Silvia Manea

A population-based registry as a source of health indicators for rare diseases: the ten-year experience of the Veneto Region’s rare diseases registry

BackgroundAlthough rare diseases have become a major public health issue, there is a paucity of population-based data on rare diseases. The aim of this epidemiological study was to provide descriptive figures referring to a sizable group of unrelated rare diseases.MethodsData from the rare diseases registry established in the Veneto Region of north-east Italy (population 4,900,000), referring to the years from 2002 to 2012, were analyzed. The registry is based on a web-based system accessed by different users. Cases are enrolled by two different sources: clinicians working at Centers of expertise officially designated to diagnose and care patients with rare diseases and health professionals working in the local health districts. Deaths of patients are monitored by Death Registry.ResultsSo far, 19,547 patients with rare diseases have been registered, and 23% of them are pediatric cases. The overall raw prevalence of the rare diseases monitored in the population under study is 33.09 per 10,000 inhabitants (95% CI 32.56-33.62), whilst the overall incidence is 3.85 per 10,000 inhabitants (95% CI 3.67-4.03). The most commonly-recorded diagnoses belong to the following nosological groups: congenital malformations (Prevalence: 5.45/10,000), hematological diseases (4.83/10,000), ocular disorders (4.47/10,000), diseases of the nervous system (3.51/10,000), and metabolic disorders (2,95/10,000). Most of the deaths in the study population occur among pediatric patients with congenital malformations, and among adult cases with neurological diseases. Rare diseases of the central nervous system carry the highest fatality rate (71.36/1,000). Rare diseases explain 4.2% of general population Years of Life Lost (YLLs), comparing to 1.2% attributable to infectious diseases and 2.6% to diabetes mellitus.ConclusionsOur estimates of the burden of rare diseases at population level confirm that these conditions are a relevant public health issue. Our snapshot of their epidemiology is important for public health planning purposes, going to show that population-based registries are useful tools for generating health indicators relating to a considerable number of rare diseases, rather than to specific conditions.

Italian experience of pediatric liver transplantation.

Abstract:  The SIGENP Group has created an Italian Liver Transplantation database. The study considers all patients under 18 yr of age on the waiting list or transplanted between 1984 and 2005. Demographic and clinical data were collected and a descriptive analysis was conducted. Kaplan–Meier survival curves were calculated and Cox’s proportional‐hazards regression analysis were performed to identify predictors of death after transplantation. Twenty‐two Italian centers took part and data were collected on 622 cases: only 53.8% of the transplants performed up until 1998 were carried out in Italy, while this was true of 97.7% of the operations performed between 1999 and 2005. Recipient survival curve analysis revealed one‐, two‐ and five‐yr survival rates of 88, 87 and 84%, respectively, and a significant improvement in survival after 1998 (p = 0.0322). Cox’s analysis identified the following risk factors for death after liver transplantation, i.e. transplantation before 1998, neoplasms or fulminant hepatic failure as indications, being in intensive care at the time of transplantation and retransplantation. The center where the transplant is performed also revealed an influence on patient survival. Thanks to a better patient follow‐up and more cooperation between specialists, the mean survival after liver transplantation is improving and Italian children can be transplanted in Italy.

The Epidemiology of Transition into Adulthood of Rare Diseases Patients: Results from a Population-Based Registry

Background: Despite the fact that a considerable number of patients diagnosed with childhood-onset rare diseases (RD) survive into adulthood, limited information is available on the epidemiology of this phenomenon, which has a considerable impact both on patients’ care and on the health services. This study describes the epidemiology of transition in a population of RD patients, using data from the Veneto Region Rare Diseases Registry (VRRDR), a web-based registry monitoring since 2002 a consistent number of RD in a defined area (4.9 million inhabitants). Methods: Longitudinal cohorts of patients born in the years 1988 to 1998 and enrolled in the VRRDR in their paediatric age were identified. Data referred to this group of patients, experiencing transition from paediatric to adult age during the years 2006–2016, are presented. Results: 2153 RD patients (44.1% females and 55.9% males) passed from childhood to adulthood in the study period, corresponding to a 3-fold increase from 2006 to 2016. The majority of these patients was affected by congenital anomalies (32.0%), by hematologic diseases (15.9%), eye disorders (12.1%) and neoplasms (7.9%). RD patients who experienced transition from paediatric age to adulthood represent the 9.2% of adult patients enrolled in the Registry at 31 December 2016. Conclusions: We described a subset of RD young adults experiencing transition into adulthood. The data reported can be considered as minimum values for estimating the size of this increasing population presenting specific transition needs. These figures are valuable for clinicians, patients and health planners. Public policy interventions are needed in order to promote dedicated care transition pathways in the broader framework of health policies devoted to RD.

Diagnosis of pervasive developmental disorders: when and how? An area-based study about health care providers

BackgroundPervasive developmental disorders (PDDs) can be very difficult to diagnose in children and to communicate such a diagnosis to their parents. Families of children with PDD learn of their child’s diagnosis long after the first symptoms are noted in the child’s behavior.MethodsAn area-based survey was conducted to assess all social and health care providers taking care of patients with PDDs in the Veneto Region (North-East Italy).ResultsOnly 28% of health care providers arrived at a definite diagnosis when the child was in his/her first year of age, 51% when the child was 2–3 years old and 21% from age of 4 years and up. On average, the latency between the time of the diagnosis and its communication to the family was 6.9 months. However, a number of families did not ever have a diagnosis communicated to them. Sometimes, 68% of the providers did not communicate a PDDs diagnosis to patient’s families, and 4% of them quite commonly.ConclusionThe well-known delay in making a diagnosis of PDDs has two distinct components: one relating to the difficulty of confirming a diagnosis of PDDs, the other, hitherto unrecognized, relating to the family being notified.

Children with Aniridia and Healthcare Systems: From Needs Assessment to a Comprehensive Program of Care and Assistance

Aniridia is a paradigm of the challenges posed to healthcare systems by childhood-onset rare diseases. The care of children with rare diseases presents peculiar aspects of complexity, due to the chronicity of these conditions and their disability spectrum, with different types of impairments and different severity levels, both within the same disease and the same patient across life. Recently, the provision of more comprehensive and effective care has been the aim of health policies specifically addressed to rare disease patients. The experience carried out in this field by the Veneto region (4.9 million inhabitants, north-east of Italy) is presented. An information system, accessed by all the different health professionals involved in patients’ care, has been developed. The system, adopted so far in other seven Italian Regions, allows patients’ recording, treatments’ prescription and provision and the formulation of care plans, according to the individual health care needs’ profile. The process of information sharing can effectively reduce the fragmentation of the care provided to these children and their families by a multiplicity of actors, medical and non-medical ones. Furthermore, it can ease the transition from paediatric to adult care, an emerging crucial issue in the care of children presenting special care needs, as children with aniridia.

The Role of a Registry in Familial Adenomatous Polyposis

The revolution in information technology has transformed the processes of collection, transmission, analysis, and storage of data, leading to the improvement of many large-scale systematic data-collection systems of health-related events. Familial adenomatous polyposis (FAP) represents a paradigmatic example of how the establishment of a data-collection system, starting from family tracing and evolving to more complex registration processes, increases knowledge on different aspects of the disease and ultimately can influence patients’ clinical management and professionals’ attitudes. Many years have passed since the establishment of the first polyposis registry at St Mark’s Hospital in London. An historical overview of FAP registries is presented, discussing potentials and limitations of population-based registries versus clinical registries. In the context of recently developed health policies on rare diseases, the experience of a registry monitoring FAP as well as other rare conditions, population-based, and at the same time with features of a clinical one, is presented. The value of FAP registries relies on their ability to provide a snapshot of aspects of disease as well as of its management, producing evidence and translating this into clinical practice. Our belief is that such registries, really patientcentered, should be developed as an integral part of the healthcare network, becoming connecting informative tools between vertical networks, namely centers of expertise, horizontal care networks, and other institutions and persons involved in the care of FAP patients.

The lot of shaken baby syndrome (SBS) cases: Follow-up of visual outcome and congnitive function

Purpose To study long-term outcome of SBS on visual and cognitive functions. Methods Case series of 10 children (7 M, 3 F) with confirmed SBS has been examined and followed-up. All chldren underwent a fundus evaluation by indirect ophtalmoscopy and wide-field digital ophtalmic camera (RetCam II) in the acute phase and until retinal hemorrhage resorption. The assessment was repeated at follow-up combined with ocular motility evaluation, visual field (BEFIE test), visual acuity by preferential looking tecnique (teller acuity cards), refractometry, cognitive-behavioural evaluations (Griffiths scales, Child Behaviour Check List), and family stress measurement (Parenting Stress Index). Results Mean age at acute episode of SBS: 6 months (range 2-20). Mean age at last follow-up evaluation: 27.6 months (range 4.5-41). At last follow-up evaluation: 1 out of 6 had a decreased visual acuity (cortical visual impairment), 3 out of 6 had mild-severe visual field deficits, 3 out of 6 has strabismus. None of the cases showed significant refractive errors. Due to age or severity of impairment and delay in global development, in any of the cases we were able to perform a recognition acuity test by symbols or E-charts. Cognitive and behavioural assessment demonstrated global delay and impaiments in speech/language development and attention problems. Conclusion SBS is characterized by severe long-term sequelae both in visual and cognitive function. Several visual impairments are observed, mainly related to cortial injury of visuo-spatial area. Although follow-up is difficult due to family history, there is strong indication for global assessment until scholar age where other impairments are demonstrated.