Electronic health records (EHRs) support powerful clinical prediction models, but existing methods typically provide coarse, post hoc explanations that offer limited value for patient-level decision making. We introduce a knowledge graph (KG)-guided chain-of-thought (CoT) framework that generates clinically grounded and temporally consistent reasoning for visit-level disease prediction in MIMIC-III. ICD-9 codes are mapped to PrimeKG, from which disease-relevant nodes and multi-hop reasoning paths are extracted and used as scaffolds for CoT generation; only explanations whose conclusions match observed outcomes are retained. Lightweight LLaMA-3.1-Instruct-8B and Gemma-7B models are then fine-tuned on this supervision corpus. Across ten PrimeKG-mapped diseases and limited training cohorts (400 and 1000 cases), KG-guided models outperform strong classical baselines, achieving AUROC values of 0.66 to 0.70 and macro-AUPR values of 0.40 to 0.47. The models also transfer zero-shot to the CRADLE cohort, improving accuracy from approximately 0.40 to 0.51 up to 0.72 to 0.77. A blinded clinician evaluation shows consistent preference for KG-guided CoT explanations in clarity, relevance, and clinical correctness.

Recurrent exacerbations remain a common yet preventable outcome for many children with asthma. Machine learning (ML) algorithms using electronic medical records (EMR) could allow accurate identification of children at risk for exacerbations and facilitate referral for preventative comprehensive care to avoid this morbidity. We developed ML algorithms to predict repeat severe exacerbations (i.e. asthma-related emergency department (ED) visits or future hospital admissions) for children with a prior asthma ED visit at a tertiary care children's hospital. Retrospective pre-COVID19 (Feb 2017 - Feb 2019, N=2716) Epic EMR data from the Children's Hospital of Eastern Ontario (CHEO) linked with environmental pollutant exposure and neighbourhood marginalization information was used to train various ML models. We used boosted trees (LGBM, XGB) and 3 open-source large language model (LLM) approaches (DistilGPT2, Llama 3.2 1B and Llama-8b-UltraMedical). Models were tuned and calibrated then validated in a second retrospective post-COVID19 dataset (Jul 2022 - Apr 2023, N=1237) from CHEO. Models were compared using the area under the curve (AUC) and F1 scores, with SHAP values used to determine the most predictive features. The LGBM ML model performed best with the most predictive features in the final AIRE-KIDS_ED model including prior asthma ED visit, the Canadian triage acuity scale, medical complexity, food allergy, prior ED visits for non-asthma respiratory diagnoses, and age for an AUC of 0.712, and F1 score of 0.51. This is a nontrivial improvement over the current decision rule which has F1=0.334. While the most predictive features in the AIRE-KIDS_HOSP model included medical complexity, prior asthma ED visit, average wait time in the ED, the pediatric respiratory assessment measure score at triage and food allergy.

Temporal context in medicine is valuable in assessing key changes in patient health over time. We developed a machine learning framework to integrate diverse context from prior visits to improve health monitoring, especially when prior visits are limited and their frequency is variable. Our model first estimates initial risk of disease using medical data from the most recent patient visit, then refines this assessment using information digested from previously collected imaging and/or clinical biomarkers. We applied our framework to prostate cancer (PCa) risk prediction using data from a large population (28,342 patients, 39,013 magnetic resonance imaging scans, 68,931 blood tests) collected over nearly a decade. For predictions of the risk of clinically significant PCa at the time of the visit, integrating prior context directly converted false positives to true negatives, increasing overall specificity while preserving high sensitivity. False positive rates were reduced progressively from 51% to 33% when integrating information from up to three prior imaging examinations, as compared to using data from a single visit, and were further reduced to 24% when also including additional context from prior clinical data. For predicting the risk of PCa within five years of the visit, incorporating prior context reduced false positive rates still further (64% to 9%). Our findings show that information collected over time provides relevant context to enhance the specificity of medical risk prediction. For a wide range of progressive conditions, sufficient reduction of false positive rates using context could offer a pathway to expand longitudinal health monitoring programs to large populations with comparatively low baseline risk of disease, leading to earlier detection and improved health outcomes.