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Polypharmacy, defined as the concurrent use of five or more medications, is highly prevalent among older adults and patients with multiple chronic conditions and is associated with an increased risk of drug–drug interactions (DDIs), leading to adverse drug events, hospitalizations, and higher healthcare costs. Existing DDI databases are often incomplete and fail to capture higher-order interactions, while many machine learning approaches overlook temporal prescription patterns and molecular structure information, limiting their effectiveness in real-world clinical settings. To address these limitations, this study proposes a graph neural network (GNN)-based framework that integrates prescription sequence data with molecular representations to improve DDI prediction. The model constructs a unified graph where drug nodes encode both known interactions and learned similarities, while a prescription sequence encoder captures temporal co-prescribing patterns and a molecular encoder processes SMILES-based structures. These multimodal representations are fused within a patient–drug interaction graph and refined using GNN layers with attention mechanisms to enhance interpretability. By combining longitudinal clinical data with chemical structure information, the framework enables more accurate, context-aware, and patient-specific prediction of DDIs, supports the identification of novel interactions, and improves risk stratification in polypharmacy settings, offering a scalable and interpretable foundation for future clinical decision support systems.

Heart failure affects over 6 million Americans, with 30-day readmission rates remaining 20–25% despite longstanding quality improvement efforts. These readmissions cost about $17 billion annually and are penalized under federal reimbursement programs, yet existing prediction models have not achieved clinically useful performance. Most current models treat patients independently and fail to capture meaningful relationships among patients with similar medication patterns, admission histories, and social circumstances. They also often exclude critical social determinants of health (SDOH), such as housing instability and food insecurity, despite their strong association with readmission risk. In addition, black-box models lack interpretability, limiting clinician trust and usability. I argue that explainable graph neural networks (GNNs) integrating clinical data, SDOH, and prior admissions should replace traditional logistic regression and tree-based models for readmission prediction. Patient similarity graphs can represent clinically relevant relationships that tabular models miss, while graph attention mechanisms provide interpretable, actionable explanations. GNNs enable direct integration of SDOH and prior utilization patterns and offer transparency by highlighting which similar patients most influence predictions. This makes them more suitable for clinical decision support than existing approaches. Overall, persistent readmission rates reflect limitations in current modeling strategies. Explainable GNNs provide a more clinically meaningful and policy-relevant approach to improving prediction and reducing preventable readmissions.

Chemotherapy remains a cornerstone of cancer treatment, but it is frequently associated with severe toxicities, with 30–80% of patients experiencing grade 3–4 adverse events that may require dose reduction, treatment delays, or hospitalization. While machine learning models have shown strong potential in predicting chemotherapy-related toxicities using electronic health records, genomic data, and clinical variables, most existing approaches generate only point estimates (e.g., a single risk probability) without quantifying uncertainty, limiting their clinical reliability. Such miscalibrated predictions can lead to overconfident risk underestimation or excessive caution, both of which may negatively impact treatment decisions and patient outcomes. This manuscript proposes a conceptual framework that integrates neural network-based toxicity prediction with adaptive conformal prediction to produce calibrated, patient-specific prediction intervals with formal coverage guarantees. The framework combines a feedforward neural network for risk estimation, a non-conformity score to measure how atypical a patient is relative to the training data, and an adaptive calibration mechanism that updates interval thresholds over time to reflect shifts in patient populations and clinical practice. This design enables narrower intervals for well-represented, predictable cases and wider intervals for atypical or high-uncertainty patients, thereby making prediction reliability explicit. Importantly, the method provides finite-sample coverage guarantees without requiring distributional assumptions, ensuring that true toxicity outcomes fall within the predicted intervals at a user-specified confidence level. By transforming point predictions into uncertainty-aware, clinically interpretable intervals, the framework supports more robust, risk-stratified decision-making in chemotherapy planning and moves toward safer, more trustworthy AI-assisted oncology care.