Medical Question Answering

Online patient inquiries are often informal, incomplete, and written before professional assessment, yet they must still be routed to an appropriate level of clinical follow-up. We study this as a four-class actionable triage task -- self-care, schedule-visit, urgent-clinician-review, or emergency-referral, and ask whether prompted large language models (LLMs) can support such routing under low-resource labeling conditions. Using the public HealthCareMagic-100K corpus, we construct a 300-example human calibrated gold evaluation set, a 700-example auto-labeled silver training set, and a 40-example few-shot pool. We compare Term Frequency-Inverse Document Frequency (TF-IDF) and Bidirectional Encoder Representations from Transformers for Biomedical Text Mining (BioBERT) baselines train on silver labels against six prompted LLMs under 0-shot, 4-shot, and 12-shot conditions respectively. Accordingly, we evaluate with macro-$F_1$ alongside safety-aware metrics, including emergency-recall, under-triage rate, and severe under-triage rate. The strongest LLM (Claude Haiku 4.5, 12-shot) reaches macro-$F_1$ 0.475, exceeding the best supervised baseline (BioBERT, 0.378) on point estimate, with overlapping confidence intervals. Few-shot prompting and two-model agreement help in label-dependent ways: self-care agreement is reliable, urgent-clinician-review is not. We conclude that LLMs can support triage prioritization and selective human review, but not autonomous deployment.

Conversational nurse-patient transcripts contain actionable observations, but converting these transcripts into structured representations at scale remains challenging. Documentation burden is substantial, with prior studies showing clinicians spend large portions of their workday on documentation and related desk work rather than direct patient care. MEDIQA-SYNUR focuses on observation extraction from conversational nurse-patient transcripts, requiring systems to normalize these narratives into a predefined schema with value-type constraints. We propose a modular retrieval-augmented generation (RAG) pipeline that uses the training set as an exemplar corpus, combines schema-constrained prompting (full schema vs. pruned candidate schema), deterministic schema-based postprocessing, and a second-pass audit, with two LLM backbones: Llama-4-Scout-17B-16E-Instruct and GPT-5.2 with corresponding embedding models for RAG. Our best configuration uses GPT-5.2 with full schema, RAG, and a second-pass auditing, achieving 80.36% F1 score. Overall, our results show that RAG consistently improves performance, while the optimal degree of schema constraint depends on the model, and second-pass auditing yields modest additional gains by correcting residual schema-adherence errors.

Biomedical retrieval-augmented large language models (LLMs) often face evidence that is incomplete, misleading, or internally contradictory, yet evaluation usually emphasizes answer accuracy under helpful context rather than reliability under conflict. Using HealthContradict, we evaluate six open-weight LLMs under five controlled evidence conditions: no retrieved context, correct-only context, incorrect-only context, and two mixed conditions containing both correct and contradictory documents in opposite orders. In this conflicting-evidence order contrast, where the same two documents are both present and only their order is reversed, accuracy drops for every model and 11.4%--25.2% of predictions flip. To support abstention in these difficult cases, we also evaluate a conflict-aware abstention score that combines model confidence with a detector of evidence conflict. In the two hardest conditions, this score improves selective accuracy over confidence-only, with mean gains of 7.2--33.4 points in incorrect-only (IC') and 3.6--14.4 points in incorrect-first conflicting (ICC') conditions across 75%, 50%, and 25% coverage. These results show that conflicting biomedical evidence is both an uncertainty and robustness problem and motivate evaluation and abstention methods that explicitly account for evidence disagreement.

Evaluating large language models (LLMs) in the biomedical domain requires benchmarks that can distinguish reasoning from pattern matching and remain discriminative as model capabilities improve. Existing biomedical question answering (QA) benchmarks are limited in this respect. Multiple-choice formats can allow models to succeed through answer elimination rather than inference, while widely circulated exam-style datasets are increasingly vulnerable to performance saturation and training data contamination. Multi-hop reasoning, defined as the ability to integrate information across multiple sources to derive an answer, is central to clinically meaningful tasks such as diagnostic support, literature-based discovery, and hypothesis generation, yet remains underrepresented in current biomedical QA benchmarks. MedHopQA is a disease-centered multi-hop reasoning benchmark consisting of 1,000 expert-curated question-answer pairs introduced as a shared task at BioCreative IX. Each question requires synthesis of information across two distinct Wikipedia articles, and answers are provided in an open-ended free-text format. Gold annotations are augmented with ontology-grounded synonym sets from MONDO, NCBI Gene, and NCBI Taxonomy to support both lexical and concept-level evaluation. MedHopQA was constructed through a structured process combining human annotation, triage, iterative verification, and LLM-as-a-judge validation. To reduce leaderboard gaming and contamination risk, the 1,000 scored questions are embedded within a publicly downloadable set of 10,000 questions, with answers withheld, on a CodaBench leaderboard. MedHopQA provides both a benchmark and a reusable framework for constructing future biomedical QA datasets that prioritize compositional reasoning, saturation resistance, and contamination resistance as core design constraints.

Multi-hop question answering (QA) remains a significant challenge in the biomedical domain, requiring systems to integrate information across multiple sources to answer complex questions. To address this problem, the BioCreative IX MedHopQA shared task was designed to benchmark in multi-hop reasoning for large language models (LLMs). We developed a novel dataset of 1,000 challenging QA pairs spanning diseases, genes, and chemicals, with particular emphasis on rare diseases. Each question was constructed to require two-hop reasoning through the integration of information from two distinct Wikipedia pages. The challenge attracted 48 submissions from 13 teams. Systems were evaluated using both surface string comparison and conceptual accuracy (MedCPT score). The results showed a substantial performance gap between baseline LLMs and enhanced systems. The top-ranked submission achieved an 89.30% F1 score on the MedCPT metric and an 87.30% exact match (EM) score, compared with 67.40% and 60.20%, respectively, for the zero-shot baseline. A central finding of the challenge was that retrieval-augmented generation (RAG) and related retrieval-based strategies were critical for strong performance. In addition, concept-level evaluation improved answer assessment when correct responses differed in surface form. The MedHopQA dataset is publicly available to support continued progress in this important area. Challenge materials: https://www.ncbi.nlm.nih.gov/research/bionlp/medhopqa and benchmark https://www.codabench.org/competitions/7609/

Automated question answering (QA) over electronic health records (EHRs) demands precise evidence retrieval, faithful answer generation, and explicit grounding of answers in clinical notes. In this work, we present Neural1.5, our method for the ArchEHR-QA 2026 shared task at CL4Health@LREC 2026, which comprises four subtasks: question interpretation, evidence identification, answer generation, and evidence alignment. Our approach decouples the task into independent, modular stages and employs DSPy"s MIPROv2 optimizer to automatically discover high-performing prompts, jointly tuning instructions and few-shot demonstrations for each stage. Within every stage, self-consistency voting over multiple stochastic inference runs suppresses spurious errors and improves reliability, while stage-specific verification mechanisms (e.g., self-reflection and chain-of-verification for alignment) further refine output quality. Among all teams that participated in all four subtasks, our method ranks second overall (mean rank 4.00), placing 4th, 1st, 4th, and 7th on Subtasks 1-4, respectively. These results demonstrate that systematic, per-stage prompt optimization combined with self-consistency mechanisms is a cost-effective alternative to model fine-tuning for multifaceted clinical QA.

The training data of large language models (LLMs) comprises a wide range of biomedical literature, reflecting data from many different patient populations. We investigate how it might be possible to recover information on correlation and causal links between patient characteristics, as a key building block for medical decision making. To avoid the pitfalls of direct elicitation, we propose an approach based on structured comparison questions, specifically patient comparison triplet questions. This is combined with a statistical model for the LLM representation that provides estimates of correlations without access to activations or model internals. Intuitively, we consider how similarity decisions of LLMs based on a first variable are affected by providing information on a second variable for one of the patients being assessed. We then induce prompt-level environment shifts to obtain correlation estimates for different subpopulations, which enables an invariant causal prediction (ICP) approach to obtain conservative candidate parent links. We demonstrate the method in two clinical domains, chronic obstructive pulmonary disease (COPD) and multiple sclerosis (MS). Across prompted environments, the elicited correlations are smooth, stable, and clinically interpretable, yet vary in a statistically significant way that supports downstream invariance testing, such that ICP provides a small set of candidate invariant parent links. These results show that indirect elicitation via triplet comparisons can recover meaningful association structure from LLMs and offer a cautious route from implicit correlations to causal statements that are congruent with LLM answering patterns.

Language models excel at diagnostic assessments on curated medical case-studies and vignettes, performing on par with, or better than, clinical professionals. However, existing studies focus on complex scenarios with rich context making it difficult to draw conclusions about how these systems perform for patients reporting symptoms in everyday life. We deployed SymptomAI, a set of conversational AI agents for end-to-end patient interviewing and differential diagnosis (DDx), via the Fitbit app in a study that randomized participants (N=13,917) to interact with five AI agents. This corpus captures diverse communication and a realistic distribution of illnesses from a real world population. A subset of 1,228 participants reported a clinician-provided diagnosis, and 517 of these were further evaluated by a panel of clinicians during over 250 hours of annotation. SymptomAI DDx were significantly more accurate (OR = 2.56, p < 0.001) than those from independent clinicians given the same dialogue in a blinded randomized comparison. Moreover, agentic strategies which conduct a dedicated symptom interview that elicit additional symptom information before providing a diagnosis, perform substantially better than baseline, user-guided conversations (p < 0.001). An auxiliary analysis on 1,509 conversations from a general US population panel validated that these results generalize beyond wearable device users. We used SymptomAI diagnoses as labels for all 13,917 participants to analyze over 500,000 days of wearable metrics across nearly 400 unique conditions. We identified strong associations between acute infections and physiological shifts (e.g., OR > 7 for influenza). While limited by self-reported ground truth, these results demonstrate the benefits of a dedicated and complete symptom interview compared to a user-guided symptom discussion, which is the default of most consumer LLMs.

Retrieval-Augmented Generation (RAG) offers a well-established path to grounding large language model (LLM) outputs in external knowledge, yet the question of which retrieval strategy works best in a high-stakes domain such as biomedicine has not received the controlled, multi-metric treatment it deserves. This paper presents a systematic empirical comparison of five retrieval strategies -- Dense Vector Search, Hybrid BM25 + Dense retrieval, Cross-Encoder Reranking, Multi-Query Expansion, and Maximal Marginal Relevance (MMR) -- within a biomedical question-answering RAG pipeline. All strategies share a fixed generation model (GPT-4o-mini), a common vector store (ChromaDB), and OpenAI's text-embedding-3-small embeddings, ensuring that observed differences are attributable to retrieval alone. Evaluation is conducted on 250 question-answer pairs drawn from a preprocessed subset of the BioASQ benchmark (rag-mini-bioasq) using four DeepEval metrics: contextual precision, contextual recall, faithfulness, and answer relevancy, each reported with 95% confidence intervals. A no-context ablation is included as a lower bound. Cross-Encoder Reranking achieves the best composite score (0.827) and highest contextual precision (0.852), confirming that query-document interaction yields measurable retrieval gains. Multi-Query Expansion, despite its recall-oriented design, produces the weakest contextual precision (0.671), suggesting naive query diversification introduces retrieval noise. MMR sacrifices answer relevancy for diversity, while the Dense baseline (composite 0.822) falls within 0.005 points of the top strategy. All RAG conditions dramatically outperform the no-context ablation on answer relevancy (0.658-0.701 vs. 0.287), confirming the practical value of retrieval. The full pipeline, hyperparameters, and evaluation code are publicly available.

Background: Patient-facing medical chatbots based on retrieval-augmented generation (RAG) are increasingly promoted to deliver accessible, grounded health information. AI-assisted development lowers the barrier to building them, but they still demand rigorous security, privacy, and governance controls. Objective: To report an anonymized, non-destructive security assessment of a publicly accessible patient-facing medical RAG chatbot and identify governance lessons for safe deployment of generative AI in health. Methods: We used a two-stage strategy. First, Claude Opus 4.6 supported exploratory prompt-based testing and structured vulnerability hypotheses. Second, candidate findings were manually verified using Chrome Developer Tools, inspecting browser-visible network traffic, payloads, API schemas, configuration objects, and stored interaction data. Results: The LLM-assisted phase identified a critical vulnerability: sensitive system and RAG configuration appeared exposed through client-server communication rather than restricted server-side. Manual verification confirmed that ordinary browser inspection allowed collection of the system prompt, model and embedding configuration, retrieval parameters, backend endpoints, API schema, document and chunk metadata, knowledge-base content, and the 1,000 most recent patient-chatbot conversations. The deployment also contradicted its privacy assurances: full conversation records, including health-related queries, were retrievable without authentication. Conclusions: Serious privacy and security failures in patient-facing RAG chatbots can be identified with standard browser tools, without specialist skills or authentication; independent review should be a prerequisite for deployment. Commercial LLMs accelerated this assessment, including under a false developer persona; assistance available to auditors is equally available to adversaries.

Medical retrieval-augmented generation (RAG) systems typically operate on text chunks extracted from biomedical literature, discarding the rich visual content (tables, figures, structured layouts) of original document pages. We propose MED-VRAG, an iterative multimodal RAG framework that retrieves and reasons over PMC document page images instead of OCR'd text. The system pairs ColQwen2.5 patch-level page embeddings with a sharded MapReduce LLM filter, scaling to ~350K pages while keeping Stage-1 retrieval under 30 ms via an offline coarse-to-fine index (C=8 centroids per page, ANN over centroids, exact two-way scoring on the top-R shortlist). A vision-language model (VLM) then iteratively refines its query and accumulates evidence in a memory bank across up to 3 reasoning rounds, with a single iteration costing ~15.9 s and the full three-round pipeline ~47.8 s on 4xA100. Across four medical QA benchmarks (MedQA, MedMCQA, PubMedQA, MMLU-Med), MEDVRAG reaches 78.6% average accuracy. Under controlled comparison with the same Qwen2.5-VL-32B backbone, retrieval contributes a +5.8 point gain over the no-retrieval baseline; we also note a +1.8 point edge over MedRAG + GPT-4 (76.8%), with the caveat that this is a cross-paper rather than head-to-head comparison. Ablations isolate +1.0 from page-image vs text-chunk retrieval, +1.5 from iteration, and +1.0 from the memory bank.

Millions of clinicians use ChatGPT to support clinical care, but evaluations of the most common use cases in model-clinician conversations are limited. We introduce HealthBench Professional, an open benchmark for evaluating large language models on real tasks that clinicians bring to ChatGPT in the course of their work. The benchmark is organized around three common use cases central to clinical practice: care consult, writing and documentation, and medical research. Each example includes a physician-authored conversation with ChatGPT for Clinicians and is scored via rubrics written and iteratively adjudicated by three or more physicians across three phases. HealthBench Professional examples were carefully selected for quality, representativeness, and difficulty for OpenAI's current frontier models, to enable continued measurement of progress. Difficult examples for recent OpenAI models were enriched by roughly 3.5 times relative to the candidate pool of 15,079 examples. Additionally, about one-third of examples involve physicians conducting deliberate adversarial testing of models. As a strong baseline, we also collected human physician responses for all tasks (unbounded time, specialist-matched, web access). The best scoring system, GPT-5.4 in ChatGPT for Clinicians, outperforms base GPT-5.4, all other models, and human physicians. We hope HealthBench Professional provides the healthcare AI community a measure to track frontier model progress in real-world clinical tasks and build systems that clinicians can trust to improve care.

Patient portals now give individuals direct access to their electronic health records (EHRs), yet access alone does not ensure patients understand or act on the complex clinical information contained in these records. The ArchEHR-QA 2026 shared task addresses this challenge by focusing on grounded question answering over EHRs, and this paper presents the system developed by the HealthNLP_Retrievers team for this task. The proposed approach uses a multi-stage cascaded pipeline powered by the Gemini 2.5 Pro large language model to interpret patient-authored questions and retrieve relevant evidence from lengthy clinical notes. Our architecture comprises four integrated modules: (1) a few-shot query reformulation unit which summarizes verbose patient queries; (2) a heuristic-based evidence scorer which ranks clinical sentences to prioritize recall; (3) a grounded response generator which synthesizes professional-caliber answers restricted strictly to identified evidence; and (4) a high-precision many-to-many alignment framework which links generated answers to supporting clinical sentences. This cascaded approach achieved competitive results. Across the individual tracks, the system ranked 1st in question interpretation, 5th in answer generation, 7th in evidence identification, and 9th in answer-evidence alignment. These results show that integrating large language models within a structured multi-stage pipeline improves grounding, precision, and the professional quality of patient-oriented health communication. To support reproducibility, our source code is publicly available in our GitHub repository

Multimodal Large Language Models (MLLMs) have shown transformative potential in medical applications, yet their performance is hindered by conventional data curation strategies that rely on coarse-grained partitioning by modality or department. Such fragmented approaches fail to capture the hierarchical and interconnected nature of clinical medical knowledge, limiting the models' ability to perform fine-grained recognition and complex reasoning. In this paper, we propose a novel Entity-Centric Medical Data Engineering framework. We automatically extract entities from authoritative medical literature to construct a Medical Entity Tree (MET), a hierarchical structure that systematically encodes diseases, anatomical structures, modalities, and symptoms into a unified knowledge repository. Building upon the MET, we propose an advanced data engine that includes: (1) node-guided retrieval to anchor raw data to specific medical concepts, (2) a two-stage hybrid filtering and alignment pipeline to ensure precise visual-semantic correspondence, and (3) knowledge-aware data synthesis to generate enriched captions and targeted reasoning VQA pairs, leveraging structural constraints. Extensive evaluations across six medical benchmarks demonstrate that our approach significantly enhances the medical capabilities of general-purpose MLLMs, improving their ability to handle complex clinical queries and achieve state-of-the-art performance in diverse medical contexts.

Large language models (LLMs) are increasingly deployed, yet their outputs can be highly sensitive to routine, non-adversarial variation in how users phrase queries, a gap not well addressed by existing red-teaming efforts. We propose Green Shielding, a user-centric agenda for building evidence-backed deployment guidance by characterizing how benign input variation shifts model behavior. We operationalize this agenda through the CUE criteria: benchmarks with authentic Context, reference standards and metrics that capture true Utility, and perturbations that reflect realistic variations in the Elicitation of model behavior. Guided by the PCS framework and developed with practicing physicians, we instantiate Green Shielding in medical diagnosis through HealthCareMagic-Diagnosis (HCM-Dx), a benchmark of patient-authored queries, together with structured reference diagnosis sets and clinically grounded metrics for evaluating differential diagnosis lists. We also study perturbation regimes that capture routine input variation and show that prompt-level factors shift model behavior along clinically meaningful dimensions. Across multiple frontier LLMs, these shifts trace out Pareto-like tradeoffs. In particular, neutralization, which removes common user-level factors while preserving clinical content, increases plausibility and yields more concise, clinician-like differentials, but reduces coverage of highly likely and safety-critical conditions. Together, these results show that interaction choices can systematically shift task-relevant properties of model outputs and support user-facing guidance for safer deployment in high-stakes domains. Although instantiated here in medical diagnosis, the agenda extends naturally to other decision-support settings and agentic AI systems.

Multiple myeloma is managed through sequential lines of therapy over years to decades, with each decision depending on cumulative disease history distributed across dozens to hundreds of heterogeneous clinical documents. Whether LLM-based systems can synthesise this evidence at a level approaching expert agreement has not been established. A retrospective evaluation was conducted on longitudinal clinical records of 811 myeloma patients treated at a tertiary centre (2001-2026), covering 44,962 documents and 1,334,677 laboratory values, with external validation on MIMIC-IV. An agentic reasoning system was compared against single-pass retrieval-augmented generation (RAG), iterative RAG, and full-context input on 469 patient-question pairs from 48 templates at three complexity levels. Reference labels came from double annotation by four oncologists with senior haematologist adjudication. Iterative RAG and full-context input converged on a shared ceiling (75.4% vs 75.8%, p = 1.00). The agentic system reached 79.6% concordance (95% CI 76.4-82.8), exceeding both baselines (+3.8 and +4.2 pp; p = 0.006 and 0.007). Gains rose with question complexity, reaching +9.4 pp on criteria-based synthesis (p = 0.032), and with record length, reaching +13.5 pp in the top decile (n = 10). The system error rate (12.2%) was comparable to expert disagreement (13.6%), but severity was inverted: 57.8% of system errors were clinically significant versus 18.8% of expert disagreements. Agentic reasoning was the only approach to exceed the shared ceiling, with gains concentrated on the most complex questions and longest records. The greater clinical consequence of residual system errors indicates that prospective evaluation in routine care is required before these findings translate into patient benefit.

Practitioners deploying small open-weight large language models (LLMs) for medical question answering face a recurring design choice: invest in a domain-fine-tuned model, or keep a general-purpose model and inject domain knowledge at inference time via retrieval-augmented generation (RAG). We isolate this trade-off by holding model size, prompt template, decoding temperature, retrieval pipeline, and evaluation protocol fixed, and varying only (i) whether the model has been domain-adapted (Gemma 3 4B vs. MedGemma 4B, both 4-bit quantized and served via Ollama) and (ii) whether retrieved passages from a medical knowledge corpus are inserted into the prompt. We evaluate all four cells of this 2x2 design on the full MedQA-USMLE 4-option test split (1,273 questions) with three repetitions per question (15,276 LLM calls). Domain fine-tuning yields a +6.8 percentage-point gain in majority-vote accuracy over the general 4B baseline (53.3% vs. 46.4%, McNemar p < 10^-4). RAG over MedMCQA explanations does not produce a statistically significant gain in either model, and in the domain-tuned model the point estimate is slightly negative (-1.9 pp, p = 0.16). At this scale and on this benchmark, domain knowledge encoded in weights dominates domain knowledge supplied in context. We release the full experiment code and JSONL traces to support replication.

Clinical framing -- the linguistic manner in which clinical information is presented -- can influence patient understanding and decision-making, with important implications for healthcare outcomes. Obstetrics is a high-stakes domain in which physicians counsel patients on delivery mode choices such as vaginal birth after cesarean (VBAC) and repeat cesarean section (RCS), yet counseling language remains underexplored in large-scale clinical text analysis. In this work, we analyze physician counseling language in 2,024 obstetric history and physical narratives for a rigorously defined cohort of patients for whom both VBAC and RCS were clinically viable options. To control for confounding due to medical contraindications, we first construct a VBAC-eligible cohort using structured clinical data supplemented by a large language model (LLM)-based extraction pipeline constrained to grounded, verbatim evidence from free-text narratives. We then apply a zero-shot LLM framework to categorize counseling segments into predefined framing categories capturing how physicians linguistically present delivery options. Our analysis reveals a significant difference in counseling framing distributions between VBAC and RCS notes; risk-focused language accounts for a substantially larger share of counseling segments in RCS documentation than in VBAC, with category-level differences confirmed by statistical testing, highlighting the value of controlled LLM-based framing analysis in obstetric care.

Psychiatric intake is a sequential, high-stakes information-gathering process in which clinicians must decide what to ask, in what order, and how to interpret incomplete or ambiguous responses under limited time. Despite growing interest in conversational AI for healthcare, there is still limited infrastructure for conversational AI in this application. Accordingly, we formulate this task as a question-selection problem with clinically grounded questions, known target information, and controllable patient difficulty. We also introduce a task-specific question-selection benchmark based on a bank of 655 clinician-authored intake questions and corresponding synthetic patient vignettes with 5 different behavioral conditions. In our evaluation, we compare random questioning, a clinical psychiatric intake form baseline, and an LLM-guided adaptive policy across 300 interview sessions spanning four patients and five behavioral conditions. Across the benchmark, the clinically ordered fixed form substantially outperforms random questioning, and the LLM-guided policy achieves the strongest overall recovery. The advantage of adaptation grows sharply under patient behavior that is less amenable to field recovery, especially under guarded-concise conditions. These findings suggest that performance in conversational clinical systems depends not only on language understanding after information is disclosed, but also on whether the system reaches the right topics within a limited interaction budget. More broadly, the benchmark provides a controlled framework for studying how clinical structure and adaptive follow-up contribute to information recovery in interactive clinical machine learning.

Large Language Models (LLMs) are increasingly deployed in healthcare, yet their communicative alignment with clinical standards remains insufficiently quantified. We conduct a multidimensional evaluation of general-purpose and domain-specialized LLMs across structured medical explanations and real-world physician-patient interactions, analyzing semantic fidelity, readability, and affective resonance. Baseline models amplify affective polarity relative to physicians (Very Negative: 43.14-45.10% vs. 37.25%) and, in larger architectures such as GPT-5 and Claude, produce substantially higher linguistic complexity (FKGL up to 16.91-17.60 vs. 11.47-12.50 in physician-authored responses). Empathy-oriented prompting reduces extreme negativity and lowers grade-level complexity (up to -6.87 FKGL points for GPT-5) but does not significantly increase semantic fidelity. Collaborative rewriting yields the strongest overall alignment. Rephrase configurations achieve the highest semantic similarity to physician answers (up to mean = 0.93) while consistently improving readability and reducing affective extremity. Dual stakeholder evaluation shows that no model surpasses physicians on epistemic criteria, whereas patients consistently prefer rewritten variants for clarity and emotional tone. These findings suggest that LLMs function most effectively as collaborative communication enhancers rather than replacements for clinical expertise.

This paper investigates Multilingual Medical Question Answering across high-resource (English, Spanish, French, Italian) and low-resource (Basque, Kazakh) languages. We evaluate three types of external evidence sources across models of varying size: curated repositories of specialized medical knowledge, web-retrieved content, and explanations from LLM's parametric knowledge. Moreover, we conduct experiments with multilingual, monolingual and cross-lingual retrieval. Our results demonstrate that larger models consistently achieve superior performance in English across baseline evaluations. When incorporating external knowledge, web-retrieved data in English proves most beneficial for high-resource languages. Conversely, for low-resource languages, the most effective strategy combines retrieval in both English and the target language, achieving comparable accuracy to high-resource language results. These findings challenge the assumption that external knowledge systematically improves performance and reveal that effective strategies depend on both the source of language resources and on model scale. Furthermore, specialized medical knowledge sources such as PubMed are limited: while they provide authoritative expert knowledge, they lack adequate multilingual coverage

Timely and interpretable early warning of sepsis remains a major clinical challenge due to the complex temporal dynamics of physiological deterioration. Traditional data-driven models often provide accurate yet opaque predictions, limiting physicians' confidence and clinical applicability. To address this limitation, we propose a Large Language Model (LLM)-guided temporal simulation framework that explicitly models physiological trajectories prior to disease onset for clinically interpretable prediction. The framework consists of a spatiotemporal feature extraction module that captures dynamic dependencies among multivariate vital signs, a Medical Prompt-as-Prefix module that embeds clinical reasoning cues into LLMs, and an agent-based post-processing component that constrains predictions within physiologically plausible ranges. By first simulating the evolution of key physiological indicators and then classifying sepsis onset, our model offers transparent prediction mechanisms that align with clinical judgment. Evaluated on the MIMIC-IV and eICU databases, the proposed method achieves superior AUC scores (0.861-0.903) across 24-4-hour pre-onset prediction tasks, outperforming conventional deep learning and rule-based approaches. More importantly, it provides interpretable trajectories and risk trends that can assist clinicians in early intervention and personalized decision-making in intensive care environments.

The use of Large Language Models (LLMs) to support patients in addressing medical questions is becoming increasingly prevalent. However, most of the measures currently used to evaluate the performance of these models in this context only measure how closely a model's answers match semantically, and therefore do not provide a true indication of the model's medical accuracy or of the health equity risks associated with it. To address these shortcomings, we present a new evaluation framework for medical question answering called VB-Score (Verification-Based Score) that provides a separate evaluation of the four components of entity recognition, semantic similarity, factual consistency, and structured information completeness for medical question-answering models. We perform rigorous reviews of the performance of three well-known and widely used LLMs on 48 public health-related topics taken from high-quality, authoritative information sources. Based on our analyses, we discover a major discrepancy between the models' semantic and entity accuracy. Our assessments of the performance of all three models show that each of them has almost uniformly severe performance failures when evaluated against our criteria. Our findings indicate alarming performance disparities across various public health topics, with most of the models exhibiting 13.8% lower performance (compared to an overall average) for all the public health topics that relate to chronic conditions that occur in older and minority populations, which indicates the existence of what's known as condition-based algorithmic discrimination. Our findings also demonstrate that prompt engineering alone does not compensate for basic architectural limitations on how these models perform in extracting medical entities and raise the question of whether semantic evaluation alone is a sufficient measure of medical AI safety.

Safe clinical deployment of Large Language Models (LLMs) requires not only high accuracy but also robust uncertainty calibration to ensure models defer to clinicians when appropriate. Our paper investigates how social descriptors of a patient (specifically sexual orientation and religious affiliation) distort these uncertainty signals and model accuracy. Evaluating nine general-purpose and biomedical LLMs on 2,364 medical questions and their counterfactual variants, we demonstrate that identity markers cause a "calibration crisis". "Homosexual" markers consistently trigger performance drops, and intersectional identities produce idiosyncratic, non-additive harms to calibration. Moreover, a clinician-validated case study in an open-ended generation setting confirms that these failures are not an artifact of the multiple-choice format. Our results demonstrate that the presence of social identity cues does not merely shift predictions; it affects the reliability of confidence signals, posing a significant risk to equitable care and safe deployment in confidence-based clinical workflows.

Process-Level Reward Models (PRMs) are essential for guiding complex reasoning in large language models, yet existing PRM benchmarks cover only general domains such as mathematics, failing to address medical reasoning -- which is uniquely characterized by safety criticality, knowledge intensity, and diverse error patterns. Without a reliable medical PRM evaluation framework, we cannot quantify models' error detection capabilities in clinical reasoning, leaving their safety in real-world healthcare applications unverified. We propose MedPRMBench, the first process-level reward model benchmark for the medical domain. Built through a three-phase pipeline based on Clinical Reasoning Blueprints (CRBs), MedPRMBench systematically generates high-quality evaluation data from seven medical QA sources, covering 14 fine-grained error types across three categories (Simplicity, Soundness, and Sensitivity) with the first 4-level severity grading system to quantify clinical impact. The benchmark comprises 6{,}500 questions with 13{,}000 reasoning chains and 113{,}910 step-level labels, plus 6{,}879 questions for training. Our medical PRM baseline achieves an 87.1% overall PRMScore -- substantially surpassing all baselines -- and serves as a plug-and-play verifier that improves downstream medical QA accuracy by 3.2--6.7 percentage points. Systematic evaluation spanning proprietary frontier models, open-source reasoning models, and medical-specialized models reveals critical weaknesses in current models' medical reasoning error detection capabilities, providing clear directions for future PRM improvement.

Large Language Models (LLMs) have shown strong promise in healthcare applications. Yet deploying general-purpose models in real-world settings remains difficult due to data privacy constraints, inference costs, and limited suitability for edge or on-device use. These challenges motivate the development of smaller, more efficient models that require robust post-training strategies to ensure reliable medical reasoning. In this work, we investigate Group Relative Policy Optimization (GRPO) for post-training LLMs on heart-focused medical question answering with rubric-based supervision derived from RaR-Medicine. We propose a Variance-Aware Reward Framework that extends the Explicit Aggregation and Implicit Aggregation strategies of Rubrics as Rewards by replacing weighted binary criterion aggregation and single overall Likert-style scoring with continuous analytical reward functions derived from criterion-level rubric outcomes. This formulation provides richer optimization signals for feedback that is sparse, multi-criteria, and difficult to verify automatically, and enables more stable on-policy reinforcement learning. On a held-out heart-related subset of HealthBench, our best GRPO variant improves accuracy from 0.362 to 0.502 and F1 from 0.532 to 0.668 relative to the Qwen3-14B base model, while remaining competitive with GPT-OSS-120B (0.508 accuracy, 0.674 F1). Our findings show that carefully designed rubric-based rewards provide a practical strategy for improving heart-focused medical question answering in LLMs, with potential to extend to other rubric-based tasks.

Large Language Models (LLMs) with reasoning capabilities have recently demonstrated strong potential in medical Question Answering (QA). Existing approaches are largely English-focused and primarily rely on distillation from general-purpose LLMs, raising concerns about the reliability of their medical knowledge. In this work, we present a method to generate multilingual reasoning traces based on medical knowledge extracted from Wikipedia. We produce 500k traces in English, Italian, and Spanish, using a retrieval-augmented generation approach over medical information from Wikipedia. The traces are generated to solve medical questions drawn from MedQA and MedMCQA, which we extend to Italian and Spanish. We test our pipeline in both in-domain and out-of-domain settings across Medical QA benchmarks, and demonstrate that our reasoning traces improve performance both when utilized via in-context learning (few-shot) and supervised fine-tuning, yielding state-of-the-art results among 8B-parameter LLMs. We believe that these resources can support the development of more transparent clinical decision-support tools in multilingual settings. We release the full suite of resources: reasoning traces, translated QA datasets, Medical-Wikipedia, and fine-tuned models.

Large language models (LLMs) and medical AI tools are routinely used by physicians and patients for medical advice, yet their clinical safety profiles remain poorly characterized. We present NOHARM (Numerous Options Harm Assessment for Risk in Medicine), a 1,100-task benchmark of primary care-to-specialist consultation cases to measure the frequency and severity of potentially harmful errors from LLM-generated medical consultation recommendations. NOHARM covers 10 specialties, with 12,747 expert annotations for 4,249 clinical management options. Across 20 notable LLMs and 4 widely used retrieval-augmented generation (RAG) clinical AI tools, direct application of recommendations carried potential for severe harm in up to 24.6% of cases, with errors of omission accounting for more than 80% of severe errors. Harm potential was not uniform across systems, with clinical AI tools outperforming generalist LLMs, and multi-agent AI teaming further improving performance in generalist models. In a randomized study of 101 U.S.-licensed generalist physicians, AI assistance improved physician performance compared to conventional resources. However, AI-assisted physicians frequently omitted valuable AI-generated recommendations and still scored lower than many AI systems alone. Had those recommendations been incorporated, combined human-AI responses would have outperformed both the human and AI system as used, suggesting complementary strengths and unrealized potential in human-AI teaming. Collectively, these results show that despite strong performance on medical knowledge benchmarks, widely used AI tools can produce medical consultation advice with the potential for severe harm, and highlight the need for explicit measurement of clinical safety. The benchmark and leaderboard are publicly available to support ongoing evaluation and improvement of AI systems used for clinical care.

Equitable access to reliable health information is vital when integrating AI into healthcare. Yet, information quality varies across languages, raising concerns about the reliability and consistency of multilingual Large Language Models (LLMs). We systematically examine cross-lingual disparities in pre-training source and factuality alignment in LLM answers for multilingual healthcare Q&A across English, German, Turkish, Chinese (Mandarin), and Italian. We (i) constructed Multilingual Wiki Health Care (MultiWikiHealthCare), a multilingual dataset from Wikipedia; (ii) analyzed cross-lingual healthcare coverage; (iii) assessed LLM response alignment with these references; and (iv) conducted a case study on factual alignment through the use of contextual information and Retrieval-Augmented Generation (RAG). Our findings reveal substantial cross-lingual disparities in both Wikipedia coverage and LLM factual alignment. Across LLMs, responses align more with English Wikipedia, even when the prompts are non-English. Providing contextual excerpts from non-English Wikipedia at inference time effectively shifts factual alignment toward culturally relevant knowledge. These results highlight practical pathways for building more equitable, multilingual AI systems for healthcare.

Interactive medical questioning is essential in clinical consultations, where physicians must actively gather necessary patient information. Yet existing medical Large Language Models (LLMs) predominantly follow a reactive paradigm, risking diagnostic errors by answering before seeking sufficient details. To bridge this gap, we propose ProMed, a reinforcement learning framework that transitions LLMs toward a proactive paradigm, enabling them to ask clinically valuable questions before decision-making. Central to ProMed is the Shapley Information Gain (SIG) reward, which quantifies a question's clinical utility as the amount of newly acquired information, while considering its contextual importance via Shapley values. We integrate SIG into a two-stage training pipeline: (1) SIG-Guided Model Initialization uses Monte Carlo Tree Search to construct high-reward interaction trajectories for supervision, and (2) SIG-Augmented Policy Optimization, with a novel SIG-guided Reward Distribution Mechanism that prioritizes informative questions for fine-grained optimization. Experiments on partial-information medical benchmarks show that ProMed significantly outperforms state-of-the-art methods by 6.29% on average and delivers a 54.45% gain over the reactive paradigm, and generalizes robustly to out-of-domain cases. Our codes are available at https://github.com/hxxding/ProMed.

Thematic analysis (TA) is a widely used qualitative approach for uncovering latent meanings in unstructured text data. TA provides valuable insights in healthcare but is resource-intensive. Large Language Models (LLMs) have been introduced to perform TA, yet their applications in high-stakes healthcare settings, particularly for qualitative clinical interview analysis, remain limited. Here, we propose TAMA: A Human-AI Collaborative Thematic Analysis framework using Multi-Agent LLMs for clinical interviews. We leverage the scalability and coherence of multi-agent systems through structured conversations between agents and coordinate the expertise of cardiac experts in TA. Using interview transcripts from parents of children with Anomalous Aortic Origin of a Coronary Artery (AAOCA), a rare congenital heart disease, we demonstrate that TAMA outperforms single-agent LLM TA approaches, achieving higher thematic hit rate, coverage, and distinctiveness. TAMA demonstrates strong potential for automated TA in clinical settings by leveraging multi-agent LLM systems with human-in-the-loop integration by enhancing quality while significantly reducing manual workload. The full implementation is publicly available at https://github.com/Charlie-Yi-SJ/TAMA.

In this paper, we propose a modified version of the MedQA-USMLE dataset, named MEDQA-OPEN, which contains open-ended medical questions without options to mimic clinical scenarios, along with clinician-approved reasoned answers. Additionally, we implement a prompt driven by Chain of Thought (CoT) reasoning, CLINICR, to mirror the prospective process of incremental reasoning, reaching a correct response to medical questions. We empirically demonstrate how CLINICR outperforms the state-of-the-art 5-shot CoT-based prompt (Liévin et al., 2022). We also present an approach that mirrors real-life clinical practice by first exploring multiple differential diagnoses through MCQ-CLINICR and subsequently narrowing down to a final diagnosis using MCQ-ELIMINATIVE. Finally, emphasizing the importance of response verification in medical settings, we utilize a reward model mechanism, replacing the elimination process performed by MCQ-ELIMINATIVE.

Large-scale language models (LLMs) often offer clinical judgments based on incomplete information, increasing the risk of misdiagnosis. Existing studies have primarily evaluated confidence in single-turn, static settings, overlooking the coupling between confidence and correctness as clinical evidence accumulates during real consultations, which limits their support for reliable decision-making. We propose the first benchmark for assessing confidence in multi-turn interaction during realistic medical consultations. Our benchmark unifies three types of medical data for open-ended diagnostic generation and introduces an information sufficiency gradient to characterize the confidence-correctness dynamics as evidence increases. We implement and compare 27 representative methods on this benchmark; two key insights emerge: (1) medical data amplifies the inherent limitations of token-level and consistency-level confidence methods, and (2) medical reasoning must be evaluated for both diagnostic accuracy and information completeness. Based on these insights, we present MedConf, an evidence-grounded linguistic self-assessment framework that constructs symptom profiles via retrieval-augmented generation, aligns patient information with supporting, missing, and contradictory relations, and aggregates them into an interpretable confidence estimate through weighted integration. Across two LLMs and three medical datasets, MedConf consistently outperforms state-of-the-art methods on both AUROC and Pearson correlation coefficient metrics, maintaining stable performance under conditions of information insufficiency and multimorbidity. These results demonstrate that information adequacy is a key determinant of credible medical confidence modeling, providing a new pathway toward building more reliable and interpretable large medical models.

Medical large language models are typically evaluated on idealized patient cases that do not reflect how real patients communicate. We introduce VeriSim, a patient simulation framework that injects controllable noise along six clinically grounded communication dimensions while substantially preserving each patient's medical record. Truth adherence is supported by a verifier that extracts atomic claims from each candidate utterance and judges them against a UMLS-grounded vector index built with BioLORD embeddings, using the retrieved atoms' structured clinical metadata (e.g., drug class, anatomical site, treats-condition relations) rather than surface-text similarity alone. Across seven open-weight LLMs, realistic noise reduces diagnostic accuracy by 15-25 percentage points and increases conversation length by 34-55%; the 7-8B models degrade 1.4x more than 70B+ models. A board-certified physician and a licensed nurse rate VeriSim's conversations highly on truth, realism, clinical utility, and noise fidelity (inter-annotator agreement >= 0.80 across all dimensions), and an LLM-as-judge closely tracks their ratings, enabling scalable evaluation. We release VeriSim as an open-source framework for rigorous stress-testing of clinical AI: https://github.com/mohitmarvania/VeriSim