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BACKGROUND: Pneumonia due to typical bacterial, atypical bacterial and viral pathogens can be difficult to clinically differentiate. Host response-based diagnostics are emerging as a complementary diagnostic strategy to pathogen detection. METHODS: We used murine models of typical bacterial, atypical bacterial and viral pneumonia to develop diagnostic signatures and understand the host's response to these types of infections. Mice were intranasally inoculated with Streptococcus pneumoniae, Mycoplasma pneumoniae, influenza or saline as a control. Peripheral blood gene expression analysis was performed at multiple time points. Differentially expressed genes were used to perform gene set enrichment analysis and generate diagnostic signatures. These murine-derived signatures were externally validated in silico using human gene expression data. The response to S. pneumoniae was the most rapid and robust. RESULTS: Mice infected with M. pneumoniae had a delayed response more similar to influenza-infected animals. Diagnostic signatures for the three types of infection had 0.94-1.00 area under the receiver operator curve (auROC). Validation in five human gene expression datasets revealed auROC of 0.82-0.96. DISCUSSION: This study identified discrete host responses to typical bacterial, atypical bacterial and viral aetiologies of pneumonia in mice. These signatures validated well in humans, highlighting the conserved nature of the host response to these pathogen classes.
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Modelos Animais de Doenças , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Streptococcus pneumoniae , Animais , Humanos , Camundongos , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificação , Pneumonia por Mycoplasma/diagnóstico , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/isolamento & purificação , Feminino , Pneumonia Pneumocócica/microbiologia , Infecções por Orthomyxoviridae/imunologia , Curva ROC , Perfilação da Expressão Gênica , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Camundongos Endogâmicos C57BL , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/diagnóstico , Interações Hospedeiro-PatógenoRESUMO
This survey study describes the perceived implications of virtual-only recruitment and the preferred application process for residents and fellows.
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Internato e Residência , Estudantes de Medicina , Humanos , Inquéritos e QuestionáriosRESUMO
PURPOSE: To quantify the extent to which internal medicine (IM) residents provided care for patients with COVID-19 and examine characteristics of residency programs with or without plans (at some point) to exclude residents from COVID-19 care during the first 6 months of the pandemic. METHOD: The authors used data from a nationally representative, annually recurring survey of U.S. IM program directors (PDs) to quantify early (March-August 2020) resident participation in COVID-19 care. The survey was fielded from August to December 2020. PDs reported whether they had planned to exclude residents from COVID-19 care (i.e., PTE status). PTE status was tested for association with program and COVID-19 temporal characteristics, resident schedule accommodations, and resident COVID-19 cases. RESULTS: The response rate was 61.5% (264/429). Nearly half of PDs (45.4%, 118/260) reported their program had planned at some point to exclude residents from COVID-19 care. Northeastern U.S. programs represented a smaller percentage of PTE than non-PTE programs (26.3% vs 36.6%; P = .050). PTE programs represented a higher percentage of programs with later surges than non-PTE programs (33.0% vs 13.6%, P = .048). Median percentage of residents involved in COVID-19 care was 75.0 (interquartile range [IQR]: 22.5-100.0) for PTE programs, compared with 95.0 (IQR: 60.0-100.0) for non-PTE programs ( P < .001). Residents participated most in intensive care units (87.6%, 227/259) and inpatient wards (80.8%, 210/260). Accommodations did not differ by PTE status. PTE programs reported fewer resident COVID-19 cases than non-PTE programs (median percentage = 2.7 [IQR: 0.0-8.6] vs 5.1 [IQR: 1.6-10.7]; P = .011). CONCLUSIONS: IM programs varied widely in their reported plans to exclude residents from COVID-19 care during the early pandemic. A high percentage of residents provided COVID-19 care, even in PTE programs. Thus, the pandemic highlighted the tension as to whether residents are learners or employees.
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COVID-19 , Internato e Residência , Humanos , Estados Unidos/epidemiologia , COVID-19/epidemiologia , Pandemias , Inquéritos e QuestionáriosRESUMO
Many aspects of the host response to invasive cryptococcal infections remain poorly understood. In order to explore the pathobiology of infection with common clinical strains, we infected BALB/cJ mice with Cryptococcus neoformans, Cryptococcus gattii, or sham control, and assayed host transcriptomic responses in peripheral blood. Infection with C. neoformans resulted in markedly greater fungal burden in the CNS than C. gattii, as well as slightly higher fungal burden in the lungs. A total of 389 genes were significantly differentially expressed in response to C. neoformans infection, which mainly clustered into pathways driving immune function, including complement activation and TH2-skewed immune responses. C. neoformans infection demonstrated dramatic up-regulation of complement-driven genes and greater up-regulation of alternatively activated macrophage activity than seen with C gattii. A 27-gene classifier was built, capable of distinguishing cryptococcal infection from animals with bacterial infection due to Staphylococcus aureus with 94% sensitivity and 89% specificity. Top genes from the murine classifiers were also differentially expressed in human PBMCs following infection, suggesting cross-species relevance of these findings. The host response, as manifested in transcriptional profiles, informs our understanding of the pathophysiology of cryptococcal infection and demonstrates promise for contributing to development of novel diagnostic approaches.
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Background: Burnout is common among physicians and physician leaders, including residency program directors (PDs). The effects of the COVID-19 pandemic and other stressors in 2020 on PDs is unknown. Objective: To measure the prevalence of burnout among internal medicine (IM) residency PDs 6 months into the COVID-19 pandemic. Methods: A total of 429 IM PDs, representing 83% of accredited residency programs, were surveyed from August to December 2020. Burnout, using a 2-item screening tool, and self-reported consideration of resigning in 2020, were compared to their annual prevalence since 2012 and tested for possible associations with pandemic stressors and program characteristics. Results: The survey response rate was 61.5% (264 of 429). One-third (33.6%, 87 of 259) of PD respondents met burnout criteria, and 45.1% (110 of 244) reported considering resigning in the past year, which were within the range of preceding years. PDs who reported feeling highly supported by institutional leadership were less likely to meet burnout criteria and to have considered resigning. There were no associations between burnout or consideration of resigning and the amount of clinical time PDs spent in their roles, duration of maximum stress on programs, budget cuts to programs, or geographic region. Conclusions: The prevalence of burnout among PDs in fall 2020 was similar to the prevalence of burnout in pre-pandemic years despite uniquely extreme stressors. PDs' perception of being highly supported by institutional leadership was associated with lower prevalence of burnout and consideration of resigning. Perceived leadership support may be a protective factor against burnout during periods of high stress.
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Esgotamento Profissional , COVID-19 , Internato e Residência , Esgotamento Profissional/epidemiologia , Esgotamento Psicológico , Humanos , Pandemias , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The learning and working environment for resident physicians shifted dramatically over the past two decades, with increased focus on work hours, resident wellness, and patient safety. Following two multi-center randomized trials comparing 16-h work limits for PGY-1 trainees to more flexible rules, the ACGME implemented new flexible work hours standards in 2017. OBJECTIVE: We sought to determine program directors' (PDs) support for the work hour changes and programmatic response. DESIGN: In 2017, US Internal Medicine PDs were surveyed about their degree of support for extension of PGY-1 work hour limits, whether they adopted the new maximum continuous work hours permitted, and reasons for their decisions. KEY RESULTS: The response rate was 70% (266/379). Fifty-seven percent of PDs (n = 151) somewhat/strongly support the new work hour rules for PGY-1 residents, while only 25% of programs (N = 66) introduced work periods greater than 16-h on any rotation. Higher rates of adopting change were seen in PDs who strongly/somewhat supported the change (56/151 [37%], P < 0.001), had tenure of 6+ years (33/93 [35%], P = 0.005), were of non-general internal medicine subspecialty (30/80 [38%], P = 0.003), at university-based programs (35/101 [35%], P = 0.009), and with increasing number of approved positions (< 38, 10/63 [16%]; 38-58, 13/69 [19%]; 59-100, 15/64 [23%]; > 100, 28/68 [41%], P = 0.005). Areas with the greatest influence for PDs not extending work hours were the 16-h rule working well (56%) and risk to PGY1 well-being (47%). CONCLUSIONS: Although the majority of PDs support the ACGME 2017 work hours rules, only 25% of programs made immediate changes to extend hours. These data reveal that complex, often competing, forces influence PDs' decisions to change trainee schedules.
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Internato e Residência , Admissão e Escalonamento de Pessoal , Humanos , Medicina Interna , Inquéritos e Questionários , Estados Unidos , Carga de TrabalhoRESUMO
Invasive aspergillosis (IA) is a major cause of critical illness in immunocompromised (IC) patients. However, current fungal tests are limited. Disease-specific gene expression patterns in circulating host cells show promise as novel diagnostics, however it is unknown whether such a 'signature' exists for IA and the effect of iatrogenic immunosuppression on any such biomarkers. Male BALB/c mice were separated into 6 experimental groups based on Aspergillus fumigatus inhalational exposure and IC status (no immunosuppression, cyclophosphamide, and corticosteroids). Mice were sacrificed 4 days postinfection. Whole blood was assayed for transcriptomic responses in peripheral white blood cells via microarray. An elastic net regularized logistic regression was employed to develop classifiers of IA based on gene expression. Aspergillus infection triggers a powerful response in non-IC hosts with 2718 genes differentially expressed between IA and controls. We generated a 146-gene classifier able to discriminate between non-IC infected and uninfected mice with an AUC of 1. However, immunosuppressive medications exhibited a confounding effect on this transcriptomic classifier. After controlling for the genomic effects of immunosuppression, we were able to generate a 187-gene classifier with an AUC of 0.92 in the absence of immunosuppression, 1 with cyclophosphamide, and 0.9 with steroids. The host transcriptomic response to IA is robust and conserved. Pharmacologic perturbation of the host immune response has powerful effects on classifier performance and must be considered when developing such novel diagnostics. When appropriately designed, host-derived peripheral blood transcriptomic responses demonstrate the ability to accurately diagnose Aspergillus infection, even in the presence of immunosuppression.
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Aspergilose/diagnóstico , Aspergillus fumigatus/genética , Genes Fúngicos , Hospedeiro Imunocomprometido , Transcrição Gênica , Animais , Aspergilose/genética , Aspergilose/microbiologia , Aspergillus fumigatus/isolamento & purificação , Aspergillus fumigatus/patogenicidade , Estudos de Casos e Controles , Contagem de Colônia Microbiana , Pulmão/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Reprodutibilidade dos TestesRESUMO
PURPOSE: To measure the association between institutional investment in high-value care (HVC) performance improvement and resident HVC experiences. METHOD: The authors analyzed data from two 2014 surveys assessing institutions' investments in HVC performance improvement as reported by program directors (PDs) and residents' perceptions of the frequency of HVC teaching, participation in HVC-focused quality improvement (QI), and views on HVC topics. The authors measured the association between institutional investment and resident-reported experiences using logistic regression, controlling for program and resident characteristics. RESULTS: The sample included 214 programs and 9,854 residents (59.3% of 361 programs, 55.2% of 17,851 residents surveyed). Most PDs (158/209; 75.6%) reported some support. Residents were more likely to report HVC discussions with faculty at least a few times weekly if they trained in programs that offered HVC-focused faculty development (odds ratio [OR] = 1.19; 95% confidence interval [CI] 1.04-1.37; P = .01), that supported such faculty development (OR = 1.21; 95% CI 1.04-1.41; P = .02), or that provided physician cost-of-care performance data (OR = 1.19; 95% CI 1.03-1.39; P = .02). Residents were more likely to report participation in HVC QI if they trained in programs with a formal HVC curriculum (OR = 1.83; 95% CI 1.48-2.27; P < .001) or with HVC-focused faculty development (OR = 1.46; 95% CI 1.15-1.85; P = .002). CONCLUSIONS: Institutional investment in HVC-related faculty development and physician feedback on costs of care may increase the frequency of HVC teaching and resident participation in HVC-related QI.
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Currículo , Medicina Interna/educação , Internato e Residência , Percepção , Estudantes de Medicina/psicologia , Competência Clínica , Estudos Transversais , Atenção à Saúde/normas , Humanos , Melhoria de Qualidade , Inquéritos e QuestionáriosAssuntos
Febre/diagnóstico , Temperatura Alta , Linfo-Histiocitose Hemofagocítica/diagnóstico , Clima Tropical , Adulto , Indústria da Construção , Diagnóstico Diferencial , Febre/sangue , Febre/etiologia , Temperatura Alta/efeitos adversos , Humanos , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/complicações , Masculino , Clima Tropical/efeitos adversosRESUMO
BACKGROUND: Failure to follow up and communicate test results to patients in outpatient settings may lead to diagnostic and therapeutic delays. Residents are less likely than attending physicians to report results to patients, and may face additional barriers to reporting, given competing clinical responsibilities. OBJECTIVE: This study aimed to improve the rates of communicating test results to patients in resident ambulatory clinics. METHODS: We performed an internal medicine, residency-wide, pre- and postintervention, quality improvement project using audit and feedback. Residents performed audits of ambulatory patients requiring laboratory or radiologic testing by means of a shared online interface. The intervention consisted of an educational module viewed with initial audits, development of a personalized improvement plan after Phase 1, and repeated real-time feedback of individual relative performance compared at clinic and program levels. Outcomes included results communicated within 14 days and prespecified "significant" results communicated within 72 hours. RESULTS: A total of 76 of 86 eligible residents (88%) reviewed 1713 individual ambulatory patients' charts in Phase 1, and 73 residents (85%) reviewed 1509 charts in Phase 2. Follow-up rates were higher in Phase 2 than Phase 1 for communicating results within 14 days and significant results within 72 hours (85% versus 78%, P < .001; and 82% versus 70%, P = .002, respectively). Communication of "significant" results was more likely to occur via telephone, compared with communication of nonsignificant results. CONCLUSIONS: Participation in a shared audit and feedback quality improvement project can improve rates of resident follow-up and communication of results, although communication gaps remained.
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Comunicação , Retroalimentação , Medicina Interna/educação , Internato e Residência , Instituições de Assistência Ambulatorial , Feminino , Seguimentos , Humanos , Internet , Masculino , Auditoria Médica , Prontuários Médicos , Médicos , Fatores de TempoRESUMO
Deficiencies in resident diabetes care quality may relate to continuity clinic design. This retrospective analysis compared diabetes care processes and outcomes within a traditional resident continuity clinic structure (2005) and after the implementation of a practice partnership system (PPS; 2009). Under PPS, patients were more likely to receive annual foot examinations (odds ratio [OR] = 11.6; 95% confidence interval [CI] = 7.2, 18.5), microalbumin screening (OR = 2.4; 95% CI = 1.6, 3.4), and aspirin use counseling (OR = 3.8; 95% CI = 2.5, 6.0) and were less likely to receive eye examinations (OR = 0.54; 95% CI = 0.36, 0.82). Hemoglobin A1c and lipid testing were similar between periods, and there was no difference in achievement of diabetes and blood pressure goals. Patients were less likely to achieve cholesterol goals under PPS (OR = 0.62; 95% CI = 0.39, 0.98). Resident practice partnerships may improve processes of diabetes care but may not affect intermediate outcomes.
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Assistência Ambulatorial/organização & administração , Diabetes Mellitus/terapia , Medicina Interna/educação , Internato e Residência/organização & administração , Qualidade da Assistência à Saúde/organização & administração , Idoso , Assistência Ambulatorial/estatística & dados numéricos , Pressão Sanguínea , Feminino , Hemoglobinas Glicadas , Humanos , Internato e Residência/estatística & dados numéricos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Indicadores de Qualidade em Assistência à Saúde , Qualidade da Assistência à Saúde/estatística & dados numéricos , Estudos RetrospectivosRESUMO
CONTEXT: Graduate medical trainees have a critical role in the teaching of other trainees. Improving their teaching requires an understanding of their attitudes towards teaching and their motivation to teach. Both have been incompletely explored in this population. We aimed to better understand graduate medical trainees' attitudes towards teaching and motivation to teach in the clinical setting in order to inform modifications to resident-as-teacher (RAT) programmes and enhance teaching practices. METHODS: We applied Q methodology, an established sorting method, to identify and quantify the factors that have an impact on trainees' engagement in teaching. We invited house officers at our institution to rank-order 47 statements regarding their attitudes to and motivation for teaching. Respondents explained their Q-sort rankings in writing and completed a demographic questionnaire. By-person factor analysis yielded groups of individuals with similar attitudes. RESULTS: One hundred and seven trainees completed the Q-sort. We found three primary groups of attitudes towards teaching in the clinical setting: enthusiasm, reluctance and rewarded. Enthusiastic teachers are committed and make time to teach. Teaching increases their job satisfaction. Reluctant teachers have enthusiasm but are earlier in training and feel limited by clinical workload and unprepared. Rewarded teachers feel teaching is worthwhile and derive satisfaction from the rewards and recognition they receive for teaching. CONCLUSIONS: This improved understanding of common attitudes shared by groups of residents will help curriculum designers create RAT programmes to further reinforce and encourage attitudes that promote teaching as well as improve trainees' motivation to teach. Designing RAT programmes that acknowledge the attitudes to and motivations for teaching should help develop effective teachers to improve educational outcomes. Directed efforts to enhance motivation for reluctant teachers and encourage more positive attitudes in rewarded teachers may lead to improved teaching behaviours among residents.
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Atitude do Pessoal de Saúde , Internato e Residência , Motivação , Estudantes de Medicina/psicologia , Ensino/psicologia , Feminino , Humanos , Masculino , North Carolina , Satisfação PessoalRESUMO
PROBLEM: The Accreditation Council for Graduate Medical Education milestones were written by physicians and thus may not reflect all the behaviors necessary for physicians to optimize their performance as a key member of an interprofessional team. APPROACH: From April to May 2013, the authors, Educational Research Outcomes Collaborative leaders, assembled interprofessional team discussion groups, including patients or family members, nurses, physician trainees, physician educators, and other staff (optional), at 11 internal medicine (IM) programs. Led by the site's principal investigator, the groups generated a list of physician behaviors related to the entrustable professional activity (EPA) of a safe and effective discharge of a patient from the hospital, and prioritized those behaviors. OUTCOMES: A total of 182 behaviors were listed, with lists consisting of between 10 and 29 behaviors. Overall, the site principal investigators described all participants as emerging from the activity with a new understanding of the complexity of training physicians for the discharge EPA. The authors batched behaviors into six components of a safe and effective discharge: medication reconciliation, discharge summary, patient/caregiver communication, team communication, active collaboration, and anticipation of posthospital needs. Specific, high-priority behavior examples for each component were identified, and an assessment tool for direct observation was developed for the discharge EPA. NEXT STEPS: The authors are currently evaluating trainee and educator perceptions of the assessment tool after implementation in 15 IM programs. Additional next steps include developing tools for other EPAs, as well as a broader evaluation of patient outcomes in the era of milestone-based assessment.
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Early, presymptomatic intervention with oseltamivir (corresponding to the onset of a published host-based genomic signature of influenza infection) resulted in decreased overall influenza symptoms (aggregate symptom scores of 23.5 vs 46.3), more rapid resolution of clinical disease (20 hours earlier), reduced viral shedding (total median tissue culture infectious dose [TCID50] 7.4 vs 9.7), and significantly reduced expression of several inflammatory cytokines (interferon-γ, tumor necrosis factor-α, interleukin-6, and others). The host genomic response to influenza infection is robust and may provide the means for early detection, more timely therapeutic interventions, a meaningful reduction in clinical disease, and an effective molecular means to track response to therapy.
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Circulação Assistida , Transplante de Coração-Pulmão , Micoses/diagnóstico , Micoses/terapia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/terapia , Adulto , Criança , Humanos , Incidência , Micoses/epidemiologia , Complicações Pós-Operatórias/epidemiologia , PrevalênciaRESUMO
BACKGROUND: Consider the problem of designing a panel of complex biomarkers to predict a patient's health or disease state when one can pair his or her current test sample, called a target sample, with the patient's previously acquired healthy sample, called a reference sample. As contrasted to a population averaged reference this reference sample is individualized. Automated predictor algorithms that compare and contrast the paired samples to each other could result in a new generation of test panels that compare to a person's healthy reference to enhance predictive accuracy. This paper develops such an individualized predictor and illustrates the added value of including the healthy reference for design of predictive gene expression panels. RESULTS: The objective is to predict each subject's state of infection, e.g., neither exposed nor infected, exposed but not infected, pre-acute phase of infection, acute phase of infection, post-acute phase of infection. Using gene microarray data collected in a large scale serially sampled respiratory virus challenge study we quantify the diagnostic advantage of pairing a person's baseline reference with his or her target sample. The full study consists of 2886 microarray chips assaying 12,023 genes of 151 human volunteer subjects under 4 different inoculation regimes (HRV, RSV, H1N1, H3N2). We train (with cross-validation) reference-aided sparse multi-class classifier algorithms on this data to show that inclusion of a subject's reference sample can improve prediction accuracy by as much as 14 %, for the H3N2 cohort, and by at least 6 %, for the H1N1 cohort. Remarkably, these gains in accuracy are achieved by using smaller panels of genes, e.g., 39 % fewer for H3N2 and 31 % fewer for H1N1. The biomarkers selected by the predictors fall into two categories: 1) contrasting genes that tend to differentially express between target and reference samples over the population; 2) reinforcement genes that remain constant over the two samples, which function as housekeeping normalization genes. Many of these genes are common to all 4 viruses and their roles in the predictor elucidate the function that they play in differentiating the different states of host immune response. CONCLUSIONS: If one uses a suitable mathematical prediction algorithm, inclusion of a healthy reference in biomarker diagnostic testing can potentially improve accuracy of disease prediction with fewer biomarkers.
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Marcadores Genéticos , Análise em Microsséries , Viroses/diagnóstico , Algoritmos , Expressão Gênica , Genes Essenciais , Humanos , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Modelos Moleculares , Vírus Sinciciais Respiratórios , RhinovirusRESUMO
Acute respiratory infections caused by bacterial or viral pathogens are among the most common reasons for seeking medical care. Despite improvements in pathogen-based diagnostics, most patients receive inappropriate antibiotics. Host response biomarkers offer an alternative diagnostic approach to direct antimicrobial use. This observational cohort study determined whether host gene expression patterns discriminate noninfectious from infectious illness and bacterial from viral causes of acute respiratory infection in the acute care setting. Peripheral whole blood gene expression from 273 subjects with community-onset acute respiratory infection (ARI) or noninfectious illness, as well as 44 healthy controls, was measured using microarrays. Sparse logistic regression was used to develop classifiers for bacterial ARI (71 probes), viral ARI (33 probes), or a noninfectious cause of illness (26 probes). Overall accuracy was 87% (238 of 273 concordant with clinical adjudication), which was more accurate than procalcitonin (78%, P < 0.03) and three published classifiers of bacterial versus viral infection (78 to 83%). The classifiers developed here externally validated in five publicly available data sets (AUC, 0.90 to 0.99). A sixth publicly available data set included 25 patients with co-identification of bacterial and viral pathogens. Applying the ARI classifiers defined four distinct groups: a host response to bacterial ARI, viral ARI, coinfection, and neither a bacterial nor a viral response. These findings create an opportunity to develop and use host gene expression classifiers as diagnostic platforms to combat inappropriate antibiotic use and emerging antibiotic resistance.
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Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Coinfecção/genética , Coinfecção/microbiologia , Coinfecção/virologia , Demografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Transdução de Sinais/genética , Adulto JovemRESUMO
BACKGROUND: Influenza infection is associated with myocardial infarction (MI), suggesting that respiratory viral infection may induce biologic pathways that contribute to MI. We tested the hypotheses that 1) a validated blood gene expression signature of respiratory viral infection (viral GES) was associated with MI and 2) respiratory viral exposure changes levels of a validated platelet gene expression signature (platelet GES) of platelet function in response to aspirin that is associated with MI. METHODS: A previously defined viral GES was projected into blood RNA data from 594 patients undergoing elective cardiac catheterization and used to classify patients as having evidence of viral infection or not and tested for association with acute MI using logistic regression. A previously defined platelet GES was projected into blood RNA data from 81 healthy subjects before and after exposure to four respiratory viruses: Respiratory Syncytial Virus (RSV) (n=20), Human Rhinovirus (HRV) (n=20), Influenza A virus subtype H1N1 (H1N1) (n=24), Influenza A Virus subtype H3N2 (H3N2) (n=17). We tested for the change in platelet GES with viral exposure using linear mixed-effects regression and by symptom status. RESULTS: In the catheterization cohort, 32 patients had evidence of viral infection based upon the viral GES, of which 25% (8/32) had MI versus 12.2% (69/567) among those without evidence of viral infection (OR 2.3; CI [1.03-5.5], p=0.04). In the infection cohorts, only H1N1 exposure increased platelet GES over time (time course p-value = 1e-04). CONCLUSIONS: A viral GES of non-specific, respiratory viral infection was associated with acute MI; 18% of the top 49 genes in the viral GES are involved with hemostasis and/or platelet aggregation. Separately, H1N1 exposure, but not exposure to other respiratory viruses, increased a platelet GES previously shown to be associated with MI. Together, these results highlight specific genes and pathways that link viral infection, platelet activation, and MI especially in the case of H1N1 influenza infection.