SEPTIC SHOCK PREDICTION FOR PATIENTS WITH MISSING DATA. Joyce C Ho, Cheng Lee, Joydeep Ghosh University of Texas at Austin

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SEPTIC SHOCK PREDICTION FOR PATIENTS WITH MISSING DATA Joyce C Ho, Cheng Lee, Joydeep Ghosh University of Texas at Austin

WHAT IS SEPSIS AND SEPTIC SHOCK? Sepsis is a systemic inflammatory response to infection 11th leading cause of death in 2010 Estimated $14.6 billion spent on sepsis in 2008 Septic shock (sepsis-induced hypotension) has a mortality rate of 45.7%

IN-HOSPITAL DETECTION Demographic Information Vital Signs Labs Patient Representation Predictive Model Clinical Notes

MISSING DATA PROBLEM Clinical studies must deal with large amounts of missing data Measurements are noisy and irregularly sampled Highly accurate measurements require invasive techniques (may not be medically necessary)

TYPICAL APPROACH Ignore subjects with missing observations Ignore features without complete data Result: Highly curated datasets with limited features and small samples

OUR SEPTIC SHOCK MODEL Problem: Given a patient has sepsis, can we predict complications at least one hour prior to onset of septic shock? Generalization to patients with partially missing observations Simple and accessible approaches Focus on commonly observed, non-invasive measurements

CLINICAL FEATURES Summary statistics (last measurement, min, mean, and max) in 8 hour window Cardiac: non-invasive blood pressure, heart rate, pulse pressure Other: respiratory rate, SpO 2, temperature Last measurement only (less observations) White blood cell count Index scores: SOFA, SAPS-I, Shock index

IMPUTATION APPROACHES Mean / median imputation Matrix factorization techniques Singular value based imputation (SVD) Probabilistic principal component analysis (PPCA) K-nearest neighbors (KNN)

IMPUTATION SELECTION CRITERIA Matrix factorization and neighborhood techniques have parameter to control resolution or locality of imputation Evaluation metric typically involves randomly removing observations and comparing fit using root mean square error (RMSE) or mean absolute error (MAE) RMSE / MAE may not necessarily translate to improved predictive performance

PERFORMANCE-ORIENTED IMPUTATION (POI) Random splits Impute Build & Evaluate Imputation parameter selection Optimal k Data Impute Construct Prediction Model

MIMIC-II DATABASE Extensive, publicly available ICU data resource Data between 2001 and 2007 from Boston s Beth Israel Deaconess Medical Center ICUs Over 40,000 ICU stays from 30,000+ patients Clinical records with physiological measures, medication records, laboratory tests, free-form text notes, etc.

IMPORTANCE OF IMPUTATION 400 Count 300 200 100 Less than 22% of the 1,353 patients have complete data 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 22 Number of Missing Features Feature 30 mins 60 mins Respiratory rate 0.67% 0.68% Temperature 1.70% 2.05% Non-invasive BP is not always available White blood cells 15.30% 14.69% Blood pressure 23.28% 23.44%

DIFFERENCES IN POPULATION Missing patients Complete only Time Sepsis (only) Shock Sepsis (only) Shock P-value 30 mins 749 79 199 110 4.56E-26 60 mins 723 79 196 106 6.99E-24 90 mins 705 79 196 103 4.63E-22 120 mins 685 74 193 103 7.06E-23 Statistically significantly higher ratio of shock patients if you ignore patients with missing data

PREDICTIVE POWER OF MEAN IMPUTED MODEL Train Data Test Data 30 minutes before (AUC) 60 minutes before (AUC) Complete Complete 0.796±0.065 0.777±0.050 Complete Imputed 0.815±0.033 0.800±0.053 Imputed Imputed 0.834±0.025 0.829±0.030 Imputed Complete 0.839±0.044 0.828±0.047 Model generalizes to broader population with slightly better predictive performance

COMPARISON OF SELECTION CRITERIA (SVM) Value 0.8 0.7 0.6 2.00 1.75 1.50 1.25 1.00 0.5 0.4 0.3 0.2 0.1 SVD PPCA KNN POI MAE RMSE POI MAE RMSE POI MAE RMSE Selection Criteria AUC Lift F1 POI is generally better for AUC + F-measure

COMPARING IMPUTATION APPROACHES (SVD + LOGR) 1.00 60 120 180 True Positive Rate 0.75 0.50 0.25 0.00 selection 0.00 0.25 0.50 0.75 1.000.00 0.25 0.50 0.75 1.000.00 0.25 0.50 0.75 1.00 False Positive Rate POI MAE RMSE Mean POI outperforms RMSE, but mean and MAE are generally the best

COMPARING IMPUTATION APPROACHES (SVD + LOGR) 25 20 60 120 180 15 K 10 5 POI MAE RMSE POI MAE RMSE POI MAE RMSE Selection Criteria RMSE favors the simplest model (k=1), MAE favors most complex (k=25), POI lies in between the two

COMPARING IMPUTATION APPROACHES (FEATURE RANK) Feature Mean AUC F1 RMSE Systolic BP 1.50 1.70 1.70 2.40 SpO2 2.22 3.00 3.22 2.56 Shock Index 4.40 4.40 4.60 3.30 Temp 5.00 5.00 7.50 Diastolic BP 11.00 8.00 8.25 5.00 Selection criteria influences feature ranking within the same imputation method

CONCLUSION Generalizes to all ICU patients Focuses on commonly observed, non-invasive clinical measurements Uses simple and accessible approaches for missing data problem

REFERENCES Joyce C Ho, Cheng H Lee, and Joydeep Ghosh. Imputation-enhanced prediction of septic shock in ICU patients. In 2012 ACM SIGKDD Workshop on Health Informatics (HI-KDD), 2012. Joyce C Ho, Cheng H Lee, and Joydeep Ghosh. Septic shock prediction for patients with missing data. ACM Transactions on Management Information Systems (TMIS), 5(1):1:1 1:15, 2014.