Yllka Kodra

Health-Related Quality of Life in Patients with Neurofibromatosis Type 1

Background/Aims: Neurofibromatosis type 1 (NF1), a genetic condition most commonly characterized by the presence of dermal neurofibromas and café au lait macules, has a significant impact upon quality of life (QoL). The study aimed to assess the impact of NF1 on QoL. Methods: A total of 129 patients with NF1 completed the study questionnaires in an Italian academic dermatological centre and a neurofibromatosis clinic at the University of Rome. Results: All domains of general-health-related QoL were affected.Patients with serious cosmetic problemsreported a greater impact on the emotional domain. Conclusion: In our study, the impact of the cosmetic features on QoL had the greatest importance. This survey demonstrates the usefulness of QoL measurements in supplementing clinical assessments.

Mortality associated with neurofibromatosis type 1: A study based on Italian death certificates (1995-2006)

BackgroundPersons affected by neurofibromatosis type 1 (NF1) have a decreased survival, yet information on NF1-associated mortality is limited.Methods/AimThe National Mortality Database and individual Multiple-Causes-of-Death records were used to estimate NF1-associated mortality in Italy in the period 1995-2006, to compare the distribution of age at death (as a proxy of survival) to that of the general population and to evaluate the relation between NF1 and other medical conditions by determining whether the distribution of underlying causes of NF1-associated deaths differs from that of general population.ResultsOf the nearly 6.75 million deaths in the study period, 632 had a diagnosis of NF1, yet for nearly three-fourths of them the underlying cause was not coded as neurofibromatosis. The age distribution showed that NF1-associated deaths also occurred among the elderly, though mortality in early ages was high. The mean age for NF1-associated death was approximately 20 years lower than that for the general population. The gender differential may suggest that women are affected by more severe NF1-related complications, or they may simply reflect a greater tendency for NF1 to be reported on the death certificates of young women. Regarding the relation with other medical conditions, we found an excess, as the underlying cause of death, for malignant neoplasm of connective and other soft tissue and brain, but not for other sites. We also found an excess for obstructive chronic bronchitis and musculoskeletal system diseases among elderly persons.ConclusionThis is the first nationally representative population-based study on NF1-associated mortality in Italy. It stresses the importance of the Multiple-Causes-of-Death Database in providing a more complete picture of mortality for conditions that are frequently not recorded as the underlying cause of death, or to study complex chronic diseases or diseases that have no specific International Classification of Diseases code, such as NF1. It also highlights the usefulness of already available data when a surveillance system is not fully operational.

Quality of life assessment in a sample of patients affected by Prader–Willi syndrome

Aim:  The goals of this study are to investigate the quality of life of Prader–Willi syndrome patients and to evaluate the relationship between quality of life and the clinical picture.

Current status of Italian Registries on inherited bleeding disorders.

Inherited bleeding disorders are a group of congenital coagulopathies resulting when deficiencies of the proteins responsible for coagulation, platelet function or fibrinolysis occur. Haemophilia A (HA, deficiency of factor VIII), Haemophilia B (HB, deficiency of factor IX) and von Willebrand Disease (vWD) are the most frequent, being >90% of all inherited bleeding disorders with a prevalence of 0.5, 0.1 and 1–5/10,000 respectively1–3. Other rare inherited bleeding disorders are represented by deficiencies of factor I, II, V, VII, X, XI, XII, XIII, combined V+VIII, combined vitamin K-dependent factors, with a general population prevalence between 1/500,000 and 1/2,000,0004. Inherited bleeding disorders require wide-ranging care and effective management within a multidisciplinary team setting. The modern treatments of inherited bleeding disorders are now remarkably effective, although expensive. In Italy the epidemiological data on inherited bleeding disorders derive from three registries: The Italian National Registry for Rare Diseases (RNMR); The National Registry of Congenital Coagulopathies (RNCC); The Haemophilia Database of the Italian Association of Haemophilia Centres (AICE). These registries differ in terms of organisation, purpose and data collection process. A general description and results for each registry is reported as follow.

The Italian National Rare Diseases Registry.

INTRODUCTION Rare disease registries are a priority at European level and specific actions are being implemented by the European Commission to support their development.In Italy, a National Registry of rare diseases has been established in 2001 as a network of regional registries. The latter have gradually been established and the full coverage of the Italian territory was attained during 2011. METHODS Here we describe the basic features of the National Registry of rare diseases; the activities carried out to promote consistent operations in the regional registries; and the overall quality and composition of the records collected. RESULTS After a validation process, including removal of duplicate records, 110,841 records of patients with rare diseases, single and with group denominations, are stored in the National Registry of rare diseases. They correspond to the overall diagnoses communicated to national registry by regional registries up to 30 June 2012.The quality of the data collected by the the National Registry of rare diseases has been assessed with respect to completeness and consistency of procedures. Variables characterising case and diagnosis showed a very limited number of missing values. Records reported at least one case of 485 rare conditions. DISCUSSION To date, the National Registry of rare diseases is a surveillance system with the main objective of producing epidemiologic evidence on rare diseases in Italy, and of supporting policy making and health services planning.Data quality still represents a limitation for any sound epidemiological estimate of rare diseases in Italy. However, improvements of the quality of collected data and the completeness of case notifications should be strengthened.

The RD-Connect Registry & Biobank Finder: a tool for sharing aggregated data and metadata among rare disease researchers

In rare disease (RD) research, there is a huge need to systematically collect biomaterials, phenotypic, and genomic data in a standardized way and to make them findable, accessible, interoperable and reusable (FAIR). RD-Connect is a 6 years global infrastructure project initiated in November 2012 that links genomic data with patient registries, biobanks, and clinical bioinformatics tools to create a central research resource for RDs. Here, we present RD-Connect Registry & Biobank Finder, a tool that helps RD researchers to find RD biobanks and registries and provide information on the availability and accessibility of content in each database. The finder concentrates information that is currently sparse on different repositories (inventories, websites, scientific journals, technical reports, etc.), including aggregated data and metadata from participating databases. Aggregated data provided by the finder, if appropriately checked, can be used by researchers who are trying to estimate the prevalence of a RD, to organize a clinical trial on a RD, or to estimate the volume of patients seen by different clinical centers. The finder is also a portal to other RD-Connect tools, providing a link to the RD-Connect Sample Catalogue, a large inventory of RD biological samples available in participating biobanks for RD research. There are several kinds of users and potential uses for the RD-Connect Registry & Biobank Finder, including researchers collaborating with academia and the industry, dealing with the questions of basic, translational, and/or clinical research. As of November 2017, the finder is populated with aggregated data for 222 registries and 21 biobanks.

The Italian National Rare Diseases Registry: a model of comparison and integration with Hospital Discharge Data

BACKGROUND Italy has been the first country at European level to implement a population-based public health registry dedicated to rare diseases. This study describes the current situation of the Italian National Rare Diseases Registry (NRDR) and compares its data with those from the National Hospital Discharge Database (HDD). METHODS Three rare diseases were analysed: Huntington disease (HD), Hereditary Haemorragic Telangiectasia (HHT) and Prader-Willi Syndrome (PWS), selected for their different characteristics. The two sources (NRDR and HDD) were linked: incidence rate ratio (IRR), sensitivity and predictive positive value (PPV) were calculated. RESULTS Incidence rates from NRDR and from HDD were compared by age groups, and IRR calculated: 1.08 for HD, 1.41 for HHT, 1.21 for PSW. For HD, sensitivity was 0.52 and PPV 0.48; for HHT sensitivity was 0.71 and PPV 0.52; for PWS the sensitivity was 0.71 and PPV 0.58. We found a strong regional variability in the results. CONCLUSIONS The integrated use of the two sources helps tracking those cases that are not captured by the Registry; further, it is a precious tool to accurately describe clinical histories of rare disease affected individuals, in terms of concomitant pathologies and medical procedures performed during hospitalization.

Italian Registries on Bleeding Disorders

To the Editor:We read with interest the review “The Growing Number of Hemophilia Registries: Quantity vs. Quality” by Keipert et al. on the current status of hemophilia registries in Europe. The authors discussed the diversity of the registries and underlined the importance of the harmonization to develop a pan-European strategy. The authors mentioned the Italian situation with some mistakes and inaccuracies, citing three different registries with no interoperability, that instead are strictly connected, so we need to supply an overview of these three tools. The correct data are reported in Table 1. The National Registry of Congenital Coagulopathies is a specific pathology registry, implemented at the National Institute of Health (ISS) and realized, in the current status, in stringent collaboration with the Italian Hemophilia Centers Association (AICE) and Patient’s Association (FedEmo). AICE is continuously monitoring and encouraging the participation of hemophilia treatment centers to data transmission, based on an electronic platform in which local physicians send data to the AICE database, shared with the ISS. AICE has identified ISS as the national organization in charge of the analysis and diffusion of the epidemiological data and the association itself utilizes the database as a research oriented instrument providing data for clinical studies. The National Registry of Congenital Coagulopathies supplies epidemiological data on the prevalence of the different congenital bleeding disorders in Italy, on therapy complications (infections and inhibitor antibodies), and on the needs of drugs for hemophilia treatment therapy. Data are published on the website of the ISS and through scientific publications. The Italian National Registry for Rare Diseases, established by law in 2001, is located at the National Centre for Rare Diseases of ISS. It collects data on 495 rare diseases, among which are congenital bleeding disorders. The person responsible for this registry is involved in several European projects (RD-Connect, EUCERD, and EPIRARE). Among the future directions of the Italian National Registry for Rare Diseases, there is the need to develop registries on specific rare diseases, to better understand their natural history, and, in this context, bleeding disorders are the subject of a collaboration with the National Registry of Congenital Coagulopathies. The Italian experience, aimed to the optimization of a national registry on bleeding disorders, can be considered adequate and can share reliable data at an international level. We agree with the value of a multinational registry, based on integration and harmonization of data, which should be the result of a network of different national registries, able to monitor and increase long-term safety of all the patients.

The Italian National Centre for Rare Diseases: where research and public health translate into action

The Italian National Centre for Rare Diseases (CNMR) is the result of a strategic approach, which the National Institute of Health (ISS) has been developing for more than 10 years, to deal with the public health challenges associated with rare diseases (RDs). The CNMR was formally established within the ISS in 20081. Its mission is to promote and develop experimental research and public health actions, as well as to provide technical expertise and information on RDs and orphan drugs, for the prevention, treatment and surveillance of these diseases. It is also the national focal point for information and communication for patients suffering from one of several thousand RDs, and for their families, collaborating with the national organisations of patients suffering from RDs. The Centre employs a wide range of scientific and technical expertise from various fields (medicine, genetics, molecular biology, epidemiology, public health, psychology, sociology etc.) and holds a network of national and international collaborations, which allow the development of a sound and integrated approach to RDs. The CNMR provides expert advice to the Italian Ministry of Health (MOH), to the National Health Council, to the National Health Service (NHS), and collaborates with the Regions, which are responsible for the provision of health services in the Italian devolved health system. Expert advice on RDs is also provided at EU and at international level. Since its establishment, the Centre has developed into a lively and propulsive hub for experimental research, public health, information, communication and training on RDs in Italy, and for patient empowerment. In addition, it has contributed to networks and scientific boards at national, European and international level and has implemented a number of strategic projects on RDs. The Centre is in continuous evolution in order to follow closely the pace of science and research, the emerging needs of patients, the solicitations of policy makers, and the demands of the health system.

Recommendations for Improving the Quality of Rare Disease Registries

Rare diseases (RD) patient registries are powerful instruments that help develop clinical research, facilitate the planning of appropriate clinical trials, improve patient care, and support healthcare management. They constitute a key information system that supports the activities of European Reference Networks (ERNs) on rare diseases. A rapid proliferation of RD registries has occurred during the last years and there is a need to develop guidance for the minimum requirements, recommendations and standards necessary to maintain a high-quality registry. In response to these heterogeneities, in the framework of RD-Connect, a European platform connecting databases, registries, biobanks and clinical bioinformatics for rare disease research, we report on a list of recommendations, developed by a group of experts, including members of patient organizations, to be used as a framework for improving the quality of RD registries. This list includes aspects of governance, Findable, Accessible, Interoperable and Reusable (FAIR) data and information, infrastructure, documentation, training, and quality audit. The list is intended to be used by established as well as new RD registries. Further work includes the development of a toolkit to enable continuous assessment and improvement of their organizational and data quality.