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1.
Transfusion ; 62(10): 2029-2038, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36004803

RESUMO

BACKGROUND: Transfusion-related adverse events can be unrecognized and unreported. As part of the US Food and Drug Administration's Center for Biologics Evaluation and Research Biologics Effectiveness and Safety initiative, we explored whether machine learning methods, such as natural language processing (NLP), can identify and report transfusion allergic reactions (ARs) from electronic health records (EHRs). STUDY DESIGN AND METHODS: In a 4-year period, all 146 reported transfusion ARs were pulled from a database of 86,764 transfusions in an academic health system, along with a random sample of 605 transfusions without reported ARs. Structured and unstructured EHR data were retrieved, including demographics, new symptoms, medications, and lab results. In unstructured data, evidence from clinicians' notes, test results, and prescriptions fields identified transfusion ARs, which were used to extract NLP features. Clinician reviews of selected validation cases assessed and confirmed model performance. RESULTS: Clinician reviews of selected validation cases yielded a sensitivity of 67.9% and a specificity of 97.5% at a threshold of 0.9, with a positive predictive value (PPV) of 84%, estimated to 4.5% when extrapolated to match transfusion AR incidence in the full transfusion dataset. A higher threshold achieved sensitivity of 43% with specificity/PPV of 100% in our validation set. Essential features predicting ARs were recognized transfusion reactions, administration of antihistamines or glucocorticoids, and skin symptoms (e.g., hives and itching). Removal of NLP features decreased model performance. DISCUSSION: NLP algorithms can identify transfusion reactions from the EHR with a reasonable level of precision for subsequent clinician review and confirmation.


Assuntos
Produtos Biológicos , Hipersensibilidade , Reação Transfusional , Algoritmos , Registros Eletrônicos de Saúde , Glucocorticoides , Humanos , Hipersensibilidade/epidemiologia , Hipersensibilidade/etiologia , Reação Transfusional/epidemiologia , Reação Transfusional/etiologia
2.
Nature ; 472(7341): 90-4, 2011 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-21399628

RESUMO

Genomic analysis provides insights into the role of copy number variation in disease, but most methods are not designed to resolve mixed populations of cells. In tumours, where genetic heterogeneity is common, very important information may be lost that would be useful for reconstructing evolutionary history. Here we show that with flow-sorted nuclei, whole genome amplification and next generation sequencing we can accurately quantify genomic copy number within an individual nucleus. We apply single-nucleus sequencing to investigate tumour population structure and evolution in two human breast cancer cases. Analysis of 100 single cells from a polygenomic tumour revealed three distinct clonal subpopulations that probably represent sequential clonal expansions. Additional analysis of 100 single cells from a monogenomic primary tumour and its liver metastasis indicated that a single clonal expansion formed the primary tumour and seeded the metastasis. In both primary tumours, we also identified an unexpectedly abundant subpopulation of genetically diverse 'pseudodiploid' cells that do not travel to the metastatic site. In contrast to gradual models of tumour progression, our data indicate that tumours grow by punctuated clonal expansions with few persistent intermediates.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Evolução Molecular , Análise de Sequência de DNA/métodos , Análise de Célula Única/métodos , Neoplasias da Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patologia , Pontos de Quebra do Cromossomo , Células Clonais/citologia , Diploide , Progressão da Doença , Feminino , Citometria de Fluxo , Heterogeneidade Genética , Genoma Humano/genética , Genômica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Perda de Heterozigosidade
3.
Genome Res ; 20(1): 68-80, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19903760

RESUMO

Cancer progression in humans is difficult to infer because we do not routinely sample patients at multiple stages of their disease. However, heterogeneous breast tumors provide a unique opportunity to study human tumor progression because they still contain evidence of early and intermediate subpopulations in the form of the phylogenetic relationships. We have developed a method we call Sector-Ploidy-Profiling (SPP) to study the clonal composition of breast tumors. SPP involves macro-dissecting tumors, flow-sorting genomic subpopulations by DNA content, and profiling genomes using comparative genomic hybridization (CGH). Breast carcinomas display two classes of genomic structural variation: (1) monogenomic and (2) polygenomic. Monogenomic tumors appear to contain a single major clonal subpopulation with a highly stable chromosome structure. Polygenomic tumors contain multiple clonal tumor subpopulations, which may occupy the same sectors, or separate anatomic locations. In polygenomic tumors, we show that heterogeneity can be ascribed to a few clonal subpopulations, rather than a series of gradual intermediates. By comparing multiple subpopulations from different anatomic locations, we have inferred pathways of cancer progression and the organization of tumor growth.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Hibridização Genômica Comparativa/métodos , Progressão da Doença , Citometria de Fluxo/métodos , Heterogeneidade Genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patologia , Pontos de Quebra do Cromossomo , Feminino , Dosagem de Genes , Humanos , Hibridização in Situ Fluorescente , Informática , Dados de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Ploidias , Análise de Sequência de DNA
4.
Blood ; 113(6): 1294-303, 2009 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-18922857

RESUMO

We examined copy number changes in the genomes of B cells from 58 patients with chronic lymphocytic leukemia (CLL) by using representational oligonucleotide microarray analysis (ROMA), a form of comparative genomic hybridization (CGH), at a resolution exceeding previously published studies. We observed at least 1 genomic lesion in each CLL sample and considerable variation in the number of abnormalities from case to case. Virtually all abnormalities previously reported also were observed here, most of which were indeed highly recurrent. We observed the boundaries of known events with greater clarity and identified previously undescribed lesions, some of which were recurrent. We profiled the genomes of CLL cells separated by the surface marker CD38 and found evidence of distinct subclones of CLL within the same patient. We discuss the potential applications of high-resolution CGH analysis in a clinical setting.


Assuntos
Aberrações Cromossômicas , Perfilação da Expressão Gênica , Leucemia Linfocítica Crônica de Células B/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , ADP-Ribosil Ciclase 1 , Mapeamento Cromossômico , Cromossomos Artificiais Bacterianos , Cromossomos Humanos/genética , Hibridização Genômica Comparativa , DNA de Neoplasias/genética , Dosagem de Genes , Regulação Leucêmica da Expressão Gênica , Genoma Humano , Instabilidade Genômica , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Leucemia Linfocítica Crônica de Células B/diagnóstico , Neutrófilos/citologia , Neutrófilos/metabolismo , Prognóstico , Células Tumorais Cultivadas
5.
Front Digit Health ; 3: 777905, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35005697

RESUMO

Introduction: The Food and Drug Administration Center for Biologics Evaluation and Research conducts post-market surveillance of biologic products to ensure their safety and effectiveness. Studies have found that common vaccine exposures may be missing from structured data elements of electronic health records (EHRs), instead being captured in clinical notes. This impacts monitoring of adverse events following immunizations (AEFIs). For example, COVID-19 vaccines have been regularly administered outside of traditional medical settings. We developed a natural language processing (NLP) algorithm to mine unstructured clinical notes for vaccinations not captured in structured EHR data. Methods: A random sample of 1,000 influenza vaccine administrations, representing 995 unique patients, was extracted from a large U.S. EHR database. NLP techniques were used to detect administrations from the clinical notes in the training dataset [80% (N = 797) of patients]. The algorithm was applied to the validation dataset [20% (N = 198) of patients] to assess performance. Full medical charts for 28 randomly selected administration events in the validation dataset were reviewed by clinicians. The NLP algorithm was then applied across the entire dataset (N = 995) to quantify the number of additional events identified. Results: A total of 3,199 administrations were identified in the structured data and clinical notes combined. Of these, 2,740 (85.7%) were identified in the structured data, while the NLP algorithm identified 1,183 (37.0%) administrations in clinical notes; 459 were not also captured in the structured data. This represents a 16.8% increase in the identification of vaccine administrations compared to using structured data alone. The validation of 28 vaccine administrations confirmed 27 (96.4%) as "definite" vaccine administrations; 18 (64.3%) had evidence of a vaccination event in the structured data, while 10 (35.7%) were found solely in the unstructured notes. Discussion: We demonstrated the utility of an NLP algorithm to identify vaccine administrations not captured in structured EHR data. NLP techniques have the potential to improve detection of vaccine administrations not otherwise reported without increasing the analysis burden on physicians or practitioners. Future applications could include refining estimates of vaccine coverage and detecting other exposures, population characteristics, and outcomes not reliably captured in structured EHR data.

6.
Paediatr Nurs ; 18(1): 41-4, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16518954

RESUMO

Educational courses for staff working in paediatric specialties may not be financially viable because of the small numbers involved and the difficulties that potential students have in getting released from their units. The UK Paediatric Cardiac Nurses Association worked with other groups to explore the feasibility of a national multi-professional paediatric cardiac education pathway. Three options were identified, including the continuation of local in-house provision with its associated variation in standards. The relative benefits and resource implications of each option were explored and approaches made to educational institutions for support in developing the pathway. A university with an established reputation for e-learning undertook this development and a post graduate certificate in Paediatric Cardiothoracic Practice will soon be available.


Assuntos
Cardiologia/educação , Educação Continuada em Enfermagem/organização & administração , Guias como Assunto , Capacitação em Serviço/organização & administração , Enfermagem Pediátrica/educação , Comportamento Cooperativo , Currículo , Estudos de Viabilidade , Necessidades e Demandas de Serviços de Saúde , Humanos , Modelos Educacionais , Pesquisa em Educação em Enfermagem , Reino Unido
9.
Nurs Stand ; 22(39): 62-3, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18578136
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