ChronoMedicalWorld: A Medical World Model for Learning Patient Trajectories from Longitudinal Care Data

Long-horizon clinical simulation -- predicting how a patient's physiology evolves over years under specified interventions -- is central to chronic-disease care, yet existing electronic health record (EHR) models are predominantly discriminative, and general-purpose large language models drift under repeated interventions. We propose the \textbf{ChronoMedicalWorld Model (CMWM)}, an action-conditioned latent world-model framework for learning patient trajectories from longitudinal care data. CMWM couples a joint-embedding state encoder with a wide action encoder that admits both structured intervention indicators and free-text communication embeddings, and trains a recurrent latent transition module under a six-term objective: next-observation supervision, next-latent prediction, SIGReg latent regularisation, and three physiology-aware shape priors (slope, continuity, large-jump penalty). A closed-loop rollout-prefix protocol matches training to deployment, so the model is optimised against the same multi-step error it exhibits at inference. As a concrete case study, we instantiate CMWM for annual estimated glomerular filtration rate (eGFR) trajectory forecasting in chronic kidney disease (CKD). On a 2{,}232-patient nephrology cohort, the CKD instantiation achieves a dynamic-50\% history rollout test mean absolute error (MAE) of 7.384 and root-mean-square error (RMSE) of 10.256, against 7.964 and 11.069 for a tuned GPT-5.5 structured-prompting baseline ($-7.28\%$ MAE, $-7.35\%$ RMSE), with the gain dominated by the dialogue portion of patient--health-coach communication. The framework is not CKD-specific: its architecture, loss design, and training protocol apply to any chronic condition that can be cast as periodic clinical state interleaved with structured and conversational interventions.

Simulating clinical interventions with a generative multimodal model of human physiology

Understanding how human health changes over time, and why responses to interventions vary between individuals, remains a central challenge in medicine. Here we present HealthFormer, a decoder-only transformer that models the human physiological trajectory generatively, by training on data from the Human Phenotype Project, a multi-visit cohort of over 15,000 deeply phenotyped individuals. We tokenise each participant's health trajectory across 667 measurements spanning seven domains: blood biomarkers, body composition, sleep physiology, continuous glucose monitoring, gut microbiome, wearable-derived physiology, and behaviour and medication exposure. We train HealthFormer to forecast individual physiological trajectories across these domains, and from this single generative objective a range of clinically relevant tasks can be expressed as queries on the model. We show that, without task-specific training, HealthFormer transfers to four independent cohorts and improves prediction for 27 of 30 incident-disease and mortality endpoints, exceeding established clinical risk scores in every comparison. We further show that the model can simulate interventions in silico: in a held-out personalised-nutrition trial, intervention-conditioned predictions recover individual six-month biomarker changes (e.g., Pearson r = 0.78 for diastolic blood pressure). Across 41 randomised intervention-outcome comparisons drawn from published trials, our results show that the predicted direction of effect agrees in every case, and the predicted mean falls within the reported 95% confidence interval in 30 cases. We position HealthFormer as an initial health world model, from which forecasting, risk stratification, and intervention-conditioned simulation arise as queries, providing a basis for clinical digital twins.