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Rare Diseases Epidemiology Research: The State-of-the-Art and Future Perspectives

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A special issue of International Journal of Environmental Research and Public Health (ISSN 1660-4601). This special issue belongs to the section "Environmental Health".

Deadline for manuscript submissions: closed (31 July 2020) | Viewed by 47692

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Special Issue Editor

Dr. Yllka Kodra

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Guest Editor

MD, PhD, National Centre for Rare Diseases, Istituto Superiore di Sanità, 00162 Rome, Italy
Interests: rare diseases; epidemiology; public health; patient disease registry; coding/classification; Patient-Centered Outcome Measures (PCOM); Neonatal Screening

Special Issue Information

Dear colleagues,

Rare diseases, as the name suggest, incorporate a statistical definition. This means that a single rare disease affects a small number of the population (less than 5 person per 10,000 citizens in Europe). But from medical point of view, there is not a unique definition: for health care providers rare diseases are complex and heterogeneous mosaic of an estimated 5000–8000 conditions with low knowledge like natural history, delay of diagnosis bottlenecks in drug development, prevention treatment and epidemiological data.

Although, The European Union has put much effort into funding rare diseases research and setting up European Reference Networks (ERN) to tackle rare diseases and complex conditions, it is important to understand that the burden of rare diseases continues to be public health priority.

At the heart of these efforts, is data generation gathered from well structured epidemiological research studies. Higher-volume and higher-variety of data are increasingly made available online and there is a need to better interpreted and managed them.

This special issue of International Journal of Environmental Research and Public Health (IJERPH) aim to present:

excellent research activities working on a particular rare disease, to improve epidemiology, to understand and facilitate diagnosis, and develop new therapies for rare diseases
model of high-quality, cost-effective healthcare, including prevention
relevant source of information system available for rare diseases (example registries, shared knowledge platforms, research network)
key rare diseases policy documents and legislation
tools, standards, guidelines and data sharing that adheres to the interoperability principles
case study of active involvement of patient as partner and as expert in epidemiological research studies.

Papers addressing these topics are invited for this Special Issue, with the overall aim not only map the state of art but also outline likely future developments in this rapidly developing field of complex medicine, such as rare diseases.

Dr. Yllka Kodra
Guest Editor

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Keywords

Rare diseases
Epidemiology
Clinical research
Information system
Standards
Interoperability
Patient registries
Prevention
Data sharing
Neonatal screening

Published Papers (14 papers)

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Research

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19 pages, 2503 KiB

Open AccessArticle

Epidemiological Challenges in Rare Bleeding Disorders: FVIII Inhibitor Incidence in Haemophilia A Patients—A Known Issue of Unknown Origin

by Christine Keipert, Ursula Drechsel-Bäuerle, Doris Oberle, Mirco Müller-Olling and Anneliese Hilger

Int. J. Environ. Res. Public Health 2021, 18(1), 225; https://doi.org/10.3390/ijerph18010225 - 30 Dec 2020

Cited by 6 | Viewed by 2528

Abstract

There is a broad range of factor products approved in Germany for haemophilia A treatment. Since the introduction of recombinant coagulation factor VIII (FVIII) products in the 1990s, there has been substantial debate whether there is a difference in inhibitor incidence between single FVIII products or product classes. Neither haemophilia registries nor clinical studies, including a randomised controlled clinical trial, provided a consistent and definite answer. The reasons were mainly related to methodological challenges in conducting controlled studies in a rare disease. In this analysis, the most relevant epidemiological challenges and main problems were examined, including study bias, potential overlap of individual studies and advanced development of therapy and methods in the course of time. Meta-analyses on two levels showed that therapies using recombinant products resulted in different event rates when compared to plasma-derived products. These results are accompanied by substantial study heterogeneity evidenced by Cochran’s Q tests. Only three studies have been identified that meet the standards of current clinical guidance. To finally resolve this ongoing and disputable safety issue of replacement therapy, collaboration among registry owners, academia and regulators must be fostered. Full article

(This article belongs to the Special Issue Rare Diseases Epidemiology Research: The State-of-the-Art and Future Perspectives)

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17 pages, 4961 KiB

Open AccessArticle

Managing Cystic Fibrosis in Polish Healthcare

by Marta Rachel, Stanisław Topolewicz, Andrzej Śliwczyński and Sabina Galiniak

Int. J. Environ. Res. Public Health 2020, 17(20), 7630; https://doi.org/10.3390/ijerph17207630 - 20 Oct 2020

Cited by 12 | Viewed by 2880

Abstract

The quality and length of life of patients with cystic fibrosis (CF) are determined by a number of factors including the quality of healthcare received by patients, as well as access to drug programs dedicated to this particular disease. The purpose of this paper is to present an overview of changes in the average life expectancy and mortality rate of the CF population in Poland between 2000 and 2018. Furthermore, we would like to evaluate access to healthcare services, including the drug program, guaranteed by public healthcare system, and funded by National Health Fund (NHF). The average life expectancy of patients with CF increased in the period in question from ca. 14.5 ± 7.6–24.5 ± 8.9 years (mean ± SD, p = 0.0001). We have observed a drop in the number of deaths in paediatric age during that period. Despite the increase in life expectancy, the use of health resources in patients with CF, especially the drug program, is dramatically low. Considering the fact that in Poland there was no active countrywide CF registry, now it is possible to estimate the frequency of use of CF healthcare services in various provinces exclusively on the basis of database maintained by the Polish NHF. Full article

(This article belongs to the Special Issue Rare Diseases Epidemiology Research: The State-of-the-Art and Future Perspectives)

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16 pages, 559 KiB

Open AccessArticle

The Value of Case Reports in Systematic Reviews from Rare Diseases. The Example of Enzyme Replacement Therapy (ERT) in Patients with Mucopolysaccharidosis Type II (MPS-II)

by Miguel Sampayo-Cordero, Bernat Miguel-Huguet, Andrea Malfettone, José Manuel Pérez-García, Antonio Llombart-Cussac, Javier Cortés, Almudena Pardo and Jordi Pérez-López

Int. J. Environ. Res. Public Health 2020, 17(18), 6590; https://doi.org/10.3390/ijerph17186590 - 10 Sep 2020

Cited by 13 | Viewed by 3272

Abstract

Background: Case reports are usually excluded from systematic reviews. Patients with rare diseases are more dependent on novel individualized strategies than patients with common diseases. We reviewed and summarized the novelties reported by case reports in mucopolysaccharidosis type II (MPS-II) patients treated with enzyme replacement therapy (ERT). Methods: We selected the case reports included in a previous meta-analysis of patients with MPS-II treated with ERT. Later clinical studies evaluating the same topic of those case reports were reported. Our primary aim was to summarize novelties reported in previous case reports. Secondary objectives analyzed the number of novelties evaluated in subsequent clinical studies and the time elapsed between the publication of the case report to the publication of the clinical study. Results: We identified 11 innovative proposals in case reports that had not been previously considered in clinical studies. Only two (18.2%) were analyzed in subsequent nonrandomized cohort studies. The other nine novelties (81.8%) were analyzed in later case reports (five) or were not included in ulterior studies (four) after more than five years from their first publication. Conclusions: Case reports should be included in systematic reviews of rare disease to obtain a comprehensive summary of the state of research and offer valuable information for healthcare practitioners. Full article

(This article belongs to the Special Issue Rare Diseases Epidemiology Research: The State-of-the-Art and Future Perspectives)

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11 pages, 422 KiB

Open AccessArticle

Biomedical Holistic Ontology for People with Rare Diseases

by Laia Subirats, Jordi Conesa and Manuel Armayones

Int. J. Environ. Res. Public Health 2020, 17(17), 6038; https://doi.org/10.3390/ijerph17176038 - 19 Aug 2020

Cited by 5 | Viewed by 3023

Abstract

This research provides a biomedical ontology to adequately represent the information necessary to manage a person with a disease in the context of a specific patient. A bottom-up approach was used to build the ontology, best ontology practices described in the literature were followed and the minimum information to reference an external ontology term (MIREOT) methodology was used to add external terms of other ontologies when possible. Public data of rare diseases from rare associations were used to build the ontology. In addition, sentiment analysis was performed in the standardized data using the Python library Textblob. A new holistic ontology was built, which models 25 real scenarios of people with rare diseases. We conclude that a comprehensive profile of patients is needed in biomedical ontologies. The generated code is openly available, so this research is partially reproducible. Depending on the knowledge needed, several views of the ontology should be generated. Links to other ontologies should be used more often to model the knowledge more precisely and improve flexibility. The proposed holistic ontology has many benefits, such as a more standardized computation of sentiment analysis between attributes. Full article

(This article belongs to the Special Issue Rare Diseases Epidemiology Research: The State-of-the-Art and Future Perspectives)

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14 pages, 796 KiB

Open AccessArticle

Social Economic Costs, Health-Related Quality of Life and Disability in Patients with Cri Du Chat Syndrome

by Yllka Kodra, Marianna Cavazza, Marta de Santis, Andrea Guala, Maria-Elena Liverani, Patrizio Armeni, Maura Masini and Domenica Taruscio

Int. J. Environ. Res. Public Health 2020, 17(16), 5951; https://doi.org/10.3390/ijerph17165951 - 17 Aug 2020

Cited by 7 | Viewed by 5707

Abstract

Background: Cri du Chat syndrome (CdC) is a rare disease caused by the deletion on the short arm of the chromosome 5, with an incidence of 1:15,000 to 1:50,000 live-born infants. No study at international level has assessed the costs, Quality of Life (QoL) and Disability through standardized quantitative tools. The aim is to estimate economic costs related to CdC from a societal perspective, to assess the QoL and Disability in patients with CdC along with their caregivers in Italy. Methods: A cross-sectional study of patients with Cri du Chat in Italy was carried out. A cost of illness approach from a societal perspective was used to estimate cost, and a micro-costing method was adopted. The QoL was measured with EuroQol 5-domain (EQ-5D) questionnaire and Disability by using World Health Organization Disability Assessment Schedule 36 item (WHODAS 2.0). Results: A total of 76 questionnaires were collected from caregivers taking care of 40 adult patients and 36 minor patients. All patients need a carer and the principal caregiver is commonly informal carer or a family member (93%). The EQ-5D VAS score for patients is 65.5 (SD = 22.4) out of 100; while the most important compromised areas of QoL are usual activities and self-care. The overall WHODAS 2.0 score is 65% (0 = no disability; 100 = full disability). The average annual cost of a patient with Cri du Chat in our population is €87,856.24; the main cost item of patients with Cri du Chat syndrome is informal care (i.e., €76,981.69 yearly) since it constitutes the 87% of total costs. Results highlight the burden of CdC in terms of its impact on QoL and Disability for patients and caregivers in Italy, with a score much lower than that of general population. The disease is associated with considerable costs of informal care. Conclusions: Cri du Chat syndrome was found to be linked with a significant socioeconomic impact which is dominated by direct non-healthcare informal costs. Full article

(This article belongs to the Special Issue Rare Diseases Epidemiology Research: The State-of-the-Art and Future Perspectives)

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12 pages, 507 KiB

Open AccessArticle

The Economic Impact and Health-Related Quality of Life of Spinal Muscular Atrophy. An Analysis across Europe

by Luz María Peña-Longobardo, Isaac Aranda-Reneo, Juan Oliva-Moreno, Svenja Litzkendorf, Isabelle Durand-Zaleski, Eduardo Tizzano and Julio López-Bastida

Int. J. Environ. Res. Public Health 2020, 17(16), 5640; https://doi.org/10.3390/ijerph17165640 - 05 Aug 2020

Cited by 21 | Viewed by 3939

Abstract

Background: this study aimed to estimate the economic impact and health-related quality of life (HRQOL) of patients with spinal muscular atrophy (SMA) in three European countries. It was used a cross-sectional study carried out in France, Germany, and the United Kingdom. Data were collected from July 2015 to November 2015. Healthcare costs (hospitalizations, emergencies, medical tests, drugs used, visits to general practitioners (GPs) and specialists, medical material and healthcare transport), and non-healthcare costs (social services and informal care) were identified and valued. EuroQol instruments, the Zarit interview, and the Barthel Index were also used to reflect the burden and the social impact of the disease beyond the cost of healthcare. Results: we included 86 children with SMA, 26.7% of them had Type I, and 73.3% Type II or III. The annual average cost associated with SMA reaches €54,295 in the UK, €32,042 in France and €51,983 in Germany. The direct non-healthcare costs ranged between 79–86% of the total cost and the informal care costs were the main component of these costs. Additionally, people suffering from this disease have a very low health-related quality of life, and there are large differences between countries. Conclusions: SMA has a high socioeconomic impact in terms of healthcare and social costs. It was also observed that the HRQOL of affected children was extremely reduced. The figures shown in this study may help to design more efficient and equitable policies, with special emphasis on the support provided to the families or on non-healthcare aid. Full article

(This article belongs to the Special Issue Rare Diseases Epidemiology Research: The State-of-the-Art and Future Perspectives)

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12 pages, 2406 KiB

Open AccessArticle

The Italian External Quality Assessment Program for Cystic Fibrosis Sweat Chloride Test: Does Active Participation Improve the Quality?

by Marco Salvatore, Annalisa Amato, Giovanna Floridia, Federica Censi, Gianluca Ferrari, Fabrizio Tosto, Rita Padoan, Valeria Raia, Natalia Cirilli, Giuseppe Castaldo, Ettore Capoluongo, Ubaldo Caruso, Carlo Corbetta and Domenica Taruscio

Int. J. Environ. Res. Public Health 2020, 17(9), 3196; https://doi.org/10.3390/ijerph17093196 - 04 May 2020

Cited by 2 | Viewed by 2310

Abstract

(1) Background: Diagnostic testing for cystic fibrosis (CF) is based on a sweat chloride test (SCT) considering the appropriate signs and symptoms of the disease and results of a gene mutation analysis. In 2014, the Istituto Superiore di Sanità (ISS) established a pilot Italian external quality assessment program for CF SCT (Italian EQA-SCT), which is now a third party service carried out by the ISS. (2) Methods: The ongoing scheme is prospective, enrollment is voluntary, and the payment of a fee is required. Results are shared through a dedicated web-facility. Assessment covers the analysis, interpretation, and reporting of results. (3) Results: Thirteen, fifteen, sixteen, and fifteen different laboratories, respectively, participated from 2015 to 2016 and from 2018 to 2019 in the Italian EQA-SCT scheme. Eleven different laboratories participated each year in all four rounds of the Italian EQA-SCT. (4) Conclusions: The overall results obtained from the laboratories participating constantly clearly show that their qualitative and quantitative performance improved significantly. This is due to the opportunity—after receiving the EQA results—to constantly review their performance and address any inconsistencies. We firmly believe that participation in the EQA program will improve the quality of participating laboratories and that EQA participation should become mandatory as a fundamental requirement for laboratory accreditation. Full article

(This article belongs to the Special Issue Rare Diseases Epidemiology Research: The State-of-the-Art and Future Perspectives)

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10 pages, 830 KiB

Open AccessArticle

Primary Sclerosing Cholangitis: Burden of Disease and Mortality Using Data from the National Rare Diseases Registry in Italy

by Marco Carbone, Yllka Kodra, Adele Rocchetti, Valerio Manno, Giada Minelli, Alessio Gerussi, Vincenzo Ronca, Federica Malinverno, Laura Cristoferi, Annarosa Floreani, Pietro Invernizzi, Susanna Conti and Domenica Taruscio

Int. J. Environ. Res. Public Health 2020, 17(9), 3095; https://doi.org/10.3390/ijerph17093095 - 29 Apr 2020

Cited by 18 | Viewed by 2779

Abstract

Introduction: Studies on the epidemiology of primary sclerosing cholangitis (PSC) are mainly based on tertiary referral centers; and are retrospective case series susceptible to selection bias. The aim of this study was to estimate incidence; survival and cause of mortality of PSC in Italy; using population-based data. Methods: Data collected from the National Rare Diseases Registry (RNMR) and the National Mortality Database (NMD) were integrated and analyzed. Results: We identified 502 PSC incident cases. The crude incidence rate between 2012 and 2014 was 0.10 per 100,000 individuals. Sixty percent were male; mean age at disease onset and at diagnosis were 33 and 37 years; respectively; highlighting a mean diagnostic delay of 4 years. The rate of interregional mobility was 12%. Ten-year survival was 92%. In 32% of cases the cause of death was biliary-related; 12% died of biliary or gallbladder cancer. Conclusions: For rare diseases such as PSC; population-based cohort’s studies are of paramount importance. Incidence rates of PSC in Italy are markedly lower and survival much longer than the ones reported from tertiary; single-centre series. Moreover; the diagnostic delay and the patient interregional mobility highlights the need for increasing awareness on the disease and for resource reallocation among Italian regions within the National Health Service Full article

(This article belongs to the Special Issue Rare Diseases Epidemiology Research: The State-of-the-Art and Future Perspectives)

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Review

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14 pages, 809 KiB

Open AccessReview

Rare Pathogenic Copy Number Variation in the 16p11.2 (BP4–BP5) Region Associated with Neurodevelopmental and Neuropsychiatric Disorders: A Review of the Literature

by Natália Oliva-Teles, Maria Chiara de Stefano, Louise Gallagher, Severin Rakic, Paula Jorge, Goran Cuturilo, Silvana Markovska-Simoska, Isabella Borg, Jeanne Wolstencroft, Zeynep Tümer, Adrian J. Harwood, Yllka Kodra and David Skuse

Int. J. Environ. Res. Public Health 2020, 17(24), 9253; https://doi.org/10.3390/ijerph17249253 - 10 Dec 2020

Viewed by 3153

Abstract

Copy number variants (CNVs) play an important role in the genetic underpinnings of neuropsychiatric/neurodevelopmental disorders. The chromosomal region 16p11.2 (BP4–BP5) harbours both deletions and duplications that are associated in carriers with neurodevelopmental and neuropsychiatric conditions as well as several rare disorders including congenital malformation syndromes. The aim of this article is to provide a review of the current knowledge of the diverse neurodevelopmental disorders (NDD) associated with 16p11.2 deletions and duplications reported in published cohorts. A literature review was conducted using the PubMed/MEDLINE electronic database limited to papers published in English between 1 January 2010 and 31 July 2020, describing 16p11.2 deletions and duplications carriers’ cohorts. Twelve articles meeting inclusion criteria were reviewed from the 75 articles identified by the search. Of these twelve papers, eight described both deletions and duplications, three described deletions only and one described duplications only. This study highlights the heterogeneity of NDD descriptions of the selected cohorts and inconsistencies concerning accuracy of data reporting. Full article

(This article belongs to the Special Issue Rare Diseases Epidemiology Research: The State-of-the-Art and Future Perspectives)

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12 pages, 1527 KiB

Open AccessReview

The EuRRECa Project as a Model for Data Access and Governance Policies for Rare Disease Registries That Collect Clinical Outcomes

by Salma R. Ali, Jillian Bryce, Li En Tan, Olaf Hiort, Alberto M. Pereira, Erica L. T. van den Akker, Natasha M. Appelman-Dijkstra, Jerome Bertherat, Martine Cools, Olaf M. Dekkers, Yllka Kodra, Luca Persani, Arelene Smyth, Christopher Smythe, Domenica Taruscio and S. Faisal Ahmed

Int. J. Environ. Res. Public Health 2020, 17(23), 8743; https://doi.org/10.3390/ijerph17238743 - 25 Nov 2020

Cited by 14 | Viewed by 2844

Abstract

Rare disease (RD) registries are important platforms that facilitate communication between health care professionals, patients and other members of the multidisciplinary team. RD registries enable data sharing and promotion of research and audits, often in an international setting, with the overall aim of improving patient care. RD registries also have a fundamental role in supporting the work of clinical networks such as the European Reference Networks (ERNs) for rare diseases. With the recent expansion of RD registries, it has become even more essential to outline standards of good practice in relation to governance, infrastructure, documentation, training, audits and adopting the Findable, Accessible, Interoperable and Reusable (FAIR) data principles to maintain registries of high quality. For the purpose of this paper, we highlight vital aspects of data access and data governance policies for RD registries, using the European Registries for Rare Endocrine Conditions (EuRRECa) as an example of a project that aims to promote good standards of practice for improving the quality of utilization of RD registries. Full article

(This article belongs to the Special Issue Rare Diseases Epidemiology Research: The State-of-the-Art and Future Perspectives)

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8 pages, 285 KiB

Open AccessReview

Shaping the Future of Rare Diseases after a Global Health Emergency: Organisational Points to Consider

by Rosaria Talarico, Diana Marinello, Sara Cannizzo, Andrea Gaglioti, Simone Ticciati, Claudio Carta, Yllka Kodra, Mojgan Azadegan, Domenica Taruscio, Marta Mosca and Giuseppe Turchetti

Int. J. Environ. Res. Public Health 2020, 17(22), 8694; https://doi.org/10.3390/ijerph17228694 - 23 Nov 2020

Cited by 9 | Viewed by 2623

Abstract

The unexpected outbreak of the COVID-19 disease had significant and enormous repercussions on the healthcare systems, such as the need to reorganise healthcare organisations in order to concentrate resources needed to the care of COVID-19 patients and to respond in general to this health emergency. Due to these challenges, the care of several chronic conditions was in many cases discontinued and patients and healthcare professionals treating these conditions had to cope with this new scenario. This was the case of the world rare diseases (RDs) that had to face this global emergency despite the vulnerability of people with RDs and the well-known need for high expertise required to treat and manage them. The numerous lessons learned so far regarding health emergencies and RDs should represent the basis for the establishment of new healthcare policies and plans aimed at ensuring the preparedness of our health systems in providing appropriate care to people living with RDs in the case of eventual new emergencies. This paper aims at providing pragmatic considerations that might be useful in designing future actions to create or optimise existing organisational models for the care of RDs in case of future emergencies or any other situation that might threaten the provision of routine care. These policies and plans should benefit from the multi-stakeholder RDs networks (such as the European Reference Networks), that should join forces at European, national, and local levels to minimise the economic, organisational, and health-related impact and the negative effects of potential emergencies on the RDs community. In order to design and develop these policies and plans, a decalogue of points to consider were developed to ensure appropriate care for people living with RDs in the case of eventual future health emergencies. Full article

(This article belongs to the Special Issue Rare Diseases Epidemiology Research: The State-of-the-Art and Future Perspectives)

17 pages, 1051 KiB

Open AccessReview

Look Alike, Sound Alike: Phenocopies in Steroid-Resistant Nephrotic Syndrome

by Francesca Becherucci, Samuela Landini, Luigi Cirillo, Benedetta Mazzinghi and Paola Romagnani

Int. J. Environ. Res. Public Health 2020, 17(22), 8363; https://doi.org/10.3390/ijerph17228363 - 12 Nov 2020

Cited by 11 | Viewed by 3903

Abstract

Steroid-resistant nephrotic syndrome (SRNS) is a clinical picture defined by the lack of response to standard steroid treatment, frequently progressing toward end-stage kidney disease. The genetic basis of SRNS has been thoroughly explored since the end of the 1990s and especially with the advent of next-generation sequencing. Genetic forms represent about 30% of cases of SRNS. However, recent evidence supports the hypothesis that “phenocopies” could account for a non-negligible fraction of SRNS patients who are currently classified as non-genetic, paving the way for a more comprehensive understanding of the genetic background of the disease. The identification of phenocopies is mandatory in order to provide patients with appropriate clinical management and to inform therapy. Extended genetic testing including phenocopy genes, coupled with reverse phenotyping, is recommended for all young patients with SRNS to avoid unnecessary and potentially harmful diagnostic procedures and treatment, and for the reclassification of the disease. The aim of this work is to review the main steps of the evolution of genetic testing in SRNS, demonstrating how a paradigm shifting from “forward” to “reverse” genetics could significantly improve the identification of the molecular mechanisms of the disease, as well as the overall clinical management of affected patients. Full article

(This article belongs to the Special Issue Rare Diseases Epidemiology Research: The State-of-the-Art and Future Perspectives)

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18 pages, 3442 KiB

Open AccessReview

Hajdu–Cheney Syndrome: A Systematic Review of the Literature

by Jonathan Cortés-Martín, Lourdes Díaz-Rodríguez, Beatriz Piqueras-Sola, Raquel Rodríguez-Blanque, Antonio Bermejo-Fernández and Juan Carlos Sánchez-García

Int. J. Environ. Res. Public Health 2020, 17(17), 6174; https://doi.org/10.3390/ijerph17176174 - 25 Aug 2020

Cited by 22 | Viewed by 4046

Abstract

Hajdu–Cheney syndrome (HCS) is a rare genetic disease that causes acroosteolysis and generalized osteoporosis, accompanied by a series of developmental skeletal disorders and multiple clinical and radiological manifestations. It has an autosomal dominant inheritance, although there are several sporadic non-hereditary cases. The gene that has been associated with Hajdu-Cheney syndrome is NOTCH2. The described phenotype and clinical signs and symptoms are many, varied, and evolve over time. As few as 50 cases of this disease, for which there is currently no curative treatment, have been reported to date. The main objective of this systematic review was to evaluate the results obtained in research regarding Hajdu–Cheney Syndrome. The findings are reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and were registered on the web PROSPERO under the registration number CRD42020164377. A bibliographic search was carried out using the online databases Orphanet, PubMed, and Scielo; articles from other open access sources were also considered. Finally, 76 articles were included, and after their analysis, we have obtained a series of hypotheses as results that will support further studies on this matter. Full article

(This article belongs to the Special Issue Rare Diseases Epidemiology Research: The State-of-the-Art and Future Perspectives)

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Other

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18 pages, 2481 KiB

Open AccessCommentary

Reflections on the Importance of Cost of Illness Analysis in Rare Diseases: A Proposal

by Patrizio Armeni, Marianna Cavazza, Entela Xoxi, Domenica Taruscio and Yllka Kodra

Int. J. Environ. Res. Public Health 2021, 18(3), 1101; https://doi.org/10.3390/ijerph18031101 - 26 Jan 2021

Cited by 8 | Viewed by 2962

Abstract

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. Full article

(This article belongs to the Special Issue Rare Diseases Epidemiology Research: The State-of-the-Art and Future Perspectives)

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