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Surveillance for genetic variation of microbial pathogens, both within and among species, plays an important role in informing research, diagnostic, prevention, and treatment activities for disease control. However, large-scale systematic screening for novel genotypes remains challenging in part due to technological limitations. Towards addressing this challenge, we present an advancement in universal microbial high resolution melting (HRM) analysis that is capable of accomplishing both known genotype identification and novel genotype detection. Specifically, this novel surveillance functionality is achieved through time-series modeling of sequence-defined HRM curves, which is uniquely enabled by the large-scale melt curve datasets generated using our high-throughput digital HRM platform. Taking the detection of bacterial genotypes as a model application, we demonstrate that our algorithms accomplish an overall classification accuracy over 99.7% and perform novelty detection with a sensitivity of 0.96, specificity of 0.96 and Youden index of 0.92. Since HRM-based DNA profiling is an inexpensive and rapid technique, our results add support for the feasibility of its use in surveillance applications.
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Genotipo , Aprendizaje Automático , ADN Bacteriano/genética , Algoritmos , Desnaturalización de Ácido Nucleico/genéticaRESUMEN
BACKGROUND: Infection prevention (IP) measures are designed to mitigate the transmission of pathogens in healthcare. Using large-scale viral genomic and social network analyses, we determined if IP measures used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic were adequate in protecting healthcare workers (HCWs) and patients from acquiring SARS-CoV-2. METHODS: We performed retrospective cross-sectional analyses of viral genomics from all available SARS-CoV-2 viral samples collected at UC San Diego Health and social network analysis using the electronic medical record to derive temporospatial overlap of infections among related viromes and supplemented with contact tracing data. The outcome measure was any instance of healthcare transmission, defined as cases with closely related viral genomes and epidemiological connection within the healthcare setting during the infection window. Between November 2020 through January 2022, 12 933 viral genomes were obtained from 35 666 patients and HCWs. RESULTS: Among 5112 SARS-CoV-2 viral samples sequenced from the second and third waves of SARS-CoV-2 (pre-Omicron), 291 pairs were derived from persons with a plausible healthcare overlap. Of these, 34 pairs (12%) were phylogenetically linked: 19 attributable to household and 14 to healthcare transmission. During the Omicron wave, 2106 contact pairs among 7821 sequences resulted in 120 (6%) related pairs among 32 clusters, of which 10 were consistent with healthcare transmission. Transmission was more likely to occur in shared spaces in the older hospital compared with the newer hospital (2.54 vs 0.63 transmission events per 1000 admissions, P < .001). CONCLUSIONS: IP strategies were effective at identifying and preventing healthcare SARS-CoV-2 transmission.
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COVID-19 , Genoma Viral , Personal de Salud , SARS-CoV-2 , Humanos , COVID-19/transmisión , COVID-19/epidemiología , COVID-19/virología , SARS-CoV-2/genética , Estudios Retrospectivos , Estudios Transversales , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Análisis de Redes Sociales , Trazado de Contacto , Genómica , Adulto Joven , Adolescente , Niño , Anciano de 80 o más Años , Infección Hospitalaria/transmisión , Infección Hospitalaria/virología , Infección Hospitalaria/epidemiología , PreescolarRESUMEN
BACKGROUND: Recent attempts at clinical phenotyping for sepsis have shown promise in identifying groups of patients with distinct treatment responses. Nonetheless, the replicability and actionability of these phenotypes remain an issue because the patient trajectory is a function of both the patient's physiological state and the interventions they receive. OBJECTIVE: We aimed to develop a novel approach for deriving clinical phenotypes using unsupervised learning and transition modeling. METHODS: Forty commonly used clinical variables from the electronic health record were used as inputs to a feed-forward neural network trained to predict the onset of sepsis. Using spectral clustering on the representations from this network, we derived and validated consistent phenotypes across a diverse cohort of patients with sepsis. We modeled phenotype dynamics as a Markov decision process with transitions as a function of the patient's current state and the interventions they received. RESULTS: Four consistent and distinct phenotypes were derived from over 11,500 adult patients who were admitted from the University of California, San Diego emergency department (ED) with sepsis between January 1, 2016, and January 31, 2020. Over 2000 adult patients admitted from the University of California, Irvine ED with sepsis between November 4, 2017, and August 4, 2022, were involved in the external validation. We demonstrate that sepsis phenotypes are not static and evolve in response to physiological factors and based on interventions. We show that roughly 45% of patients change phenotype membership within the first 6 hours of ED arrival. We observed consistent trends in patient dynamics as a function of interventions including early administration of antibiotics. CONCLUSIONS: We derived and describe 4 sepsis phenotypes present within 6 hours of triage in the ED. We observe that the administration of a 30 mL/kg fluid bolus may be associated with worse outcomes in certain phenotypes, whereas prompt antimicrobial therapy is associated with improved outcomes.
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Sepsis , Humanos , Estudios Retrospectivos , Sepsis/diagnóstico , Sepsis/terapia , Estudios de Cohortes , Servicio de Urgencia en Hospital , Fenotipo , Análisis por ConglomeradosRESUMEN
BACKGROUND: Sepsis costs and incidence vary dramatically across diagnostic categories, warranting a customized approach for implementing predictive models. OBJECTIVE: The aim of this study was to optimize the parameters of a sepsis prediction model within distinct patient groups to minimize the excess cost of sepsis care and analyze the potential effect of factors contributing to end-user response to sepsis alerts on overall model utility. METHODS: We calculated the excess costs of sepsis to the Centers for Medicare and Medicaid Services (CMS) by comparing patients with and without a secondary sepsis diagnosis but with the same primary diagnosis and baseline comorbidities. We optimized the parameters of a sepsis prediction algorithm across different diagnostic categories to minimize these excess costs. At the optima, we evaluated diagnostic odds ratios and analyzed the impact of compliance factors such as noncompliance, treatment efficacy, and tolerance for false alarms on the net benefit of triggering sepsis alerts. RESULTS: Compliance factors significantly contributed to the net benefit of triggering a sepsis alert. However, a customized deployment policy can achieve a significantly higher diagnostic odds ratio and reduced costs of sepsis care. Implementing our optimization routine with powerful predictive models could result in US $4.6 billion in excess cost savings for CMS. CONCLUSIONS: We designed a framework for customizing sepsis alert protocols within different diagnostic categories to minimize excess costs and analyzed model performance as a function of false alarm tolerance and compliance with model recommendations. We provide a framework that CMS policymakers could use to recommend minimum adherence rates to the early recognition and appropriate care of sepsis that is sensitive to hospital department-level incidence rates and national excess costs. Customizing the implementation of clinical predictive models by accounting for various behavioral and economic factors may improve the practical benefit of predictive models.
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Medicare , Sepsis , Anciano , Humanos , Estados Unidos , Sepsis/diagnóstico , Sepsis/terapia , Algoritmos , Resultado del TratamientoRESUMEN
Social Determinants of Health (SDoH) have been shown to have profound impacts on health-related outcomes, yet this data suffers from high rates of missingness in electronic health records (EHR). Moreover, limited English proficiency in the United States can be a barrier to communication with health care providers. In this study, we have designed a multilingual conversational agent capable of conducting SDoH surveys for use in healthcare environments. The agent asks questions in the patient's native language, translates responses into English, and subsequently maps these responses via a large language model (LLM) to structured options in a SDoH survey. This tool can be extended to a variety of survey instruments in either hospital or home settings, enabling the extraction of structured insights from free-text answers. The proposed approach heralds a shift towards more inclusive and insightful data collection, marking a significant stride in SDoH data enrichment for optimizing health outcome predictions and interventions.
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Sepsis remains a major cause of mortality and morbidity worldwide. Algorithms that assist with the early recognition of sepsis may improve outcomes, but relatively few studies have examined their impact on real-world patient outcomes. Our objective was to assess the impact of a deep-learning model (COMPOSER) for the early prediction of sepsis on patient outcomes. We completed a before-and-after quasi-experimental study at two distinct Emergency Departments (EDs) within the UC San Diego Health System. We included 6217 adult septic patients from 1/1/2021 through 4/30/2023. The exposure tested was a nurse-facing Best Practice Advisory (BPA) triggered by COMPOSER. In-hospital mortality, sepsis bundle compliance, 72-h change in sequential organ failure assessment (SOFA) score following sepsis onset, ICU-free days, and the number of ICU encounters were evaluated in the pre-intervention period (705 days) and the post-intervention period (145 days). The causal impact analysis was performed using a Bayesian structural time-series approach with confounder adjustments to assess the significance of the exposure at the 95% confidence level. The deployment of COMPOSER was significantly associated with a 1.9% absolute reduction (17% relative decrease) in in-hospital sepsis mortality (95% CI, 0.3%-3.5%), a 5.0% absolute increase (10% relative increase) in sepsis bundle compliance (95% CI, 2.4%-8.0%), and a 4% (95% CI, 1.1%-7.1%) reduction in 72-h SOFA change after sepsis onset in causal inference analysis. This study suggests that the deployment of COMPOSER for early prediction of sepsis was associated with a significant reduction in mortality and a significant increase in sepsis bundle compliance.
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The deployment of predictive analytic algorithms that can safely and seamlessly integrate into existing healthcare workflows remains a significant challenge. Here, we present a scalable, cloud-based, fault-tolerant platform that is capable of extracting and processing electronic health record (EHR) data for any patient at any time following admission and transferring results back into the EHR. This platform has been successfully deployed within the UC San Diego Health system and utilizes interoperable data standards to enable portability.
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Sepsis is a major cause of morbidity and mortality worldwide, and is caused by bacterial infection in a majority of cases. However, fungal sepsis often carries a higher mortality rate both due to its prevalence in immunocompromised patients as well as delayed recognition. Using chest x-rays, associated radiology reports, and structured patient data from the MIMIC-IV clinical dataset, the authors present a machine learning methodology to differentiate between bacterial, fungal, and viral sepsis. Model performance shows AUCs of 0.81, 0.83, 0.79 for detecting bacterial, fungal, and viral sepsis respectively, with best performance achieved using embeddings from image reports and structured clinical data. By improving early detection of an often missed causative septic agent, predictive models could facilitate earlier treatment of non-bacterial sepsis with resultant associated mortality reduction.
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The deployment of predictive analytic algorithms that can safely and seamlessly integrate into existing healthcare workflows remains a significant challenge. Here, we present a scalable, cloud-based, fault-tolerant platform that is capable of extracting and processing electronic health record (EHR) data for any patient at any time following admission and transferring results back into the EHR. This platform has been successfully deployed within the UC San Diego Health system and utilizes interoperable data standards to enable portability.Clinical relevance- This platform is currently hosting a deep learning model for the early prediction of sepsis that is operational in two emergency departments.
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Algoritmos , Registros Electrónicos de Salud , Humanos , Atención a la Salud , Hospitalización , Servicio de Urgencia en HospitalRESUMEN
Predictive models have been suggested as potential tools for identifying highest risk patients for hospital readmissions, in order to improve care coordination and ultimately long-term patient outcomes. However, the accuracy of current predictive models for readmission prediction is still moderate and further data enrichment is needed to identify at risk patients. This paper describes models to predict 90-day readmission, focusing on testing the predictive performance of wearable sensor features generated using multiscale entropy techniques and clinical features. Our study explores ways to incorporate pre-discharge and post-discharge wearable sensor features to make robust patient predictions. Data were used from participants enrolled in the AllofUs Research program. We extracted the inpatient cohort of patients and integrated clinical data from the electronic health records (EHR) and Fitbit sensor measurements. Entropy features were calculated from the longitudinal wearable sensor data, such as heart rate and mobility-related measurements, in order to characterize time series variability and complexity. Our best performing model acheived an AUC of 83%, and at 80% sensitivity acheived 75% specificity and 57% positive predictive value. Our results indicate that it would be possible to improve the ability to predict unplanned hospital readmissions by considering pre-discharge and post-discharge wearable features.
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Sepsis is a life-threatening condition that occurs due to a dysregulated host response to infection. Recent data demonstrate that patients with sepsis have a significantly higher readmission risk than other common conditions, such as heart failure, pneumonia and myocardial infarction and associated economic burden. Prior studies have demonstrated an association between a patient's physical activity levels and readmission risk. In this study, we show that distribution of activity level prior and post-discharge among patients with sepsis are predictive of unplanned rehospitalization in 90 days (P-value<1e-3). Our preliminary results indicate that integrating Fitbit data with clinical measurements may improve model performance on predicting 90 days readmission.Clinical relevance Sepsis, Activity level, Hospital readmission, Wearable data.
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Sepsis , Dispositivos Electrónicos Vestibles , Humanos , Readmisión del Paciente , Cuidados Posteriores , Alta del Paciente , Sepsis/diagnósticoRESUMEN
Social Determinants of Health (SDoH) have been shown to have profound impacts on health-related outcomes, yet this data suffers from high rates of missingness in electronic health records (EHR). Moreover, limited English proficiency in the United States can be a barrier to communication with health care providers. In this study, we have designed a multilingual conversational agent capable of conducting SDoH surveys for use in healthcare environments. The agent asks questions in the patient's native language, translates responses into English, and subsequently maps these responses via a large language model (LLM) to structured options in a SDoH survey. This tool can be extended to a variety of survey instruments in either hospital or home settings, enabling the extraction of structured insights from free-text answers. The proposed approach heralds a shift towards more inclusive and insightful data collection, marking a significant stride in SDoH data enrichment for optimizing health outcome predictions and interventions.
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Microbial sulfate reduction is a primary cause of oil reservoir souring. Here we show that amendment with chlorate or perchlorate [collectively (per)chlorate] potentially resolves this issue. Triplicate packed columns inoculated with marine sediment were flushed with coastal water amended with yeast extract and one of nitrate, chlorate, or perchlorate. Results showed that although sulfide production was dramatically reduced by all treatments, effluent sulfide was observed in the nitrate (10 mM) treatment after an initial inhibition period. In contrast, no effluent sulfide was observed with (per)chlorate (10 mM). Microbial community analyses indicated temporal community shifts and phylogenetic clustering by treatment. Nitrate addition stimulated Xanthomonadaceae and Rhizobiaceae growth, supporting their role in nitrate metabolism. (Per)chlorate showed distinct effects on microbial community structure compared with nitrate and resulted in a general suppression of the community relative to the untreated control combined with a significant decrease in sulfate reducing species abundance indicating specific toxicity. Furthermore, chlorate stimulated Pseudomonadaceae and Pseudoalteromonadaceae, members of which are known chlorate respirers, suggesting that chlorate may also control sulfidogenesis by biocompetitive exclusion of sulfate-reduction. Perchlorate addition stimulated Desulfobulbaceae and Desulfomonadaceae, which contain sulfide oxidizing and elemental sulfur-reducing species respectively, suggesting that effluent sulfide concentrations may be controlled through sulfur redox cycling in addition to toxicity and biocompetitive exclusion. Sulfur isotope analyses further support sulfur cycling in the columns, even when sulfide is not detected. This study indicates that (per)chlorate show great promise as inhibitors of sulfidogenesis in natural communities and provides insight into which organisms and respiratory processes are involved.