal products intended for rare diseases but without the orphan designation in Europe also received the European marketing authorization. (6) In addition, an increasing number of applications for orphan designation are submitted to EMA each year (Fig. 1). (7) As a consequence, an increasing number of applications for a marketing authorization of an orphan medicinal product is observed each year. …

Guidelines for clinical pharmacological practices in Huntington's disease

ObjectiveEvidence-based medicine is a difficult goal to achieve in rare diseases where randomized controlled trials are lacking. This report provides guidelines that capitalize on both the literature and expertise of the French National Huntington Disease Reference Centre to optimalize pharmacological therapeutic interventions for Huntington's disease (HD). Material and methodsHD experts conducted a systematic analysis of the literature from 1965 to 2013, using a scoring procedure established by the French National Authority for Health. These experts offered their views when evidence was missing to set up provisional guidelines for care in HD. These guidelines were then scored and amended through two subsequent online questionnaires (using SurveyMonkey® scoring), and one face-to-face meeting with an external multidisciplinary working group as a step towards validation. ResultsExcept for the beneficial effects of tetrabenazine in chorea, none of the published recommendations were grounded on established scientific evidence. Second-generation antipsychotics are nevertheless the first choice for patients with psychiatric manifestations (low level of evidence). All other guidelines are based on low-level evidence and little professional agreement. ConclusionPatients’ care has greatly improved over the last few years despite the lack of high-level evidence standards. Guidelines are based on the expertise of trained specialists from the French National Plan for Rare Diseases. This strategy should now be extended internationally to promote future studies and to harmonize worldwide care of HD.

The attitudes of medical students towards rare diseases: A cross-sectional study

Rare diseases are chronic, degenerative and may lead to permanent disability. We aimed to assess knowledge and attitudes of the 3rd and 6th year medical students towards the treatment of rare diseases in Serbia. Methods. In this cross-sectional study, two samples of students were questioned for a survey: 350/446 (78.48%) students of the 3rd year, and 242/517 (46.81%) students of the 6th year. In this cross-sectional study, two samples of students were questioned for a survey: 350/446 (78.48%) students of the 3rd year, and 242/517 (46.81%) students of the 6th year. Sixth year students estimated that they were more informed on the issue analyzed than the 3rd year students (median value of 4 and 3, interquartile range of 3-5, and 1-4, respectively; p < 0.05). However, a significant percentage of participants estimated incorrectly the prevalence of rare diseases according to the European Union standards (3rd year - 42.68%, 6th year - 49.55%). Core curriculum subjects were the main source of information on rare diseases (3rd year - 63.14%; 6th year - 92.14%). Our participants agreed that the most important problems are the following: high drug prices, difficult access to drugs and lack of public information. Students found, without any differences, that community access to effective drugs for rare disease should be improved (median value - 10, interquartile range 8-10 in both groups, p < 0.05). In order to improve pharmacotherapy of rare diseases in Serbia, the participants suggested establishment of a National Plan for Rare Diseases, approval of more appropriate drugs, simplified access to appropriate medicines, and more rapid diagnostics. It is necessary to improve the knowledge and attitudes of medical students towards pharmacotherapy of rare diseases. [Projekat Ministarstva nauke Republike Srbije, br. 175023]

Which support from the French Foundation of rare disease towards clinical trial set up in rare diseases?

The French Foundation for rare diseases (Fondation maladies rares) is a new private non-profit organisation started in 2012 by Pr. Nicolas Levy and Celine Hubert, which pooled together their complementary experiences in the field of rare diseases, from academia and the pharmaceutical industry respectively. Headquartered in Paris at the heart of the ‘Rare Diseases Platform’, the Foundation reaches out to the whole national territory with its network of regional delegates. The team is now composed of 14 dedicated professionals. The Foundation was foreseen in the 2nd French National Rare Diseases Plan, as the flagship measure of the research axis. It was created and financially supported by 5 founders representing the patients, the research sector and the medical sector (AFM-Telethon, Alliance Maladies Rares, National Institute of Health and Medical Research - Inserm, Conference of University Presidents – CPU and Conference of University Hospitals Directors-General). The Foundation carries out a mission of general interest: it aims at accelerating rare diseases research programs by improving the coordination among rare diseases players, contributing to the understanding of rare diseases, the development of new treatments and the improvement of patient's care and lives. Since its creation, 168 research projects were funded, for an amount granted in excess of €4M, and over 100 ‘proofs of concepts’ detected, half of which actively followed to help fill the gaps towards clinical development (e.g. strengthening of the proof of concept, orphan drug designation, agreement with a private partner, European funding, etc.).

Evans Syndrome in Children: Long-Term Outcome in a Prospective French National Observational Cohort.

Evans syndrome (ES) is a rare autoimmune disorder whose long-term outcome is not well known. In France, a collaborative pediatric network set up via the National Rare Disease Plan now provides comprehensive clinical data in children with this disease. Patients aged less than 18 years at the initial presentation of autoimmune cytopenia have been prospectively included into a national observational cohort since 2004. The definition of ES was restricted to the simultaneous or sequential association of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP). Cases were deemed secondary if associated with a primitive immunodeficiency or systemic lupus erythematosus. In December 2014, we analyzed the data pertaining to 156 children from 26 centers with ES whose diagnosis was made between 1981 and 2014. Median age (range) at the onset of cytopenia was 5.4 years (0.2–17.2). In 85 sequential cases, the time lapse between the first episodes of AIHA and ITP was 2.4 years (0.1–16.3). The follow-up period as from ES diagnosis was 6.5 years (0.1–28.8). ES was secondary, revealing another underlying disease, in 10% of cases; various associated immune manifestations (mainly lymphoproliferation, other autoimmune diseases, and hypogammaglobulinemia) were observed in 60% of cases; and ES remained primary in 30% of cases. Five-year ITP and AIHA relapse-free survival were 25 and 61%, respectively. Overall, 69% of children required one or more second-line immune treatments, and 15 patients (10%) died at the age of 14.3 years (1.7–28.1). To our knowledge, this is the first consistent long-term clinical description of this rare syndrome. It underscores the high rate of associated immune manifestations and the burden of long-term complications and treatment toxicity. Future challenges include (1) the identification of the underlying genetic defects inducing immune dysregulation and (2) the need to better characterize patient subgroups and second-line treatment strategies.

Rare diseases: role of the orthodontist in the management of implant rehabilitation

Article received: 11-08-2014. Accepted for publication: 04-09-2014. Address for correspondence: Sylvie Legris 47, Rue des Jacobins – 60000 Beauvais, France E-mail: syl-legris@orange.fr Implant rehabilitation is the main device covered by the French national health insurance system under the rare diseases plan. It improves care access for oligodontic patients requiring rehabilitation. The concept