Algorithm 1 Hard-gating Algorithm for In-Stage IDKCascade Input Ds: Training data containing Ns samples in stage-s Ms: Sorted list of the models trained for stage-s C: Dictionary of models' spatio-temporal costs cs: User-defined budget of spatio-temporal cost for stage-s q: Confidence function maxA: Value for the upper bound of the cutoffs to avoid over-fitting nBins: Number of bins for the grid search Output s: The optimal IDK cutoff vector for stage-s 1: procedure HARDGATING(Ds, Ms, cs, C, q, maxA, nBins) 2: s =[], ModelAssign = 1, cost = P We use the Sepsis-3 toolkit3 to obtain the suspected infection time in patients, and following the process in Seymour et al. (2016) to finally label the onset of sepsis. We result at a total number of 20,009 sepsis patients out of the 52,902 adult patients from MIMIC-III database. We exclude those patients who stay in ICUs less than 6 hours and also exclude those patients who developed sepsis within the first 6 hours after ICU admission. This reduces our cohort to a total of 34,475ICU patient, and only 2,370(6.8%) Then according to Singer et al. (2016), we identify the onset of septic shock as Algorithm 3 End-to-End Training algorithm for UnfoldML Input D: Full training data containing N instances M: Full model zoo C: Dictionary of models' spatio-temporal costs q: Confidence criterion Output: the optimal ICK1 gate parameters (or a,b): the optimal IDK gate parameters 1: procedure END-TO-ENDTRAINING (D, M) 2: Pre-allocate costs cs for each stage s. Figure 4: Transitions in model calls: both cascades always call the first model per each stage for an entrance and transition to next models (IDK) or next stage (ICK).

Abstract: Antibiotic resistance poses a significant threat in in - patient settings with high mortality. Using MIMIC - III data, we generated Sentence - BERT embeddings from clinical notes and applied Neural Networks and XGBoost to predict antibiotic susceptibility. XGBoost achieved an average F1 score of 0.86, while Neural Networks scored 0.84. This study is among the first to use document embeddings for predicting antibiotic resistance, offering a novel pathway for improving antimicrobial stewardship. Introduction: Sepsis and septic shock are life threatening conditions, with mortality rates as high as 50 - 60%. [1] Delays in appropriate antibiotic administration lead to an 8% decrease in survival for every hour of delay, underscoring the need for prompt and precise treatment.

ABSTRACT 2 Background: The search for new biomarkers that allow an early diagnosis in sepsis has become a necessity in medicine. The objective of this study is to identify potential protein biomarkers of differential expression between sepsis and non - infectious systemic inflamm atory response syndrome (NISIRS). Methods: Prospective observational study of a cohort of septic patients activated by the Sepsis Code and patients admitted with NISIRS, during the period 2016 - 2017. A mass spectrometry - based approach was used to analyze the plasma proteins in the enrolled subjects . Subsequently, using recursive feature elimination (RFE) classification and cross - validation with a vector classifier, an association of these proteins in patients with sepsis compared to patients with NISIRS. The protein - protein interaction netwo rk was analyzed with String software. Results: A total of 277 patients (141 with sepsis and 136 with NISIRS) were included. Conclusion: There are proteomic patterns associated with sepsis compared to NISIRS with different strength of association. Advances in understanding these protein changes may allow for the identification of new biomarkers or therapeutic targets in the future. Key words: Sepsis, Septic shock, SIRS, Proteomics, Omics, Diagnosis INTRODUCTION 3 Sepsis is known as a clinical syndrome where life - threatening organ dysfunction occurs due to a dysregulated host response to infection.

Our goal is to $\textit{efficiently}$ discover a compact set of temporal logic rules to explain irregular events of interest. We introduce a neural-symbolic rule induction framework within the temporal point process model. The negative log-likelihood is the loss that guides the learning, where the explanatory logic rules and their weights are learned end-to-end in a $\textit{differentiable}$ way. Specifically, predicates and logic rules are represented as $\textit{vector embeddings}$, where the predicate embeddings are fixed and the rule embeddings are trained via gradient descent to obtain the most appropriate compositional representations of the predicate embeddings. To make the rule learning process more efficient and flexible, we adopt a $\textit{sequential covering algorithm}$, which progressively adds rules to the model and removes the event sequences that have been explained until all event sequences have been covered. All the found rules will be fed back to the models for a final rule embedding and weight refinement. Our approach showcases notable efficiency and accuracy across synthetic and real datasets, surpassing state-of-the-art baselines by a wide margin in terms of efficiency.

Accurate predictions, as with machine learning, may not suffice to provide optimal healthcare for every patient. Indeed, prediction can be driven by shortcuts in the data, such as racial biases. Causal thinking is needed for data-driven decisions. Here, we give an introduction to the key elements, focusing on routinely-collected data, electronic health records (EHRs) and claims data. Using such data to assess the value of an intervention requires care: temporal dependencies and existing practices easily confound the causal effect. We present a step-by-step framework to help build valid decision making from real-life patient records by emulating a randomized trial before individualizing decisions, eg with machine learning. Our framework highlights the most important pitfalls and considerations in analysing EHRs or claims data to draw causal conclusions. We illustrate the various choices in studying the effect of albumin on sepsis mortality in the Medical Information Mart for Intensive Care database (MIMIC-IV). We study the impact of various choices at every step, from feature extraction to causal-estimator selection. In a tutorial spirit, the code and the data are openly available.

Detecting and predicting septic shock early is crucial for the best possible outcome for patients. Accurately forecasting the vital signs of patients with sepsis provides valuable insights to clinicians for timely interventions, such as administering stabilizing drugs or optimizing infusion strategies. Our research examines N-BEATS, an interpretable deep-learning forecasting model that can forecast 3 hours of vital signs for sepsis patients in intensive care units (ICUs). In this work, we use the N-BEATS interpretable configuration to forecast the vital sign trends and compare them with the actual trend to understand better the patient's changing condition and the effects of infused drugs on their vital signs. We evaluate our approach using the publicly available eICU Collaborative Research Database dataset and rigorously evaluate the vital sign forecasts using out-of-sample evaluation criteria. We present the performance of our model using error metrics, including mean squared error (MSE), mean average percentage error (MAPE), and dynamic time warping (DTW), where the best scores achieved are 18.52e-4, 7.60, and 17.63e-3, respectively. We analyze the samples where the forecasted trend does not match the actual trend and study the impact of infused drugs on changing the actual vital signs compared to the forecasted trend. Additionally, we examined the mortality rates of patients where the actual trend and the forecasted trend did not match. We observed that the mortality rate was higher (92%) when the actual and forecasted trends closely matched, compared to when they were not similar (84%).

Sepsis is a life-threatening condition with organ dysfunction and is a leading cause of death and critical illness worldwide. Even a few hours of delay in the treatment of sepsis results in increased mortality. Early detection of sepsis during emergency department triage would allow early initiation of lab analysis, antibiotic administration, and other sepsis treatment protocols. The purpose of this study was to compare sepsis detection performance at ED triage (prior to the use of laboratory diagnostics) of the standard sepsis screening algorithm (SIRS with source of infection) and a machine learning algorithm trained on EHR triage data. A machine learning model (KATE Sepsis) was developed using patient encounters with triage data from 16participating hospitals. KATE Sepsis and standard screening were retrospectively evaluated on the adult population of 512,949 medical records. KATE Sepsis demonstrates an AUC of 0.9423 (0.9401 - 0.9441) with sensitivity of 71.09% (70.12% - 71.98%) and specificity of 94.81% (94.75% - 94.87%). Standard screening demonstrates an AUC of 0.6826 (0.6774 - 0.6878) with sensitivity of 40.8% (39.71% - 41.86%) and specificity of 95.72% (95.68% - 95.78%). The KATE Sepsis model trained to detect sepsis demonstrates 77.67% (75.78% -79.42%) sensitivity in detecting severe sepsis and 86.95% (84.2% - 88.81%) sensitivity in detecting septic shock. The standard screening protocol demonstrates 43.06% (41% - 45.87%) sensitivity in detecting severe sepsis and40% (36.55% - 43.26%) sensitivity in detecting septic shock. Future research should focus on the prospective impact of KATE Sepsis on administration of antibiotics, readmission rate, morbidity and mortality.

Machine Learning (ML) research has focused on maximizing the accuracy of predictive tasks. ML models, however, are increasingly more complex, resource intensive, and costlier to deploy in resource-constrained environments. These issues are exacerbated for prediction tasks with sequential classification on progressively transitioned stages with ''happens-before'' relation between them.We argue that it is possible to ''unfold'' a monolithic single multi-class classifier, typically trained for all stages using all data, into a series of single-stage classifiers. Each single-stage classifier can be cascaded gradually from cheaper to more expensive binary classifiers that are trained using only the necessary data modalities or features required for that stage. UnfoldML is a cost-aware and uncertainty-based dynamic 2D prediction pipeline for multi-stage classification that enables (1) navigation of the accuracy/cost tradeoff space, (2) reducing the spatio-temporal cost of inference by orders of magnitude, and (3) early prediction on proceeding stages. UnfoldML achieves orders of magnitude better cost in clinical settings, while detecting multi-stage disease development in real time. It achieves within 0.1% accuracy from the highest-performing multi-class baseline, while saving close to 20X on spatio-temporal cost of inference and earlier (3.5hrs) disease onset prediction. We also show that UnfoldML generalizes to image classification, where it can predict different level of labels (from coarse to fine) given different level of abstractions of a image, saving close to 5X cost with as little as 0.4% accuracy reduction.

Guideline-based treatment for sepsis and septic shock is difficult because sepsis is a disparate range of life-threatening organ dysfunctions whose pathophysiology is not fully understood. Early intervention in sepsis is crucial for patient outcome, yet those interventions have adverse effects and are frequently overadministered. Greater personalization is necessary, as no single action is suitable for all patients. We present a novel application of reinforcement learning in which we identify optimal recommendations for sepsis treatment from data, estimate their confidence level, and identify treatment options infrequently observed in training data. Rather than a single recommendation, our method can present several treatment options. We examine learned policies and discover that reinforcement learning is biased against aggressive intervention due to the confounding relationship between mortality and level of treatment received. We mitigate this bias using subspace learning, and develop methodology that can yield more accurate learning policies across healthcare applications.