Survival Meets Classification: A Novel Framework for Early Risk Prediction Models of Chronic Diseases

Obesity is a major health problem, increasing the risk of various major chronic diseases, such as diabetes, cancer, and stroke. While the role of obesity identified by cross-sectional BMI recordings has been heavily studied, the role of BMI trajectories is much less explored. In this study, we use a machine-learning approach to subtype individuals' risk of developing 18 major chronic diseases by using their BMI trajectories extracted from a large and geographically diverse EHR dataset capturing the health status of around two million individuals for a period of six years. We define nine new interpretable and evidence-based variables based on the BMI trajectories to cluster the patients into subgroups using the k-means clustering method. We thoroughly review each cluster's characteristics in terms of demographic, socioeconomic, and physiological measurement variables to specify the distinct properties of the patients in the clusters. In our experiments, the direct relationship of obesity with diabetes, hypertension, Alzheimer's, and dementia has been re-established and distinct clusters with specific characteristics for several of the chronic diseases have been found to be conforming or complementary to the existing body of knowledge.

To overcome the limitations of manual administrative coding in geriatric Cardiovascular Risk Management, this study introduces an automated classification framework leveraging unstructured Electronic Health Records (EHRs). Using a dataset of 3,482 patients, we benchmarked three distinct modeling paradigms on longitudinal Dutch clinical narratives: classical machine learning baselines, specialized deep learning architectures optimized for large-context sequences, and general-purpose generative Large Language Models (LLMs) in a zero-shot setting. Additionally, we evaluated a late fusion strategy to integrate unstructured text with structured medication embeddings and anthropometric data. Our analysis reveals that the custom Transformer architecture outperforms both traditional methods and generative \acs{llm}s, achieving the highest F1-scores and Matthews Correlation Coefficients. These findings underscore the critical role of specialized hierarchical attention mechanisms in capturing long-range dependencies within medical texts, presenting a robust, automated alternative to manual workflows for clinical risk stratification.

Deep learning architectures are increasingly proposed for patient trajectory modeling in electronic health records (EHRs), yet their advantage over simpler, more interpretable models is rarely subjected to rigorous empirical scrutiny in real-world clinical settings. We present a comprehensive patient timeline pipeline applied to elderly patients in CPRD Aurum, incorporating 260 clinical conditions classified via a three-tier automated framework including specialised detection logic for 17 complex conditions. Using this infrastructure, we benchmark Temporal Graph Convolutional Neural Networks (TG-CNN) against Logistic Regression with LASSO regularisation and Random Forests for predicting 12-month all-cause emergency hospitalisation risk, motivated by (but not filtered to) the elevated risk of adverse drug reactions. Under cross-validation, TG-CNN achieves a marginally higher mean AUC-ROC than LASSO (0.712 vs. 0.705), whereas on the held-out test set LASSO achieves the highest discrimination of three models (AUC-ROC 0.733, versus 0.710 for Random Forest and 0.702 for TG-CNN). We show, that discrimination alone is an incomplete criterion for clinical deployment: after Platt calibration, LASSO is the only model with an acceptable calibration slope (0.817), while Random Forest (0.759) and, TG-CNN (0.391) remain substantially miscalibrated. We argue that LASSO, not the highest-discriminating model, is the model best suited to direct clinical deployment. We present lessons for the machine learning and healthcare community regarding data infrastructure, model selection, and value of calibration and interpretability in high-stakes decision support.