Rare Disease Patients Research Articles

Integrated omics analyses clarifies ATRX copy number variant of uncertain significance.

Partial duplications of genes can be challenging to detect and interpret and, therefore, likely represent an underreported cause of human disease. X-linked dominant variants in ATRX are associated with Alpha-thalassemia/impaired intellectual development syndrome, X-linked (ATR-X syndrome), a clinically heterogeneous disease generally presenting with intellectual disability, hypotonia, characteristic facies, genital anomalies, and alpha-thalassemia. We describe an affected male with a de novo hemizygous intragenic duplication of ~43.6 kb in ATRX, detected by research genome sequencing following non-diagnostic clinical testing. RNA sequencing and DNA methylation episignature analyses were central in variant interpretation, and this duplication was subsequently interpreted as disease-causing. This represents the smallest reported tandem duplication within ATRX associated with disease. This case demonstrates the diagnostic utility of integrating multiple omics technologies, which can ultimately lead to a definitive diagnosis for rare disease patients.

Assistance and Delivery of COVID-19 Vaccinations to Patients with Rare Diseases.

The COVID-19 vaccination campaign has been fortified by the positive effects of immunization: data from official government organizations and communication channels show that infection rates, hospitalizations, and deaths have continued to fall since its implementation. In Brazil, the effective and free National Vaccination Program has failed to prioritize patients with rare diseases, who have extreme comorbidities, and who adhere to the calendar prepared by the government. The question is why these "rare people" were not considered priorities during the vaccination program. This study aims to understand the reasoning behind this decision and to resume the debate around the rights of patients with rare diseases based on regular descriptors issued by official government agencies and by critics of rare disease issues in scientific articles. The objectives of this study were as follows: to analyze the dispensed care of rare disease patients in the COVID-19 vaccination campaign; to identify the procedures implemented by the National Vaccination Plan for the Brazilian population over 18 years of age and to evaluate the effectiveness of the plan implemented from the perspective of a "rare person".

KNOWLEDGE AND SKILLS OF NURSES REGARDING ORPHAN DISEASES

Introduction. The role of the nurse in providing comprehensive and individualized care to patients with rare diseases is one ofthe key roles. Nurses work closely with physicians and patients and play an educational role for patients and their families, facilitating coordination, monitoring and continuity of care. Therefore, nurses should have a certain range of knowledge and skills regarding the most common rare diseases.The aim of research was to determine the knowledge and skills of nurses regarding some specifi c rare diseases.Material and methods. An anonymous and voluntary survey of nurses was conducted at the regional children’s clinical hospitalfrom April to May 2023. A total of 63 nurses from the hospital participated in the survey. The questionnaire consisted of 27 questions related to the sociodemographic data of the respondents and rare diseases. The most common rare diseases encountered in the practice of nurses at the hospital were primary immunodefi ciencies (PID), spina bifi da (SB), cystic fi brosis, and juvenile idiopathic arthritis.The research results are presented in the form of descriptive statistics. Comparisons of frequency parameters were made using the Chi-square test. Diff erences between parameters were considered statistically signifi cant at p<0.05. Statistical analysis of the survey results was performed using the statistical package STATISTICA 10.0 and Microsoft Excel 2003 spreadsheet editor.The research and the publication of the materials were approved by the Bioethics Committee of the I. Horbachevsky Ternopil National Medical University (protocol № 73 dated 03.04.2023).The study was conducted within the framework of the research project of the Department of Children’s Diseases with PediatricSurgery of the I. Horbachevsky Ternopil National Medical University “Improvement of methods of diagnostics, treatment and rehabilitation of the most common children’s diseases”, registration number 0122U000039.Results. The majority of respondents were female (96.8%), between the ages of 31 and 50 (63.5%), and employed in the hospitalsetting (90.5%). Most were experienced workers with more than 20 years of experience (52.4%). Overall, the majority of respondents (71.0%) correctly identifi ed which diseases are rare. The percentage of correct answers regarding knowledge of rare diseases ranged from 47.9% for PID to 77.5% for SB, while correct answers regarding skills ranged from 41.3% for SB to 63.0% for PID. Overall, nurses demonstrated better knowledge than skills regarding rare diseases (p=0.0003). The most problematic issues were that HIV/AIDS was classifi ed as PID (31.7%), lack of knowledge about standards of neurogenic bladder control in children with SB (49.2%), unfamiliarity with the technique of subcutaneous immunoglobulin administration (87.3%), and bowel cleansing procedures in children with SB (95.2%), as well as infection control in patients with cystic fi brosis (66.1%).Conclusion. The study revealed a lack of awareness among nurses regarding certain rare diseases. The lowest level of knowledge was found for primary immunodefi ciencies. There is a need to improve nurses’ knowledge and skills regarding rare diseases, which can improve the quality of care for rare disease patients and their families. The development of educational interventions for nurses can help to increase their awareness of rare diseases.

Impacts of adjustment of National Reimbursement Drug List on orphan drugs volume and spending in China: an interrupted time series analysis

ObjectiveTo evaluate the impacts of the 2017 adjustment of National Reimbursement Drug List (NRDL) on orphan drugs hospital procurement volumes and spending in China.DesignWe used an interrupted time series design...

Cannabis for medicinal use in patients with rare diseases

BACKGROUND: Patients with Rare Diseases (RDs) present with chronic and debilitating symptoms such as pain, anxiety and epileptic seizures. Symptoms can be unresponsive to conventional treatment and may lead to a decreased Quality of Life for patients. Cannabinoids have been reported to be efficacious against chronic pain refractory to conventional analgesics, anxiety and seizures. OBJECTIVE: Identification of RDs for which Medicinal Cannabis (MC) can be used and identification of issues related to RDs and perceptions on the use of MC in patients with RDs. METHODS: Study was divided into 2 phases. Phase 1: Literature Review to identify RDs in which cannabis or cannabinoids are used Phase 2: Development, validation and dissemination of 2 questionnaires for: (i) Health Care Professionals (HCPs) and (ii) RD patients. RESULTS: Cannabinoids were described as possible therapeutic agents in 20 RDs. The questionnaires were completed by 101 HCPs and 38 RD patients. Thirty-three HCPs had no experience on use of MC but would consider using it in their practice for management of RDs. Most patients (n = 29) did not have experience with use of MC and 20 patients would consider using MC to treat their condition or relieve symptoms of their disease. CONCLUSION: The study helps identify the potential of MC use in RDs associated with chronic symptoms such as pain, muscle spasticity, seizures and anxiety.

Caring for People with Rare Diseases: A Systematic Review of the Challenges of, and Strategies for Dealing with, COVID-19.

The COVID-19 pandemic took a toll on everyone's lives, and patients with rare diseases (RDs) had to pay an even higher price. In this systematic review, we explored the impact of the COVID-19 pandemic on individuals with RDs from a psychological perspective. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we retrieved articles from the Google Scholar, Scopus, and PubMed databases focusing on 'COVID-19,' 'psychology,' and 'rare diseases.' Seventeen primary articles were identified (mainly from continental Europe). The results revealed the psychological effects of the pandemic on rare disease patients, including increased anxiety, stress, and depressive moods. This review also highlighted the increased vulnerability and reduced quality of life of rare disease patients during the pandemic, as well as the importance of telecare and psychological support as critical interventions for improving their well-being. There is an urgent need for multidisciplinary research and stronger healthcare systems to meet the unique challenges of rare disease patients, who represent 3.5-5.9% of the global population.

ClinPrior: an algorithm for diagnosis and novel gene discovery by network-based prioritization

BackgroundWhole-exome sequencing (WES) and whole-genome sequencing (WGS) have become indispensable tools to solve rare Mendelian genetic conditions. Nevertheless, there is still an urgent need for sensitive, fast algorithms to maximise WES/WGS diagnostic yield in rare disease patients. Most tools devoted to this aim take advantage of patient phenotype information for prioritization of genomic data, although are often limited by incomplete gene-phenotype knowledge stored in biomedical databases and a lack of proper benchmarking on real-world patient cohorts.MethodsWe developed ClinPrior, a novel method for the analysis of WES/WGS data that ranks candidate causal variants based on the patient’s standardized phenotypic features (in Human Phenotype Ontology (HPO) terms). The algorithm propagates the data through an interactome network-based prioritization approach. This algorithm was thoroughly benchmarked using a synthetic patient cohort and was subsequently tested on a heterogeneous prospective, real-world series of 135 families affected by hereditary spastic paraplegia (HSP) and/or cerebellar ataxia (CA).ResultsClinPrior successfully identified causative variants achieving a final positive diagnostic yield of 70% in our real-world cohort. This includes 10 novel candidate genes not previously associated with disease, 7 of which were functionally validated within this project. We used the knowledge generated by ClinPrior to create a specific interactome for HSP/CA disorders thus enabling future diagnoses as well as the discovery of novel disease genes.ConclusionsClinPrior is an algorithm that uses standardized phenotype information and interactome data to improve clinical genomic diagnosis. It helps in identifying atypical cases and efficiently predicts novel disease-causing genes. This leads to increasing diagnostic yield, shortening of the diagnostic Odysseys and advancing our understanding of human illnesses.

ORPHAcodes use for the coding of rare diseases: comparison of the accuracy and cross country comparability

BackgroundEstimates of rare disease (RD) population impact in terms of number of affected patients and accurate disease definition is hampered by their under-representation in current coding systems. This study tested the use of a specific RD codification system (ORPHAcodes) in five European countries/regions (Czech Republic, Malta, Romania, Spain, Veneto region-Italy) across different data sources over the period January 2019-September 2021.ResultsOverall, 3133 ORPHAcodes were used to describe RD diagnoses, mainly corresponding to the disease/subtype of disease aggregation level of the Orphanet classification (82.2%). More than half of the ORPHAcodes (53.6%) described diseases having a very low prevalence (< 1 case per million), and most commonly captured rare developmental defects during embryogenesis (31.3%) and rare neurological diseases (17.6%). ORPHAcodes described disease entities more precisely than corresponding ICD-10 codes in 83.4% of cases.ConclusionsORPHAcodes were found to be a versatile resource for the coding of RD, able to assure easiness of use and inter-country comparability across population and hospital databases. Future research on the impact of ORPHAcoding as to the impact of numbers of RD patients with improved coding in health information systems is needed to inform on the real magnitude of this public health issue.

Analysis of marketed orphan drugs in China.

In recent years, China has increased attention on the issue of rare diseases, and the government has promulgated rare disease-related policies to gradually improve rare disease diagnosis, treatment, drug marketing, and patient burden. Orphan drugs were added to the medical insurance directory in 7 batches, of which 22 drugs were first included in the 2004 medical insurance directory and 8, 16, 12, 7, 8, and 7 were included in the 2009, 2017, 2019, 2020, 2021, and 2022 versions, respectively. Currently, 106 orphan drugs are marketed in China, which are suitable for treating 53 rare diseases such as hematologic diseases, congenital metabolism disorders, neuropathies, and digestive system diseases and for other treatment fields. The drugs are mainly manufactured in 15 countries such as China, Switzerland, and the USA, of which 10 drugs can be used to treat different rare diseases. At the same time, there are multiple treatments available for 25 rare diseases. In this paper, we examined the manufacturers, marketing status, indications, and inclusion of orphan drugs in the National Basic Medical Insurance Directory to describe and analyze the current status of 106 orphan drugs that are currently marketed in China to provide a reference for rare disease policy formulation and drug development.

Analysis on the Marketing Trend and Approval Lag of Imported Orphan Drugs from 2010 to 2021 in China.

In order to meet the unmet needs of rare disease patients in China, importing orphan drugs is an important way. The objectives of this study were to investigate the marketing trend of orphan drugs approved by the US Food and Drug Administration (FDA) and imported by China, to examine the orphan drug lag between China and the United States. This study analyzes the orphan drugs approved by FDA and imported by China from January 2010 to December 2021. The approval lag for orphan drugs between China and the US was calculated and analyzed by approval time. Factors potentially affecting the approval lag, such as target disease, ATC classification, formulation, corporation name, drug type, and whether the indications belong to the first batch of rare diseases catalogue were investigated. The number of FDA-approved orphan drugs imported by China is increasing year by year, and the approval lag of these drugs is gradually decreasing, especially in the classification of Non-L, Injections, Non-United States, and biological product. Compared with 2010-2015, the approval lag of total drugs in the study was significantly improved in 2016-2021 (1977days) compared with 2010-2015 (3928days). China's groundbreaking regulatory reforms of drugs since 2015 had made significant progress in reducing orphan drug lags, but there is still considerable room for progress. We should more actively promote the approval of rare disease drugs in China, establish a better approval mechanism, and enable Chinese patients with rare diseases to receive drug treatment in a timely manner.

Initiatives to promote access to medicines after publication of the Brazilian Policy on the Comprehensive Care of People with Rare Diseases

BackgroundRare diseases affect a small number of people compared to prevalent diseases. The vast majority of these diseases are of genetic origin, have no cure, are chronic and can lead to death. Although the right to access medicines is included in the constitutionally guaranteed right to health in Brazil, problems in the supply of medicines for rare diseases are reported in the country. This study aimed to describe and analyse the initiatives to promote access to medicines for treating rare diseases in the Unified Health System, Brazil, after the publication of the Brazilian Policy on the Comprehensive Care of People with Rare Diseases. Based on the model published by the WHO Regional Office for Europe, which described access to medicines in prelaunch, perilaunch and postlaunch policies, the initiatives referring to each category were summarized based on documentary research searched in online databases from January 2014 to December 2020.ResultsDifferent actions and policy interventions were identified, which went through the expansion of resources for research and development, health regulations, incorporation of new drugs, review and publication of clinical guidelines, and expansion of the network of care facilities by the Ministry of Health. On the other hand, aspects related to care policies, pricing methods, technological development, and development of pharmaceutical service processes were not implemented.ConclusionsAlthough it is impossible to determine the explicit motivation of such actions concerning the Policy, its publication certainly was a landmark in Brazilian society, allowing greater recognition of the needs of rare disease patients and the specificities of treatment’. However, this study suggests that the steps that make up the life cycle of medicines are not linked, lacking articulation and integration of the care network, and consequently, there is no evidence that rare disease policy publication has generated a broad impact on the promotion of access to medicines to treat rare diseases in Brazil.

Increasing orphan drug loss in Japan: Trends and R&D strategy for rare diseases

Rare disease (RD) patients face significant unmet therapeutic needs worldwide. However, orphan drugs approved in the United States, but not approved or developed in Japan, have increased rapidly with recently increasing US approvals, indicating greater RD drug loss in Japan. US/EU-based startups have become key players in RD drug R&D, significantly contributing to this drug loss trend. They successfully develop drugs in the United States by combining in-licensing with in-house drug discovery. Out-licensing to Japanese companies or large pharma is critical for expansion into Japan, with successes attributed to drug innovation, target indications, and transactional capabilities. These findings highlight the need to foster partnerships with startups and cultivate an ecosystem in Japan that nurtures local startups, to address drug loss and ensure access to promising drugs.

Insulin Signaling Through the Insulin Receptor Increases Linear Growth Through Effects on Bone and the GH-IGF-1 Axis.

Childhood overnutrition is associated with increased growth and bone mineral density (BMD) vs the opposite for undernutrition. The role of insulin receptor (InsR) signaling in these phenotypes is unclear. Rare disease patients with hyperinsulinemia and impaired InsR function (homozygous [-/-] or heterozygous [+/-] INSR pathogenic variants, type B insulin resistance [TBIR]) model increased InsR signaling, while patients with intact InsR function (congenital generalized lipodystrophy, CGL) model decreased InsR signaling. This work aimed to understand mechanisms whereby InsR signaling influences growth. A cross-sectional comparison was conducted of CGL (N = 23), INSR-/- (N = 13), INSR+/- (N = 17), and TBIR (N = 8) at the National Institutes of Health. Main outcome measures included SD scores (SDS) for height, body mass index, insulin-like growth factor (IGF)-1, and BMD, and IGF binding proteins (IGFBP)-1 and -3. INSR-/- vs CGL had higher insulin (median 266 [222-457] vs 33 [15-55] mcU/mL), higher IGFBP-1 (72 350 [55 571-103 107] vs 6453 [1634-26 674] pg/mL), lower BMI SDS (-0.7 ± 1.1 vs 0.5 ± 0.9), lower height SDS (-1.9[-4.3 to -1.3] vs 1.1 [0.5-2.5]), lower BMD SDS (-1.9 ± 1.4 vs 1.9 ± 0.7), and lower IGFBP-3 (0.37 [0.19-1.05] vs 2.00 [1.45-2.67] μg/mL) (P < .05 for all). INSR +/- were variable. Remission of TBIR lowered insulin and IGFBP-1, and increased IGF-1 and IGFBP-3 (P < .05). Patients with hyperinsulinemia and impaired InsR function exhibit impaired growth and lower BMD, whereas elevated InsR signaling (CGL) causes accelerated growth and higher BMD. These patients demonstrate that insulin action through the InsR stimulates direct anabolic effects in bone and indirect actions through the growth hormone (GH)-IGF-1 axis. TBIR patients exhibit abnormalities in the GH axis that resolve when InsR signaling is restored, supporting a causal relationship between InsR and GH axis signaling.

Transposable element insertions in 1000 Swedish individuals.

The majority of rare diseases are genetic, and regardless of advanced high-throughput genomics-based investigations, 60% of patients remain undiagnosed. A major factor limiting our ability to identify disease-causing alterations is a poor understanding of the morbid and normal human genome. A major genomic contributor of which function and distribution remain largely unstudied are the transposable elements (TE), which constitute 50% of our genome. Here we aim to resolve this knowledge gap and increase the diagnostic yield of rare disease patients investigated with clinical genome sequencing. To this end we characterized TE insertions in 1000 Swedish individuals from the SweGen dataset and 2504 individuals from the 1000 Genomes Project (1KGP), creating seven population-specific TE insertion databases. Of note, 66% of TE insertions in SweGen were present at >1% in the 1KGP databases, proving that most insertions are common across populations. Focusing on the rare TE insertions, we show that even though ~0.7% of those insertions affect protein coding genes, they rarely affect known disease casing genes (<0.1%). Finally, we applied a TE insertion identification workflow on two clinical cases where disease causing TE insertions were suspected and could verify the presence of pathogenic TE insertions in both. Altogether we demonstrate the importance of TE insertion detection and highlight possible clinical implications in rare disease diagnostics.

The Minimum Data Set for Rare Diseases: Systematic Review.

The minimum data set (MDS) is a collection of data elements to be grouped using a standard approach to allow the use of data for clinical and research purposes. Health data are typically voluminous, complex, and sometimes too ambiguous to generate indicators that can provide knowledge and information on health. This complexity extends further to the rare disease (RD) domain. MDSs are essential for health surveillance as they help provide services and generate recommended population indicators. There is a bottleneck in international literature that reveals a global problem with data collection, recording, and structuring in RD. This study aimed to identify and analyze the MDSs used for RD in health care networks worldwide and compare them with World Health Organization (WHO) guidelines. The population, concept, and context methodology proposed by the Joanna Briggs Institute was used to define the research question of this systematic review. A total of 4 databases were reviewed, and all the processes were reported using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology. The data elements were analyzed, extracted, and organized into 10 categories according to WHO digital health guidelines. The quality assessment used the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist. We included 20 studies in our review, 70% (n=14) of which focused on a specific health domain and 30% (n=6) of which referred to RD in general. WHO recommends that health systems and networks use standard terminology to exchange data, information, knowledge, and intelligence in health. However, there was a lack of terminological standardization of the concepts in MDSs. Moreover, the selected studies did not follow the same standard structure for classifying the data from their MDSs. All studies presented MDSs with limitations or restrictions because they covered only a specific RD, or their scope of application was restricted to a specific context or geographic region. Data science methods and clinical experience were used to design, structure, and recommend a fundamental global MDS for RD patient records in health care networks. Our study highlights the difficulties in standardizing and categorizing findings from MDSs for RD because of the varying structures used in different studies. The fundamental RD MDS designed in this study comprehensively covers the data needs in the clinical and management sectors. These results can help public policy makers support other aspects of their policies. We highlight the potential of our results to help strategic decisions related to RD. PROSPERO CRD42021221593; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=221593. RR2-10.1016/j.procs.2021.12.034.

FindZebra online search delving into rare disease case reports using natural language processing.

Early diagnosis is crucial for well-being and life quality of the rare disease patient. Access to the most complete knowledge about diseases through intelligent user interfaces can play an important role in supporting the physician reaching the correct diagnosis. Case reports may offer information about heterogeneous phenotypes which often further complicate rare disease diagnosis. The rare disease search engine FindZebra.com is extended to also access case report abstracts extracted from PubMed for several diseases. A search index for each disease is built in Apache Solr adding age, sex and clinical features extracted using text segmentation to enhance the specificity of search. Clinical experts performed retrospective validation of the search engine, utilising real-world Outcomes Survey data on Gaucher and Fabry patients. Medical experts evaluated the search results as being clinically relevant for the Fabry patients and less clinically relevant for the Gaucher patients. The shortcomings for Gaucher patients mainly reflect a mismatch between the current understanding and treatment of the disease and how it is reported in PubMed, notably in the older case reports. In response to this observation, a filter for the publication date was added in the final version of the tool available from deep.findzebra.com/<disease> with <disease> = gaucher, fabry, hae (Hereditary angioedema).

Stimulating solidarity to improve knowledge on medications used during pregnancy

BackgroundPregnant people have been overlooked or excluded from clinical research, resulting in a lack of scientific knowledge on medication safety and efficacy during pregnancy. Thus far, both the opportunities to generate evidence-based knowledge beyond clinical trials and the role of pregnant people in changing their status quo have not been discussed. Some scholars have argued that for rare disease patients, for whom, just like pregnant people, a poor evidence base exists regarding treatments, solidarity has played an important role in addressing the evidence gap. This paper explores whether and how the enactment of solidarity among pregnant people can be stimulated to help address the poor evidence base on medications used during pregnancy.MethodWe use the concept of solidarity formulated by Prainsack and Buyx and enrich their concept by providing an account for stimulating the enactment of solidarity. Then we apply this account to the case of pregnant people who use medication.ResultsSolidarity means enacted commitment on the part of an individual to assisting others with whom the person recognizes a similarity in a relevant respect. Although solidarity cannot be imposed, we argue that the empowerment of people is a crucial concept in understanding how solidarity can be stimulated. Empowerment in the context of pregnant people means creating awareness about their status quo, explaining how scientific research can help close the knowledge gap, and how pregnant people can themselves contribute. In particular, how pregnant people can contribute to the collection of health data to strengthen the evidence base for medications used during pregnancy.ConclusionsWe conclude that acting in solidarity can help change the status quo for pregnant people. Furthermore, we argue that the empowerment of pregnant people and other relevant stakeholders is a way to stimulate the enactment of solidarity. The process of empowerment starts by raising awareness about the lack of evidence on medications used during prengnacy and by explaining to pregnant people how they can contribute to changing the way knowledge is being generated by, for example, sharing data on the health effects of medications.

A IMPORTANCE OF RARE DISEASES AWARENESS FOR MEDICAL AND NURSING STUDENTS AT KSA

Consequently, there is a need to increase the standards of medical education in the field of Rare Diseases and to revise the undergraduate and postgraduate training programs. However, while studies on medical education in the field of RDs has been conducted in various countries across the both Americas, Asia or the European Union, still little is known about the awareness of RDs among healthcare professionals in the kingdom of Saudi Arabia. Thus, we conducted a survey among 200 medical students and 200 nursing students from the college of applied medical sciences at aseer region. The questionnaire assessed their knowledge about the number, examples, aetiology and estimated frequency of RDs. It also evaluated respondents’ self-assessment of competence in RDs. Although the majority of respondents agreed that RDs constitute a serious public health issue both medical students and nursing students showed insufficient knowledge on the aetiology, epidemiology and prevalence of RDs, and many had problems with separating RDs from more common disorders. Moreover, they also lacked knowledge about and the central register of RD patients and reimbursement of orphan drugs in Saudi Arabia. Finally, while almost half respondents declared having had classes about RDs during their studies most perceived their knowledge about RDs as insufficient or poor and felt unprepared for caring for RD patients. Additionally, although majority of respondents in both groups believed that all physicians, regardless of their specialization, should possess knowledge on RDs many respondents did not look for such information at all. While genetics constitutes an important part of medical education, one can observe a lack of knowledge about rare diseases (RD) among medical students and healthcare professionals. Meanwhile, many RD are life threatening and chronically debilitating conditions that significantly reduce patients' quality of life. Most RD patients experience various psychiatric symptoms, behavioural changes and mental retardation. Consequently, physicians should be educated on RD. Thus, the aim of this paper is to assess the knowledge about RD among future medical professionals.

Is sub-national healthcare social protection sufficient for protecting rare disease patients? the case of China.

Failing to provide social support to cover healthcare costs for rare diseases would lead to great financial distress for the patients and their families. People from countries without a well-developed health safety-net are particularly vulnerable. Existing literature on rare diseases in China focuses on the unmet needs for care of the patients and the difficulties of caregivers and physicians. Very few studies examine the state of social safety-net, the unresolved issues and whether the current localized arrangements are sufficient. This study aimed to gain in-depth knowledge of the current policy system and make sense of the local varieties, which would be essential for developing strategies for future policy changes. This systematic policy review focuses on the provincial level policies on subsidizing the healthcare costs for people with rare diseases in China. The cut-off point for the policies was March 19, 2022. The researchers coded the healthcare cost reimbursement policies and identified the different provincial level models based on the usage of reimbursement components in each provinces reimbursement arrangements. 257 documents were collected. Five provincial level models (Process I, II, III, IV and V) have been identified with the five components across the country: Basic Medical Insurance for Outpatient Special Diseases (OSD), Catastrophic Medical Insurance for Rare Diseases (CMIRD), Medical Assistance for Rare Diseases (MARD), Special Fund for Rare Diseases (SFRD) and Mutual Medical Fund (MMF). The local health safety-net in each region is a combination of one or more of the five processes. Regions vary greatly in their rare diseases coverage and reimbursement policies. In China, the provincial health authorities have developed some level of social protection for rare disease patients. However, there are still gaps regarding coverage and regional inequality; and there is room for a more integrated healthcare safety-net for people suffering from rare diseases at the national level.

DECIPHER: Improving Genetic Diagnosis Through Dynamic Integration of Genomic and Clinical Data.

DECIPHER (Database of Genomic Variation and Phenotype in Humans Using Ensembl Resources) shares candidate diagnostic variants and phenotypic data from patients with genetic disorders to facilitate research and improve the diagnosis, management, and therapy of rare diseases. The platform sits at the boundary between genomic research and the clinical community. DECIPHER aims to ensure that the most up-to-date data are made rapidly available within its interpretation interfaces to improve clinical care. Newly integrated cardiac case-control data that provide evidence of gene-disease associations and inform variant interpretation exemplify this mission. New research resources are presented in a format optimized for use by a broad range of professionals supporting the delivery of genomic medicine. The interfaces within DECIPHER integrate and contextualize variant and phenotypic data, helping to determine a robust clinico-molecular diagnosis for rare-disease patients, which combines both variant classification and clinical fit. DECIPHER supports discovery research, connecting individuals within the rare-disease community to pursue hypothesis-driven research.