scholarly journals A 2-Biomarker Model Augments Clinical Prediction of Mortality in Melioidosis

Author(s):  
Shelton W Wright ◽  
Taniya Kaewarpai ◽  
Lara Lovelace-Macon ◽  
Deirdre Ducken ◽  
Viriya Hantrakun ◽  
...  

Abstract Background Melioidosis, infection caused by Burkholderia pseudomallei, is a common cause of sepsis with high associated mortality in Southeast Asia. Identification of patients at high likelihood of clinical deterioration is important for guiding decisions about resource allocation and management. We sought to develop a biomarker-based model for 28-day mortality prediction in melioidosis. Methods In a derivation set (N = 113) of prospectively enrolled, hospitalized Thai patients with melioidosis, we measured concentrations of interferon-γ, interleukin-1β, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-ɑ, granulocyte-colony stimulating factor, and interleukin-17A. We used least absolute shrinkage and selection operator (LASSO) regression to identify a subset of predictive biomarkers and performed logistic regression and receiver operating characteristic curve analysis to evaluate biomarker-based prediction of 28-day mortality compared with clinical variables. We repeated select analyses in an internal validation set (N = 78) and in a prospectively enrolled external validation set (N = 161) of hospitalized adults with melioidosis. Results All 8 cytokines were positively associated with 28-day mortality. Of these, interleukin-6 and interleukin-8 were selected by LASSO regression. A model consisting of interleukin-6, interleukin-8, and clinical variables significantly improved 28-day mortality prediction over a model of only clinical variables [AUC (95% confidence interval [CI]): 0.86 (.79–.92) vs 0.78 (.69–.87); P = .01]. In both the internal validation set (0.91 [0.84–0.97]) and the external validation set (0.81 [0.74–0.88]), the combined model including biomarkers significantly improved 28-day mortality prediction over a model limited to clinical variables. Conclusions A 2-biomarker model augments clinical prediction of 28-day mortality in melioidosis.

2020 ◽  
Vol 7 (11) ◽  
Author(s):  
David N Fisman ◽  
Amy L Greer ◽  
Michael Hillmer ◽  
R Tuite

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a high-mortality global pandemic. The clinical spectrum of disease caused by this virus is broad, ranging from asymptomatic infection to organ failure and death. Risk stratification of individuals with coronavirus disease 2019 (COVID-19) is desirable for management, and prioritization for trial enrollment. We developed a prediction rule for COVID-19 mortality in a population-based cohort in Ontario, Canada. Methods Data from Ontario’s provincial iPHIS system were extracted for the period from January 23 to May 15, 2020. Logistic regression–based prediction rules and a rule derived using a Cox proportional hazards model were developed and validated using split-halves validation. Sensitivity analyses were performed, with varying approaches to missing data. Results Of 21 922 COVID-19 cases, 1734 with complete data were included in the derivation set; 1796 were included in the validation set. Age and comorbidities (notably diabetes, renal disease, and immune compromise) were strong predictors of mortality. Four point-based prediction rules were derived (base case, smoking excluded, long-term care excluded, and Cox model–based). All displayed excellent discrimination (area under the curve for all rules > 0.92) and calibration (P > .50 by Hosmer-Lemeshow test) in the derivation set. All performed well in the validation set and were robust to varying approaches to replacement of missing variables. Conclusions We used a public health case management data system to build and validate 4 accurate, well-calibrated, robust clinical prediction rules for COVID-19 mortality in Ontario, Canada. While these rules need external validation, they may be useful tools for management, risk stratification, and clinical trials.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S544-S544
Author(s):  
Joel Iverson Howard ◽  
Joni Aoki ◽  
Jeffrey Ferraro ◽  
Ben Haaland ◽  
Andrew Pavia ◽  
...  

Abstract Background Infectious diarrheal illness is a significant contributor to healthcare costs in the US pediatric population. New multi-pathogen PCR-based panels have shown increased sensitivity over previous methods; however, they are costly and clinical utility may be limited in many cases. Clinical Prediction Rules (CPRs) may help optimize the appropriate use of these tests. Furthermore, Natural Language Processing (NLP) is an emerging tool to extract clinical history for decision support. Here, we examine NLP for the validation of a CPR for pediatric diarrhea. Methods Using data from a prospective clinical trial at 5 US pediatric hospitals, 961 diarrheal cases were assessed for etiology and relevant clinical variables. Of 65 variables collected in that study, 42 were excluded in our models based on a scarcity of documentation in reviewed clinical charts. The remaining 23 variables were ranked by random forest (RF) variable importance and utilized in both an RF and stepwise logistic regression (LR) model for viral-only etiology. We investigated whether NLP could accurately extract data from clinical notes comparable to study questionnaires. We used the eHOST abstraction software to abstract 6 clinical variables from patient charts that were useful in our CPR. These data will be used to train an NLP algorithm to extract the same variables from additional charts, and be combined with data from 2 other variables coded in the EMR to externally validate our model. Results Both RF and LR models achieved cross-validated area under the receiver operating characteristic curves of 0.74 using the top 5 variables (season, age, bloody diarrhea, vomiting/nausea, and fever), which did not improve significantly with the addition of more variables. Of 270 charts abstracted for NLP training, there were 41 occurrences of bloody diarrhea annotated, 339 occurrences of vomiting, and 145 occurrences of fever. Inter-annotator agreement over 9 training sets ranged between 0.63 and 0.83. Conclusion We have constructed a parsimonious CPR involving only 5 inputs for the prediction of a viral-only etiology for pediatric diarrheal illness using prospectively collected data. With the training of an NLP algorithm for automated chart abstraction we will validate the CPR. NLP could allow a CPR to run without manual data entry to improve care. Disclosures All authors: No reported disclosures.


2019 ◽  
Vol 31 (5) ◽  
pp. 665-673 ◽  
Author(s):  
Maud Menard ◽  
Alexis Lecoindre ◽  
Jean-Luc Cadoré ◽  
Michèle Chevallier ◽  
Aurélie Pagnon ◽  
...  

Accurate staging of hepatic fibrosis (HF) is important for treatment and prognosis of canine chronic hepatitis. HF scores are used in human medicine to indirectly stage and monitor HF, decreasing the need for liver biopsy. We developed a canine HF score to screen for moderate or greater HF. We included 96 dogs in our study, including 5 healthy dogs. A liver biopsy for histologic examination and a biochemistry profile were performed on all dogs. The dogs were randomly split into a training set of 58 dogs and a validation set of 38 dogs. A HF score that included alanine aminotransferase, alkaline phosphatase, total bilirubin, potassium, and gamma-glutamyl transferase was developed in the training set. Model performance was confirmed using the internal validation set, and was similar to the performance in the training set. The overall sensitivity and specificity for the study group were 80% and 70% respectively, with an area under the curve of 0.80 (0.71–0.90). This HF score could be used for indirect diagnosis of canine HF when biochemistry panels are performed on the Konelab 30i (Thermo Scientific), using reagents as in our study. External validation is required to determine if the score is sufficiently robust to utilize biochemical results measured in other laboratories with different instruments and methodologies.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Lin Wang ◽  
Mulalibieke Heizhati ◽  
Xintian Cai ◽  
Mei Li ◽  
Zhikang Yang ◽  
...  

Background. This study aims to evaluate the risk factors associated with untreated hypertension and develop and internally validate untreated risk nomograms in patients with hypertension among primary health care of less developed Northwest China. Methods. A total of 895 eligible patients with hypertension in primary health care of less developed Northwest China were divided into a training set (n = 626) and a validation set (n = 269). Untreated hypertension was defined as not taking antihypertensive medication during the past two weeks. Using least absolute shrinkage and selection operator (LASSO) regression model, we identified the optimized risk factors of nontreatment, followed by establishment of a prediction nomogram. The discriminative ability, calibration, and clinical usefulness were determined using the area under the receiver operating characteristic curve (AUC), calibration curve, and decision analysis. The results were assessed by internal validation in the validation set. Results. Five independent risk factors were derived from LASSO regression model and entered into the nomogram: age, herdsman, family income per member, altitude of habitation, and comorbidity. The nomogram displayed a robust discrimination with an AUC of 0.859 (95% confidence interval: 0.812–0.906) and good calibration. The nomogram was clinically useful when the intervention was decided at the untreated possibility threshold of 7% to 91% in the decision curve analysis. Results were confirmed by internal validation. Conclusions. Our nomogram showed favorable predictive accuracy for untreated hypertension in primary health care of less developed Northwest China and might help primary health care assess the risk of nontreatment in patients with hypertension.


2021 ◽  
Author(s):  
Zhi-Chun Gu ◽  
Shou-Rui Huang ◽  
Dong Li ◽  
Qin Zhou ◽  
Jing Wang ◽  
...  

Abstract Background Tailoring warfarin use poses a challenge for physicians and pharmacists due to its narrow therapeutic window and huge inter-individual variability. This study aimed to create an adapted neural-fuzzy inference system (ANFIS) model using preprocessed balance data to improve the predictive accuracy of warfarin maintenance dosing in Chinese patients undergoing heart valve replacement (HVR). Methods This retrospective study enrolled patients who underwent HVR between June 1, 2012 and June 1, 2016 from 35 centers in China. The primary outcomes were the mean difference between predicted warfarin dose by ANFIS models and actual dose, and the models’ predictive accuracy, including the ideal predicted percentage, the mean absolute error (MAE), and the mean squared error (MSE). The eligible cases were divided into training, internal validation, and external validation groups. We explored input variables by univariate analysis of a general liner model and created two ANFIS models using imbalanced and balanced training sets. We finally compared the primary outcomes between the imbalanced and balanced ANFIS models in both internal and external validation sets. Stratified analyses were conducted across warfarin doses (low, medium, and high doses). Results A total of 15,108 patients were included and grouped as follows: 12,086 in the imbalanced training set; 2,820 in the balanced training set; 1,511 in the internal validation set; and 1,511 in the external validation set. Eight variables were explored as predictors related to warfarin maintenance doses, and imbalanced and balanced ANFIS models with multi-fuzzy rules were developed. The results showed a low mean difference between predicted and actual doses (< 0.3 mg/d for each model) and an accurate prediction property in both the imbalanced model (ideal prediction percentage: 74.39–78.16%, MAE: 0.37 mg/daily, MSE: 0.39 mg/daily) and the balanced model (ideal prediction percentage: 73.46–75.31%, MAE: 0.42 mg/daily; MSE, 0.43 mg/daily). Compared to the imbalanced model, the balanced model had a significantly higher prediction accuracy in the low-dose (14.46% vs. 3.01%; P < 0.001) and the high-dose warfarin groups (34.71% vs. 23.14%; P = 0.047). The results from the external validation cohort confirmed this finding. Conclusions The ANFIS model can accurately predict the warfarin maintenance dose in patients after HVR. Through data preprocessing, the balanced model contributed to improved prediction ability in the low- and high-dose warfarin groups.


2021 ◽  
Vol 11 ◽  
Author(s):  
Aihua Wu ◽  
Zhigang Liang ◽  
Songbo Yuan ◽  
Shanshan Wang ◽  
Weidong Peng ◽  
...  

BackgroundThe diagnostic value of clinical and laboratory features to differentiate between malignant pleural effusion (MPE) and benign pleural effusion (BPE) has not yet been established.ObjectivesThe present study aimed to develop and validate the diagnostic accuracy of a scoring system based on a nomogram to distinguish MPE from BPE.MethodsA total of 1,239 eligible patients with PE were recruited in this study and randomly divided into a training set and an internal validation set at a ratio of 7:3. Logistic regression analysis was performed in the training set, and a nomogram was developed using selected predictors. The diagnostic accuracy of an innovative scoring system based on the nomogram was established and validated in the training, internal validation, and external validation sets (n = 217). The discriminatory power and the calibration and clinical values of the prediction model were evaluated.ResultsSeven variables [effusion carcinoembryonic antigen (CEA), effusion adenosine deaminase (ADA), erythrocyte sedimentation rate (ESR), PE/serum CEA ratio (CEA ratio), effusion carbohydrate antigen 19-9 (CA19-9), effusion cytokeratin 19 fragment (CYFRA 21-1), and serum lactate dehydrogenase (LDH)/effusion ADA ratio (cancer ratio, CR)] were validated and used to develop a nomogram. The prediction model showed both good discrimination and calibration capabilities for all sets. A scoring system was established based on the nomogram scores to distinguish MPE from BPE. The scoring system showed favorable diagnostic performance in the training set [area under the curve (AUC) = 0.955, 95% confidence interval (CI) = 0.942–0.968], the internal validation set (AUC = 0.952, 95% CI = 0.932–0.973), and the external validation set (AUC = 0.973, 95% CI = 0.956–0.990). In addition, the scoring system achieved satisfactory discriminative abilities at separating lung cancer-associated MPE from tuberculous pleurisy effusion (TPE) in the combined training and validation sets.ConclusionsThe present study developed and validated a scoring system based on seven parameters. The scoring system exhibited a reliable diagnostic performance in distinguishing MPE from BPE and might guide clinical decision-making.


2021 ◽  
Author(s):  
Yushu Liu ◽  
Jiantao Gong ◽  
Yanyi Huang ◽  
Qunguang Jiang

Abstract Background:Colon cancer is a common malignant cancer with high incidence and poor prognosis. Cell senescence and apoptosis are important mechanisms of tumor occurrence and development, in which aging-related genes(ARGs) play an important role. This study aimed to establish a prognostic risk model based on ARGs for diagnosis and prognosis prediction of colon cancer .Methods: We downloaded transcriptome data and clinical information of colon cancer patients from the Cancer Genome Atlas(TCGA) database and the microarray dataset(GSE39582) from the Gene Expression Omnibus(GEO) database. Univariate COX, least absolute shrinkage and selection operator(LASSO) regression algorithm and multivariate COX regression analysis were used to construct a 6-ARG prognosis model and calculated the riskScore. The prognostic signatures is validated by internal validation cohort and external validation cohort(GSE39582).In addition, functional enrichment pathways and immune microenvironment of aging-related genes(ARGs) were also analyzed. We also analyzed the correlation between rsikScore and clinical features and constructed a nomogram based on riskScore. We are the first to construct prognostic nomogram based on ARGs.Results: Through univariate COX,LASSO regression algorithm and multivariate COX regression analysis,6 prognostic ARGs (PDPK1,RAD52,GSR,IL7,BDNF and SERPINE1) were screened out and riskScore was constructed. We have verified that riskScore has good prognostic value in both internal validation cohort and external validation cohort. Pathway enrichment and immunoanalysis of ARGs provide a direction for the treatment of colon cancer patients. We also found that riskScore was closely related to the clinical characteristics of patients. Based on riskScore and related clinical features, we constructed a nomogram, which has good predictive performance.Conclusion: The 6-ARG prognostic signature we constructed has a certain clinical predictive ability. Its riskScore is also closely related to clinical characteristics, and nomogram based on this has stronger predictive ability than a single indicator. ARGs and the nomogram we constructed may provide a promising treatment for colon cancer patients.


2021 ◽  
Vol 7 ◽  
Author(s):  
Kai Zhang ◽  
Shufang Zhang ◽  
Wei Cui ◽  
Yucai Hong ◽  
Gensheng Zhang ◽  
...  

Background: Many severity scores are widely used for clinical outcome prediction for critically ill patients in the intensive care unit (ICU). However, for patients identified by sepsis-3 criteria, none of these have been developed. This study aimed to develop and validate a risk stratification score for mortality prediction in sepsis-3 patients.Methods: In this retrospective cohort study, we employed the Medical Information Mart for Intensive Care III (MIMIC III) database for model development and the eICU database for external validation. We identified septic patients by sepsis-3 criteria on day 1 of ICU entry. The Least Absolute Shrinkage and Selection Operator (LASSO) technique was performed to select predictive variables. We also developed a sepsis mortality prediction model and associated risk stratification score. We then compared model discrimination and calibration with other traditional severity scores.Results: For model development, we enrolled a total of 5,443 patients fulfilling the sepsis-3 criteria. The 30-day mortality was 16.7%. With 5,658 septic patients in the validation set, there were 1,135 deaths (mortality 20.1%). The score had good discrimination in development and validation sets (area under curve: 0.789 and 0.765). In the validation set, the calibration slope was 0.862, and the Brier value was 0.140. In the development dataset, the score divided patients according to mortality risk of low (3.2%), moderate (12.4%), high (30.7%), and very high (68.1%). The corresponding mortality in the validation dataset was 2.8, 10.5, 21.1, and 51.2%. As shown by the decision curve analysis, the score always had a positive net benefit.Conclusion: We observed moderate discrimination and calibration for the score termed Sepsis Mortality Risk Score (SMRS), allowing stratification of patients according to mortality risk. However, we still require further modification and external validation.


2021 ◽  
Vol 11 ◽  
Author(s):  
Dongdong Xiao ◽  
Zhen Zhao ◽  
Jun Liu ◽  
Xuan Wang ◽  
Peng Fu ◽  
...  

BackgroundMeningioma invasion can be preoperatively recognized by radiomics features, which significantly contributes to treatment decision-making. Here, we aimed to evaluate the comparative performance of radiomics signatures derived from varying regions of interests (ROIs) in predicting BI and ascertaining the optimal width of the peritumoral regions needed for accurate analysis.MethodsFive hundred and five patients from Wuhan Union Hospital (internal cohort) and 214 cases from Taihe Hospital (external validation cohort) pathologically diagnosed as meningioma were included in our study. Feature selection was performed from 1,015 radiomics features respectively obtained from nine different ROIs (brain-tumor interface (BTI)2–5mm; whole tumor; the amalgamation of the two regions) on contrast-enhanced T1-weighted imaging using least-absolute shrinkage and selection operator and random forest. Principal component analysis with varimax rotation was employed for feature reduction. Receiver operator curve was utilized for assessing discrimination of the classifier. Furthermore, clinical index was used to detect the predictive power.ResultsModel obtained from BTI4mm ROI has the maximum AUC in the training set (0.891 (0.85, 0.932)), internal validation set (0.851 (0.743, 0.96)), and external validation set (0.881 (0.833, 0.928)) and displayed statistically significant results between nine radiomics models. The most predictive radiomics features are almost entirely generated from GLCM and GLDM statistics. The addition of PEV to radiomics features (BTI4mm) enhanced model discrimination of invasive meningiomas.ConclusionsThe combined model (radiomics classifier with BTI4mm ROI + PEV) had greater diagnostic performance than other models and its clinical application may positively contribute to the management of meningioma patients.


2021 ◽  
Author(s):  
Luis Serviá ◽  
Juan Antonio Llompart-Pou ◽  
Mario Chico-Fernández ◽  
Neus Montserrat ◽  
Mariona Badia ◽  
...  

Abstract BackgroundSeverity scores are commonly used for outcome adjustment and benchmarking of trauma care provided. No specific models performed only with critically ill patients are available. Our objective was to develop a new score for early mortality prediction in trauma ICU patients.MethodsRetrospective study using the Spanish Trauma ICU registry (RETRAUCI) 2015-2019. Patients were divided and analysed into the derivation (2015-2017) and validation sets (2018-2019). We used as candidate variables to be associated with mortality those available in RETRAUCI that could be collected in the first 24 hours after ICU admission. Using logistic regression methodology, a simple score (RETRASCORE) was created with points assigned to each selected variable. The performance of the model was carried out according to global measures, discrimination and calibration.ResultsThe analysis included 9465 patients. Derivation set 5976 and validation set 3489. Thirty-day mortality was 12.2%. The predicted probability of 30-day mortality was determined by the following equation: 1 / (1+exp (-y)), where y=0.598 (Age 50–65) + 1.239 (Age 66–75) + 2.198 (Age > 75) + 0.349 (PRECOAG) + 0.336 (Pre-hospital intubation) + 0.662 (High risk mechanism) + 0.950 (unilateral mydriasis) + 3.217 (bilateral mydriasis) + 0.841 (Glasgow ≤ 8) + 0.495 (MAIS-Head) - 0.271 (MAIS-Thorax) + 1.148 (Hemodynamic failure) + 0.708 (Respiratory failure) + 0.567 (Coagulopathy) + 0.580 (Mechanical ventilation) + 0.452 (Massive haemorrhage) - 5.432. The AUROC was 0.913 (0.903-0.923) in the derivation set and 0.929 (0.918-0.940) in the validation set.ConclusionsThe newly developed RETRASCORE is an early, easy-to-calculate and specific score to predict in-hospital mortality in trauma ICU patients. Although it has achieved adequate internal validation, it must be externally validated.


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