Clinical Decision Support

Introduction. Early detection of malignant skin lesions is critical for prognosis, yet dermatologist shortages in Russian regions limit screening coverage. Mobile dermoscopy clinical decision support systems (CDSS) offer a promising approach, with model interpretability and standardised patient routing remaining key barriers to adoption. Aim. To develop a quantitative interpretability assessment method for cascade deep learning models and a three-zone patient routing algorithm, and to conduct a preliminary single-centre prospective clinical validation of the Melanoscope AI CDSS in Russian outpatient practice. Material and methods. Two-stage cascade classification of dermoscopic images; attention map visualisation (attention rollout for ViT and Swin; Grad-CAM for ConvNeXt and EfficientNetV2); quantitative IoU-based agreement assessment between activation maps and expert annotations; prospective single-centre validation across four "Melanoma Day" sessions (Orel, Russia, June 2025 - April 2026). Results. On 176 patients: agreement with expert assessment 88.6%; no false negatives among 5 malignant lesions (95% CI: 47.8-100.0%); specificity 88.3%. Three melanomas and two basal cell carcinomas were histologically confirmed; six dysplastic naevi placed under follow-up. Mean IoU (n=180): ViT - 0.69; Swin - 0.64; ConvNeXt - 0.53; EfficientNetV2 - 0.51. Routing thresholds: P<0.15 / 0.15-0.50 / >=0.50. Conclusion. No false negatives were observed; specificity was 88.3%, supporting screening use. The integrated cascade classification, attention map visualisation with IoU assessment, and three-zone routing provide reproducible, interpretable clinical decision support adaptable to varying resource levels.

Clinical practice guidelines (CPGs) encode evidence-based decision logic that clinicians apply by evaluating patient variables, conditional criteria, and recommendation rules. However, existing methods often use CPGs as free-text training data or retrieval sources, underutilizing their procedural decision structure. To better exploit this structure, we introduce a guideline-derived training pipeline that transforms CPG recommendations into executable clinical decision logic and uses it to generate factual and counterfactual question-answering data. Theses data teach models both guideline-supported decisions and how decisions change under different patient conditions. Post-training a medical LLM on the generated data yields MedGuideX. Across four clinical reasoning benchmarks, MedGuideX achieves a 10.28% relative improvement in average accuracy. Physician evaluation further shows that MedGuideX better recovers clinician authored reasoning steps and produces physician-preferred rationales in faithfulness, validity, completeness, and clarity. Overall, our results show that executable decision logic from CPGs can be transformed into scalable supervision for building reliable medical LLMs.

Objective: To describe the design and early clinical evaluation of The Daily Dose (TDD), an LLM-driven, automated clinical summarization and clinical-trial identification system integrated into routine radiation oncology practice. Design: Mixed-methods evaluation using a cross-sectional, anonymous clinician survey administered after 1 month of system deployment. Exposure: Daily automated delivery of physician-specific email summaries generated using RadOnc-GPT, including patient schedules, concise EHR-derived clinical-status summaries, and automated identification of potentially relevant clinical trials for new or consult visits. Main Outcomes and Measures: Primary outcomes included self-reported usability, satisfaction, perceived usefulness, perceived impact on workflow, time savings, and intention for continued use. Internal consistency reliability was assessed using Cronbach's $α$. Results: Among 55 respondents, 52 (94.5%) worked in radiation oncology, and 38 (69.1%) were attending physicians. Most participants (83.6%) reported using TDD daily or several times per week. Mean (SD) scores were 3.89 (1.04) for usability and satisfaction, 3.43 (1.24) for perceived usefulness, and 3.80 (1.17) for impact and future use (5-point Likert scale). Overall satisfaction was positively associated with perceived time savings ($p < .001$). Participants reported variable time savings, with 27% estimating $\geq 10$ minutes saved per day. The questionnaire demonstrated excellent internal consistency (overall Cronbach's $α$ = 0.97).

Clinical pathways are disseminated as visual flowcharts where spatial topology, arrow direction, colour coding, and font weight encode critical triage logic that remains inaccessible to computational systems. We present PathWISE, a five-phase pipeline combining four LLM-based agents with a deterministic depth-first search auditor and a Java compiler critic, transforming these non-computable artefacts into validated, executable HL7 Clinical Quality Language (CQL) libraries deployable as FHIR CDS Hooks services. Purpose-built agents extract flowchart structure into a typed directed graph, perform deterministic path enumeration, conduct a structured semantic audit of every node's computability, generate terminology-constrained CQL definitions verified by the official Java CQL-to-ELM compiler, and produce routing logic covering 100% of enumerated patient journeys. Demonstrated across five UK NHS cancer pathways (colorectal, lung, skin, upper GI, and breast), PathWISE audits up to 183 nodes (182 under the Hybrid configuration), identifies 544 structured governance findings across four issue categories, achieves 100% syntactic compilation success, with UNCOMPUTABLE nodes receiving false placeholders that preserve compilability while surfacing governance gaps for clinical review, and produces zero hallucinated terminology codes for dictionary-covered concepts. Critically, PathWISE confines non-deterministic LLM inference to knowledge extraction while deterministic graph mathematics and a standard compiler underpin every verification step.

Urgent suspected colorectal cancer (CRC) referrals create operational bottlenecks because semi-structured clinical documents often require manual review and transcription. The original RAPTOR system used Large Language Models for structured extraction but relied on a separate OCR stage, making it vulnerable to handwriting, layout variation, and loss of visual evidence linkage. We present RAPTOR+, a multimodal extension that uses Vision-Language Models (VLMs) for end-to-end referral understanding. We evaluate fine-tuned VLMs, commercial and open-source zero-shot VLMs, and the original OCR-based pipeline on 223 clinically curated CRC urgent referral forms. We also introduce a grounding-aware evaluation framework that measures both extraction accuracy and evidence localisation. Results show a clear grounding gap in zero-shot models. Gemini 2.5 Flash achieved 92.6% Reading Accuracy but only 1.2% Strict Safety. In contrast, fine-tuned Qwen3-VL-8B achieved 96.1% Reading Accuracy and 60.6% Strict Safety, substantially improving verifiable evidence grounding. These findings show that task-specific fine-tuning is essential for reliable, auditable clinical document understanding. RAPTOR+ enables extracted referral decisions to be linked to visual evidence, supporting safer and more efficient cancer referral triage.

Pathological assessment guides lung cancer diagnosis, treatment selection, and prognostic evaluation, yet current CPath approaches rely on task-specific models for isolated objectives. Although pan-cancer foundation models offer versatility, they lack subspecialty-level depth and have not been evaluated across clinical workflows or prospectively validated in real-world settings. We introduce PulmoFoundation, a multi-center, prospectively validated, randomized controlled trial (RCT)-evaluated foundation model for comprehensive lung pathology assessment across pre-operative, intra-operative, and post-operative care. Built upon Virchow2 via subspecialty-specific pretraining using ~40,000 diagnostic H&E-stained whole-slide images (WSIs), PulmoFoundation was systematically evaluated on ~26,000 WSIs across 32 clinically relevant tasks. In addition to accurately predicting molecular markers and patient survival, our model achieves clinical-grade performance in core diagnostic tasks across biopsy, frozen section, and surgical resection slides. In a registered prospective study of 1,357 patients across 11 diagnostic tasks, our model achieved an average AUC of 92.3%. Using pre-specified triage thresholds, PulmoFoundation could reduce additional second-review burden for 68.8% of biopsies and 83.0% of frozen sections, and defer 44.5% of IHC stain orders, with PPVs of 1.0, 0.991, and 0.966. Beyond prospective validation, we conducted a crossover RCT with eight pathologists, in which AI assistance improved diagnostic accuracy across 4,928 case-reader pairs (91.7% w/ AI vs. 83.8% w/o AI). AI assistance also reduced median diagnostic time by 19.6%, increased diagnostic confidence by 8.7%, and improved inter-rater agreement from moderate (kappa = 0.56) to substantial (kappa = 0.76). Together, these evaluations support PulmoFoundation as a clinically validated decision-support system for lung pathology.

We evaluate whether clinician pairwise preferences provide a reliable signal of clinical safety in large language model (LLM) evaluation using expert feedback from MOOVE (Massive Open Online Validation and Evaluation), a clinician-led platform collecting blinded pairwise preferences alongside multi-criterion rubric ratings. Clinicians assign scores on a discrete $[-2, +2]$ scale, where negative values indicate clinically unsafe or misleading content. Using 26{,}804 pairwise judgments across outputs from 13 LLMs, contributed by more than 736 clinicians across 28+ countries, we find that clinician preference is a poor proxy for safety-critical performance. Models ranking highly under pairwise preference can still exhibit substantial rates of clinically meaningful failures ($\leq -1$) on dimensions such as \emph{Harmlessness} and \emph{Accuracy}. These failures are unevenly distributed across specialties, creating domain-specific ``no-go zones'' not visible in aggregate rankings or single-number leaderboards. We further analyze contributing factors including prompt length, refusal and escalation behavior, and the relative contributions of safety-critical versus surface-level features. A substantial fraction of preference votes carry no positive safety signal, while feature decomposition shows that surface-level characteristics explain slightly more preference variation than safety-critical rubric differences. Finally, we introduce a clinically adjusted preference ranking combining pairwise preference with rubric-derived feedback, producing a more safety-aware ordering than raw Bradley--Terry strength alone. Our findings support evaluation practices that separate preference from safety, report safety-critical failure rates directly, and incorporate clinically grounded adjustments when ranking LLMs for clinical decision making.

Clinical decision-making requires reasoning over incomplete, imprecise, and linguistically expressed patient narratives. While large language models (LLMs) excel at extracting latent information from natural language, they lack the verifiability and interpretability essential for trustworthy medical AI. We propose a neuro-symbolic reasoning framework that aligns LLMs with formal logic to enable explainable and formally verifiable medical diagnosis. Patient descriptions and clinical guidelines are embedded into a neural knowledge base, where LLMs extract structured medical entities, temporal relations, and fuzzy symptom patterns, which are decoded into a symbolic knowledge base expressed in fuzzy logic and declarative rules. We perform two-stage reasoning: (1) inductive symbolic generalization to capture diagnostic patterns from encoded narratives, and (2) inference verification via a logic programming engine to derive and validate diagnoses consistent with clinical standards. Each symptom is treated as a fuzzy predicate with probabilistic weights, and inference paths are auditable, adjustable, and compatible with physician feedback. Unlike purely statistical methods, our system supports iterative refinement: misalignment between LLM-generated diagnoses and ground truth can be traced, explained, and corrected through formal rules. By combining logic-based transparency, LLM adaptability, and probabilistic robustness, the framework enables human-aligned healthcare inference with strong generalization and verifiable, step-by-step reasoning chains. We validate our framework on public benchmarks, demonstrating effective reconciliation of symbolic reasoning and LLMs with real-world clinical narratives. Results show performance comparable to state-of-the-art LLMs, while additionally providing interpretable reasoning paths and formally verifiable diagnostic conclusions.

Effective pre-polysomnography screening for obstructive sleep apnea-hypopnea syndrome (OSAHS) requires combining clinical risk factors with visible craniofacial and neck cues. Directly prompting general-purpose multimodal foundation models for medical yes/no decisions can yield unstable, poorly calibrated outputs. We propose EviOSAHS, an evidence-grounded multimodal reasoning framework that separates image-only anatomical evidence acquisition from final clinical adjudication. Each frontal facial image is decomposed into seven fixed anatomical queries covering the neck, chin, mouth, face/neck fat, lower jaw, midface, and nose. Visual responses are converted into structured evidence cards recording target anatomy, visibility, risk direction, evidence strength, confidence, and a concise summary. These cards are combined with a cleaned clinical profile only in the final stage, where a large language model performs balanced binary screening adjudication. We evaluated EviOSAHS on a 642-subject cohort, mapping normal subjects to screening-negative and mild, moderate, or severe OSAHS subjects to screening-positive. EviOSAHS achieved 88.47% accuracy, 94.86% sensitivity, 93.74% F1-score, and a 5.14% false-negative rate, outperforming clinical-only prompting, direct multimodal prompting, and naive two-stage pipelines under a unified protocol. Ablations showed that seven-question visual decomposition and balanced final adjudication were critical to the high-sensitivity operating point. A question-level audit of 4,494 visual outputs showed a 100% structured parse rate and 93.88% high-visibility rate. EviOSAHS provides an auditable, high-sensitivity workflow for binary pre-polysomnography OSAHS screening, but should be viewed as a triage assistant rather than a diagnostic system. Prospective validation, external testing, and calibrated operating-point control are needed before clinical deployment.

A critical challenge facing clinicians managing chronic disease interventions is sustaining long-run patient health given limited information and resources. Digital therapeutics (DTs) provide a cost-effective way to manage interventions at scale through repeated interactions (e.g. daily treatment recommendations), but patient success is highly dependent on their adherence. Behavioral psychology suggests that both treatment recommendations and past adherence affect future adherence, yet existing decision support frameworks for DTs model only recommendation effects or treat adherence as exogenous context, leaving a key gap in model and algorithm development. To address this gap, we present a DT decision support framework that captures both recommendation and adherence effects, allowing clinicians to better plan treatment recommendations. We model a patient's time-varying capacity for engagement with treatment using a linear dynamical system (LDS) that captures both recommendation and adherence effects, endogenously connected to adherence behavior with a logit link. We establish finite-time identification guarantees for this model, extending LDS results to our setting. Next, we propose an optimism-based algorithm, UCB-BOLD, for online treatment selection and prove that it achieves sublinear regret. We evaluate UCB-BOLD against benchmarks via ablation studies on a synthetic patient cohort generated using micro-randomized trial data. DT decision support tools can include dynamical models to enable decision makers to efficiently use the data in DT settings to improve patient health through effective resource allocation. While myopic or heuristic approaches suffice for some patient types, the benefits of explicitly planning around recommendation and adherence effects are significant for others; UCB-BOLD achieves 2-3x lower conditional value-at-risk regret than the next-best benchmark.

Ventilator decision support requires sequential decisions that track evolving physiology and disease trajectories while respecting safety boundaries and clinician specific tuning styles. Rule based approaches rarely generalize personalization, and end to end reinforcement learning or single large language model systems remain difficult to control and audit. We propose the Ventilator Decision Support System (VDSS), a human in the loop multi agent framework that coordinates modular decision components through contract driven structured interfaces and produces traceable evidence for review. VDSS performs online preference adaptation with a contextual bandit, updating clinician specific preferences from the final accepted decision at each adjustment cycle and using them to guide subsequent recommendations. Structured rejection feedback triggers targeted replanning to reduce unproductive iterations and improve interaction stability. Retrospective ICU trajectory replay with expert review indicates higher recommendation acceptability and fewer interaction rounds to reach an acceptable plan, supporting clinically deployable human AI collaboration.

Machine learning methods provide a methodological innovation that can help screen for cardiovascular disease through noninvasive and readily available measurement modalities. Recent investments in using electrocardiogram (ECG) data to screen for structural heart disease (SHD) are one example, where ECGs provide a low-cost, available modality for screening. This has led to the EchoNext dataset, a paired ECG-echocardiogram data repository for testing new methods of SHD detection. However, relatively few studies have investigated how more probabilistic classification through Bayesian inference may improve uncertainty quantification in this setting. Moreover, few studies have considered how triage systems can be developed to alleviate healthcare bottlenecks, such as the review of data from underserved, rural clinics by expert sonographers for SHD assessment. In this study, we leverage existing ECG-echocardiogram data to compare frequentist and Bayesian neural network classifiers. We show that the Bayesian approach is comparable or better than frequentist methods in SHD classification, and that they have a more robust uncertainty quantification attached to them. We provide an example of how this uncertainty-aware classification scheme can be used for screening SHD, providing a proof-of-concept for how machine learning can help with triage in getting individuals expert sonographer input when SHD is highly likely or measurements are highly uncertain.

Large language models perform well on static medical examinations, yet clinical diagnosis often requires iterative evidence gathering under uncertainty. Building on prior interactive evaluation efforts, we introduce an OSCE-inspired standardized patient simulator and a controlled, reproducible benchmark for active diagnostic inquiry. Across 468 cases and 15 models in our protocol, we observe that multi-turn evidence seeking reduces diagnostic accuracy by 12.75% and lowers supporting-evidence quality by 24.36% relative to full-context evaluation; error analyses associate these drops with premature diagnostic closure and inefficient questioning. Together, these results suggest that static full-context benchmarks may overestimate performance in interactive evidence-seeking settings, motivating complementary interactive assessment for safer clinical decision support.

In pediatrics, patients, caregivers, and clinicians share responsibility for health decisions, but limited collaboration can undermine outcomes. We conducted a qualitative study examining decision-makers perceptions toward collaborative decision-making technologies, including interactive dashboards, VR simulators, and AI voice assistants. Findings reveal differences in user opinions across groups and indicate technology acceptance is linked to users trust of these technologies. Technology developers and researchers need to explore design and implementation strategies that build and facilitate trust or appropriate distrust between users and these novel technologies before these tools can effectively support collaborative decision-making.

Conformal triage converts predictive scores into deployment actions that either release a case, flag it for urgent attention, or defer it to human review. Under prevalence shift, however, the usual summaries of marginal coverage and human-review rate can miss the safety-critical question of whether patients who truly experience the target event are released without review. To address this gap, we introduce a leakage-aware deployment audit for release-side conformal triage. It first assigns target subjects to three non-overlapping roles: prevalence correction, conformal calibration, and held-out release-safety evaluation. This separation then lets the audit evaluate release directly: how many event-positive patients are cleared without review, whether the pilot has enough event labels for calibration, and how the safety-review trade-off shifts. Applying this audit to a retrospective NSCLC pilot shows why lower review can be misleading: after prevalence correction, the pooled conformal branch lowers review by releasing more patients, some of whom are event-positive. Within the audit, the classwise branch acts as a scarcity diagnostic: the pilot has too few event labels to certify safe low-review release.

Effective medication management in Parkinson's Disease (PD) is challenging due to heterogeneous disease progression, variable patient response, and medication side effects. While AI models can forecast levodopa equivalent daily dose (LEDD) as a measure of medication needs, standard uncertainty quantification often fails to communicate the reliability of these predictions, treating high and low confidence clinical decisions identically. We introduce CASCADE (Calibrated Adaptive Scaling via Conformal And Distributional Estimation), a novel conformal prediction framework that propagates epistemic uncertainty from a screening classifier to adapt downstream predictions. Unlike standard conformal methods that rely on auxiliary residual regression, we leverage epistemic uncertainty from a primary classification task (identifying whether a medication change is needed) to dynamically scale the prediction intervals of a secondary regression task (predicting how much change). By mapping Venn-Abers multi-probabilistic uncertainty directly to non-conformity scores, our framework achieves continuous risk adaptation. We demonstrate that this cascade effect produces highly efficient intervals for confident patients (38.9% narrower than standard conformal baselines) while automatically expanding intervals to ensure robust coverage for uncertain cases, bridging the gap between discrete clinical decision-making and continuous dose forecasting in PD.

Large language models (LLMs) and agentic systems have shown promise for clinical decision support, but existing works largely assume that evidence has already been curated and handed to the model. Real-world clinical workflows instead require agents to actively seek, iteratively plan, and synthesize multimodal evidence from heterogeneous sources. In this paper, we introduce ClinSeekAgent, an automated agentic framework for dynamic multimodal evidence seeking that shifts the paradigm from passive evidence consumption to active evidence acquisition. Given only a clinical query and access to raw data sources, ClinSeekAgent gathers evidence by querying medical knowledge bases, navigating raw EHRs, and invoking medical imaging tools; refines its hypotheses as new information emerges; and integrates the collected evidence into grounded clinical decisions. ClinSeekAgent serves both as an inference-time agent for frontier LLMs and as a training-time pipeline for distilling high-quality agent trajectories into compact open-source models. To validate its inference-time effectiveness, we construct ClinSeek-Bench, which pairs Curated Input reasoning from fixed pre-selected evidence with Automated Evidence-Seeking over raw clinical data. On text-only EHR tasks, ClinSeekAgent improves Claude Opus 4.6 from 60.0 to 63.2 overall F1 and MiniMax M2.5 from 43.1 to 47.3, with positive risk-prediction gains in 7 out of 9 evaluated host models. On multimodal tasks, ClinSeekAgent improves Claude Opus 4.6 from 47.5 to 62.6 (+15.1); all evaluated models improve across the three CXR-related task groups. We further validate ClinSeekAgent as a training pipeline by distilling agentic evidence-seeking trajectories into ClinSeek-35B-A3B, which achieves 34.0 average F1 on existing AgentEHR-Bench, improving over its Qwen3.5-35B-A3B baseline by +11.9 points and approaching Claude Opus 4.6.

Clinical decision support systems (CDSS) require scrutable, auditable pipelines that enable rigorous, reproducible validation. Yet current LLM-based CDSS remain largely opaque. Most "open" models are open-weight only, releasing parameters while withholding the data provenance, curation procedures, and generation pipelines that determine model behavior. Fully Open (FO) models, which expose the complete training stack end-to-end, do not currently exist in medicine. We introduce Fully Open Meditron, the first fully open pipeline for building LLM-CDSS, comprising a clinician-audited training corpus, a reproducible data construction and training framework, and a use-aligned evaluation protocol. The corpus unifies eight public medical QA datasets into a normalized conversational format and expands coverage with three clinician-vetted synthetic extensions: exam-style QA, guideline-grounded QA derived from 46,469 clinical practice guidelines, and clinical vignettes. The pipeline enforces system-wide decontamination, gold-label resampling of teacher generations, and end-to-end validation by a four-physician panel. We evaluate using an LLM-as-a-judge protocol over expert-written clinical vignettes, calibrated against 204 human raters. We apply the recipe to five FO base models (Apertus-70B/8B-Instruct, OLMo-2-32B-SFT, EuroLLM-22B/9B-Instruct). All MeditronFO variants are preferred over their bases. Apertus-70B-MeditronFO improves +6.6 points over its base (47.2% to 53.8%) on aggregate medical benchmarks, establishing a new FO SoTA. Gemma-3-27B-MeditronFO is preferred over MedGemma in 58.6% of LLM-as-a-judge comparisons and outperforms it on HealthBench (58% vs 55.9%). These results show that fully open pipelines can achieve state-of-the-art domain-specific performance without sacrificing auditability or reproducibility.

Pediatric critical care is a dynamic, high-stakes process involving constant monitoring and adjustments in life-saving treatments. Modeling these interventions is crucial for effective decision support. To address the challenges of high complexity and data scarcity in pediatric Extracorporeal Membrane Oxygenation (ECMO), we frame clinical decision-making as learning to act from trajectories, i.e., imitation learning that learns action models from observational data, with a key feature that actions are not directly observed. We consider TabPFN, a recent transformer-based approach for tabular data, and traditional baselines including XGBoost and Multi-Layer Perceptrons(MLPs) on real-world pediatric ECMO data to learn the action models. We find that the TabPFN-based approach consistently outperforms these classical baselines, supporting its use as a strong clinician-behavior baseline for pediatric ECMO decision support.

As large language models empower healthcare, intelligent clinical decision support has developed rapidly. Longitudinal electronic health records (EHR) provide essential temporal evidence for accurate clinical diagnosis and analysis. However, current large language models have critical flaws in longitudinal EHR reasoning. First, lacking fine-grained statistical reasoning, they often hallucinate clinical trends and metrics when quantitative evidence is textually implied, biasing diagnostic inference. Second, non-uniform time series and scarce labels in longitudinal EHR hinder models from capturing long-range temporal dependencies, limiting reliable clinical reasoning. To address the above limitations, this work presents the Probabilistic Chain-of-Thought Completion Agent (COTCAgent), a hierarchical reasoning framework for longitudinal electronic health records. It consists of three core modules. The Temporal-Statistics Adapter (TSA) converts analytical plans into executable code for standardized trend output. The Chain-of-Thought Completion (COTC) layer leverages a symptom-trend-disease knowledge base with weighted scoring to evaluate disease risk, while the bounded completion module acquires structured evidence through standardized inquiries and iterative scoring constraints to ensure rigorous reasoning. By decoupling statistical computation, feature matching, and language generation, the framework eliminates reliance on complex multi-modal inputs and enables efficient longitudinal record analysis with lower computational overhead. Experimental results show that COTCAgent powered by Baichuan-M2 achieves 90.47% Top-1 accuracy on the self-built dataset and 70.41% on HealthBench, outperforming existing medical agents and mainstream large language models. The code is available at https://github.com/FrankDengAI/COTCAgent/.

Sepsis management in the ICU requires sequential treatment decisions under rapidly evolving patient physiology. Although large language models (LLMs) encode broad clinical knowledge and can reason over guidelines, they are not inherently grounded in action-conditioned patient dynamics. We introduce SepsisAgent, a world model-augmented LLM agent for sepsis treatment recommendation. SepsisAgent uses a learned Clinical World Model to simulate patient responses under candidate fluid--vasopressor interventions, and follows a propose--simulate--refine workflow before committing to a prescription. We first show that world-model access alone yields inconsistent LLM decision performance, motivating agent-specific training. We then train SepsisAgent through a three-stage curriculum: patient-dynamics supervised fine-tuning, propose--simulate--refine behavior cloning, and world-model-based agentic reinforcement learning. On MIMIC-IV sepsis trajectories, SepsisAgent outperforms all traditional RL and LLM-based baselines in off-policy value while achieving the best safety profile under guideline adherence and unsafe-action metrics. Further analysis shows that repeated interaction with the Clinical World Model enables the agent to learn regularities in patient evolution, which remain useful even when simulator access is removed.

Inpatient medication recommendation requires clinicians to repeatedly select specific medications, doses, and routes as a patient's condition evolves. Existing benchmarks formulate this task as admission-level prediction over coarse drug codes with multi-hot diagnostic and procedure code inputs, failing to capture the per-timepoint, information-rich nature of real prescribing. We propose RxEval, a prescription-level benchmark that evaluates LLM prescribing capability by multiple-choice questions: each question presents a detailed patient profile and time-ordered clinical trajectory, requiring selection of specific medication-dose-route triples from real prescriptions and patient-specific distractors generated via reasoning-chain perturbation. RxEval comprises 1,547 questions spanning 584 patients, 18 diagnostic categories, and 969 unique medications. Evaluation of 16 LLMs shows that RxEval is both challenging and discriminative: F1 ranges from 45.18 to 77.10 across models, and the best Exact Match is only 46.10%. Error analysis reveals that even frontier models may overlook stated patient information and fail to derive clinical conclusions.

Clinical decision-support systems are expert systems whose recommendations clinicians act on directly, yet they are usually cleared on one aggregate accuracy number from a held-out test set. That number says nothing about input reliability under encoding shifts, subgroup gaps, threshold sensitivity, or operational feasibility. We present RISED, a pre-deployment evaluation framework operationalising five dimensions (Reliability, Inclusivity, Sensitivity, Equity, Deployability) through BCa bootstrap 95% confidence intervals, literature-grounded thresholds, and Holm-Bonferroni-corrected PASS / FAIL / INCONCLUSIVE verdicts; Equity is a proxy-dependence diagnostic rather than a gating test. Applied to seven cohorts spanning 35 years (n from 303 to 99,492), RISED surfaces failures invisible to AUROC: on Diabetes 130, Reliability passes by three orders of magnitude (PSS = 0.0004) while Inclusivity (AUC parity gap = 0.262) and Sensitivity (max threshold-flip rate 49.1%) fail decisively; both NHIS cohorts reproduce this. NHANES 2021-2023, with a complete feature profile, achieves INCONCLUSIVE verdicts; BRFSS 2024 produces the suite's most severe Sensitivity failure (max threshold-flip rate 64.2%) after instrument rotation removed hypertension and cholesterol. The pattern recurs on credit- and income-prediction cohorts, confirming domain-agnosticity; a multi-model check shows the failures are data-driven, not model-specific. RISED ships as an open-source Python package complementing TRIPOD+AI, FUTURE-AI, and Fairlearn with the structured numerical evidence those standards require but do not prescribe.

Clinical check-up reports are multimodal documents that combine page layouts, tables, numerical biomarkers, abnormality flags, imaging findings, and domain-specific terminology. Such heterogeneous evidence is difficult for laypersons to interpret and translate into concrete follow-up actions. Although large language models show promise in medical summarisation and triage support, their ability to generate safe, prioritised, and patient-oriented actions from multimodal check-up reports remains under-benchmarked. We present \textbf{Checkup2Action}, a multimodal clinical check-up report dataset and benchmark for structured \textit{Action Card} generation. Each card describes one clinically relevant issue and specifies its priority, recommended department, follow-up time window, patient-facing explanation, and questions for clinicians, while avoiding diagnostic or treatment-prescriptive claims. The dataset contains 2,000 de-identified real-world check-up reports covering demographic information, physical examinations, laboratory tests, cardiovascular assessments, and imaging-related evidence. We formulate checkup-to-action generation as a constrained structured generation task and introduce an evaluation protocol covering issue coverage and precision, priority consistency, department and time recommendation accuracy, action complexity, usefulness, readability, and safety compliance. Experiments with general-purpose and medical large language models reveal clear trade-offs between issue coverage, action correctness, conciseness, and safety alignment. Checkup2Action provides a new multimodal benchmark for evaluating patient-oriented reasoning over clinical check-up reports.

We introduce AcuityBench, a benchmark for evaluating whether language models identify the appropriate urgency of care from user medical presentations. Existing health benchmarks emphasize medical question answering, broad health interactions, or narrow workflow-specific triage tasks, but they do not offer a unified evaluation of acuity identification across these settings. AcuityBench addresses this gap by harmonizing five public datasets spanning user conversations, online forum posts, clinical vignettes, and patient portal messages under a shared four-level acuity framework ranging from home monitoring to immediate emergency care. The benchmark contains 914 cases, including 697 consensus cases for standard accuracy evaluation and 217 physician-confirmed ambiguous cases for uncertainty-aware evaluation. It supports two complementary task formats: explicit four-way classification in a QA setting, and free-form conversational responses evaluated with a rubric-based judge anchored to the same framework. Across 12 frontier proprietary and open-weight models, we find substantial variation in clear-case acuity accuracy and error direction. Comparing task formats reveals a systematic tradeoff: conversational responses reduce over-triage but increase under-triage relative to QA, especially in higher-acuity cases. In ambiguous cases, no model closely matches the distribution of physician judgments, and model predictions are more concentrated than expert clinical uncertainty. We also compare expert and model adjudication on a subset of maximally ambiguous cases, using those cases to examine the role of clinical uncertainty in label disagreement. Together, these results position acuity identification as a distinct safety-critical capability and show that AcuityBench enables systematic comparison and stress-testing of how well models guide users to the right level of care in real-world health use.

Anomaly detection methods can be very useful in identifying unusual or interesting patterns in data. A recently proposed conditional anomaly detection framework extends anomaly detection to the problem of identifying anomalous patterns on a subset of attributes in the data. The anomaly always depends (is conditioned) on the value of remaining attributes. The work presented in this paper focuses on instance-based methods for detecting conditional anomalies. The methods rely on the distance metric to identify examples in the dataset that are most critical for detecting the anomaly. We investigate various metrics and metric learning methods to optimize the performance of the instance-based anomaly detection methods. We show the benefits of the instance-based methods on two real-world detection problems: detection of unusual admission decisions for patients with the community-acquired pneumonia and detection of unusual orders of an HPF4 test that is used to confirm Heparin induced thrombocytopenia - a life-threatening condition caused by the Heparin therapy.

Inpatient clinical reasoning is a sequential decision under partial observability: the clinician sees the admission so far and must choose the next action whose downstream consequences are not yet visible. Existing clinical-LLM evaluations and RL rewards signals collapse this into closed-form retrieval, clinical journey leakage, or unanchored LLM-as-judge scoring. We introduce CLR-voyance, a framework that reformulates inpatient reasoning as a Partially Observable Markov Decision Process (POMDP) and supervises it with rewards that are simultaneously outcome-grounded and clinician-validated. We instantiate the formulation as CLR-POMDP, which partitions successful patient journeys into a policy-visible past and an oracle-only future. Using the past information, an oracle LLM generates a case-specific query-answer pair, and the first adaptive rubric for clinical reasoning which is verifiable in the future of the patient journey. These rubrics are used for both post-training and evaluation of models for inpatient clinical reasoning. We post-train Qwen3-8B and MedGemma-4B with GRPO followed by model merging, yielding state-of-the-art inpatient clinical reasoning while retaining generalist capabilities. CLR-voyance-8B achieves 84.91% on CLR-POMDP, ahead of frontier medical reasoning models like GPT-5 (77.83%) and MedGemma-27B (66.66%) and has comparable or better performance on existing medical benchmarks. To ensure a clinically meaningful setting, we conduct a large-scale clinician alignment study, where physicians curate per-case rubrics, grade candidate responses, and provide blinded pairwise preferences of model reasoning. This study provides insights on clinical LLM-as-a-judge and clinical preference-model selection, which can inform the community at large. CLR-voyance has been deployed for 6+ months at a partner public hospital, drafting thousands of reasoning-heavy inpatient notes.

Early identification of individuals at elevated risk of Chlamydia trachomatis infection may enable optimal use of molecular testing in resource-aware screening. We evaluate the feasibility of pre-test risk stratification (PTRS) using machine-learning models trained on routinely available, non-invasive clinical data. A curated dataset of 93 urine samples with PCR reference labels was analyzed using three feature groups: patient-reported history and symptoms, urine biomarkers from standard urinalysis, and their combination. Five supervised classifiers were evaluated using stratified 5-fold cross-validation with out-of-fold probability estimates. Performance was assessed using area under the receiver operating characteristic curve (AUC) and threshold-dependent metrics, with uncertainty quantified via bootstrap confidence intervals. Models using only patient-reported data showed moderate discrimination (AUC up to 0.72). Urine biomarker-based models demonstrated slightly lower peak discrimination but more consistent performance, with ensemble methods yielding the strongest results. Combining feature groups marginally increased the peak AUC and reduced performance variability across models, indicating improved robustness. Findings indicate that urine biomarkers provide a reliable predictive signal for PTRS that is complementary to patient-reported information, while feature integration enhances robustness. This work supports the integration of non-invasive, routinely available information for PTRS into screening workflows, including decentralized or home-based PCR contexts, to optimize testing prioritization.

We develop and evaluate a data-driven approach for detecting unusual (anomalous) patient-management decisions using past patient cases stored in electronic health records (EHRs). Our hypothesis is that a patient-management decision that is unusual with respect to past patient care may be due to an error and that it is worthwhile to generate an alert if such a decision is encountered. We evaluate this hypothesis using data obtained from EHRs of 4486 post-cardiac surgical patients and a subset of 222 alerts generated from the data. We base the evaluation on the opinions of a panel of experts. The results of the study support our hypothesis that the outlier-based alerting can lead to promising true alert rates. We observed true alert rates that ranged from 25% to 66% for a variety of patient-management actions, with 66% corresponding to the strongest outliers.

Activated PI3K8 Syndrome (APDS) is a rare genetic immune disorder caused by variants in PIK3CD or PIK3R1, with highly heterogeneous symptoms that often delay diagnosis. Early recognition is hampered by overlapping clinical presentations and limited clinician awareness, motivating systematic, data-driven approaches to detect APDS-associated phenotypic patterns in routine electronic health records. Traditional linear scoring systems cannot capture complex symptom interactions, while deep learning models, though expressive, often lack interpretability. To bridge this gap, we propose Shapley regression, a novel game-theoretic model replacing the linear predictor with a k-additive cooperative game, explicitly modeling co-occurrence of symptoms while maintaining the transparency and convexity of logistic regression. We carry out an empirical study of our lightweight method on eight public biomedical datasets, showing that a 2-additive model with $l_{2}$ regularization achieves an optimal trade-off between predictive power and noise robustness. We also apply it to a real-world cohort of 222 patients, on which Shapley regression accurately distinguished APDS cases from matched controls, confirming and validating phenotypes known to be associated with APDS, and facilitating the exploration of pairwise interactions between symptoms, validated by clinical experts.