Evidence for 28 genetic disorders discovered by combining healthcare and research data.
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ABSTRACT:
SUBMITTER: Kaplanis J
PROVIDER: S-EPMC7116826 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC9846327 | biostudies-literature
Project description:BACKGROUND:Health services researchers spend a substantial amount of time performing integration, cleansing, interpretation, and aggregation of raw data from multiple public or private data sources. Often, each researcher (or someone in their team) duplicates this effort for their own project, facing the same challenges and experiencing the same pitfalls discovered by those before them. OBJECTIVE:This paper described a design process for creating a data warehouse that includes the most frequently used databases in health services research. METHODS:The design is based on a conceptual iterative process model framework that utilizes the sociotechnical systems theory approach and includes the capacity for subsequent updates of the existing data sources and the addition of new ones. We introduce the theory and the framework and then explain how they are used to inform the methodology of this study. RESULTS:The application of the iterative process model to the design research process of problem identification and solution design for the Healthcare Research and Analytics Data Infrastructure Solution (HRADIS) is described. Each phase of the iterative model produced end products to inform the implementation of HRADIS. The analysis phase produced the problem statement and requirements documents. The projection phase produced a list of tasks and goals for the ideal system. Finally, the synthesis phase provided the process for a plan to implement HRADIS. HRADIS structures and integrates data dictionaries provided by the data sources, allowing the creation of dimensions and measures for a multidimensional business intelligence system. We discuss how HRADIS is complemented with a set of data mining, analytics, and visualization tools to enable researchers to more efficiently apply multiple methods to a given research project. HRADIS also includes a built-in security and account management framework for data governance purposes to ensure customized authorization depending on user roles and parts of the data the roles are authorized to access. CONCLUSIONS:To address existing inefficiencies during the obtaining, extracting, preprocessing, cleansing, and filtering stages of data processing in health services research, we envision HRADIS as a full-service data warehouse integrating frequently used data sources, processes, and methods along with a variety of data analytics and visualization tools. This paper presents the application of the iterative process model to build such a solution. It also includes a discussion on several prominent issues, lessons learned, reflections and recommendations, and future considerations, as this model was applied.
| S-EPMC7303827 | biostudies-literature
Project description:Background and aimsOver the last decade, regulators have taken significant steps towards tackling perceptions that regulatory systems are burdensome. There has been much international research activity in the regulation of health and care professionals. This article reports a review of studies on health professions regulation between January 2011 and March 2020. Its chief object was to provide robust and up-to-date evidence to assist regulators in policy development and implementation. The main objectives of this study were to: 1. Identify and retrieve research in the field of health and care professions regulation in English since 2011; 2. Evaluate the published research, exploring its utility to regulators and practitioners, and drawing out any key messages; 3. Draw conclusions concerning the scope and limitations of the research literature and identify areas for further research.MethodsWe undertook a rapid evidence assessment (REA) of the international literature on health and care professions regulation, including reviewing ten UK regulators' websites to identify issues of concern and strategic priorities. We retrieved 3833 references, using a four-stage screening process to select the 81 most relevant.ResultsResults are reported within six key themes: harm prevention and patient safety; fitness to practise; quality assurance of education and training; registration including maintenance of registers; guidelines and standards and relations with regulatory bodies.ConclusionsRegulation of professionals in health and care is comparatively undeveloped as a field of academic study. Consequently, the published evidence is diffuse and small-scale. Most work presents relatively weak data of low relevance to regulators, mainly reporting or describing the current position. Few studies are able to show the impact of regulation or demonstrate a causal link between regulation and its effects. To inform their research and policy agendas health and social care regulators need to commission, interpret and apply the scholarly literature more effectively; academics need to engage with regulators to ensure that their research provides high-quality evidence with practical relevance to the regulators' agendas. Further study is needed to explore how effective academic collaborations between regulators and researchers may be created and sustained.
| S-EPMC8425088 | biostudies-literature
Project description:PurposeWithin this study, we aimed to discover novel gene-disease associations in patients with no genetic diagnosis after exome/genome sequencing (ES/GS).MethodsWe followed two approaches: (1) a patient-centered approach, which after routine diagnostic analysis systematically interrogates variants in genes not yet associated to human diseases; and (2) a gene variant centered approach. For the latter, we focused on de novo variants in patients that presented with neurodevelopmental delay (NDD) and/or intellectual disability (ID), which are the most common reasons for genetic testing referrals. Gene-disease association was assessed using our data repository that combines ES/GS data and Human Phenotype Ontology terms from over 33,000 patients.ResultsWe propose six novel gene-disease associations based on 38 patients with variants in the BLOC1S1, IPO8, MMP15, PLK1, RAP1GDS1, and ZNF699 genes. Furthermore, our results support causality of 31 additional candidate genes that had little published evidence and no registered OMIM phenotype (56 patients). The phenotypes included syndromic/nonsyndromic NDD/ID, oral-facial-digital syndrome, cardiomyopathies, malformation syndrome, short stature, skeletal dysplasia, and ciliary dyskinesia.ConclusionOur results demonstrate the value of data repositories which combine clinical and genetic data for discovering and confirming gene-disease associations. Genetic laboratories should be encouraged to pursue such analyses for the benefit of undiagnosed patients and their families.
| S-EPMC8354858 | biostudies-literature
Project description:BackgroundHuman genome sequencing has transformed our understanding of genomic variation and its relevance to health and disease, and is now starting to enter clinical practice for the diagnosis of rare diseases. The question of whether and how some categories of genomic findings should be shared with individual research participants is currently a topic of international debate, and development of robust analytical workflows to identify and communicate clinically relevant variants is paramount.MethodsThe Deciphering Developmental Disorders (DDD) study has developed a UK-wide patient recruitment network involving over 180 clinicians across all 24 regional genetics services, and has performed genome-wide microarray and whole exome sequencing on children with undiagnosed developmental disorders and their parents. After data analysis, pertinent genomic variants were returned to individual research participants via their local clinical genetics team.FindingsAround 80,000 genomic variants were identified from exome sequencing and microarray analysis in each individual, of which on average 400 were rare and predicted to be protein altering. By focusing only on de novo and segregating variants in known developmental disorder genes, we achieved a diagnostic yield of 27% among 1133 previously investigated yet undiagnosed children with developmental disorders, whilst minimising incidental findings. In families with developmentally normal parents, whole exome sequencing of the child and both parents resulted in a 10-fold reduction in the number of potential causal variants that needed clinical evaluation compared to sequencing only the child. Most diagnostic variants identified in known genes were novel and not present in current databases of known disease variation.InterpretationImplementation of a robust translational genomics workflow is achievable within a large-scale rare disease research study to allow feedback of potentially diagnostic findings to clinicians and research participants. Systematic recording of relevant clinical data, curation of a gene-phenotype knowledge base, and development of clinical decision support software are needed in addition to automated exclusion of almost all variants, which is crucial for scalable prioritisation and review of possible diagnostic variants. However, the resource requirements of development and maintenance of a clinical reporting system within a research setting are substantial.FundingHealth Innovation Challenge Fund, a parallel funding partnership between the Wellcome Trust and the UK Department of Health.
| S-EPMC4392068 | biostudies-literature
Project description:The role of microfinance in alleviating poverty and poor health is significant. Its health programs have been shown to improve healthcare utilization and strengthen a healthcare system. In the Philippines, microfinance's widespread presence is seen as instrumental in achieving the objectives of Healthy Philippines 2022, particularly in reducing poverty-driven healthcare costs. However, little is known on how microfinance can reduce the cost of healthcare services and treatment. Also, few studies that consider the practice of integrated microfinance and health programs in the Philippines have been seen. Secondary data was used to explore the structure and function of microfinance and health initiatives and their influence in mitigating healthcare costs. A review criterion was developed to examine the data using the three key elements identified in Ruducha and Jadhav's framework: organisational arrangement, health products and health outcomes. Findings revealed that most health initiatives are delivered through partnerships and collaboration, could favour a reduction in healthcare costs and protection from out-of-pocket health expenditure. They are designed to operate in three structures-subsidised or outreach, microinsurance and health loans, and patronage refunds. The cooperative's business venture providing pharmaceuticals facilitated access to affordable medicine and offered its members financial viability. Health loans and microinsurance also offered healthcare cost reductions; however, uptakes are low. The study found no data to assess the output of the completed health initiatives. More studies that will evaluate the integrated MFI health initiatives are recommended to further identify gaps, outcomes, or impacts of the program.
| S-EPMC7578378 | biostudies-literature
Project description:Anorexia nervosa (AN) and bulimia nervosa (BN) are complex disorders characterized by disordered eating behavior where the patient's attitude towards weight and shape, as well as their perception of body shape, are disturbed. Formal genetic studies on twins and families suggested a substantial genetic influence for AN and BN. Candidate gene studies have initially focused on the serotonergic and other central neurotransmitter systems and on genes involved in body weight regulation. Hardly any of the positive findings achieved in these studies were unequivocally confirmed or substantiated in meta-analyses. This might be due to too small sample sizes and thus low power and/or the genes underlying eating disorders have not yet been analyzed. However, some studies that also used subphenotypes (e.g., restricting type of AN) led to more specific results; however, confirmation is as yet mostly lacking. Systematic genome-wide linkage scans based on families with at least two individuals with an eating disorder (AN or BN) revealed initial linkage regions on chromosomes 1, 3 and 4 (AN) and 10p (BN). Analyses on candidate genes in the chromosome 1 linkage region led to the (as yet unconfirmed) identification of certain variants associated with AN. Genome-wide association studies are under way and will presumably help to identify genes and pathways involved in these eating disorders. The elucidation of the molecular mechanisms underlying eating disorders might improve therapeutic approaches.
| S-EPMC2839487 | biostudies-literature
Project description: Not available
| S-EPMC9669996 | biostudies-literature
Project description:Contextual factors influencing population health have received substantial attention, especially with regard to people's social networks and the roles of built environments in their activity spaces. Yet little health research has considered spatial and social contexts simultaneously, often because of a lack of existing data. This paper presents a tool for collecting relational data on social network and activity space that extends an existing map-based questionnaire with the addition of a name generator. We then illustrate how network analysis provides a useful framework for studying connections between social and spatial contexts using data collected in the Contrasted Urban settings for Healthy Aging research project.
| S-EPMC7534796 | biostudies-literature
Project description:ObjectiveThe rapidly evolving COVID-19 pandemic has created a need for timely data from the healthcare systems for research. To meet this need, several large new data consortia have been developed that require frequent updating and sharing of electronic health record (EHR) data in different common data models (CDMs) to create multi-institutional databases for research. Traditionally, each CDM has had a custom pipeline for extract, transform, and load operations for production and incremental updates of data feeds to the networks from raw EHR data. However, the demands of COVID-19 research for timely data are far higher, and the requirements for updating faster than previous collaborative research using national data networks have increased. New approaches need to be developed to address these demands.MethodsIn this article, we describe the use of the Fast Healthcare Interoperability Resource (FHIR) data model as a canonical data model and the automated transformation of clinical data to the Patient-Centered Outcomes Research Network (PCORnet) and Observational Medical Outcomes Partnership (OMOP) CDMs for data sharing and research collaboration on COVID-19.ResultsFHIR data resources could be transformed to operational PCORnet and OMOP CDMs with minimal production delays through a combination of real-time and postprocessing steps, leveraging the FHIR data subscription feature.ConclusionsThe approach leverages evolving standards for the availability of EHR data developed to facilitate data exchange under the 21st Century Cures Act and could greatly enhance the availability of standardized datasets for research.
| S-EPMC8243354 | biostudies-literature