The performance of predictive models in clinical settings often degrades when deployed in new hospitals due to distribution shifts. This paper presents a large-scale study of causality-inspired domain generalization on heterogeneous multi-center intensive care unit (ICU) data. We apply anchor regression and introduce anchor boosting, a novel, tree-based nonlinear extension, to a large dataset comprising 400,000 patients from nine distinct ICU databases. The anchor regularization consistently improves out-of-distribution performance, particularly for the most dissimilar target domains. The methods appear robust to violations of theoretical assumptions, such as anchor exogeneity. Furthermore, we propose a novel conceptual framework to quantify the utility of large external data datasets. By evaluating performance as a function of available target-domain data, we identify three regimes: (i) a domain generalization regime, where only the external model should be used, (ii) a domain adaptation regime, where refitting the external model is optimal, and (iii) a data-rich regime, where external data provides no additional value.

Postoperative stroke remains a critical complication in elderly surgical intensive care unit (SICU) patients, contributing to prolonged hospitalization, elevated healthcare costs, and increased mortality. Accurate early risk stratification is essential to enable timely intervention and improve clinical outcomes. We constructed a combined cohort of 19,085 elderly SICU admissions from the MIMIC-III and MIMIC-IV databases and developed an interpretable machine learning (ML) framework to predict in-hospital stroke using clinical data from the first 24 hours of Intensive Care Unit (ICU) stay. The preprocessing pipeline included removal of high-missingness features, iterative Singular Value Decomposition (SVD) imputation, z-score normalization, one-hot encoding, and class imbalance correction via the Adaptive Synthetic Sampling (ADASYN) algorithm. A two-stage feature selection process-combining Recursive Feature Elimination with Cross-Validation (RFECV) and SHapley Additive exPlanations (SHAP)-reduced the initial 80 variables to 20 clinically informative predictors. Among eight ML models evaluated, CatBoost achieved the best performance with an AUROC of 0.8868 (95% CI: 0.8802--0.8937). SHAP analysis and ablation studies identified prior cerebrovascular disease, serum creatinine, and systolic blood pressure as the most influential risk factors. Our results highlight the potential of interpretable ML approaches to support early detection of postoperative stroke and inform decision-making in perioperative critical care.

Detecting Type 2 Diabetes (T2D) and Prediabetes (PD) is a real challenge for medicine due to the absence of pathogenic symptoms and the lack of known associated risk factors. Even though some proposals for machine learning models enable the identification of people at risk, the nature of the condition makes it so that a model suitable for one population may not necessarily be suitable for another. In this article, the development and assessment of predictive models to identify people at risk for T2D and PD specifically in Argentina are discussed. First, the database was thoroughly preprocessed and three specific datasets were generated considering a compromise between the number of records and the amount of available variables. After applying 5 different classification models, the results obtained show that a very good performance was observed for two datasets with some of these models. In particular, RF, DT, and ANN demonstrated great classification power, with good values for the metrics under consideration. Given the lack of this type of tool in Argentina, this work represents the first step towards the development of more sophisticated models.

Most AI systems are black boxes generating reasonable outputs for given inputs. Some domains, however, have explainability and trustworthiness requirements that cannot be directly met by these approaches. Various methods have therefore been developed to interpret black-box models after training. This paper advocates an alternative approach where the models are transparent and explainable to begin with. This approach, EVOTER, evolves rule-sets based on simple logical expressions. The approach is evaluated in several prediction/classification and prescription/policy search domains with and without a surrogate. It is shown to discover meaningful rule sets that perform similarly to black-box models. The rules can provide insight into the domain, and make biases hidden in the data explicit. It may also be possible to edit them directly to remove biases and add constraints. EVOTER thus forms a promising foundation for building trustworthy AI systems for real-world applications in the future.

Objective: Imbalances of the electrolyte concentration levels in the body can lead to catastrophic consequences, but accurate and accessible measurements could improve patient outcomes. While blood tests provide accurate measurements, they are invasive and the laboratory analysis can be slow or inaccessible. In contrast, an electrocardiogram (ECG) is a widely adopted tool which is quick and simple to acquire. However, the problem of estimating continuous electrolyte concentrations directly from ECGs is not well-studied. We therefore investigate if regression methods can be used for accurate ECG-based prediction of electrolyte concentrations. Methods: We explore the use of deep neural networks (DNNs) for this task. We analyze the regression performance across four electrolytes, utilizing a novel dataset containing over 290000 ECGs. For improved understanding, we also study the full spectrum from continuous predictions to binary classification of extreme concentration levels. To enhance clinical usefulness, we finally extend to a probabilistic regression approach and evaluate different uncertainty estimates. Results: We find that the performance varies significantly between different electrolytes, which is clinically justified in the interplay of electrolytes and their manifestation in the ECG. We also compare the regression accuracy with that of traditional machine learning models, demonstrating superior performance of DNNs. Conclusion: Discretization can lead to good classification performance, but does not help solve the original problem of predicting continuous concentration levels. While probabilistic regression demonstrates potential practical usefulness, the uncertainty estimates are not particularly well-calibrated. Significance: Our study is a first step towards accurate and reliable ECG-based prediction of electrolyte concentration levels.

Are the most common cause of deaths globally, taking an estimated 17.9 million lives each year, which accounts for 31% of all deaths worldwide. Heart failure is a common event caused by Cardiovascular diseases. It is characterized by the heart's inability to pump an adequate supply of blood to the body. Without sufficient blood flow, all major body functions are disrupted. Heart failure is a condition or a collection of symptoms that weaken the heart.

Cardiovascular diseases and their associated disorder of heart failure are one of the major death causes globally, being a priority for doctors to detect and predict its onset and medical consequences. Artificial Intelligence (AI) allows doctors to discover clinical indicators and enhance their diagnosis and treatments. Specifically, explainable AI offers tools to improve the clinical prediction models that experience poor interpretability of their results. This work presents an explainability analysis and evaluation of a prediction model for heart failure survival by using a dataset that comprises 299 patients who suffered heart failure. The model employs a data workflow pipeline able to select the best ensemble tree algorithm as well as the best feature selection technique. Moreover, different post-hoc techniques have been used for the explainability analysis of the model. The paper's main contribution is an explainability-driven approach to select the best prediction model for HF survival based on an accuracy-explainability balance. Therefore, the most balanced explainable prediction model implements an Extra Trees classifier over 5 selected features (follow-up time, serum creatinine, ejection fraction, age and diabetes) out of 12, achieving a balanced-accuracy of 85.1% and 79.5% with cross-validation and new unseen data respectively. The follow-up time is the most influencing feature followed by serum-creatinine and ejection-fraction. The explainable prediction model for HF survival presented in this paper would improve a further adoption of clinical prediction models by providing doctors with intuitions to better understand the reasoning of, usually, black-box AI clinical solutions, and make more reasonable and data-driven decisions.

The incidence of Acute Kidney Injury (AKI) commonly happens in the Intensive Care Unit (ICU) patients, especially in the adults, which is an independent risk factor affecting short-term and long-term mortality. Though researchers in recent years highlight the early prediction of AKI, the performance of existing models are not precise enough. The objective of this research is to precisely predict AKI by means of Convolutional Neural Network on Electronic Health Record (EHR) data. The data sets used in this research are two public Electronic Health Record (EHR) databases: MIMIC-III and eICU database. In this study, we take several Convolutional Neural Network models to train and test our AKI predictor, which can precisely predict whether a certain patient will suffer from AKI after admission in ICU according to the last measurements of the 16 blood gas and demographic features. The research is based on Kidney Disease Improving Global Outcomes (KDIGO) criteria for AKI definition. Our work greatly improves the AKI prediction precision, and the best AUROC is up to 0.988 on MIMIC-III data set and 0.936 on eICU data set, both of which outperform the state-of-art predictors. And the dimension of the input vector used in this predictor is much fewer than that used in other existing researches. Compared with the existing AKI predictors, the predictor in this work greatly improves the precision of early prediction of AKI by using the Convolutional Neural Network architecture and a more concise input vector. Early and precise prediction of AKI will bring much benefit to the decision of treatment, so it is believed that our work is a very helpful clinical application.

Objective: Deriving disease subtypes from electronic health records (EHRs) can guide next-generation personalized medicine. However, challenges in summarizing and representing patient data prevent widespread practice of scalable EHR-based stratification analysis. Here, we present a novel unsupervised framework based on deep learning to process heterogeneous EHRs and derive patient representations that can efficiently and effectively enable patient stratification at scale. Materials and methods: We considered EHRs of $1,608,741$ patients from a diverse hospital cohort comprising of a total of $57,464$ clinical concepts. We introduce a representation learning model based on word embeddings, convolutional neural networks and autoencoders (i.e., "ConvAE") to transform patient trajectories into low-dimensional latent vectors. We evaluated these representations as broadly enabling patient stratification by applying hierarchical clustering to different multi-disease and disease-specific patient cohorts. Results: ConvAE significantly outperformed several common baselines in a clustering task to identify patients with different complex conditions, with $2.61$ entropy and $0.31$ purity average scores. When applied to stratify patients within a certain condition, ConvAE led to various clinically relevant subtypes for different disorders, including type 2 diabetes, Parkinson's disease and Alzheimer's disease, largely related to comorbidities, disease progression, and symptom severity. Conclusions: Patient representations derived from modeling EHRs with ConvAE can help develop personalized medicine therapeutic strategies and better understand varying etiologies in heterogeneous sub-populations.

Laboratory testing is an integral tool in the management of patient care in hospitals, particularly in intensive care units (ICUs). There exists an inherent trade-off in the selection and timing of lab tests between considerations of the expected utility in clinical decision-making of a given test at a specific time, and the associated cost or risk it poses to the patient. In this work, we introduce a framework that learns policies for ordering lab tests which optimizes for this trade-off. Our approach uses batch off-policy reinforcement learning with a composite reward function based on clinical imperatives, applied to data that include examples of clinicians ordering labs for patients. To this end, we develop and extend principles of Pareto optimality to improve the selection of actions based on multiple reward function components while respecting typical procedural considerations and prioritization of clinical goals in the ICU. Our experiments show that we can estimate a policy that reduces the frequency of lab tests and optimizes timing to minimize information redundancy. We also find that the estimated policies typically suggest ordering lab tests well ahead of critical onsets--such as mechanical ventilation or dialysis--that depend on the lab results. We evaluate our approach by quantifying how these policies may initiate earlier onset of treatment.