Benchmarking Machine Learning Architectures for Antimicrobial Stewardship in Pediatric ICUs

Background: Clinical decision support systems degrade silently as treatment protocols evolve, yet standard adaptation methods treat models as monolithic blocks, unable to distinguish stable patient physiology from shifting institutional practice. Methods: We propose an adaptive clinical intelligence architecture for ICU intervention prediction that structurally decouples physiological from treatment representations, confining parameter updates to the treatment stream upon a dual distributional and accuracy trigger. Automated audit logs record which treatment features drove each adaptation event and how their importance shifted. At inference, an attribution-driven Temporal RAG module grounds each prediction in patient-specific, era-matched PubMed evidence anchored to the patient's dominant physiological features. Experiments used 84,792 MIMIC-IV stays (2008-2022) under strict chronological split. Results: Drift localised entirely to the treatment stream, validating the structural prior. Selective adaptation improved vasopressor and septic shock discrimination and calibration over the static source model. A fully retrained baseline yielded marginally higher aggregate discrimination but missed 26 septic shock cases the framework correctly identified, with none in the reverse direction; retrieval consistency with the pre-adaptation source model was preserved by the framework but degraded substantially in the retrained baseline. Conclusions: Structurally constraining adaptation to drifting components while preserving stable physiological representations enables clinical AI to evolve with practice without distorting learned patient biology. This architecture offers a template for governable, interpretable deployment of adaptive models in high-stakes clinical environments.

Post-deployment monitoring of healthcare AI requires statistically valid, label-efficient methods, but gold-standard labels from clinician chart review are expensive. Prediction-powered inference (PPI) and active statistical inference (ASI) reduce label cost by combining a small labeled sample with abundant model predictions, but both are restricted to a single predictor, a poor fit for modern clinical pipelines that have multiple predictors of differing cost and accuracy available at inference time. We propose Active Multiple-Prediction-Powered Inference (AM-PPI), which routes each instance to a cost-appropriate predictor subset, samples gold-standard labels in proportion to the chosen subset's residual uncertainty, and reweights predictions to minimize estimator variance, all under a single deployment-time budget. AM-PPI generalizes ASI to leverage multiple predictors and extends Multiple-PPI from global per-predictor allocation to per-instance adaptive routing. We derive closed-form Karush-Kuhn-Tucker (KKT) conditions for all three decisions and prove, via biconvexity and strong duality, that the resulting fixed point is a global optimum despite the joint problem being non-jointly-convex. We establish asymptotic normality with valid coverage, minimum-variance unbiasedness within the linear-prediction augmented inverse propensity weighted (AIPW) class, and a closed-form criterion identifying when multiple predictors help. On synthetic data and three healthcare monitoring tasks, AM-PPI produces 10 to 40 percent narrower confidence intervals (CIs) than single-predictor ASI in the budget regime where routing matters, and matches the better baseline elsewhere.

Accurate ICU mortality prediction requires modeling irregular clinical observations across heterogeneous entity types. Existing sequence models handle irregular sampling but ignore typed relational structure; existing graph models assume fixed-interval inputs. We introduce the Continuous-Time Heterogeneous EHR Graph (CT-HEG) schema and evaluate which architectural choices drive predictive performance. CT-HEG encodes each ICU stay as a typed, timestamped graph with three node types (visit, vital, lab_event) and 2D edge attributes (t_hours/48, value_norm) encoding timing and value without imputation. We instantiate CT-HEG as CHIRP-Net, a four-layer heterogeneous GATv2Conv network, evaluated on MIMIC-IV v3.1 (31,142 ICU stays, LOS>=48h, 13.4% mortality) with five seeds and bootstrapped confidence intervals, against logistic regression, mTAND, a Transformer, and GRU-D, plus an ablation study. CHIRP-Net achieved 5-seed mean AUROC 0.8449+/-0.0071 (AUPRC 0.4958+/-0.0209); the ensemble achieved AUROC 0.8618 (95% CI: 0.8485-0.8745). Removing reverse edges disconnected observation nodes from the visit readout, cutting AUROC by 0.1968+/-0.0073. Time-attentive edge features contributed 0.0247+/-0.0093 AUROC. Collapsing heterogeneous edge types into one relation (7x fewer parameters) outperformed the full model on all seeds. Post-calibration ECE was 0.0307. Temporal and demographic subgroup analyses were explored but not reported here, pending follow-up work. Bidirectional connectivity was necessary for the model to use its inputs at all, and CT-HEG was reasonably well calibrated after validation-fitted temperature scaling. These results support CT-HEG for irregular EHR data, while external validation, a pre-specified temporal evaluation, and a demographic fairness audit remain necessary before any claim of robustness. Code: https://github.com/nasiruddinstudents-ctrl/chirp-net-mimic-iv.