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Clinical and Translational Science Nov 2023Artificial intelligence (AI) utilization in health care has grown over the past few years. It also has demonstrated potential in improving the efficiency of diagnosis... (Review)
Review
Artificial intelligence (AI) utilization in health care has grown over the past few years. It also has demonstrated potential in improving the efficiency of diagnosis and treatment. Some types of AI, such as machine learning, allow for the efficient analysis of vast datasets, identifying patterns, and generating key insights. Predictions can then be made for medical diagnosis and personalized treatment recommendations. The use of AI can bypass some conventional limitations associated with rare diseases. Namely, it can optimize traditional randomized control trials, and may eventually reduce costs for drug research and development. Recent advancements have enabled researchers to train models based on large datasets and then fine-tune these models on smaller datasets typically associated with rare diseases. In this mini-review, we discuss recent advancements in AI and how AI can be applied to streamline rare disease diagnosis and optimize treatment.
Topics: Humans; Artificial Intelligence; Rare Diseases; Machine Learning; Precision Medicine; Delivery of Health Care
PubMed: 37646577
DOI: 10.1111/cts.13619 -
Nature Reviews. Drug Discovery Feb 2020A lack of robust knowledge of the number of rare diseases and the number of people affected by them limits the development of approaches to ameliorate the substantial...
A lack of robust knowledge of the number of rare diseases and the number of people affected by them limits the development of approaches to ameliorate the substantial cumulative burden of rare diseases. Here, we call for coordinated efforts to more precisely define rare diseases.
Topics: Humans; Phenotype; Rare Diseases
PubMed: 32020066
DOI: 10.1038/d41573-019-00180-y -
Genome Medicine Feb 2022Rare diseases affect 30 million people in the USA and more than 300-400 million worldwide, often causing chronic illness, disability, and premature death. Traditional... (Review)
Review
Rare diseases affect 30 million people in the USA and more than 300-400 million worldwide, often causing chronic illness, disability, and premature death. Traditional diagnostic techniques rely heavily on heuristic approaches, coupling clinical experience from prior rare disease presentations with the medical literature. A large number of rare disease patients remain undiagnosed for years and many even die without an accurate diagnosis. In recent years, gene panels, microarrays, and exome sequencing have helped to identify the molecular cause of such rare and undiagnosed diseases. These technologies have allowed diagnoses for a sizable proportion (25-35%) of undiagnosed patients, often with actionable findings. However, a large proportion of these patients remain undiagnosed. In this review, we focus on technologies that can be adopted if exome sequencing is unrevealing. We discuss the benefits of sequencing the whole genome and the additional benefit that may be offered by long-read technology, pan-genome reference, transcriptomics, metabolomics, proteomics, and methyl profiling. We highlight computational methods to help identify regionally distant patients with similar phenotypes or similar genetic mutations. Finally, we describe approaches to automate and accelerate genomic analysis. The strategies discussed here are intended to serve as a guide for clinicians and researchers in the next steps when encountering patients with non-diagnostic exomes.
Topics: Exome; Genomics; Humans; Rare Diseases; Undiagnosed Diseases; Exome Sequencing
PubMed: 35220969
DOI: 10.1186/s13073-022-01026-w -
Genome Medicine Jan 2023Rare diseases collectively impose a significant burden on healthcare systems, especially in underserved regions, like the Middle East, which lack access to genomic...
BACKGROUND
Rare diseases collectively impose a significant burden on healthcare systems, especially in underserved regions, like the Middle East, which lack access to genomic diagnostic services and the associated personalized management plans.
METHODS
We established a clinical genomics and genetic counseling facility, within a multidisciplinary tertiary pediatric center, in the United Arab Emirates to locally diagnose and manage patients with rare diseases. Clinical genomic investigations included exome-based sequencing, chromosomal microarrays, and/or targeted testing. We assessed the diagnostic yield and implications for clinical management among this population. Variables were compared using the Fisher exact test. Tests were 2-tailed, and P < .05 was considered statistically significant.
RESULTS
We present data on 1000 patients with rare diseases (46.2% females; average age, 4.6 years) representing 47 countries primarily from the Arabian Peninsula, the Levant, Africa, and Asia. The cumulative diagnostic yield was 32.5% (95% CI, 29.7-35.5%) and was higher for genomic sequencing-based testing than chromosomal microarrays (37.9% versus 17.2%, P = 0.0001) across all indications, consistent with the higher burden of single gene disorders. Of the 221 Mendelian disorders identified in this cohort, the majority (N = 184) were encountered only once, and those with recessive inheritance accounted for ~ 62% of sequencing diagnoses. Of patients with positive genetic findings (N = 325), 67.7% were less than 5 years of age, and 60% were offered modified management and/or intervention plans. Interestingly, 24% of patients with positive genetic findings received delayed diagnoses (average age, 12.4 years; range 7-37 years), most likely due to a lack of access to genomic investigations in this region. One such genetic finding ended a 15-year-long diagnostic odyssey, leading to a life-threatening diagnosis in one patient, who was then successfully treated using an experimental allogenic bone marrow transplant. Finally, we present cases with candidate genes within regions of homozygosity, likely underlying novel recessive disorders.
CONCLUSIONS
Early access to genomic diagnostics for patients with suspected rare disorders in the Middle East is likely to improve clinical outcomes while driving gene discovery in this genetically underrepresented population.
Topics: Child; Child, Preschool; Female; Humans; Male; Exome; Genetic Testing; Genomics; Middle East; Rare Diseases; Adolescent; Young Adult; Adult
PubMed: 36703223
DOI: 10.1186/s13073-023-01157-8 -
European Respiratory Review : An... Sep 2015http://ow.ly/PYUCC
http://ow.ly/PYUCC
Topics: Biomedical Research; Forecasting; Humans; Lung; Lung Diseases; Orphan Drug Production; Rare Diseases; Respiratory System Agents
PubMed: 26324798
DOI: 10.1183/16000617.0051-2015 -
International Journal of Molecular... Jan 2021There is no single global definition of a rare disease, and for different geographical areas the definition is based on the disease occurrence in that population [...].
There is no single global definition of a rare disease, and for different geographical areas the definition is based on the disease occurrence in that population [...].
Topics: Biomarkers; Disease Management; Disease Susceptibility; Humans; Rare Diseases
PubMed: 33445477
DOI: 10.3390/ijms22020673 -
Value in Health : the Journal of the... Sep 2015At present, there is no universal definition of rare disease. (Review)
Review
BACKGROUND
At present, there is no universal definition of rare disease.
OBJECTIVE
To provide an overview of rare disease definitions currently used globally.
METHODS
We systematically searched for definitions related to rare disease from organizations in 32 international jurisdictions. Descriptive statistics of definitions were generated and prevalence thresholds were calculated.
RESULTS
We identified 296 definitions from 1109 organizations. The terms "rare disease(s)" and "orphan drug(s)" were used most frequently (38% and 27% of the definitions, respectively). Qualitative descriptors such as "life-threatening" were used infrequently. A prevalence threshold was specified in at least one definition in 88% of the jurisdictions. The average prevalence threshold across organizations within individual jurisdictions ranged from 5 to 76 cases/100,000 people. Most jurisdictions (66%) had an average prevalence threshold between 40 and 50 cases/100,000 people, with a global average of 40 cases/100,000 people. Prevalence thresholds used by different organizations within individual jurisdictions varied substantially. Across jurisdictions, umbrella patient organizations had the highest (most liberal) average prevalence threshold (47 cases/100,000 people), whereas private payers had the lowest threshold (18 cases/100,000 people).
CONCLUSIONS
Despite variation in the terminology and prevalence thresholds used to define rare diseases among different jurisdictions and organizations, the terms "rare disease" and "orphan drug" are used most widely and the average prevalence threshold is between 40 and 50 cases/100,000 people. These findings highlight the existing diversity among definitions of rare diseases, but suggest that any attempts to harmonize rare disease definitions should focus on standardizing objective criteria such as prevalence thresholds and avoid qualitative descriptors.
Topics: Consensus; Global Health; Humans; Orphan Drug Production; Prevalence; Prognosis; Rare Diseases; Risk Assessment; Risk Factors; Terminology as Topic
PubMed: 26409619
DOI: 10.1016/j.jval.2015.05.008 -
Frontiers in Public Health 2022The genomics revolution over the past three decades has led to great strides in rare disease (RD) research, which presents a major shift in global policy landscape.... (Review)
Review
The genomics revolution over the past three decades has led to great strides in rare disease (RD) research, which presents a major shift in global policy landscape. While RDs are individually rare, there are common challenges and unmet medical and social needs experienced by the RD population globally. The various disabilities arising from RDs as well as diagnostic and treatment uncertainty were demonstrated to have detrimental influence on the health, psychosocial, and economic aspects of RD families. Despite the collective large number of patients and families affected by RDs internationally, the general lack of public awareness and expertise constraints have neglected and marginalized the RD population in health systems and in health- and social-care policies. The current Coronavirus Disease of 2019 (COVID-19) pandemic has exposed the long-standing and fundamental challenges of the RD population, and has reminded us of the critical need of addressing the systemic inequalities and widespread disparities across populations and jurisdictions. Owing to the commonality in goals between RD movements and universal health coverage targets, the United Nations (UN) has highlighted the importance of recognizing RDs in policies, and has recently adopted the UN Resolution to promote greater integration of RDs in the UN agenda, advancing UN's commitment in achieving the 2030 Sustainable Development Goals of "leav[ing] no one behind." Governments have also started to launch Genome Projects in their respective jurisdictions, aiming to integrate genomic medicine into mainstream healthcare. In this paper, we review the challenges experienced by the RD population, the establishment and adoption of RD policies, and the state of evidence in addressing these challenges from a global perspective. The Hong Kong Genome Project was illustrated as a case study to highlight the role of Genome Projects in enhancing clinical application of genomic medicine for personalized medicine and in improving equity of access and return in global genomics. Through reviewing what has been achieved to date, this paper will provide future directions as RD emerges as a global public health priority, in hopes of moving a step toward a more equitable and inclusive community for the RD population in times of pandemics and beyond.
Topics: Humans; Rare Diseases; Health Priorities; COVID-19; Public Health; Public Policy
PubMed: 36339196
DOI: 10.3389/fpubh.2022.1028545 -
Gaceta Medica de Mexico 2019Morphea, or localized scleroderma, is a rare disease of the connective tissue that manifests itself with localized sclerosis of the skin and, in some cases, with... (Review)
Review
Morphea, or localized scleroderma, is a rare disease of the connective tissue that manifests itself with localized sclerosis of the skin and, in some cases, with extracutaneous manifestations. Its etiology is not fully understood, but it is believed that there is genetic predisposition, in addition to environmental triggering factors. Classification of the disease is not simple due to its multiple presentations; however, it is useful in order to define the treatment, which should be individualized and started early to avoid cosmetic and functional complications. In this review, we summarize the most important practical aspects of the classification, diagnostic methods and evaluation of morphea activity, as well as available therapeutic options, with an emphasis on existing clinical evidence regarding their efficacy and safety.
Topics: Gene-Environment Interaction; Genetic Predisposition to Disease; Humans; Rare Diseases; Scleroderma, Localized
PubMed: 31695234
DOI: 10.24875/GMM.18004288 -
International Journal of Environmental... Mar 2023This document provides a comprehensive summary of evidence on the current situation of rare diseases (RDs) globally and regionally, including conditions, practices,... (Review)
Review
This document provides a comprehensive summary of evidence on the current situation of rare diseases (RDs) globally and regionally, including conditions, practices, policies, and regulations, as well as the challenges and barriers faced by RD patients, their families, and caregivers. The document builds on a review of academic literature and policies and a process of validation and feedback by a group of seven experts from across the globe. Panelists were selected based on their academic merit, expertise, and knowledge regarding the RD environment. The document is divided into five main sections: (1) methodology and objective; (2) background and context; (3) overview of the current situation and key challenges related to RDs covering six dimensions: burden of disease, patient journey, social impact, disease management, RD-related policies, and research and development; (4) recommendations; and (5) conclusions. The recommendations are derived from the discussion undertaken by the experts on the findings of this review and provide a set of actionable solutions to the challenges and barriers to improving access to RD diagnosis and treatment around the world. The recommendations can support critical decision-making, guiding efforts by a broad range of RDs stakeholders, including governments, international organizations, manufacturers, researchers, and patient advocacy groups.
Topics: Humans; Rare Diseases; Health Policy
PubMed: 36981643
DOI: 10.3390/ijerph20064732