Clinical Decision Support

Timely detection of concerning events is an important problem in clinical practice. In this paper, we consider the problem of conditional anomaly detection that aims to identify data instances with an unusual response, such as the omission of an important lab test. We develop a new non-parametric approach for conditional anomaly detection based on the soft harmonic solution, with which we estimate the confidence of the label to detect anomalous mislabeling. We further regularize the solution to avoid the detection of isolated examples and examples on the boundary of the distribution support. We demonstrate the efficacy of the proposed method in detecting unusual labels on a real-world electronic health record dataset and compare it to several baseline approaches.

Background: Regulatory frameworks for AI in healthcare, including the EU AI Act and FDA guidance on AI/ML-based medical devices, require clinical decision support to demonstrate not only accuracy but auditability. Existing formal languages for clinical logic validate syntactic and structural correctness but not whether decision rules use epistemologically appropriate evidence. Methods: Drawing on design-by-contract principles, we introduce meta-predicates -- predicates about predicates -- for asserting epistemological constraints on clinical decision rules expressed in a DSL. An epistemological type system classifies annotations along four dimensions: purpose, knowledge domain, scale, and method of acquisition. Meta-predicates assert which evidence types are permissible in any given rule. The framework is instantiated in AnFiSA, an open-source platform for genetic variant curation, and demonstrated using the Brigham Genomics Medicine protocol on 5.6 million variants from the Genome in a Bottle benchmark. Results: Decision trees used in variant interpretation can be reformulated as unate cascades, enabling per-variant audit trails that identify which rule classified each variant and why. Meta-predicate validation catches epistemological errors before deployment, whether rules are human-written or AI-generated. The approach complements post-hoc methods such as LIME and SHAP: where explanation reveals what evidence was used after the fact, meta-predicates constrain what evidence may be used before deployment, while preserving human readability. Conclusions: Meta-predicate validation is a step toward demonstrating not only that decisions are accurate but that they rest on appropriate evidence in ways that can be independently audited. While demonstrated in genomics, the approach generalises to any domain requiring auditable decision logic.

Large language models (LLMs) are increasingly used for conversational clinical decision support, yet they conflate next token prediction with probabilistic decision making. We argue that this conflation reflects an architectural limitation: such systems lack explicit posterior tracking, controllable abstention thresholds, and auditable reasoning chains. We introduce MoBayes, a Modular Bayesian dialogue framework that separates reasoning from language. The LLM acts only as a language interface, parsing patient conversation into structured observations, while a Bayesian module performs probabilistic inference over these observations to update posteriors, select follow-up questions via expected-information-gain and determine when to stop or defer through calibrated decision thresholds. This design enables explicit posterior tracking, controllable selective decision-making, and replaceable population-specific statistical backends without retraining the language model. Across empirical and LLM-generated knowledge bases, MoBayes outperforms standalone frontier LLM doctors, including matched model-family comparisons where inexpensive sensor models paired with MoBayes exceed larger autonomous models at lower cost. The advantage persists under adversarial patient communication styles and across varying diagnostic scenarios. These results suggest that reliable conversational clinical decision support systems should separate probabilistic reasoning from language generation rather than scaling model size alone. Code is available at https://anonymous.4open.science/r/MoBayes/

Privacy represents one of the most critical yet underaddressed barriers to AI adoption in mental healthcare -- particularly in high-sensitivity operational environments such as military, correctional, and remote healthcare settings, where the risk of patient data exposure can deter help-seeking behavior entirely. Existing AI-enabled psychiatric decision support systems predominantly rely on cloud-based inference pipelines, requiring sensitive patient data to leave the device and traverse external servers, creating unacceptable privacy and security risks in these contexts. In this paper, we propose a zero-egress, on-device AI platform for privacy-preserving psychiatric decision support, deployed as a cross-platform mobile application. The proposed system extends our prior work on fine-tuned LLM consortiums for psychiatric diagnosis standardization by fundamentally re-architecting the inference pipeline for fully local execution -- ensuring that no patient data is transmitted to, processed by, or stored on any external server at any stage. The platform integrates a consortium of three lightweight, fine-tuned, and quantized open-source LLMs -- Gemma, Phi-3.5-mini, and Qwen2 -- selected for their compact architectures and proven efficiency on resource-constrained mobile hardware. An on-device orchestration layer coordinates ensemble inference and consensus-based diagnostic reasoning, producing DSM-5-aligned assessments for conditions. The platform is designed to assist clinicians with differential diagnosis and evidence-linked symptom mapping, as well as to support patient-facing self-screening with appropriate clinical safeguards. Initial evaluation demonstrates that the proposed zero-egress deployment achieves diagnostic accuracy comparable to its server-side predecessor while sustaining real-time inference latency on commodity mobile hardware.

Clinical guidelines, typically developed by independent specialty societies, inherently exhibit substantial fragmentation, redundancy, and logical contradiction. These inconsistencies, particularly when applied to patients with multimorbidity, not only cause cognitive dissonance for clinicians but also introduce catastrophic noise into AI systems, rendering the standard Retrieval-Augmented Generation (RAG) system fragile and prone to hallucination. To address this fundamental reliability crisis, we introduce a Neuro-Symbolic framework that automates the detection of recommendation redundancies and conflicts. Our pipeline employs a multi-agent system to translate unstructured clinical natural language into rigorous symbolic logic language, which is then verified by a Satisfiability (SAT) solver. By formulating a hierarchical taxonomy of logical rule interactions, we identify a critical category termed Local Conflict - a decision conflict arising from the intersection of comorbidities. Evaluating our system on a curated benchmark of 12 authoritative SGLT2 inhibitor guidelines, we reveal that 90.6% of conflicts are Local, a structural complexity that single-disease guidelines fail to address. While state-of-the-art LLMs fail in detecting these conflicts, our neuro-symbolic approach achieves an F1 score of 0.861. This work demonstrates that logical verification must precede retrieval, establishing a new technical standard for automated knowledge coordination in medical AI.

Trustworthiness and transparency are essential for the clinical adoption of artificial intelligence (AI) in healthcare and biomedical research. Recent deep research systems aim to accelerate evidence-grounded scientific discovery by integrating AI agents with multi-hop information retrieval, reasoning, and synthesis. However, most existing systems lack explicit and inspectable criteria for evidence appraisal, creating a risk of compounding errors and making it difficult for researchers and clinicians to assess the reliability of their outputs. In parallel, current benchmarking approaches rarely evaluate performance on complex, real-world medical questions. Here, we introduce DeepER-Med, a Deep Evidence-based Research framework for Medicine with an agentic AI system. DeepER-Med frames deep medical research as an explicit and inspectable workflow of evidence-based generation, consisting of three modules: research planning, agentic collaboration, and evidence synthesis. To support realistic evaluation, we also present DeepER-MedQA, an evidence-grounded dataset comprising 100 expert-level research questions derived from authentic medical research scenarios and curated by a multidisciplinary panel of 11 biomedical experts. Expert manual evaluation demonstrates that DeepER-Med consistently outperforms widely used production-grade platforms across multiple criteria, including the generation of novel scientific insights. We further demonstrate the practical utility of DeepER-Med through eight real-world clinical cases. Human clinician assessment indicates that DeepER-Med's conclusions align with clinical recommendations in seven cases, highlighting its potential for medical research and decision support.

Continuous glucose monitoring (CGM) is central to diabetes care, but explaining CGM patterns clearly and empathetically remains time-intensive. Evidence for retrieval-grounded large language model (LLM) systems in CGM-informed counseling remains limited. To evaluate whether a retrieval-grounded LLM-based conversational agent (CA) could support patient understanding of CGM data and preparation for routine diabetes consultations. We developed a retrieval-grounded LLM-based CA for CGM interpretation and diabetes counseling support. The system generated plain-language responses while avoiding individualized therapeutic advice. Twelve CGM-informed cases were constructed from publicly available datasets. Between Oct 2025 and Feb 2026, 6 senior UK diabetes clinicians each reviewed 2 assigned cases and answered 24 questions. In a blinded multi-rater evaluation, each CA-generated and clinician-authored response was independently rated by 3 clinicians on 6 quality dimensions. Safety flags and perceived source labels were also recorded. Primary analyses used linear mixed-effects models. A total of 288 unique responses (144 CA and 144 clinician) generated 864 ratings. The CA received higher quality scores than clinician responses (mean 4.37 vs 3.58), with an estimated mean difference of 0.782 points (95% CI 0.692-0.872; P<.001). The largest differences were for empathy (1.062, 95% CI 0.948-1.177) and actionability (0.992, 95% CI 0.877-1.106). Safety flag distributions were similar, with major concerns rare in both groups (3/432, 0.7% each). Retrieval-grounded LLM systems may have value as adjunct tools for CGM review, patient education, and preconsultation preparation. However, these findings do not support autonomous therapeutic decision-making or unsupervised real-world use.

Artificial intelligence has advanced rapidly in biomedicine through large-scale multimodal data integration, enabling increasingly accurate prediction of clinical outcomes and patient stratification. These systems, however, remain fundamentally observational: they learn statistical associations from historical data and operate within previously observed biological and clinical states, limiting their ability to generalize to novel therapies or unobserved interventions. We argue that AI in biomedicine is undergoing a structural transition. As biomedical decision-making increasingly depends on reasoning about intervention rather than extrapolation from past observations, predictive architectures become structurally insufficient. Systems that learn from historical data cannot, by construction, represent how biological systems evolve under perturbation, and therefore cannot reliably support decision-making in the presence of novel interventions. We introduce a conceptual framework distinguishing observational and interventional intelligence and define disease-level models as systems that explicitly represent the state, dynamics, and intervention response of biological processes. These models enable a shift from inference to simulation -- reasoning about what will happen under intervention rather than what is likely based on the past. This transition also implies a shift in where value is created: from data processing and prediction toward systems that support and define decision-making under intervention. It follows directly from the structure of biomedical decision-making and defines the next stage of AI in medicine. Systems that cannot model intervention will be structurally excluded from decision-making.

Tumor boards are multidisciplinary conferences dedicated to producing actionable patient care recommendations with live review of primary radiology and pathology data. Succinct patient case summaries are needed to drive efficient and accurate case discussions. We developed a manual AI-based workflow to generate patient summaries to display live at the Stanford Thoracic Tumor board. To improve on this manually intensive process, we developed several automated AI chart summarization methods and evaluated them against physician gold standard summaries and fact-based scoring rubrics. We report these comparative evaluations as well as our deployment of the final state automated AI chart summarization tool along with post-deployment monitoring. We also validate the use of an LLM as a judge evaluation strategy for fact-based scoring. This work is an example of integrating AI-based workflows into routine clinical practice.

The integration of Large Language Models (LLMs) into clinical decision support is critically obstructed by their opaque and often unreliable reasoning. In the high-stakes domain of healthcare, correct answers alone are insufficient; clinical practice demands full transparency to ensure patient safety and enable professional accountability. A pervasive and dangerous weakness of current LLMs is their tendency to produce "correct answers through flawed reasoning." This issue is far more than a minor academic flaw; such process errors signal a fundamental lack of robust understanding, making the model prone to broader hallucinations and unpredictable failures when faced with real-world clinical complexity. In this paper, we establish a framework for trustworthy clinical argumentation by adapting the Toulmin model to the diagnostic process. We propose a novel training pipeline: Curriculum Goal-Conditioned Learning (CGCL), designed to progressively train LLM to generate diagnostic arguments that explicitly follow this Toulmin structure. CGCL's progressive three-stage curriculum systematically builds a solid clinical argument: (1) extracting facts and generating differential diagnoses; (2) justifying a core hypothesis while rebutting alternatives; and (3) synthesizing the analysis into a final, qualified conclusion. We validate CGCL using T-Eval, a quantitative framework measuring the integrity of the diagnosis reasoning. Experiments show that our method achieves diagnostic accuracy and reasoning quality comparable to resource-intensive Reinforcement Learning (RL) methods, while offering a more stable and efficient training pipeline.

Clinical diagnosis requires answers that are accurate, verifiable, and explicitly grounded in official guidelines. While large language models excel at natural language processing, their tendency to hallucinate undermines their utility in high-stakes medical contexts where precision is essential. Existing retrieval-augmented generation (RAG) systems treat all evidence equally, producing noisy context and generic answers misaligned with clinical practice. We present ClinicBot, an AI system that translates guideline recommendations into trustworthy clinical support through three key advances: (1) structured extraction of clinical guidelines into semantic units (recommendations, tables, definitions, narrative) with explicit provenance, (2) evidence prioritization that ranks content by clinical significance and guideline structure rather than textual similarity, and (3) a web-based interface that presents concise, actionable answers with verifiable evidence. We will demonstrate ClinicBot using diabetes questions from real patients and an additional diabetes risk assessment tool that is faithful to the American Diabetes Association (ADA) Standards of Care in Diabetes (2025). The demonstration will illustrate how semantic knowledge extraction and hierarchical evidence ranking can reliably operate in a multi-agent setting to process complex clinical guidelines at scale.

The development of AI-assisted Early Intensive Behavioral Intervention (EIBI) for Autism Spectrum Disorder (ASD) is severely constrained by data scarcity. Furthermore, while Applied Behavior Analysis (ABA) serves as the gold standard for clinical intervention, general-purpose Large Language Models (LLMs) struggle to strictly adhere to its standardized procedures, often resulting in interactions that are linguistically fluent but strategically inconsistent. To address these challenges, we introduce ASDAgent, a strategy-aware framework designed to unify high-fidelity intervention dialogue synthesis and clinical decision support. ASDAgent incorporates two specialized components to solve distinct problems: (i) a DoctorAgent equipped with an Observe-Think-Act-Correct (O-T-A-C) reasoning loop, which resolves the issue of strategy collapse in LLMs by making ABA execution explicit and controllable; and (ii) a ChildAgent that utilizes probabilistic behavior modeling to mitigate data homogeneity, simulating diverse and non-deterministic ASD response patterns. Experiments demonstrate that dialogues generated by ASDAgent closely mirror the strategy distribution of human therapists (KL divergence: 0.083). In real autism intervention, ASDAgent achieves nearly 80% strategic consistency with human experts. Moreover, we show that synthetic data produced by ASDAgent effectively distills professional clinical knowledge into small language models (SLMs), significantly enhancing their therapeutic capabilities.

AI-driven symptom analysis systems face persistent challenges in reliability, interpretability, and hallucination. End-to-end generative approaches often lack traceability and may produce unsupported or inconsistent diagnostic outputs in safety-critical settings. We present SymptomWise, a framework that separates language understanding from diagnostic reasoning. The system combines expert-curated medical knowledge, deterministic codex-driven inference, and constrained use of large language models. Free-text input is mapped to validated symptom representations, then evaluated by a deterministic reasoning module operating over a finite hypothesis space to produce a ranked differential diagnosis. Language models are used only for symptom extraction and optional explanation, not for diagnostic inference. This architecture improves traceability, reduces unsupported conclusions, and enables modular evaluation of system components. Preliminary evaluation on 42 expert-authored challenging pediatric neurology cases shows meaningful overlap with clinician consensus, with the correct diagnosis appearing in the top five differentials in 88% of cases. Beyond medicine, the framework generalizes to other abductive reasoning domains and may serve as a deterministic structuring and routing layer for foundation models, improving precision and potentially reducing unnecessary computational overhead in bounded tasks.

Clinical practice guidelines are long, multimodal documents whose branching recommendations are difficult to convert into executable clinical decision support (CDS), and one-shot parsing often breaks cross-page continuity. Recent LLM/VLM extractors are mostly local or text-centric, under-specifying section interfaces and failing to consolidate cross-page control flow across full documents into one coherent decision graph. We present a decomposition-first pipeline that converts full-guideline evidence into an executable clinical decision graph through topology-aware chunking, interface-constrained chunk graph generation, and provenance-preserving global aggregation. Rather than relying on single-pass generation, the pipeline uses explicit entry/terminal interfaces and semantic deduplication to preserve cross-page continuity while keeping the induced control flow auditable and structurally consistent. We evaluate on an adjudicated prostate-guideline benchmark with matched inputs and the same underlying VLM backbone across compared methods. On the complete merged graph, our approach improves edge and triplet precision/recall from $19.6\%/16.1\%$ in existing models to $69.0\%/87.5\%$, while node recall rises from $78.1\%$ to $93.8\%$. These results support decomposition-first, auditable guideline-to-CDS conversion on this benchmark, while current evidence remains limited to one adjudicated prostate guideline and motivates broader multi-guideline validation.

Clinical AI systems routinely train on health data structurally distorted by documentation workflows, billing incentives, and terminology fragmentation. Prior work has characterised the mechanisms of this distortion: the three-forces model of documentary enactment, the reification feedback loop through which AI may amplify coding artefacts, and terminology governance failures that allow semantic drift to accumulate. Yet translating these insights into implementable software architecture remains an open problem. This paper proposes seven ontology-aware design patterns in Gang-of-Four pattern language for building clinical AI pipelines resilient to ontological distortion. The patterns address data ingestion validation (Ontological Checkpoint), low-frequency signal preservation (Dormancy-Aware Pipeline), continuous drift monitoring (Drift Sentinel), parallel representation maintenance (Dual-Ontology Layer), feedback loop interruption (Reification Circuit Breaker), terminology evolution management (Terminology Version Gate), and pluggable regulatory compliance (Regulatory Compliance Adapter). Each pattern is specified with Problem, Forces, Solution, Consequences, Known Uses, and Related Patterns. We illustrate their composition in a reference architecture for a primary care AI system and provide a walkthrough tracing all seven patterns through a diabetes risk prediction scenario. This paper does not report empirical validation; it offers a design vocabulary grounded in theoretical analysis, subject to future evaluation in production systems. Three patterns have partial precedent in existing systems; the remaining four have not been formally described. Limitations include the absence of runtime benchmarks and restriction to the German and EU regulatory context.

Artificial intelligence (AI) systems are increasingly integrated into healthcare and pharmacy workflows, supporting tasks such as medication recommendations, dosage determination, and drug interaction detection. While these systems often demonstrate strong performance under standard evaluation metrics, their reliability in real-world decision-making remains insufficiently understood. In high-risk domains such as medication management, even a single incorrect recommendation can result in severe patient harm. This paper examines the reliability of AI-assisted medication systems by focusing on system failures and their potential clinical consequences. Rather than evaluating performance solely through aggregate metrics, this work shifts attention towards how errors occur and what happens when AI systems produce incorrect outputs. Through a series of controlled, simulated scenarios involving drug interactions and dosage decisions, we analyse different types of system failures, including missed interactions, incorrect risk flagging, and inappropriate dosage recommendations. The findings highlight that AI errors in medication-related contexts can lead to adverse drug reactions, ineffective treatment, or delayed care, particularly when systems are used without sufficient human oversight. Furthermore, the paper discusses the risks of over-reliance on AI recommendations and the challenges posed by limited transparency in decision-making processes. This work contributes a reliability-focused perspective on AI evaluation in healthcare, emphasising the importance of understanding failure behavior and real-world impact. It highlights the need to complement traditional performance metrics with risk-aware evaluation approaches, particularly in safety-critical domains such as pharmacy practice.

In recent years, the advances of large language models and autonomous agents have revolutionized the healthcare field, facilitating diagnosis and improving treatment results. However, most existing AI systems rely on pre-trained knowledge and predefined pipelines, which struggle to learn dynamically from the interactive chat session history that contains patient outcomes and past failures. To address this limitation, we propose VIBEMed, a multi-agent framework with a built-in self-evolution mechanism and architecture-level safety sandbox for robust clinical decision support. The system integrates three specialized agents, including a Clinical Diagnostic Agent (CDA) for hypothesis generation, a Therapeutic Execution Agent (TEA) for treatment planning, and a Clinical Evolution Manager Agent (CEMA) that distills longitudinal clinical feedback into reusable knowledge, transforming multimodal patient information into personalized medical decisions. Through self-evolution mechanism, the framework enables iterative updates across memory, model behavior, and decision strategies, allowing the system to improve over time. Experimental results show that VIBEMed demonstrates superior performance through its evolving mechanism in complex clinical cases, particularly in tasks that require integrated decision-making and longitudinal planning. The framework also supports reliable end-to-end decisions in challenging scenarios such as oncology treatment planning, highlighting its feasibility in real-world clinical contexts. Overall, VIBEMed provides a practical path beyond static AI systems toward adaptive, experience-driven clinical decision support, demonstrating the value of combining multi-agent collaboration with continuous evolution for advancing precision medicine.

Acute poly-substance intoxication requires rapid, life-saving decisions under substantial uncertainty, as clinicians must rely on incomplete ingestion details and nonspecific symptoms. Effective diagnostic reasoning in this chaotic environment requires fusing unstructured, non-medical narratives (e.g. paramedic scene descriptions and unreliable patient self-reports or known histories), with structured medical data like vital signs. While Large Language Models (LLMs) show potential for processing such heterogeneous inputs, they struggle in this setting, often underperforming simple baselines that rely solely on patient histories. To address this, we present DeToxR (Decision-support for Toxicology with Reasoning), the first adaptation of Reinforcement Learning (RL) to emergency toxicology. We design a robust data-fusion engine for multi-label prediction across 14 substance classes based on an LLM finetuned with Group Relative Policy Optimization (GRPO). We optimize the model's reasoning directly using a clinical performance reward. By formulating a multi-label agreement metric as the reward signal, the model is explicitly penalized for missing co-ingested substances and hallucinating absent poisons. Our model significantly outperforms its unadapted base LLM counterpart and supervised baselines. Furthermore, in a preliminary clinical validation study, the model indicates a clinical advantage by achieving higher micro-F1 (0.644 vs 0.473) and recall in identifying the correct poisons. These results demonstrate the potential of RL-aligned LLMs to synthesize unstructured pre-clinical narratives and structured medical data for decision support in high-stakes environments.

Clinical diagnosis is a complex reasoning process in which clinicians gather evidence, form hypotheses, and test them against alternative explanations. In medical training, this reasoning is explicitly developed through counterfactual questioning--e.g., asking how a diagnosis would change if a key symptom were absent or altered--to strengthen differential diagnosis skills. As large language model (LLM)-based systems are increasingly used for diagnostic support, ensuring the interpretability of their recommendations becomes critical. However, most existing LLM-based diagnostic agents reason over fixed clinical evidence without explicitly testing how individual findings support or weaken competing diagnoses. In this work, we propose a counterfactual multi-agent diagnostic framework inspired by clinician training that makes hypothesis testing explicit and evidence-grounded. Our framework introduces counterfactual case editing to modify clinical findings and evaluate how these changes affect competing diagnoses. We further define the Counterfactual Probability Gap, a method that quantifies how strongly individual findings support a diagnosis by measuring confidence shifts under these edits. These counterfactual signals guide multi-round specialist discussions, enabling agents to challenge unsupported hypotheses, refine differential diagnoses, and produce more interpretable reasoning trajectories. Across three diagnostic benchmarks and seven LLMs, our method consistently improves diagnostic accuracy over prompting and prior multi-agent baselines, with the largest gains observed in complex and ambiguous cases. Human evaluation further indicates that our framework produces more clinically useful, reliable, and coherent reasoning. These results suggest that incorporating counterfactual evidence verification is an important step toward building reliable AI systems for clinical decision support.

Background: More than 80% of U.S. cancer care is delivered in community settings, where survival remains worse than at academic centers. Clinicians must integrate genomics, staging, radiology, pathology, and changing guidelines, creating cognitive burden. We evaluated OncoBrain, an AI clinical reasoning platform for oncology treatment-plan generation, as an early step toward OGI. Methods: OncoBrain combines general-purpose LLMs with a cancer-specific graph retrieval-augmented generation layer, a gold-standard treatment-plan corpus as long-term memory, and a model-agnostic safety layer (CHECK) for hallucination detection and suppression. We evaluated clinician-enriched case summaries across gynecologic, genitourinary, neuro-oncology, gastrointestinal/hepatobiliary, and hematologic malignancies. Three clinician groups completed structured evaluations of 173 cases using a common 16-item instrument: subspecialist oncologists reviewed 50 cases, physician reviewers 78, and advanced practice providers 45. Results: Ratings were highest for scientific accuracy, evidence support, and safety, with lower but favorable scores for workflow integration and time savings. On a 5-point scale, mean alignment with evidence and guidelines was 4.60, 4.56, and 4.70 across subspecialists, physician reviewers, and advanced practice providers. Mean scores for absence of safety or misinformation concerns were 4.80, 4.40, and 4.60. Workflow integration averaged 4.50, 3.94, and 4.00; perceived time savings averaged 5.00, 3.89, and 3.60. Conclusions: In this multi-specialty vignette-based evaluation, OncoBrain generated oncology treatment plans judged guideline-concordant, clinically acceptable, and easy to supervise. These findings support the potential of a carefully engineered AI reasoning platform to assist oncology treatment planning and justify prospective real-world evaluation in community settings.

Alzheimer's disease (AD) is a growing global health challenge as populations age, and timely, accurate diagnosis is essential to reduce individual and societal burden. However, real-world AD assessment is hampered by incomplete, heterogeneous multimodal data and variability across sites and patient demographics. Although large language models (LLMs) have shown promise in biomedicine, their use in AD has largely been confined to answering narrow, disease-specific questions rather than generating comprehensive diagnostic reports that support clinical decision-making. Here we expand LLM capabilities for clinical decision support by introducing AD-CARE, a modality-agnostic agent that performs guideline-grounded diagnostic assessment from incomplete, heterogeneous inputs without imputing missing modalities. By dynamically orchestrating specialized diagnostic tools and embedding clinical guidelines into LLM-driven reasoning, AD-CARE generates transparent, report-style outputs aligned with real-world clinical workflows. Across six cohorts comprising 10,303 cases, AD-CARE achieved 84.9% diagnostic accuracy, delivering 4.2%-13.7% relative improvements over baseline methods. Despite cohort-level differences, dataset-specific accuracies remain robust (80.4%-98.8%), and the agent consistently outperforms all baselines. AD-CARE reduced performance disparities across racial and age subgroups, decreasing the average dispersion of four metrics by 21%-68% and 28%-51%, respectively. In a controlled reader study, the agent improved neurologist and radiologist accuracy by 6%-11% and more than halved decision time. The framework yielded 2.29%-10.66% absolute gains over eight backbone LLMs and converges their performance. These results show that AD-CARE is a scalable, practically deployable framework that can be integrated into routine clinical workflows for multimodal decision support in AD.

Current clinical decision support systems (CDSSs) typically base their predictions on correlation, not causation. In recent years, causal machine learning (ML) has emerged as a promising way to improve decision-making with CDSSs by offering interpretable, treatment-specific reasoning. However, existing research often emphasizes model development rather than designing clinician-facing interfaces. To address this gap, we investigated how CDSSs based on causal ML should be designed to effectively support collaborative clinical decision-making. Using a design science research methodology, we conducted a structured literature review and interviewed experienced physicians. From these, we derived eight empirically grounded design requirements, developed seven design principles, and proposed nine practical design features. Our results establish guidance for designing CDSSs that deliver causal insights, integrate seamlessly into clinical workflows, and support trust, usability, and human-AI collaboration. We also reveal tensions around automation, responsibility, and regulation, highlighting the need for an adaptive certification process for ML-based medical products.

Evidence-based medicine (EBM) is central to high-quality care, but remains difficult to implement in fast-paced primary care settings. Physicians face short consultations, increasing patient loads, and lengthy guideline documents that are impractical to consult in real time. To address this gap, we investigate the feasibility of using large language models (LLMs) as ambient assistants that surface targeted, evidence-based questions during physician-patient encounters. Our study focuses on question generation rather than question answering, with the aim of scaffolding physician reasoning and integrating guideline-based practice into brief consultations. We implemented two prompting strategies, a zero-shot baseline and a multi-stage reasoning variant, using Gemini 2.5 as the backbone model. We evaluated on a benchmark of 80 de-identified transcripts from real clinical encounters, with six experienced physicians contributing over 90 hours of structured review. Results indicate that while general-purpose LLMs are not yet fully reliable, they can produce clinically meaningful and guideline-relevant questions, suggesting significant potential to reduce cognitive burden and make EBM more actionable at the point of care.

In this work, we propose Oph-Guid-RAG, a multimodal visual RAG system for ophthalmology clinical question answering and decision support. We treat each guideline page as an independent evidence unit and directly retrieve page images, preserving tables, flowcharts, and layout information. We further design a controllable retrieval framework with routing and filtering, which selectively introduces external evidence and reduces noise. The system integrates query decomposition, query rewriting, retrieval, reranking, and multimodal reasoning, and provides traceable outputs with guideline page references. We evaluate our method on HealthBench using a doctor-based scoring protocol. On the hard subset, our approach improves the overall score from 0.2969 to 0.3861 (+0.0892, +30.0%) compared to GPT-5.2, and achieves higher accuracy, improving from 0.5956 to 0.6576 (+0.0620, +10.4%). Compared to GPT-5.4, our method achieves a larger accuracy gain of +0.1289 (+24.4%). These results show that our method is more effective on challenging cases that require precise, evidence-based reasoning. Ablation studies further show that reranking, routing, and retrieval design are critical for stable performance, especially under difficult settings. Overall, we show how combining visionbased retrieval with controllable reasoning can improve evidence grounding and robustness in clinical AI applications,while pointing out that further work is needed to be more complete.

Recommending safe and effective medication combinations from electronic health records (EHRs) is a core clinical AI problem, yet it remains difficult because patient trajectories are long, noisy, and clinically heterogeneous. Existing methods typically excel at either temporal modeling across visits or pharmacological knowledge integration (e.g., drug-drug interactions, DDIs), but rarely achieve both while robustly suppressing noise. We present GraphDiffMed, a knowledge-constrained medication recommendation framework built on dual-scale Differential Attention v2. Differential attention is applied at both intra-visit and inter-visit levels to filter spurious signals within encounters and across longitudinal history, while pharmacological constraints are incorporated during learning. Experiments on MIMIC-III and ablation studies show that this design consistently improves recommendation quality and ranking over strong baselines while achieving a more favorable safety performance balance. We further find that the strongest-performing configuration uses only demographic auxiliary features under our experimental setting. Overall, GraphDiffMed demonstrates that combining noise-aware attention with pharmacological constraints yields more reliable and clinically meaningful medication recommendation. We open-source our code at https://github.com/saxenakrati09/GraphDiffMed.

Medication recommendations aim to generate safe and effective medication sets from health records. However, accurately recommending medications hinges on inferring a patient's latent clinical condition from sparse and noisy observations, which requires both (i) preserving the visit-level combinatorial semantics of co-occurring entities and (ii) leveraging informative historical references through effective, visit-conditioned retrieval. Most existing methods fall short in one of both aspects: graph-based modeling often fragments higher-order intra-visit patterns into pairwise relations, while inter-visit augmentation methods commonly exhibit an imbalance between learning a globally stable representation space and performing dynamic retrieval within it. To address these limitations, this paper proposes HypeMed, a two-stage hypergraph-based framework unifying intra-visit coherence modeling and inter-visit augmentation. HypeMed consists of two core modules: MedRep for representation pre-training, and SimMR for similarity-enhanced recommendation. In the first stage, MedRep encodes clinical visits as hyperedges via knowledge-aware contrastive pre-training, creating a globally consistent, retrieval-friendly embedding space. In the second stage, SimMR performs dynamic retrieval within this space, fusing retrieved references with the patient's longitudinal data to refine medication prediction. Evaluation on real-world benchmarks shows that HypeMed outperforms state-of-the-art baselines in both recommendation precision and DDI reduction, simultaneously enhancing the effectiveness and safety of clinical decision support.

Most dialogue-based electronic medical record (EMR) systems still behave as passive pipelines: transcribe speech, extract information, and generate the final note after the consultation. That design improves documentation efficiency, but it is insufficient for proactive consultation support because it does not explicitly address streaming speech noise, missing punctuation, unstable diagnostic belief, objectification quality, or measurable next-action gains. We present an end-to-end proactive EMR assistant built around streaming speech recognition, punctuation restoration, stateful extraction, belief stabilization, objectified retrieval, action planning, and replayable report generation. The system is evaluated in a preliminary controlled setting using ten streamed doctor-patient dialogues and a 300-query retrieval benchmark aggregated across dialogues. The full system reaches state-event F1 of 0.84, retrieval Recall@5 of 0.87, and end-to-end pilot scores of 83.3% coverage, 81.4% structural completeness, and 80.0% risk recall. Ablations further suggest that punctuation restoration and belief stabilization may improve downstream extraction, retrieval, and action selection within this pilot. These results were obtained under a controlled simulated pilot setting rather than broad deployment claims, and they should not be read as evidence of clinical deployment readiness, clinical safety, or real-world clinical utility. Instead, they suggest that the proposed online architecture may be technically coherent and directionally supportive under tightly controlled pilot conditions. The present study should be read as a pilot concept demonstration under tightly controlled pilot conditions rather than as evidence of clinical deployment readiness or clinical generalizability.

Drug recommendation requires a deep understanding of individual patient context, especially for complex conditions like Parkinson's disease. While LLMs possess broad medical knowledge, they fail to capture the subtle nuances of actual prescribing patterns. Existing RAG methods also struggle with these complexities because guideline-based retrieval remains too generic and similar-patient retrieval often replicates majority patterns without accounting for the unique clinical nuances of individual patients. To bridge this gap, we propose PACE-RAG (Patient-Aware Contextual and Evidence-Constrained RAG). Rather than directly copying frequent medications from retrieved patients, PACE-RAG personalizes recommendations by first extracting patient-specific clinical features, retrieving cases around these features, and then refining the final prescription using the patient's current symptoms, active medication history, and focus-specific prescribing tendencies. By analyzing treatment patterns tailored to specific clinical features, PACE-RAG generates patient-specific medication recommendations along with an explainable clinical summary. PACE-RAG achieved the strongest performance among the evaluated inference-only LLM-based methods, reaching F1 scores of 80.84% and 47.22% on the Parkinson's disease and MIMIC-IV cohorts, respectively. Our code is available at: https://github.com/ChaeYoungHuh/PACE-RAG.

Surgical co-management (SCM) is an evidence-based model in which hospitalists jointly manage medically complex perioperative patients alongside surgical teams. Despite its clinical and financial value, SCM is limited by the need to manually identify eligible patients. To determine whether SCM triage can be automated, we conducted a prospective, unblinded study at Stanford Health Care in which an LLM-based, electronic health record (EHR)-integrated triage tool (SCM Navigator) provided SCM recommendations followed by physician review. Using pre-operative documentation, structured data, and clinical criteria for perioperative morbidity, SCM Navigator categorized patients as appropriate, not appropriate, or possibly appropriate for SCM. Faculty indicated their clinical judgment and provided free-text feedback when they disagreed. Sensitivity, specificity, positive predictive value, and negative predictive value were measured using physician determinations as a reference. Free-text reasons were thematically categorized, and manual chart review was conducted on all false-negative cases and 30 randomly selected cases from the largest false-positive category. Since deployment, 6,193 cases have been triaged, of which 1,582 (23%) were recommended for hospitalist consultation. SCM Navigator displayed high sensitivity (0.94, 95% CI 0.91-0.96) and moderate specificity (0.74, 95% CI 0.71-0.77). Post-hoc chart review suggested most discrepancies reflect modifiable gaps in clinical criteria, institutional workflow, or physician practice variability rather than LLM misclassification, which accounted for 2 of 19 (11%) false-negative cases. These findings demonstrate that an LLM-powered, EHR-integrated, human-in-the-loop AI system can accurately and safely triage surgical patients for SCM, and that AI-enabled screening tools can augment and potentially automate time-intensive clinical workflows.

This research paper outlines the development and implementation of a novel Clinical Decision Support System (CDSS) that integrates AI predictive modeling with medical knowledge bases. It utilizes the quantifiable information elements in lab results for inferring likely diagnoses a patient might have. Subsequently, suggesting investigations to confirm the likely diagnoses -- an assistive tool for physicians. The system fuses knowledge contained in a rule-base expert system with inferences of data driven predictors based on the features in labs. The data for 593,055 patients was collected from 547 primary care centers across the US to model our decision support system and derive Real-Word Evidence (RWE) to make it relevant for a large demographic of patients. Our Rule-Base comprises clinically validated rules, modeling 59 health conditions that can directly confirm one or more of diseases and assign ICD-10 codes to them. The Likely Diagnosis system uses multi-class classification, covering 37 ICD-10 codes, which are grouped together into 11 categories based on the labs that physicians prescribe to confirm the diagnosis. This research offers a novel system that assists a physician by utilizing medical profile of a patient and routine lab investigations to predict a group of likely diseases and then confirm them, coupled with providing explanations for inferences, thereby assisting physicians to reduce misdiagnosis of patients in clinical decision-making.