Self-supervised respiratory encoders lack semantic grounding in clinical domain needed for zero-shot inference, limiting their utility without task-specific labeled data. We propose a framework that aligns these encoders with medical terminology in a shared latent space turning them into a zero-shot-capable foundation model. To address paired data scarcity, we use a medical LLM to synthesize structured reports from metadata, creating dense semantic anchors for contrastive learning. Our training combines a sigmoid-based contrastive loss with encoder's native SSL objective and similarity-aware negative sampling to sharpen pathological boundaries. Across 9 tasks on 6 datasets, our method achieves a 61.3% mean zero-shot AUC, surpassing CLAP (51.4%) and Qwen2-Audio (54.9%) while reaching the highest linear probing AUC (71.6%) with only 43% of data used by full-scale baselines, showing that structured semantic alignment outperforms large-scale, general-purpose models in clinical diagnostics.
Following clinical decision pathways (CDPs) defined by clinical practice guidelines is essential for safe and reliable medical decision-making. However, existing medical large language model (LLM) benchmarks mainly evaluate final-answer accuracy, providing limited evaluation of models' ability to adhere to guidelines. To address this gap, we introduce MEGA-CDP, a benchmark for evaluating whether medical LLMs can generate guideline-adherent CDPs using provided guidelines as references. MEGA-CDP is constructed from 2,274 English and Chinese clinical practice guidelines through a guideline-to-case pipeline, yielding 42,353 clinical cases with explicit reference CDPs. It supports both single-turn vignette and multi-turn interactive settings, and introduces a CDP-oriented evaluation framework for measuring pathway consistency. Experiments on 16 representative LLMs show that reliable clinical decision support remains challenging for current models, demonstrating the need for CDP-oriented evaluation and the value of MEGA-CDP for advancing guideline adherence in medical LLMs.
Medical large language models are often judged by how many clinical questions they answer correctly. That view is useful, but it misses a practical risk. A model may know the right answer and still change its response when the same case is written in a different patient voice. This paper evaluates that risk as SDoH aware narrative anchoring bias. We use NarrativeShield SDoH MedQA, a counterfactual medical question answering dataset in which each case appears in persona based narratives while the answer key remains fixed. The dataset is reshaped from wide format into case grouped persona rows. We evaluate three open source instruction tuned LLMs from the Qwen2.5 family: 1.5B, 3B, and 7B. The final experiment uses 300 clinical cases and produces 8,100 model responses across three prompting conditions. We report persona level accuracy, counterfactual consistency, correct consistency, and narrative sensitivity error. Qwen2.5 7B achieves the best accuracy at 56.33 percent and the best correct consistency at 40.33 percent. Paired McNemar exact tests show significant accuracy gains for 7B over 3B in all prompt settings. Even so, narrative sensitivity remains, with the lowest error still at 31.67 percent. These results suggest that trustworthy clinical decision support should be evaluated by both average correctness and stability across medically equivalent patient narratives.
Specialist language models are usually understood through endpoint gains: the generalist scores lower, the specialist scores higher, and the difference is treated as evidence of specialization. This leaves the released update itself largely unexamined. We propose a paired weight-delta path audit and apply it to two public, aligned generalist-to-medical-specialist checkpoint pairs: Gemma-3-4B-IT to MedGemma-4B-IT and Qwen2.5-7B-Instruct to HuatuoGPT-o1-7B. In both pairs, the full decoder-side update strongly reconstructs measured medical benchmark movement (0.974 and 1.183 endpoint-normalized retention), making each decoder delta an appropriate substrate for the audit. Yet the movement is not cleanly localized. MLP is the strongest broad component family in both pairs, but mixed off-domain movements, 10-seed matched controls, and endpoint-anchored rollbacks prevent a unique coarse-family explanation. The audit therefore separates update-level reconstruction from component-level explanation. Its claims concern text-only multiple-choice benchmark movement, not clinical validation, repair, or circuit-level mechanism.
Clinical-AI guidance increasingly recommends prompting language models to reason with attention to diversity, equity, and inclusion (DEI). We measure a side effect that misrepresents patients: a one-sentence DEI prompt appended to a medical question leads models to add patient demographic attributes (race, socioeconomic status, sex) the question never stated, in effect rewriting who the patient is. We call this demographic injection. Across 47 models, four medical benchmarks, and 376,000 responses scored by a validated model-judge pipeline, a single DEI prompt raises the injection rate from 0.7% to 33.1% (47x) in all 47 of 47 models, attributable to the equity content rather than to added length (18x above a length-matched control; p=1.4x10^-14). Most added content is a general population statement that leaves the answer unchanged, but a smaller subset attaches an attribute to the specific patient or changes the selected option (0.25-2.4% of responses, 99.8% toward the incorrect option), where the invented demographic changes the answer the model recommends. Phrasing scales the effect from 14% to 56%. DEI prompts are just one example of a more general mechanism. Any instruction that nudges how a model reasons can make it add unrequested details, including details about the patient. Flagged outputs are treated as model errors under study, not clinical guidance.
Safety evaluation of large language models is conducted predominantly in English and predominantly on frontier systems. Neither condition describes how such models are encountered in low-resource health settings, where small quantised systems are run locally and queried in local languages. We ask whether clinical safety established in English transfers to Hausa, and whether any failure is attributable to the language, the clinical task, or the class of model that low-resource deployment admits. Matched English-Hausa question pairs were built for three conditions of high burden in northern Nigeria: malaria, sickle cell disease, and tuberculosis, probing knowledge recall, emergency triage, a leading question inviting a contraindicated action, and a traditional-remedy claim. Six models were evaluated: five locally deployable systems of 4-9 billion parameters, two medically fine-tuned, and one frontier system. All 128 responses were scored against Nigerian national treatment guidelines by two fluent Hausa speakers working independently and blind to one another. Among locally deployable models, mean clinical correctness fell from 1.57 in English to -0.03 in Hausa, on a scale where 2 denotes a correct answer and -1 an actively harmful one. The frontier model moved from 2.00 to 1.75 and produced no response judged harmful in either language. Drift was consistent across all three conditions. Inter-rater agreement was substantial for clinical correctness (kappa = 0.70); agreement on harm was initially poor (kappa = 0.22) and is examined in detail. Because a frontier model answers the same questions competently in Hausa, the deficit is a property neither of the language nor of the clinical material, but of the deployable tier.
Hallucination remains one of the central obstacles to deploying medical LLMs. Yet, even when hallucination can be detected, it is still unclear whether the internal representations associated with it can be used for control rather than detection alone. Using four open-source models across a suite of medical question-answering datasets, we show that a simple, carefully conditioned probe can reliably detect hallucination, with AUROC scores between 0.77 and 0.86 in our case. We further show that this signal is distributed and redundant rather than narrowly localized. Systematically selected neurons outperform random neurons only at very small subset sizes, whereas random subsets of a few hundred neurons recover nearly the full signal, and low-dimensional random projections preserve most of the detection performance. Beyond detection, we test whether this representation is causally actionable. Across 16 model--dataset combinations, our results reveal a sharp gap between decodability and controllability. The same internal structure that makes hallucination easy to detect does not translate into reliable neuron-level control. These findings show that medical hallucination seems to be readily visible in internal activations, but not easily corrected by steering the neurons most associated with it. More broadly, our results suggest that hallucination mitigation is not simply a matter of identifying the right neurons, and point to a deeper separation between what representations reveal and what they allow us to change.
Rare disease differential diagnosis is a critical yet arduous clinical task, requiring physicians to identify precise phenotypes from complex, unstructured patient symptoms and execute intricate reasoning within a vast search space. However, existing AI approaches typically rely on pipeline-based phenotype extraction or retrieval-augmented generation, which suffer from critical information loss due to predefined ontologies, retrieval bottlenecks, and a lack of diagnostic logic. To address these challenges, we introduce RareDxR1, an end-to-end reasoning-centric large language model designed for open-domain rare disease diagnosis directly from unstructured clinical notes. We design a progressive end-to-end training framework by synergizing knowledge internalization with autonomous evolutionary learning, thereby bypassing reliance on structured phenotypes and closed-set decision-making. To overcome the limitations of RAG and phenotype restriction, we enabled the deep internalization of fragmented rare-disease knowledge directly into the model's parameters. Moreover, to bridge the gap between model generation and expert reasoning, we propose Reflection-Enhanced Reasoning Sampling (RERS), a strategy that synthesizes expert-level diagnostic trajectories by learning from failures without human annotation. Additionally, we propose a dual-level curriculum reinforcement learning approach for gradually mastering rare disease diagnosis. Experimental results demonstrate that RareDxR1 achieves state-of-the-art accuracy across different benchmarks, marking a significant breakthrough in open-domain rare disease diagnosis. Our code and dataset will be publicly available.
Large language models (LLMs) are increasingly considered for use in clinical consultation tasks, yet most medical evaluations remain static, single-turn, or narrowly outcome-based, limiting their ability to reflect the sequential, uncertain, and interactive nature of real-world care. Here, we propose AIPatient Arena, an EHRs-grounded evaluation framework for assessing the clinical utility of LLMs across eight dimensions of clinical competence. The framework integrates EHR data into patient-specific knowledge graphs, enabling multi-turn physician-patient interactions. We applied AIPatient Arena on a primary cohort of 437 patients and two out-of-distribution validation cohorts of 119 and 67 patients. We observe that LLMs performed well in medical interview questioning skills (QS; mean scores, 4.43-4.99/5), ethical and professional conduct (ET; 4.38-4.93/5), and clarity and transparency of clinical explanations (EX; 3.80-4.72/5). Performance was moderate in information integration (II; 3.19-4.21/5) and medication safety and justification (MS; 3.13-3.78/5), but persistent weaknesses were observed in handling of ambiguous patient responses (HR; 2.57-3.32/5), information coverage (IC; 2.08-3.02/5), and diagnostic accuracy and reasoning (Dx; 2.63-3.55/5). Process-based evaluation revealed recurrent interaction failures, including repetitive questioning, omission of past medical history, and inadequate handling of uncertainty. Richer conversational context improved diagnostic reasoning but yielded limited gains in treatment planning. These findings indicate that final-answer accuracy alone is insufficient for evaluating clinical readiness and highlight the importance of assessing how models gather, interpret, and communicate information throughout a consultation. AIPatient Arena provides an EHR-grounded framework for workflow-oriented pre-deployment evaluation of medical LLMs.
Large language models (LLMs) have been widely adopted in healthcare, yet they still encounter significant challenges in complex clinical decision-making scenarios. Existing benchmarks primarily assess LLM performance in single-course settings and lack systematic evaluation in multi-course scenarios, where a patient's condition evolves over time. To address this gap, we propose ClinicalMC, a benchmark for multi-course clinical decision-making. It includes 1,275 Chinese and 5,804 English samples across four stages from admission to discharge. These stages cover triage, first-course examination/diagnosis/treatment, subsequent multi-course examination/assessment/treatment, and final diagnosis. In ClinicalMC, patients in the English dataset undergo an average of 5.11 clinical courses, whereas those in the Chinese dataset undergo 3.42. To assess LLM performance, we construct a multi-agent evaluation framework that includes patient, examiner, and doctor agents. Based on the benchmark and framework, we design two experimental settings -- a single-turn static setting and a multi-turn dynamic setting -- and assess three categories of LLMs: 1) closed-source LLMs like GPT5-mini; 2) open-source LLMs like DeepSeek-V3.2; and 3) medical LLMs like HuatuoGPT-o1. Through extensive evaluation, we aim to better understand LLM performance in the medical domain and support its effective deployment in healthcare.
Sunday Oyinlola Ogundoyin, Muhammad Ikram, Rahat Masoodcs.CL cs.CY
Medical large language models (LLMs), including custom medical GPTs (MedGPTs) and open-source models, are increasingly deployed on web platforms to provide clinical guidance. However, they pose risks of hallucination, policy noncompliance, and unsafe design. We conduct a large-scale assessment of 6,233 MedGPTs, evaluating a stratified sample of 1,500, together with 10 open-source LLMs. We introduce two frameworks: MedGPT-HEval for hallucination detection and an LLM-based pipeline for assessing policy violations and developer intent. Our results show that 25-30% of MedGPTs exhibit low factual accuracy, with bottom- and middle-tier models at highest risk; 33.6-54.3% violate operational thresholds, and 57.06% of Action-enabled models lack adequate privacy disclosures. Compared with open-source models, MedGPTs achieve higher factual accuracy and semantic alignment, though open-source models are more stable. These results reveal systemic gaps in hallucination and compliance, highlighting the need for multi-metric evaluation and stronger safeguards. We release HAA-MedGPT, a structured dataset that supports future research on the safety of web-facing medical LLMs.