Registro Nazionale Malattie Rare: malformazioni congenite e acido folico

It is estimated that in Italy at least 3% of babies are born with some congenital malformation. Scientific evidence demonstrates that the intake of folic acid by a woman prior the conception and during the early stages of pregnancy plays a role in preventing neural tube defects and severe birth anomalies due to the lack of neural tube closure at either the upper or lower end during the third and fourth week of pregnancy. The intake of folic acid during the periconception period can reduce the risk of other neonatal malformations such as congenital heart defects, urinary tract anomalies, oral facial clefts, limb defects. The Italian Network for Folic Acid Promotion, established in 2004 and coordinated by the National Centre for Rare Diseases of the Istituto Suepriore di Sanit? has elaborated and diffused a recommendation for the periconceptional supplementation of folic acid. This article provides an overview of the available scientific evidence on the effect of folic acid in the prevention of congenital malformations and possible public health strategies.Si stima che nel nostro Paese circa il 3% dei nati siano affetti da malformazioni congenite: L\u27assunzione di acido folico prima del concepimento e nelle prime fasi della gravidanza ha un effetto preventivo riguardo ai difetti del tubo neurale, severe anomalie congenite determinate dalla mancata chiusura del tubo neurale che si completa nella terza-quarta settimana dal concepimento, e di altre malformazioni quali difetti cardiaci congeniti, anomalie congenite del tratto urinario, labio-palatoschisi, difetti in riduzione degli arti.Il Network Italiano Promozione Acido Folico, costituitosi nel 2004 e al cui coordinamento collabora il Centro Nazionale Malattie Rare dell\u27Istituto Superiore di Sanit?, ha elaborato e diffuso una raccomandazione per la supplementazione peri-concezionale di acido folico. Questo lavoro fornisce una revisione delle evidenze scientifiche disponibili in letteratura sull\u27efficacia dell\u27acido folico nella prevenzione di difetti congeniti e possibili strategie di sanit? pubblica

Reflections on the importance of cost of illness analysis in rare diseases: a proposal

In the field of rare diseases (RDs), the evidence standard is often lower than that required by health technology assessment (HTA) and payer authorities. In this commentary, we propose that appropriate economic evaluation for rare disease treatments should be initially informed by cost-of-illness (COI) studies conducted using a societal perspective. Such an approach contributes to improving countries’ understanding of RDs in their entirety as societal and not merely clinical, or product-specific issues. In order to exemplify how the disease burden’s distribution has changed over the last fifteen years, key COI studies for Hemophilia, Fragile X Syndrome, Cystic Fibrosis, and Juvenile Idiopathic Arthritis are examined. Evidence shows that, besides methodological variability and cross-country differences, the disease burden’s share represented by direct costs generally grows over time as novel treatments become available. Hence, to support effective decision-making processes, it seems necessary to assess the re-allocation of the burden produced by new medicinal products, and this approach requires identifying cost drivers through COI studies with robust design and standardized methodology

The rare malformation holoprosencephaly: pathogenesis, association with pregestational diabetes and the possible link with food pollutants

Background. Holoprosencephaly is a rare (1/16,000 livebirths) and severe brain malformation occurring during early embryogenesis. The malformation originates from absent or incomplete forebrain division and is associated with altered embryonic patterning. Objectives. A narrative review to identify and assess the evidence on non-genetic risk factors. Results. Genes involved include sonic hedgehog, Zinc finger protein, SIX homeobox 3. Pregestational diabetes, with periconceptional hyperglycaemia, is the main non-genetic  risk factor; increased oxidative stress in neuroectoderm, in particular neural crest cells, appears as the main mechanism. Several widespread pollutants, including inorganic arsenic, PFAS and PCBs, may increase the risk of pregestational diabetes by altering metabolic factors, including lipids and insulin. A scenario “widespread exposures-rare outcomes in susceptible subjects” suggests that exposure to dietary pollutants may increase the risk of pregestational diabetes, hence of holoprosencephaly in susceptible embryos. Conclusions. This complex pathway is plausible and worth being investigated; moreover, it highlights the importance of assessing risk factors, and the associated uncertainties,  in order to support primary prevention strategies for multifactorial malformations

Policies and actions to tackle rare diseases at European level

 Rare diseases (RDs) are defined by the European Union as life-threatening or chronically debilitating conditions, with a prevalence lower than 5 per 10 000 inhabitants. Around 6000 diseases are described, affecting between 6% and 8% of the European population. Due to their severity, diffusion and multi-faceted aspects, RD are an area where collaboration in public health, health care and research provides a major integrated added value. Main areas for policy actions include: the development and implementation of European Reference Networks, as a main strategy for sharing of knowledge, clinical expertise and foster research; integration of high-quality patient registries, biobanks, and bioinformatics support, as key infrastructure tools addressing research and healthcare needs; the implementation of National Plans on RD in EU Member States by sharing experiences, capacity building and linking national efforts through a common strategy at a European level; actions driven by the recommendations for primary prevention of congenital anomalies (the main RD group with multifactorial aetiology); policy provisions to fosterresearch and development of orphan drugs.

Registro nazionale malattie rare. Epidemiologia di 44 malformazioni congenite rare in Italia

The main purpose of this report is to provide health operators and the scientific community with information about the epidemiology of some Rare Congenital Malformations (RCMs). Statistical analysis was carried out on data of selected RCMs, detected both among births and induced abortions following prenatal malformation diagnosis. Data were collected by Birth Defects Registries according to homogeneous approaches, in order to produce valid estimates of prevalence rates

EPIRARE survey on activities and needs of rare disease registries in the European Union

The EPIRARE project[1] aims to build consensus and synergies for the development of an EU platform for rare disease registries and to address relevant regulatory, ethical and technical issues associated with the registration of rare disease patients. To this aim, a survey was carried out among existing rare disease registries and databases to get information on their objectives, needs, governance mechanisms, sustainability, and measures for the compliance with regulatory and ethical requirements and for quality assurance, as well as expectations from and opinions on a registry platform. Responses were received from 255 registries, of which 220 active registries were selected based on the completeness of the response. Among responding registries, 18, 61, 17 and 3% were international, national, regional or local. The fraction of registries population based, hospital based and following case series or cohorts was, respectively 56, 23 and 20%. Epidemiological and clinical researches were the most declared scopes (respectively 71, 61% in a multiple answer question) and characterized two clearly different clusters of registries. Treatment efficacy and safety was the scope indicated by 45% registries. A wide heterogeneity is found regarding the disease coding system used, with 62% using their own or no code. Twenty-seven percent registries are established by law or to comply with regulatory requirements, while 73% as part of research projects or as an autonomous decision of clinicians or patients. Half of the registries shares data with other registries and 33% with centres of expertise, while 30% do not exchange with neither of them or with bio banks. Registries were established with no initial funding (21%) or with funding by public authorities (37%), industries and foundations (21%), research institutes and hospitals (25%), patients associations (16%) and the European Commission (15%). After the initial phase, more registries (25%) are run without specific funding; frequency of funding sources remains stable but for the European Commission, which decreases to 6%. Different procedures are applied for quality assessment, but each of them is applied by 46-58% registries. A main governing body is not present in 34% registries and 48% registries have no policy to ensure long-term sustainability. Main needs expressed are financial support, improved communication strategies and more extended geographical coverage, data sources and registry networking. The vast majority of respondents (80%) is favourable to a platform for registries and 60% doubts that new legislation can facilitate registration. Popularly expected platform services are technological tools, specific expert advice and resources

Il MONITORAGGIO E I REGISTRI CHE ACCOMPAGNAMO UN LEA: Registri di casi o registri di incidenza ?

XXXLe MR raggruppano circa 7-8.000 forme morbose con una bassa diffusione nella popolazione (prevalenza <5/10.000), molto differenti tra loro, ma che dal punto di vista di sanit? pubblica vengono affrontate come un unico contenitore globale, in quanto rispondono a comuni problematiche assistenziali . Le MR richiedono competenze mediche esperte; costituiscono la sfida specialistica e tecnologica pi? avanzata (maggior parte delle MR sono di origine genetica); necessitano di avanzamenti nella ricerca scientifica ed in particolare della ricerca clinica . La bassa prevalenza si accompagna spesso a scarse conoscenze, ci? causa ritardo nella diagnosi e nel corretto trattamento . Le MR presentano numerosi quesiti, molto complessi legati a: organizzazione sanitaria, ricerca, eticam metodi per il monitoraggio; . Il quadro complessivo configura le MR come un grande tema di sanit? pubblica Partendo dalla necessit? di migliorare l\u27assistenza sanitaria dei pazienti con malattie rare, di pianificare gli interventi, nonche\u27 migliorare le conoscenze scientifiche sono state intraprese specifiche politiche sanitarie a riguardo: . Le MR sono considerate una priorit? di sanit? pubblica in tutti i PSN dal 1998 in poi . Sono stati predisposti specifici atti normativi (dal DLg.vo 124/1998 al DM 279/2001, agli Accordi Stato-Regioni) . Sono stati predisposti finanziamenti speciali per il cofinanziamento di specifici programmi regionali per l\u27attuazione dei PSN in matteria di MR . Tutte le iniziative in Italia sono coerenti con le indicazioni della Commissione Europe

Registri malformazioni Congenite della Toscana e dell\u27Emilia Romagna: aggiornamento sulla sorveglianza dei difetti del tubo neurale.

not availableIntroduzione: Il Network Italiano Promozione Acido Folico per la Prevenzione Primaria dei Difetti Congeniti ? una rete coordinata dall\u27ISS il cui obiettivo ? diffondere le conoscenze riguardo al ruolo dell\u27acido folico (AF) nel ridurre il rischio di malformazioni congenite gravi, in particolare dei difetti del tubo neurale (DTN), promuovendo il suo corretto impiego (raccomandazione della dose e del periodo di assunzione) tra le donne in et? fertile che stanno programmando una gravidanza. Nel 2006 sono stati pubblicati i risultati del progetto ISS "Registro Nazionale Malattie Rare" che ha utilizzato i dati dei registri dei difetti congeniti attivi in Italia (Nord-Est Italia, Emilia Romagna, Toscana, Campania, Sicilia), relativi al periodo 1996-2002, sulle malformazioni che sono o possono essere sensibili all\u27assunzione di AF (DTN, cardiopatie, schisi orofacciali, atresia/stenosi ano-rettale, onfalocele, difetti in riduzione degli arti e malformazioni urinarie). Per tutte le malformazioni analizzate, ad eccezione delle cardiopatie e delle malformazioni urinarie, era emersa una condizione di omogeneit?, sia per i nati che per i casi totali, comprensivi delle interruzioni di gravidanza (IVG), che aveva consentito di pervenire a valide stime di prevalenza a livello nazionale, indispensabili anche ai fini di una valutazione dell\u27impatto dell\u27utilizzo dell\u27AF negli anni successivi. Metodi: E\u27 stato effettuato un aggiornamento dei dati raccolti dai Registri Malformazioni Congenite della Toscana e dell\u27Emilia Romagna nel periodo 1996-2006 su circa 620.000 nati sorvegliati. I casi comprendono i nati vivi, le morti fetali oltre le 20 settimane di et? gestazionale e le IVG con DTN, anencefalia, spina bifida ed encefalocele. Sono state effettuate analisi del trend sui dati individuali di ciascun registro e sui dati complessivi rilevati dall\u27insieme dei due registri. Risultati: Sui dati totali non si segnala alcun trend statisticamente significativo, mentre sono state individuate condizioni di eterogeneit? a causa di andamenti non lineari della prevalenza osservata, dovuti alla presenza di alcuni picchi annuali (per i DTN negli anni 1998, 2000 e 2004, per l\u27anencefalia nel 1998 e per la spina bifida nel 1998 e nel 2004). Conclusioni: Tenendo in debita considerazione la modesta capacit? di risoluzione dello strumento osservazionale su un breve periodo, l\u27assenza di un trend decrescente per i DTN non ci permette di ipotizzare un effetto ascrivibile ad azione preventiva secondaria alla campagna di sensibilizzazione seguita all\u27attivazione del Network Italiano Promozione Acido Folico nel 2004. Presso l\u27ISS ? stato programmato un progetto specifico che comprende tra i vari obiettivi anche un\u27attivit? di sorveglianza da svolgersi in aree selezionate delle regioni coperte dai Registri MC. I risultati conseguiti consentiranno di valutare le dimensioni del fenomeno valutando l\u27impatto delle azioni di prevenzione primaria dell\u27utilizzo in epoca periconcezionale dell\u27AF, cos? come di aggiornare i risultati relativi alle precedenti indagini conoscitive sull\u27AF

The EPIRARE proposal of a set of indicators and common data elements for the European platform for rare disease registration

BACKGROUND: The European Union acknowledges the relevance of registries as key instruments for developing rare disease (RD) clinical research, improving patient care and health service (HS) planning and funded the EPIRARE project to improve standardization and data comparability among patient registries and to support new registries and data collections. METHODS: A reference list of patient registry-based indicators has been prepared building on the work of previous EU projects and on the platform stakeholders' information needs resulting from the EPIRARE surveys and consultations. The variables necessary to compute these indicators have been analysed for their scope and use and then organized in data domains. RESULTS: The reference indicators span from disease surveillance, to socio-economic burden, HS monitoring, research and product development, policy equity and effectiveness. The variables necessary to compute these reference indicators have been selected and, with the exception of more sophisticated indicators for research and clinical care quality, they can be collected as data elements common (CDE) to all rare diseases. They have been organized in data domains characterized by their contents and main goal and a limited set of mandatory data elements has been defined, which allows case notification independently of the physician or the health service. CONCLUSIONS: The definition of a set of CDE for the European platform for RD patient registration is the first step in the promotion of the use of common tools for the collection of comparable data. The proposed organization of the CDE contributes to the completeness of case ascertainment, with the possible involvement of patients and patient associations in the registration process.This work is part of the activities of the project titled “Building Consensus and synergies for the EU Registration of Rare Disease Patients” (EPIRARE), funded by the European Commission within the framework of the Health Project, Work Plan 2010 (Grant n. 20101202).S