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1.
J Clin Med ; 13(9)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38731134

RESUMO

Background: Pitt-Hopkins syndrome (PTHS) is a rare genetic disorder affecting psychomotor, social, and intellectual development, caused by a mutation in the TCF4 gene. The study aims to gather the phenotype and genotype data of PTHS patients from Poland and to assess the quality of life (QoL) and the impact of the disorders on the family. Methods: Eight families with PTHS participated in the study. To obtain data, the following standardized questionnaires were used: Questionnaire on Clinical Problems (QCP), the PedsQL™ Family Impact Module, and the QL-Disability Questionnaire. Additionally, a retrospective analysis of clinical examination, genetic consult, medical history, and genotype of each individual was performed. Results: All of the examined children exhibited a mutation in the TCF4 gene and typical features of PTHS. The most prevalent clinical symptoms in the study group included typical PTHS appearance, intellectual disability (n = 5; as the rest of the patients were too young to be assessed), abnormal speech development (n = 8), reduced pain response (n = 7), constipation (n = 7), drooling (n = 7), cold extremities (n = 7), and disturbances in sensory integration processes (n = 7). The QL-Disability Questionnaire revealed a total QoL score of 67.7/100 for children with PTHS, while the QoL for their families in the PedsQL Family Impact Module was 53.82/100. The highest-rated domain was cognitive functioning (Median (Me) = 67.50; Standard Deviation (SD) = 21.95), while the lowest was daily activities (Me = 25.00; SD = 29.86). Conclusions: The study allowed the collection of data on the phenotype and genotype of children with PTHS living in Poland. Overall, our study showed that the QoL of children with PTHS is impaired.

2.
Cureus ; 16(4): e58127, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38741870

RESUMO

Beta-propeller protein-associated neurodegeneration (BPAN), a subtype of neurodegeneration with brain iron accumulation, is caused by variants in the WDR45 gene. In this paper, we describe a patient with an atypical presentation of BPAN whose whole exome sequencing revealed a previously unattested truncating variant in the WDR45 gene (c.830+3G>C/p.Leu278Ter), the pathogenicity of which was verified by RNA transcriptomics. A number of uncommon neuroanatomic and clinical findings in our patient are discussed, expanding the phenotype associated with BPAN. This unique case challenges existing genotype-phenotype correlations and highlights the role of X chromosome skewing in shaping the clinical spectrum of BPAN.

3.
Orphanet J Rare Dis ; 19(1): 187, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711103

RESUMO

BACKGROUND: Rare disease registries (RDRs) are valuable tools for improving clinical care and advancing research. However, they often vary qualitatively, structurally, and operationally in ways that can determine their potential utility as a source of evidence to support decision-making regarding the approval and funding of new treatments for rare diseases. OBJECTIVES: The goal of this research project was to review the literature on rare disease registries and identify best practices to improve the quality of RDRs. METHODS: In this scoping review, we searched MEDLINE and EMBASE as well as the websites of regulatory bodies and health technology assessment agencies from 2010 to April 2023 for literature offering guidance or recommendations to ensure, improve, or maintain quality RDRs. RESULTS: The search yielded 1,175 unique references, of which 64 met the inclusion criteria. The characteristics of RDRs deemed to be relevant to their quality align with three main domains and several sub-domains considered to be best practices for quality RDRs: (1) governance (registry purpose and description; governance structure; stakeholder engagement; sustainability; ethics/legal/privacy; data governance; documentation; and training and support); (2) data (standardized disease classification; common data elements; data dictionary; data collection; data quality and assurance; and data analysis and reporting); and (3) information technology (IT) infrastructure (physical and virtual infrastructure; and software infrastructure guided by FAIR principles (Findability; Accessibility; Interoperability; and Reusability). CONCLUSIONS: Although RDRs face numerous challenges due to their small and dispersed populations, RDRs can generate quality data to support healthcare decision-making through the use of standards and principles on strong governance, quality data practices, and IT infrastructure.


Assuntos
Doenças Raras , Sistema de Registros , Humanos
4.
Health Expect ; 27(3): e14063, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38711219

RESUMO

INTRODUCTION: Advanced therapies offer unprecedented opportunities for treating rare neurological disorders (RNDs) in children. However, health literacy, perceptions and understanding of novel therapies need elucidation across the RND community. This study explored healthcare professionals' and carers' perspectives of advanced therapies in childhood-onset RNDs. METHODS: In this mixed-methodology cross-sectional study, 20 healthcare professionals (clinicians, genetic counsellors and scientists) and 20 carers completed qualitative semistructured interviews and custom-designed surveys. Carers undertook validated psychosocial questionnaires. Thematic and quantitative data analysis followed. RESULTS: Participants described high positive interest in advanced therapies, but low knowledge of, and access to, reliable information. The substantial 'therapeutic gap' and 'therapeutic odyssey' common to RNDs were recognised in five key themes: (i) unmet need and urgency for access; (ii) seeking information; (iii) access, equity and sustainability; (iv) a multidisciplinary and integrated approach to care and support and (v) difficult decision-making. Participants were motivated to intensify RND clinical trial activity and access to advanced therapies; however, concerns around informed consent, first-in-human trials and clinical trial procedures were evident. There was high-risk tolerance despite substantial uncertainties and knowledge gaps. RNDs with high mortality, increased functional burdens and no alternative therapies were consistently prioritised for the development of advanced therapies. However, little consensus existed on prioritisation to treatment access. CONCLUSIONS: This study highlights the need to increase clinician and health system readiness for the clinical translation of advanced therapeutics for RNDs. Co-development and use of educational and psychosocial resources to support clinical decision-making, set therapeutic expectations and promotion of equitable, effective and safe delivery of advanced therapies are essential. PATIENT OR PUBLIC CONTRIBUTION: Participant insights into the psychosocial burden and information need to enhance the delivery of care in this formative study are informing ongoing partnerships with families, including co-production and dissemination of psychoeducational resources featuring their voices hosted on the Sydney Children's Hospitals Network website SCHN Brain-Aid Resources.


Assuntos
Doenças do Sistema Nervoso , Doenças Raras , Humanos , Doenças Raras/terapia , Estudos Transversais , Doenças do Sistema Nervoso/terapia , Feminino , Masculino , Austrália , Adulto , Cuidadores/psicologia , Inquéritos e Questionários , Entrevistas como Assunto , Participação dos Interessados , Pessoa de Meia-Idade , Pessoal de Saúde/psicologia , Pesquisa Translacional Biomédica , Pesquisa Qualitativa
5.
Ther Adv Rare Dis ; 5: 26330040241249189, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38716233

RESUMO

Dentatorubral-pallidoluysian atrophy (DRPLA) is an ultra-rare neurodegenerative disorder characterized by ataxia, cognitive decline, myoclonus, chorea, epilepsy, and psychiatric manifestations. This article delves into the multifaceted efforts of CureDRPLA, a family-driven non-profit organization, in advancing research, raising awareness, and developing therapeutic strategies for this complex condition. CureDRPLA's inception in 2019 led to the establishment of the DRPLA Research Program, and since then have funded research projects to advance the understanding of DRPLA including but not limited to human cellular and mouse models, a natural history and biomarkers study, and a patient registry. There are currently no disease-modifying treatments for DRPLA, motivating a concerted effort on behalf of CureDRPLA to hasten their development by funding and coordinating preclinical studies of therapies in multiple modalities. Of particular interest are therapies focused on lowering the expression (or downregulation) of ATN1, the mutant gene that causes DRPLA, in hopes of tackling the pathology at its root. As with many ultra-rare diseases, a key challenge in DRPLA remains the complexity of coordinating both basic and clinical research efforts across multiple sites around the world. Finally, despite the generous financial support provided by CureDRPLA, more funding and collective efforts are still required to advance research toward the clinic and develop effective treatments for individuals with DRPLA.


Funding research projects and activities to advance research towards treatments for dentatorubral-pallidoluysian atrophy (DRPLA) This article describes the journey of CureDRPLA, a family-driven non-profit organization dedicated to making strides against dentatorubral-pallidoluysian atrophy (DRPLA), an ultra-rare brain disorder. It describes CureDRPLA's tireless efforts to understand, treat, and raise awareness about DRPLA, a condition marked by movement difficulties (ataxia), intellectual disability, uncontrollable jerky movements (myoclonus), involuntary or irregular muscle movements (chorea) and seizures. This disorder is caused by a mutation in a gene called ATN1. The gene produces a protein called atrophin-1, and when the DRPLA-causing mutation is present, the protein becomes abnormal and can build up in the brain, affecting its normal functions. Since its founding in 2019, CureDRPLA has funded research projects to unravel the mysteries of the disease and provide support for affected individuals. CureDRPLA has funded projects to create models of DRPLA using human cells and mice, which helps scientists study the disease and test potential treatments. We have started a study to learn more about how DRPLA progresses in people and are building a global database of information from individuals with DRPLA. Due to the absence of a treatment or cure, CureDRPLA is focused on testing treatments. We are particularly interested in exploring different approaches to lower the levels of the abnormal protein in the brain. CureDRPLA is actively involving the DRPLA community worldwide, raising awareness through events, conferences, and social media. We aim to connect with medical professionals, researchers, and affected families to build a strong community focused on understanding and managing DRPLA. In summary, CureDRPLA is working hard to better understand DRPLA, support affected families, and accelerate the development of treatments for this challenging condition. Our collaborative efforts and dedication underscore the importance of a united global approach to address the complexities of DRPLA.

6.
medRxiv ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38699301

RESUMO

The biological mechanisms giving rise to the extreme symptoms exhibited by rare disease patients are complex, heterogenous, and difficult to discern. Understanding these mechanisms is critical for developing treatments that address the underlying causes of diseases rather than merely the presenting symptoms. Moreover, the same dysfunctional biological mechanisms implicated in rare recessive diseases may also lead to milder and potentially preventable symptoms in carriers in the general population. Seizures are a common, extreme phenotype that can result from diverse and often elusive biological pathways in patients with ultrarare or undiagnosed disorders. In this pilot study, we present an approach to understand the biological pathways leading to seizures in patients from the Undiagnosed Diseases Network (UDN) by analyzing aggregated genotype and phenotype data from the UK Biobank (UKB). Specifically, we look for enriched phenotypes across UKB participants who harbor rare variants in the same gene known or suspected to be causally implicated in a UDN patient's recessively manifesting disorder. Analyzing these milder but related associated phenotypes in UKB participants can provide insight into the disease-causing molecular mechanisms at play in the rare disease UDN patient. We present six vignettes of undiagnosed patients experiencing seizures as part of their recessive genetic condition, and we discuss the potential mechanisms underlying the spectrum of symptoms associated with UKB participants to the severe presentations exhibited by UDN patients. We find that in our set of rare disease patients, seizures may result from diverse, multi-step pathways that involve multiple body systems. Analyses of large-scale population cohorts such as the UKB can be a critical tool to further our understanding of rare diseases in general.

7.
Osong Public Health Res Perspect ; 15(2): 174-181, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38725125

RESUMO

Rare diseases are predominantly genetic or inherited, and patients with these conditions frequently exhibit neurological symptoms. Diagnosing and treating many rare diseases is a complex challenge, and their low prevalence complicates the performance of research, which in turn hinders the advancement of therapeutic options. One strategy to address this issue is the creation of national or international registries for rare diseases, which can help researchers monitor and investigate their natural progression. In the Republic of Korea, we established a registry across 5 centers that focuses on 3 rare diseases, all of which are characterized by gait disturbances resulting from motor system dysfunction. The registry will collect clinical information and human bioresources from patients with amyotrophic lateral sclerosis, spinocerebellar ataxia, and hereditary spastic paraplegia. These resources will be stored at ICreaT and the National Biobank of Korea. Once the registry is complete, the data will be made publicly available for further research. Through this registry, our research team is dedicated to identifying genetic variants that are specific to Korean patients, uncovering biomarkers that show a strong correlation with clinical symptoms, and leveraging this information for early diagnosis and the development of treatments.

8.
Health Policy ; 144: 105080, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38733643

RESUMO

Access to drugs for rare diseases constitutes a challenge to healthcare systems, especially those with public funding. This study aimed to map and summarize the criteria used by HTA agencies in different healthcare systems to evaluate reimbursement recommendations for orphan drugs. A comprehensive literature search was performed on the databases PubMed, LILACS, Scopus, and Embase and the gray literature (Google Scholar and websites of HTA agencies). Publications addressing the criteria used by HTA agencies in countries with public healthcare systems when evaluating reimbursement recommendations for orphan drugs were included. This scoping review included 23 studies published between 2014 and 2023, mostly consisting of reviews of HTA reports, guidance documents, and original articles. The criteria were mapped from 19 countries and ranked within three models of healthcare systems (National Health System, National Health Insurance, and Social Health Insurance). All models shared concerns about unmet needs and disease nature. In addition, NHS countries (e.g., United Kingdom, Sweden, and Italy) prioritized innovation and system-level impact, while SHI countries (e.g., Germany, France, the Netherlands) usually valued budget impact and employed expedited evaluation processes. This review provides a comprehensive understanding of the general tendencies of each healthcare system model in establishing differentiated criteria to address the challenges posed by the limited evidence and investment in the field of rare diseases.

9.
Orphanet J Rare Dis ; 19(1): 184, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698457

RESUMO

Regulatory marketing authorisation is not enough to ensure patient access to new medicinal products. Health Technology Assessment bodies may require data on effectiveness, relative effectiveness, and cost-effectiveness. Healthcare systems may require data on clinical utility, savings, and budget impact. Furthermore, the exact requirements of these bodies vary country by country and sometimes even region to region, resulting in a patchwork of different data requirements to achieve effective, reimbursed patient access to new therapies. In addition, clinicians require data to make informed clinical management decisions. This requirement is of key importance in rare diseases where there is often limited data and clinical experience at the time of regulatory approval.This paper describes an innovative initiative that is called Project SATURN: Systematic Accumulation of Treatment practices and Utilization, Real world evidence, and Natural history data for the rare disease Osteogenesis Imperfecta. The objective of this project is to generate a common core dataset by utilising existing data sources to meet the needs of the various stakeholders and avoiding fragmentation through multiple approaches (e.g., a series of individual national requests/approaches, and unconnected with the regulators' potential requirements). It is expected that such an approach will reduce the time for patient access to life-changing medications. Whilst Project SATURN applies to Osteogenesis Imperfecta, it is anticipated that the principles could also be applied to other rare diseases and reduce the time for patient access to new medications.


Assuntos
Osteogênese Imperfeita , Humanos , Europa (Continente) , Doenças Raras , Avaliação da Tecnologia Biomédica
10.
Contin Educ ; 5(1): 22-30, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774600

RESUMO

Thanks to medical successes and new treatment options, children and adolescents with rare diseases can now attend school more often playing an important role in their recovery as well as improving their social inclusion. For this reason, it is important for teachers to address the issue and acquire skills in dealing with rare diseases. In this context, a multi-professional team at the Salzburg University of Teacher Education organized a blended learning seminar on the topic of rare diseases at schools. Participants were provided with videos, texts, and case studies on a learning platform, which were worked on over a period of three weeks. There were also two online lectures in which questions could be asked. In order to evaluate the tool, 21 participants took part in a quantitative longitudinal study by means of a pretest and a posttest with a four-month interval. The participants completed a questionnaire consisting of a competence screening dealing with rare diseases together with questions to measure general and teacher self-efficacy. As expected, there was a statistically significant increase in both general and teacher self-efficacy with medium effect sizes. In addition, the theoretical and practical skills for supporting affected students at school were also shown to improve in a self-assessment. In view of the positive response from participants, it is recommended to further expand this offering in order to reach a broader population of teachers. In other words, only through raising awareness and increasing the competence of professionals working in schools can an environment be created for affected children and adolescents in which their specific needs are addressed.

11.
Cells ; 13(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38727275

RESUMO

ATP-binding cassette (ABC) transporters play a crucial role for the efflux of a wide range of substrates across different cellular membranes. In the central nervous system (CNS), ABC transporters have recently gathered significant attention due to their pivotal involvement in brain physiology and neurodegenerative disorders, such as Alzheimer's disease (AD). Glial cells are fundamental for normal CNS function and engage with several ABC transporters in different ways. Here, we specifically highlight ABC transporters involved in the maintenance of brain homeostasis and their implications in its metabolic regulation. We also show new aspects related to ABC transporter function found in less recognized diseases, such as Huntington's disease (HD) and experimental autoimmune encephalomyelitis (EAE), as a model for multiple sclerosis (MS). Understanding both their impact on the physiological regulation of the CNS and their roles in brain diseases holds promise for uncovering new therapeutic options. Further investigations and preclinical studies are warranted to elucidate the complex interplay between glial ABC transporters and physiological brain functions, potentially leading to effective therapeutic interventions also for rare CNS disorders.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Sistema Nervoso Central , Neuroglia , Humanos , Transportadores de Cassetes de Ligação de ATP/metabolismo , Neuroglia/metabolismo , Animais , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/patologia , Doenças do Sistema Nervoso Central/metabolismo , Doenças do Sistema Nervoso Central/patologia
12.
Front Med (Lausanne) ; 11: 1384026, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38695032

RESUMO

Background: The lack of harmonization of evaluation criteria by Ethics Committees in the European Union (EU) has led to inconsistent ethics reviews received by research sites participating in multicenter non-interventional studies. The European General Data Protection Regulation (GDPR) appears to be implemented at national level with a substantial degree of variance in interpretation. The European Reference Networks (ERNs) were struggling in setting an Informed Consent Form (ICF) for registries, allowing reuse of data for research purposes. The aim of this work is to develop an adaptable ICF for research purposes to be used in ERN registries. Methods: To work on this challenge, a team was established within the European Joint Programme on Rare Diseases (EJP RD) to develop a patients' registry ICF template allowing easy adaptation to ERNs, country, and site-level specificities. ERN and patients' representatives validated the choice of developing a GDPR-compliant template for research purposes. The feedback received from 34 Ethics Committees on the Clinical Patient Management System ICF, including the submission of patients' data to the ERN registries and the EU consent regulatory framework were analyzed along with existing ontologies for data access and reuse. An adaptable ICF was developed following iterative cycles of consultation and review by clinicians, research experts, ethics and regulatory advisors, and patients' representatives. The development of pediatric material for minor participants was also undertaken. Results and Conclusion: Research oriented ICF templates for adults and for parents/legal representatives of patients were released in 26 national languages. This adaptable ICF aims to foster, according to patients' preferences, the reuse of registries data for research purposes in compliance with the applicable laws and standards. Pediatric material is being finalized to collect minors' assent. ICF machine-readability is also progressing to enhance data discovery and facilitate its access and reuse conditions.

13.
Br J Nurs ; 33(9): 424-429, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722008

RESUMO

Amyloidosis can affect any organ in the body by deposition of amyloid fibrils. When these aggregate in the heart, it leads to cardiac amyloidosis a life-threatening and progressive disease. Although considered a rare condition, advances in imaging techniques and raised awareness have shown that it might be more frequent than has been historically estimated. Cardiac amyloidosis can be hereditary or occur as a consequence of the ageing process but, regardless of type, patients experience a heavy symptomatic burden. This article provides an overview of its pathophysiology, signs and symptoms and how any nurse can look for the main red flags in clinical practice. Early referral for specialist care can have a significant impact on disease progression and patient quality of life.


Assuntos
Amiloidose , Humanos , Amiloidose/diagnóstico , Cardiomiopatias/diagnóstico , Cardiomiopatias/enfermagem
14.
Adv Rheumatol ; 64(1): 35, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702764

RESUMO

Immunoglobulin G4-related disease is a systemic immune-mediated disease with insidious evolution characterized by fibroinflammatory lesions over virtually any organ system. Despite the remarkable progression of knowledge, its etiology remains undefined. Due to its relapse-remitting pattern, it could accumulate irreversible damage, increasing comorbidities and mortality. This paper emphasizes key concepts for diagnosing and treating patients with this condition.


Assuntos
Doença Relacionada a Imunoglobulina G4 , Humanos , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/complicações , Doenças Raras , Imunoglobulina G/sangue
15.
Artigo em Inglês | MEDLINE | ID: mdl-38663712

RESUMO

Gyrate atrophy of the choroid and retina (GACR) is a rare autosomal recessive disease characterised by elevated plasma ornithine levels due to deficiency of the enzyme ornithine aminotransferase (OAT). The accumulation of this amino acid in plasma leads to the development of patches of chorioretinal atrophy in the peripheral retina extending into the macular area. Patients usually present with night blindness followed by constriction of the visual field and, finally, decreased central vision and blindness. The disease is diagnosed by the presence of the characteristic clinical picture, the presence of hyperornithinaemia in plasma and the detection of mutations in the OAT enzyme gene. There is currently no effective gene therapy and the most common therapeutic intervention mainly involves dietary modifications with arginine restriction. This article aims to summarise the pathogenesis, clinical and diagnostic findings and treatment options in patients with GACR.

16.
Rev Clin Esp (Barc) ; 224(5): 272-280, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38642893

RESUMO

BACKGROUND: Acute hepatic porphyrias (AHPs) are a group of rare diseases that encompasses acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and 5-aminolaevulinic acid dehydratase deficiency porphyria. Symptoms of AHP are nonspecific which, together with its low prevalence, difficult the diagnosis and follow-up of these patients. MATERIAL AND METHODS: This project used DELPHI methodology to answer PICO questions related to management of patients with AHPs. The objective was to reach a consensus among multidisciplinary porhyria experts providing answers to those PICO questions for improving diagnosis and follow-up of patients with AHP. RESULTS: Ten PICO questions were defined and grouped in four domains: 1. Biochemical diagnosis of patients with AHP. 2. Molecular tests for patients with AHP. 3. Follow-up of patients with AHP. 4. Screening for long-term complications of patients with AHP. CONCLUSIONS: PICO questions and DELPHI methodology have provided a consensus on relevant and controversial issues for improving the management of patients with AHP.


Assuntos
Técnica Delphi , Sintase do Porfobilinogênio/deficiência , Porfirias Hepáticas , Humanos , Porfirias Hepáticas/diagnóstico , Porfirias Hepáticas/terapia , Melhoria de Qualidade , Consenso
17.
Arterioscler Thromb Vasc Biol ; 44(6): 1432-1446, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38660800

RESUMO

BACKGROUND: Vascular calcification causes significant morbidity and occurs frequently in diseases of calcium/phosphate imbalance. Radiolabeled sodium fluoride positron emission tomography/computed tomography has emerged as a sensitive and specific method for detecting and quantifying active microcalcifications. We developed a novel technique to quantify and map total vasculature microcalcification to a common space, allowing simultaneous assessment of global disease burden and precise tracking of site-specific microcalcifications across time and individuals. METHODS: To develop this technique, 4 patients with hyperphosphatemic familial tumoral calcinosis, a monogenic disorder of FGF23 (fibroblast growth factor-23) deficiency with a high prevalence of vascular calcification, underwent radiolabeled sodium fluoride positron emission tomography/computed tomography imaging. One patient received serial imaging 1 year after treatment with an IL-1 (interleukin-1) antagonist. A radiolabeled sodium fluoride-based microcalcification score, as well as calcification volume, was computed at all perpendicular slices, which were then mapped onto a standardized vascular atlas. Segment-wise mCSmean and mCSmax were computed to compare microcalcification score levels at predefined vascular segments within subjects. RESULTS: Patients with hyperphosphatemic familial tumoral calcinosis had notable peaks in microcalcification score near the aortic bifurcation and distal femoral arteries, compared with a control subject who had uniform distribution of vascular radiolabeled sodium fluoride uptake. This technique also identified microcalcification in a 17-year-old patient, who had no computed tomography-defined calcification. This technique could not only detect a decrease in microcalcification score throughout the patient treated with an IL-1 antagonist but it also identified anatomic areas that had increased responsiveness while there was no change in computed tomography-defined macrocalcification after treatment. CONCLUSIONS: This technique affords the ability to visualize spatial patterns of the active microcalcification process in the peripheral vasculature. Further, this technique affords the ability to track microcalcifications at precise locations not only across time but also across subjects. This technique is readily adaptable to other diseases of vascular calcification and may represent a significant advance in the field of vascular biology.


Assuntos
Fator de Crescimento de Fibroblastos 23 , Radioisótopos de Flúor , Hiperfosfatemia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Fluoreto de Sódio , Calcificação Vascular , Humanos , Hiperfosfatemia/genética , Hiperfosfatemia/diagnóstico por imagem , Masculino , Feminino , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/genética , Adulto , Valor Preditivo dos Testes , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Calcinose/genética , Calcinose/diagnóstico por imagem , Hiperostose Cortical Congênita
19.
Am J Hum Genet ; 111(5): 825-832, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38636509

RESUMO

Next-generation sequencing has revolutionized the speed of rare disease (RD) diagnoses. While clinical exome and genome sequencing represent an effective tool for many RD diagnoses, there is room to further improve the diagnostic odyssey of many RD patients. One recognizable intervention lies in increasing equitable access to genomic testing. Rural communities represent a significant portion of underserved and underrepresented individuals facing additional barriers to diagnosis and treatment. Primary care providers (PCPs) at local clinics, though sometimes suspicious of a potential benefit of genetic testing for their patients, have significant constraints in pursuing it themselves and rely on referrals to specialists. Yet, these referrals are typically followed by long waitlists and significant delays in clinical assessment, insurance clearance, testing, and initiation of diagnosis-informed care management. Not only is this process time intensive, but it also often requires multiple visits to urban medical centers for which distance may be a significant barrier to rural families. Therefore, providing early, "direct-to-provider" (DTP) local access to unrestrictive genomic testing is likely to help speed up diagnostic times and access to care for RD patients in rural communities. In a pilot study with a PCP clinic in rural Kansas, we observed a minimum 5.5 months shortening of time to diagnosis through the DTP exome sequencing program as compared to rural patients receiving genetic testing through the "traditional" PCP-referral-to-specialist scheme. We share our experience to encourage future partnerships beyond our center. Our efforts represent just one step in fostering greater diversity and equity in genomic studies.


Assuntos
Testes Genéticos , Genômica , Acessibilidade aos Serviços de Saúde , Doenças Raras , População Rural , Humanos , Testes Genéticos/métodos , Doenças Raras/genética , Doenças Raras/diagnóstico , Genômica/métodos , Criança , Masculino , Sequenciamento de Nucleotídeos em Larga Escala , Feminino
20.
JMIR Res Protoc ; 13: e53362, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38648088

RESUMO

BACKGROUND: Rare diseases in Europe are defined as diseases with a prevalence of less than 5 per 10,000 people. Despite their individual rarity, the total number of rare diseases is considerable. Rare diseases are often chronic and complex, affecting physical, mental, and neurological health. People with rare diseases face challenges such as delayed diagnosis, limited medical support, and financial burden. Caregivers, usually family members, bear significant physical and emotional burdens. Understanding the experiences of patients with rare disease and their caregivers is critical to effective care, but this is still underresearched. Better support and understanding of the challenges faced by both patients and caregivers is clearly needed. Our study will explore the experiences and needs of people with rare diseases and caregivers of people with rare diseases in relation to accessing health services. OBJECTIVE: This study aims to explore the experiences of patients with rare disease and their caregivers with Slovenian health care providers and to create a theoretical model of needs and experiences. METHODS: This is a qualitative thematic analysis study, using the codebook approach. The study will conduct semi-open-ended interviews to understand the experiences and needs of people with rare diseases and caregivers of people with rare diseases in relation to accessing health services. The interview questions will be based on an extensive literature review. Data from the interviews will be analyzed using thematic analysis to identify patterns and build a thematic map. Data will be analyzed by at least 2 coders. To ensure reliability, respondent validation will be conducted and negative cases investigated. Any discrepancies will be resolved by consulting the entire research team until a consensus is reached. RESULTS: This study was not specifically funded. However, author TC is supported by grant number P3-0339 from the Slovenian Agency for Research and Innovation. This study was approved by the Medical Ethics Committee of the Republic of Slovenia (0120-47/2022/3), and recruitment is expected to begin in May 2024, with data analysis results anticipated by the end of 2025. CONCLUSIONS: This study will fill an important research gap in Slovenia by exploring the needs and experiences of people living with rare diseases and their caregivers. The results will contribute to the broader field of rare diseases and add knowledge that can inform future research processes and intervention strategies. It also aims to identify neglected areas that have a significant impact on the lives of people with rare diseases. This study is important not only because it addresses the immediate needs of the Slovenian rare disease community, but also because it contributes to a discussion on patient-centered care, health policy design, and the inclusion of psychosocial components in health care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/53362.


Assuntos
Cuidadores , Pessoal de Saúde , Avaliação das Necessidades , Doenças Raras , Adulto , Feminino , Humanos , Masculino , Cuidadores/psicologia , Pessoal de Saúde/psicologia , Necessidades e Demandas de Serviços de Saúde , Pesquisa Qualitativa , Doenças Raras/psicologia , Doenças Raras/terapia , Eslovênia
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