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At least 73 records · Page 4Linked to original sources
PubMed2005

The use of routinely collected computer data for research in primary care: opportunities and challenges.

INTRODUCTION: Routinely collected primary care data has underpinned research that has helped define primary care as a specialty. In the early years of the discipline, data were collected manually, but digital data collection now makes large volumes of data readily available. Primary care informatics is emerging as an academic discipline for the scientific study of how to harness these data. This paper reviews how data are stored in primary care computer systems; current use of large primary care research databases; and, the opportunities and challenges for using routinely collected primary care data in research. OPPORTUNITIES: (1) Growing volumes of routinely recorded data. (2) Improving data quality. (3) Technological progress enabling large datasets to be processed. (4) The potential to link clinical data in family practice with other data including genetic databases. (5) An established body of know-how within the international health informatics community. CHALLENGES: (1) Research methods for working with large primary care datasets are limited. (2) How to infer meaning from data. (3) Pace of change in medicine and technology. (4) Integrating systems where there is often no reliable unique identifier and between health (person-based records) and social care (care-based records-e.g. child protection). (5) Achieving appropriate levels of information security, confidentiality, and privacy. CONCLUSION: Routinely collected primary care computer data, aggregated into large databases, is used for audit, quality improvement, health service planning, epidemiological study and research. However, gaps exist in the literature about how to find relevant data, select appropriate research methods and ensure that the correct inferences are drawn.

Biomedical Research↗
PubMed2006

Status of clinical gene sequencing data reporting and associated risks for information loss.

Clinical gene sequencing is growing in importance and cost-effectiveness. In the past two years, the number of genes associated with disease has grown by roughly 25%. Knowledge of genetic variations will soon guide drug selection and dosages, predict risks from toxin exposures, and inform nutritional needs. Despite the significance of sequencing, methods for reporting results are problematic. Frequent use of paper and infrequent use of naming standards impede data exchange and make incorporation into the electronic medical record difficult. Reports often describe only variations found, rather than all data (all patient bases sequenced). Also, reports frequently do not describe reference data used to define variations. These practices create risks for loss of both data and information. Standardized electronic reporting of all data (all bases sequenced and all reference data) and electronic record systems capable of storing these results would both prevent data loss and simplify the preservation of information those data provide.

Computer Security↗
PubMed2002

International consensus statement on malignant peripheral nerve sheath tumors in neurofibromatosis.

Neurofibromatosis 1 (NF1) is an autosomal dominant tumor predisposition syndrome in which affected individuals have a greatly increased risk of developing malignant peripheral nerve sheath tumors (MPNSTs). These cancers are difficult to detect and have a poor prognosis. Because patients may present to specialists from widely differing disciplines, the association with NF1 is often not appreciated, and there is no cohesive pattern of care. A multidisciplinary group of 33 clinicians and scientists with specialist knowledge in MPNST and NF1 reviewed the current published and unpublished data in this field, and distilled their collective experience to produce a consensus summary on MPNST in NF1. The known clinical, pathological, and genetic information on MPNST in NF1was collated, and a database was established to record information in a uniform manner. Subgroups with a higher risk of developing MPNSTwere identified within the NF1 population. The consortium formulated proposals and guidelines for clinical and pathological diagnosis, surgical management, and medical treatment of MPNST in individuals with NF1.A multidisciplinary team approach to the management of this complex disorder is advocated. Progress can be made by adopting the guidelines proposed by this consortium and by widespread dissemination of standardized information. Collaborative research should be promoted with the aim of harnessing advances in molecular genetics to develop targeted therapies for MPNST in people with NF1.

Adolescent↗
PubMed2006

Rare bleeding disorders.

Deficiencies of coagulation factors other than factor VIII and factor IX (afibrinogenemia, FII, FV, FV+FVIII, FVII, FX, FXI, FXIII) that cause bleeding disorders (RBDs) are inherited as autosomal recessive traits and are rare, with prevalences in the general population varying between 1 in 500,000 and 1 in 2 million for the homozygous forms. As a consequence of the rarity of these deficiencies, the type and severity of bleeding symptoms, the underlying molecular defects, and the actual management of bleeding episodes are not as well established as for hemophilia A and B. The study of the genetic basis of these disorders could represent an important tool for prevention through prenatal diagnosis. Treatment of patients with RBDs during bleeding episodes or surgery is a challenge because of the lack of experience and the paucity of data. For some deficiency factor concentrates are still non available and severe complications can occur. These complications can be minimized by assessment of risks of bleeding and thrombosis, use of haemostatic means other than blood components or no therapy at all. The RBDs pose a problem for guideline writers because there are no suitable clinical trials to supply good evidence for how these people are best treated. The lack of adequate information on clinical manifestations, treatment and genetic basis of RBDs could be improved by the collection of data in an International Database (http://www.rbdd.org), linkable to others previously published. This could be a useful tool to fill the gap between clinical data and clinical practice. This article reviews the genetic basis of RBDs, problems and complications of treatment, problems in the preparation of suitable guidelines for treatment and the future perspectives of the International Registry on RBDs.

Blood Coagulation Disorders, Inherited↗
PubMed2002

Mutation databases and other online sites as a resource for transfusion medicine: history and attributes.

Recent advances in molecular biology and technology have provided evidence, at a molecular level, for long-known observations that the human genome is not unique but is characterized by individual sequence variation. At the present time, documentation of genetic variation occurring in a large number of genes is increasing exponentially. The characterization of alleles that encode a variety of blood group antigens has been particularly fruitful for transfusion medicine. Phenotypic variation, as identified by the serologic study of blood group variants, is required to identify the presence of a variant allele. Many of the other alleles currently recorded have been selected and identified on the basis of inherited disease traits. New approaches document single nucleotide polymorphisms that occur throughout the genome and best show how the DNA sequence varies in the human population. The primary data dealing with variant alleles or more general genomic variation are scattered throughout the scientific literature and only within the last few years has information begun to be organized into databases. This article provides guidance on how to access those databases online as a source of information about genetic variation for purposes of molecular, clinical, and diagnostic medicine, research, and teaching. The attributes of the sites are described. A more detailed view of the database dealing specifically with alleles of genes encoding the blood group antigens includes a brief preliminary analysis of the molecular basis for observed polymorphisms. Other online sites that may be particularly useful to the transfusion medicine readership as well as a brief historical account are also presented.

Blood Group Antigens↗
PubMed2003

Tissue microarrays.

High-throughput tissue microarray (TMA) technology facilitates the assessment of the clinical relevance of molecular markers by enabling the simultaneous analysis of hundreds of tissue specimens. The widespread adoption of TMAs in many laboratories replaces the conventional one-slide-one-section approach, in which individual archival clinical specimens were placed on separate microscope slides, with the ability to assess RNA, DNA, or protein expression in hundreds of individual patient specimens in a single experiment. One of the applications of this technology is to significantly accelerate advances in translational research through more efficient assessment of novel markers of outcome and response, and as a result, a more rapid application of this knowledge to clinical practice.

Animals↗
PubMedDate not supplied

[Structure, use, and risks of biomaterial repositories of embryonal tumors].

Availability of statistically sufficient numbers of tumor samples and other biomaterials in high quality together with corresponding clinical data is crucial for biomedical research. Tumor repositories from individual scientists are mostly not sufficient to satisfy these criteria, especially since pediatric tumors are rare. In 2000 three centralized tumor repositories (neuroblastoma in Cologne, nephroblastoma in Würzburg, hepatoblastoma, brain tumors in Bonn) have been established by the "German Competence Net Pediatric Oncology und Hematology". The aim was to collect biomaterial including tumor samples, normal tissue, and blood in high quality for research and diagnostic purposes at a central institution. Informed consent of the parents or patients is a prerequisite for scientific use of the samples and is requested by the therapy trial. The samples are collected according to accepted standards and shipped in the specially designed Tumorbox. The tumor repository organizes the distribution of the samples to the cooperating diagnostic laboratories. The number of collected tumor samples has increased over the years. In 2000, samples from 200 patients were collected while the patient number increased to 321 in 2005. Over the years the tumor repositories collected more than 7,150 samples (fresh frozen tumor, fresh frozen normal tissue, and blood). Through links with clinical trial databases the samples can be connected with clinical data. 12 of 14 applications for tumor material to be used in specific scientific projects have been approved by an independent supervisory board. The establishment of central tumor repositories represents a major step for biomedical research activities and quality control in pediatric oncology.

Biocompatible Materials↗
PubMed2005

Clinical pharmacogenomics and transcriptional profiling in early phase oncology clinical trials.

Microarray-based expression profiling studies in the field of oncology have demonstrated encouraging correlations between tumor transcriptional profiles and eventual patient outcomes. These findings have fueled great interest in the application of transcriptional profiling to samples available from real-time clinical trials, and clinical pharmacogenomic objectives utilizing transcriptional profiling strategies are becoming increasingly incorporated into clinical trial study designs. Over the last few years several retrospective studies based on the profiling of archival tumor tissues suggest that transcriptional analysis of oncology samples may provide general prognosis measures, and in some cases may even predict response to specific therapies. Recently the FDA released a voluntary genomic data guidance meant to assist both regulatory agencies and pharmaceutical companies alike in evaluating the potential benefit of implementing expression profiling studies during the preclinical and clinical phases of drug development. Despite the great promise afforded by this technology, the ultimate benefit of applying transcriptional profiling in prospective clinical trials has yet to be realized because a number of practical impediments to this process exist. The multi-fold purpose of the current review is to highlight the increasing evidence from studies that have identified transcriptional signatures in archived tumors prognostic of patient outcome, to describe some of the drivers for the implementation of transcriptional profiling strategies in real-time drug development, to discuss the use of transcriptional profiling in the context of increasingly complex translational medicine strategies, and to highlight the practical issues and potential approaches involved in the successful application of clinical pharmacogenomic objectives during real-time clinical trials. Strategic implementation of transcriptional profiling in early oncology clinical trials can provide an opportunity to identify predictive markers of clinical response and eventually provide a substantial step forward towards the era of personalized medicine.

Antineoplastic Agents↗
PubMed2026

Large-scale functional annotation establishes a reference framework for human LRRK2 variants.

Pathogenic variants in leucine-rich repeat kinase 2 (LRRK2)1are among the most frequent monogenic causes of Parkinson's disease (PD)2 and act through a gain-of-function mechanism of increased kinase activity. LRRK2-targeted therapies are in clinical development, but interpretation of the rapidly expanding catalogue of rare LRRK2 variants remains a barrier to translation. Here, we present functionally annotated data on >350 LRRK2 coding variants using a standardized cellular assay with Rab10 phosphorylation as a readout of kinase activity and integrated these data with curated genetic and clinical annotations from the Movement Disorders Society Genetic Mutation Database (MDSGene). Variants differed in activation magnitude, ranging from modest increases (e.g., p.G2019S) to strongly activating substitutions such as p.Y1699C or p.L1795F. Activating variants occurred across the full length of LRRK2, although the largest effects clustered within the ROC-COR regulatory hub, where structural analysis identified subdomains forming an allosteric scaffold controlling kinase output. All known/established pathogenic variants showed increased activity, whereas benign and likely benign variants remained within the wild-type range. Functional effect sizes correlated with pathway activation in patient-derived immune cells, altogether providing a framework for ACMG-based variant interpretation in which kinase activation can support PS3 functional evidence for reclassification of variants.

Protein phosphorylation↗
PubMed2004

Construction, training and clinical validation of an interpretation system for genotypic HIV-1 drug resistance based on fuzzy rules revised by virological outcomes.

OBJECTIVES: To evaluate whether fuzzy operators can be usefully applied to the interpretation of genotypic HIV-1 drug resistance by experts, and to improve the prediction of salvage therapy outcome by adapting interpretation rules of genotypic resistance on the basis of their association with virological response data. METHODS: We used a clinical dataset of 231 patients failing highly active antiretroviral therapy (HAART) and starting salvage therapy with baseline resistance genotyping and virological outcomes after 3 and 6 months. A set of rules predicting genotypic resistance was initially derived from an expert (ADL). Rules were implemented using a fuzzy logic approach and the virological outcomes dataset used for the training phase. The resulting algorithm was validated using a separate set of 184 selected patients by correlating the resulting predicted activity with observed virological response at 3 months. For comparison, the expert systems from the drug resistance group of the Agence Nationale de Recherches sur le SIDA (ANRS-AC11) and the algorithm from the Stanford's HIV drug resistance database (Stanford HIVdb) were evaluated on the same set. RESULTS: The starting algorithm had a correlation with virological outcomes of R2=0.06 (P=0.0001). After the training phase the correlation with virological outcomes increased to R2=0.19 (P<0.000001). In the validation set of patients, the activity of the salvage regimen predicted by the fuzzy algorithm was the only variable independently predictive of the 3-month viral load change even after adjusting by the activity predicted by the two expert systems and baseline viral load (for each 10% salvage regimen's activity increase, mean HIV RNA change from baseline: -0.27 log10 copies/ml; 95% CI -0.39, -0.15). CONCLUSION: Using fuzzy operators in a virological outcomes training database to implement a rules-based algorithm for genotypic resistance interpretation, significant improvements of outcomes prediction were obtained. The resulting algorithm showed an independent predictive capability of virological outcomes over that of two rules-based interpretation algorithms made by experts. Although the system was trained and validated on a limited number of cases, the approach deserves further evaluation.

Adolescent↗
PubMed2006

Designing new methodologies for integrating biomedical information in clinical trials.

OBJECTIVES: To propose a modification to current methodologies for clinical trials, improving data collection and cost-efficiency. To describe a system to integrate distributed and heterogeneous medical and genetic databases for improving information access, retrieval and analysis of biomedical information. METHODS: Data for clinical trials can be collected from remote, distributed and heterogeneous data sources. In this distributed scenario, we propose an ontologybased approach, with two basic operations: mapping and unification. Mapping outputs the semantic model of a virtual repository with the information model of a specific database. Unification provides a single schema for two or more previously available virtual repositories. In both processes, domain ontologies can improve other traditional approaches. RESULTS: Private clinical databases and public genomic and disease databases (e.g., OMIM, Prosite and others) were integrated. We successfully tested the system using thirteen databases containing clinical and biological information and biomedical vocabularies. CONCLUSIONS: We present a domain-independent approach to biomedical database integration, used in this paper as a reference for the design of future models of clinico-genomic trials where information will be integrated, retrieved and analyzed. Such an approach to biomedical data integration has been one of the goals of the IST INFOBIOMED Network of Excellence in Biomedical Informatics, funded by the European Commission, and the new ACGT (Advanced Clinico-Genomic Trials on Cancer) project, where the authors will apply these methods to research experiments.

Clinical Trials as Topic↗
PubMed1998

Creation and maintenance of Helix, a Web based database of medical genetics laboratories, to serve the needs of the genetics community.

Helix (healthlinks.washington.edu/helix) is a web accessible database that serves as the main U.S. directory of laboratories offering genetic testing. The database was designed to address the previously unmet need for a centralized, continuously updated source of information about clinical and research genetic testing to keep pace with the rapid rate of gene discovery resulting from the Human Genome Project. The Helix project began in 1992 at the University of Washington and Children's Hospital and Regional Medical Center. It has evolved from a single user stand alone relational database to a fully Web enabled database queried and maintained via the web and linked to other web accessible genomic databases. As of February, 1998 it lists more than 500 diseases and 290 laboratories, with over 5,200 registered users making approximately 250 queries/day (90% via the Internet). We describe the iterative design, implementation, population and assessment of the database over a six year period.

Database Management Systems↗
PubMed2002

Bioinformatic methods for allergenicity assessment using a comprehensive allergen database.

BACKGROUND: A principal aim of the safety assessment of genetically modified crops is to prevent the introduction of known or clinically cross-reactive allergens. Current bioinformatic tools and a database of allergens and gliadins were tested for the ability to identify potential allergens by analyzing 6 Bacillus thuringiensis insecticidal proteins, 3 common non-allergenic food proteins and 50 randomly selected corn (Zea mays) proteins. METHODS: Protein sequences were compared to allergens using the FASTA algorithm and by searching for matches of 6, 7 or 8 contiguous identical amino acids. RESULTS: No significant sequence similarities or matches of 8 contiguous amino acids were found with the B. thuringiensis or food proteins. Surprisingly, 41 of 50 corn proteins matched at least one allergen with 6 contiguous identical amino acids. Only 7 of 50 corn proteins matched an allergen with 8 contiguous identical amino acids. When assessed for overall structural similarity to allergens, these 7 plus 2 additional corn proteins shared >or=35% identity in an overlap of >or=80 amino acids, but only 6 of the 7 were similar across the length of the protein, or shared >50% identity to an allergen. CONCLUSIONS: An evaluation of a protein by the FASTA algorithm is the most predictive of a clinically relevant cross-reactive allergen. An additional search for matches of 8 amino acids may provide an added margin of safety when assessing the potential allergenicity of a protein, but a search with a 6-amino-acid window produces many random, irrelevant matches.

Algorithms↗
PubMed2004

An Atlas on genes and chromosomes in oncology and haematology.

The "Atlas of Genetics and Cytogenetics in Oncology and Haematology" http://www.infobiogen.fr/services/chromcancer is a peer-reviewed and free internet database aimed at genes involved in cancer, cytogenetics and clinical entities in cancer, and cancer-prone diseases. It contains concise and updated review articles, a huge portal towards genetics and/or cancer databases, and teaching materials in genetics for the students. This database is made for and by clinicians and researchers, who are encouraged to contribute. The Atlas is part of the genome project. It provides information in cancer epidemiology. It contributes to research, university and post-university teaching, and telemedicine. It contributes to 'meta-medicine', a mediation using new information technology, between the overflowing information provided by the scientific community and the individual practitioner.

Chromosome Aberrations↗