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1.
Nat Med ; 27(4): 668-676, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33837377

RESUMO

Drug repurposing provides a rapid approach to meet the urgent need for therapeutics to address COVID-19. To identify therapeutic targets relevant to COVID-19, we conducted Mendelian randomization analyses, deriving genetic instruments based on transcriptomic and proteomic data for 1,263 actionable proteins that are targeted by approved drugs or in clinical phase of drug development. Using summary statistics from the Host Genetics Initiative and the Million Veteran Program, we studied 7,554 patients hospitalized with COVID-19 and >1 million controls. We found significant Mendelian randomization results for three proteins (ACE2, P = 1.6 × 10-6; IFNAR2, P = 9.8 × 10-11 and IL-10RB, P = 2.3 × 10-14) using cis-expression quantitative trait loci genetic instruments that also had strong evidence for colocalization with COVID-19 hospitalization. To disentangle the shared expression quantitative trait loci signal for IL10RB and IFNAR2, we conducted phenome-wide association scans and pathway enrichment analysis, which suggested that IFNAR2 is more likely to play a role in COVID-19 hospitalization. Our findings prioritize trials of drugs targeting IFNAR2 and ACE2 for early management of COVID-19.

2.
PLoS One ; 16(3): e0248128, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33730088

RESUMO

BACKGROUND: The COVID-19 pandemic remains a significant global threat. However, despite urgent need, there remains uncertainty surrounding best practices for pharmaceutical interventions to treat COVID-19. In particular, conflicting evidence has emerged surrounding the use of hydroxychloroquine and azithromycin, alone or in combination, for COVID-19. The COVID-19 Evidence Accelerator convened by the Reagan-Udall Foundation for the FDA, in collaboration with Friends of Cancer Research, assembled experts from the health systems research, regulatory science, data science, and epidemiology to participate in a large parallel analysis of different data sets to further explore the effectiveness of these treatments. METHODS: Electronic health record (EHR) and claims data were extracted from seven separate databases. Parallel analyses were undertaken on data extracted from each source. Each analysis examined time to mortality in hospitalized patients treated with hydroxychloroquine, azithromycin, and the two in combination as compared to patients not treated with either drug. Cox proportional hazards models were used, and propensity score methods were undertaken to adjust for confounding. Frequencies of adverse events in each treatment group were also examined. RESULTS: Neither hydroxychloroquine nor azithromycin, alone or in combination, were significantly associated with time to mortality among hospitalized COVID-19 patients. No treatment groups appeared to have an elevated risk of adverse events. CONCLUSION: Administration of hydroxychloroquine, azithromycin, and their combination appeared to have no effect on time to mortality in hospitalized COVID-19 patients. Continued research is needed to clarify best practices surrounding treatment of COVID-19.


Assuntos
Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Hidroxicloroquina/uso terapêutico , Pandemias/prevenção & controle , Gerenciamento de Dados/métodos , Quimioterapia Combinada/métodos , Feminino , Hospitalização , Humanos , Masculino , /efeitos dos fármacos
3.
Clin Nutr ESPEN ; 42: 201-205, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33745578

RESUMO

BACKGROUND: Potato consumption is highly prevalent around the world. Previous studies have reported a positive association of potato intake with hypertension and type 2 diabetes. However, data are scarce on potato consumption and risk of coronary artery disease (CAD). OBJECTIVE: We hypothesized that potato consumption is positively associated with the incidence of CAD among US veterans. DESIGN: We prospectively studied 148,671 participants from Million Veteran Program (MVP). We used a semi-quantitative food frequency questionnaire to assess consumption of baked, boiled, and mashed potatoes. The incidence of CAD was assessed through electronic health record. We used Cox Proportional hazard model to compute hazard ratios (HR) and 95% confidence intervals (95% CI) for CAD events across categories of potato intake. RESULT: The average age of participants was 64 years at the time of potato assessment. A total of 6309 new cases of CAD occurred during a mean follow up of 2.7 ± 1.4 y. Median potato consumption was 1 cup/week. The crude incidence of CAD from lowest to highest category of potato consumption was 14.5, 15.0, 15.2, 16.1, and 18.9 per 1000 person-years, respectively. Hazard ratios (95% CI) of CAD were 1.00 (reference), 1.02 (0.93-1.11), 1.02 (0.93-1.12), 1.04 (0.95-1.15), and 1.21 (1.07-1.37) for potato intake of <1 cup/month, 1-3 cups/month, 1 cup/week, 2-4 cups/week, and 5+ cups/week respectively, adjusting for age, gender, race, body mass index (BMI), alcohol consumption, exercise, smoking, DASH (Dietary Approaches to Stop Hypertension) score, and education. The observed relation of potato consumption with CAD was not modified by age, BMI, gender, and ethnicity in a secondary analysis. In a sensitivity analysis, exclusion of CAD events occurred during the first year of follow up did not alter the findings. CONCLUSION: Frequent (5+ cups/week) but not infrequent potato consumption was associated with a higher risk of CAD among MVP participants.

4.
BMJ ; 372: n311, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33574135

RESUMO

OBJECTIVE: To evaluate whether early initiation of prophylactic anticoagulation compared with no anticoagulation was associated with decreased risk of death among patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United States. DESIGN: Observational cohort study. SETTING: Nationwide cohort of patients receiving care in the Department of Veterans Affairs, a large integrated national healthcare system. PARTICIPANTS: All 4297 patients admitted to hospital from 1 March to 31 July 2020 with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and without a history of anticoagulation. MAIN OUTCOME MEASURES: The main outcome was 30 day mortality. Secondary outcomes were inpatient mortality, initiating therapeutic anticoagulation (a proxy for clinical deterioration, including thromboembolic events), and bleeding that required transfusion. RESULTS: Of 4297 patients admitted to hospital with covid-19, 3627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3600) of treated patients received subcutaneous heparin or enoxaparin. 622 deaths occurred within 30 days of hospital admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospital stay. Using inverse probability of treatment weighted analyses, the cumulative incidence of mortality at 30 days was 14.3% (95% confidence interval 13.1% to 15.5%) among those who received prophylactic anticoagulation and 18.7% (15.1% to 22.9%) among those who did not. Compared with patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30 day mortality (hazard ratio 0.73, 95% confidence interval 0.66 to 0.81). Similar associations were found for inpatient mortality and initiation of therapeutic anticoagulation. Receipt of prophylactic anticoagulation was not associated with increased risk of bleeding that required transfusion (hazard ratio 0.87, 0.71 to 1.05). Quantitative bias analysis showed that results were robust to unmeasured confounding (e-value lower 95% confidence interval 1.77 for 30 day mortality). Results persisted in several sensitivity analyses. CONCLUSIONS: Early initiation of prophylactic anticoagulation compared with no anticoagulation among patients admitted to hospital with covid-19 was associated with a decreased risk of 30 day mortality and no increased risk of serious bleeding events. These findings provide strong real world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with covid-19 on hospital admission.


Assuntos
Anticoagulantes/uso terapêutico , Enoxaparina/uso terapêutico , Tromboembolia/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Enoxaparina/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Tromboembolia/virologia , Fatores de Tempo , Estados Unidos/epidemiologia
5.
Nat Genet ; 53(2): 174-184, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33510476

RESUMO

We conducted genome-wide association analyses of over 250,000 participants of European (EUR) and African (AFR) ancestry from the Million Veteran Program using electronic health record-validated post-traumatic stress disorder (PTSD) diagnosis and quantitative symptom phenotypes. Applying genome-wide multiple testing correction, we identified three significant loci in European case-control analyses and 15 loci in quantitative symptom analyses. Genomic structural equation modeling indicated tight coherence of a PTSD symptom factor that shares genetic variance with a distinct internalizing (mood-anxiety-neuroticism) factor. Partitioned heritability indicated enrichment in several cortical and subcortical regions, and imputed genetically regulated gene expression in these regions was used to identify potential drug repositioning candidates. These results validate the biological coherence of the PTSD syndrome, inform its relationship to comorbid anxiety and depressive disorders and provide new considerations for treatment.


Assuntos
Transtornos de Estresse Pós-Traumáticos/genética , Afro-Americanos/genética , Transtornos de Ansiedade/genética , Estudos de Casos e Controles , Reposicionamento de Medicamentos , Grupo com Ancestrais do Continente Europeu , Estudo de Associação Genômica Ampla , Humanos , Desequilíbrio de Ligação , Transtornos Mentais/genética , Polimorfismo de Nucleotídeo Único , Transtornos de Estresse Pós-Traumáticos/etiologia , Estados Unidos , Veteranos
6.
Circ Cardiovasc Qual Outcomes ; : CIRCOUTCOMES120006528, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32862698

RESUMO

BACKGROUND: Estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk in diabetes mellitus patients is used to guide primary prevention, but the performance of risk estimators (2013 Pooled Cohort Equations [PCE] and Risk Equations for Complications of Diabetes [RECODe]) varies across populations. Data from electronic health records could be used to improve risk estimation for a health system's patients. We aimed to evaluate risk equations for initial ASCVD events in US veterans with diabetes mellitus and improve model performance in this population. METHODS AND RESULTS: We studied 183 096 adults with diabetes mellitus and without prior ASCVD who received care in the Veterans Affairs Healthcare System (VA) from 2002 to 2016 with mean follow-up of 4.6 years. We evaluated model discrimination, using Harrell's C statistic, and calibration, using the reclassification χ2 test, of the PCE and RECODe equations to predict fatal or nonfatal myocardial infarction or stroke and cardiovascular mortality. We then tested whether model performance was affected by deriving VA-specific ß-coefficients. Discrimination of ASCVD events by the PCE was improved by deriving VA-specific ß-coefficients (C statistic increased from 0.560 to 0.597) and improved further by including measures of glycemia, renal function, and diabetes mellitus treatment (C statistic, 0.632). Discrimination by the RECODe equations was improved by substituting VA-specific coefficients (C statistic increased from 0.604 to 0.621). Absolute risk estimation by PCE and RECODe equations also improved with VA-specific coefficients; the calibration P increased from <0.001 to 0.08 for PCE and from <0.001 to 0.005 for RECODe, where higher P indicates better calibration. Approximately two-thirds of veterans would meet a guideline indication for high-intensity statin therapy based on the PCE versus only 10% to 15% using VA-fitted models. CONCLUSIONS: Existing ASCVD risk equations overestimate risk in veterans with diabetes mellitus, potentially impacting guideline-indicated statin therapy. Prediction model performance can be improved for a health system's patients using readily available electronic health record data.

7.
JAMA ; 324(1): 68-78, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32633800

RESUMO

Importance: Data are limited regarding statin therapy for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in adults 75 years and older. Objective: To evaluate the role of statin use for mortality and primary prevention of ASCVD in veterans 75 years and older. Design, Setting, and Participants: Retrospective cohort study that used Veterans Health Administration (VHA) data on adults 75 years and older, free of ASCVD, and with a clinical visit in 2002-2012. Follow-up continued through December 31, 2016. All data were linked to Medicare and Medicaid claims and pharmaceutical data. A new-user design was used, excluding those with any prior statin use. Cox proportional hazards models were fit to evaluate the association of statin use with outcomes. Analyses were conducted using propensity score overlap weighting to balance baseline characteristics. Exposures: Any new statin prescription. Main Outcomes and Measures: The primary outcomes were all-cause and cardiovascular mortality. Secondary outcomes included a composite of ASCVD events (myocardial infarction, ischemic stroke, and revascularization with coronary artery bypass graft surgery or percutaneous coronary intervention). Results: Of 326 981 eligible veterans (mean [SD] age, 81.1 [4.1] years; 97% men; 91% white), 57 178 (17.5%) newly initiated statins during the study period. During a mean follow-up of 6.8 (SD, 3.9) years, a total 206 902 deaths occurred including 53 296 cardiovascular deaths, with 78.7 and 98.2 total deaths/1000 person-years among statin users and nonusers, respectively (weighted incidence rate difference [IRD]/1000 person-years, -19.5 [95% CI, -20.4 to -18.5]). There were 22.6 and 25.7 cardiovascular deaths per 1000 person-years among statin users and nonusers, respectively (weighted IRD/1000 person-years, -3.1 [95 CI, -3.6 to -2.6]). For the composite ASCVD outcome there were 123 379 events, with 66.3 and 70.4 events/1000 person-years among statin users and nonusers, respectively (weighted IRD/1000 person-years, -4.1 [95% CI, -5.1 to -3.0]). After propensity score overlap weighting was applied, the hazard ratio was 0.75 (95% CI, 0.74-0.76) for all-cause mortality, 0.80 (95% CI, 0.78-0.81) for cardiovascular mortality, and 0.92 (95% CI, 0.91-0.94) for a composite of ASCVD events when comparing statin users with nonusers. Conclusions and Relevance: Among US veterans 75 years and older and free of ASCVD at baseline, new statin use was significantly associated with a lower risk of all-cause and cardiovascular mortality. Further research, including from randomized clinical trials, is needed to more definitively determine the role of statin therapy in older adults for primary prevention of ASCVD.


Assuntos
Aterosclerose/prevenção & controle , Doenças Cardiovasculares/mortalidade , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Veteranos , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/prevenção & controle , Causas de Morte , Fatores de Confusão Epidemiológicos , Feminino , Humanos , Masculino , Mortalidade , Pontuação de Propensão , Estudos Retrospectivos , Estados Unidos/epidemiologia , Serviços de Saúde para Veteranos Militares
8.
JAMA Netw Open ; 3(7): e208236, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32662843

RESUMO

Importance: Current guidelines recommend statin therapy for millions of US residents for the primary prevention of atherosclerotic cardiovascular disease (ASCVD). It is unclear whether traditional prediction models that do not account for current widespread statin use are sufficient for risk assessment. Objectives: To examine the performance of the Pooled Cohort Equations (PCE) for 5-year ASCVD risk estimation in a contemporary cohort and to test the hypothesis that inclusion of statin therapy improves model performance. Design, Setting, and Participants: This cohort study included adult patients in the Veterans Affairs health care system without baseline ASCVD. Using national electronic health record data, 3 Cox proportional hazards models were developed to estimate 5-year ASCVD risk, as follows: the variables and published ß coefficients from the PCE (model 1), the PCE variables with cohort-derived ß coefficients (model 2), and model 2 plus baseline statin use (model 3). Data were collected from January 2002 to December 2012 and analyzed from June 2016 to March 2020. Exposures: Traditional ASCVD risk factors from the PCE plus baseline statin use. Main Outcomes and Measures: Incident ASCVD and ASCVD mortality. Results: Of 1 672 336 patients in the cohort (mean [SD] baseline age 58.0 [13.8] years, 1 575 163 [94.2%] men, 1 383 993 [82.8%] white), 312 155 (18.7%) were receiving statin therapy at baseline. During 5 years of follow-up, 66 605 (4.0%) experienced an ASCVD event, and 31 878 (1.9%) experienced ASCVD death. Compared with the original PCE, the cohort-derived model did not improve model discrimination in any of the 4 age-sex strata but did improve model calibration. The PCE overestimated ASCVD risk compared with the cohort-derived model; 211 237 of 1 136 161 white men (18.6%), 29 634 of 218 463 black men (13.6%), 1741 of 44 399 white women (3.9%), and 836 of 16 034 black women (5.2%) would be potentially eligible for statin therapy under the PCE but not the cohort-derived model. When added to the cohort-derived model, baseline statin therapy was associated with a 7% (95% CI, 5%-9%) lower relative risk of ASCVD and a 25% (95% CI, 23%-28%) lower relative risk for ASCVD death. Conclusions and Relevance: In this study, lower than expected rates of incident ASCVD events in a contemporary national cohort were observed. The PCE overestimated ASCVD risk, and more than 15% of patients would be potentially eligible for statin therapy based on the PCE but not on a cohort-derived model. In the statin era, health care professionals and systems should base ASCVD risk assessment on models calibrated to their patient populations.

9.
AMIA Jt Summits Transl Sci Proc ; 2020: 326-334, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32477652

RESUMO

Electronic health records (EHRs) provide a wealth of data for phenotype development in population health studies, and researchers invest considerable time to curate data elements and validate disease definitions. The ability to reproduce well-defined phenotypes increases data quality, comparability of results and expedites research. In this paper, we present a standardized approach to organize and capture phenotype definitions, resulting in the creation of an open, online repository of phenotypes. This resource captures phenotype development, provenance and process from the Million Veteran Program, a national mega-biobank embedded in the Veterans Health Administration (VHA). To ensure that the repository is searchable, extendable, and sustainable, it is necessary to develop both a proper digital catalog architecture and underlying metadata infrastructure to enable effective management of the data fields required to define each phenotype. Our methods provide a resource for VHA investigators and a roadmap for researchers interested in standardizing their phenotype definitions to increase portability.

10.
AMIA Jt Summits Transl Sci Proc ; 2020: 533-541, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32477675

RESUMO

The Department of Veteran's Affairs (VA) archives one of the largest corpora of clinical notes in their corporate data warehouse as unstructured text data. Unstructured text easily supports keyword searches and regular expressions. Often these simple searches do not adequately support the complex searches that need to be performed on notes. For example, a researcher may want all notes with a Duke Treadmill Score of less than five or people that smoke more than one pack per day. Range queries like this and more can be supported by modelling text as semi-structured documents. In this paper, we implement a scalable machine learning pipeline that models plain medical text as useful semi-structured documents. We improve on existing models and achieve an F1-score of 0.912 and scale our methods to the entire VA corpus.

11.
PLoS Genet ; 16(3): e1008684, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32226016

RESUMO

Lipid levels are important markers for the development of cardio-metabolic diseases. Although hundreds of associated loci have been identified through genetic association studies, the contribution of genetic factors to variation in lipids is not fully understood, particularly in U.S. minority groups. We performed genome-wide association analyses for four lipid traits in over 45,000 ancestrally diverse participants from the Population Architecture using Genomics and Epidemiology (PAGE) Study, followed by a meta-analysis with several European ancestry studies. We identified nine novel lipid loci, five of which showed evidence of replication in independent studies. Furthermore, we discovered one novel gene in a PrediXcan analysis, minority-specific independent signals at eight previously reported loci, and potential functional variants at two known loci through fine-mapping. Systematic examination of known lipid loci revealed smaller effect estimates in African American and Hispanic ancestry populations than those in Europeans, and better performance of polygenic risk scores based on minority-specific effect estimates. Our findings provide new insight into the genetic architecture of lipid traits and highlight the importance of conducting genetic studies in diverse populations in the era of precision medicine.


Assuntos
Grupos de Populações Continentais/genética , Lipídeos/sangue , Lipídeos/genética , Bases de Dados Genéticas , Feminino , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Lipídeos/análise , Masculino , Metagenômica/métodos , Grupos Minoritários , Herança Multifatorial/genética , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Estados Unidos/epidemiologia
12.
Clin Nutr ; 39(9): 2842-2847, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31902601

RESUMO

BACKGROUND & AIMS: Limited and inconsistent data are available on the relation between egg consumption and risk of myocardial infarction (MI) and it is unclear if adiposity or type 2 diabetes modifies egg-MI relation. We tested the primary hypothesis that egg consumption is positively associated with incidence of MI among veterans. In secondary analyses, we examined potential effect modification of egg-MI relation by adiposity and type 2 diabetes. METHODS: We analyzed data collected on 188,267 US veterans who were enrolled in the Million Veteran Program (MVP) from 2011 to 2018. Information on egg consumption was obtained via self-administered food frequency questionnaire and we used electronic health records to identify incident MI. RESULTS: The mean age was 64.4 (SD = 12.0) years and 9.9% of the population were female. We ascertained 10,260 new cases of non-fatal MI during an average follow up of 3.24 years (range: 0.002 to 7.49 y). Hazard ratio (95% CI) for non-fatal MI were 1.00 (ref), 0.93 (0.85-0.1.02), 0.96 (0.87-1.05), 0.98 (0.89-1.07), 1.08 (0.98-1.19), 1.11 (1.00-1.24), and 1.13 (1.00-1.28) for egg consumption of <1/month, 1-3/month, 1/week, 2-4/week, 5-6/week, 1/d, and 2+/d, respectively, controlling for age, sex, race, body mass index, smoking, exercise, alcohol intake, and overall dietary pattern (p non-linear trend 0.019). In secondary analyses, we observed similar results with a composite endpoint including fatal MI, coronary angioplasty and revascularization. CONCLUSIONS: Our data showed no association of infrequent consumption of eggs with non-fatal MI but a slightly elevated risk with intake of 1 or more eggs per day among US veterans.

13.
Clin Nutr ; 39(2): 574-579, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30914216

RESUMO

BACKGROUND & AIMS: Observational and clinical trial evidence suggests an inverse association of omega-3 polyunsaturated fatty acids with coronary artery disease (CAD) mortality, although relationships with non-fatal CAD and stroke are less clear. We investigated whether omega-3 fatty acid supplement use and fish intake were associated with incident non-fatal CAD and ischemic stroke among US Veterans. METHODS: The Million Veteran Program (MVP) is an ongoing nation-wide longitudinal cohort study of US Veterans with self-reported survey, biospecimen, and electronic health record data. Regular use of omega-3 supplements (yes/no) and frequency of fish intake within the past year were assessed using a food frequency questionnaire. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the associations of omega-3 supplement use and fish intake with incident non-fatal CAD and ischemic stroke, defined from electronic health records using validated algorithms. Multivariable models included demographics, body mass index, education, smoking status, alcohol intake, and exercise frequency. RESULTS: Among 197,761 participants with food frequency data (mean age: 66 ± 12 years, 92% men), 21% regularly took omega-3 supplements and median fish intake was 1 (3-5 ounce) serving/week. Over a median follow-up of 2.9 years for non-fatal CAD and 3.3 years for non-fatal ischemic stroke, we observed 6265 and 4042 incident cases of non-fatal CAD and non-fatal ischemic stroke, respectively. Omega-3 fatty acid supplement use was independently associated with a lower risk of non-fatal ischemic stroke [HR (95% CI): 0.88 (0.81, 0.95)] but not non-fatal CAD [0.99 (0.93, 1.06)]. Fish intake was not independently associated with non-fatal CAD [1.01 (0.94, 1.09) for 1-3 servings/month, 1.03 (0.98, 1.11) for 1 serving/week, 1.02 (0.93, 1.11) for 2-4 servings/week, and 1.15 (0.98, 1.35) for ≥5 servings/week, reference = <1 serving/month, linear p-trend = 0.09] or non-fatal ischemic stroke [0.92 (0.84, 1.00) for 1-3 servings/month, 0.93 (0.85, 1.02) for 1 serving/week, 0.96 (0.86, 1.07) for 2-4 servings/week, and 1.13 (0.93-1.38) for ≥5 servings/week, linear p-trend = 0.16]. CONCLUSIONS: Neither omega-3 supplement use, nor fish intake, was associated with non-fatal CAD among US Veterans. While omega-3 supplement use was associated with lower risk of non-fatal ischemic stroke, fish intake was not. Randomized controlled trials are needed to confirm whether omega-3 supplementation is protective against ischemic stroke in a US population.

14.
Clin Nutr ; 39(4): 1203-1208, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31279615

RESUMO

INTRODUCTION: Previous studies of the relationship between fried food consumption and coronary artery disease (CAD) have yielded conflicting results. We tested the hypothesis that frequent fried food consumption is associated with a higher risk of incident CAD events in Million Veteran Program (MVP) participants. METHODS: Veterans Health Administration electronic health record data were linked to questionnaires completed at MVP enrollment. Self-reported fried food consumption at baseline was categorized: (<1, 1-3, 4-6 times per week or daily). The outcome of interest was non-fatal myocardial infarction or CAD events. We fitted a Cox regression model adjusting for age, sex, race, education, exercise, smoking and alcohol consumption. RESULTS: Of 154,663 MVP enrollees with survey data, mean age was 64 years and 90% were men. During a mean follow-up of approximately 3 years, there were 6,725 CAD events. There was a positive linear relationship between frequency of fried food consumption and risk of CAD (p for trend 0.0015). Multivariable adjusted hazard ratios (95% CI) were 1.0 (ref), 1.07 (1.01-1.13), 1.08 (1.01-1.16), and 1.14 (1.03-1.27) across consecutive increasing categories of fried food intake. CONCLUSIONS: In a large national cohort of U.S. Veterans, fried food consumption has a positive, dose-dependent association with CAD.

15.
J Biomed Inform ; 100: 103322, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31672532

RESUMO

OBJECTIVE: With its increasingly widespread adoption, electronic health records (EHR) have enabled phenotypic information extraction at an unprecedented granularity and scale. However, often a medical concept (e.g. diagnosis, prescription, symptom) is described in various synonyms across different EHR systems, hindering data integration for signal enhancement and complicating dimensionality reduction for knowledge discovery. Despite existing ontologies and hierarchies, tremendous human effort is needed for curation and maintenance - a process that is both unscalable and susceptible to subjective biases. This paper aims to develop a data-driven approach to automate grouping medical terms into clinically relevant concepts by combining multiple up-to-date data sources in an unbiased manner. METHODS: We present a novel data-driven grouping approach - multi-view banded spectral clustering (mvBSC) combining summary data from multiple healthcare systems. The proposed method consists of a banding step that leverages the prior knowledge from the existing coding hierarchy, and a combining step that performs spectral clustering on an optimally weighted matrix. RESULTS: We apply the proposed method to group ICD-9 and ICD-10-CM codes together by integrating data from two healthcare systems. We show grouping results and hierarchies for 13 representative disease categories. Individual grouping qualities were evaluated using normalized mutual information, adjusted Rand index, and F1-measure, and were found to consistently exhibit great similarity to the existing manual grouping counterpart. The resulting ICD groupings also enjoy comparable interpretability and are well aligned with the current ICD hierarchy. CONCLUSION: The proposed approach, by systematically leveraging multiple data sources, is able to overcome bias while maximizing consensus to achieve generalizability. It has the advantage of being efficient, scalable, and adaptive to the evolving human knowledge reflected in the data, showing a significant step toward automating medical knowledge integration.


Assuntos
Registros Eletrônicos de Saúde , Classificação Internacional de Doenças , Algoritmos , Automação , Análise por Conglomerados , Humanos
16.
Nat Protoc ; 14(12): 3426-3444, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31748751

RESUMO

Phenotypes are the foundation for clinical and genetic studies of disease risk and outcomes. The growth of biobanks linked to electronic medical record (EMR) data has both facilitated and increased the demand for efficient, accurate, and robust approaches for phenotyping millions of patients. Challenges to phenotyping with EMR data include variation in the accuracy of codes, as well as the high level of manual input required to identify features for the algorithm and to obtain gold standard labels. To address these challenges, we developed PheCAP, a high-throughput semi-supervised phenotyping pipeline. PheCAP begins with data from the EMR, including structured data and information extracted from the narrative notes using natural language processing (NLP). The standardized steps integrate automated procedures, which reduce the level of manual input, and machine learning approaches for algorithm training. PheCAP itself can be executed in 1-2 d if all data are available; however, the timing is largely dependent on the chart review stage, which typically requires at least 2 weeks. The final products of PheCAP include a phenotype algorithm, the probability of the phenotype for all patients, and a phenotype classification (yes or no).


Assuntos
Análise de Dados , Registros Eletrônicos de Saúde/estatística & dados numéricos , Ensaios de Triagem em Larga Escala/métodos , Algoritmos , Interpretação Estatística de Dados , Humanos , Aprendizado de Máquina , Processamento de Linguagem Natural , Fenótipo
17.
J Am Med Inform Assoc ; 26(11): 1255-1262, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31613361

RESUMO

OBJECTIVE: Electronic health records linked with biorepositories are a powerful platform for translational studies. A major bottleneck exists in the ability to phenotype patients accurately and efficiently. The objective of this study was to develop an automated high-throughput phenotyping method integrating International Classification of Diseases (ICD) codes and narrative data extracted using natural language processing (NLP). MATERIALS AND METHODS: We developed a mapping method for automatically identifying relevant ICD and NLP concepts for a specific phenotype leveraging the Unified Medical Language System. Along with health care utilization, aggregated ICD and NLP counts were jointly analyzed by fitting an ensemble of latent mixture models. The multimodal automated phenotyping (MAP) algorithm yields a predicted probability of phenotype for each patient and a threshold for classifying participants with phenotype yes/no. The algorithm was validated using labeled data for 16 phenotypes from a biorepository and further tested in an independent cohort phenome-wide association studies (PheWAS) for 2 single nucleotide polymorphisms with known associations. RESULTS: The MAP algorithm achieved higher or similar AUC and F-scores compared to the ICD code across all 16 phenotypes. The features assembled via the automated approach had comparable accuracy to those assembled via manual curation (AUCMAP 0.943, AUCmanual 0.941). The PheWAS results suggest that the MAP approach detected previously validated associations with higher power when compared to the standard PheWAS method based on ICD codes. CONCLUSION: The MAP approach increased the accuracy of phenotype definition while maintaining scalability, thereby facilitating use in studies requiring large-scale phenotyping, such as PheWAS.

18.
Diabetes Care ; 42(10): 1995-2003, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31515207

RESUMO

OBJECTIVE: Guidelines for hypertension treatment in patients with diabetes diverge regarding the systolic blood pressure (SBP) threshold at which treatment should be initiated and treatment goal. We examined associations of early SBP treatment with atherosclerotic cardiovascular disease (ASCVD) events in U.S. adults with diabetes. RESEARCH DESIGN AND METHODS: We studied 43,986 patients with diabetes who newly initiated antihypertensive therapy between 2002 and 2007. Patients were classified into categories based on SBP at treatment initiation (130-139 or ≥140 mmHg) and after 2 years of treatment (100-119, 120-129, 130-139, 140-159, and ≥160 mmHg). The primary outcome was composite ASCVD events (fatal and nonfatal myocardial infarction and stroke), estimated using inverse probability of treatment-weighted Poisson regression and multivariable Cox proportional hazards regression. RESULTS: Relative to individuals who initiated treatment when SBP was 130-139 mmHg, those with pretreatment SBP ≥140 mmHg had higher ASCVD risk (hazard ratio 1.10 [95% CI 1.02, 1.19]). Relative to those with pretreatment SBP of 130-139 mmHg and on-treatment SBP of 120-129 mmHg (reference group), ASCVD incidence was higher in those with pretreatment SBP ≥140 mmHg and on-treatment SBP 120-129 mmHg (adjusted incidence rate difference [IRD] 1.0 [-0.2 to 2.1] events/1,000 person-years) and in those who achieved on-treatment SBP 130-139 mmHg (IRD 1.9 [0.6, 3.2] and 1.1 [0.04, 2.2] events/1,000 person-years for those with pretreatment SBP 130-139 mmHg and ≥140 mmHg, respectively). CONCLUSIONS: In this observational study, patients with diabetes initiating antihypertensive therapy when SBP was 130-139 mmHg and those achieving on-treatment SBP <130 mmHg had better outcomes than those with higher SBP levels when initiating or after 2 years on treatment.


Assuntos
Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/tratamento farmacológico , Intervenção Médica Precoce , Hipertensão/tratamento farmacológico , Veteranos , Adulto , Idoso , Aterosclerose/complicações , Aterosclerose/tratamento farmacológico , Aterosclerose/epidemiologia , Aterosclerose/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/complicações , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/fisiopatologia , Diabetes Mellitus/fisiopatologia , Intervenção Médica Precoce/métodos , Feminino , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Veteranos/estatística & dados numéricos
19.
PLoS One ; 14(7): e0219964, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31323063

RESUMO

AIMS/HYPOTHESIS: Early recognition of those at high risk for diabetes as well as diabetes itself can permit preventive management, but many Americans with diabetes are undiagnosed. We sought to determine whether routinely available outpatient random plasma glucose (RPG) would be useful to facilitate the diagnosis of diabetes. METHODS: Retrospective cohort study of 942,446 U.S. Veterans without diagnosed diabetes, ≥3 RPG in a baseline year, and ≥1 primary care visit/year during 5-year follow-up. The primary outcome was incident diabetes (defined by diagnostic codes and outpatient prescription of a diabetes drug). RESULTS: Over 5 years, 94,599 were diagnosed with diabetes [DIAB] while 847,847 were not [NONDIAB]. Baseline demographics of DIAB and NONDIAB were clinically similar, except DIAB had higher BMI (32 vs. 28 kg/m2) and RPG (150 vs. 107 mg/dl), and were more likely to have Black race (18% vs. 15%), all p<0.001. ROC area for prediction of DIAB diagnosis within 1 year by demographic factors was 0.701, and 0.708 with addition of SBP, non-HDL cholesterol, and smoking. These were significantly less than that for prediction by baseline RPG alone (≥2 RPGs at/above a given level, ROC 0.878, p<0.001), which improved slightly when other factors were added (ROC 0.900, p<0.001). Having ≥2 RPGs ≥115 mg/dl had specificity 77% and sensitivity 87%, and ≥2 RPGs ≥130 mg/dl had specificity 93% and sensitivity 59%. For predicting diagnosis within 3 and 5 years by RPG alone, ROC was reduced but remained substantial (ROC 0.839 and 0.803, respectively). CONCLUSIONS: RPG levels below the diabetes "diagnostic" range (≥200 mg/dl) provide good discrimination for follow-up diagnosis. Use of such levels-obtained opportunistically, during outpatient visits-could signal the need for further testing, allow preventive intervention in high risk individuals before onset of disease, and lead to earlier identification of diabetes.


Assuntos
Glicemia , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Adulto , Idoso , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Razão de Chances , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
20.
Int J Cardiol ; 290: 119-124, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30929975

RESUMO

OBJECTIVE: The purpose of our study is to examine whether serial measurements of serum sodium values after diagnosis identify a higher-risk subset of patients with heart failure with preserved ejection fraction. METHODS: We identified 50,932 subjects with HFpEF with 759,577 recorded sNa measurements (mean age 72 ±â€¯11 years) using a validated algorithm in the VA national database from 2002 to 2012. We examined the association of repeated measures of sNa with mortality using a multivariable Cox proportional hazards model. RESULTS: After a median follow-up of 2.9 years (IQR: 1.2-5.4), 19,011 deaths occurred. After adjusting for age, sex, race, BMI, glomerular filtration rate, potassium, coronary artery disease, hypertension, hyperlipidemia, atrial fibrillation, pulmonary disease, diabetes, anemia, and medications, we found J-shaped associations of serum sodium with mortality. HRs for all-cause mortality were 2.48 (95% CI: 2.38-2.60) for the sNA 115.00-133.99 category; and 1.40 (95% CI: 1.35-1.46) for the sNA 143.00-175.00 category compared to the 137.01-140.99 category (ref). We used generalized estimating equation-based negative binomial regression to compute the incidence density ratios (IDR) to examine days hospitalized for heart failure and for all causes. There were a total of 1,275,614 days of all-cause hospitalization and 104,006 days of heart-failure hospitalization. The IDRs for the lowest sNA group were 2.03 (95% CI: 1.90-2.18) for all-cause hospitalization and 1.73 (95% CI: 1.39-2.16) for heart-failure hospitalization. CONCLUSIONS: Our findings suggest that monitoring of serum sodium values during longitudinal follow-up can identify HFpEF patients at risk of adverse outcomes.


Assuntos
Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Sódio/sangue , Volume Sistólico/fisiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Resultado do Tratamento
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