Pharmacokinetic State Space Models for Unbiased Prediction of Haemodynamic Collapse

Many time-series forecasts depend not only on prior observations but also on actions specified during the forecast period. In intensive care units (ICUs), future vital signs and laboratory values are influenced by treatments such as vasopressors. However, models that predict the full future sequence all at once make little use of these treatments, whereas autoregressive models can accumulate errors. We introduce DRIFT, a hybrid framework in which a direct model produces the primary forecast and a recursive, action-conditioned model contributes constrained corrections. We evaluate DRIFT on 6,046 admissions from MIMIC-IV and 8,345 admissions from eICU-CRD. Averaged across the 8-, 24-, and 48-hour forecast endpoints, DRIFT reduces mean absolute error for mean arterial pressure (MAP) by 0.673% relative to an action-conditioned Temporal Fusion Transformer (TFT-action) on MIMIC-IV and achieves the lowest corresponding error among the compared models on eICU-CRD. Although the overall accuracy improvement is modest, a MIMIC-IV audit restricted to windows in which the supplied treatment sequence was altered showed that DRIFT achieved lower observed-target MAP error than TFT-action at 8 and 24 hours. Treatment-sequence alteration increased DRIFT's MAP error by 0.21-0.26 mmHg more than it increased TFT-action's error, with prediction changes occurring primarily after the supplied paths diverged. In a separate robustness experiment, the MAP advantage persisted under three shared checkpoint-selection rules emphasizing overall endpoint error, MAP error, or both equally.

Electronic Health Record (EHR) prediction models in the intensive care unit must learn from sparse and irregular measurements while preserving the clinical meaning of time and supporting transparent decision-making. We present INTERVenE, a family of Transformer architectures whose input is an interval-based, knowledge-based temporal abstraction (KBTA), a token stream of named clinical concepts (states, trends, events, contexts) drawn from a curated medical ontology, rather than an unnamed bin index or a raw measurement triplet. This naming layer is what we ask KBTA to do: it makes the model's per-token attributions resolve to clinical concepts by construction. INTERVenE offers two complementary variants: an auto-regressive decoder that generates future abstraction trajectories with a per-step risk readout (localizing \emph{when} and \emph{after which events} risk rises), and a bidirectional encoder for single-pass joint risk and time-to-event prediction. Evaluated on 57,078 MIMIC-IV admissions against GRU-D, STraTS, and KarmaLego, INTERVenE-Enc reaches a support-weighted AUPRC$_w$ of 0.672, improving by 0.041 over the strongest neural baseline with non-overlapping 95% bootstrap CIs, while also taking the best AUROC$_w$ (0.901) and length-of-stay MAE (44.4,h). INTERVenE-Ar (AUROC$_w$ $0.854$, AUPRC$_w$ $0.587$ under the same evaluation contract - a strictly harder generative readout) provides a complementary token-level risk trajectory. An input-representation ablation confirms the lift transfers across structured discretizations, positioning KBTA-based intervals as the interpretable substrate that makes per-token attributions resolve to meaningful clinical concepts within the deployed model.

Continuous hemodynamic monitoring guides treatment decisions in surgery and intensive care. However, gold-standard signals are only measured in severe cases due to risks associated with invasive measurement. In this work, we introduce HIPNO (Hemodynamic Inference via Physics-informed Neural Operators) to recover hemodynamic state from ubiquitous, non-invasive signals and expand access to advanced monitoring. HIPNO addresses a problem of scale symmetry in physics-informed hemodynamic inference, where different combinations of flow, resistance, and compliance can generate the same observed pressure. We identify the symmetry group of the observation model and parameterize the network in its quotient space. For the 3-element Windkessel model, the quotient coordinates are the compliance-normalized flow $U=Q/C$, the decay time constant $τ_{WK}=R_2 C$, and the characteristic-impedance coordinate $κ=R_1 C$. Across 945499 intraoperative windows from 2562 patients, HIPNO predicts $τ_{wave}$, a proxy for vascular decay derived from pressure, with 32% lower error on the log scale than a population baseline while preserving mean arterial pressure accuracy. Because vascular decay and flow drive occupy separate coordinates, counterfactual perturbations produce the expected directional responses in at least 90% of windows in almost all prespecified scenarios, a separation unavailable to pressure-only baselines. The coordinates are also used as inputs to a calibration model for monitored cardiac output. Finally, the formulation identifies the external compliance or flow reference required to recover absolute physical scale.