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1.
Cancers (Basel) ; 13(15)2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34359631

RESUMO

Cardiovascular side effects are major shortcomings of cancer treatments causing cardiotoxicity and late-onset cardiomyopathy. While doxorubicin (Dox) has been reported as an effective chemotherapy agent, unspecific impairment in cardiomyocyte mitochondria activity has been documented. We demonstrated that the human fetal amniotic fluid-stem cell (hAFS) secretome, namely the secreted paracrine factors within the hAFS-conditioned medium (hAFS-CM), exerts pro-survival effects on Dox-exposed cardiomyocytes. Here, we provide a detailed comparison of the cardioprotective potential of hAFS-CM over the secretome of mesenchymal stromal cells from adipose tissue (hMSC-CM). hAFS and hMSC were preconditioned under hypoxia to enrich their secretome. The cardioprotective effects of hAFS/hMSC-CM were evaluated on murine neonatal ventricular cardiomyocytes (mNVCM) and on their fibroblast counterpart (mNVFib), and their long-term paracrine effects were investigated in a mouse model of Dox-induced cardiomyopathy. Both secretomes significantly contributed to preserving mitochondrial metabolism within Dox-injured cardiac cells. hAFS-CM and hMSC-CM inhibited body weight loss, improved myocardial function, reduced lipid peroxidation and counteracted the impairment of mitochondrial complex I activity, oxygen consumption, and ATP synthesis induced by Dox. The hAFS and hMSC secretomes can be exploited for inhibiting cardiotoxic detrimental side effects of Dox during cancer therapy, thus ensuring cardioprotection via combinatorial paracrine therapy in association with standard oncological treatments.

2.
Intell Based Med ; 5: 100036, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34179855

RESUMO

Objective: Among the stakeholders of COVID-19 research, clinicians particularly experience difficulty keeping up with the deluge of SARS-CoV-2 literature while performing their much needed clinical duties. By revealing major topics, this study proposes a text-mining approach as an alternative to navigating large volumes of COVID-19 literature. Materials and methods: We obtained 85,268 references from the NIH COVID-19 Portfolio as of November 21. After the exclusion based on inadequate abstracts, 65,262 articles remained in the final corpus. We utilized natural language processing to curate and generate the term list. We applied topic modeling analyses and multiple correspondence analyses to reveal the major topics and the associations among topics, journal countries, and publication sources. Results: In our text mining analyses of NIH's COVID-19 Portfolio, we discovered two sets of eleven major research topics by analyzing abstracts and titles of the articles separately. The eleven major areas of COVID-19 research based on abstracts included the following topics: 1) Public Health, 2) Patient Care & Outcomes, 3) Epidemiologic Modeling, 4) Diagnosis and Complications, 5) Mechanism of Disease, 6) Health System Response, 7) Pandemic Control, 8) Protection/Prevention, 9) Mental/Behavioral Health, 10) Detection/Testing, 11) Treatment Options. Further analyses revealed that five (2,3,4,5, and 9) of the eleven abstract-based topics showed a significant correlation (ranked from moderate to weak) with title-based topics. Conclusion: By offering up the more dynamic, scalable, and responsive categorization of published literature, our study provides valuable insights to the stakeholders of COVID-19 research, particularly clinicians.

3.
J Clin Transl Sci ; 5(1): e110, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-34192063

RESUMO

The recipients of NIH's Clinical and Translational Science Awards (CTSA) have worked for over a decade to build informatics infrastructure in support of clinical and translational research. This infrastructure has proved invaluable for supporting responses to the current COVID-19 pandemic through direct patient care, clinical decision support, training researchers and practitioners, as well as public health surveillance and clinical research to levels that could not have been accomplished without the years of ground-laying work by the CTSAs. In this paper, we provide a perspective on our COVID-19 work and present relevant results of a survey of CTSA sites to broaden our understanding of the key features of their informatics programs, the informatics-related challenges they have experienced under COVID-19, and some of the innovations and solutions they developed in response to the pandemic. Responses demonstrated increased reliance by healthcare providers and researchers on access to electronic health record (EHR) data, both for local needs and for sharing with other institutions and national consortia. The initial work of the CTSAs on data capture, standards, interchange, and sharing policies all contributed to solutions, best illustrated by the creation, in record time, of a national clinical data repository in the National COVID-19 Cohort Collaborative (N3C). The survey data support seven recommendations for areas of informatics and public health investment and further study to support clinical and translational research in the post-COVID-19 era.

4.
Int J Med Inform ; 151: 104475, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33975266

RESUMO

OBJECTIVE: To assess physicians' perceptions about narrative note sections format and content commonly reported in visit notes to inform future research and EHR development. METHODS: We conducted two online surveys with a multi-specialty panel of outpatient physicians from a large health system to collect their perceptions of the usefulness of three narrative formats and the relevance of content reported in the note sections history of present illness (HPI) and assessment and plan (AP). Survey questions were responded with a 7-point Likert scale and include two open-ended questions for comments on challenges and suggestions related to electronic clinical documentation. RESULTS: Eighty-eight physicians completed the surveys. The most preferred format for HPI was story (i.e., coherent paragraph), followed by list without categories (i.e., non-categorized sentences) and list with categories (i.e., categorized sentences). The most preferred format for AP was list with categories, followed by story and list without categories. The most relevant type of content in HPI was temporal information and finding/condition. The most relevant type of content reported in AP was intervention and reasons and justifications. Challenges frequently mentioned include suboptimal note creation interfaces and bloated notes, and the most common suggestions for improvements are related to note entry facilitators and organizational improvements. CONCLUSION: Physicians' input is extremely valuable to inform improvements to EHRs. More effective clinical documentation systems should include less intrusive, more intuitive and automated user interfaces for note creation, smarter autopoluation functionality and linkage between note content and data from other parts of the record.


Assuntos
Registros Eletrônicos de Saúde , Médicos , Documentação , Humanos , Narração , Percepção
5.
J Med Internet Res ; 23(3): e22219, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33600347

RESUMO

Coincident with the tsunami of COVID-19-related publications, there has been a surge of studies using real-world data, including those obtained from the electronic health record (EHR). Unfortunately, several of these high-profile publications were retracted because of concerns regarding the soundness and quality of the studies and the EHR data they purported to analyze. These retractions highlight that although a small community of EHR informatics experts can readily identify strengths and flaws in EHR-derived studies, many medical editorial teams and otherwise sophisticated medical readers lack the framework to fully critically appraise these studies. In addition, conventional statistical analyses cannot overcome the need for an understanding of the opportunities and limitations of EHR-derived studies. We distill here from the broader informatics literature six key considerations that are crucial for appraising studies utilizing EHR data: data completeness, data collection and handling (eg, transformation), data type (ie, codified, textual), robustness of methods against EHR variability (within and across institutions, countries, and time), transparency of data and analytic code, and the multidisciplinary approach. These considerations will inform researchers, clinicians, and other stakeholders as to the recommended best practices in reviewing manuscripts, grants, and other outputs from EHR-data derived studies, and thereby promote and foster rigor, quality, and reliability of this rapidly growing field.


Assuntos
COVID-19/epidemiologia , Coleta de Dados/métodos , Registros Eletrônicos de Saúde , Coleta de Dados/normas , Humanos , Revisão da Pesquisa por Pares/normas , Editoração/normas , Reprodutibilidade dos Testes , SARS-CoV-2/isolamento & purificação
6.
Clin Pharmacol Ther ; 110(1): 179-188, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33428770

RESUMO

The value of utilizing a multigene pharmacogenetic panel to tailor pharmacotherapy is contingent on the prevalence of prescribed medications with an actionable pharmacogenetic association. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has categorized over 35 gene-drug pairs as "level A," for which there is sufficiently strong evidence to recommend that genetic information be used to guide drug prescribing. The opportunity to use genetic information to tailor pharmacotherapy among adult patients was determined by elucidating the exposure to CPIC level A drugs among 11 Implementing Genomics In Practice Network (IGNITE)-affiliated health systems across the US. Inpatient and/or outpatient electronic-prescribing data were collected between January 1, 2011 and December 31, 2016 for patients ≥ 18 years of age who had at least one medical encounter that was eligible for drug prescribing in a calendar year. A median of ~ 7.2 million adult patients was available for assessment of drug prescribing per year. From 2011 to 2016, the annual estimated prevalence of exposure to at least one CPIC level A drug prescribed to unique patients ranged between 15,719 (95% confidence interval (CI): 15,658-15,781) in 2011 to 17,335 (CI: 17,283-17,386) in 2016 per 100,000 patients. The estimated annual exposure to at least 2 drugs was above 7,200 per 100,000 patients in most years of the study, reaching an apex of 7,660 (CI: 7,632-7,687) per 100,000 patients in 2014. An estimated 4,748 per 100,000 prescribing events were potentially eligible for a genotype-guided intervention. Results from this study show that a significant portion of adults treated at medical institutions across the United States is exposed to medications for which genetic information, if available, should be used to guide prescribing.


Assuntos
Prescrições de Medicamentos/estatística & dados numéricos , Genótipo , Farmacogenética , Testes Farmacogenômicos , Adulto , Idoso , Prescrição Eletrônica/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos
7.
J Am Med Inform Assoc ; 28(3): 427-443, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32805036

RESUMO

OBJECTIVE: Coronavirus disease 2019 (COVID-19) poses societal challenges that require expeditious data and knowledge sharing. Though organizational clinical data are abundant, these are largely inaccessible to outside researchers. Statistical, machine learning, and causal analyses are most successful with large-scale data beyond what is available in any given organization. Here, we introduce the National COVID Cohort Collaborative (N3C), an open science community focused on analyzing patient-level data from many centers. MATERIALS AND METHODS: The Clinical and Translational Science Award Program and scientific community created N3C to overcome technical, regulatory, policy, and governance barriers to sharing and harmonizing individual-level clinical data. We developed solutions to extract, aggregate, and harmonize data across organizations and data models, and created a secure data enclave to enable efficient, transparent, and reproducible collaborative analytics. RESULTS: Organized in inclusive workstreams, we created legal agreements and governance for organizations and researchers; data extraction scripts to identify and ingest positive, negative, and possible COVID-19 cases; a data quality assurance and harmonization pipeline to create a single harmonized dataset; population of the secure data enclave with data, machine learning, and statistical analytics tools; dissemination mechanisms; and a synthetic data pilot to democratize data access. CONCLUSIONS: The N3C has demonstrated that a multisite collaborative learning health network can overcome barriers to rapidly build a scalable infrastructure incorporating multiorganizational clinical data for COVID-19 analytics. We expect this effort to save lives by enabling rapid collaboration among clinicians, researchers, and data scientists to identify treatments and specialized care and thereby reduce the immediate and long-term impacts of COVID-19.


Assuntos
COVID-19 , Ciência de Dados/organização & administração , Disseminação de Informação , Colaboração Intersetorial , Segurança Computacional , Análise de Dados , Comitês de Ética em Pesquisa , Regulamentação Governamental , Humanos , National Institutes of Health (U.S.) , Estados Unidos
8.
Cardiovasc Res ; 117(1): 43-59, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32365197

RESUMO

Echocardiography is a reliable and reproducible method to assess non-invasively cardiac function in clinical and experimental research. Significant progress in the development of echocardiographic equipment and transducers has led to the successful translation of this methodology from humans to rodents, allowing for the scoring of disease severity and progression, testing of new drugs, and monitoring cardiac function in genetically modified or pharmacologically treated animals. However, as yet, there is no standardization in the procedure to acquire echocardiographic measurements in small animals. This position paper focuses on the appropriate acquisition and analysis of echocardiographic parameters in adult mice and rats, and provides reference values, representative images, and videos for the accurate and reproducible quantification of left ventricular function in healthy and pathological conditions.


Assuntos
Pesquisa Biomédica/normas , Doenças Cardiovasculares/diagnóstico por imagem , Ecocardiografia/normas , Função Ventricular Esquerda , Animais , Doenças Cardiovasculares/fisiopatologia , Consenso , Diástole , Modelos Animais de Doenças , Camundongos , Ratos , Sístole
9.
Nucleic Acids Res ; 49(D1): D589-D599, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33245774

RESUMO

PAGER-CoV (http://discovery.informatics.uab.edu/PAGER-CoV/) is a new web-based database that can help biomedical researchers interpret coronavirus-related functional genomic study results in the context of curated knowledge of host viral infection, inflammatory response, organ damage, and tissue repair. The new database consists of 11 835 PAGs (Pathways, Annotated gene-lists, or Gene signatures) from 33 public data sources. Through the web user interface, users can search by a query gene or a query term and retrieve significantly matched PAGs with all the curated information. Users can navigate from a PAG of interest to other related PAGs through either shared PAG-to-PAG co-membership relationships or PAG-to-PAG regulatory relationships, totaling 19 996 993. Users can also retrieve enriched PAGs from an input list of COVID-19 functional study result genes, customize the search data sources, and export all results for subsequent offline data analysis. In a case study, we performed a gene set enrichment analysis (GSEA) of a COVID-19 RNA-seq data set from the Gene Expression Omnibus database. Compared with the results using the standard PAGER database, PAGER-CoV allows for more sensitive matching of known immune-related gene signatures. We expect PAGER-CoV to be invaluable for biomedical researchers to find molecular biology mechanisms and tailored therapeutics to treat COVID-19 patients.


Assuntos
Algoritmos , COVID-19/prevenção & controle , Biologia Computacional/métodos , Coronavirus/genética , Bases de Dados Genéticas , SARS-CoV-2/genética , COVID-19/epidemiologia , COVID-19/virologia , Coronavirus/metabolismo , Curadoria de Dados/métodos , Epidemias , Redes Reguladoras de Genes , Humanos , Armazenamento e Recuperação da Informação/métodos , Internet , Anotação de Sequência Molecular/métodos , SARS-CoV-2/metabolismo , SARS-CoV-2/fisiologia , Interface Usuário-Computador
10.
Genet Med ; 23(4): 777-781, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33244164

RESUMO

PURPOSE: The Alabama Genomic Health Initiative (AGHI) is a state-funded effort to provide genomic testing. AGHI engages two distinct cohorts across the state of Alabama. One cohort includes children and adults with undiagnosed rare disease; a second includes an unselected adult population. Here we describe findings from the first 176 rare disease and 5369 population cohort AGHI participants. METHODS: AGHI participants enroll in one of two arms of a research protocol that provides access to genomic testing results and biobank participation. Rare disease cohort participants receive genome sequencing to identify primary and secondary findings. Population cohort participants receive genotyping to identify pathogenic and likely pathogenic variants for actionable conditions. RESULTS: Within the rare disease cohort, genome sequencing identified likely pathogenic or pathogenic variation in 20% of affected individuals. Within the population cohort, 1.5% of individuals received a positive genotyping result. The rate of genotyping results corroborated by reported personal or family history varied by gene. CONCLUSIONS: AGHI demonstrates the ability to provide useful health information in two contexts: rare undiagnosed disease and population screening. This utility should motivate continued exploration of ways in which emerging genomic technologies might benefit broad populations.


Assuntos
Genômica , Doenças Raras , Adulto , Alabama , Criança , Mapeamento Cromossômico , Estudos de Coortes , Humanos , Doenças Raras/diagnóstico , Doenças Raras/genética
11.
JAMA Netw Open ; 3(12): e2029411, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33315113

RESUMO

Importance: Genotype-guided prescribing in pediatrics could prevent adverse drug reactions and improve therapeutic response. Clinical pharmacogenetic implementation guidelines are available for many medications commonly prescribed to children. Frequencies of medication prescription and actionable genotypes (genotypes where a prescribing change may be indicated) inform the potential value of pharmacogenetic implementation. Objective: To assess potential opportunities for genotype-guided prescribing in pediatric populations among multiple health systems by examining the prevalence of prescriptions for each drug with the highest level of evidence (Clinical Pharmacogenetics Implementation Consortium level A) and estimating the prevalence of potential actionable prescribing decisions. Design, Setting, and Participants: This serial cross-sectional study of prescribing prevalences in 16 health systems included electronic health records data from pediatric inpatient and outpatient encounters from January 1, 2011, to December 31, 2017. The health systems included academic medical centers with free-standing children's hospitals and community hospitals that were part of an adult health care system. Participants included approximately 2.9 million patients younger than 21 years observed per year. Data were analyzed from June 5, 2018, to April 14, 2020. Exposures: Prescription of 38 level A medications based on electronic health records. Main Outcomes and Measures: Annual prevalence of level A medication prescribing and estimated actionable exposures, calculated by combining estimated site-year prevalences across sites with each site weighted equally. Results: Data from approximately 2.9 million pediatric patients (median age, 8 [interquartile range, 2-16] years; 50.7% female, 62.3% White) were analyzed for a typical calendar year. The annual prescribing prevalence of at least 1 level A drug ranged from 7987 to 10 629 per 100 000 patients with increasing trends from 2011 to 2014. The most prescribed level A drug was the antiemetic ondansetron (annual prevalence of exposure, 8107 [95% CI, 8077-8137] per 100 000 children). Among commonly prescribed opioids, annual prevalence per 100 000 patients was 295 (95% CI, 273-317) for tramadol, 571 (95% CI, 557-586) for codeine, and 2116 (95% CI, 2097-2135) for oxycodone. The antidepressants citalopram, escitalopram, and amitriptyline were also commonly prescribed (annual prevalence, approximately 250 per 100 000 patients for each). Estimated prevalences of actionable exposures were highest for oxycodone and ondansetron (>300 per 100 000 patients annually). CYP2D6 and CYP2C19 substrates were more frequently prescribed than medications influenced by other genes. Conclusions and Relevance: These findings suggest that opportunities for pharmacogenetic implementation among pediatric patients in the US are abundant. As expected, the greatest opportunity exists with implementing CYP2D6 and CYP2C19 pharmacogenetic guidance for commonly prescribed antiemetics, analgesics, and antidepressants.


Assuntos
Serviços de Saúde da Criança , Cálculos da Dosagem de Medicamento , Testes Farmacogenômicos , Padrões de Prática Médica , Medicamentos sob Prescrição , Criança , Serviços de Saúde da Criança/normas , Serviços de Saúde da Criança/estatística & dados numéricos , Estudos Transversais , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2D6/genética , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Perfil Genético , Humanos , Masculino , Pediatria/métodos , Pediatria/normas , Testes Farmacogenômicos/métodos , Testes Farmacogenômicos/estatística & dados numéricos , Padrões de Prática Médica/normas , Padrões de Prática Médica/estatística & dados numéricos , Medicina de Precisão/métodos , Medicamentos sob Prescrição/classificação , Medicamentos sob Prescrição/uso terapêutico , Estados Unidos
12.
J Am Med Inform Assoc ; 27(11): 1648-1657, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32935127

RESUMO

OBJECTIVE: To develop a collection of concept-relationship-concept tuples to formally represent patients' care context data to inform electronic health record (EHR) development. MATERIALS AND METHODS: We reviewed semantic relationships reported in the literature and developed a manual annotation schema. We used the initial schema to annotate sentences extracted from narrative note sections of cardiology, urology, and ear, nose, and throat (ENT) notes. We audio recorded ENT visits and annotated their parsed transcripts. We combined the results of each annotation into a consolidated set of concept-relationship-concept tuples. We then compared the tuples used within and across the multiple data sources. RESULTS: We annotated a total of 626 sentences. Starting with 8 relationships from the literature, we annotated 182 sentences from 8 inpatient consult notes (initial set of tuples = 43). Next, we annotated 232 sentences from 10 outpatient visit notes (enhanced set of tuples = 75). Then, we annotated 212 sentences from transcripts of 5 outpatient visits (final set of tuples = 82). The tuples from the visit transcripts covered 103 (74%) concepts documented in the notes of their respective visits. There were 20 (24%) tuples used across all data sources, 10 (12%) used only in inpatient notes, 15 (18%) used only in visit notes, and 7 (9%) used only in the visit transcripts. CONCLUSIONS: We produced a robust set of 82 tuples useful to represent patients' care context data. We propose several applications of our tuples to improve EHR navigation, data entry, learning health systems, and decision support.


Assuntos
Inteligência Artificial , Registros Eletrônicos de Saúde/organização & administração , Cardiologia , Tomada de Decisões Assistida por Computador , Humanos , Processamento de Linguagem Natural , Otolaringologia
13.
NPJ Digit Med ; 3: 109, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32864472

RESUMO

We leveraged the largely untapped resource of electronic health record data to address critical clinical and epidemiological questions about Coronavirus Disease 2019 (COVID-19). To do this, we formed an international consortium (4CE) of 96 hospitals across five countries (www.covidclinical.net). Contributors utilized the Informatics for Integrating Biology and the Bedside (i2b2) or Observational Medical Outcomes Partnership (OMOP) platforms to map to a common data model. The group focused on temporal changes in key laboratory test values. Harmonized data were analyzed locally and converted to a shared aggregate form for rapid analysis and visualization of regional differences and global commonalities. Data covered 27,584 COVID-19 cases with 187,802 laboratory tests. Case counts and laboratory trajectories were concordant with existing literature. Laboratory tests at the time of diagnosis showed hospital-level differences equivalent to country-level variation across the consortium partners. Despite the limitations of decentralized data generation, we established a framework to capture the trajectory of COVID-19 disease in patients and their response to interventions.

14.
J Am Med Inform Assoc ; 27(10): 1625-1638, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32766692

RESUMO

OBJECTIVE: The study sought to describe the literature related to the development of methods for auditing the Unified Medical Language System (UMLS), with particular attention to identifying errors and inconsistencies of attributes of the concepts in the UMLS Metathesaurus. MATERIALS AND METHODS: We applied the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) approach by searching the MEDLINE database and Google Scholar for studies referencing the UMLS and any of several terms related to auditing, error detection, and quality assurance. A qualitative analysis and summarization of articles that met inclusion criteria were performed. RESULTS: Eighty-three studies were reviewed in detail. We first categorized techniques based on various aspects including concepts, concept names, and synonymy (n = 37), semantic type assignments (n = 36), hierarchical relationships (n = 24), lateral relationships (n = 12), ontology enrichment (n = 8), and ontology alignment (n = 18). We also categorized the methods according to their level of automation (ie, automated systematic, automated heuristic, or manual) and the type of knowledge used (ie, intrinsic or extrinsic knowledge). CONCLUSIONS: This study is a comprehensive review of the published methods for auditing the various conceptual aspects of the UMLS. Categorizing the auditing techniques according to the various aspects will enable the curators of the UMLS as well as researchers comprehensive easy access to this wealth of knowledge (eg, for auditing lateral relationships in the UMLS). We also reviewed ontology enrichment and alignment techniques due to their critical use of and impact on the UMLS.


Assuntos
Controle de Qualidade , Unified Medical Language System , Heurística Computacional , Web Semântica
15.
Mol Ther Methods Clin Dev ; 18: 62-72, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32577433

RESUMO

Myocarditis can lead to autoimmune disease, dilated cardiomyopathy, and heart failure, which is modeled in the mouse by cardiac myosin immunization (experimental autoimmune myocarditis [EAM]). Signal transducer and activator of transcription 3 (STAT3) systemic inhibition exerts both preventive and therapeutic effects in EAM, and STAT3 constitutive activation elicits immune-mediated myocarditis dependent on complement C3 and correlating with activation of the STAT3-interleukin 6 (IL-6) axis in the liver. Thus, liver-specific STAT3 inhibition may represent a therapeutic option, allowing to bypass the heart toxicity, predicted by systemic STAT3 inhibition. We therefore decided to explore the effectiveness of silencing liver Stat3 and C3 in preventing EAM onset and/or the recovery of cardiac functions. We first show that complement C3 and C5 genetic depletion significantly prevents the onset of spontaneous myocarditis, supporting the complement cascade as a viable target. In order to interfere with complement production and STAT3 activity specifically in the liver, we took advantage of liver-specific Stat3 or C3 small interfering (si)RNA nanoparticles, demonstrating that both siRNAs can significantly prevent myocarditis onset and improve the recovery of heart functions in EAM. Our data demonstrate that liver-specific Stat3/C3 siRNAs may represent a therapeutic option for autoimmune myocarditis and suggest that complement levels and activation might be predictive of progression to dilated cardiomyopathy.

16.
Appl Clin Inform ; 11(2): 356-365, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32434224

RESUMO

OBJECTIVES: This study aimed to understand if and how homegrown electronic health record (EHR) systems are used in the post-Meaningful Use (MU) era according to the experience of six traditional EHR developers. METHODS: We invited informatics leaders from a convenience sample of six health care organizations that have recently replaced their long used homegrown systems with commercial EHRs. Participants were asked to complete a written questionnaire with open-ended questions designed to explore if and how their homegrown system(s) is being used and maintained after adoption of a commercial EHR. We used snowball sampling to identify other potential respondents and institutions. RESULTS: Participants from all six organizations included in our initial sample completed the questionnaire and provided referrals to four other organizations; from these, two did not respond to our invitations and two had not yet replaced their system and were excluded. Two organizations (Columbia University and University of Alabama at Birmingham) still use their homegrown system for direct patient care and as a downtime system. Four organizations (Intermountain Healthcare, Partners Healthcare, Regenstrief Institute, and Vanderbilt University) kept their systems primarily to access historical data. All organizations reported the need to continue to develop or maintain local applications despite having adopted a commercial EHR. The most common applications developed include display and visualization tools and clinical decision support systems. CONCLUSION: Homegrown EHR systems continue to be used for different purposes according to the experience of six traditional homegrown EHR developers. The annual cost to maintain these systems varies from $21,000 to over 1 million. The collective experience of these organizations indicates that commercial EHRs have not been able to provide all functionality needed for patient care and local applications are often developed for multiple purposes, which presents opportunities for future research and EHR development.


Assuntos
Registros Eletrônicos de Saúde , Uso Significativo
17.
J Genet Couns ; 29(3): 471-478, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32220047

RESUMO

Lack of diversity among genomic research participants results in disparities in benefits from genetic testing. To address this, the Alabama Genomic Health Initiative employed community engagement strategies to recruit diverse populations where they lived. In this paper, we describe our engagement techniques and recruitment strategies, which resulted in significant improvement in representation of African American participants. While African American participation has not reached the representation of this community as a percentage of Alabama's overall population (26%-27%), we have achieved an overall representation exceeding 20% for African Americans. We believe this demonstrates the value of engagement and recruitment where diverse populations reside.


Assuntos
Afro-Americanos/genética , Diversidade Cultural , Genoma Humano , Alabama , Humanos
18.
Learn Health Syst ; 4(1): e10207, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31989030

RESUMO

After over half a century of computer application development in medicine, the US health system has gone digital with an enthusiastic confidence for rapid improvements in care outcomes, especially those of quality of care, safety, and productivity. The bad news is that evidence for the justification of the hype around health information technology (HIT) is conflicting, and the expected benefits of a digital health system have not yet materialized. We propose a national system for monitoring HIT impact based on the paradigm of the learning health system (LHS): learning from practical experience through high-quality, ongoing monitoring of care outcomes. Our proposal aims at leveraging current de facto standard research data repositories used to support large-scale clinical studies by incorporating data needed for more robust HIT assessments and application of rigorous research designs that are now feasible on a large scale.

19.
J Am Med Inform Assoc ; 27(1): 159-174, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31592534

RESUMO

OBJECTIVE: The study sought to describe the literature describing clinical reasoning ontology (CRO)-based clinical decision support systems (CDSSs) and identify and classify the medical knowledge and reasoning concepts and their properties within these ontologies to guide future research. METHODS: MEDLINE, Scopus, and Google Scholar were searched through January 30, 2019, for studies describing CRO-based CDSSs. Articles that explored the development or application of CROs or terminology were selected. Eligible articles were assessed for quality features of both CDSSs and CROs to determine the current practices. We then compiled concepts and properties used within the articles. RESULTS: We included 38 CRO-based CDSSs for the analysis. Diversity of the purpose and scope of their ontologies was seen, with a variety of knowledge sources were used for ontology development. We found 126 unique medical knowledge concepts, 38 unique reasoning concepts, and 240 unique properties (137 relationships and 103 attributes). Although there is a great diversity among the terms used across CROs, there is a significant overlap based on their descriptions. Only 5 studies described high quality assessment. CONCLUSION: We identified current practices used in CRO development and provided lists of medical knowledge concepts, reasoning concepts, and properties (relationships and attributes) used by CRO-based CDSSs. CRO developers reason that the inclusion of concepts used by clinicians' during medical decision making has the potential to improve CDSS performance. However, at present, few CROs have been used for CDSSs, and high-quality studies describing CROs are sparse. Further research is required in developing high-quality CDSSs based on CROs.


Assuntos
Ontologias Biológicas , Raciocínio Clínico , Sistemas de Apoio a Decisões Clínicas , Humanos
20.
AMIA Annu Symp Proc ; 2020: 311-318, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33936403

RESUMO

Monitoring response to antihypertensive medications is a frequent reason for outpatient visits. Blood pressure (BP) is often documented as elevated, but no change in medication occurs (Medication Non-adjustment or MNA). We studied the frequency of MNA, reasons for non-adjustment, how reasons (including reasons for patient nonadherence) were documented, and whether they could be represented in a clinical care context ontology. We examined 129 visit notes with MNA occurring in 80 cases (59%). We coded MNA as Conscious Maintenance (patient adherent but clinician continues therapy for stated reason), Nonadherence (clinician attributes BP elevation to patient nonadherence), and Finding Not Addressed (clinician does not indicate reasoning for MNA). We characterized Conscious Maintenance with 11 subcodes and Nonadherence with 6 subcodes. Our ontology successfully represented relationships between concepts and reasoning, supporting the feasibility of formal representation of clinical care contexts for patient care, decision support and research.


Assuntos
Anti-Hipertensivos/uso terapêutico , Raciocínio Clínico , Técnicas de Apoio para a Decisão , Registros Eletrônicos de Saúde , Hipertensão Essencial/tratamento farmacológico , Adulto , Anti-Hipertensivos/administração & dosagem , Ontologias Biológicas , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Assistência ao Paciente
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