Clinical Decision Support

In automated clinical coding, where the label space spans tens of thousands of diagnosis and procedure codes, models are currently evaluated against a single gold annotation, treating any deviation as error. But we find when two teams code the same 110 ACI-Bench encounters, they agree on only 73% of codes (Jaccard similarity) for the same note; even after an independent clinical audit removes erroneous codes, agreement rises only to 77%. Is that gap error or something systematic? We model the systematic component as coding style $ψ$, a coder- or site-specific policy over what to code and how much to document, and recast coding as $p(\mathrm{code}\mid\mathrm{note},ψ)$, estimating $ψ$ with a 10-dimension rubric. If style were noise, conditioning on it would do nothing. Instead, across five datasets a model conditioned with a data-matching style raises ICD F1 by up to 26 points and an extreme mismatched one lowers it by up to 21. Four prompt based coding methods spanning 39-49 F1 converge to 52-56 once style is supplied (All p<0.05). Much of what single-gold evaluation charges to model error is recoverable, unmodeled style.

Hallucinations can undermine clinician trust in LLMs, making it important that evaluation methods capture clinically relevant errors. Rubric-based evaluation has become the leading approach for assessing LLMs in medicine, but it is unclear whether rubric scores reflect such errors. We first study this in a controlled setting using MedHallu, finding that more specific rubrics better distinguish correct from hallucinated responses. To test this systematically, we develop a taxonomy of medical hallucination types and a clinician-validated error-injection pipeline that creates matched correct and error-injected responses. Across HealthBench, HealthBench Professional, and LiveMedBench, our clinically relevant hallucinations are missed by rubrics, often leaving scores unchanged. We find that rubrics are most effective when explicitly checking facts, and are less effective for additional or unexpected errors they do not anticipate. A preliminary retrieval-based factuality check recovers some of the rubric-blind errors, suggesting a complementary approach. These findings reveal systematic blind spots in current medical evaluation of LLMs and suggest that rubric scores alone are insufficient to establish clinical reliability, potentially undermining clinician trust and confidence in clinical deployment.

Generative artificial intelligence (AI) tools are increasingly accessible and have the potential to improve efficiency across clinical workflows. However, clinicians may also use non-institutional AI tools that are not provided, managed, or governed by their healthcare institutions, creating potential concerns related to privacy, security, accuracy, and clinician-AI interaction. Little is known about how clinicians currently use these tools for work-related tasks. We conducted a descriptive survey of clinicians recruited from the University of Arizona College of Medicine-Tucson and Banner University Medical Center-Tucson between May 20 and June 26, 2026. Participants reported their use of AI tool categories and the frequency with which they used AI for specific tasks across five workload categories: administrative work, clinical work, research, studying/continued education, and teaching. Forty-four respondents completed the survey. Forty-three respondents reported using AI for at least one work-related task during the preceding 6 months. Conversational AI and clinical decision support/diagnostic AI were the most used tool categories, each reported by 28 respondents. Administrative and clinical tasks demonstrated the most frequent use. AI was also used for higher-risk activities, including diagnostic assistance and clinical decision support. Non-institutional AI use was common among surveyed clinicians and extended across a broad range of work-related activities, including tasks with potential implications for clinical reasoning and patient care. Further research is needed to characterize how clinicians use these tools, how they evaluate AI-generated outputs, and how AI can be safely and effectively integrated into clinical workflows.

This work presents a proof of concept for auditable LLM-assisted medical billing verification based on a decision-basis contract. The contract separates deterministic checks of versioned fee-catalog rules from LLM-based assessment of free-text documentation. The deterministic layer resolves the applicable catalog release and checks code availability, quantity limits, and exclusions. The semantic layer classifies each claimed item as supported, contradicted, or missing required information. Support and contradiction require a verbatim evidence span; unavailable rule context, unsuccessful assessment, or missing required evidence prevents support through fail-closed abstention. We evaluated four locally run open-weight models on a synthetic catalog and 36 curated cases under the contract, an ablation without explicit documentation requirements, and an end-to-end baseline. Outcome agreement varied across models and showed no consistent advantage over the baseline. Explicit documentation requirements improved identification of missing information for all four models. The evidence gate also exposed cases in which correct raw judgments lacked valid evidence and were converted to incomplete decision-basis entries. The results show how explicit decision records can make rule findings, documentation judgments, and abstention reasons inspectable. Evaluation on real catalogs, independently annotated documentation, and with human reviewers is required to assess practical value.

Genetic Programming and its variants, such as grammatical evolution, are widely used in Symbolic Regression to derive mathematical expressions from multivariate data. In addition to predictive accuracy, models are appreciated for their potential to provide interpretability, offering explicit equations that relate input variables to outcomes. However, achieving interpretability and plausibility remains challenging, as evolved models may be complex or scientifically inconsistent. In this study, we explore whether Large Language Models, can assist in improving the explainability of Symbolic Regression models generated by evolutionary computation methods. Building upon our previous work on estimating body fat percentage using grammar-based Genetic Programming , we investigate the use of LLMs as post-processing tools to analyze and rank evolved expressions according to their interpretability and medical plausibility. Four symbolic expressions are analysed by three LLMs over three repeated runs, and the resulting interpretations and rankings are assessed by a panel of three clinicians. Across the three LLMs, comparative model-ranking outputs received more favorable clinician assessments than isolated term-level interpretations. However, the LLMs also produced physiologically and mathematically questionable explanations, indicating that they are better suited to comparative auditing under expert oversight than to autonomous validation.\blfootnote{The present work is an extended version of a paper submitted into a journal.

Clinical diagnosis agents must decide not only what test to request next, but also when to diagnose or defer. Existing agent benchmarks largely evaluate accuracy after fixed or unconstrained interaction, leaving autonomous stopping reliability implicit. We present Cros, a risk-constrained stopping layer combining state-wise error ranking, policy design on disjoint development splits, and LTT-style exact tests of selective diagnostic error and minimum autonomous coverage for complete sequential policies. Its finite-sample guarantee requires the candidate family, testing rule, and any randomization to be frozen before calibration labels are accessed. On a 1,834-episode MIMIC-derived abdominal-pain benchmark, the full ranker achieves exploratory state-error AUROC 0.853, compared with 0.715 for maximum class probability and 0.552 for the backbone's native stop score. On the previously viewed 367-episode evaluation split, analytically averaging over the frozen Cros weights yields 16.9% selective error at 78.8% coverage, cost 5.57, and 0.68 tests, versus 30.8% error at 100% coverage, cost 8.14, and 1.53 tests under native stopping. Forced continuation is non-monotone: error is 28.3% with HPI alone and 34.3% after full workup. However, the uniform-weight mixture ablation is cheaper on this viewed split despite missing the locked development margins, and Cros nominally satisfies the joint criterion in only 6 of 20 development resplits. Because evaluation labels were inspected during earlier development, these findings provide exploratory feasibility and audit evidence, not a confirmatory safety certificate.

Counterfactual audits are the standard tool for checking whether a clinical agent treats demographically distinct but clinically identical patients differently. They report a flip rate: how often an action changes when only the patient descriptor changes. We show that this quantity is uninterpretable on its own. Re-running an identical condition ten times over sixteen vignettes (same narrative, same descriptor string, nothing varied) moved a clinical agent's action in 8.7% of outcome-vignette cells, and instability was heterogeneous across actions by a factor of eight, from 0.022 for ICU escalation to 0.179 for controlled-substance caution. No demographic contrast in our data was distinguishable from that floor. A second model gives a pooled floor of 6.7% and ranks the six actions almost identically (Spearman 0.94, exact p=0.017), so the floor is not one system's artefact. Majority-vote aggregation over five draws removes 39% of it and then flattens, and a null simulation attributes the residue to heterogeneous per-cell rates, so replication mitigates without eliminating. Any counterfactual fairness estimate reported without a per-action floor beside it therefore cannot be read as evidence of disparity. The measurements were taken with FairMedAgent, an evaluation harness for disparity in the actions of clinical LLM agents whose estimand, the within-range counterfactual flip rate, counts only flips between actions a published decision rule admits and a clinician has adjudicated. That estimand requires band adjudication, which is under way; no disparity result is claimed here. Each synthetic vignette runs a six-stage trajectory (five model-facing decisions around a deterministic environment step) under fixed-form conditions spanning race, sex, age, insurance, English proficiency, and their intersections. The harness, the floor protocol, and every analysis script are released.

Large language models (LLMs) offer promising clinical decision support but remain vulnerable to hallucinated facts, unsupported recommendations, and citation errors. We present DIASENTINEL, a fully on-premise multi-agent system for one-year type 2 diabetes mellitus (T2DM) risk screening and guideline-grounded report generation from electronic health records (EHRs). The system integrates calibrated risk prediction, deterministic clinical signal extraction, Reciprocal Rank Fusion over American Diabetes Association (ADA) guidelines, and a hybrid verification layer combining rule-based checks with LLM entailment. The demonstration provides a real-time batch-screening dashboard and an interactive patient report interface with cited recommendations, verification results, and raw EHR comparison. DIASENTINEL demonstrates a practical framework for reliable, auditable, and privacy-preserving LLM-based clinical decision support.

Understanding how psychiatric patients subjectively experienced a clinical conversation is important for feedback and alliance-related process monitoring. While interviewers form post-session judgments about patient experience, these judgments do not always match patients' self-reports. Automatic approaches for predicting perceived interaction quality from conversation have been proposed, but it remains unclear whether such approaches can complement human judgment rather than simply replicate it. To address this gap, we evaluate a clinician-support framework in which post-session interviewer ratings are combined with automatic language-based predictions to estimate patient-reported interaction quality in free clinical interviews. We assess this integration across multiple standard model types, including Ridge, SVR, MLP, GRU, and BiLSTM, all trained on sentence embeddings extracted from dyadic transcripts of 107 free conversations between psychiatric patients and interviewers. Our results show that combining interviewer judgments with model predictions through simple averaging yields the strongest overall performance. The interviewer-only baseline reached a Pearson correlation of 0.365. Among fully automatic models, Ridge achieved the strongest Pearson correlation (r = 0.286), while BiLSTM achieved r = 0.270. The strongest result was obtained by BiLSTM interviewer integration (r = 0.403). Our findings suggest that automatic language analysis and interviewer judgment capture complementary aspects of patient experience and that their combination provides a more accurate approximation of the patient's own report than either source alone.

Offline reinforcement learning (RL) offers considerable promise for optimizing ICU treatment decisions, yet standard evaluation metrics Mean Squared Error (MSE) and Fitted Q-Evaluation (FQE) assess only behavioral imitation and cannot detect Toxic Mimicry, a failure mode in which agents replicate harmful patterns such as treatment withdrawal during comfort-care transitions. Using the MIMIC-III database, we propose the Counterfactual Clinical Audit (CCA) framework, which stress-tests RL agents through physiological perturbations anchored in Surviving Sepsis Campaign (SSC) guidelines. We audit a Medical Decision Transformer (MedDT) and a Historical Causal Transformer (HCT-RL), the latter employing Causal Action Shielding, propensity-based importance weighting, and Conservative Q-Learning. CCA reveals that MedDT paradoxically reduces vasopressor dosage as lactate escalates, contradicting resuscitation guidelines, while HCT-RL maintains physiologically consistent responses. These findings expose a systemic misalignment between statistical fit and clinical safety, supporting counterfactual audits as a necessary evaluation standard for medical RL.

Perioperative risk prediction models are often limited by narrow surgical populations, incomplete intraoperative data, poor calibration, and limited interpretability. We present a domain-structured ensemble framework for perioperative outcome prediction using routinely collected electronic health record (EHR) data. Predictors are organized into patient-related, surgery-related, and anesthetics-related domains. Domain-specific gradient boosting models generate independent risk estimates that are integrated through a logistic regression meta-learner. We demonstrate the framework using postoperative delirium (POD) in a case-control sample of 5,386 surgical encounters (2,693 cases, 2,693 controls) from a statewide health information exchange. POD required both delirium-related ICD codes and a positive Confusion Assessment Method screening within seven postoperative days; patients with preexisting dementia were excluded. The stacked meta-learner achieved AUROC 0.899 (95% CI: 0.891-0.906), precision-recall AUC 0.881, and Brier score 0.126, compared with AUROC 0.849 for the best single-stage model. Domain ablation showed improved discrimination and calibration over a surgery-only model (AUROC 0.879, Brier 0.140). Temporal validation on held-out post-2017 data yielded AUROC 0.915. Calibration was excellent, with intercept -0.006 (95% CI: -0.083 to 0.070) and slope 1.035 (95% CI: 0.982 to 1.088). Decision curve analysis, corrected for case-control sampling, showed positive net benefit across clinically plausible thresholds. The modular framework supports alternative outcomes, extension of predictor domains, and dynamic risk updating, providing a scalable foundation for interpretable, calibration-aware perioperative clinical decision support.

Estimating counterfactual outcomes over time from longitudinal observational data is central to clinical decision support. Existing methods rely on domain confusion -- adversarial training that renders representations invariant to treatment assignment -- yet this invariance creates a mutual information conflict: it suppresses treatment-correlated covariate signals necessary for accurate outcome prediction. We formalise this tension via a Jensen-Shannon divergence bound on counterfactual prediction error and develop two complementary models. CSSD (Causal State-Space model with Direct decoder) adapts selective State Space Models with a parallel multi-step decoder that eliminates accumulated rollout error by producing all prediction horizons simultaneously in a single forward pass. CSSPD (Causal State-Space model with Predictive regularisation and Direct decoder) augments CSSD with Contrastive Predictive Coding and Local Information Maximisation to reinforce temporal predictability in the balancing representation and recover local covariate information destroyed by domain confusion. On MIMIC-III, CSSPD achieves lower counterfactual RMSE than the Causal Transformer at every horizon tau >= 2 at O(T) encoder cost, with gains from 0.02 (2-step) to 0.07 (6-step). On Cancer Simulation across confounding strengths gamma in {0,1,2,3,4}, CSSPD outperforms CT at gamma <= 3 (margins 25.9%--37.0%), and CSSD achieves the lowest overall average RMSE (12.7% reduction over CT), confirming the MI conflict analysis. To our knowledge, this is the first work to formalise the balancing-prediction MI conflict and propose a structured resolution through complementary predictive and information-theoretic training objectives.

Clinical decision support is moving toward committees of language-model agents deliberating on a shared workspace. We ask whether such committees can be gamed by shortcuts, cues a benchmark rewards but a clinician would ignore. Across seven cohorts on six public datasets spanning text (MedQA-USMLE, MedMCQA, MIMIC-CXR reports), imaging (NIH ChestX-ray14, MIMIC-CXR-JPG, CheXpert) and tabular ICU records (SUPPORT2), Gemini committees resist these cues in isolation (flip 5-16%), yet a socially plausible shortcut spreads: when two peers assert the same wrong answer, the holdout under test adopts it in 38% of cases, as does a false "pre-screen" system flag, on both capability tiers. Of three oversight agents, a gate cannot separate adoption from honest agreement (false-positive rate 100%); a same-lineage judge reading only the transcript flags adoption on text (precision 100%, recall 93%) but collapses onto the gate in imaging; a referee that privately re-queries the holdout transfers to imaging (77-88% precision, 13-21% false-positive rate). Tripling a cue's visual salience does not move contagion, whereas a second peer voice raises it by half again. Gaming a hidden rubric is near-silent: only 1/10 text and 1/134 imaging drifters name the rubric they moved toward. What games a committee is social plausibility, and only a referee independent of self-report catches it. Code: https://github.com/criticaldata/benchmaxxing

Neuro-oncology decisions require coordinated interpretation of serial MRI, pathology, molecular markers, treatment history, performance status, and evolving guidelines. We present TumorBoard, a multi-agent decision-support system built around a shared longitudinal case state and an auditable claim-evidence ledger. Specialist agents for radiology, neuropathology, molecular diagnosis, guidelines, and therapy planning produce atomic claims with provenance. An adversarial critic exposes contradictions, and a safety governor releases, qualifies, or defers recommendations according to evidence sufficiency and temporal validity. On a 360-case hidden benchmark at a matched token budget, TumorBoard achieved an action F1 of 0.772 and evidence entailment of 0.914. It exceeded the strongest typed-council baseline by 3.1 percentage points (95% CI: 1.6 to 4.7, adjusted p = 0.0012), while recommendation-to-evidence coverage reached 0.927. Under evidence deletion, the system deferred 84.2% of unsafe cases and limited harmful recommendations to 5.8%. The safety governor reduced harmful release by 7.8 percentage points at a false-deferral cost of 4.3 percentage points. Ablation studies of the ledger, critic, and governor produced the predicted failure patterns, establishing structured coordination as the source of the measured multi-agent advantage.

Artificial intelligence (AI) is increasingly integrated into medical decision-making, yet its liability implications remain complex, particularly when physicians differ in diagnostic skills and their quality is unobservable. This paper develops a principal-agent model in which a social planner designs medical liability to regulate a physician with private quality information who chooses between a standard treatment, a personalized judgment-based treatment, or following an imperfect AI recommendation. Our analysis yields several novel insights. First, we show that the optimal mechanism under asymmetric information is surprisingly simple: a uniform, one-size-fits-all liability level for all physician types who deviate from the standard of care. Despite physician heterogeneity, this simple policy often achieves the full-information first-best outcome, particularly when standard care is reliable or AI is highly accurate. Second, the relationship between AI accuracy and optimal liability is non-monotonic. Contrary to common intuition, better AI does not always imply more relaxed liability. As AI accuracy increases, the optimal liability either decreases monotonically or follows an inverted-U pattern, depending on the uncertainty of the standard treatment. Third, asymmetric information does not universally reduce social welfare. Welfare loss arises only when standard care is unreliable and AI accuracy is too low; even then, its magnitude follows an inverted U-shape, initially increasing as AI complicates the regulatory problem, but declining as more accurate AI helps mitigate it. Finally, we find that information asymmetry is a double-edged sword in the presence of AI, and greater transparency does not benefit all stakeholders equally.

Vision-language models return structured chest-radiograph findings through interfaces exposing no confidence score, so a receiving institution cannot read off how far to trust an individual judgment. Whether agreement with an institution's reference standard transfers across sites, findings, prediction directions and question formats is largely unmeasured. We evaluated three generative vision-language models on three institutional chest-radiograph corpora and six findings under two elicitation protocols, comprising more than 345,000 finding-level predictions, and estimated finding-by-direction reference agreement at a receiving institution from a small budget of local labels. Estimation strategies were then stress-tested under repeated strict institution-held-out evaluation. Under evaluation excluding the receiving institution from development entirely, adaptive selection among the seven estimators that design admits did not improve on simple fixed alternatives: it achieved a mean Brier score of 0.1083, against 0.0853 for always using a Beta-Binomial empirical-Bayes estimator and 0.0855 for a target-only logistic model. Those two differ by 0.0003, less than this family's own sensitivity to a change of solver version, and each leads in about half the settings, so no default can be recommended. Their advantage over estimators pooling across institutions was concentrated at one site and not confirmatory once clustered by institution, and a plug-in empirical-Bayes posterior-predictive count interval at a nominal 95% level covered 87.0%, less at the hardest institution. Reference agreement therefore has to be re-evaluated per site and per interface; these results concern agreement with institutional labels, not clinical correctness.

Depression is a major mental disorder for which diagnosis relies primarily on clinical assessments. Automated methods to support its detection via the psychiatric MADRS scale are getting more and more attention. While existing solutions primarily focus on detecting the disorder from different text sources (e.g., online text, social media), there is still limited support for clinical trials, where clinical assessments are conducted through structured interviews based on standard guidelines such as SIGMA. In this work, we develop a LLM pipeline specifically designed to support clinicians in supporting the assessment of depression in patients enrolled in clinical trials. Our pipeline converts audio interviews into transcripts, maps them into the ten MADRS symptom items, estimates their severity, and identify problematic clinical ratings associated with them. Evaluation on real clinical interviews shows a strong overall correlation of 0.867 with expert ratings, providing interpretable support for future assessments in clinical trials.

LLM now pass medical licensing examinations and, in curated cases, can rival physicians at diagnostic reasoning. These developments have accelerated the use of LLMs for symptom assessment and clinical decision support in diagnostic and treatment guidance, administrative documentation, and rules-based alert enhancement. This Perspective concerns the most consequential of these applications: the autonomous triage of self-presenting, undifferentiated patients, with little or no clinician in the loop. For that task, the evidence of safety does not yet exist. The gap is not in medical knowledge but in the fidelity of clinical evaluation: a model optimized to continue the most probable text is not optimized to act safely when the safe answer is the improbable must-not-miss diagnosis. Safe triage is not the selection of the most likely diagnosis; it is a sequential decision under asymmetric cost, in which the single catastrophic miss outweighs many false alarms, and the decisive signal may be one the patient has not volunteered - and that the model has not been trained to seek. The core deficit is therefore one of information gathering under uncertainty. Under incomplete histories, LLM systems may fail to show the behaviors safe triage requires: broadening the differential; seeking the missing red flag; lowering the threshold for escalation; deferring judgement until sufficient information is obtained; and escalating concern where high-harm diagnoses remain unexcluded. These modes of failure for LLMs can be difficult to detect considering that evaluations to date often use complete, well-curated, confidence-gated simulations. The application of LLMs under these conditions may be amplified by assistant-like behaviors and positive bias, including credulity, agreeableness, and miscalibration - when these are not constrained by clinical triage logic.

Health AI is evolving from answering questions to agentic systems that converse with patients, reason about health records, and act on their behalf. Primary care guards against diagnostic errors and unsafe care; agents assisting in this domain warrant evaluation against the same risks. Current benchmarks focus on medical knowledge, assessed through isolated question-answering or clinician-facing tasks. PatientAgentBench benchmarks patient-facing agentic healthcare; it evaluates a foundation model, wrapped in an agent with a sandbox of healthcare tools, conversing with a simulated patient. Each conversation is scored by an LLM-as-a-Jury across six dimensions via over a hundred conversation-agnostic, clinician-grounded criteria. To validate alignment, licensed clinicians annotated shared conversations, yielding 79-93% adjacent agreement between jury and expert raters, on par with or exceeding clinician inter-rater agreement. We benchmarked 10 models across four families on the same 1,200 scenarios and found clinical gaps. Triage quality is the most discriminating dimension: pass rates rise from 32% for the weakest models to 88% for the strongest, with agents often acting on administrative requests without clinical screening. Clinical safety and workflow accuracy follow the same pattern: the weakest models fail often, fabricating unexecuted actions, while frontier models fail on only 1-3% of cases, from unverified tool outputs and omitted crisis resources in an emergency. More capable models narrow these gaps but do not close them; the strongest scores only 4.25 of 5 overall. These failures surface only in sustained, tool-using conversations against realistic patient records, confirming that static benchmarks are insufficient as healthcare agentic systems gain autonomy. We release the framework as a reproducible, clinician-validated evaluation standard to help the field close this gap.

The same episode of atrial fibrillation is a minor finding in a healthy adult and grounds for anticoagulation in an elderly patient with hypertension: identical signal, opposite decision. Naming the rhythm is only the start; what determines a patient's outcome is the judgement that follows -- what the arrhythmia is across the whole record, what it means for this patient, and what should be done about it. Recent work pairing large language models with the ECG stops short of this, reading one recording without assembling a patient-level finding; and agentic systems built around it either receive the arrhythmia a device has already detected or target a different diagnostic task, stopping before the decision this task requires. We formulate patient-level arrhythmia decision support as a task and present Cardiologent, a multi-agent system that spans it from detection to decision. An agent for each signal -- a single ECG lead and the photoplethysmogram a wearable acquires -- grounds its window reading in measured features rather than a bare label; the readings are assembled into the patient's rhythm profile and, with the patient's own data, reasoned against clinical guidelines retrieved for the case, with a critic checking each conclusion against the guideline it cites. We evaluate the clinical decision rather than the report, across integrated diagnosis, clinical significance, and urgency and management. Cardiologent scores highest on every axis, first on every patient-level task under both cardiologists and an at-scale LLM judge -- whose agreement with the cardiologists (ICC 0.74, 0.66) matches theirs with each other (0.67). Because each conclusion traces to a cited guideline and is validated against expert cardiologists, it yields decisions a clinician can audit rather than act on blindly -- a step toward use in continuous monitoring.

Long COVID (LC) poses a challenge for clinical decision support because relevant evidence is distributed across sources with different update cycles, evidentiary roles, and levels of clinical maturity. We present a clinician-facing chatbot that organizes four sources within a retrieval-augmented workflow: expert-curated consensus guidance, current PubMed literature, registered interventional trials, and evidence from living systematic reviews. Consensus guidance is always included to frame responses, while the remaining sources are retrieved in parallel when selected by the user. In an exploratory automated evaluation on 50 clinician-facing questions, our chatbot showed comparable mean ratings to OpenEvidence, with numerically higher scores and lower score variability in an LLM-judged comparison.

Machine learning models for medical image analysis typically lack a reliable measure of confidence, limiting their use in ambiguous or atypical cases. Here we show that Monte Carlo dropout, applied to a multi-task chest-radiograph classifier (eight thoracic findings, 137,593 training images), provides an epistemic uncertainty signal that tracks generalisation across training-set scales and flags confident yet error-prone predictions. Adding this signal to the point prediction raised error-detection AUROC from 0.74 to 0.77 ($Δ$AUROC +0.023, 95% CI [+0.014, +0.033]). In a controlled 2x2 factorial experiment, a clinical-decision-support agent exploited this uncertainty only when it was delivered as a binary error-risk flag rather than as raw scores, cutting confident misdiagnoses on unreliable findings from 8.5% to 2.7%. Epistemic uncertainty estimation thus carries decision-relevant information beyond point predictions, but its value for downstream agents depends on how it is communicated.

Readiness stress-testing of medical AI has focused on closed-ended and multimodal benchmarks. We extend it to open-ended clinical conversation under missing information, where safe behavior means recognizing absent information and qualifying, clarifying, or not over-committing - and where the evaluator becomes part of the measurement. We stress-test four models - three flagships (Claude Opus 4.8, GPT-5.5, Grok 4.3) and one mid-tier model (Gemini 3.5 Flash) - by deleting the latter half of the final user turn in HealthBench conversations, grading responses with a four-provider LLM-judge panel and a blinded clinician-anchored reference. Two evaluator-facing results are robust. First, judge choice materially changes apparent safety: inter-judge agreement is only moderate (Fleiss' kappa = 0.65), and after adjusting for each judge's general leniency (vote-level logistic regression), a positive same-provider association remains (exact permutation p = 0.04; GPT-5.5 ~ +0.10 on the probability scale) - large enough to change which model appears to over-commit least once its own-provider judge is excluded. Second, LLM judges are more permissive than clinicians on a blinded 50-item subsample: all four are significantly more lenient than the stricter independent clinician (crediting appropriate uncertainty on 66-84% of items vs 52%), and three of four than the author-influenced consensus (Grok directional only; judge-vs-consensus kappa = 0.20-0.43). On the author-audited clinical-underdetermined subset the permissiveness gap widened and the point-estimate model ordering held. A closed-ended MedQA anchor confirms accuracy is high and option-order effects are within a +/-5-point equivalence region for three of four models, so the safety gap is about calibration, not knowledge. We release the harness, prompts, per-item outputs, judge panel, perturbation audit, and human-annotation protocol.

Large language models (LLMs) are increasingly being explored for clinical decision support, but their reliability in complex oncology treatment planning remains unclear. We evaluated agentic LLM systems for breast cancer treatment recommendation generation using 72 real clinical cases across stages I to IV and 1,147 case-specific rubrics generated through Asymmetric Information Rubric Generation (AIRG), in which the rubric generator had access to real clinical decisions unavailable to the evaluated models. Seven pipelines were compared, including single-LLM baselines, tool-augmented systems, and multi-agent architectures with fact checking and autonomous subagent spawning. The best-performing configuration, Claude Opus 4.8 with the D&C+SA pipeline, achieved a global score of 0.594 $\pm$ 0.025. Tool use and increased agent autonomy had mixed effects, improving performance in some settings but degrading it in others. Performance varied by clinical domain and disease stage, and oncologist-led error analysis revealed persistent clinically relevant failures, including incorrect or missing recommendations, flawed justifications, citation errors, outdated claims, and overconfidence. These findings suggest that agentic LLM systems can generate clinically relevant breast cancer recommendations, but remain insufficient for unsupervised clinical use.

Neural networks increasingly guide decisions in high-stakes domains such as medical diagnosis, credit approval, and energy bidding. Audit in these settings requires case-level evidence: which training cases support an action and what outcomes they carried. Case-based decision theory (CBDT) formalizes this reasoning by aggregating outcome support from remembered cases. We show that an OLS action readout fitted on a fixed neural representation admits an exact case-based decomposition. Each action score is a weighted sum of training-case returns, with coefficients determined by empirical Gram geometry. We identify a sufficient regime for CBDT similarity semantics; outside it, the coefficients should generally be treated as signed Gram-geometric influence. The decomposition yields audit signals that trace scores to training cases, measure action coherence, and identify weak support. Across synthetic CBDT, PJM, Adult Income, and Default Credit tasks, the method recovers case-level preference structure and achieves the highest mean Top-30 consistency among compared attribution baselines, while remaining competitive on support reconstruction. The audit requires only fitting an OLS top-layer probe, without retraining the representation or accessing the original optimization trajectory; probe fidelity is measured by score reconstruction.

Mobile C-arm cone-beam computed tomography (CBCT) has been widely used for real-time intraoperative 3D imaging. However, current practice often mechanically applies the fan-beam CT criterion of "180° plus fan angle" in pursuit of "data completeness" in reconstruction. This review argues that, under the single circular trajectory of three-dimensional cone-beam geometry, complete data are mathematically unattainable; moreover, blindly increasing sampling may exacerbate the trade-off among intraoperative image quality (Q), imaging time (T), and radiation dose (D). Against this background, this review reframes the evaluation of intraoperative CBCT around "data sufficiency" rather than "data completeness." This perspective moves beyond the excessive pursuit of absolute mathematical and analytic accuracy, and instead emphasizes task-specific minimum image-quality thresholds required for clinical decision-making. By synthesizing evidence from multiple clinical scenarios, this review suggests that approximation errors can be acceptable when clinical decision-making requirements are satisfied, thereby achieving a Q-T-D balance.

We present LLM4SDM, the first study of open-source smaller language models (OS-sLLMs) for automated assessment of shared decision making (SDM) using the Observer OPTION12 framework. Unlike previous work that relies on large commercial models and the shorter OPTION5 instrument, our study focuses on privacy-preserving locally deployable models and Dutch melanoma consultation transcripts. Using expert-annotated clinical consultations, we evaluate three general-domain and two medical-domain OS-sLLMs during a development-phase pilot study. Results show that general-domain models outperform medical-domain models, which exhibit substantial hallucination and instruction-following failures. Gemma3:12b achieves the strongest agreement with human annotations (Pearson r=0.51, Spearman \r{ho}=0.59). Item-level and qualitative analyses reveal systematic challenges related to temporal discourse reasoning, conversational role attribution, and evidence grounding. We further introduce a Judge-LLM consensus framework designed to support disagreement resolution among multiple models. Our findings suggest that while current OS-sLLMs cannot replace human annotators, they offer a promising foundation for privacy-preserving human-in-the-loop SDM assessment.

Deploying Large Language Models (LLMs) in high-stakes clinical settings remains limited by structural hallucinations, weak deterministic reasoning over tabular patient data, and omissions in vector retrieval. This paper presents the architecture and validation of Medi-Gemma, a Clinical Decision Support System (CDSS) for wound pathology triage and workflow automation. The platform introduces a decoupled framework that separates clinical perception from data orchestration while preserving traceable reasoning. Medi-Gemma uses a multi-stage pipeline coordinated by a centralized ClinicalOrchestrator. Data requests are handled without generative inference by a DataManager that cleans unstructured Electronic Medical Record (EMR) files through type coercion. Natural language queries are processed by a hierarchical IntentRouter, which routes requests to deterministic analytics paths executed by a PandasQueryEngine or to patient-specific reasoning managed by a ClinicalRAGEngine using a CPU-optimized vector store. A key contribution is the Ground Truth Injection Module, which intercepts patient-specific queries, extracts numeric identification tokens, queries the structured dataframe via Pandas, retrieves the latest validated clinical state, and embeds this snapshot as an overriding context block in the LLM prompt before generation. Safety compliance is enforced by a deterministic ProtocolManager that maps clinical terminology to fixed evidence-based risk pathways, while a SafetyVerifier phrase filter prevents output rule violations. Validation shows that this architecture eliminates semantic context drift, prevents database compilation crashes, and improves factual adherence to backend clinical repositories. These results support Medi-Gemma as a safer pattern for LLM-based clinical decision support where structured data fidelity, retrieval grounding, and deterministic safeguards are essential.

Traditional Chinese Medicine (TCM) diagnosis, particularly through tongue inspection, faces persistent challenges in subjectivity and reproducibility. The application of multimodal artificial intelligence to TCM clinical tasks, such as syndrome differentiation and prescription generation, is significantly hampered by the semantic gap between visual tongue features and textual reasoning, as well as the lack of large-scale, standardized datasets. To address these challenges, we introduce MMIR-TCM, a novel framework that emulates the diagnostic process of TCM experts by integrating multimodal large language model(MLLM) with memory-augmented segmentation and retrieval-augmented generation (RAG). Employing a three-stage architecture, MMIR-TCM integrates a training-free Memory-SAM module for robust tongue extraction, a fine-tuned Qwen3-VL model for structured tongue diagnosis generation, and a Qwen3-based RAG component for evidence-grounded clinical decision support generation. The framework was developed and validated using MedTCM, a new large-scale multimodal dataset that we introduce specifically for advanced TCM research. To properly evaluate our framework's clinical accuracy, which existing metrics fail to capture, we also developed TDEU, a domain-specific evaluation metric incorporating semantic understanding and diagnostic importance. Our comprehensive experiments demonstrate that MMIR-TCM significantly outperforms leading models, including GPT-4o and Gemini 2.5 Flash.

Open-response evaluation provides stronger clinical validity than multiple-choice benchmarks but creates a scoring bottleneck that motivates automated LLM-asa-Judge approaches. Whether such evaluators replicate clinical calibration and caution, however, remains untested. We introduce MedQADE, the first standardised open-response clinical benchmark for German, a major clinical language lacking native evaluation infrastructure, comprising 3,800 items annotated by ten practising physicians and nine Large Language Model (LLM) evaluators. The top-performing evaluator model, Gemini 3 Flash, reached alignment consistent with the physician ceiling (\k{appa} = 0.694 vs. \k{appa} = 0.709), though wide confidence intervals limit interpretation. Despite this statistical alignment, automated evaluators exhibited near-absent clinical metacognition: physicians scaled abstention with item difficulty, while frontier models assigned definitive scores in every case. We additionally quantified systematic lineage-dependent biases, where models preferentially scored architectural siblings, an effect independent of language. These results show that statistical alignment does not ensure clinical caution, and that evaluator independence requires explicit verification.

Despite recent progress, the reasoning capabilities of large multimodal language models (MLLMs) remain fundamentally constrained by static supervision, where fixed prompts, rules, or reward models provide non-adaptive guidance throughout training. Such static signals are often sufficient to enforce output formats, but fail to shape the underlying reasoning process, leading to brittle generalization and performance saturation in complex decision-making tasks. We propose Evo-PI, a principle-centric learning framework that treats reasoning principles as explicit, language-based supervision signals that can be generated, evaluated, and iteratively evolved. Instead of relying on fixed rewards, Evo-PI enables a co-evolutionary loop in which principles guide model reasoning, while model behaviors in turn refine the principles that supervise them. This dynamic alignment mechanism allows supervision to progressively adapt to the model's reasoning deficiencies. We instantiate Evo-PI in medical visual question answering as a high-stakes testbed requiring structured visual-textual reasoning. Across eight benchmarks and multiple model backbones, Evo-PI consistently improves reasoning accuracy, achieving gains of up to 24.6%. Our results suggest that evolving principle-guided supervision offers a scalable and general paradigm for training expert-aligned reasoning in MLLMs. Code is available at https://github.com/zhengxianda/Evo_PI.

Autonomous AI systems are transitioning from advisory to autonomous roles for medication prescriptions. Recent United States bill H.R. 238 and Utah's prescription-renewal pilot both authorize AI to prescribe medications in an agentic capacity. While some regulatory guidelines suggest aggregate model performance metrics for clearance, they do not require i) calibrated per-prediction confidence for action-gated thresholds, ii) differentiated communication of uncertainty arising from model ignorance (epistemic) versus genuine clinical ambiguity (aleatoric), and iii) inferential transparency at the moment of decision that allows for liability allocation. Here, we present a regulatory and technical argument (tested with a survey of 136 U.S. prescribing clinicians) positioning these as minimum architectural requirements for safe autonomous prescribing. Our results suggest prescribing clinicians i) would not permit autonomous prescribing without a calibrated confidence-based escalation mechanism, ii) preferred a competing-options summary when uncertainty was aleatoric but shifted to abstention when uncertainty was epistemic, and iii) were only willing to accept additional liability when inferential transparency enabled a substantive judgment under acknowledged uncertainty. These findings indicate our recommended architectural features would encourage higher rates of clinician adoption, largely through collapsing much of what "autonomy" conventionally means. A system meeting these requirements would function less as an autonomous agent and more as a heavily supervised decision-support tool. As legislation and state pilots proceed, our technical argument backed by clinician perspectives provides opportunities for regulation to constrain the degree of autonomy ethically granted to AI in prescribing while aligning liability with the institutional actors who control system design and deployment.

Cryopathy syndromes are difficult to classify because laboratory patterns often overlap across diagnostic categories, while some diagnoses are rare. This makes routine interpretation of cryoglobulin-related tests challenging and increases dependence on expert judgment. The aim of this study was to develop and compare machine learning approaches for automated classification of cryopathy syndromes from laboratory data and to identify a practical strategy for clinical decision support. Methods: We analysed laboratory records from 2,686 patients assigned to 14 diagnostic categories. The dataset included demographic variables, cryoglobulin measurements, precipitation tests, and hemagglutinin and hemolysin titers. Data preprocessing included cleaning, encoding, imputation, normalization, and construction of clinically informed interaction features. We evaluated 12 modelling strategies, including Random Forest, Gradient Boosted Trees, Multi-Layer Perceptron, soft-voting ensembles, class balancing with Synthetic Minority Over-sampling Technique, hierarchical classification, period-aware models, targeted binary classifiers, and probability calibration. Performance was assessed using stratified train-test evaluation and stratified 5-fold cross-validation. The main metrics were macro-averaged F1 score, accuracy, Top-3 accuracy, and expected calibration error. The overall task proved difficult because of marked class imbalance and clinical overlap between diagnoses. The best multiclass performance was achieved by a soft-voting ensemble of Random Forest and Gradient Boosted Trees. Cross-validation confirmed stable performance for the balanced Random Forest model. Tree-based methods consistently outperformed the neural network model. Feature engineering improved discrimination, and the most informative predictors were derived cryoglobulin-based interaction features.

Clinical NLP increasingly relies on electronic health record (EHR) data to detect suicidal behaviors, treating clinical documentation as more reliable ground truth than social media. We argue that this framing obscures how EHR-based suicidality datasets encode a particular operationalization of suicidality, shaped by who authors the data, how episodes are bounded, and how ambiguity is resolved. We ground this argument in a case study of the ScAN dataset, built over MIMIC-III clinical notes. We show how governance constraints, ICD-based cohort selection, single-annotator labeling, and hospital-stay-level aggregation produce labels that reflect clinician-documented judgments, treat suicidality as a bounded episode, and assume that intent can be reliably inferred from documentation. A linguistic analysis demonstrates that identical labels subsume heterogeneous clinical framings differing in temporality, negation, and uncertainty. We argue that clinical NLP should examine the assumptions embedded in suicidality datasets before interpreting their labels as ground truth.

Large language models (LLMs) can make clinical decision support more accessible by interpreting free-text documentation, but their direct use as diagnostic engines is limited by sensitivity to prompts, information order, and plausible but incorrect outputs. Structured machine-learning models offer more stable risk prediction, yet they require tabular inputs that are difficult to integrate with narrative clinical workflows. We present ClaMPAPP (Clinical Language-assisted Machine-learning Pipeline for Appendicitis), a hybrid system that uses an LLM as an interface rather than as the final decision-maker. ClaMPAPP extracts schema-constrained clinical features from note-like narratives, applies deterministic plausibility checks, and passes validated features to an XGBoost classifier trained on clinical, laboratory, and ultrasound variables. We evaluated ClaMPAPP on two independent pediatric appendicitis cohorts from German hospitals and compared it with end-to-end LLM baselines, including open-source and proprietary models. To preserve ground truth while testing free-text input, narratives were generated from structured electronic health records through template rendering and constrained LLM rewriting, with additional sentence-order permutation to assess positional robustness. ClaMPAPP achieved the strongest overall diagnostic performance in both internal and external validation while minimizing missed appendicitis cases, the key safety concern in acute triage. End-to-end LLMs showed unstable sensitivity-specificity trade-offs and greater degradation under narrative reordering. These results support an LLM-as-interface, ML-as-predictor design that separates natural-language usability from predictive inference and provides a more auditable pathway for clinical decision support.

Clinician-centered evaluation is critical for validating medical AI systems, especially in ultrasound imaging where quantitative metrics do not always capture clinical usability. Existing medical image platforms primarily focus on dataset labeling. They lack integrated support for blinded model comparison and reproducible evaluation workflows. We present a clinician-centered pipeline for remote annotation and evaluation in ultrasound AI studies. The proposed pipeline uses a centralized server and lightweight browser interfaces to enable clinicians to perform annotation, blinded ranking, and review without local dataset downloads. The pipeline also supports multi-rater participation, centralized result aggregation, and automated statistical analysis. We validate the pipeline in a fetal ultrasound segmentation study with six raters spanning expert, generalist, and non-expert experience levels. The system automatically generated Spearman correlation, Kendall's $τ$, and top-1 selection statistics. Results indicated moderate to strong agreement across experts and other groups. The blinded evaluation results showed a tendency for later active learning models to be preferred. These outcomes suggest that the pipeline can support clinician-centered annotation and reproducible human-\ac{AI} evaluation studies in ultrasound imaging. The proposed pipeline is available on \href{https://github.com/13204942/SonoRate}{GitHub}.

Medical AI has shifted from reasoning to agentic AI, a new paradigm that autonomously invokes external tools during reasoning, rendering intermediate reasoning steps and tool outputs transparent to users. Although proven to outperform previous models, physician trust in agentic AI remains largely unexplored. To address this, three physicians evaluated 315 multimodal clinical cases quantifying both process-oriented cognitive trust and outcome-oriented behavioral reliance. Comparing agentic AI against non-agentic baselines, physicians exhibited significantly higher cognitive and behavioral trust for the agentic model (P < 0.001). Specifically, on treatment planning tasks, physicians trusted the agentic reasoning most, preferring it in 89.57% of cases. Furthermore, process-oriented cognitive trust is significantly associated with outcome-oriented behavioral reliance (P < 0.001). However, measurable over-reliance on incorrect agentic outputs still exists, highlighting the inherent limitations of decision-logic transparency alone and underscoring the continuous need for rigorous clinician oversight.

Clinical decision support AI systems (CDSASs) must adapt to evolving patient conditions in real-time while adhering to strict safety constraints. We present an online adaptive framework that integrates Treatment Effect (TE) estimation to quantify clinical benefits, a patient Digital Twin (DT) to simulate treatment trajectories, and Reinforcement Learning (RL) for sequential decision-making. The AI system is initially trained on historical medical records and operates in a continuous learning loop. To ensure safety, a rule-based module monitors vital signs and blocks contraindicated treatments. Cases with strong internal model disagreement are flagged for clinician review, simulated in our experiments via a pre-trained outcome model. We validate our framework using both a synthetic clinical simulator and a real-world ovarian cancer dataset from The Cancer Genome Atlas (TCGA). In both simulated and clinical settings, our method demonstrated superior effectiveness and stability in recommending treatments compared to standard computational baselines. Furthermore, the AI system maintains low latency and requires expert consultation for only a minority of cases in our experimental validation, demonstrating its potential as a safe, clinician-supervised tool for personalized medicine that continuously improves through practical use.

Delirium is common in hospitalized patients and is often missed in routine care. We present a user-centered interactive machine learning (UC-iML) framework for delirium detection support that combines physician-guided feature refinement with interpretable modeling. Using 3,862 labeled admissions from six Toronto hospitals in the General Medicine Inpatient Initiative (GEMINI), we integrate administrative variables, laboratory results, medications, and a radiology-derived text indicator. Physicians guide feature refinement and model evaluation, and Shapley Additive exPlanations (SHAP) are used to summarize feature attribution. We evaluate standard supervised classifiers with temporally separated holdout testing and a later-phase validation cohort. Compared with automated and baseline variants, the proposed framework shows better overall discrimination and stronger temporal robustness, while the explanations highlight clinically meaningful signals. These results support UC-iML as a practical human-in-the-loop framework for clinically relevant delirium modeling.

Predictive modeling for clinical decision support requires both strong predictive performance and transparent, auditable, and human-reviewable decision logic. Although deep learning and tree-based ensemble methods can achieve high accuracy, their black-box nature remains a major obstacle to trustworthy clinical deployment. Moreover, clinical prediction often operates under practical constraints, including limited sample sizes, severe class imbalance, and feature evolution arising from changes in diagnostic criteria or clinical documentation practices. We propose Medical Heuristic Learning (MHL), a constrained paradigm for LLM-assisted rule learning. Rather than relying on updates to implicit model weights, MHL integrates statistical probes, medical knowledge probes, initial rule synthesis, and iterative rule optimization to construct an executable rule-based expert system. The resulting rule system is expressed entirely using the native logical and control-flow constructs of a programming language. Valid rule versions are recorded and retained along the search trajectory, making the decision logic explicit, interpretable, and auditable. MHL also supports continual learning by using previously validated rules as a starting point and iteratively revising them in response to updated feature information under data drift or feature evolution. MHL is not tied to any specific programming language. Comprehensive experiments on medical datasets show that MHL achieves predictive performance comparable to that of state-of-the-art methods, performs favorably in small-sample and highly imbalanced settings, and supports the transfer and adaptive revision of validated rules under feature evolution. Overall, these findings suggest that non-gradient-based heuristic systems offer an approach to balancing predictive performance and transparency in clinical decision support.

AI Scientist agents are often evaluated as if capability were mainly a function of model quality, prompting, or reasoning scaffolds. We test a different hypothesis in drug-asset valuation: for knowledge-intensive scientific decisions, the limiting factor is often the evidence substrate the agent can access. We run a controlled three-arm ablation on a production valuation agent: A is a plain web-only LLM analyst, B adds public structured tools plus a 14-dimension valuation playbook, verifier, objectivity policy and red-team, and C adds the proprietary Noah AI corpus of curated pipeline, trial and deal intelligence. Across a 13-asset stratified benchmark, B improves calibration and audit discipline: tier-in-range accuracy rises from 0.80 to 0.89 and objectivity from 3.16 to 3.30. But B does not remove the factual ceiling. Under capability-superset accounting, A and B recover only 0.25 and 0.38 of the curated gold competitive record, while C recovers 0.96; on the curated long-tail subset, C reaches 0.93 vs. 0.26/0.30. Raw blind-panel decision quality is similar for A and B (7.01 vs. 6.96), so we introduce completeness-aware decision utility: informed decision-quality = decision-quality x gold-coverage. On this metric, C reaches 7.43 vs. 1.76/2.57 for A/B. Even a perfect non-proprietary-data report would be capped at 3.83 by B's coverage. The result is not that reasoning scaffolds are unimportant; they improve calibration and discipline. Rather, proprietary evidence sets the upper bound of what the AI Scientist can know and therefore decide.

Large language models (LLMs) are increasingly used for medical summarization, but their outputs can omit medically important information and introduce unsupported claims. Existing error-detection methods produce heuristic or uncalibrated scores, providing no formal control over missed errors and no principled way to trade off safety against clinician review burden. We introduce Conformal Assessment for Risk Evaluation (CARE), a post-hoc, model-agnostic safety layer that uses conformal risk control to overlay calibrated omission and hallucination flags onto summaries from any LLM without retraining. CARE provides finite-sample, distribution-free guarantees through two controllers: a hallucination controller that bounds the probability of a document containing any unflagged hallucinated sentence, and an omission controller that bounds the expected fraction of important omissions not surfaced for review. Unlike hallucination detection, omissions depend jointly on whether a source sentence is important and whether it is covered by the summary. We show that calibrating only one dimension can violate the target risk bound, while marginal decompositions remain valid but overly conservative. By jointly calibrating over the full $(τ,γ)$ threshold space, CARE preserves formal guarantees while surfacing up to 5$\times$ fewer sentences than alternative calibrated baselines. Across five medical summarization tasks, CARE satisfies the target risk bound at $α= 0.15$ with 95% confidence across 100 calibration/test resplits, using only ~100 labeled documents per domain. In a preliminary clinician study (75 document reviews), calibrated flags improved omission detection by 28.6 percentage points on average. These results show that sentence-level safety guarantees are feasible for LLM-assisted medical summarization and offer a tunable mechanism for balancing residual risk and review effort.

Clinical AI evaluation increasingly delegates scoring to large language models (LLMs) acting as AI raters, yet their scoring behavior across evaluation conditions has not been quantitatively characterized. We address this gap through a factorial study of AI rater behavior in adult type 2 diabetes (T2D) pharmacotherapy at 12-month outpatient follow-up, a clinical task involving complex decision-making operationalized across seven evaluation questions. Four open-source LLMs served simultaneously as clinical decision support system (CDSS) models and AI raters. Each CDSS output was scored under two scoring protocols: a rubric-anchored Gold Rubric (GR) protocol incorporating a patient-specific rubric, and a rubric-free Non Gold Rubric (Non-GR) protocol. Linear mixed effects models crossed the scoring protocol factor with five design factors -- CDSS model, CDSS prompt configuration (document-referenced generation [DRG] vs.\ Baseline), rater model, prompt character, and prompt type -- and estimated main effects together with their protocol interactions. Across all questions, AI raters yielded consistently higher scores within a very narrow range (74--78 points on average) under Non-GR compared to those under GR (7.69 to 49.64 points lower mean scores; 1.68 to 3.67 times wider interquartile ranges). Within each question, GR amplified the AI rater's discrimination between DRG and Baseline CDSS outputs by factors of 1.76 to 5.10, while also revealing substantial behavioral variation across rater models that Non-GR suppressed. These findings support rubric anchoring as the scoring protocol that preserves discriminative power in clinical AI evaluation; rubric-free scoring cannot substitute when questions require patient-specific or jurisdiction-specific criteria that rater models cannot infer from parametric knowledge alone.

Medical imaging is central to modern diagnostics, and artificial intelligence (AI) systems are increasingly used to support image-based analysis by improving efficiency, accuracy, and access to care. However, inequities in healthcare access and differential disease prevalence create severe demographic imbalances in clinical image data. Such imbalances are compounded by the fact that diseases can manifest with distinct features across demographic groups, rendering certain phenotypic presentations naturally rare. AI models trained on such imbalanced data risk perpetuating diagnostic bias and widening healthcare disparities. Here we introduce FairGen, a fairness-aware diffusion framework that synthesizes demographically balanced medical images while preserving pathology-relevant visual features. By embedding physician-aligned preferences into the generation process, FairGen improves subgroup coverage during synthesis and downstream classification. Applied to dermatology, radiology, and neuroimaging benchmark tasks, FairGen achieves fairness improvements of 95.9% for skin images, 80.0% for chest radiography, and 35.2% for brain MRI, while maintaining competitive diagnostic accuracy relative to models trained on original clinical data. Clinician-facing expert review and external validation on independent cohorts further support that these gains extend beyond standard fidelity metrics and are not confined to the original in-distribution datasets.

Managers in manufacturing settings rely on digital interfaces to interpret operational data for decision-making, but growing data volume and complexity can make relevant insights difficult to identify efficiently. While dashboards remain dominant in industrial contexts, Large Language Model (LLM)-based conversational agents (CAs), accessed through conversational user interfaces (CUIs), may provide more direct access to such data. However, their effectiveness may depend on the information-processing demands of the task. This study compares an LLM-based CA delivered through a CUI with a dashboard in a manufacturing decision-support scenario. In a mixed factorial experiment with a 2x3 design, 134 industrial decision-makers were assigned to one interface condition and completed three tasks of increasing complexity. We examined perceived Mental Workload (MWL), decision accuracy, completion time, and intended reliance, and tested self-reported data literacy as a moderator. Results showed that the CUI reduced perceived MWL overall and supported faster completion in less demanding tasks, but both advantages diminished as task complexity increased. Neither interface produced a consistent overall advantage in decision accuracy, and the CUI was not preferred as a sole basis for subsequent decisions. Furthermore, data literacy did not reliably moderate interface effects. These findings indicate that conversational interaction offers conditional rather than universal benefits for industrial decision support. LLM-based CAs may reduce information-access effort, whereas complex decisions continue to benefit from persistent, inspectable visual representations.

Clinical decision-making (CDM) is central to real-world clinical workflows, where clinicians infer diagnoses, select treatments, or anticipate future health outcomes under incomplete evidence. LLMs are increasingly used to support these decisions due to strong language capabilities, broad biomedical knowledge, and efficiency, yet the reliability of LLMs on real-world clinical decision tasks remains insufficiently understood. To evaluate CDM models, especially LLM-based models, an ideal and practical medical decision benchmark should be constructed via an automated yet reliable pipeline to ensure both scale and quality. Moreover, the grounding of a CDM benchmark in real patient EHRs can better support evaluation on practical CDM tasks that require substantive biomedical knowledge and clinical inference. To fill the gaps, we introduce EHRBench, an automated and reliable EHR-grounded benchmark for evaluating LLM-based clinical decision-making at scale. To ensure scalability and reliability, EHRBench is constructed through an EHR-LLM-KB(knowledge-base) interaction pipeline. For efficiency, we use a specialized LLM to automatically convert encounter-level EHR trajectories into structured templates and deterministically instantiate the templates into QA items. In parallel, we apply systematic KB-based verification and enrichment to filter hallucinated or ambiguous relations and to improve reliability. Using this pipeline, we construct nearly 1M (960,067) QA items spanning three core inference-required clinical decision tasks: diagnosis, treatment, and prognosis. We benchmark more than 30 representative LLMs on EHRBench and provide detailed analyses of performance and robustness. The results show consistent capability trends across settings, further validating the reliability of EHRBench and highlighting actionable gaps toward clinically reliable LLM systems.

Clinical foundation models are evaluated with factual or exam-style medical QA, but treatment decisions must change when patient context changes. We introduce ClinPivot, an auditable treatment-decision benchmark built from biomedical relations and pivoted patient contexts. ClinPivot asks whether models change treatment choices when new clinical constraints shift the action space. We find that strong medical QA performance does not reliably predict decision-making performance: frontier models and task-adapted Qwen variants often fail to change decisions correctly, and model rankings shift across evaluation regimes. Decision-structured supervision improves pivot-sensitive decision-making and medical QA under matched knowledge budgets, while lightweight replay reduces losses in general assistant ability.

Humans increasingly make decisions with AI assistance; for example, doctors may follow AI-recommended diagnostic tests and base their diagnoses on the results. A natural question is which tests should AI recommend to balance short-term decision quality and long-term human learning when different features (e.g., test results) are correlated. While prior work establishes that stationary policies that recommend the same tests repeatedly are optimal when features are independent, we prove that feature correlations lead such policies to perform arbitrarily poorly. Instead, we prove that any optimal policy must follow an explore-then-commit structure; initially, the AI should offer diverse tests so humans can learn accurate feature coefficients, then the AI should commit to a single set of tests, with exploration length that depends on the degree of feature correlation. We prove that computing the optimal policy is NP-hard and derive a dynamic programming-based algorithm that finds the optimal policy for finite horizons. We additionally develop an approximation that plans for shorter horizons and appends a stationary suffix, achieving near-optimal performance. Our empirical results complement our theory by showing that stronger feature correlation leads to longer exploration phases.

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.

Speech and language technologies offer valuable opportunities for supporting mental health assessment through objective and interpretable cues. We present a systematic feature-based analysis framework leveraging perceptually grounded acoustic and linguistic characteristics, including prosody, vocal quality, semantic coherence, syntactic structure, and sarcasm. Using statistical analysis and interpretable machine learning (XGBoost with SHAP and LIME), we examine associations between speech features and validated symptom measures of depression, anxiety, and ADHD. Evaluated on both controlled benchmark datasets (StressID, DAIC-WOZ, Androids, EATD) and a real-world clinical dataset, the framework reveals stable and consistent relationships between symptom severity and vocal irregularities (e.g., shimmer, jitter), lexical-syntactic patterns, and affective tone. An ablation study conducted across all datasets further identifies the most informative feature groups. This work explores a transparent and clinically interpretable approach to speech-based mental health analysis.

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.

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.

Clinicians are expected to disclose harmful medical errors to patients and families in line with ethical, regulatory, and patient care standards, yet these conversations remain challenging because of their emotional complexity and limited training opportunities. Most physicians still learn primarily through lectures and observation, while static video tools-though available-are underused, lack adaptability across specialties, and deliver delayed, generic feedback. These gaps restrict skill development, reduce self-efficacy, and contribute to avoidance of disclosure conversations, ultimately compromising patient care and eroding trust. To address these needs, we designed CandorMD -- an AI-assisted simulation system that provides real-time practice, actionable feedback, and diverse practice environments tailored to individual learning needs. We conducted semi-structured interviews with physicians, risk managers, patient advocates, and communication experts to understand current practices, identify gaps, and collect feedback on CandorMD. Based on these insights, we present findings and design recommendations for the future of AI-supported medical communication training.

Large language models (LLMs) are increasingly explored for clinical decision support, yet most evaluations are conducted in English, leaving their reliability in other languages uncertain. Here we evaluate the impact of prompting language on diagnostic reasoning and final diagnosis accuracy by comparing English and French performance across five LLMs (o3, DeepSeek-R1, GPT-4-Turbo, Llama-3.1-405B-Instruct, and BioMistral-7B). A total of 180 clinical vignettes covering 16 medical specialties were assessed by two physicians using an 18-point scale evaluating both diagnosis accuracy and reasoning quality. Four of the five models performed better in English (mean difference 0.37-0.91, adjusted p < 0.05), with the gap spanning multiple aspects of reasoning, including differential diagnosis, logical structure, and internal validity. o3 was the only model showing no overall language effect. These findings demonstrate that prompting language remains a critical determinant of LLM clinical performance, with implications for equitable linguistico-cultural deployment worldwide.

Medicine is inherently pluralistic. Principles such as autonomy, beneficence, nonmaleficence, and justice routinely conflict, and such ethical dilemmas often sharply divide reasonable physicians. Good clinical practice navigates these tensions in concert with each patient's values rather than imposing a single ethical stance. The ethical values that large language models bring to medical advice, however, have not been systematically examined. We present a framework for auditing value pluralism in medical AI, comprising a benchmark of clinician-verified dilemmas and an attribution method that recovers value priorities directly from decisions. The ecosystem of frontier models spans physician-level value heterogeneity, and models discuss competing values in their reasoning (Overton pluralism) before committing to a decision. However, individual model decisions are near-deterministic across repeated sampling and semantic variations, failing to reproduce the distributional pluralism of the physician panel. Across benchmark cases, these consistent decisions reflect committed, systematic value preferences. While most model priorities fall within the natural range of inter-physician variation, some significantly underweight patient autonomy. A single LLM deployed without regard for its value priorities could amplify those priorities at scale to every patient it serves. Without explicit efforts to balance ethical perspectives with one or multiple models, these tools risk replacing clinical pluralism with a deployment monoculture.

Patient-managed Personal Health Records (PHRs) promises to empower patients to better understand their health; but information in the record is complex, potentially hindering insights. In this study, we assess the potential of large language models (LLMs, Gemini 3.0 Flash) to provide helpful answers to user health queries, when provided clinical data from PHRs as context. A total of 2,257 user queries were drawn from 3 different distributions to represent patient questions: shorter web search queries, longer questions derived from templates of chatbot conversations, and questions patients asked to their healthcare team (patient calls). Queries were matched with de-identified PHRs (from a pool of 1,945). Gemini responses were generated (1) without PHR context; (2) with a basic summary of demographics, conditions, and medications; (3) with full, extensive clinical notes. For evaluation, we leveraged an existing rating framework (SHARP), and developed a new framework for specific error modes when interpreting PHRs. Evaluation was performed using autoraters for the full set, and with clinician ratings for a subset (n=95), with both sets of raters knowing the full PHR context. We see significant improvements in the helpfulness of answers to all question types with PHR data (p < 0.001, paired t-test). We also observe potential gains in safety, accuracy, relevance and personalization of answers. Our PHR evaluation framework further identifies gaps in LLM understanding of particular aspects of complex PHRs, such as temporal disorientation, and rare but meaningful confabulations. These results suggest potential for PHR data to help people with a wide range of user needs; and provide a framework for monitoring for gaps in LLM answers based on PHR context. This study motivates further work to assess and realize potential benefits to users from understanding their health records.

Vision-language models (VLMs) are increasingly proposed for clinical decision support, yet their reliability in real-world scenarios that require integrating both visual and textual context from medical records remains poorly characterized. This paper identifies three failure modes: (1) modality over-reliance on text over images, (2) spurious reliance on irrelevant clinical history, and (3) prompt sensitivity across semantically equivalent inputs. We evaluate a diverse set of general-domain and medically-tuned open and closed VLMs on chest x-ray tasks using MIMIC-CXR. By systematically manipulating image-text alignment, clinical history, and prompt formulations, we found that VLM decisions are dominated by the text modality, even when visual evidence is available. Moreover, we observed that VLMs are heavily influenced by irrelevant reports, while minor prompt changes can reverse correct image-based predictions. Our findings underscore the need for explicit safeguards and stress-testing before considering the use of these models in clinical practice.

Clinical decision-making is a feedback system where risk estimates influence treatment, which in turn changes disease trajectories, and both shape clinicians' measurement practices. Static prediction often fails clinically: models trained on observational care logs conflate disease biology with clinician behavior, particularly under treatment confounder feedback and irregular or informative observation. This Review focuses on intervention-aware disease trajectory modeling in clinical AI--methods estimating patient-specific longitudinal disease evolution and assessing trajectory changes under alternative treatments. We organize the field around six linked components: three decision tasks (factual forecasting, counterfactual estimation, policy evaluation) and three data-generating mechanisms (disease evolution, treatment assignment, observation process) that determine identifiability. We present the first unified framework bridging forecasting, counterfactual trajectories, and policy evaluation across discrete/continuous time, explicitly addressing treatment assignment, time-varying confounding, and observation bias. We synthesize key method families (multistate/joint models, temporal point-process, deep sequence architectures, longitudinal causal inference), map them to relevant components, and align evaluation with claim strength via overlap diagnostics, uncertainty quantification, off-policy robustness, and target-trial validation. This synthesis advances benchmark prediction to decision-grade clinical evidence, enabling treatment-sensitive individualized futures, pre-deployment policy stress-testing, and safer closed-loop learning health systems that adapt/abstain when evidence is insufficient.

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.