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  1. Article ; Online: CPT to RVU conversion improves model performance in the prediction of surgical case length

    Nicholas Garside / Hamed Zaribafzadeh / Ricardo Henao / Royce Chung / Daniel Buckland

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 7

    Abstract: Abstract Methods used to predict surgical case time often rely upon the current procedural terminology (CPT) code as a nominal variable to train machine-learned models, however this limits the ability of the model to incorporate new procedures and adds ... ...

    Abstract Abstract Methods used to predict surgical case time often rely upon the current procedural terminology (CPT) code as a nominal variable to train machine-learned models, however this limits the ability of the model to incorporate new procedures and adds complexity as the number of unique procedures increases. The relative value unit (RVU, a consensus-derived billing indicator) can serve as a proxy for procedure workload and could replace the CPT code as a primary feature for models that predict surgical case length. Using 11,696 surgical cases from Duke University Health System electronic health records data, we compared boosted decision tree models that predict individual case length, changing the method by which the model coded procedure type; CPT, RVU, and CPT–RVU combined. Performance of each model was assessed by inference time, MAE, and RMSE compared to the actual case length on a test set. Models were compared to each other and to the manual scheduler method that currently exists. RMSE for the RVU model (60.8 min) was similar to the CPT model (61.9 min), both of which were lower than scheduler (90.2 min). 65.2% of our RVU model’s predictions (compared to 43.2% from the current human scheduler method) fell within 20% of actual case time. Using RVUs reduced model prediction time by ninefold and reduced the number of training features from 485 to 44. Replacing pre-operative CPT codes with RVUs maintains model performance while decreasing overall model complexity in the prediction of surgical case length.
    Keywords Medicine ; R ; Science ; Q
    Subject code 612
    Language English
    Publishing date 2021-07-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Predicting in-hospital length of stay

    Zhenhui Xu / Congwen Zhao / Charles D. Scales / Ricardo Henao / Benjamin A. Goldstein

    BMC Medical Informatics and Decision Making, Vol 22, Iss 1, Pp 1-

    a two-stage modeling approach to account for highly skewed data

    2022  Volume 12

    Abstract: Abstract Background In the early stages of the COVID-19 pandemic our institution was interested in forecasting how long surgical patients receiving elective procedures would spend in the hospital. Initial examination of our models indicated that, due to ... ...

    Abstract Abstract Background In the early stages of the COVID-19 pandemic our institution was interested in forecasting how long surgical patients receiving elective procedures would spend in the hospital. Initial examination of our models indicated that, due to the skewed nature of the length of stay, accurate prediction was challenging and we instead opted for a simpler classification model. In this work we perform a deeper examination of predicting in-hospital length of stay. Methods We used electronic health record data on length of stay from 42,209 elective surgeries. We compare different loss-functions (mean squared error, mean absolute error, mean relative error), algorithms (LASSO, Random Forests, multilayer perceptron) and data transformations (log and truncation). We also assess the performance of two stage hybrid classification-regression approach. Results Our results show that while it is possible to accurately predict short length of stays, predicting longer length of stay is extremely challenging. As such, we opt for a two-stage model that first classifies patients into long versus short length of stays and then a second stage that fits a regresssor among those predicted to have a short length of stay. Discussion The results indicate both the challenges and considerations necessary to applying machine-learning methods to skewed outcomes. Conclusions Two-stage models allow those developing clinical decision support tools to explicitly acknowledge where they can and cannot make accurate predictions.
    Keywords Electronic health records ; Machine learning ; Clinical decision support ; Surgical outcomes ; Computer applications to medicine. Medical informatics ; R858-859.7
    Subject code 006
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Epigenetic and transcriptional responses in circulating leukocytes are associated with future decompensation during SARS-CoV-2 infection

    Micah T. McClain / Ilya Zhbannikov / Lisa L. Satterwhite / Ricardo Henao / Nicholas S. Giroux / Shengli Ding / Thomas W. Burke / Ephraim L. Tsalik / Christina Nix / Jorge Prado Balcazar / Elizabeth A. Petzold / Xiling Shen / Christopher W. Woods

    iScience, Vol 27, Iss 1, Pp 108288- (2024)

    1481  

    Abstract: Summary: To elucidate host response elements that define impending decompensation during SARS-CoV-2 infection, we enrolled subjects hospitalized with COVID-19 who were matched for disease severity and comorbidities at the time of admission. We performed ... ...

    Abstract Summary: To elucidate host response elements that define impending decompensation during SARS-CoV-2 infection, we enrolled subjects hospitalized with COVID-19 who were matched for disease severity and comorbidities at the time of admission. We performed combined single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) on peripheral blood mononuclear cells (PBMCs) at admission and compared subjects who improved from their moderate disease with those who later clinically decompensated and required invasive mechanical ventilation or died. Chromatin accessibility and transcriptomic immune profiles were markedly altered between the two groups, with strong signals in CD4+ T cells, inflammatory T cells, dendritic cells, and NK cells. Multiomic signature scores at admission were tightly associated with future clinical deterioration (auROC 1.0). Epigenetic and transcriptional changes in PBMCs reveal early, broad immune dysregulation before typical clinical signs of decompensation are apparent and thus may act as biomarkers to predict future severity in COVID-19.
    Keywords Health sciences ; Molecular mechanism of gene regulation ; Epigenetics ; Immune response ; Components of the immune system ; Virology ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2024-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: The importance of weight stabilization amongst those with overweight or obesity

    Neha J. Pagidipati / Matthew Phelan / Courtney Page / Megan Clowse / Ricardo Henao / Eric D. Peterson / Benjamin A. Goldstein

    Preventive Medicine Reports, Vol 24, Iss , Pp 101615- (2021)

    Results from a large health care system

    2021  

    Abstract: Data on patterns of weight change among adults with overweight or obesity are minimal. We aimed to examine patterns of weight change and associated hospitalizations in a large health system, and to develop a model to predict 2-year significant weight ... ...

    Abstract Data on patterns of weight change among adults with overweight or obesity are minimal. We aimed to examine patterns of weight change and associated hospitalizations in a large health system, and to develop a model to predict 2-year significant weight gain.Data from the Duke University Health System was abstracted from 1/1/13 to 12/31/16 on patients with BMI ≥ 25 kg/m2 in 2014. A regression model was developed to predict patients that would increase their weight by 10% within 2 years. We estimated the association between weight change category and all-cause hospitalization using Cox proportional hazards models.Of the 37,253 patients in our cohort, 59% had stable weight over 2 years, while 24% gained ≥ 5% weight and 17% lost ≥ 5% weight. Our predictive model had reasonable discriminatory capacity to predict which individuals would gain ≥ 10% weight over 2 years (AUC 0.73). Compared with stable weight, the risk of hospitalization was increased by 37% for individuals with > 10% weight loss [adj. HR (95% CI): 1.37 (1.25,1.5)], by 30% for those with > 10% weight gain [adj. HR (95% CI): 1.3 (1.19,1.42)], by 18% for those with 5–10% weight loss [adj. HR (95% CI): 1.18 (1.09,1.28)], and by 10% for those with 5–10% weight gain [adj. HR (95% CI): 1.1 (1.02,1.19)].In this examination of a large health system, significant weight gain or loss of > 10% was associated with increased all-cause hospitalization over 2 years compared with stable weight. This analysis adds to the increasing observational evidence that weight stability may be a key health driver.
    Keywords Obesity ; Weight change ; Risk prediction ; Medicine ; R
    Subject code 796 ; 616
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Systematic comparison of published host gene expression signatures for bacterial/viral discrimination

    Nicholas Bodkin / Melissa Ross / Micah T. McClain / Emily R. Ko / Christopher W. Woods / Geoffrey S. Ginsburg / Ricardo Henao / Ephraim L. Tsalik

    Genome Medicine, Vol 14, Iss 1, Pp 1-

    2022  Volume 14

    Abstract: Abstract Background Measuring host gene expression is a promising diagnostic strategy to discriminate bacterial and viral infections. Multiple signatures of varying size, complexity, and target populations have been described. However, there is little ... ...

    Abstract Abstract Background Measuring host gene expression is a promising diagnostic strategy to discriminate bacterial and viral infections. Multiple signatures of varying size, complexity, and target populations have been described. However, there is little information to indicate how the performance of various published signatures compare to one another. Methods This systematic comparison of host gene expression signatures evaluated the performance of 28 signatures, validating them in 4589 subjects from 51 publicly available datasets. Thirteen COVID-specific datasets with 1416 subjects were included in a separate analysis. Individual signature performance was evaluated using the area under the receiving operating characteristic curve (AUC) value. Overall signature performance was evaluated using median AUCs and accuracies. Results Signature performance varied widely, with median AUCs ranging from 0.55 to 0.96 for bacterial classification and 0.69–0.97 for viral classification. Signature size varied (1–398 genes), with smaller signatures generally performing more poorly (P < 0.04). Viral infection was easier to diagnose than bacterial infection (84% vs. 79% overall accuracy, respectively; P < .001). Host gene expression classifiers performed more poorly in some pediatric populations (3 months–1 year and 2–11 years) compared to the adult population for both bacterial infection (73% and 70% vs. 82%, respectively; P < .001) and viral infection (80% and 79% vs. 88%, respectively; P < .001). We did not observe classification differences based on illness severity as defined by ICU admission for bacterial or viral infections. The median AUC across all signatures for COVID-19 classification was 0.80 compared to 0.83 for viral classification in the same datasets. Conclusions In this systematic comparison of 28 host gene expression signatures, we observed differences based on a signature’s size and characteristics of the validation population, including age and infection type. However, populations used for signature ...
    Keywords Biomarkers ; Infectious disease ; Diagnostics ; Gene expression ; Machine learning ; Medicine ; R ; Genetics ; QH426-470
    Subject code 572
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Health system utilization before age 1 among children later diagnosed with autism or ADHD

    Matthew M. Engelhard / Samuel I. Berchuck / Jyotsna Garg / Ricardo Henao / Andrew Olson / Shelley Rusincovitch / Geraldine Dawson / Scott H. Kollins

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    2020  Volume 10

    Abstract: Abstract Children with autism spectrum disorder (ASD) or attention deficit hyperactivity disorder (ADHD) have 2–3 times increased healthcare utilization and annual costs once diagnosed, but little is known about their utilization patterns early in life. ... ...

    Abstract Abstract Children with autism spectrum disorder (ASD) or attention deficit hyperactivity disorder (ADHD) have 2–3 times increased healthcare utilization and annual costs once diagnosed, but little is known about their utilization patterns early in life. Quantifying their early health system utilization could uncover condition-specific health trajectories to facilitate earlier detection and intervention. Patients born 10/1/2006–10/1/2016 with ≥ 2 well-child visits within the Duke University Health System before age 1 were grouped as ASD, ADHD, ASD + ADHD, or No Diagnosis using retrospective billing codes. An additional comparison group was defined by later upper respiratory infection diagnosis. Adjusted odds ratios (AOR) for hospital admissions, procedures, emergency department (ED) visits, and outpatient clinic encounters before age 1 were compared between groups via logistic regression models. Length of hospital encounters were compared between groups via Mann–Whitney U test. In total, 29,929 patients met study criteria (ASD N = 343; ADHD N = 1175; ASD + ADHD N = 140). ASD was associated with increased procedures (AOR = 1.5, p < 0.001), including intubation and ventilation (AOR = 2.4, p < 0.001); and outpatient specialty care, including physical therapy (AOR = 3.5, p < 0.001) and ophthalmology (AOR = 3.1, p < 0.001). ADHD was associated with increased procedures (AOR = 1.41, p < 0.001), including blood transfusion (AOR = 4.7, p < 0.001); hospital admission (AOR = 1.60, p < 0.001); and ED visits (AOR = 1.58, p < 0.001). Median length of stay was increased after birth in ASD (+ 6.5 h, p < 0.001) and ADHD (+ 3.8 h, p < 0.001), and after non-birth admission in ADHD (+ 1.1 d, p < 0.001) and ASD + ADHD (+ 2.4 d, p = 0.003). Each condition was associated with increased health system utilization and distinctive patterns of utilization before age 1. Recognizing these patterns may contribute to earlier detection and intervention.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Antibody signatures of asymptomatic Plasmodium falciparum malaria infections measured from dried blood spots

    Christine F. Markwalter / Myat Htut Nyunt / Zay Yar Han / Ricardo Henao / Aarti Jain / Omid Taghavian / Philip L. Felgner / Kay Thwe Han / Myaing M. Nyunt / Christopher V. Plowe

    Malaria Journal, Vol 20, Iss 1, Pp 1-

    2021  Volume 10

    Abstract: Abstract Background Screening malaria-specific antibody responses on protein microarrays can help identify immune factors that mediate protection against malaria infection, disease, and transmission, as well as markers of past exposure to both malaria ... ...

    Abstract Abstract Background Screening malaria-specific antibody responses on protein microarrays can help identify immune factors that mediate protection against malaria infection, disease, and transmission, as well as markers of past exposure to both malaria parasites and mosquito vectors. Most malaria protein microarray work has used serum as the sample matrix, requiring prompt laboratory processing and a continuous cold chain, thus limiting applications in remote locations. Dried blood spots (DBS) pose minimal biohazard, do not require immediate laboratory processing, and are stable at room temperature for transport, making them potentially superior alternatives to serum. The goals of this study were to assess the viability of DBS as a source for antibody profiling and to use DBS to identify serological signatures of low-density Plasmodium falciparum infections in malaria-endemic regions of Myanmar. Methods Matched DBS and serum samples from a cross-sectional study in Ingapu Township, Myanmar were probed on protein microarrays populated with P. falciparum antigen fragments. Signal and trends in both sample matrices were compared. A case-control study was then performed using banked DBS samples from malaria-endemic regions of Myanmar, and a regularized logistic regression model was used to identify antibody signatures of ultrasensitive PCR-positive P. falciparum infections. Results Approximately 30% of serum IgG activity was recovered from DBS. Despite this loss of antibody activity, antigen and population trends were well-matched between the two sample matrices. Responses to 18 protein fragments were associated with the odds of asymptomatic P. falciparum infection, albeit with modest diagnostic characteristics (sensitivity 58%, specificity 85%, negative predictive value 88%, and positive predictive value 52%). Conclusions Malaria-specific antibody responses can be reliably detected, quantified, and analysed from DBS, opening the door to serological studies in populations where serum collection, transport, and storage would otherwise be impossible. While test characteristics of antibody signatures were insufficient for individual diagnosis, serological testing may be useful for identifying exposure to asymptomatic, low-density malaria infections, particularly if sero-surveillance strategies target individuals with low previous exposure as sentinels for population exposure.
    Keywords Serology ; Antibody responses ; Protein microarrays ; Asymptomatic malaria ; Arctic medicine. Tropical medicine ; RC955-962 ; Infectious and parasitic diseases ; RC109-216
    Subject code 616
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: A comparison of host response strategies to distinguish bacterial and viral infection.

    Melissa Ross / Ricardo Henao / Thomas W Burke / Emily R Ko / Micah T McClain / Geoffrey S Ginsburg / Christopher W Woods / Ephraim L Tsalik

    PLoS ONE, Vol 16, Iss 12, p e

    2021  Volume 0261385

    Abstract: Objectives Compare three host response strategies to distinguish bacterial and viral etiologies of acute respiratory illness (ARI). Methods In this observational cohort study, procalcitonin, a 3-protein panel (CRP, IP-10, TRAIL), and a host gene ... ...

    Abstract Objectives Compare three host response strategies to distinguish bacterial and viral etiologies of acute respiratory illness (ARI). Methods In this observational cohort study, procalcitonin, a 3-protein panel (CRP, IP-10, TRAIL), and a host gene expression mRNA panel were measured in 286 subjects with ARI from four emergency departments. Multinomial logistic regression and leave-one-out cross validation were used to evaluate the protein and mRNA tests. Results The mRNA panel performed better than alternative strategies to identify bacterial infection: AUC 0.93 vs. 0.83 for the protein panel and 0.84 for procalcitonin (P<0.02 for each comparison). This corresponded to a sensitivity and specificity of 92% and 83% for the mRNA panel, 81% and 73% for the protein panel, and 68% and 87% for procalcitonin, respectively. A model utilizing all three strategies was the same as mRNA alone. For the diagnosis of viral infection, the AUC was 0.93 for mRNA and 0.84 for the protein panel (p<0.05). This corresponded to a sensitivity and specificity of 89% and 82% for the mRNA panel, and 85% and 62% for the protein panel, respectively. Conclusions A gene expression signature was the most accurate host response strategy for classifying subjects with bacterial, viral, or non-infectious ARI.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Evaluation of an RNAseq-Based Immunogenomic Liquid Biopsy Approach in Early-Stage Prostate Cancer

    Leander Van Neste / Kirk J. Wojno / Ricardo Henao / Shrikant Mane / Howard Korman / Jason Hafron / Kenneth Kernen / Rima Tinawi-Aljundi / Mathew Putzi / Amin I. Kassis / Philip W. Kantoff

    Cells, Vol 10, Iss 2567, p

    2021  Volume 2567

    Abstract: The primary objective of this study is to detect biomarkers and develop models that enable the identification of clinically significant prostate cancer and to understand the biologic implications of the genes involved. Peripheral blood samples (1018 ... ...

    Abstract The primary objective of this study is to detect biomarkers and develop models that enable the identification of clinically significant prostate cancer and to understand the biologic implications of the genes involved. Peripheral blood samples (1018 patients) were split chronologically into independent training ( n = 713) and validation ( n = 305) sets. Whole transcriptome RNA sequencing was performed on isolated phagocytic CD14+ and non-phagocytic CD2+ cells and their gene expression levels were used to develop predictive models that correlate to adverse pathologic features. The immune-transcriptomic model with the highest performance for predicting adverse pathology, based on a subtraction of the log-transformed expression signals of the two cell types, displayed an area under the curve (AUC) of the receiver operating characteristic of 0.70. The addition of biomarkers in combination with traditional clinical risk factors (age, serum prostate-specific antigen (PSA), PSA density, race, digital rectal examination (DRE), and family history) enhanced the AUC to 0.91 and 0.83 for the training and validation sets, respectively. The markers identified by this approach uncovered specific pathway associations relevant to (prostate) cancer biology. Increased phagocytic activity in conjunction with cancer-associated (mis-)regulation is also represented by these markers. Differential gene expression of circulating immune cells gives insight into the cellular immune response to early tumor development and immune surveillance.
    Keywords cancer ; immune ; cells ; transcriptomics ; phagocytosis ; CD14+ ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: The host transcriptional response to Candidemia is dominated by neutrophil activation and heme biosynthesis and supports novel diagnostic approaches

    Julie M. Steinbrink / Rachel A. Myers / Kaiyuan Hua / Melissa D. Johnson / Jessica L. Seidelman / Ephraim L. Tsalik / Ricardo Henao / Geoffrey S. Ginsburg / Christopher W. Woods / Barbara D. Alexander / Micah T. McClain

    Genome Medicine, Vol 13, Iss 1, Pp 1-

    2021  Volume 13

    Abstract: Abstract Background Candidemia is one of the most common nosocomial bloodstream infections in the United States, causing significant morbidity and mortality in hospitalized patients, but the breadth of the host response to Candida infections in human ... ...

    Abstract Abstract Background Candidemia is one of the most common nosocomial bloodstream infections in the United States, causing significant morbidity and mortality in hospitalized patients, but the breadth of the host response to Candida infections in human patients remains poorly defined. Methods In order to better define the host response to Candida infection at the transcriptional level, we performed RNA sequencing on serial peripheral blood samples from 48 hospitalized patients with blood cultures positive for Candida species and compared them to patients with other acute viral, bacterial, and non-infectious illnesses. Regularized multinomial regression was utilized to develop pathogen class-specific gene expression classifiers. Results Candidemia triggers a unique, robust, and conserved transcriptomic response in human hosts with 1641 genes differentially upregulated compared to healthy controls. Many of these genes corresponded to components of the immune response to fungal infection, heavily weighted toward neutrophil activation, heme biosynthesis, and T cell signaling. We developed pathogen class-specific classifiers from these unique signals capable of identifying and differentiating candidemia, viral, or bacterial infection across a variety of hosts with a high degree of accuracy (auROC 0.98 for candidemia, 0.99 for viral and bacterial infection). This classifier was validated on two separate human cohorts (auROC 0.88 for viral infection and 0.87 for bacterial infection in one cohort; auROC 0.97 in another cohort) and an in vitro model (auROC 0.94 for fungal infection, 0.96 for bacterial, and 0.90 for viral infection). Conclusions Transcriptional analysis of circulating leukocytes in patients with acute Candida infections defines novel aspects of the breadth of the human immune response during candidemia and suggests promising diagnostic approaches for simultaneously differentiating multiple types of clinical illnesses in at-risk, acutely ill patients.
    Keywords Candidemia ; Gene expression ; Biomarkers ; Host response ; Fungal diagnostics ; Medicine ; R ; Genetics ; QH426-470
    Subject code 572
    Language English
    Publishing date 2021-07-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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