Daily Papers

Large-language models have recently demonstrated impressive zero-shot capabilities in a variety of natural language tasks such as summarization, dialogue generation, and question-answering. Despite many promising applications in clinical medicine, adoption of these models in real-world settings has been largely limited by their tendency to generate incorrect and sometimes even toxic statements. In this study, we develop Almanac, a large language model framework augmented with retrieval capabilities for medical guideline and treatment recommendations. Performance on a novel dataset of clinical scenarios (n = 130) evaluated by a panel of 5 board-certified and resident physicians demonstrates significant increases in factuality (mean of 18% at p-value < 0.05) across all specialties, with improvements in completeness and safety. Our results demonstrate the potential for large language models to be effective tools in the clinical decision-making process, while also emphasizing the importance of careful testing and deployment to mitigate their shortcomings.

Large Language Models (LLMs) have attained human-level accuracy on medical question-answer (QA) benchmarks. However, their limitations in navigating open-ended clinical scenarios have recently been shown, raising concerns about the robustness and generalizability of LLM reasoning across diverse, real-world medical tasks. To probe potential LLM failure modes in clinical problem-solving, we present the medical abstraction and reasoning corpus (M-ARC). M-ARC assesses clinical reasoning through scenarios designed to exploit the Einstellung effect -- the fixation of thought arising from prior experience, targeting LLM inductive biases toward inflexible pattern matching from their training data rather than engaging in flexible reasoning. We find that LLMs, including current state-of-the-art o1 and Gemini models, perform poorly compared to physicians on M-ARC, often demonstrating lack of commonsense medical reasoning and a propensity to hallucinate. In addition, uncertainty estimation analyses indicate that LLMs exhibit overconfidence in their answers, despite their limited accuracy. The failure modes revealed by M-ARC in LLM medical reasoning underscore the need to exercise caution when deploying these models in clinical settings.

Diagnosing and treating skin diseases require advanced visual skills across domains and the ability to synthesize information from multiple imaging modalities. While current deep learning models excel at specific tasks like skin cancer diagnosis from dermoscopic images, they struggle to meet the complex, multimodal requirements of clinical practice. Here, we introduce PanDerm, a multimodal dermatology foundation model pretrained through self-supervised learning on over 2 million real-world skin disease images from 11 clinical institutions across 4 imaging modalities. We evaluated PanDerm on 28 diverse benchmarks, including skin cancer screening, risk stratification, differential diagnosis of common and rare skin conditions, lesion segmentation, longitudinal monitoring, and metastasis prediction and prognosis. PanDerm achieved state-of-the-art performance across all evaluated tasks, often outperforming existing models when using only 10% of labeled data. We conducted three reader studies to assess PanDerm's potential clinical utility. PanDerm outperformed clinicians by 10.2% in early-stage melanoma detection through longitudinal analysis, improved clinicians' skin cancer diagnostic accuracy by 11% on dermoscopy images, and enhanced non-dermatologist healthcare providers' differential diagnosis by 16.5% across 128 skin conditions on clinical photographs. These results demonstrate PanDerm's potential to improve patient care across diverse clinical scenarios and serve as a model for developing multimodal foundation models in other medical specialties, potentially accelerating the integration of AI support in healthcare. The code can be found at https://github.com/SiyuanYan1/PanDerm.

Users typically engage with LLMs interactively, yet most existing benchmarks evaluate them in a static, single-turn format, posing reliability concerns in interactive scenarios. We identify a key obstacle towards reliability: LLMs are trained to answer any question, even with incomplete context or insufficient knowledge. In this paper, we propose to change the static paradigm to an interactive one, develop systems that proactively ask questions to gather more information and respond reliably, and introduce an benchmark - MediQ - to evaluate question-asking ability in LLMs. MediQ simulates clinical interactions consisting of a Patient System and an adaptive Expert System; with potentially incomplete initial information, the Expert refrains from making diagnostic decisions when unconfident, and instead elicits missing details via follow-up questions. We provide a pipeline to convert single-turn medical benchmarks into an interactive format. Our results show that directly prompting state-of-the-art LLMs to ask questions degrades performance, indicating that adapting LLMs to proactive information-seeking settings is nontrivial. We experiment with abstention strategies to better estimate model confidence and decide when to ask questions, improving diagnostic accuracy by 22.3%; however, performance still lags compared to an (unrealistic in practice) upper bound with complete information upfront. Further analyses show improved interactive performance with filtering irrelevant contexts and reformatting conversations. Overall, we introduce a novel problem towards LLM reliability, an interactive MediQ benchmark and a novel question-asking system, and highlight directions to extend LLMs' information-seeking abilities in critical domains.

Clinical Question Answering (QA) systems enable doctors to quickly access patient information from electronic health records (EHRs). However, training these systems requires significant annotated data, which is limited due to the expertise needed and the privacy concerns associated with clinical data. This paper explores generating Clinical QA data using large language models (LLMs) in a zero-shot setting. We find that naive prompting often results in easy questions that do not reflect the complexity of clinical scenarios. To address this, we propose two prompting strategies: 1) instructing the model to generate questions that do not overlap with the input context, and 2) summarizing the input record using a predefined schema to scaffold question generation. Experiments on two Clinical QA datasets demonstrate that our method generates more challenging questions, significantly improving fine-tuning performance over baselines. We compare synthetic and gold data and find a gap between their training efficacy resulting from the quality of synthetically generated answers.

Artificial intelligence (AI) and large language models (LLMs) in healthcare require advanced clinical skills (CS), yet current benchmarks fail to evaluate these comprehensively. We introduce MedQA-CS, an AI-SCE framework inspired by medical education's Objective Structured Clinical Examinations (OSCEs), to address this gap. MedQA-CS evaluates LLMs through two instruction-following tasks, LLM-as-medical-student and LLM-as-CS-examiner, designed to reflect real clinical scenarios. Our contributions include developing MedQA-CS, a comprehensive evaluation framework with publicly available data and expert annotations, and providing the quantitative and qualitative assessment of LLMs as reliable judges in CS evaluation. Our experiments show that MedQA-CS is a more challenging benchmark for evaluating clinical skills than traditional multiple-choice QA benchmarks (e.g., MedQA). Combined with existing benchmarks, MedQA-CS enables a more comprehensive evaluation of LLMs' clinical capabilities for both open- and closed-source LLMs.

Diffusion-weighted MRI (DWI) is essential for stroke diagnosis, treatment decisions, and prognosis. However, image and disease variability hinder the development of generalizable AI algorithms with clinical value. We address this gap by presenting a novel ensemble algorithm derived from the 2022 Ischemic Stroke Lesion Segmentation (ISLES) challenge. ISLES'22 provided 400 patient scans with ischemic stroke from various medical centers, facilitating the development of a wide range of cutting-edge segmentation algorithms by the research community. Through collaboration with leading teams, we combined top-performing algorithms into an ensemble model that overcomes the limitations of individual solutions. Our ensemble model achieved superior ischemic lesion detection and segmentation accuracy on our internal test set compared to individual algorithms. This accuracy generalized well across diverse image and disease variables. Furthermore, the model excelled in extracting clinical biomarkers. Notably, in a Turing-like test, neuroradiologists consistently preferred the algorithm's segmentations over manual expert efforts, highlighting increased comprehensiveness and precision. Validation using a real-world external dataset (N=1686) confirmed the model's generalizability. The algorithm's outputs also demonstrated strong correlations with clinical scores (admission NIHSS and 90-day mRS) on par with or exceeding expert-derived results, underlining its clinical relevance. This study offers two key findings. First, we present an ensemble algorithm (https://github.com/Tabrisrei/ISLES22_Ensemble) that detects and segments ischemic stroke lesions on DWI across diverse scenarios on par with expert (neuro)radiologists. Second, we show the potential for biomedical challenge outputs to extend beyond the challenge's initial objectives, demonstrating their real-world clinical applicability.

Although large language models (LLMs) have been assessed for general medical knowledge using medical licensing exams, their ability to effectively support clinical decision-making tasks, such as selecting and using medical calculators, remains uncertain. Here, we evaluate the capability of both medical trainees and LLMs to recommend medical calculators in response to various multiple-choice clinical scenarios such as risk stratification, prognosis, and disease diagnosis. We assessed eight LLMs, including open-source, proprietary, and domain-specific models, with 1,009 question-answer pairs across 35 clinical calculators and measured human performance on a subset of 100 questions. While the highest-performing LLM, GPT-4o, provided an answer accuracy of 74.3% (CI: 71.5-76.9%), human annotators, on average, outperformed LLMs with an accuracy of 79.5% (CI: 73.5-85.0%). With error analysis showing that the highest-performing LLMs continue to make mistakes in comprehension (56.6%) and calculator knowledge (8.1%), our findings emphasize that humans continue to surpass LLMs on complex clinical tasks such as calculator recommendation.

We introduce RJUA-QA, a novel medical dataset for question answering (QA) and reasoning with clinical evidence, contributing to bridge the gap between general large language models (LLMs) and medical-specific LLM applications. RJUA-QA is derived from realistic clinical scenarios and aims to facilitate LLMs in generating reliable diagnostic and advice. The dataset contains 2,132 curated Question-Context-Answer pairs, corresponding about 25,000 diagnostic records and clinical cases. The dataset covers 67 common urological disease categories, where the disease coverage exceeds 97.6\% of the population seeking medical services in urology. Each data instance in RJUA-QA comprises: (1) a question mirroring real patient to inquiry about clinical symptoms and medical conditions, (2) a context including comprehensive expert knowledge, serving as a reference for medical examination and diagnosis, (3) a doctor response offering the diagnostic conclusion and suggested examination guidance, (4) a diagnosed clinical disease as the recommended diagnostic outcome, and (5) clinical advice providing recommendations for medical examination. RJUA-QA is the first medical QA dataset for clinical reasoning over the patient inquiries, where expert-level knowledge and experience are required for yielding diagnostic conclusions and medical examination advice. A comprehensive evaluation is conducted to evaluate the performance of both medical-specific and general LLMs on the RJUA-QA dataset.

Bias in Large Language Models (LLMs) significantly undermines their reliability and fairness. We focus on a common form of bias: when two reference concepts in the model's concept space, such as sentiment polarities (e.g., "positive" and "negative"), are asymmetrically correlated with a third, target concept, such as a reviewing aspect, the model exhibits unintended bias. For instance, the understanding of "food" should not skew toward any particular sentiment. Existing bias evaluation methods assess behavioral differences of LLMs by constructing labeled data for different social groups and measuring model responses across them, a process that requires substantial human effort and captures only a limited set of social concepts. To overcome these limitations, we propose BiasLens, a test-set-free bias analysis framework based on the structure of the model's vector space. BiasLens combines Concept Activation Vectors (CAVs) with Sparse Autoencoders (SAEs) to extract interpretable concept representations, and quantifies bias by measuring the variation in representational similarity between the target concept and each of the reference concepts. Even without labeled data, BiasLens shows strong agreement with traditional bias evaluation metrics (Spearman correlation r > 0.85). Moreover, BiasLens reveals forms of bias that are difficult to detect using existing methods. For example, in simulated clinical scenarios, a patient's insurance status can cause the LLM to produce biased diagnostic assessments. Overall, BiasLens offers a scalable, interpretable, and efficient paradigm for bias discovery, paving the way for improving fairness and transparency in LLMs.

Large language models (LLMs) are increasingly envisioned as decision-support tools in clinical practice, yet safe clinical reasoning demands integrating heterogeneous knowledge bases -- trials, primary studies, regulatory documents, and cost data -- under strict accuracy constraints. Existing evaluations often rely on synthetic prompts, reduce the task to single-hop factoid queries, or conflate reasoning with open-ended generation, leaving their real-world utility unclear. To close this gap, we present MedBrowseComp, the first benchmark that systematically tests an agent's ability to reliably retrieve and synthesize multi-hop medical facts from live, domain-specific knowledge bases. MedBrowseComp contains more than 1,000 human-curated questions that mirror clinical scenarios where practitioners must reconcile fragmented or conflicting information to reach an up-to-date conclusion. Applying MedBrowseComp to frontier agentic systems reveals performance shortfalls as low as ten percent, exposing a critical gap between current LLM capabilities and the rigor demanded in clinical settings. MedBrowseComp therefore offers a clear testbed for reliable medical information seeking and sets concrete goals for future model and toolchain upgrades. You can visit our project page at: https://moreirap12.github.io/mbc-browse-app/

Medical Visual Question Answering (MedVQA) is a promising field for developing clinical decision support systems, yet progress is often limited by the available datasets, which can lack clinical complexity and visual diversity. To address these gaps, we introduce Kvasir-VQA-x1, a new, large-scale dataset for gastrointestinal (GI) endoscopy. Our work significantly expands upon the original Kvasir-VQA by incorporating 159,549 new question-answer pairs that are designed to test deeper clinical reasoning. We developed a systematic method using large language models to generate these questions, which are stratified by complexity to better assess a model's inference capabilities. To ensure our dataset prepares models for real-world clinical scenarios, we have also introduced a variety of visual augmentations that mimic common imaging artifacts. The dataset is structured to support two main evaluation tracks: one for standard VQA performance and another to test model robustness against these visual perturbations. By providing a more challenging and clinically relevant benchmark, Kvasir-VQA-x1 aims to accelerate the development of more reliable and effective multimodal AI systems for use in clinical settings. The dataset is fully accessible and adheres to FAIR data principles, making it a valuable resource for the wider research community. Code and data: https://github.com/Simula/Kvasir-VQA-x1 and https://huggingface.co/datasets/SimulaMet/Kvasir-VQA-x1

Current medical artificial intelligence systems are often limited to narrow applications, hindering their widespread adoption in clinical practice. To address this limitation, we propose MedVersa, a generalist learner that enables flexible learning and tasking for medical image interpretation. By leveraging a large language model as a learnable orchestrator, MedVersa can learn from both visual and linguistic supervision, support multimodal inputs, and perform real-time task specification. This versatility allows MedVersa to adapt to various clinical scenarios and perform multifaceted medical image analysis. We introduce MedInterp, the largest multimodal dataset to date for medical image interpretation, consisting of over 13 million annotated instances spanning 11 tasks across 3 modalities, to support the development of MedVersa. Our experiments demonstrate that MedVersa achieves state-of-the-art performance in 9 tasks, sometimes outperforming specialist counterparts by over 10%. MedVersa is the first to showcase the viability of multimodal generative medical AI in implementing multimodal outputs, inputs, and dynamic task specification, highlighting its potential as a multifunctional system for comprehensive medical image analysis. This generalist approach to medical image interpretation paves the way for more adaptable and efficient AI-assisted clinical decision-making.

Intraoperative bleeding during Endoscopic Submucosal Dissection (ESD) poses significant risks, demanding precise, real-time localization and continuous monitoring of the bleeding source for effective hemostatic intervention. In particular, endoscopists have to repeatedly flush to clear blood, allowing only milliseconds to identify bleeding sources, an inefficient process that prolongs operations and elevates patient risks. However, current Artificial Intelligence (AI) methods primarily focus on bleeding region segmentation, overlooking the critical need for accurate bleeding source detection and temporal tracking in the challenging ESD environment, which is marked by frequent visual obstructions and dynamic scene changes. This gap is widened by the lack of specialized datasets, hindering the development of robust AI-assisted guidance systems. To address these challenges, we introduce BleedOrigin-Bench, the first comprehensive ESD bleeding source dataset, featuring 1,771 expert-annotated bleeding sources across 106,222 frames from 44 procedures, supplemented with 39,755 pseudo-labeled frames. This benchmark covers 8 anatomical sites and 6 challenging clinical scenarios. We also present BleedOrigin-Net, a novel dual-stage detection-tracking framework for the bleeding source localization in ESD procedures, addressing the complete workflow from bleeding onset detection to continuous spatial tracking. We compare with widely-used object detection models (YOLOv11/v12), multimodal large language models, and point tracking methods. Extensive evaluation demonstrates state-of-the-art performance, achieving 96.85% frame-level accuracy (pmleq8 frames) for bleeding onset detection, 70.24% pixel-level accuracy (leq100 px) for initial source detection, and 96.11% pixel-level accuracy (leq100 px) for point tracking.

Artificial intelligence has significantly advanced healthcare, particularly through large language models (LLMs) that excel in medical question answering benchmarks. However, their real-world clinical application remains limited due to the complexities of doctor-patient interactions. To address this, we introduce AI Hospital, a multi-agent framework simulating dynamic medical interactions between Doctor as player and NPCs including Patient, Examiner, Chief Physician. This setup allows for realistic assessments of LLMs in clinical scenarios. We develop the Multi-View Medical Evaluation (MVME) benchmark, utilizing high-quality Chinese medical records and NPCs to evaluate LLMs' performance in symptom collection, examination recommendations, and diagnoses. Additionally, a dispute resolution collaborative mechanism is proposed to enhance diagnostic accuracy through iterative discussions. Despite improvements, current LLMs exhibit significant performance gaps in multi-turn interactions compared to one-step approaches. Our findings highlight the need for further research to bridge these gaps and improve LLMs' clinical diagnostic capabilities. Our data, code, and experimental results are all open-sourced at https://github.com/LibertFan/AI_Hospital.

The field of computational pathology has been transformed with recent advances in foundation models that encode histopathology region-of-interests (ROIs) into versatile and transferable feature representations via self-supervised learning (SSL). However, translating these advancements to address complex clinical challenges at the patient and slide level remains constrained by limited clinical data in disease-specific cohorts, especially for rare clinical conditions. We propose TITAN, a multimodal whole slide foundation model pretrained using 335,645 WSIs via visual self-supervised learning and vision-language alignment with corresponding pathology reports and 423,122 synthetic captions generated from a multimodal generative AI copilot for pathology. Without any finetuning or requiring clinical labels, TITAN can extract general-purpose slide representations and generate pathology reports that generalize to resource-limited clinical scenarios such as rare disease retrieval and cancer prognosis. We evaluate TITAN on diverse clinical tasks and find that TITAN outperforms both ROI and slide foundation models across machine learning settings such as linear probing, few-shot and zero-shot classification, rare cancer retrieval and cross-modal retrieval, and pathology report generation.

Recent advancements in large language models (LLMs) have shown promise in medical applications such as disease diagnosis and treatment planning. However, most existing medical LLMs struggle with the advanced reasoning required for complex clinical scenarios, such as differential diagnosis or personalized treatment suggestions. We proposed FineMedLM-o1, which leverages high-quality synthetic medical data and long-form reasoning data for Supervised Fine-Tuning (SFT) and Direct Preference Optimization (DPO), enabling advanced dialogue and deep reasoning capabilities. Additionally, we introduced Test-Time Training (TTT) in the medical domain for the first time, facilitating domain adaptation and ensuring reliable, accurate reasoning. Experimental results demonstrate that FineMedLM-o1 achieves a 23% average performance improvement over prior models on key medical benchmarks. Furthermore, the introduction of TTT provides an additional 14% performance boost, highlighting its effectiveness in enhancing medical reasoning capabilities. To support this process, we also proposed a novel method for synthesizing medical dialogue. Compared to other open-source datasets, our dataset stands out as superior in both quality and complexity. The project and data will be released on GitHub.

Large language models have exhibited exceptional performance on various Natural Language Processing (NLP) tasks, leveraging techniques such as the pre-training, and instruction fine-tuning. Despite these advances, their effectiveness in medical applications is limited, due to challenges such as factual inaccuracies, reasoning abilities, and lack grounding in real-world experience. In this study, we present ClinicalGPT, a language model explicitly designed and optimized for clinical scenarios. By incorporating extensive and diverse real-world data, such as medical records, domain-specific knowledge, and multi-round dialogue consultations in the training process, ClinicalGPT is better prepared to handle multiple clinical task. Furthermore, we introduce a comprehensive evaluation framework that includes medical knowledge question-answering, medical exams, patient consultations, and diagnostic analysis of medical records. Our results demonstrate that ClinicalGPT significantly outperforms other models in these tasks, highlighting the effectiveness of our approach in adapting large language models to the critical domain of healthcare.

LLMs have demonstrated impressive performance in answering medical questions, such as passing scores on medical licensing examinations. However, medical board exam questions or general clinical questions do not capture the complexity of realistic clinical cases. Moreover, the lack of reference explanations means we cannot easily evaluate the reasoning of model decisions, a crucial component of supporting doctors in making complex medical decisions. To address these challenges, we construct two new datasets: JAMA Clinical Challenge and Medbullets. JAMA Clinical Challenge consists of questions based on challenging clinical cases, while Medbullets comprises USMLE Step 2&3 style clinical questions. Both datasets are structured as multiple-choice question-answering tasks, where each question is accompanied by an expert-written explanation. We evaluate four LLMs on the two datasets using various prompts. Experiments demonstrate that our datasets are harder than previous benchmarks. The inconsistency between automatic and human evaluations of model-generated explanations highlights the need to develop new metrics to support future research on explainable medical QA.

Large Language Models (LLMs) have shown impressive performance on existing medical question-answering benchmarks. This high performance makes it increasingly difficult to meaningfully evaluate and differentiate advanced methods. We present MedAgentsBench, a benchmark that focuses on challenging medical questions requiring multi-step clinical reasoning, diagnosis formulation, and treatment planning-scenarios where current models still struggle despite their strong performance on standard tests. Drawing from seven established medical datasets, our benchmark addresses three key limitations in existing evaluations: (1) the prevalence of straightforward questions where even base models achieve high performance, (2) inconsistent sampling and evaluation protocols across studies, and (3) lack of systematic analysis of the interplay between performance, cost, and inference time. Through experiments with various base models and reasoning methods, we demonstrate that the latest thinking models, DeepSeek R1 and OpenAI o3, exhibit exceptional performance in complex medical reasoning tasks. Additionally, advanced search-based agent methods offer promising performance-to-cost ratios compared to traditional approaches. Our analysis reveals substantial performance gaps between model families on complex questions and identifies optimal model selections for different computational constraints. Our benchmark and evaluation framework are publicly available at https://github.com/gersteinlab/medagents-benchmark.

Large language models (LLMs) have the potential to transform medicine, but real-world clinical scenarios contain extraneous information that can hinder performance. The rise of assistive technologies like ambient dictation, which automatically generates draft notes from live patient encounters, has the potential to introduce additional noise making it crucial to assess the ability of LLM's to filter relevant data. To investigate this, we developed MedDistractQA, a benchmark using USMLE-style questions embedded with simulated real-world distractions. Our findings show that distracting statements (polysemous words with clinical meanings used in a non-clinical context or references to unrelated health conditions) can reduce LLM accuracy by up to 17.9%. Commonly proposed solutions to improve model performance such as retrieval-augmented generation (RAG) and medical fine-tuning did not change this effect and in some cases introduced their own confounders and further degraded performance. Our findings suggest that LLMs natively lack the logical mechanisms necessary to distinguish relevant from irrelevant clinical information, posing challenges for real-world applications. MedDistractQA and our results highlights the need for robust mitigation strategies to enhance LLM resilience to extraneous information.

Learning anatomical segmentation from heterogeneous labels in multi-center datasets is a common situation encountered in clinical scenarios, where certain anatomical structures are only annotated in images coming from particular medical centers, but not in the full database. Here we first show how state-of-the-art pixel-level segmentation models fail in naively learning this task due to domain memorization issues and conflicting labels. We then propose to adopt HybridGNet, a landmark-based segmentation model which learns the available anatomical structures using graph-based representations. By analyzing the latent space learned by both models, we show that HybridGNet naturally learns more domain-invariant feature representations, and provide empirical evidence in the context of chest X-ray multiclass segmentation. We hope these insights will shed light on the training of deep learning models with heterogeneous labels from public and multi-center datasets.

Multimodal large language models (MLLMs) have demonstrated promising prospects in healthcare, particularly for addressing complex medical tasks, supporting multidisciplinary treatment (MDT), and enabling personalized precision medicine. However, their practical deployment faces critical challenges in resource efficiency, diagnostic accuracy, clinical considerations, and ethical privacy. To address these limitations, we propose Infi-Med, a comprehensive framework for medical MLLMs that introduces three key innovations: (1) a resource-efficient approach through curating and constructing high-quality supervised fine-tuning (SFT) datasets with minimal sample requirements, with a forward-looking design that extends to both pretraining and posttraining phases; (2) enhanced multimodal reasoning capabilities for cross-modal integration and clinical task understanding; and (3) a systematic evaluation system that assesses model performance across medical modalities and task types. Our experiments demonstrate that Infi-Med achieves state-of-the-art (SOTA) performance in general medical reasoning while maintaining rapid adaptability to clinical scenarios. The framework establishes a solid foundation for deploying MLLMs in real-world healthcare settings by balancing model effectiveness with operational constraints.

Doctor-patient consultations require multi-turn, context-aware communication tailored to diverse patient personas. Training or evaluating doctor LLMs in such settings requires realistic patient interaction systems. However, existing simulators often fail to reflect the full range of personas seen in clinical practice. To address this, we introduce PatientSim, a patient simulator that generates realistic and diverse patient personas for clinical scenarios, grounded in medical expertise. PatientSim operates using: 1) clinical profiles, including symptoms and medical history, derived from real-world data in the MIMIC-ED and MIMIC-IV datasets, and 2) personas defined by four axes: personality, language proficiency, medical history recall level, and cognitive confusion level, resulting in 37 unique combinations. We evaluated eight LLMs for factual accuracy and persona consistency. The top-performing open-source model, Llama 3.3, was validated by four clinicians to confirm the robustness of our framework. As an open-source, customizable platform, PatientSim provides a reproducible and scalable solution that can be customized for specific training needs. Offering a privacy-compliant environment, it serves as a robust testbed for evaluating medical dialogue systems across diverse patient presentations and shows promise as an educational tool for healthcare.

This work introduces MediQAl, a French medical question answering dataset designed to evaluate the capabilities of language models in factual medical recall and reasoning over real-world clinical scenarios. MediQAl contains 32,603 questions sourced from French medical examinations across 41 medical subjects. The dataset includes three tasks: (i) Multiple-Choice Question with Unique answer, (ii) Multiple-Choice Question with Multiple answer, and (iii) Open-Ended Question with Short-Answer. Each question is labeled as Understanding or Reasoning, enabling a detailed analysis of models' cognitive capabilities. We validate the MediQAl dataset through extensive evaluation with 14 large language models, including recent reasoning-augmented models, and observe a significant performance gap between factual recall and reasoning tasks. Our evaluation provides a comprehensive benchmark for assessing language models' performance on French medical question answering, addressing a crucial gap in multilingual resources for the medical domain.

Recent advances in large language models (LLMs) have demonstrated notable performance in medical licensing exams. However, comprehensive evaluation of LLMs across various healthcare roles, particularly in high-stakes clinical scenarios, remains a challenge. Existing benchmarks are typically text-based, English-centric, and focus primarily on medicines, which limits their ability to assess broader healthcare knowledge and multimodal reasoning. To address these gaps, we introduce KokushiMD-10, the first multimodal benchmark constructed from ten Japanese national healthcare licensing exams. This benchmark spans multiple fields, including Medicine, Dentistry, Nursing, Pharmacy, and allied health professions. It contains over 11588 real exam questions, incorporating clinical images and expert-annotated rationales to evaluate both textual and visual reasoning. We benchmark over 30 state-of-the-art LLMs, including GPT-4o, Claude 3.5, and Gemini, across both text and image-based settings. Despite promising results, no model consistently meets passing thresholds across domains, highlighting the ongoing challenges in medical AI. KokushiMD-10 provides a comprehensive and linguistically grounded resource for evaluating and advancing reasoning-centric medical AI across multilingual and multimodal clinical tasks.

Synthetic medical data generation has opened up new possibilities in the healthcare domain, offering a powerful tool for simulating clinical scenarios, enhancing diagnostic and treatment quality, gaining granular medical knowledge, and accelerating the development of unbiased algorithms. In this context, we present a novel approach called ViewXGen, designed to overcome the limitations of existing methods that rely on general domain pipelines using only radiology reports to generate frontal-view chest X-rays. Our approach takes into consideration the diverse view positions found in the dataset, enabling the generation of chest X-rays with specific views, which marks a significant advancement in the field. To achieve this, we introduce a set of specially designed tokens for each view position, tailoring the generation process to the user's preferences. Furthermore, we leverage multi-view chest X-rays as input, incorporating valuable information from different views within the same study. This integration rectifies potential errors and contributes to faithfully capturing abnormal findings in chest X-ray generation. To validate the effectiveness of our approach, we conducted statistical analyses, evaluating its performance in a clinical efficacy metric on the MIMIC-CXR dataset. Also, human evaluation demonstrates the remarkable capabilities of ViewXGen, particularly in producing realistic view-specific X-rays that closely resemble the original images.

Large language models (LLMs) have exhibited remarkable capabilities across various domains and tasks, pushing the boundaries of our knowledge in learning and cognition. The latest model, OpenAI's o1, stands out as the first LLM with an internalized chain-of-thought technique using reinforcement learning strategies. While it has demonstrated surprisingly strong capabilities on various general language tasks, its performance in specialized fields such as medicine remains unknown. To this end, this report provides a comprehensive exploration of o1 on different medical scenarios, examining 3 key aspects: understanding, reasoning, and multilinguality. Specifically, our evaluation encompasses 6 tasks using data from 37 medical datasets, including two newly constructed and more challenging question-answering (QA) tasks based on professional medical quizzes from the New England Journal of Medicine (NEJM) and The Lancet. These datasets offer greater clinical relevance compared to standard medical QA benchmarks such as MedQA, translating more effectively into real-world clinical utility. Our analysis of o1 suggests that the enhanced reasoning ability of LLMs may (significantly) benefit their capability to understand various medical instructions and reason through complex clinical scenarios. Notably, o1 surpasses the previous GPT-4 in accuracy by an average of 6.2% and 6.6% across 19 datasets and two newly created complex QA scenarios. But meanwhile, we identify several weaknesses in both the model capability and the existing evaluation protocols, including hallucination, inconsistent multilingual ability, and discrepant metrics for evaluation. We release our raw data and model outputs at https://ucsc-vlaa.github.io/o1_medicine/ for future research.

Recent advances such as Chain-of-Thought prompting have significantly improved large language models (LLMs) in zero-shot medical reasoning. However, prompting-based methods often remain shallow and unstable, while fine-tuned medical LLMs suffer from poor generalization under distribution shifts and limited adaptability to unseen clinical scenarios. To address these limitations, we present TAGS, a test-time framework that combines a broadly capable generalist with a domain-specific specialist to offer complementary perspectives without any model fine-tuning or parameter updates. To support this generalist-specialist reasoning process, we introduce two auxiliary modules: a hierarchical retrieval mechanism that provides multi-scale exemplars by selecting examples based on both semantic and rationale-level similarity, and a reliability scorer that evaluates reasoning consistency to guide final answer aggregation. TAGS achieves strong performance across nine MedQA benchmarks, boosting GPT-4o accuracy by 13.8%, DeepSeek-R1 by 16.8%, and improving a vanilla 7B model from 14.1% to 23.9%. These results surpass several fine-tuned medical LLMs, without any parameter updates. The code will be available at https://github.com/JianghaoWu/TAGS.

Deep learning-based medical image classification techniques are rapidly advancing in medical image analysis, making it crucial to develop accurate and trustworthy models that can be efficiently deployed across diverse clinical scenarios. Concept Bottleneck Models (CBMs), which first predict a set of explainable concepts from images and then perform classification based on these concepts, are increasingly being adopted for explainable medical image classification. However, the inherent explainability of CBMs introduces new challenges when deploying trained models to new environments. Variations in imaging protocols and staining methods may induce concept-level shifts, such as alterations in color distribution and scale. Furthermore, since CBM training requires explicit concept annotations, fine-tuning models solely with image-level labels could compromise concept prediction accuracy and faithfulness - a critical limitation given the high cost of acquiring expert-annotated concept labels in medical domains. To address these challenges, we propose a training-free confusion concept identification strategy. By leveraging minimal new data (e.g., 4 images per class) with only image-level labels, our approach enhances out-of-domain performance without sacrificing source domain accuracy through two key operations: masking misactivated confounding concepts and amplifying under-activated discriminative concepts. The efficacy of our method is validated on both skin and white blood cell images. Our code is available at: https://github.com/riverback/TF-TTI-XMed.

Intra-fraction motion in radiotherapy is commonly modeled using deformable image registration (DIR). However, existing methods often struggle to balance speed and accuracy, limiting their applicability in clinical scenarios. This study introduces a novel approach that harnesses Neural Graphics Primitives (NGP) to optimize the displacement vector field (DVF). Our method leverages learned primitives, processed as splats, and interpolates within space using a shallow neural network. Uniquely, it enables self-supervised optimization at an ultra-fast speed, negating the need for pre-training on extensive datasets and allowing seamless adaptation to new cases. We validated this approach on the 4D-CT lung dataset DIR-lab, achieving a target registration error (TRE) of 1.15\pm1.15 mm within a remarkable time of 1.77 seconds. Notably, our method also addresses the sliding boundary problem, a common challenge in conventional DIR methods.

The emergence of groundbreaking large language models capable of performing complex reasoning tasks holds significant promise for addressing various scientific challenges, including those arising in complex clinical scenarios. To enable their safe and effective deployment in real-world healthcare settings, it is urgently necessary to benchmark the diagnostic capabilities of current models systematically. Given the limitations of existing medical benchmarks in evaluating advanced diagnostic reasoning, we present DiagnosisArena, a comprehensive and challenging benchmark designed to rigorously assess professional-level diagnostic competence. DiagnosisArena consists of 1,113 pairs of segmented patient cases and corresponding diagnoses, spanning 28 medical specialties, deriving from clinical case reports published in 10 top-tier medical journals. The benchmark is developed through a meticulous construction pipeline, involving multiple rounds of screening and review by both AI systems and human experts, with thorough checks conducted to prevent data leakage. Our study reveals that even the most advanced reasoning models, o3-mini, o1, and DeepSeek-R1, achieve only 45.82%, 31.09%, and 17.79% accuracy, respectively. This finding highlights a significant generalization bottleneck in current large language models when faced with clinical diagnostic reasoning challenges. Through DiagnosisArena, we aim to drive further advancements in AIs diagnostic reasoning capabilities, enabling more effective solutions for real-world clinical diagnostic challenges. We provide the benchmark and evaluation tools for further research and development https://github.com/SPIRAL-MED/DiagnosisArena.

Large Language Model (LLM)-based agents have demonstrated strong capabilities across a wide range of tasks, and their application in the medical domain holds particular promise due to the demand for high generalizability and reliance on interdisciplinary knowledge. However, existing medical agent systems often rely on static, manually crafted workflows that lack the flexibility to accommodate diverse diagnostic requirements and adapt to emerging clinical scenarios. Motivated by the success of automated machine learning (AutoML), this paper introduces a novel framework for the automated design of medical agent architectures. Specifically, we define a hierarchical and expressive agent search space that enables dynamic workflow adaptation through structured modifications at the node, structural, and framework levels. Our framework conceptualizes medical agents as graph-based architectures composed of diverse, functional node types and supports iterative self-improvement guided by diagnostic feedback. Experimental results on skin disease diagnosis tasks demonstrate that the proposed method effectively evolves workflow structures and significantly enhances diagnostic accuracy over time. This work represents the first fully automated framework for medical agent architecture design and offers a scalable, adaptable foundation for deploying intelligent agents in real-world clinical environments.

The conversion from 2D X-ray to 3D shape holds significant potential for improving diagnostic efficiency and safety. However, existing reconstruction methods often rely on hand-crafted features, manual intervention, and prior knowledge, resulting in unstable shape errors and additional processing costs. In this paper, we introduce Swin-X2S, an end-to-end deep learning method for directly reconstructing 3D segmentation and labeling from 2D biplanar orthogonal X-ray images. Swin-X2S employs an encoder-decoder architecture: the encoder leverages 2D Swin Transformer for X-ray information extraction, while the decoder employs 3D convolution with cross-attention to integrate structural features from orthogonal views. A dimension-expanding module is introduced to bridge the encoder and decoder, ensuring a smooth conversion from 2D pixels to 3D voxels. We evaluate proposed method through extensive qualitative and quantitative experiments across nine publicly available datasets covering four anatomies (femur, hip, spine, and rib), with a total of 54 categories. Significant improvements over previous methods have been observed not only in the segmentation and labeling metrics but also in the clinically relevant parameters that are of primary concern in practical applications, which demonstrates the promise of Swin-X2S to provide an effective option for anatomical shape reconstruction in clinical scenarios. Code implementation is available at: https://github.com/liukuan5625/Swin-X2S.

The Segment Anything Model (SAM) has demonstrated outstanding adaptation to medical image segmentation but still faces three major challenges. Firstly, the huge computational costs of SAM limit its real-world applicability. Secondly, SAM depends on manual annotations (e.g., points, boxes) as prompts, which are laborious and impractical in clinical scenarios. Thirdly, SAM handles all segmentation targets equally, which is suboptimal for diverse medical modalities with inherent heterogeneity. To address these issues, we propose an Efficient Self-Prompting SAM for universal medical image segmentation, named ESP-MedSAM. We devise a Multi-Modal Decoupled Knowledge Distillation (MMDKD) strategy to distil common image knowledge and domain-specific medical knowledge from the foundation model to train a lightweight image encoder and a modality controller. Further, they combine with the additionally introduced Self-Patch Prompt Generator (SPPG) and Query-Decoupled Modality Decoder (QDMD) to construct ESP-MedSAM. Specifically, SPPG aims to generate a set of patch prompts automatically and QDMD leverages a one-to-one strategy to provide an independent decoding channel for every modality. Extensive experiments indicate that ESP-MedSAM outperforms state-of-the-arts in diverse medical imaging segmentation takes, displaying superior zero-shot learning and modality transfer ability. Especially, our framework uses only 31.4% parameters compared to SAM-Base.

Automated interpretation of CT images-particularly localizing and describing abnormal findings across multi-plane and whole-body scans-remains a significant challenge in clinical radiology. This work aims to address this challenge through four key contributions: (i) On taxonomy, we collaborate with senior radiologists to propose a comprehensive hierarchical classification system, with 404 representative abnormal findings across all body regions; (ii) On data, we contribute a dataset containing over 14.5K CT images from multiple planes and all human body regions, and meticulously provide grounding annotations for over 19K abnormalities, each linked to the detailed description and cast into the taxonomy; (iii) On model development, we propose OminiAbnorm-CT, which can automatically ground and describe abnormal findings on multi-plane and whole-body CT images based on text queries, while also allowing flexible interaction through visual prompts; (iv) On benchmarks, we establish three representative evaluation tasks based on real clinical scenarios. Through extensive experiments, we show that OminiAbnorm-CT can significantly outperform existing methods on all the tasks and metrics.

Data science plays a critical role in clinical research, but it requires professionals with expertise in coding and medical data analysis. Large language models (LLMs) have shown great potential in supporting medical tasks and performing well in general coding tests. However, these tests do not assess LLMs' ability to handle data science tasks in medicine, nor do they explore their practical utility in clinical research. To address this, we developed a dataset consisting of 293 real-world data science coding tasks, based on 39 published clinical studies, covering 128 tasks in Python and 165 tasks in R. This dataset simulates realistic clinical research scenarios using patient data. Our findings reveal that cutting-edge LLMs struggle to generate perfect solutions, frequently failing to follow input instructions, understand target data, and adhere to standard analysis practices. Consequently, LLMs are not yet ready to fully automate data science tasks. We benchmarked advanced adaptation methods and found two to be particularly effective: chain-of-thought prompting, which provides a step-by-step plan for data analysis, which led to a 60% improvement in code accuracy; and self-reflection, enabling LLMs to iteratively refine their code, yielding a 38% accuracy improvement. Building on these insights, we developed a platform that integrates LLMs into the data science workflow for medical professionals. In a user study with five medical doctors, we found that while LLMs cannot fully automate coding tasks, they significantly streamline the programming process. We found that 80% of their submitted code solutions were incorporated from LLM-generated code, with up to 96% reuse in some cases. Our analysis highlights the potential of LLMs, when integrated into expert workflows, to enhance data science efficiency in clinical research.

Data harmonization is an essential task that entails integrating datasets from diverse sources. Despite years of research in this area, it remains a time-consuming and challenging task due to schema mismatches, varying terminologies, and differences in data collection methodologies. This paper presents the case for agentic data harmonization as a means to both empower experts to harmonize their data and to streamline the process. We introduce Harmonia, a system that combines LLM-based reasoning, an interactive user interface, and a library of data harmonization primitives to automate the synthesis of data harmonization pipelines. We demonstrate Harmonia in a clinical data harmonization scenario, where it helps to interactively create reusable pipelines that map datasets to a standard format. Finally, we discuss challenges and open problems, and suggest research directions for advancing our vision.

At the heart of medicine lies the physician-patient dialogue, where skillful history-taking paves the way for accurate diagnosis, effective management, and enduring trust. Artificial Intelligence (AI) systems capable of diagnostic dialogue could increase accessibility, consistency, and quality of care. However, approximating clinicians' expertise is an outstanding grand challenge. Here, we introduce AMIE (Articulate Medical Intelligence Explorer), a Large Language Model (LLM) based AI system optimized for diagnostic dialogue. AMIE uses a novel self-play based simulated environment with automated feedback mechanisms for scaling learning across diverse disease conditions, specialties, and contexts. We designed a framework for evaluating clinically-meaningful axes of performance including history-taking, diagnostic accuracy, management reasoning, communication skills, and empathy. We compared AMIE's performance to that of primary care physicians (PCPs) in a randomized, double-blind crossover study of text-based consultations with validated patient actors in the style of an Objective Structured Clinical Examination (OSCE). The study included 149 case scenarios from clinical providers in Canada, the UK, and India, 20 PCPs for comparison with AMIE, and evaluations by specialist physicians and patient actors. AMIE demonstrated greater diagnostic accuracy and superior performance on 28 of 32 axes according to specialist physicians and 24 of 26 axes according to patient actors. Our research has several limitations and should be interpreted with appropriate caution. Clinicians were limited to unfamiliar synchronous text-chat which permits large-scale LLM-patient interactions but is not representative of usual clinical practice. While further research is required before AMIE could be translated to real-world settings, the results represent a milestone towards conversational diagnostic AI.

Global healthcare providers are exploring use of large language models (LLMs) to provide medical advice to the public. LLMs now achieve nearly perfect scores on medical licensing exams, but this does not necessarily translate to accurate performance in real-world settings. We tested if LLMs can assist members of the public in identifying underlying conditions and choosing a course of action (disposition) in ten medical scenarios in a controlled study with 1,298 participants. Participants were randomly assigned to receive assistance from an LLM (GPT-4o, Llama 3, Command R+) or a source of their choice (control). Tested alone, LLMs complete the scenarios accurately, correctly identifying conditions in 94.9% of cases and disposition in 56.3% on average. However, participants using the same LLMs identified relevant conditions in less than 34.5% of cases and disposition in less than 44.2%, both no better than the control group. We identify user interactions as a challenge to the deployment of LLMs for medical advice. Standard benchmarks for medical knowledge and simulated patient interactions do not predict the failures we find with human participants. Moving forward, we recommend systematic human user testing to evaluate interactive capabilities prior to public deployments in healthcare.

In this work, we introduce MedAgentSim, an open-source simulated clinical environment with doctor, patient, and measurement agents designed to evaluate and enhance LLM performance in dynamic diagnostic settings. Unlike prior approaches, our framework requires doctor agents to actively engage with patients through multi-turn conversations, requesting relevant medical examinations (e.g., temperature, blood pressure, ECG) and imaging results (e.g., MRI, X-ray) from a measurement agent to mimic the real-world diagnostic process. Additionally, we incorporate self improvement mechanisms that allow models to iteratively refine their diagnostic strategies. We enhance LLM performance in our simulated setting by integrating multi-agent discussions, chain-of-thought reasoning, and experience-based knowledge retrieval, facilitating progressive learning as doctor agents interact with more patients. We also introduce an evaluation benchmark for assessing the LLM's ability to engage in dynamic, context-aware diagnostic interactions. While MedAgentSim is fully automated, it also supports a user-controlled mode, enabling human interaction with either the doctor or patient agent. Comprehensive evaluations in various simulated diagnostic scenarios demonstrate the effectiveness of our approach. Our code, simulation tool, and benchmark are available at https://medagentsim.netlify.app/.

Advances in natural language processing techniques, such as named entity recognition and normalization to widely used standardized terminologies like UMLS or SNOMED-CT, along with the digitalization of electronic health records, have significantly advanced clinical text analysis. This study presents ClinLinker, a novel approach employing a two-phase pipeline for medical entity linking that leverages the potential of in-domain adapted language models for biomedical text mining: initial candidate retrieval using a SapBERT-based bi-encoder and subsequent re-ranking with a cross-encoder, trained by following a contrastive-learning strategy to be tailored to medical concepts in Spanish. This methodology, focused initially on content in Spanish, substantially outperforming multilingual language models designed for the same purpose. This is true even for complex scenarios involving heterogeneous medical terminologies and being trained on a subset of the original data. Our results, evaluated using top-k accuracy at 25 and other top-k metrics, demonstrate our approach's performance on two distinct clinical entity linking Gold Standard corpora, DisTEMIST (diseases) and MedProcNER (clinical procedures), outperforming previous benchmarks by 40 points in DisTEMIST and 43 points in MedProcNER, both normalized to SNOMED-CT codes. These findings highlight our approach's ability to address language-specific nuances and set a new benchmark in entity linking, offering a potent tool for enhancing the utility of digital medical records. The resulting system is of practical value, both for large scale automatic generation of structured data derived from clinical records, as well as for exhaustive extraction and harmonization of predefined clinical variables of interest.

Large language models (LLMs) hold great promise for medical applications and are evolving rapidly, with new models being released at an accelerated pace. However, current evaluations of LLMs in clinical contexts remain limited. Most existing benchmarks rely on medical exam-style questions or PubMed-derived text, failing to capture the complexity of real-world electronic health record (EHR) data. Others focus narrowly on specific application scenarios, limiting their generalizability across broader clinical use. To address this gap, we present BRIDGE, a comprehensive multilingual benchmark comprising 87 tasks sourced from real-world clinical data sources across nine languages. We systematically evaluated 52 state-of-the-art LLMs (including DeepSeek-R1, GPT-4o, Gemini, and Llama 4) under various inference strategies. With a total of 13,572 experiments, our results reveal substantial performance variation across model sizes, languages, natural language processing tasks, and clinical specialties. Notably, we demonstrate that open-source LLMs can achieve performance comparable to proprietary models, while medically fine-tuned LLMs based on older architectures often underperform versus updated general-purpose models. The BRIDGE and its corresponding leaderboard serve as a foundational resource and a unique reference for the development and evaluation of new LLMs in real-world clinical text understanding.

We study the problem of adaptively identifying patient subpopulations that benefit from a given treatment during a confirmatory clinical trial. This type of adaptive clinical trial has been thoroughly studied in biostatistics, but has been allowed only limited adaptivity so far. Here, we aim to relax classical restrictions on such designs and investigate how to incorporate ideas from the recent machine learning literature on adaptive and online experimentation to make trials more flexible and efficient. We find that the unique characteristics of the subpopulation selection problem -- most importantly that (i) one is usually interested in finding subpopulations with any treatment benefit (and not necessarily the single subgroup with largest effect) given a limited budget and that (ii) effectiveness only has to be demonstrated across the subpopulation on average -- give rise to interesting challenges and new desiderata when designing algorithmic solutions. Building on these findings, we propose AdaGGI and AdaGCPI, two meta-algorithms for subpopulation construction. We empirically investigate their performance across a range of simulation scenarios and derive insights into their (dis)advantages across different settings.

VR simulation in Health Professions (HP) education demonstrates huge potential, but fixed learning content with little customization limits its application beyond lab environments. To address these limitations in the context of VR for patient communication training, we conducted a user-centered study involving semi-structured interviews with advanced HP students to understand their challenges in clinical communication training and perceptions of VR-based solutions. From this, we derived design insights emphasizing the importance of realistic scenarios, simple interactions, and unpredictable dialogues. Building on these insights, we developed the Virtual AI Patient Simulator (VAPS), a novel VR system powered by Large Language Models (LLMs) and Embodied Conversational Agents (ECAs), supporting dynamic and customizable patient interactions for immersive learning. We also provided an example of how clinical professors could use user-friendly design forms to create personalized scenarios that align with course objectives in VAPS and discuss future implications of integrating AI-driven technologies into VR education.

Background: Recent advancements in large language models (LLMs) offer potential benefits in healthcare, particularly in processing extensive patient records. However, existing benchmarks do not fully assess LLMs' capability in handling real-world, lengthy clinical data. Methods: We present the LongHealth benchmark, comprising 20 detailed fictional patient cases across various diseases, with each case containing 5,090 to 6,754 words. The benchmark challenges LLMs with 400 multiple-choice questions in three categories: information extraction, negation, and sorting, challenging LLMs to extract and interpret information from large clinical documents. Results: We evaluated nine open-source LLMs with a minimum of 16,000 tokens and also included OpenAI's proprietary and cost-efficient GPT-3.5 Turbo for comparison. The highest accuracy was observed for Mixtral-8x7B-Instruct-v0.1, particularly in tasks focused on information retrieval from single and multiple patient documents. However, all models struggled significantly in tasks requiring the identification of missing information, highlighting a critical area for improvement in clinical data interpretation. Conclusion: While LLMs show considerable potential for processing long clinical documents, their current accuracy levels are insufficient for reliable clinical use, especially in scenarios requiring the identification of missing information. The LongHealth benchmark provides a more realistic assessment of LLMs in a healthcare setting and highlights the need for further model refinement for safe and effective clinical application. We make the benchmark and evaluation code publicly available.

Extracting patient information from unstructured text is a critical task in health decision-support and clinical research. Large language models (LLMs) have shown the potential to accelerate clinical curation via few-shot in-context learning, in contrast to supervised learning which requires much more costly human annotations. However, despite drastic advances in modern LLMs such as GPT-4, they still struggle with issues regarding accuracy and interpretability, especially in mission-critical domains such as health. Here, we explore a general mitigation framework using self-verification, which leverages the LLM to provide provenance for its own extraction and check its own outputs. This is made possible by the asymmetry between verification and generation, where the latter is often much easier than the former. Experimental results show that our method consistently improves accuracy for various LLMs in standard clinical information extraction tasks. Additionally, self-verification yields interpretations in the form of a short text span corresponding to each output, which makes it very efficient for human experts to audit the results, paving the way towards trustworthy extraction of clinical information in resource-constrained scenarios. To facilitate future research in this direction, we release our code and prompts.

Learning to represent free text is a core task in many clinical machine learning (ML) applications, as clinical text contains observations and plans not otherwise available for inference. State-of-the-art methods use large language models developed with immense computational resources and training data; however, applying these models is challenging because of the highly varying syntax and vocabulary in clinical free text. Structured information such as International Classification of Disease (ICD) codes often succinctly abstracts the most important facts of a clinical encounter and yields good performance, but is often not as available as clinical text in real-world scenarios. We propose a multi-view learning framework that jointly learns from codes and text to combine the availability and forward-looking nature of text and better performance of ICD codes. The learned text embeddings can be used as inputs to predictive algorithms independent of the ICD codes during inference. Our approach uses a Graph Neural Network (GNN) to process ICD codes, and Bi-LSTM to process text. We apply Deep Canonical Correlation Analysis (DCCA) to enforce the two views to learn a similar representation of each patient. In experiments using planned surgical procedure text, our model outperforms BERT models fine-tuned to clinical data, and in experiments using diverse text in MIMIC-III, our model is competitive to a fine-tuned BERT at a tiny fraction of its computational effort.

Artificial intelligence is poised to augment dermatological care by enabling scalable image-based diagnostics. Yet, the development of robust and equitable models remains hindered by datasets that fail to capture the clinical and demographic complexity of real-world practice. This complexity stems from region-specific disease distributions, wide variation in skin tones, and the underrepresentation of outpatient scenarios from non-Western populations. We introduce DermaCon-IN, a prospectively curated dermatology dataset comprising over 5,450 clinical images from approximately 3,000 patients across outpatient clinics in South India. Each image is annotated by board-certified dermatologists with over 240 distinct diagnoses, structured under a hierarchical, etiology-based taxonomy adapted from Rook's classification. The dataset captures a wide spectrum of dermatologic conditions and tonal variation commonly seen in Indian outpatient care. We benchmark a range of architectures including convolutional models (ResNet, DenseNet, EfficientNet), transformer-based models (ViT, MaxViT, Swin), and Concept Bottleneck Models to establish baseline performance and explore how anatomical and concept-level cues may be integrated. These results are intended to guide future efforts toward interpretable and clinically realistic models. DermaCon-IN provides a scalable and representative foundation for advancing dermatology AI in real-world settings.

Medical reasoning in large language models (LLMs) aims to emulate clinicians' diagnostic thinking, but current benchmarks such as MedQA-USMLE, MedMCQA, and PubMedQA often mix reasoning with factual recall. We address this by separating 11 biomedical QA benchmarks into reasoning- and knowledge-focused subsets using a PubMedBERT classifier that reaches 81 percent accuracy, comparable to human performance. Our analysis shows that only 32.8 percent of questions require complex reasoning. We evaluate biomedical models (HuatuoGPT-o1, MedReason, m1) and general-domain models (DeepSeek-R1, o4-mini, Qwen3), finding consistent gaps between knowledge and reasoning performance. For example, m1 scores 60.5 on knowledge but only 47.1 on reasoning. In adversarial tests where models are misled with incorrect initial reasoning, biomedical models degrade sharply, while larger or RL-trained general models show more robustness. To address this, we train BioMed-R1 using fine-tuning and reinforcement learning on reasoning-heavy examples. It achieves the strongest performance among similarly sized models. Further gains may come from incorporating clinical case reports and training with adversarial and backtracking scenarios.

Integrating tools into Large Language Models (LLMs) has facilitated the widespread application. Despite this, in specialized downstream task contexts, reliance solely on tools is insufficient to fully address the complexities of the real world. This particularly restricts the effective deployment of LLMs in fields such as medicine. In this paper, we focus on the downstream tasks of medical calculators, which use standardized tests to assess an individual's health status. We introduce MeNTi, a universal agent architecture for LLMs. MeNTi integrates a specialized medical toolkit and employs meta-tool and nested calling mechanisms to enhance LLM tool utilization. Specifically, it achieves flexible tool selection and nested tool calling to address practical issues faced in intricate medical scenarios, including calculator selection, slot filling, and unit conversion. To assess the capabilities of LLMs for quantitative assessment throughout the clinical process of calculator scenarios, we introduce CalcQA. This benchmark requires LLMs to use medical calculators to perform calculations and assess patient health status. CalcQA is constructed by professional physicians and includes 100 case-calculator pairs, complemented by a toolkit of 281 medical tools. The experimental results demonstrate significant performance improvements with our framework. This research paves new directions for applying LLMs in demanding scenarios of medicine.

When applying offline reinforcement learning (RL) in healthcare scenarios, the out-of-distribution (OOD) issues pose significant risks, as inappropriate generalization beyond clinical expertise can result in potentially harmful recommendations. While existing methods like conservative Q-learning (CQL) attempt to address the OOD issue, their effectiveness is limited by only constraining action selection by suppressing uncertain actions. This action-only regularization imitates clinician actions that prioritize short-term rewards, but it fails to regulate downstream state trajectories, thereby limiting the discovery of improved long-term treatment strategies. To safely improve policy beyond clinician recommendations while ensuring that state-action trajectories remain in-distribution, we propose Offline Guarded Safe Reinforcement Learning (OGSRL), a theoretically grounded model-based offline RL framework. OGSRL introduces a novel dual constraint mechanism for improving policy with reliability and safety. First, the OOD guardian is established to specify clinically validated regions for safe policy exploration. By constraining optimization within these regions, it enables the reliable exploration of treatment strategies that outperform clinician behavior by leveraging the full patient state history, without drifting into unsupported state-action trajectories. Second, we introduce a safety cost constraint that encodes medical knowledge about physiological safety boundaries, providing domain-specific safeguards even in areas where training data might contain potentially unsafe interventions. Notably, we provide theoretical guarantees on safety and near-optimality: policies that satisfy these constraints remain in safe and reliable regions and achieve performance close to the best possible policy supported by the data.

Electrocardiogram (ECG) interpretation requires specialized expertise, often involving synthesizing insights from ECG signals with complex clinical queries posed in natural language. The scarcity of labeled ECG data coupled with the diverse nature of clinical inquiries presents a significant challenge for developing robust and adaptable ECG diagnostic systems. This work introduces a novel multimodal meta-learning method for few-shot ECG question answering, addressing the challenge of limited labeled data while leveraging the rich knowledge encoded within large language models (LLMs). Our LLM-agnostic approach integrates a pre-trained ECG encoder with a frozen LLM (e.g., LLaMA and Gemma) via a trainable fusion module, enabling the language model to reason about ECG data and generate clinically meaningful answers. Extensive experiments demonstrate superior generalization to unseen diagnostic tasks compared to supervised baselines, achieving notable performance even with limited ECG leads. For instance, in a 5-way 5-shot setting, our method using LLaMA-3.1-8B achieves accuracy of 84.6%, 77.3%, and 69.6% on single verify, choose and query question types, respectively. These results highlight the potential of our method to enhance clinical ECG interpretation by combining signal processing with the nuanced language understanding capabilities of LLMs, particularly in data-constrained scenarios.

Medical Visual Language Models have shown great potential in various healthcare applications, including medical image captioning and diagnostic assistance. However, most existing models rely on text-based instructions, limiting their usability in real-world clinical environments especially in scenarios such as surgery, text-based interaction is often impractical for physicians. In addition, current medical image analysis models typically lack comprehensive reasoning behind their predictions, which reduces their reliability for clinical decision-making. Given that medical diagnosis errors can have life-changing consequences, there is a critical need for interpretable and rational medical assistance. To address these challenges, we introduce an end-to-end speech-driven medical VLM, SilVar-Med, a multimodal medical image assistant that integrates speech interaction with VLMs, pioneering the task of voice-based communication for medical image analysis. In addition, we focus on the interpretation of the reasoning behind each prediction of medical abnormalities with a proposed reasoning dataset. Through extensive experiments, we demonstrate a proof-of-concept study for reasoning-driven medical image interpretation with end-to-end speech interaction. We believe this work will advance the field of medical AI by fostering more transparent, interactive, and clinically viable diagnostic support systems. Our code and dataset are publicly available at SiVar-Med.

As opposed to evaluating computation and logic-based reasoning, current benchmarks for evaluating large language models (LLMs) in medicine are primarily focused on question-answering involving domain knowledge and descriptive reasoning. While such qualitative capabilities are vital to medical diagnosis, in real-world scenarios, doctors frequently use clinical calculators that follow quantitative equations and rule-based reasoning paradigms for evidence-based decision support. To this end, we propose MedCalc-Bench, a first-of-its-kind dataset focused on evaluating the medical calculation capability of LLMs. MedCalc-Bench contains an evaluation set of over 1000 manually reviewed instances from 55 different medical calculation tasks. Each instance in MedCalc-Bench consists of a patient note, a question requesting to compute a specific medical value, a ground truth answer, and a step-by-step explanation showing how the answer is obtained. While our evaluation results show the potential of LLMs in this area, none of them are effective enough for clinical settings. Common issues include extracting the incorrect entities, not using the correct equation or rules for a calculation task, or incorrectly performing the arithmetic for the computation. We hope our study highlights the quantitative knowledge and reasoning gaps in LLMs within medical settings, encouraging future improvements of LLMs for various clinical calculation tasks.

Electronic Health Records (EHRs), which contain patients' medical histories in various multi-modal formats, often overlook the potential for joint reasoning across imaging and table modalities underexplored in current EHR Question Answering (QA) systems. In this paper, we introduce EHRXQA, a novel multi-modal question answering dataset combining structured EHRs and chest X-ray images. To develop our dataset, we first construct two uni-modal resources: 1) The MIMIC- CXR-VQA dataset, our newly created medical visual question answering (VQA) benchmark, specifically designed to augment the imaging modality in EHR QA, and 2) EHRSQL (MIMIC-IV), a refashioned version of a previously established table-based EHR QA dataset. By integrating these two uni-modal resources, we successfully construct a multi-modal EHR QA dataset that necessitates both uni-modal and cross-modal reasoning. To address the unique challenges of multi-modal questions within EHRs, we propose a NeuralSQL-based strategy equipped with an external VQA API. This pioneering endeavor enhances engagement with multi-modal EHR sources and we believe that our dataset can catalyze advances in real-world medical scenarios such as clinical decision-making and research. EHRXQA is available at https://github.com/baeseongsu/ehrxqa.

Representation learning of pathology whole-slide images (WSIs) has been has primarily relied on weak supervision with Multiple Instance Learning (MIL). However, the slide representations resulting from this approach are highly tailored to specific clinical tasks, which limits their expressivity and generalization, particularly in scenarios with limited data. Instead, we hypothesize that morphological redundancy in tissue can be leveraged to build a task-agnostic slide representation in an unsupervised fashion. To this end, we introduce PANTHER, a prototype-based approach rooted in the Gaussian mixture model that summarizes the set of WSI patches into a much smaller set of morphological prototypes. Specifically, each patch is assumed to have been generated from a mixture distribution, where each mixture component represents a morphological exemplar. Utilizing the estimated mixture parameters, we then construct a compact slide representation that can be readily used for a wide range of downstream tasks. By performing an extensive evaluation of PANTHER on subtyping and survival tasks using 13 datasets, we show that 1) PANTHER outperforms or is on par with supervised MIL baselines and 2) the analysis of morphological prototypes brings new qualitative and quantitative insights into model interpretability.

Finding relevant literature underpins the practice of evidence-based medicine. From 2014 to 2016, TREC conducted a clinical decision support track, wherein participants were tasked with finding articles relevant to clinical questions posed by physicians. In total, 87 teams have participated over the past three years, generating 395 runs. During this period, each team has trialled a variety of methods. While there was significant overlap in the methods employed by different teams, the results were varied. Due to the diversity of the platforms used, the results arising from the different techniques are not directly comparable, reducing the ability to build on previous work. By using a stable platform, we have been able to compare different document and query processing techniques, allowing us to experiment with different search parameters. We have used our system to reproduce leading teams runs, and compare the results obtained. By benchmarking our indexing and search techniques, we can statistically test a variety of hypotheses, paving the way for further research.

Large language models (LLMs) have been applied to tasks in healthcare, ranging from medical exam questions to responding to patient questions. With increasing institutional partnerships between companies producing LLMs and healthcare systems, real world clinical application is coming closer to reality. As these models gain traction, it is essential for healthcare practitioners to understand what LLMs are, their development, their current and potential applications, and the associated pitfalls when utilized in medicine. This review and accompanying tutorial aim to give an overview of these topics to aid healthcare practitioners in understanding the rapidly changing landscape of LLMs as applied to medicine.

The increased capabilities of generative AI have dramatically expanded its possible use cases in medicine. We provide a comprehensive overview of generative AI use cases for clinicians, patients, clinical trial organizers, researchers, and trainees. We then discuss the many challenges -- including maintaining privacy and security, improving transparency and interpretability, upholding equity, and rigorously evaluating models -- which must be overcome to realize this potential, and the open research directions they give rise to.

Throughout the course of my Ph.D., I have been designing the user experience (UX) of various machine learning (ML) systems. In this workshop, I share two projects as case studies in which people engage with ML in much more complicated and nuanced ways than the technical HCML work might assume. The first case study describes how cardiology teams in three hospitals used a clinical decision-support system that helps them decide whether and when to implant an artificial heart to a heart failure patient. I demonstrate that physicians cannot draw on their decision-making experience by seeing only patient data on paper. They are also confused by some fundamental premises upon which ML operates. For example, physicians asked: Are ML predictions made based on clinicians' best efforts? Is it ethical to make decisions based on previous patients' collective outcomes? In the second case study, my collaborators and I designed an intelligent text editor, with the goal of improving authors' writing experience with NLP (Natural Language Processing) technologies. We prototyped a number of generative functionalities where the system provides phrase-or-sentence-level writing suggestions upon user request. When writing with the prototype, however, authors shared that they need to "see where the sentence is going two paragraphs later" in order to decide whether the suggestion aligns with their writing; Some even considered adopting machine suggestions as plagiarism, therefore "is simply wrong". By sharing these unexpected and intriguing responses from these real-world ML users, I hope to start a discussion about such previously-unknown complexities and nuances of -- as the workshop proposal states -- "putting ML at the service of people in a way that is accessible, useful, and trustworthy to all".

Problem: Effective patient-centered communication is a core competency for physicians. However, both seasoned providers and medical trainees report decreased confidence in leading conversations on sensitive topics such as goals of care or end-of-life discussions. The significant administrative burden and the resources required to provide dedicated training in leading difficult conversations has been a long-standing problem in medical education. Approach: In this work, we present a novel educational tool designed to facilitate interactive, real-time simulations of difficult conversations in a video-based format through the use of multimodal generative artificial intelligence (AI). Leveraging recent advances in language modeling, computer vision, and generative audio, this tool creates realistic, interactive scenarios with avatars, or "synthetic patients." These synthetic patients interact with users throughout various stages of medical care using a custom-built video chat application, offering learners the chance to practice conversations with patients from diverse belief systems, personalities, and ethnic backgrounds. Outcomes: While the development of this platform demanded substantial upfront investment in labor, it offers a highly-realistic simulation experience with minimal financial investment. For medical trainees, this educational tool can be implemented within programs to simulate patient-provider conversations and can be incorporated into existing palliative care curriculum to provide a scalable, high-fidelity simulation environment for mastering difficult conversations. Next Steps: Future developments will explore enhancing the authenticity of these encounters by working with patients to incorporate their histories and personalities, as well as employing the use of AI-generated evaluations to offer immediate, constructive feedback to learners post-simulation.

In this review, we explore the potential applications of Artificial General Intelligence (AGI) models in healthcare, focusing on foundational Large Language Models (LLMs), Large Vision Models, and Large Multimodal Models. We emphasize the importance of integrating clinical expertise, domain knowledge, and multimodal capabilities into AGI models. In addition, we lay out key roadmaps that guide the development and deployment of healthcare AGI models. Throughout the review, we provide critical perspectives on the potential challenges and pitfalls associated with deploying large-scale AGI models in the medical field. This comprehensive review aims to offer insights into the future implications of AGI in medical imaging, healthcare and beyond.

Background: Electronic Health Records hold detailed longitudinal information about each patient's health status and general clinical history, a large portion of which is stored within the unstructured text. Existing approaches focus mostly on structured data and a subset of single-domain outcomes. We explore how temporal modelling of patients from free text and structured data, using deep generative transformers can be used to forecast a wide range of future disorders, substances, procedures or findings. Methods: We present Foresight, a novel transformer-based pipeline that uses named entity recognition and linking tools to convert document text into structured, coded concepts, followed by providing probabilistic forecasts for future medical events such as disorders, substances, procedures and findings. We processed the entire free-text portion from three different hospital datasets totalling 811336 patients covering both physical and mental health. Findings: On tests in two UK hospitals (King's College Hospital, South London and Maudsley) and the US MIMIC-III dataset precision@10 0.68, 0.76 and 0.88 was achieved for forecasting the next disorder in a patient timeline, while precision@10 of 0.80, 0.81 and 0.91 was achieved for forecasting the next biomedical concept. Foresight was also validated on 34 synthetic patient timelines by five clinicians and achieved relevancy of 97% for the top forecasted candidate disorder. As a generative model, it can forecast follow-on biomedical concepts for as many steps as required. Interpretation: Foresight is a general-purpose model for biomedical concept modelling that can be used for real-world risk forecasting, virtual trials and clinical research to study the progression of disorders, simulate interventions and counterfactuals, and educational purposes.

Clinical natural language processing requires methods that can address domain-specific challenges, such as complex medical terminology and clinical contexts. Recently, large language models (LLMs) have shown promise in this domain. Yet, their direct deployment can lead to privacy issues and are constrained by resources. To address this challenge, we delve into synthetic clinical text generation using LLMs for clinical NLP tasks. We propose an innovative, resource-efficient approach, ClinGen, which infuses knowledge into the process. Our model involves clinical knowledge extraction and context-informed LLM prompting. Both clinical topics and writing styles are drawn from external domain-specific knowledge graphs and LLMs to guide data generation. Our extensive empirical study across 7 clinical NLP tasks and 16 datasets reveals that ClinGen consistently enhances performance across various tasks, effectively aligning the distribution of real datasets and significantly enriching the diversity of generated training instances. We will publish our code and all the generated data in https://github.com/ritaranx/ClinGen.

Machine learning techniques are effective for building predictive models because they identify patterns in large datasets. Development of a model for complex real-life problems often stop at the point of publication, proof of concept or when made accessible through some mode of deployment. However, a model in the medical domain risks becoming obsolete as patient demographics, systems and clinical practices change. The maintenance and monitoring of predictive model performance post-publication is crucial to enable their safe and effective long-term use. We will assess the infrastructure required to monitor the outputs of a machine learning algorithm, and present two scenarios with examples of monitoring and updates of models, firstly on a breast cancer prognosis model trained on public longitudinal data, and secondly on a neurodegenerative stratification algorithm that is currently being developed and tested in clinic.

With the course of progress in the field of medicine, most of the patients lives can be saved. The only thing required is the proper attention at the proper time. Our wearable solution tries to solve this issue by taking the patients vitals and transmitting them to the server for live monitoring using the mobile app along with the patients current location. In case of an emergency, that is if any vitals show any abnormalities, an SMS is sent to the caregiver of the patient with the patients location so that he can reach there on time.

In recent years, there have been significant breakthroughs in the field of natural language processing, particularly with the development of large language models (LLMs). These LLMs have showcased remarkable capabilities on various benchmarks. In the healthcare field, the exact role LLMs and other future AI models will play remains unclear. There is a potential for these models in the future to be used as part of adaptive physician training, medical co-pilot applications, and digital patient interaction scenarios. The ability of AI models to participate in medical training and patient care will depend in part on their mastery of the knowledge content of specific medical fields. This study investigated the medical knowledge capability of LLMs, specifically in the context of internal medicine subspecialty multiple-choice test-taking ability. We compared the performance of several open-source LLMs (Koala 7B, Falcon 7B, Stable-Vicuna 13B, and Orca Mini 13B), to GPT-4 and Claude 2 on multiple-choice questions in the field of Nephrology. Nephrology was chosen as an example of a particularly conceptually complex subspecialty field within internal medicine. The study was conducted to evaluate the ability of LLM models to provide correct answers to nephSAP (Nephrology Self-Assessment Program) multiple-choice questions. The overall success of open-sourced LLMs in answering the 858 nephSAP multiple-choice questions correctly was 17.1% - 25.5%. In contrast, Claude 2 answered 54.4% of the questions correctly, whereas GPT-4 achieved a score of 73.3%. We show that current widely used open-sourced LLMs do poorly in their ability for zero-shot reasoning when compared to GPT-4 and Claude 2. The findings of this study potentially have significant implications for the future of subspecialty medical training and patient care.

Large language models (LLMs) represent a transformative class of AI tools capable of revolutionizing various aspects of healthcare by generating human-like responses across diverse contexts and adapting to novel tasks following human instructions. Their potential application spans a broad range of medical tasks, such as clinical documentation, matching patients to clinical trials, and answering medical questions. In this primer paper, we propose an actionable guideline to help healthcare professionals more efficiently utilize LLMs in their work, along with a set of best practices. This approach consists of several main phases, including formulating the task, choosing LLMs, prompt engineering, fine-tuning, and deployment. We start with the discussion of critical considerations in identifying healthcare tasks that align with the core capabilities of LLMs and selecting models based on the selected task and data, performance requirements, and model interface. We then review the strategies, such as prompt engineering and fine-tuning, to adapt standard LLMs to specialized medical tasks. Deployment considerations, including regulatory compliance, ethical guidelines, and continuous monitoring for fairness and bias, are also discussed. By providing a structured step-by-step methodology, this tutorial aims to equip healthcare professionals with the tools necessary to effectively integrate LLMs into clinical practice, ensuring that these powerful technologies are applied in a safe, reliable, and impactful manner.

We present a corpus of 5,000 richly annotated abstracts of medical articles describing clinical randomized controlled trials. Annotations include demarcations of text spans that describe the Patient population enrolled, the Interventions studied and to what they were Compared, and the Outcomes measured (the `PICO' elements). These spans are further annotated at a more granular level, e.g., individual interventions within them are marked and mapped onto a structured medical vocabulary. We acquired annotations from a diverse set of workers with varying levels of expertise and cost. We describe our data collection process and the corpus itself in detail. We then outline a set of challenging NLP tasks that would aid searching of the medical literature and the practice of evidence-based medicine.

Clinical notes contain rich data, which is unexploited in predictive modeling compared to structured data. In this work, we developed a new text representation Clinical XLNet for clinical notes which also leverages the temporal information of the sequence of the notes. We evaluated our models on prolonged mechanical ventilation prediction problem and our experiments demonstrated that Clinical XLNet outperforms the best baselines consistently.

In response to the pressing need for advanced clinical problem-solving tools in healthcare, we introduce BooksMed, a novel framework based on a Large Language Model (LLM). BooksMed uniquely emulates human cognitive processes to deliver evidence-based and reliable responses, utilizing the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework to effectively quantify evidence strength. For clinical decision-making to be appropriately assessed, an evaluation metric that is clinically aligned and validated is required. As a solution, we present ExpertMedQA, a multispecialty clinical benchmark comprised of open-ended, expert-level clinical questions, and validated by a diverse group of medical professionals. By demanding an in-depth understanding and critical appraisal of up-to-date clinical literature, ExpertMedQA rigorously evaluates LLM performance. BooksMed outperforms existing state-of-the-art models Med-PaLM 2, Almanac, and ChatGPT in a variety of medical scenarios. Therefore, a framework that mimics human cognitive stages could be a useful tool for providing reliable and evidence-based responses to clinical inquiries.

Recent advances in generative models, including large language models (LLMs), vision language models (VLMs), and diffusion models, have accelerated the field of natural language and image processing in medicine and marked a significant paradigm shift in how biomedical models can be developed and deployed. While these models are highly adaptable to new tasks, scaling and evaluating their usage presents new challenges not addressed in previous frameworks. In particular, the ability of these models to produce useful outputs with little to no specialized training data ("zero-" or "few-shot" approaches), as well as the open-ended nature of their outputs, necessitate the development of new guidelines for robust reporting of clinical generative model research. In response to gaps in standards and best practices for the development of clinical AI tools identified by US Executive Order 141103 and several emerging national networks for clinical AI evaluation, we begin to formalize some of these guidelines by building on the original MI-CLAIM checklist. The new checklist, MI-CLAIM-GEN (Table 1), aims to address differences in training, evaluation, interpretability, and reproducibility of new generative models compared to non-generative ("predictive") AI models. This MI-CLAIM-GEN checklist also seeks to clarify cohort selection reporting with unstructured clinical data and adds additional items on alignment with ethical standards for clinical AI research.

With the rapid development of artificial intelligence, large language models (LLMs) have shown promising capabilities in mimicking human-level language comprehension and reasoning. This has sparked significant interest in applying LLMs to enhance various aspects of healthcare, ranging from medical education to clinical decision support. However, medicine involves multifaceted data modalities and nuanced reasoning skills, presenting challenges for integrating LLMs. This paper provides a comprehensive review on the applications and implications of LLMs in medicine. It begins by examining the fundamental applications of general-purpose and specialized LLMs, demonstrating their utilities in knowledge retrieval, research support, clinical workflow automation, and diagnostic assistance. Recognizing the inherent multimodality of medicine, the review then focuses on multimodal LLMs, investigating their ability to process diverse data types like medical imaging and EHRs to augment diagnostic accuracy. To address LLMs' limitations regarding personalization and complex clinical reasoning, the paper explores the emerging development of LLM-powered autonomous agents for healthcare. Furthermore, it summarizes the evaluation methodologies for assessing LLMs' reliability and safety in medical contexts. Overall, this review offers an extensive analysis on the transformative potential of LLMs in modern medicine. It also highlights the pivotal need for continuous optimizations and ethical oversight before these models can be effectively integrated into clinical practice. Visit https://github.com/mingze-yuan/Awesome-LLM-Healthcare for an accompanying GitHub repository containing latest papers.

Clinical trial matching is a key process in health delivery and discovery. In practice, it is plagued by overwhelming unstructured data and unscalable manual processing. In this paper, we conduct a systematic study on scaling clinical trial matching using large language models (LLMs), with oncology as the focus area. Our study is grounded in a clinical trial matching system currently in test deployment at a large U.S. health network. Initial findings are promising: out of box, cutting-edge LLMs, such as GPT-4, can already structure elaborate eligibility criteria of clinical trials and extract complex matching logic (e.g., nested AND/OR/NOT). While still far from perfect, LLMs substantially outperform prior strong baselines and may serve as a preliminary solution to help triage patient-trial candidates with humans in the loop. Our study also reveals a few significant growth areas for applying LLMs to end-to-end clinical trial matching, such as context limitation and accuracy, especially in structuring patient information from longitudinal medical records.

With the advent of Large Language Models (LLMs), medical artificial intelligence (AI) has experienced substantial technological progress and paradigm shifts, highlighting the potential of LLMs to streamline healthcare delivery and improve patient outcomes. Considering this rapid technical progress, in this survey, we trace the recent advances of Medical Large Language Models (Med-LLMs), including the background, key findings, and mainstream techniques, especially for the evolution from general-purpose models to medical-specialized applications. Firstly, we delve into the foundational technology of Med-LLMs, indicating how general models can be progressively adapted and refined for the complicated medical tasks. Secondly, the wide-ranging applications of Med-LLMs are investigated across various healthcare domains, as well as an up-to-date review of existing Med-LLMs. The transformative impact of these models on daily medical practice is evident through their ability to assist clinicians, educators, and patients. Recognizing the importance of responsible innovation, we discuss the challenges associated with ensuring fairness, accountability, privacy, and robustness. Ethical considerations, rigorous evaluation methodologies, and the establishment of regulatory frameworks are crucial for building trustworthiness in the real-world system. We emphasize the need for ongoing scrutiny and development to maintain high standards of safety and reliability. Finally, we anticipate possible future trajectories for Med-LLMs, identifying key avenues for prudent expansion. By consolidating these insights, our review aims to provide professionals and researchers with a thorough understanding of the strengths and limitations of Med-LLMs, fostering a balanced and ethical approach to their integration into the healthcare ecosystem.

Large Language Models (LLMs) have gained significant attention in the medical domain for their human-level capabilities, leading to increased efforts to explore their potential in various healthcare applications. However, despite such a promising future, there are multiple challenges and obstacles that remain for their real-world uses in practical settings. This work discusses key challenges for LLMs in medical applications from four unique aspects: operational vulnerabilities, ethical and social considerations, performance and assessment difficulties, and legal and regulatory compliance. Addressing these challenges is crucial for leveraging LLMs to their full potential and ensuring their responsible integration into healthcare.

Despite growing interest in using large language models (LLMs) in healthcare, current explorations do not assess the real-world utility and safety of LLMs in clinical settings. Our objective was to determine whether two LLMs can serve information needs submitted by physicians as questions to an informatics consultation service in a safe and concordant manner. Sixty six questions from an informatics consult service were submitted to GPT-3.5 and GPT-4 via simple prompts. 12 physicians assessed the LLM responses' possibility of patient harm and concordance with existing reports from an informatics consultation service. Physician assessments were summarized based on majority vote. For no questions did a majority of physicians deem either LLM response as harmful. For GPT-3.5, responses to 8 questions were concordant with the informatics consult report, 20 discordant, and 9 were unable to be assessed. There were 29 responses with no majority on "Agree", "Disagree", and "Unable to assess". For GPT-4, responses to 13 questions were concordant, 15 discordant, and 3 were unable to be assessed. There were 35 responses with no majority. Responses from both LLMs were largely devoid of overt harm, but less than 20% of the responses agreed with an answer from an informatics consultation service, responses contained hallucinated references, and physicians were divided on what constitutes harm. These results suggest that while general purpose LLMs are able to provide safe and credible responses, they often do not meet the specific information need of a given question. A definitive evaluation of the usefulness of LLMs in healthcare settings will likely require additional research on prompt engineering, calibration, and custom-tailoring of general purpose models.

Factuality can play an important role when automatically processing clinical text, as it makes a difference if particular symptoms are explicitly not present, possibly present, not mentioned, or affirmed. In most cases, a sufficient number of examples is necessary to handle such phenomena in a supervised machine learning setting. However, as clinical text might contain sensitive information, data cannot be easily shared. In the context of factuality detection, this work presents a simple solution using machine translation to translate English data to German to train a transformer-based factuality detection model.

We aim to present a comprehensive overview of the latest advancements in utilizing Large Language Models (LLMs) within the healthcare sector, emphasizing their transformative impact across various medical domains. LLMs have become pivotal in supporting healthcare, including physicians, healthcare providers, and patients. Our review provides insight into the applications of Large Language Models (LLMs) in healthcare, specifically focusing on diagnostic and treatment-related functionalities. We shed light on how LLMs are applied in cancer care, dermatology, dental care, neurodegenerative disorders, and mental health, highlighting their innovative contributions to medical diagnostics and patient care. Throughout our analysis, we explore the challenges and opportunities associated with integrating LLMs in healthcare, recognizing their potential across various medical specialties despite existing limitations. Additionally, we offer an overview of handling diverse data types within the medical field.

Clinical notes contain information about patients that goes beyond structured data like lab values and medications. However, clinical notes have been underused relative to structured data, because notes are high-dimensional and sparse. This work develops and evaluates representations of clinical notes using bidirectional transformers (ClinicalBERT). ClinicalBERT uncovers high-quality relationships between medical concepts as judged by humans. ClinicalBert outperforms baselines on 30-day hospital readmission prediction using both discharge summaries and the first few days of notes in the intensive care unit. Code and model parameters are available.

The increasing use of tools and solutions based on Large Language Models (LLMs) for various tasks in the medical domain has become a prominent trend. Their use in this highly critical and sensitive domain has thus raised important questions about their robustness, especially in response to variations in input, and the reliability of the generated outputs. This study addresses these questions by constructing a textual dataset based on the ICD-10-CM code descriptions, widely used in US hospitals and containing many clinical terms, and their easily reproducible rephrasing. We then benchmarked existing embedding models, either generalist or specialized in the clinical domain, in a semantic search task where the goal was to correctly match the rephrased text to the original description. Our results showed that generalist models performed better than clinical models, suggesting that existing clinical specialized models are more sensitive to small changes in input that confuse them. The highlighted problem of specialized models may be due to the fact that they have not been trained on sufficient data, and in particular on datasets that are not diverse enough to have a reliable global language understanding, which is still necessary for accurate handling of medical documents.

Recent advances in large language models have led to renewed interest in natural language processing in healthcare using the free text of clinical notes. One distinguishing characteristic of clinical notes is their long time span over multiple long documents. The unique structure of clinical notes creates a new design choice: when the context length for a language model predictor is limited, which part of clinical notes should we choose as the input? Existing studies either choose the inputs with domain knowledge or simply truncate them. We propose a framework to analyze the sections with high predictive power. Using MIMIC-III, we show that: 1) predictive power distribution is different between nursing notes and discharge notes and 2) combining different types of notes could improve performance when the context length is large. Our findings suggest that a carefully selected sampling function could enable more efficient information extraction from clinical notes.

Should a large language model (LLM) be used as a therapist? In this paper, we investigate the use of LLMs to *replace* mental health providers, a use case promoted in the tech startup and research space. We conduct a mapping review of therapy guides used by major medical institutions to identify crucial aspects of therapeutic relationships, such as the importance of a therapeutic alliance between therapist and client. We then assess the ability of LLMs to reproduce and adhere to these aspects of therapeutic relationships by conducting several experiments investigating the responses of current LLMs, such as `gpt-4o`. Contrary to best practices in the medical community, LLMs 1) express stigma toward those with mental health conditions and 2) respond inappropriately to certain common (and critical) conditions in naturalistic therapy settings -- e.g., LLMs encourage clients' delusional thinking, likely due to their sycophancy. This occurs even with larger and newer LLMs, indicating that current safety practices may not address these gaps. Furthermore, we note foundational and practical barriers to the adoption of LLMs as therapists, such as that a therapeutic alliance requires human characteristics (e.g., identity and stakes). For these reasons, we conclude that LLMs should not replace therapists, and we discuss alternative roles for LLMs in clinical therapy.

Large Language Models (LLMs) hold great promise to revolutionize current clinical systems for their superior capacities on medical text processing tasks and medical licensing exams. Meanwhile, traditional ML models such as SVM and XGBoost have still been mainly adopted in clinical prediction tasks. An emerging question is Can LLMs beat traditional ML models in clinical prediction? Thus, we build a new benchmark ClinicalBench to comprehensively study the clinical predictive modeling capacities of both general-purpose and medical LLMs, and compare them with traditional ML models. ClinicalBench embraces three common clinical prediction tasks, two databases, 14 general-purpose LLMs, 8 medical LLMs, and 11 traditional ML models. Through extensive empirical investigation, we discover that both general-purpose and medical LLMs, even with different model scales, diverse prompting or fine-tuning strategies, still cannot beat traditional ML models in clinical prediction yet, shedding light on their potential deficiency in clinical reasoning and decision-making. We call for caution when practitioners adopt LLMs in clinical applications. ClinicalBench can be utilized to bridge the gap between LLMs' development for healthcare and real-world clinical practice.

Current Large Language Models (LLMs) exhibit significant limitations, notably in structured, interpretable, and verifiable medical reasoning, alongside practical deployment challenges related to computational resources and data privacy. This report focused on the development of WiNGPT-3.0, the 32-billion parameter LLMs, engineered with the objective of enhancing its capacity for medical reasoning and exploring its potential for effective integration within healthcare IT infrastructures. The broader aim is to advance towards clinically applicable models. The approach involved a multi-stage training pipeline tailored for general, medical, and clinical reasoning. This pipeline incorporated supervised fine-tuning (SFT) and reinforcement learning (RL), leveraging curated Long Chain-of-Thought (CoT) datasets, auxiliary reward models, and an evidence-based diagnostic chain simulation. WiNGPT-3.0 demonstrated strong performance: specific model variants achieved scores of 66.6 on MedCalc and 87.1 on MedQA-USMLE. Furthermore, targeted training improved performance on a clinical reasoning task from a baseline score of 58.1 to 62.5. These findings suggest that reinforcement learning, even when applied with a limited dataset of only a few thousand examples, can enhance medical reasoning accuracy. Crucially, this demonstration of RL's efficacy with limited data and computation paves the way for more trustworthy and practically deployable LLMs within clinical workflows and health information infrastructures.

In the pharmaceutical industry, the use of artificial intelligence (AI) has seen consistent growth over the past decade. This rise is attributed to major advancements in statistical machine learning methodologies, computational capabilities and the increased availability of large datasets. AI techniques are applied throughout different stages of drug development, ranging from drug discovery to post-marketing benefit-risk assessment. Kolluri et al. provided a review of several case studies that span these stages, featuring key applications such as protein structure prediction, success probability estimation, subgroup identification, and AI-assisted clinical trial monitoring. From a regulatory standpoint, there was a notable uptick in submissions incorporating AI components in 2021. The most prevalent therapeutic areas leveraging AI were oncology (27%), psychiatry (15%), gastroenterology (12%), and neurology (11%). The paradigm of personalized or precision medicine has gained significant traction in recent research, partly due to advancements in AI techniques hamburg2010path. This shift has had a transformative impact on the pharmaceutical industry. Departing from the traditional "one-size-fits-all" model, personalized medicine incorporates various individual factors, such as environmental conditions, lifestyle choices, and health histories, to formulate customized treatment plans. By utilizing sophisticated machine learning algorithms, clinicians and researchers are better equipped to make informed decisions in areas such as disease prevention, diagnosis, and treatment selection, thereby optimizing health outcomes for each individual.

Large language models (LLMs), such as ChatGPT, have received substantial attention due to their impressive human language understanding and generation capabilities. Therefore, the application of LLMs in medicine to assist physicians and patient care emerges as a promising research direction in both artificial intelligence and clinical medicine. To reflect this trend, this survey provides a comprehensive overview of the principles, applications, and challenges faced by LLMs in medicine. Specifically, we aim to address the following questions: 1) How can medical LLMs be built? 2) What are the downstream performances of medical LLMs? 3) How can medical LLMs be utilized in real-world clinical practice? 4) What challenges arise from the use of medical LLMs? and 5) How can we better construct and utilize medical LLMs? As a result, this survey aims to provide insights into the opportunities and challenges of LLMs in medicine and serve as a valuable resource for constructing practical and effective medical LLMs. A regularly updated list of practical guides on medical LLMs can be found at https://github.com/AI-in-Health/MedLLMsPracticalGuide.

This technical report introduces a Named Clinical Entity Recognition Benchmark for evaluating language models in healthcare, addressing the crucial natural language processing (NLP) task of extracting structured information from clinical narratives to support applications like automated coding, clinical trial cohort identification, and clinical decision support. The leaderboard provides a standardized platform for assessing diverse language models, including encoder and decoder architectures, on their ability to identify and classify clinical entities across multiple medical domains. A curated collection of openly available clinical datasets is utilized, encompassing entities such as diseases, symptoms, medications, procedures, and laboratory measurements. Importantly, these entities are standardized according to the Observational Medical Outcomes Partnership (OMOP) Common Data Model, ensuring consistency and interoperability across different healthcare systems and datasets, and a comprehensive evaluation of model performance. Performance of models is primarily assessed using the F1-score, and it is complemented by various assessment modes to provide comprehensive insights into model performance. The report also includes a brief analysis of models evaluated to date, highlighting observed trends and limitations. By establishing this benchmarking framework, the leaderboard aims to promote transparency, facilitate comparative analyses, and drive innovation in clinical entity recognition tasks, addressing the need for robust evaluation methods in healthcare NLP.

There has been a rapidly growing interest in Automatic Symptom Detection (ASD) and Automatic Diagnosis (AD) systems in the machine learning research literature, aiming to assist doctors in telemedicine services. These systems are designed to interact with patients, collect evidence about their symptoms and relevant antecedents, and possibly make predictions about the underlying diseases. Doctors would review the interactions, including the evidence and the predictions, collect if necessary additional information from patients, before deciding on next steps. Despite recent progress in this area, an important piece of doctors' interactions with patients is missing in the design of these systems, namely the differential diagnosis. Its absence is largely due to the lack of datasets that include such information for models to train on. In this work, we present a large-scale synthetic dataset of roughly 1.3 million patients that includes a differential diagnosis, along with the ground truth pathology, symptoms and antecedents for each patient. Unlike existing datasets which only contain binary symptoms and antecedents, this dataset also contains categorical and multi-choice symptoms and antecedents useful for efficient data collection. Moreover, some symptoms are organized in a hierarchy, making it possible to design systems able to interact with patients in a logical way. As a proof-of-concept, we extend two existing AD and ASD systems to incorporate the differential diagnosis, and provide empirical evidence that using differentials as training signals is essential for the efficiency of such systems or for helping doctors better understand the reasoning of those systems.

The demand for emergency department (ED) services is increasing across the globe, particularly during the current COVID-19 pandemic. Clinical triage and risk assessment have become increasingly challenging due to the shortage of medical resources and the strain on hospital infrastructure caused by the pandemic. As a result of the widespread use of electronic health records (EHRs), we now have access to a vast amount of clinical data, which allows us to develop predictive models and decision support systems to address these challenges. To date, however, there are no widely accepted benchmark ED triage prediction models based on large-scale public EHR data. An open-source benchmarking platform would streamline research workflows by eliminating cumbersome data preprocessing, and facilitate comparisons among different studies and methodologies. In this paper, based on the Medical Information Mart for Intensive Care IV Emergency Department (MIMIC-IV-ED) database, we developed a publicly available benchmark suite for ED triage predictive models and created a benchmark dataset that contains over 400,000 ED visits from 2011 to 2019. We introduced three ED-based outcomes (hospitalization, critical outcomes, and 72-hour ED reattendance) and implemented a variety of popular methodologies, ranging from machine learning methods to clinical scoring systems. We evaluated and compared the performance of these methods against benchmark tasks. Our codes are open-source, allowing anyone with MIMIC-IV-ED data access to perform the same steps in data processing, benchmark model building, and experiments. This study provides future researchers with insights, suggestions, and protocols for managing raw data and developing risk triaging tools for emergency care.

Clinical diagnosis is critical in medical practice, typically requiring a continuous and evolving process that includes primary diagnosis, differential diagnosis, and final diagnosis. However, most existing clinical diagnostic tasks are single-step processes, which does not align with the complex multi-step diagnostic procedures found in real-world clinical settings. In this paper, we propose a multi-step diagnostic task and annotate a clinical diagnostic dataset (MSDiagnosis). This dataset includes primary diagnosis, differential diagnosis, and final diagnosis questions. Additionally, we propose a novel and effective framework. This framework combines forward inference, backward inference, reflection, and refinement, enabling the LLM to self-evaluate and adjust its diagnostic results. To assess the effectiveness of our proposed method, we design and conduct extensive experiments. The experimental results demonstrate the effectiveness of the proposed method. We also provide a comprehensive experimental analysis and suggest future research directions for this task.

A comprehensive bibliographic review with R statistical methods of the COVID pandemic in PubMed literature and Web of Science Core Collection, supported with Google Scholar search. In addition, a case study review of emerging new approaches in different regions, using medical literature, academic literature, news articles and other reliable data sources. Public responses of mistrust about privacy data misuse differ across countries, depending on the chosen public communication strategy.

The COVID-19 pandemic swept across the world rapidly, infecting millions of people. An efficient tool that can accurately recognize important clinical concepts of COVID-19 from free text in electronic health records (EHRs) will be valuable to accelerate COVID-19 clinical research. To this end, this study aims at adapting the existing CLAMP natural language processing tool to quickly build COVID-19 SignSym, which can extract COVID-19 signs/symptoms and their 8 attributes (body location, severity, temporal expression, subject, condition, uncertainty, negation, and course) from clinical text. The extracted information is also mapped to standard concepts in the Observational Medical Outcomes Partnership common data model. A hybrid approach of combining deep learning-based models, curated lexicons, and pattern-based rules was applied to quickly build the COVID-19 SignSym from CLAMP, with optimized performance. Our extensive evaluation using 3 external sites with clinical notes of COVID-19 patients, as well as the online medical dialogues of COVID-19, shows COVID-19 Sign-Sym can achieve high performance across data sources. The workflow used for this study can be generalized to other use cases, where existing clinical natural language processing tools need to be customized for specific information needs within a short time. COVID-19 SignSym is freely accessible to the research community as a downloadable package (https://clamp.uth.edu/covid/nlp.php) and has been used by 16 healthcare organizations to support clinical research of COVID-19.

How do we most effectively treat a disease or condition? Ideally, we could consult a database of evidence gleaned from clinical trials to answer such questions. Unfortunately, no such database exists; clinical trial results are instead disseminated primarily via lengthy natural language articles. Perusing all such articles would be prohibitively time-consuming for healthcare practitioners; they instead tend to depend on manually compiled systematic reviews of medical literature to inform care. NLP may speed this process up, and eventually facilitate immediate consult of published evidence. The Evidence Inference dataset was recently released to facilitate research toward this end. This task entails inferring the comparative performance of two treatments, with respect to a given outcome, from a particular article (describing a clinical trial) and identifying supporting evidence. For instance: Does this article report that chemotherapy performed better than surgery for five-year survival rates of operable cancers? In this paper, we collect additional annotations to expand the Evidence Inference dataset by 25\%, provide stronger baseline models, systematically inspect the errors that these make, and probe dataset quality. We also release an abstract only (as opposed to full-texts) version of the task for rapid model prototyping. The updated corpus, documentation, and code for new baselines and evaluations are available at http://evidence-inference.ebm-nlp.com/.

Although large language models (LLMs) have demonstrated impressive reasoning capabilities across general domains, their effectiveness in real-world clinical practice remains limited. This is likely due to their insufficient exposure to real-world clinical data during training, as such data is typically not included due to privacy concerns. To address this, we propose enhancing the clinical reasoning capabilities of LLMs by leveraging real-world clinical data. We constructed reasoning-intensive questions from a nationwide sepsis registry and fine-tuned Phi-4 on these questions using reinforcement learning, resulting in C-Reason. C-Reason exhibited strong clinical reasoning capabilities on the in-domain test set, as evidenced by both quantitative metrics and expert evaluations. Furthermore, its enhanced reasoning capabilities generalized to a sepsis dataset involving different tasks and patient cohorts, an open-ended consultations on antibiotics use task, and other diseases. Future research should focus on training LLMs with large-scale, multi-disease clinical datasets to develop more powerful, general-purpose clinical reasoning models.

The meaningful use of electronic health records (EHR) continues to progress in the digital era with clinical decision support systems augmented by artificial intelligence. A priority in improving provider experience is to overcome information overload and reduce the cognitive burden so fewer medical errors and cognitive biases are introduced during patient care. One major type of medical error is diagnostic error due to systematic or predictable errors in judgment that rely on heuristics. The potential for clinical natural language processing (cNLP) to model diagnostic reasoning in humans with forward reasoning from data to diagnosis and potentially reduce the cognitive burden and medical error has not been investigated. Existing tasks to advance the science in cNLP have largely focused on information extraction and named entity recognition through classification tasks. We introduce a novel suite of tasks coined as Diagnostic Reasoning Benchmarks, DR.BENCH, as a new benchmark for developing and evaluating cNLP models with clinical diagnostic reasoning ability. The suite includes six tasks from ten publicly available datasets addressing clinical text understanding, medical knowledge reasoning, and diagnosis generation. DR.BENCH is the first clinical suite of tasks designed to be a natural language generation framework to evaluate pre-trained language models. Experiments with state-of-the-art pre-trained generative language models using large general domain models and models that were continually trained on a medical corpus demonstrate opportunities for improvement when evaluated in DR. BENCH. We share DR. BENCH as a publicly available GitLab repository with a systematic approach to load and evaluate models for the cNLP community.

Large Language Models (LLMs) have rapidly become important tools in Biomedical and Health Informatics (BHI), enabling new ways to analyze data, treat patients, and conduct research. This bibliometric review aims to provide a panoramic view of how LLMs have been used in BHI by examining research articles and collaboration networks from 2022 to 2023. It further explores how LLMs can improve Natural Language Processing (NLP) applications in various BHI areas like medical diagnosis, patient engagement, electronic health record management, and personalized medicine. To do this, our bibliometric review identifies key trends, maps out research networks, and highlights major developments in this fast-moving field. Lastly, it discusses the ethical concerns and practical challenges of using LLMs in BHI, such as data privacy and reliable medical recommendations. Looking ahead, we consider how LLMs could further transform biomedical research as well as healthcare delivery and patient outcomes. This bibliometric review serves as a resource for stakeholders in healthcare, including researchers, clinicians, and policymakers, to understand the current state and future potential of LLMs in BHI.

Continuity of care is crucial to ensuring positive health outcomes for patients discharged from an inpatient hospital setting, and improved information sharing can help. To share information, caregivers write discharge notes containing action items to share with patients and their future caregivers, but these action items are easily lost due to the lengthiness of the documents. In this work, we describe our creation of a dataset of clinical action items annotated over MIMIC-III, the largest publicly available dataset of real clinical notes. This dataset, which we call CLIP, is annotated by physicians and covers 718 documents representing 100K sentences. We describe the task of extracting the action items from these documents as multi-aspect extractive summarization, with each aspect representing a type of action to be taken. We evaluate several machine learning models on this task, and show that the best models exploit in-domain language model pre-training on 59K unannotated documents, and incorporate context from neighboring sentences. We also propose an approach to pre-training data selection that allows us to explore the trade-off between size and domain-specificity of pre-training datasets for this task.

Automatic disease diagnosis has become increasingly valuable in clinical practice. The advent of large language models (LLMs) has catalyzed a paradigm shift in artificial intelligence, with growing evidence supporting the efficacy of LLMs in diagnostic tasks. Despite the increasing attention in this field, a holistic view is still lacking. Many critical aspects remain unclear, such as the diseases and clinical data to which LLMs have been applied, the LLM techniques employed, and the evaluation methods used. In this article, we perform a comprehensive review of LLM-based methods for disease diagnosis. Our review examines the existing literature across various dimensions, including disease types and associated clinical specialties, clinical data, LLM techniques, and evaluation methods. Additionally, we offer recommendations for applying and evaluating LLMs for diagnostic tasks. Furthermore, we assess the limitations of current research and discuss future directions. To our knowledge, this is the first comprehensive review for LLM-based disease diagnosis.

Medical dialogue systems are promising in assisting in telemedicine to increase access to healthcare services, improve the quality of patient care, and reduce medical costs. To facilitate the research and development of medical dialogue systems, we build two large-scale medical dialogue datasets: MedDialog-EN and MedDialog-CN. MedDialog-EN is an English dataset containing 0.3 million conversations between patients and doctors and 0.5 million utterances. MedDialog-CN is an Chinese dataset containing 1.1 million conversations and 4 million utterances. To our best knowledge, MedDialog-(EN,CN) are the largest medical dialogue datasets to date. The dataset is available at https://github.com/UCSD-AI4H/Medical-Dialogue-System

Med42-v2 introduces a suite of clinical large language models (LLMs) designed to address the limitations of generic models in healthcare settings. These models are built on Llama3 architecture and fine-tuned using specialized clinical data. They underwent multi-stage preference alignment to effectively respond to natural prompts. While generic models are often preference-aligned to avoid answering clinical queries as a precaution, Med42-v2 is specifically trained to overcome this limitation, enabling its use in clinical settings. Med42-v2 models demonstrate superior performance compared to the original Llama3 models in both 8B and 70B parameter configurations and GPT-4 across various medical benchmarks. These LLMs are developed to understand clinical queries, perform reasoning tasks, and provide valuable assistance in clinical environments. The models are now publicly available at https://huggingface.co/m42-health{https://huggingface.co/m42-health}.

To assess the effectiveness of any medical intervention, researchers must conduct a time-intensive and highly manual literature review. NLP systems can help to automate or assist in parts of this expensive process. In support of this goal, we release MS^2 (Multi-Document Summarization of Medical Studies), a dataset of over 470k documents and 20k summaries derived from the scientific literature. This dataset facilitates the development of systems that can assess and aggregate contradictory evidence across multiple studies, and is the first large-scale, publicly available multi-document summarization dataset in the biomedical domain. We experiment with a summarization system based on BART, with promising early results. We formulate our summarization inputs and targets in both free text and structured forms and modify a recently proposed metric to assess the quality of our system's generated summaries. Data and models are available at https://github.com/allenai/ms2

Large language models have the potential to be valuable in the healthcare industry, but it's crucial to verify their safety and effectiveness through rigorous evaluation. For this purpose, we comprehensively evaluated both open-source LLMs and Google's new multimodal LLM called Gemini across Medical reasoning, hallucination detection, and Medical Visual Question Answering tasks. While Gemini showed competence, it lagged behind state-of-the-art models like MedPaLM 2 and GPT-4 in diagnostic accuracy. Additionally, Gemini achieved an accuracy of 61.45\% on the medical VQA dataset, significantly lower than GPT-4V's score of 88\%. Our analysis revealed that Gemini is highly susceptible to hallucinations, overconfidence, and knowledge gaps, which indicate risks if deployed uncritically. We also performed a detailed analysis by medical subject and test type, providing actionable feedback for developers and clinicians. To mitigate risks, we applied prompting strategies that improved performance. Additionally, we facilitated future research and development by releasing a Python module for medical LLM evaluation and establishing a dedicated leaderboard on Hugging Face for medical domain LLMs. Python module can be found at https://github.com/promptslab/RosettaEval

Clinical trial matching is the task of identifying trials for which patients may be potentially eligible. Typically, this task is labor-intensive and requires detailed verification of patient electronic health records (EHRs) against the stringent inclusion and exclusion criteria of clinical trials. This process is manual, time-intensive, and challenging to scale up, resulting in many patients missing out on potential therapeutic options. Recent advancements in Large Language Models (LLMs) have made automating patient-trial matching possible, as shown in multiple concurrent research studies. However, the current approaches are confined to constrained, often synthetic datasets that do not adequately mirror the complexities encountered in real-world medical data. In this study, we present the first, end-to-end large-scale empirical evaluation of clinical trial matching using real-world EHRs. Our study showcases the capability of LLMs to accurately match patients with appropriate clinical trials. We perform experiments with proprietary LLMs, including GPT-4 and GPT-3.5, as well as our custom fine-tuned model called OncoLLM and show that OncoLLM, despite its significantly smaller size, not only outperforms GPT-3.5 but also matches the performance of qualified medical doctors. All experiments were carried out on real-world EHRs that include clinical notes and available clinical trials from a single cancer center in the United States.

Objective: To transform heterogeneous clinical data from electronic health records into clinically meaningful constructed features using data driven method that rely, in part, on temporal relations among data. Materials and Methods: The clinically meaningful representations of medical concepts and patients are the key for health analytic applications. Most of existing approaches directly construct features mapped to raw data (e.g., ICD or CPT codes), or utilize some ontology mapping such as SNOMED codes. However, none of the existing approaches leverage EHR data directly for learning such concept representation. We propose a new way to represent heterogeneous medical concepts (e.g., diagnoses, medications and procedures) based on co-occurrence patterns in longitudinal electronic health records. The intuition behind the method is to map medical concepts that are co-occuring closely in time to similar concept vectors so that their distance will be small. We also derive a simple method to construct patient vectors from the related medical concept vectors. Results: For qualitative evaluation, we study similar medical concepts across diagnosis, medication and procedure. In quantitative evaluation, our proposed representation significantly improves the predictive modeling performance for onset of heart failure (HF), where classification methods (e.g. logistic regression, neural network, support vector machine and K-nearest neighbors) achieve up to 23% improvement in area under the ROC curve (AUC) using this proposed representation. Conclusion: We proposed an effective method for patient and medical concept representation learning. The resulting representation can map relevant concepts together and also improves predictive modeling performance.

Over the past several years, across the globe, there has been an increase in people seeking care in emergency departments (EDs). ED resources, including nurse staffing, are strained by such increases in patient volume. Accurate forecasting of incoming patient volume in emergency departments (ED) is crucial for efficient utilization and allocation of ED resources. Working with a suburban ED in the Pacific Northwest, we developed a tool powered by machine learning models, to forecast ED arrivals and ED patient volume to assist end-users, such as ED nurses, in resource allocation. In this paper, we discuss the results from our predictive models, the challenges, and the learnings from users' experiences with the tool in active clinical deployment in a real world setting.

Objective: Data unavailability has been one of the biggest barriers in clinical natural language processing. This paper is aimed at providing a large-scale and publicly available patient note dataset, named PMC-Patients, with relevant articles and similar patients annotations. The ultimate goal of PMC-Patients is to facilitate the development of retrieval-based clinical decision support systems. Materials and Methods: To collect PMC-Patients, we extract patient notes from case reports in PubMed Central by recognizing certain section patterns. Patient-article relevance and patient-patient similarity are annotated by citation relationships in PubMed. In addition, we perform three tasks with PMC-Patients to demonstrate its utility in providing clinical decision support for a given patient, including (1) classifying whether another patient is similar, (2) retrieving similar patients in PMC-Patients, and (3) retrieving relevant articles in PubMed. Results: We collect and release PMC-Patients under the CC BY-NC-SA license, which becomes the largest publicly available patient note dataset so far. PMC-Patients contains 167k patient notes that are annotated with 3.1M relevant articles and 293k similar patients. Qualitative and quantitative analyses reveal the high quality and richness of our dataset. Experiments show that classifying the similarity of patient pairs is relatively easy, but it is hard to retrieve similar patients or relevant articles for a given patient from a large set of candidates. Conclusion: We present PMC-Patients, a large-scale dataset of patient notes with high quality, easy access, diverse conditions, and rich annotations. The proposed dataset can also serve as a hard benchmark for evaluating retrieval-based clinical decision support systems.

Generalist Large Language Models (LLMs), such as GPT-4, have shown considerable promise in various domains, including medical diagnosis. Rare diseases, affecting approximately 300 million people worldwide, often have unsatisfactory clinical diagnosis rates primarily due to a lack of experienced physicians and the complexity of differentiating among many rare diseases. In this context, recent news such as "ChatGPT correctly diagnosed a 4-year-old's rare disease after 17 doctors failed" underscore LLMs' potential, yet underexplored, role in clinically diagnosing rare diseases. To bridge this research gap, we introduce RareBench, a pioneering benchmark designed to systematically evaluate the capabilities of LLMs on 4 critical dimensions within the realm of rare diseases. Meanwhile, we have compiled the largest open-source dataset on rare disease patients, establishing a benchmark for future studies in this domain. To facilitate differential diagnosis of rare diseases, we develop a dynamic few-shot prompt methodology, leveraging a comprehensive rare disease knowledge graph synthesized from multiple knowledge bases, significantly enhancing LLMs' diagnostic performance. Moreover, we present an exhaustive comparative study of GPT-4's diagnostic capabilities against those of specialist physicians. Our experimental findings underscore the promising potential of integrating LLMs into the clinical diagnostic process for rare diseases. This paves the way for exciting possibilities in future advancements in this field.

Like other fields of Traditional Medicines, Unani Medicines have been found as an effective medical practice for ages. It is still widely used in the subcontinent, particularly in Pakistan and India. However, Unani Medicines Practitioners are lacking modern IT applications in their everyday clinical practices. An Online Clinical Decision Support System may address this challenge to assist apprentice Unani Medicines practitioners in their diagnostic processes. The proposed system provides a web-based interface to enter the patient's symptoms, which are then automatically analyzed by our system to generate a list of probable diseases. The system allows practitioners to choose the most likely disease and inform patients about the associated treatment options remotely. The system consists of three modules: an Online Clinical Decision Support System, an Artificial Intelligence Inference Engine, and a comprehensive Unani Medicines Database. The system employs advanced AI techniques such as Decision Trees, Deep Learning, and Natural Language Processing. For system development, the project team used a technology stack that includes React, FastAPI, and MySQL. Data and functionality of the application is exposed using APIs for integration and extension with similar domain applications. The novelty of the project is that it addresses the challenge of diagnosing diseases accurately and efficiently in the context of Unani Medicines principles. By leveraging the power of technology, the proposed Clinical Decision Support System has the potential to ease access to healthcare services and information, reduce cost, boost practitioner and patient satisfaction, improve speed and accuracy of the diagnostic process, and provide effective treatments remotely. The application will be useful for Unani Medicines Practitioners, Patients, Government Drug Regulators, Software Developers, and Medical Researchers.

We survey clinical document corpora, with focus on German textual data. Due to rigid data privacy legislation in Germany these resources, with only few exceptions, are stored in safe clinical data spaces and locked against clinic-external researchers. This situation stands in stark contrast with established workflows in the field of natural language processing where easy accessibility and reuse of data collections are common practice. Hence, alternative corpus designs have been examined to escape from this data poverty. Besides machine translation of English clinical datasets and the generation of synthetic corpora with fictitious clinical contents, several other types of domain proxies have come up as substitutes for authentic clinical documents. Common instances of close proxies are medical journal publications, clinical therapy guidelines, drug labels, etc., more distant proxies include online encyclopedic medical articles or medical contents from social media channels. After PRISM-conformant screening of 359 hits from four bibliographic systems, 75 relevant documents were finally selected for this review and 59 distinct corpora were determined. We identified 24 real clinical corpora (from 40 publications) out of which only 5 are publicly distributable. 2 translations of real corpora and 3 synthetic ones complement the set of clinical corpora. 14 corpora were categorized as close domain proxies, 16 as distant ones. There is a clear divide between the large number of non-accessible authentic clinical German-language corpora and their publicly accessible substitutes: translated or synthetic, close or more distant proxies. So on first sight, the data bottleneck seems broken. Intuitively yet, differences in genre-specific writing style, wording and medical domain expertise in this typological space are also obvious. This raises the question how valid alternative corpus designs really are.

Large Language Models (LLMs) and multi-agent systems have shown impressive capabilities in natural language tasks but face challenges in clinical trial applications, primarily due to limited access to external knowledge. Recognizing the potential of advanced clinical trial tools that aggregate and predict based on the latest medical data, we propose an integrated solution to enhance their accessibility and utility. We introduce Clinical Agent System (ClinicalAgent), a clinical multi-agent system designed for clinical trial tasks, leveraging GPT-4, multi-agent architectures, LEAST-TO-MOST, and ReAct reasoning technology. This integration not only boosts LLM performance in clinical contexts but also introduces novel functionalities. The proposed method achieves competitive predictive performance in clinical trial outcome prediction (0.7908 PR-AUC), obtaining a 0.3326 improvement over the standard prompt Method. Publicly available code can be found at https://anonymous.4open.science/r/ClinicalAgent-6671.

In recent years, medical information technology has made it possible for electronic health record (EHR) to store fairly complete clinical data. This has brought health care into the era of "big data". However, medical data are often sparse and strongly correlated, which means that medical problems cannot be solved effectively. With the rapid development of deep learning in recent years, it has provided opportunities for the use of big data in healthcare. In this paper, we propose a temporal-saptial correlation attention network (TSCAN) to handle some clinical characteristic prediction problems, such as predicting death, predicting length of stay, detecting physiologic decline, and classifying phenotypes. Based on the design of the attention mechanism model, our approach can effectively remove irrelevant items in clinical data and irrelevant nodes in time according to different tasks, so as to obtain more accurate prediction results. Our method can also find key clinical indicators of important outcomes that can be used to improve treatment options. Our experiments use information from the Medical Information Mart for Intensive Care (MIMIC-IV) database, which is open to the public. Finally, we have achieved significant performance benefits of 2.0\% (metric) compared to other SOTA prediction methods. We achieved a staggering 90.7\% on mortality rate, 45.1\% on length of stay. The source code can be find: https://github.com/yuyuheintju/TSCAN.

Keeping track of scientific challenges, advances and emerging directions is a fundamental part of research. However, researchers face a flood of papers that hinders discovery of important knowledge. In biomedicine, this directly impacts human lives. To address this problem, we present a novel task of extraction and search of scientific challenges and directions, to facilitate rapid knowledge discovery. We construct and release an expert-annotated corpus of texts sampled from full-length papers, labeled with novel semantic categories that generalize across many types of challenges and directions. We focus on a large corpus of interdisciplinary work relating to the COVID-19 pandemic, ranging from biomedicine to areas such as AI and economics. We apply a model trained on our data to identify challenges and directions across the corpus and build a dedicated search engine. In experiments with 19 researchers and clinicians using our system, we outperform a popular scientific search engine in assisting knowledge discovery. Finally, we show that models trained on our resource generalize to the wider biomedical domain and to AI papers, highlighting its broad utility. We make our data, model and search engine publicly available. https://challenges.apps.allenai.org/

Urgent care clinics and emergency departments around the world periodically suffer from extended wait times beyond patient expectations due to inadequate staffing levels. These delays have been linked with adverse clinical outcomes. Previous research into forecasting demand this domain has mostly used a collection of statistical techniques, with machine learning approaches only now beginning to emerge in recent literature. The forecasting problem for this domain is difficult and has also been complicated by the COVID-19 pandemic which has introduced an additional complexity to this estimation due to typical demand patterns being disrupted. This study explores the ability of machine learning methods to generate accurate patient presentations at two large urgent care clinics located in Auckland, New Zealand. A number of machine learning algorithms were explored in order to determine the most effective technique for this problem domain, with the task of making forecasts of daily patient demand three months in advance. The study also performed an in-depth analysis into the model behaviour in respect to the exploration of which features are most effective at predicting demand and which features are capable of adaptation to the volatility caused by the COVID-19 pandemic lockdowns. The results showed that ensemble-based methods delivered the most accurate and consistent solutions on average, generating improvements in the range of 23%-27% over the existing in-house methods for estimating the daily demand.

Clinical diagnosis prediction models, when provided with a patient's medical history, aim to detect potential diseases early, facilitating timely intervention and improving prognostic outcomes. However, the inherent scarcity of patient data and large disease candidate space often pose challenges in developing satisfactory models for this intricate task. The exploration of leveraging Large Language Models (LLMs) for encapsulating clinical decision processes has been limited. We introduce MERA, a clinical diagnosis prediction model that bridges pertaining natural language knowledge with medical practice. We apply hierarchical contrastive learning on a disease candidate ranking list to alleviate the large decision space issue. With concept memorization through fine-tuning, we bridge the natural language clinical knowledge with medical codes. Experimental results on MIMIC-III and IV datasets show that MERA achieves the state-of-the-art diagnosis prediction performance and dramatically elevates the diagnosis prediction capabilities of generative LMs.

In medical applications, deep learning methods are built to automate diagnostic tasks. However, a clinically relevant question that practitioners usually face, is how to predict the future trajectory of a disease (prognosis). Current methods for such a problem often require domain knowledge, and are complicated to apply. In this paper, we formulate the prognosis prediction problem as a one-to-many forecasting problem from multimodal data. Inspired by a clinical decision-making process with two agents -- a radiologist and a general practitioner, we model a prognosis prediction problem with two transformer-based components that share information between each other. The first block in this model aims to analyze the imaging data, and the second block leverages the internal representations of the first one as inputs, also fusing them with auxiliary patient data. We show the effectiveness of our method in predicting the development of structural knee osteoarthritis changes over time. Our results show that the proposed method outperforms the state-of-the-art baselines in terms of various performance metrics. In addition, we empirically show that the existence of the multi-agent transformers with depths of 2 is sufficient to achieve good performances. Our code is publicly available at https://github.com/MIPT-Oulu/CLIMAT.

The COVID-19 pandemic has posed a heavy burden to the healthcare system worldwide and caused huge social disruption and economic loss. Many deep learning models have been proposed to conduct clinical predictive tasks such as mortality prediction for COVID-19 patients in intensive care units using Electronic Health Record (EHR) data. Despite their initial success in certain clinical applications, there is currently a lack of benchmarking results to achieve a fair comparison so that we can select the optimal model for clinical use. Furthermore, there is a discrepancy between the formulation of traditional prediction tasks and real-world clinical practice in intensive care. To fill these gaps, we propose two clinical prediction tasks, Outcome-specific length-of-stay prediction and Early mortality prediction for COVID-19 patients in intensive care units. The two tasks are adapted from the naive length-of-stay and mortality prediction tasks to accommodate the clinical practice for COVID-19 patients. We propose fair, detailed, open-source data-preprocessing pipelines and evaluate 17 state-of-the-art predictive models on two tasks, including 5 machine learning models, 6 basic deep learning models and 6 deep learning predictive models specifically designed for EHR data. We provide benchmarking results using data from two real-world COVID-19 EHR datasets. One dataset is publicly available without needing any inquiry and another dataset can be accessed on request. We provide fair, reproducible benchmarking results for two tasks. We deploy all experiment results and models on an online platform. We also allow clinicians and researchers to upload their data to the platform and get quick prediction results using our trained models. We hope our efforts can further facilitate deep learning and machine learning research for COVID-19 predictive modeling.

Background: Rapid advancements in natural language processing have led to the development of large language models with the potential to revolutionize mental health care. These models have shown promise in assisting clinicians and providing support to individuals experiencing various psychological challenges. Objective: This study aims to compare the performance of two large language models, GPT-4 and Chat-GPT, in responding to a set of 18 psychological prompts, to assess their potential applicability in mental health care settings. Methods: A blind methodology was employed, with a clinical psychologist evaluating the models' responses without knowledge of their origins. The prompts encompassed a diverse range of mental health topics, including depression, anxiety, and trauma, to ensure a comprehensive assessment. Results: The results demonstrated a significant difference in performance between the two models (p > 0.05). GPT-4 achieved an average rating of 8.29 out of 10, while Chat-GPT received an average rating of 6.52. The clinical psychologist's evaluation suggested that GPT-4 was more effective at generating clinically relevant and empathetic responses, thereby providing better support and guidance to potential users. Conclusions: This study contributes to the growing body of literature on the applicability of large language models in mental health care settings. The findings underscore the importance of continued research and development in the field to optimize these models for clinical use. Further investigation is necessary to understand the specific factors underlying the performance differences between the two models and to explore their generalizability across various populations and mental health conditions.

Medical benchmark datasets significantly contribute to developing Large Language Models (LLMs) for medical knowledge extraction, diagnosis, summarization, and other uses. Yet, current benchmarks are mainly derived from exam questions given to medical students or cases described in the medical literature, lacking the complexity of real-world patient cases that deviate from classic textbook abstractions. These include rare diseases, uncommon presentations of common diseases, and unexpected treatment responses. Here, we construct Clinically Uncommon Patient Cases and Diagnosis Dataset (CUPCase) based on 3,562 real-world case reports from BMC, including diagnoses in open-ended textual format and as multiple-choice options with distractors. Using this dataset, we evaluate the ability of state-of-the-art LLMs, including both general-purpose and Clinical LLMs, to identify and correctly diagnose a patient case, and test models' performance when only partial information about cases is available. Our findings show that general-purpose GPT-4o attains the best performance in both the multiple-choice task (average accuracy of 87.9%) and the open-ended task (BERTScore F1 of 0.764), outperforming several LLMs with a focus on the medical domain such as Meditron-70B and MedLM-Large. Moreover, GPT-4o was able to maintain 87% and 88% of its performance with only the first 20% of tokens of the case presentation in multiple-choice and free text, respectively, highlighting the potential of LLMs to aid in early diagnosis in real-world cases. CUPCase expands our ability to evaluate LLMs for clinical decision support in an open and reproducible manner.

The burgeoning integration of 3D medical imaging into healthcare has led to a substantial increase in the workload of medical professionals. To assist clinicians in their diagnostic processes and alleviate their workload, the development of a robust system for retrieving similar case studies presents a viable solution. While the concept holds great promise, the field of 3D medical text-image retrieval is currently limited by the absence of robust evaluation benchmarks and curated datasets. To remedy this, our study presents a groundbreaking dataset, BIMCV-R (This dataset will be released upon acceptance.), which includes an extensive collection of 8,069 3D CT volumes, encompassing over 2 million slices, paired with their respective radiological reports. Expanding upon the foundational work of our dataset, we craft a retrieval strategy, MedFinder. This approach employs a dual-stream network architecture, harnessing the potential of large language models to advance the field of medical image retrieval beyond existing text-image retrieval solutions. It marks our preliminary step towards developing a system capable of facilitating text-to-image, image-to-text, and keyword-based retrieval tasks.

Hospital information systems (HIS) have become an essential part of healthcare institutions and now incorporate prescribing support software. Prescription support software allows for structured information capture, which improves the safety, appropriateness and efficiency of prescriptions and reduces the number of adverse drug events (ADEs). However, such a system increases the amount of time physicians spend at a computer entering information instead of providing medical care. In addition, any new visiting clinician must learn to manage complex interfaces since each HIS has its own interfaces. In this paper, we present a natural language interface for e-prescribing software in the form of a spoken dialogue system accessible on a smartphone. This system allows prescribers to record their prescriptions verbally, a form of interaction closer to their usual practice. The system extracts the formal representation of the prescription ready to be checked by the prescribing software and uses the dialogue to request mandatory information, correct errors or warn of particular situations. Since, to the best of our knowledge, there is no existing voice-based prescription dialogue system, we present the system developed in a low-resource environment, focusing on dialogue modeling, semantic extraction and data augmentation. The system was evaluated in the wild with 55 participants. This evaluation showed that our system has an average prescription time of 66.15 seconds for physicians and 35.64 seconds for other experts, and a task success rate of 76\% for physicians and 72\% for other experts. All evaluation data were recorded and annotated to form PxCorpus, the first spoken drug prescription corpus that has been made fully available to the community (https://doi.org/10.5281/zenodo.6524162).

Global rates of mental health concerns are rising and there is increasing realization that existing models of mental healthcare will not adequately expand to meet the demand. With the emergence of large language models (LLMs) has come great optimism regarding their promise to create novel, large-scale solutions to support mental health. Despite their nascence, LLMs have already been applied to mental health-related tasks. In this review, we summarize the extant literature on efforts to use LLMs to provide mental health education, assessment, and intervention and highlight key opportunities for positive impact in each area. We then highlight risks associated with LLMs application to mental health and encourage adoption of strategies to mitigate these risks. The urgent need for mental health support must be balanced with responsible development, testing, and deployment of mental health LLMs. Especially critical is ensuring that mental health LLMs are fine-tuned for mental health, enhance mental health equity, adhere to ethical standards, and that people, including those with lived experience with mental health concerns, are involved in all stages from development through deployment. Prioritizing these efforts will minimize potential harms to mental health and maximize the likelihood that LLMs will positively impact mental health globally.

The increasing threat of emerging infectious diseases and antimicrobial resistance requires more efficient, high-quality research. Perpetual Observational Studies (POS) nested within a clinical research network can improve planning, quality and efficiency of interventional and observational studies, although real-life benefits and challenges need to be assessed. Ecraid (European Clinical Research Alliance on Infectious Diseases) has initiated POS and will monitor the impact for five specific infectious syndromes.

Objective: Using natural language processing (NLP) to find sentences that state treatment plans in a clinical note, would automate plan extraction and would further enable their use in tools that help providers and care managers. However, as in the most NLP tasks on clinical text, creating gold standard to train and test NLP models is tedious and expensive. Fortuitously, sometimes but not always clinical notes contain sections with a heading that identifies the section as a plan. Leveraging contents of such labeled sections as a noisy training data, we assessed accuracy of NLP models trained with the data. Methods: We used common variations of plan headings and rule-based heuristics to find plan sections with headings in clinical notes, and we extracted sentences from them and formed a noisy training data of plan sentences. We trained Support Vector Machine (SVM) and Convolutional Neural Network (CNN) models with the data. We measured accuracy of the trained models on the noisy dataset using ten-fold cross validation and separately on a set-aside manually annotated dataset. Results: About 13% of 117,730 clinical notes contained treatment plans sections with recognizable headings in the 1001 longitudinal patient records that were obtained from Cleveland Clinic under an IRB approval. We were able to extract and create a noisy training data of 13,492 plan sentences from the clinical notes. CNN achieved best F measures, 0.91 and 0.97 in the cross-validation and set-aside evaluation experiments respectively. SVM slightly underperformed with F measures of 0.89 and 0.96 in the same experiments. Conclusion: Our study showed that the training supervised learning models using noisy plan sentences was effective in identifying them in all clinical notes. More broadly, sections with informal headings in clinical notes can be a good source for generating effective training data.

Large language models (LLMs) have received much attention and shown their potential in digital health, while their application in mental health is subject to ongoing debate. This systematic review aims to summarize and characterize the use of LLMs in mental health by investigating the strengths and limitations of the latest work in LLMs and discusses the challenges and opportunities for early screening, digital interventions, and other clinical applications in mental health. Following PRISMA guidelines, we examined English articles from PubMed, DBLP Computer Science Bibliography, and IEEE Xplore, published between 1 January 2017, and 1 September 2023, focusing on mental health and LLMs. The review analyzed 32 articles, including mental health analysis using social media datasets (n=13), mental health chatbots (n=10), and other mental health applications (n=9). Findings reveal LLMs' effectiveness in mental health issue detection and the enhancement of telepsychological services through personalised healthcare. Nonetheless, risks like text inconsistencies, hallucinatory content, and the lack of an ethical framework raise concerns about their clinical use. Despite these challenges, the advancement of LLMs underscores their potential as innovative clinical tools, necessitating further research and development. The review emphasizes that LLMs should complement, not replace, professional mental health services.

Recruiting patients to participate in clinical trials can be challenging and time-consuming. Usually, participation in a clinical trial is initiated by a healthcare professional and proposed to the patient. Promoting clinical trials directly to patients via online recruitment might help to reach them more efficiently. In this study, we address the case where a patient is initiating their own recruitment process and wants to determine whether they are eligible for a given clinical trial, using their own language to describe their medical profile. To study whether this creates difficulties in the patient trial matching process, we design a new dataset and task, Natural Language Inference for Patient Recruitment (NLI4PR), in which patient language profiles must be matched to clinical trials. We create it by adapting the TREC 2022 Clinical Trial Track dataset, which provides patients' medical profiles, and rephrasing them manually using patient language. We also use the associated clinical trial reports where the patients are either eligible or excluded. We prompt several open-source Large Language Models on our task and achieve from 56.5 to 71.8 of F1 score using patient language, against 64.7 to 73.1 for the same task using medical language. When using patient language, we observe only a small loss in performance for the best model, suggesting that having the patient as a starting point could be adopted to help recruit patients for clinical trials. The corpus and code bases are all freely available on our Github and HuggingFace repositories.

Diabetes is a chronic disease that poses a significant global health burden, and optimizing diabetes management requires multi-stakeholder collaboration. Large language models (LLMs) have shown promise in various healthcare scenarios, but their effectiveness across a diverse range of diabetes tasks remains unproven. In this study, we introduced a framework to train and validate diabetes-specific LLMs. We first developed a comprehensive data processing pipeline that includes data collection, filtering, augmentation and refinement. This approach contributes to creating a high-quality, diabetes-specific dataset, and several evaluation benchmarks entirely from scratch. Utilizing the collected training dataset, we fine-tuned a diabetes-specific LLM family that demonstrated state-of-the-art proficiency in understanding and processing various diabetes tasks compared to other LLMs. Furthermore, clinical studies showed the potential applications of our models in diabetes care, including providing personalized healthcare, assisting medical education, and streamlining clinical tasks. In conclusion, our study introduced a framework to develop and evaluate a diabetes-specific LLM family, and highlighted its potential to enhance clinical practice and provide personalized, data-driven support for diabetes support when facing different end users. The code is provided via GitHub at https://github.com/waltonfuture/Diabetica.

The integration of Artificial Intelligence (AI), especially Large Language Models (LLMs), into the clinical diagnosis process offers significant potential to improve the efficiency and accessibility of medical care. While LLMs have shown some promise in the medical domain, their application in clinical diagnosis remains underexplored, especially in real-world clinical practice, where highly sophisticated, patient-specific decisions need to be made. Current evaluations of LLMs in this field are often narrow in scope, focusing on specific diseases or specialties and employing simplified diagnostic tasks. To bridge this gap, we introduce CliBench, a novel benchmark developed from the MIMIC IV dataset, offering a comprehensive and realistic assessment of LLMs' capabilities in clinical diagnosis. This benchmark not only covers diagnoses from a diverse range of medical cases across various specialties but also incorporates tasks of clinical significance: treatment procedure identification, lab test ordering and medication prescriptions. Supported by structured output ontologies, CliBench enables a precise and multi-granular evaluation, offering an in-depth understanding of LLM's capability on diverse clinical tasks of desired granularity. We conduct a zero-shot evaluation of leading LLMs to assess their proficiency in clinical decision-making. Our preliminary results shed light on the potential and limitations of current LLMs in clinical settings, providing valuable insights for future advancements in LLM-powered healthcare.

This paper introduces a new testbed CLIFT (Clinical Shift) for the clinical domain Question-answering task. The testbed includes 7.5k high-quality question answering samples to provide a diverse and reliable benchmark. We performed a comprehensive experimental study and evaluated several QA deep-learning models under the proposed testbed. Despite impressive results on the original test set, the performance degrades when applied to new test sets, which shows the distribution shift. Our findings emphasize the need for and the potential for increasing the robustness of clinical domain models under distributional shifts. The testbed offers one way to track progress in that direction. It also highlights the necessity of adopting evaluation metrics that consider robustness to natural distribution shifts. We plan to expand the corpus by adding more samples and model results. The full paper and the updated benchmark are available at github.com/openlifescience-ai/clift

Electronic medical records (EMR) contain sensitive personal information. For example, they may include details about infectious diseases, such as human immunodeficiency virus (HIV), or they may contain information about a mental illness. They may also contain other sensitive information such as medical details related to fertility treatments. Because EMRs are subject to confidentiality requirements, accessing and analyzing EMR databases is a privilege given to only a small number of individuals. Individuals who work at institutions that do not have access to EMR systems have no opportunity to gain hands-on experience with this valuable resource. Simulated medical databases are currently available; however, they are difficult to configure and are limited in their resemblance to real clinical databases. Generating highly accessible repositories of virtual patient EMRs while relying only minimally on real patient data is expected to serve as a valuable resource to a broader audience of medical personnel, including those who reside in underdeveloped countries.

Large Language Models (LLMs) are at the forefront of NLP achievements but fall short in dealing with shortcut learning, factual inconsistency, and vulnerability to adversarial inputs.These shortcomings are especially critical in medical contexts, where they can misrepresent actual model capabilities. Addressing this, we present SemEval-2024 Task 2: Safe Biomedical Natural Language Inference for ClinicalTrials. Our contributions include the refined NLI4CT-P dataset (i.e., Natural Language Inference for Clinical Trials - Perturbed), designed to challenge LLMs with interventional and causal reasoning tasks, along with a comprehensive evaluation of methods and results for participant submissions. A total of 106 participants registered for the task contributing to over 1200 individual submissions and 25 system overview papers. This initiative aims to advance the robustness and applicability of NLI models in healthcare, ensuring safer and more dependable AI assistance in clinical decision-making. We anticipate that the dataset, models, and outcomes of this task can support future research in the field of biomedical NLI. The dataset, competition leaderboard, and website are publicly available.

Recent large language models (LLMs) in the general domain, such as ChatGPT, have shown remarkable success in following instructions and producing human-like responses. However, such language models have not been learned individually and carefully for the medical domain, resulting in poor diagnostic accuracy and inability to give correct recommendations for medical diagnosis, medications, etc. To address this issue, we collected more than 700 diseases and their corresponding symptoms, recommended medications, and required medical tests, and then generated 5K doctor-patient conversations. By fine-tuning models of doctor-patient conversations, these models emerge with great potential to understand patients' needs, provide informed advice, and offer valuable assistance in a variety of medical-related fields. The integration of these advanced language models into healthcare can revolutionize the way healthcare professionals and patients communicate, ultimately improving the overall quality of care and patient outcomes. In addition, we will open all source code, datasets and model weights to advance the further development of dialogue models in the medical field. In addition, the training data, code, and weights of this project are available at: https://github.com/Kent0n-Li/ChatDoctor.

Large language models (LLMs) have demonstrated remarkable capabilities in natural language understanding and generation across various domains, including medicine. We present a comprehensive evaluation of GPT-4, a state-of-the-art LLM, on medical competency examinations and benchmark datasets. GPT-4 is a general-purpose model that is not specialized for medical problems through training or engineered to solve clinical tasks. Our analysis covers two sets of official practice materials for the USMLE, a three-step examination program used to assess clinical competency and grant licensure in the United States. We also evaluate performance on the MultiMedQA suite of benchmark datasets. Beyond measuring model performance, experiments were conducted to investigate the influence of test questions containing both text and images on model performance, probe for memorization of content during training, and study probability calibration, which is of critical importance in high-stakes applications like medicine. Our results show that GPT-4, without any specialized prompt crafting, exceeds the passing score on USMLE by over 20 points and outperforms earlier general-purpose models (GPT-3.5) as well as models specifically fine-tuned on medical knowledge (Med-PaLM, a prompt-tuned version of Flan-PaLM 540B). In addition, GPT-4 is significantly better calibrated than GPT-3.5, demonstrating a much-improved ability to predict the likelihood that its answers are correct. We also explore the behavior of the model qualitatively through a case study that shows the ability of GPT-4 to explain medical reasoning, personalize explanations to students, and interactively craft new counterfactual scenarios around a medical case. Implications of the findings are discussed for potential uses of GPT-4 in medical education, assessment, and clinical practice, with appropriate attention to challenges of accuracy and safety.

A promising application of AI to healthcare is the retrieval of information from electronic health records (EHRs), e.g. to aid clinicians in finding relevant information for a consultation or to recruit suitable patients for a study. This requires search capabilities far beyond simple string matching, including the retrieval of concepts (diagnoses, symptoms, medications, etc.) related to the one in question. The suitability of AI methods for such applications is tested by predicting the relatedness of concepts with known relatedness scores. However, all existing biomedical concept relatedness datasets are notoriously small and consist of hand-picked concept pairs. We open-source a novel concept relatedness benchmark overcoming these issues: it is six times larger than existing datasets and concept pairs are chosen based on co-occurrence in EHRs, ensuring their relevance for the application of interest. We present an in-depth analysis of our new dataset and compare it to existing ones, highlighting that it is not only larger but also complements existing datasets in terms of the types of concepts included. Initial experiments with state-of-the-art embedding methods show that our dataset is a challenging new benchmark for testing concept relatedness models.

Medical systematic reviews can be very costly and resource intensive. We explore how Large Language Models (LLMs) can support and be trained to perform literature screening when provided with a detailed set of selection criteria. Specifically, we instruction tune LLaMA and Guanaco models to perform abstract screening for medical systematic reviews. Our best model, Bio-SIEVE, outperforms both ChatGPT and trained traditional approaches, and generalises better across medical domains. However, there remains the challenge of adapting the model to safety-first scenarios. We also explore the impact of multi-task training with Bio-SIEVE-Multi, including tasks such as PICO extraction and exclusion reasoning, but find that it is unable to match single-task Bio-SIEVE's performance. We see Bio-SIEVE as an important step towards specialising LLMs for the biomedical systematic review process and explore its future developmental opportunities. We release our models, code and a list of DOIs to reconstruct our dataset for reproducibility.

Summarization of clinical narratives is a long-standing research problem. Here, we introduce the task of hospital-course summarization. Given the documentation authored throughout a patient's hospitalization, generate a paragraph that tells the story of the patient admission. We construct an English, text-to-text dataset of 109,000 hospitalizations (2M source notes) and their corresponding summary proxy: the clinician-authored "Brief Hospital Course" paragraph written as part of a discharge note. Exploratory analyses reveal that the BHC paragraphs are highly abstractive with some long extracted fragments; are concise yet comprehensive; differ in style and content organization from the source notes; exhibit minimal lexical cohesion; and represent silver-standard references. Our analysis identifies multiple implications for modeling this complex, multi-document summarization task.

With the advent of Vision-Language Models (VLMs), medical artificial intelligence (AI) has experienced significant technological progress and paradigm shifts. This survey provides an extensive review of recent advancements in Medical Vision-Language Models (Med-VLMs), which integrate visual and textual data to enhance healthcare outcomes. We discuss the foundational technology behind Med-VLMs, illustrating how general models are adapted for complex medical tasks, and examine their applications in healthcare. The transformative impact of Med-VLMs on clinical practice, education, and patient care is highlighted, alongside challenges such as data scarcity, narrow task generalization, interpretability issues, and ethical concerns like fairness, accountability, and privacy. These limitations are exacerbated by uneven dataset distribution, computational demands, and regulatory hurdles. Rigorous evaluation methods and robust regulatory frameworks are essential for safe integration into healthcare workflows. Future directions include leveraging large-scale, diverse datasets, improving cross-modal generalization, and enhancing interpretability. Innovations like federated learning, lightweight architectures, and Electronic Health Record (EHR) integration are explored as pathways to democratize access and improve clinical relevance. This review aims to provide a comprehensive understanding of Med-VLMs' strengths and limitations, fostering their ethical and balanced adoption in healthcare.

As the field of artificial intelligence progresses, assistive technologies are becoming more widely used across all industries. The healthcare industry is no different, with numerous studies being done to develop assistive tools for healthcare professionals. Automatic diagnostic systems are one such beneficial tool that can assist with a variety of tasks, including collecting patient information, analyzing test results, and diagnosing patients. However, the idea of developing systems that can provide a differential diagnosis has been largely overlooked in most of these research studies. In this study, we propose a transformer-based approach for providing differential diagnoses based on a patient's age, sex, medical history, and symptoms. We use the DDXPlus dataset, which provides differential diagnosis information for patients based on 49 disease types. Firstly, we propose a method to process the tabular patient data from the dataset and engineer them into patient reports to make them suitable for our research. In addition, we introduce two data modification modules to diversify the training data and consequently improve the robustness of the models. We approach the task as a multi-label classification problem and conduct extensive experiments using four transformer models. All the models displayed promising results by achieving over 97% F1 score on the held-out test set. Moreover, we design additional behavioral tests to get a broader understanding of the models. In particular, for one of our test cases, we prepared a custom test set of 100 samples with the assistance of a doctor. The results on the custom set showed that our proposed data modification modules improved the model's generalization capabilities. We hope our findings will provide future researchers with valuable insights and inspire them to develop reliable systems for automatic differential diagnosis.

Specialised pre-trained language models are becoming more frequent in NLP since they can potentially outperform models trained on generic texts. BioBERT and BioClinicalBERT are two examples of such models that have shown promise in medical NLP tasks. Many of these models are overparametrised and resource-intensive, but thanks to techniques like Knowledge Distillation (KD), it is possible to create smaller versions that perform almost as well as their larger counterparts. In this work, we specifically focus on development of compact language models for processing clinical texts (i.e. progress notes, discharge summaries etc). We developed a number of efficient lightweight clinical transformers using knowledge distillation and continual learning, with the number of parameters ranging from 15 million to 65 million. These models performed comparably to larger models such as BioBERT and ClinicalBioBERT and significantly outperformed other compact models trained on general or biomedical data. Our extensive evaluation was done across several standard datasets and covered a wide range of clinical text-mining tasks, including Natural Language Inference, Relation Extraction, Named Entity Recognition, and Sequence Classification. To our knowledge, this is the first comprehensive study specifically focused on creating efficient and compact transformers for clinical NLP tasks. The models and code used in this study can be found on our Huggingface profile at https://huggingface.co/nlpie and Github page at https://github.com/nlpie-research/Lightweight-Clinical-Transformers, respectively, promoting reproducibility of our results.

Documentation burden is a major contributor to clinician burnout, which is rising nationally and is an urgent threat to our ability to care for patients. Artificial intelligence (AI) chatbots, such as ChatGPT, could reduce clinician burden by assisting with documentation. Although many hospitals are actively integrating such systems into electronic medical record systems, AI chatbots utility and impact on clinical decision-making have not been studied for this intended use. We are the first to examine the utility of large language models in assisting clinicians draft responses to patient questions. In our two-stage cross-sectional study, 6 oncologists responded to 100 realistic synthetic cancer patient scenarios and portal messages developed to reflect common medical situations, first manually, then with AI assistance. We find AI-assisted responses were longer, less readable, but provided acceptable drafts without edits 58% of time. AI assistance improved efficiency 77% of time, with low harm risk (82% safe). However, 7.7% unedited AI responses could severely harm. In 31% cases, physicians thought AI drafts were human-written. AI assistance led to more patient education recommendations, fewer clinical actions than manual responses. Results show promise for AI to improve clinician efficiency and patient care through assisting documentation, if used judiciously. Monitoring model outputs and human-AI interaction remains crucial for safe implementation.

The World Health Organization added Disease X to their shortlist of blueprint priority diseases to represent a hypothetical, unknown pathogen that could cause a future epidemic. During different virus outbreaks of the past, such as COVID-19, Influenza, Lyme Disease, and Zika virus, researchers from various disciplines utilized Google Trends to mine multimodal components of web behavior to study, investigate, and analyze the global awareness, preparedness, and response associated with these respective virus outbreaks. As the world prepares for Disease X, a dataset on web behavior related to Disease X would be crucial to contribute towards the timely advancement of research in this field. Furthermore, none of the prior works in this field have focused on the development of a dataset to compile relevant web behavior data, which would help to prepare for Disease X. To address these research challenges, this work presents a dataset of web behavior related to Disease X, which emerged from different geographic regions of the world, between February 2018 and August 2023. Specifically, this dataset presents the search interests related to Disease X from 94 geographic regions. The dataset was developed by collecting data using Google Trends. The relevant search interests for all these regions for each month in this time range are available in this dataset. This paper also discusses the compliance of this dataset with the FAIR principles of scientific data management. Finally, an analysis of this dataset is presented to uphold the applicability, relevance, and usefulness of this dataset for the investigation of different research questions in the interrelated fields of Big Data, Data Mining, Healthcare, Epidemiology, and Data Analysis with a specific focus on Disease X.

Under the pandemic of COVID-19, people experiencing COVID19-related symptoms or exposed to risk factors have a pressing need to consult doctors. Due to hospital closure, a lot of consulting services have been moved online. Because of the shortage of medical professionals, many people cannot receive online consultations timely. To address this problem, we aim to develop a medical dialogue system that can provide COVID19-related consultations. We collected two dialogue datasets -- CovidDialog -- (in English and Chinese respectively) containing conversations between doctors and patients about COVID-19. On these two datasets, we train several dialogue generation models based on Transformer, GPT, and BERT-GPT. Since the two COVID-19 dialogue datasets are small in size, which bear high risk of overfitting, we leverage transfer learning to mitigate data deficiency. Specifically, we take the pretrained models of Transformer, GPT, and BERT-GPT on dialog datasets and other large-scale texts, then finetune them on our CovidDialog tasks. We perform both automatic and human evaluation of responses generated by these models. The results show that the generated responses are promising in being doctor-like, relevant to the conversation history, and clinically informative. The data and code are available at https://github.com/UCSD-AI4H/COVID-Dialogue.

Alzheimer's disease (AD) is a degenerative brain disease impairing a person's ability to perform day to day activities. The clinical manifestations of Alzheimer's disease are characterized by heterogeneity in age, disease span, progression rate, impairment of memory and cognitive abilities. Due to these variabilities, personalized care and treatment planning, as well as patient counseling about their individual progression is limited. Recent developments in machine learning to detect hidden patterns in complex, multi-dimensional datasets provides significant opportunities to address this critical need. In this work, we use unsupervised and supervised machine learning approaches for subtype identification and prediction. We apply machine learning methods to the extensive clinical observations available at the Alzheimer's Disease Neuroimaging Initiative (ADNI) data set to identify patient subtypes and to predict disease progression. Our analysis depicts the progression space for the Alzheimer's disease into low, moderate and high disease progression zones. The proposed work will enable early detection and characterization of distinct disease subtypes based on clinical heterogeneity. We anticipate that our models will enable patient counseling, clinical trial design, and ultimately individualized clinical care.

There is an increasing interest in developing artificial intelligence (AI) systems to process and interpret electronic health records (EHRs). Natural language processing (NLP) powered by pretrained language models is the key technology for medical AI systems utilizing clinical narratives. However, there are few clinical language models, the largest of which trained in the clinical domain is comparatively small at 110 million parameters (compared with billions of parameters in the general domain). It is not clear how large clinical language models with billions of parameters can help medical AI systems utilize unstructured EHRs. In this study, we develop from scratch a large clinical language model - GatorTron - using >90 billion words of text (including >82 billion words of de-identified clinical text) and systematically evaluate it on 5 clinical NLP tasks including clinical concept extraction, medical relation extraction, semantic textual similarity, natural language inference (NLI), and medical question answering (MQA). We examine how (1) scaling up the number of parameters and (2) scaling up the size of the training data could benefit these NLP tasks. GatorTron models scale up the clinical language model from 110 million to 8.9 billion parameters and improve 5 clinical NLP tasks (e.g., 9.6% and 9.5% improvement in accuracy for NLI and MQA), which can be applied to medical AI systems to improve healthcare delivery. The GatorTron models are publicly available at: https://catalog.ngc.nvidia.com/orgs/nvidia/teams/clara/models/gatortron_og.

Online medical consultation (OMC) restricts doctors to gathering patient information solely through inquiries, making the already complex sequential decision-making process of diagnosis even more challenging. Recently, the rapid advancement of large language models has demonstrated a significant potential to transform OMC. However, most studies have primarily focused on improving diagnostic accuracy under conditions of relatively sufficient information, while paying limited attention to the "inquiry" phase of the consultation process. This lack of focus has left the relationship between "inquiry" and "diagnosis" insufficiently explored. In this paper, we first extract real patient interaction strategies from authentic doctor-patient conversations and use these strategies to guide the training of a patient simulator that closely mirrors real-world behavior. By inputting medical records into our patient simulator to simulate patient responses, we conduct extensive experiments to explore the relationship between "inquiry" and "diagnosis" in the consultation process. Experimental results demonstrate that inquiry and diagnosis adhere to the Liebig's law: poor inquiry quality limits the effectiveness of diagnosis, regardless of diagnostic capability, and vice versa. Furthermore, the experiments reveal significant differences in the inquiry performance of various models. To investigate this phenomenon, we categorize the inquiry process into four types: (1) chief complaint inquiry; (2) specification of known symptoms; (3) inquiry about accompanying symptoms; and (4) gathering family or medical history. We analyze the distribution of inquiries across the four types for different models to explore the reasons behind their significant performance differences. We plan to open-source the weights and related code of our patient simulator at https://github.com/LIO-H-ZEN/PatientSimulator.

Given the dominance of dense retrievers that do not generalize well beyond their training dataset distributions, domain-specific test sets are essential in evaluating retrieval. There are few test datasets for retrieval systems intended for use by healthcare providers in a point-of-care setting. To fill this gap we have collaborated with medical professionals to create CURE, an ad-hoc retrieval test dataset for passage ranking with 2000 queries spanning 10 medical domains with a monolingual (English) and two cross-lingual (French/Spanish -> English) conditions. In this paper, we describe how CURE was constructed and provide baseline results to showcase its effectiveness as an evaluation tool. CURE is published with a Creative Commons Attribution Non Commercial 4.0 license and can be accessed on Hugging Face.

Since the launch of ChatGPT in late 2022, the capacities of Large Language Models and their evaluation have been in constant discussion and evaluation both in academic research and in the industry. Scenarios and benchmarks have been developed in several areas such as law, medicine and math (Bommasani et al., 2023) and there is continuous evaluation of model variants. One area that has not received sufficient scenario development attention is journalism, and in particular journalistic sourcing and ethics. Journalism is a crucial truth-determination function in democracy (Vincent, 2023), and sourcing is a crucial pillar to all original journalistic output. Evaluating the capacities of LLMs to annotate stories for the different signals of sourcing and how reporters justify them is a crucial scenario that warrants a benchmark approach. It offers potential to build automated systems to contrast more transparent and ethically rigorous forms of journalism with everyday fare. In this paper we lay out a scenario to evaluate LLM performance on identifying and annotating sourcing in news stories on a five-category schema inspired from journalism studies (Gans, 2004). We offer the use case, our dataset and metrics and as the first step towards systematic benchmarking. Our accuracy findings indicate LLM-based approaches have more catching to do in identifying all the sourced statements in a story, and equally, in matching the type of sources. An even harder task is spotting source justifications.

We develop Polaris, the first safety-focused LLM constellation for real-time patient-AI healthcare conversations. Unlike prior LLM works in healthcare focusing on tasks like question answering, our work specifically focuses on long multi-turn voice conversations. Our one-trillion parameter constellation system is composed of several multibillion parameter LLMs as co-operative agents: a stateful primary agent that focuses on driving an engaging conversation and several specialist support agents focused on healthcare tasks performed by nurses to increase safety and reduce hallucinations. We develop a sophisticated training protocol for iterative co-training of the agents that optimize for diverse objectives. We train our models on proprietary data, clinical care plans, healthcare regulatory documents, medical manuals, and other medical reasoning documents. We align our models to speak like medical professionals, using organic healthcare conversations and simulated ones between patient actors and experienced nurses. This allows our system to express unique capabilities such as rapport building, trust building, empathy and bedside manner. Finally, we present the first comprehensive clinician evaluation of an LLM system for healthcare. We recruited over 1100 U.S. licensed nurses and over 130 U.S. licensed physicians to perform end-to-end conversational evaluations of our system by posing as patients and rating the system on several measures. We demonstrate Polaris performs on par with human nurses on aggregate across dimensions such as medical safety, clinical readiness, conversational quality, and bedside manner. Additionally, we conduct a challenging task-based evaluation of the individual specialist support agents, where we demonstrate our LLM agents significantly outperform a much larger general-purpose LLM (GPT-4) as well as from its own medium-size class (LLaMA-2 70B).

We collected a large dataset consisting of nearly 900 unique participants. For every participant we recorded two 30 second uncompressed videos, synchronized PPG waveforms and a single blood pressure measurement. Gender, age and skin color were also registered for every participant. The dataset includes roughly equal numbers of males and females, as well as participants of all ages. While the skin color distribution could have been more balanced, the dataset contains individuals from every skin color. The data was collected in a diverse set of locations to ensure a wide variety of backgrounds and lighting conditions. In an effort to assist in the research and development of remote vital sign measurement we are now opening up access to this dataset.

Since the COVID-19 pandemic, clinicians have seen a large and sustained influx in patient portal messages, significantly contributing to clinician burnout. To the best of our knowledge, there are no large-scale public patient portal messages corpora researchers can use to build tools to optimize clinician portal workflows. Informed by our ongoing work with a regional hospital, this study introduces an LLM-powered framework for configurable and realistic patient portal message generation. Our approach leverages few-shot grounded text generation, requiring only a small number of de-identified patient portal messages to help LLMs better match the true style and tone of real data. Clinical experts in our team deem this framework as HIPAA-friendly, unlike existing privacy-preserving approaches to synthetic text generation which cannot guarantee all sensitive attributes will be protected. Through extensive quantitative and human evaluation, we show that our framework produces data of higher quality than comparable generation methods as well as all related datasets. We believe this work provides a path forward for (i) the release of large-scale synthetic patient message datasets that are stylistically similar to ground-truth samples and (ii) HIPAA-friendly data generation which requires minimal human de-identification efforts.

We present ReXGradient-160K, representing the largest publicly available chest X-ray dataset to date in terms of the number of patients. This dataset contains 160,000 chest X-ray studies with paired radiological reports from 109,487 unique patients across 3 U.S. health systems (79 medical sites). This comprehensive dataset includes multiple images per study and detailed radiology reports, making it particularly valuable for the development and evaluation of AI systems for medical imaging and automated report generation models. The dataset is divided into training (140,000 studies), validation (10,000 studies), and public test (10,000 studies) sets, with an additional private test set (10,000 studies) reserved for model evaluation on the ReXrank benchmark. By providing this extensive dataset, we aim to accelerate research in medical imaging AI and advance the state-of-the-art in automated radiological analysis. Our dataset will be open-sourced at https://huggingface.co/datasets/rajpurkarlab/ReXGradient-160K.

We developed an explainable artificial intelligence (AI) early warning score (xAI-EWS) system for early detection of acute critical illness. While maintaining a high predictive performance, our system explains to the clinician on which relevant electronic health records (EHRs) data the prediction is grounded. Acute critical illness is often preceded by deterioration of routinely measured clinical parameters, e.g., blood pressure and heart rate. Early clinical prediction is typically based on manually calculated screening metrics that simply weigh these parameters, such as Early Warning Scores (EWS). The predictive performance of EWSs yields a tradeoff between sensitivity and specificity that can lead to negative outcomes for the patient. Previous work on EHR-trained AI systems offers promising results with high levels of predictive performance in relation to the early, real-time prediction of acute critical illness. However, without insight into the complex decisions by such system, clinical translation is hindered. In this letter, we present our xAI-EWS system, which potentiates clinical translation by accompanying a prediction with information on the EHR data explaining it.

Objectives: While Large Language Models (LLMs) have been widely used to assist clinicians and support patients, no existing work has explored dialogue systems for standard diagnostic interviews and assessments. This study aims to bridge the gap in mental healthcare accessibility by developing an LLM-powered dialogue system that replicates clinician behavior. Materials and Methods: We introduce TRUST, a framework of cooperative LLM modules capable of conducting formal diagnostic interviews and assessments for Post-Traumatic Stress Disorder (PTSD). To guide the generation of appropriate clinical responses, we propose a Dialogue Acts schema specifically designed for clinical interviews. Additionally, we develop a patient simulation approach based on real-life interview transcripts to replace time-consuming and costly manual testing by clinicians. Results: A comprehensive set of evaluation metrics is designed to assess the dialogue system from both the agent and patient simulation perspectives. Expert evaluations by conversation and clinical specialists show that TRUST performs comparably to real-life clinical interviews. Discussion: Our system performs at the level of average clinicians, with room for future enhancements in communication styles and response appropriateness. Conclusions: Our TRUST framework shows its potential to facilitate mental healthcare availability.

We present a novel contribution to Spanish clinical natural language processing by introducing the largest publicly available clinical corpus, ClinText-SP, along with a state-of-the-art clinical encoder language model, RigoBERTa Clinical. Our corpus was meticulously curated from diverse open sources, including clinical cases from medical journals and annotated corpora from shared tasks, providing a rich and diverse dataset that was previously difficult to access. RigoBERTa Clinical, developed through domain-adaptive pretraining on this comprehensive dataset, significantly outperforms existing models on multiple clinical NLP benchmarks. By publicly releasing both the dataset and the model, we aim to empower the research community with robust resources that can drive further advancements in clinical NLP and ultimately contribute to improved healthcare applications.

Laboratory test results are an important and generally high dimensional component of a patient's Electronic Health Record (EHR). We train embedding representations (via Word2Vec and GloVe) for LOINC codes of laboratory tests from the EHRs of about 80,000 patients at a cancer center. To include information about lab test outcomes, we also train embeddings on the concatenation of a LOINC code with a symbol indicating normality or abnormality of the result. We observe several clinically meaningful similarities among LOINC embeddings trained over our data. For the embeddings of the concatenation of LOINCs with abnormality codes, we evaluate the performance for mortality prediction tasks and the ability to preserve ordinality properties: i.e. a lab test with normal outcome should be more similar to an abnormal one than to the a very abnormal one.

The third ML4H symposium was held in person on December 10, 2023, in New Orleans, Louisiana, USA. The symposium included research roundtable sessions to foster discussions between participants and senior researchers on timely and relevant topics for the ML4H community. Encouraged by the successful virtual roundtables in the previous year, we organized eleven in-person roundtables and four virtual roundtables at ML4H 2022. The organization of the research roundtables at the conference involved 17 Senior Chairs and 19 Junior Chairs across 11 tables. Each roundtable session included invited senior chairs (with substantial experience in the field), junior chairs (responsible for facilitating the discussion), and attendees from diverse backgrounds with interest in the session's topic. Herein we detail the organization process and compile takeaways from these roundtable discussions, including recent advances, applications, and open challenges for each topic. We conclude with a summary and lessons learned across all roundtables. This document serves as a comprehensive review paper, summarizing the recent advancements in machine learning for healthcare as contributed by foremost researchers in the field.

Recent research on large language models (LLMs) has primarily focused on their adaptation and application in specialized domains. The application of LLMs in the medical field is mainly concentrated on tasks such as the automation of medical report generation, summarization, diagnostic reasoning, and question-and-answer interactions between doctors and patients. The challenge of becoming a good teacher is more formidable than that of becoming a good student, and this study pioneers the application of LLMs in the field of medical education. In this work, we investigate the extent to which LLMs can generate medical qualification exam questions and corresponding answers based on few-shot prompts. Utilizing a real-world Chinese dataset of elderly chronic diseases, we tasked the LLMs with generating open-ended questions and answers based on a subset of sampled admission reports across eight widely used LLMs, including ERNIE 4, ChatGLM 4, Doubao, Hunyuan, Spark 4, Qwen, Llama 3, and Mistral. Furthermore, we engaged medical experts to manually evaluate these open-ended questions and answers across multiple dimensions. The study found that LLMs, after using few-shot prompts, can effectively mimic real-world medical qualification exam questions, whereas there is room for improvement in the correctness, evidence-based statements, and professionalism of the generated answers. Moreover, LLMs also demonstrate a decent level of ability to correct and rectify reference answers. Given the immense potential of artificial intelligence in the medical field, the task of generating questions and answers for medical qualification exams aimed at medical students, interns and residents can be a significant focus of future research.

Recent advances in reasoning with large language models (LLMs)has shown remarkable reasoning capabilities in domains such as mathematics and coding, yet their application to clinical diagnosis remains underexplored. Here, we introduce ClinicalGPT-R1, a reasoning enhanced generalist large language model for disease diagnosis. Trained on a dataset of 20,000 real-world clinical records, ClinicalGPT-R1 leverages diverse training strategies to enhance diagnostic reasoning. To benchmark performance, we curated MedBench-Hard, a challenging dataset spanning seven major medical specialties and representative diseases. Experimental results demonstrate that ClinicalGPT-R1 outperforms GPT-4o in Chinese diagnostic tasks and achieves comparable performance to GPT-4 in English settings. This comparative study effectively validates the superior performance of ClinicalGPT-R1 in disease diagnosis tasks. Resources are available at https://github.com/medfound/medfound.

The face is a rich source of information that can be utilized to infer a person's biological age, sex, phenotype, genetic defects, and health status. All of these factors are relevant for predicting an individual's remaining lifespan. In this study, we collected a dataset of over 24,000 images (from Wikidata/Wikipedia) of individuals who died of natural causes, along with the number of years between when the image was taken and when the person passed away. We made this dataset publicly available. We fine-tuned multiple Convolutional Neural Network (CNN) models on this data, at best achieving a mean absolute error of 8.3 years in the validation data using VGGFace. However, the model's performance diminishes when the person was younger at the time of the image. To demonstrate the potential applications of our remaining lifespan model, we present examples of using it to estimate the average loss of life (in years) due to the COVID-19 pandemic and to predict the increase in life expectancy that might result from a health intervention such as weight loss. Additionally, we discuss the ethical considerations associated with such models.

Providing high quality explanations for AI predictions based on machine learning is a challenging and complex task. To work well it requires, among other factors: selecting a proper level of generality/specificity of the explanation; considering assumptions about the familiarity of the explanation beneficiary with the AI task under consideration; referring to specific elements that have contributed to the decision; making use of additional knowledge (e.g. expert evidence) which might not be part of the prediction process; and providing evidence supporting negative hypothesis. Finally, the system needs to formulate the explanation in a clearly interpretable, and possibly convincing, way. Given these considerations, ANTIDOTE fosters an integrated vision of explainable AI, where low-level characteristics of the deep learning process are combined with higher level schemes proper of the human argumentation capacity. ANTIDOTE will exploit cross-disciplinary competences in deep learning and argumentation to support a broader and innovative view of explainable AI, where the need for high-quality explanations for clinical cases deliberation is critical. As a first result of the project, we publish the Antidote CasiMedicos dataset to facilitate research on explainable AI in general, and argumentation in the medical domain in particular.

Introduction: Recently, the effectiveness of Large Language Models (LLMs) has increased rapidly, allowing them to be used in a great number of applications. However, the risks posed by the generation of false information through LLMs significantly limit their applications in sensitive areas such as healthcare, highlighting the necessity for rigorous validations to determine their utility and reliability. To date, no study has extensively compared the performance of LLMs on Polish medical examinations across a broad spectrum of specialties on a very large dataset. Objectives: This study evaluated the performance of three Generative Pretrained Transformer (GPT) models on the Polish Board Certification Exam (Pa\'nstwowy Egzamin Specjalizacyjny, PES) dataset, which consists of 297 tests. Methods: We developed a software program to download and process PES exams and tested the performance of GPT models using OpenAI Application Programming Interface. Results: Our findings reveal that GPT-3.5 did not pass any of the analyzed exams. In contrast, the GPT-4 models demonstrated the capability to pass the majority of the exams evaluated, with the most recent model, gpt-4-0125, successfully passing 222 (75%) of them. The performance of the GPT models varied significantly, displaying excellence in exams related to certain specialties while completely failing others. Conclusions: The significant progress and impressive performance of LLM models hold great promise for the increased application of AI in the field of medicine in Poland. For instance, this advancement could lead to the development of AI-based medical assistants for healthcare professionals, enhancing the efficiency and accuracy of medical services.

Clinical question answering systems have the potential to provide clinicians with relevant and timely answers to their questions. Nonetheless, despite the advances that have been made, adoption of these systems in clinical settings has been slow. One issue is a lack of question-answering datasets which reflect the real-world needs of health professionals. In this work, we present RealMedQA, a dataset of realistic clinical questions generated by humans and an LLM. We describe the process for generating and verifying the QA pairs and assess several QA models on BioASQ and RealMedQA to assess the relative difficulty of matching answers to questions. We show that the LLM is more cost-efficient for generating "ideal" QA pairs. Additionally, we achieve a lower lexical similarity between questions and answers than BioASQ which provides an additional challenge to the top two QA models, as per the results. We release our code and our dataset publicly to encourage further research.

This study aims to explore the implementation of Natural Language Processing (NLP) and machine learning (ML) techniques to automate the coding of medical letters with visualised explainability and light-weighted local computer settings. Currently in clinical settings, coding is a manual process that involves assigning codes to each condition, procedure, and medication in a patient's paperwork (e.g., 56265001 heart disease using SNOMED CT code). There are preliminary research on automatic coding in this field using state-of-the-art ML models; however, due to the complexity and size of the models, the real-world deployment is not achieved. To further facilitate the possibility of automatic coding practice, we explore some solutions in a local computer setting; in addition, we explore the function of explainability for transparency of AI models. We used the publicly available MIMIC-III database and the HAN/HLAN network models for ICD code prediction purposes. We also experimented with the mapping between ICD and SNOMED CT knowledge bases. In our experiments, the models provided useful information for 97.98\% of codes. The result of this investigation can shed some light on implementing automatic clinical coding in practice, such as in hospital settings, on the local computers used by clinicians , project page https://github.com/Glenj01/Medical-Coding.

Large Language Models (LLMs), despite their remarkable progress across various general domains, encounter significant barriers in medicine and healthcare. This field faces unique challenges such as domain-specific terminologies and the reasoning over specialized knowledge. To address these obstinate issues, we propose a novel Multi-disciplinary Collaboration (MC) framework for the medical domain that leverages role-playing LLM-based agents who participate in a collaborative multi-round discussion, thereby enhancing LLM proficiency and reasoning capabilities. This training-free and interpretable framework encompasses five critical steps: gathering domain experts, proposing individual analyses, summarising these analyses into a report, iterating over discussions until a consensus is reached, and ultimately making a decision. Our work particularly focuses on the zero-shot scenario, our results on nine data sets (MedQA, MedMCQA, PubMedQA, and six subtasks from MMLU) establish that our proposed MC framework excels at mining and harnessing the medical expertise in LLMs, as well as extending its reasoning abilities. Based on these outcomes, we further conduct a human evaluation to pinpoint and categorize common errors within our method, as well as ablation studies aimed at understanding the impact of various factors on overall performance. Our code can be found at https://github.com/gersteinlab/MedAgents.

Large language models (LLMs) have shown remarkable progress in encoding clinical knowledge and responding to complex medical queries with appropriate clinical reasoning. However, their applicability in subspecialist or complex medical settings remains underexplored. In this work, we probe the performance of AMIE, a research conversational diagnostic AI system, in the subspecialist domain of breast oncology care without specific fine-tuning to this challenging domain. To perform this evaluation, we curated a set of 50 synthetic breast cancer vignettes representing a range of treatment-naive and treatment-refractory cases and mirroring the key information available to a multidisciplinary tumor board for decision-making (openly released with this work). We developed a detailed clinical rubric for evaluating management plans, including axes such as the quality of case summarization, safety of the proposed care plan, and recommendations for chemotherapy, radiotherapy, surgery and hormonal therapy. To improve performance, we enhanced AMIE with the inference-time ability to perform web search retrieval to gather relevant and up-to-date clinical knowledge and refine its responses with a multi-stage self-critique pipeline. We compare response quality of AMIE with internal medicine trainees, oncology fellows, and general oncology attendings under both automated and specialist clinician evaluations. In our evaluations, AMIE outperformed trainees and fellows demonstrating the potential of the system in this challenging and important domain. We further demonstrate through qualitative examples, how systems such as AMIE might facilitate conversational interactions to assist clinicians in their decision making. However, AMIE's performance was overall inferior to attending oncologists suggesting that further research is needed prior to consideration of prospective uses.

Clinical trials are fundamental in developing new drugs, medical devices, and treatments. However, they are often time-consuming and have low success rates. Although there have been initial attempts to create large language models (LLMs) for clinical trial design and patient-trial matching, these models remain task-specific and not adaptable to diverse clinical trial tasks. To address this challenge, we propose a clinical trial foundation model named Panacea, designed to handle multiple tasks, including trial search, trial summarization, trial design, and patient-trial matching. We also assemble a large-scale dataset, named TrialAlign, of 793,279 trial documents and 1,113,207 trial-related scientific papers, to infuse clinical knowledge into the model by pre-training. We further curate TrialInstruct, which has 200,866 of instruction data for fine-tuning. These resources enable Panacea to be widely applicable for a range of clinical trial tasks based on user requirements. We evaluated Panacea on a new benchmark, named TrialPanorama, which covers eight clinical trial tasks. Our method performed the best on seven of the eight tasks compared to six cutting-edge generic or medicine-specific LLMs. Specifically, Panacea showed great potential to collaborate with human experts in crafting the design of eligibility criteria, study arms, and outcome measures, in multi-round conversations. In addition, Panacea achieved 14.42% improvement in patient-trial matching, 41.78% to 52.02% improvement in trial search, and consistently ranked at the top for five aspects of trial summarization. Our approach demonstrates the effectiveness of Panacea in clinical trials and establishes a comprehensive resource, including training data, model, and benchmark, for developing clinical trial foundation models, paving the path for AI-based clinical trial development.

This article presents the Cogni-CISMeF project, which aims at improving medical information search in the CISMeF system (Catalog and Index of French-language health resources) by including a conversational agent to interact with the user in natural language. To study the cognitive processes involved during the information search, a bottom-up methodology was adopted. Experimentation has been set up to obtain human dialogs between a user (playing the role of patient) dealing with medical information search and a CISMeF expert refining the request. The analysis of these dialogs underlined the use of discursive evidence: vocabulary, reformulation, implicit or explicit expression of user intentions, conversational sequences, etc. A model of artificial agent is proposed. It leads the user in its information search by proposing to him examples, assistance and choices. This model was implemented and integrated in the CISMeF system. ---- Cet article d\'ecrit le projet Cogni-CISMeF qui propose un module de dialogue Homme-Machine \`a int\'egrer dans le syst\`eme d'indexation de connaissances m\'edicales CISMeF (Catalogue et Index des Sites M\'edicaux Francophones). Nous avons adopt\'e une d\'emarche de mod\'elisation cognitive en proc\'edant \`a un recueil de corpus de dialogues entre un utilisateur (jouant le r\^ole d'un patient) d\'esirant une information m\'edicale et un expert CISMeF af inant cette demande pour construire la requ\^ete. Nous avons analys\'e la structure des dialogues ainsi obtenus et avons \'etudi\'e un certain nombre d'indices discursifs : vocabulaire employ\'e, marques de reformulation, commentaires m\'eta et \'epilinguistiques, expression implicite ou explicite des intentions de l'utilisateur, encha\^inement conversationnel, etc. De cette analyse, nous avons construit un mod\`ele d'agent artificiel dot\'e de capacit\'es cognitives capables d'aider l'utilisateur dans sa t\^ache de recherche d'information. Ce mod\`ele a \'et\'e impl\'ement\'e et int\'egr\'e dans le syst\`eme CISMeF.

Stanford Medicine is building a new data platform for our academic research community to do better clinical data science. Hospitals have a large amount of patient data and researchers have demonstrated the ability to reuse that data and AI approaches to derive novel insights, support patient care, and improve care quality. However, the traditional data warehouse and Honest Broker approaches that are in current use, are not scalable. We are establishing a new secure Big Data platform that aims to reduce time to access and analyze data. In this platform, data is anonymized to preserve patient data privacy and made available preparatory to Institutional Review Board (IRB) submission. Furthermore, the data is standardized such that analysis done at Stanford can be replicated elsewhere using the same analytical code and clinical concepts. Finally, the analytics data warehouse integrates with a secure data science computational facility to support large scale data analytics. The ecosystem is designed to bring the modern data science community to highly sensitive clinical data in a secure and collaborative big data analytics environment with a goal to enable bigger, better and faster science.

The emerging trend of advancing generalist artificial intelligence, such as GPTv4 and Gemini, has reshaped the landscape of research (academia and industry) in machine learning and many other research areas. However, domain-specific applications of such foundation models (e.g., in medicine) remain untouched or often at their very early stages. It will require an individual set of transfer learning and model adaptation techniques by further expanding and injecting these models with domain knowledge and data. The development of such technologies could be largely accelerated if the bundle of data, algorithms, and pre-trained foundation models were gathered together and open-sourced in an organized manner. In this work, we present OpenMEDLab, an open-source platform for multi-modality foundation models. It encapsulates not only solutions of pioneering attempts in prompting and fine-tuning large language and vision models for frontline clinical and bioinformatic applications but also building domain-specific foundation models with large-scale multi-modal medical data. Importantly, it opens access to a group of pre-trained foundation models for various medical image modalities, clinical text, protein engineering, etc. Inspiring and competitive results are also demonstrated for each collected approach and model in a variety of benchmarks for downstream tasks. We welcome researchers in the field of medical artificial intelligence to continuously contribute cutting-edge methods and models to OpenMEDLab, which can be accessed via https://github.com/openmedlab.

As the performance of large language models (LLMs) continues to advance, their adoption is expanding across a wide range of domains, including the medical field. The integration of LLMs into medical applications raises critical safety concerns, particularly due to their use by users with diverse roles, e.g. patients and clinicians, and the potential for model's outputs to directly affect human health. Despite the domain-specific capabilities of medical LLMs, prior safety evaluations have largely focused only on general safety benchmarks. In this paper, we introduce a safety evaluation protocol tailored to the medical domain in both patient user and clinician user perspectives, alongside general safety assessments and quantitatively analyze the safety of medical LLMs. We bridge a gap in the literature by building the PatientSafetyBench containing 466 samples over 5 critical categories to measure safety from the perspective of the patient. We apply our red-teaming protocols on the MediPhi model collection as a case study. To our knowledge, this is the first work to define safety evaluation criteria for medical LLMs through targeted red-teaming taking three different points of view - patient, clinician, and general user - establishing a foundation for safer deployment in medical domains.

Codification of free-text clinical narratives have long been recognised to be beneficial for secondary uses such as funding, insurance claim processing and research. The current scenario of assigning codes is a manual process which is very expensive, time-consuming and error prone. In recent years, many researchers have studied the use of Natural Language Processing (NLP), related Machine Learning (ML) and Deep Learning (DL) methods and techniques to resolve the problem of manual coding of clinical narratives and to assist human coders to assign clinical codes more accurately and efficiently. This systematic literature review provides a comprehensive overview of automated clinical coding systems that utilises appropriate NLP, ML and DL methods and techniques to assign ICD codes to discharge summaries. We have followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) guidelines and conducted a comprehensive search of publications from January, 2010 to December 2020 in four academic databases- PubMed, ScienceDirect, Association for Computing Machinery(ACM) Digital Library, and the Association for Computational Linguistics(ACL) Anthology. We reviewed 7,556 publications; 38 met the inclusion criteria. This review identified: datasets having discharge summaries; NLP techniques along with some other data extraction processes, different feature extraction and embedding techniques. To measure the performance of classification methods, different evaluation metrics are used. Lastly, future research directions are provided to scholars who are interested in automated ICD code assignment. Efforts are still required to improve ICD code prediction accuracy, availability of large-scale de-identified clinical corpora with the latest version of the classification system. This can be a platform to guide and share knowledge with the less experienced coders and researchers.

While the general machine learning (ML) community has benefited from public datasets, tasks, and models, the progress of ML in healthcare has been hampered by a lack of such shared assets. The success of foundation models creates new challenges for healthcare ML by requiring access to shared pretrained models to validate performance benefits. We help address these challenges through three contributions. First, we publish a new dataset, EHRSHOT, which contains deidentified structured data from the electronic health records (EHRs) of 6,739 patients from Stanford Medicine. Unlike MIMIC-III/IV and other popular EHR datasets, EHRSHOT is longitudinal and not restricted to ICU/ED patients. Second, we publish the weights of CLMBR-T-base, a 141M parameter clinical foundation model pretrained on the structured EHR data of 2.57M patients. We are one of the first to fully release such a model for coded EHR data; in contrast, most prior models released for clinical data (e.g. GatorTron, ClinicalBERT) only work with unstructured text and cannot process the rich, structured data within an EHR. We provide an end-to-end pipeline for the community to validate and build upon its performance. Third, we define 15 few-shot clinical prediction tasks, enabling evaluation of foundation models on benefits such as sample efficiency and task adaptation. Our model and dataset are available via a research data use agreement from the Stanford AIMI Center. Code to reproduce our results are available at our Github repo: https://github.com/som-shahlab/ehrshot-benchmark

Medical applications of machine learning (ML) have experienced a surge in popularity in recent years. The intensive care unit (ICU) is a natural habitat for ML given the abundance of available data from electronic health records. Models have been proposed to address numerous ICU prediction tasks like the early detection of complications. While authors frequently report state-of-the-art performance, it is challenging to verify claims of superiority. Datasets and code are not always published, and cohort definitions, preprocessing pipelines, and training setups are difficult to reproduce. This work introduces Yet Another ICU Benchmark (YAIB), a modular framework that allows researchers to define reproducible and comparable clinical ML experiments; we offer an end-to-end solution from cohort definition to model evaluation. The framework natively supports most open-access ICU datasets (MIMIC III/IV, eICU, HiRID, AUMCdb) and is easily adaptable to future ICU datasets. Combined with a transparent preprocessing pipeline and extensible training code for multiple ML and deep learning models, YAIB enables unified model development. Our benchmark comes with five predefined established prediction tasks (mortality, acute kidney injury, sepsis, kidney function, and length of stay) developed in collaboration with clinicians. Adding further tasks is straightforward by design. Using YAIB, we demonstrate that the choice of dataset, cohort definition, and preprocessing have a major impact on the prediction performance - often more so than model class - indicating an urgent need for YAIB as a holistic benchmarking tool. We provide our work to the clinical ML community to accelerate method development and enable real-world clinical implementations. Software Repository: https://github.com/rvandewater/YAIB.

Recent advances in generative AI have brought incredible breakthroughs in several areas, including medical imaging. These generative models have tremendous potential not only to help safely share medical data via synthetic datasets but also to perform an array of diverse applications, such as anomaly detection, image-to-image translation, denoising, and MRI reconstruction. However, due to the complexity of these models, their implementation and reproducibility can be difficult. This complexity can hinder progress, act as a use barrier, and dissuade the comparison of new methods with existing works. In this study, we present MONAI Generative Models, a freely available open-source platform that allows researchers and developers to easily train, evaluate, and deploy generative models and related applications. Our platform reproduces state-of-art studies in a standardised way involving different architectures (such as diffusion models, autoregressive transformers, and GANs), and provides pre-trained models for the community. We have implemented these models in a generalisable fashion, illustrating that their results can be extended to 2D or 3D scenarios, including medical images with different modalities (like CT, MRI, and X-Ray data) and from different anatomical areas. Finally, we adopt a modular and extensible approach, ensuring long-term maintainability and the extension of current applications for future features.

The discharge summary is a one of critical documents in the patient journey, encompassing all events experienced during hospitalization, including multiple visits, medications, tests, surgery/procedures, and admissions/discharge. Providing a summary of the patient's progress is crucial, as it significantly influences future care and planning. Consequently, clinicians face the laborious and resource-intensive task of manually collecting, organizing, and combining all the necessary data for a discharge summary. Therefore, we propose "NOTE", which stands for "Notable generation Of patient Text summaries through an Efficient approach based on direct preference optimization". NOTE is based on Medical Information Mart for Intensive Care- III dataset and summarizes a single hospitalization of a patient. Patient events are sequentially combined and used to generate a discharge summary for each hospitalization. In the present circumstances, large language models' application programming interfaces (LLMs' APIs) are widely available, but importing and exporting medical data presents significant challenges due to privacy protection policies in healthcare institutions. Moreover, to ensure optimal performance, it is essential to implement a lightweight model for internal server or program within the hospital. Therefore, we utilized DPO and parameter efficient fine tuning (PEFT) techniques to apply a fine-tuning method that guarantees superior performance. To demonstrate the practical application of the developed NOTE, we provide a webpage-based demonstration software. In the future, we will aim to deploy the software available for actual use by clinicians in hospital. NOTE can be utilized to generate various summaries not only discharge summaries but also throughout a patient's journey, thereby alleviating the labor-intensive workload of clinicians and aiming for increased efficiency.

This paper introduces MedMCQA, a new large-scale, Multiple-Choice Question Answering (MCQA) dataset designed to address real-world medical entrance exam questions. More than 194k high-quality AIIMS \& NEET PG entrance exam MCQs covering 2.4k healthcare topics and 21 medical subjects are collected with an average token length of 12.77 and high topical diversity. Each sample contains a question, correct answer(s), and other options which requires a deeper language understanding as it tests the 10+ reasoning abilities of a model across a wide range of medical subjects \& topics. A detailed explanation of the solution, along with the above information, is provided in this study.

In clinical radiology reports, doctors capture important information about the patient's health status. They convey their observations from raw medical imaging data about the inner structures of a patient. As such, formulating reports requires medical experts to possess wide-ranging knowledge about anatomical regions with their normal, healthy appearance as well as the ability to recognize abnormalities. This explicit grasp on both the patient's anatomy and their appearance is missing in current medical image-processing systems as annotations are especially difficult to gather. This renders the models to be narrow experts e.g. for identifying specific diseases. In this work, we recover this missing link by adding human anatomy into the mix and enable the association of content in medical reports to their occurrence in associated imagery (medical phrase grounding). To exploit anatomical structures in this scenario, we present a sophisticated automatic pipeline to gather and integrate human bodily structures from computed tomography datasets, which we incorporate in our PAXRay: A Projected dataset for the segmentation of Anatomical structures in X-Ray data. Our evaluation shows that methods that take advantage of anatomical information benefit heavily in visually grounding radiologists' findings, as our anatomical segmentations allow for up to absolute 50% better grounding results on the OpenI dataset as compared to commonly used region proposals. The PAXRay dataset is available at https://constantinseibold.github.io/paxray/.

Several studies showed that Large Language Models (LLMs) can answer medical questions correctly, even outperforming the average human score in some medical exams. However, to our knowledge, no study has been conducted to assess the ability of language models to validate existing or generated medical text for correctness and consistency. In this paper, we introduce MEDEC (https://github.com/abachaa/MEDEC), the first publicly available benchmark for medical error detection and correction in clinical notes, covering five types of errors (Diagnosis, Management, Treatment, Pharmacotherapy, and Causal Organism). MEDEC consists of 3,848 clinical texts, including 488 clinical notes from three US hospital systems that were not previously seen by any LLM. The dataset has been used for the MEDIQA-CORR shared task to evaluate seventeen participating systems [Ben Abacha et al., 2024]. In this paper, we describe the data creation methods and we evaluate recent LLMs (e.g., o1-preview, GPT-4, Claude 3.5 Sonnet, and Gemini 2.0 Flash) for the tasks of detecting and correcting medical errors requiring both medical knowledge and reasoning capabilities. We also conducted a comparative study where two medical doctors performed the same task on the MEDEC test set. The results showed that MEDEC is a sufficiently challenging benchmark to assess the ability of models to validate existing or generated notes and to correct medical errors. We also found that although recent LLMs have a good performance in error detection and correction, they are still outperformed by medical doctors in these tasks. We discuss the potential factors behind this gap, the insights from our experiments, the limitations of current evaluation metrics, and share potential pointers for future research.

Combination therapies have become the standard of care for diseases such as cancer, tuberculosis, malaria and HIV. However, the combinatorial set of available multi-drug treatments creates a challenge in identifying effective combination therapies available in a situation. To assist medical professionals in identifying beneficial drug-combinations, we construct an expert-annotated dataset for extracting information about the efficacy of drug combinations from the scientific literature. Beyond its practical utility, the dataset also presents a unique NLP challenge, as the first relation extraction dataset consisting of variable-length relations. Furthermore, the relations in this dataset predominantly require language understanding beyond the sentence level, adding to the challenge of this task. We provide a promising baseline model and identify clear areas for further improvement. We release our dataset, code, and baseline models publicly to encourage the NLP community to participate in this task.

Large Language Models (LLMs) have shown the potential to significantly contribute to patient care, diagnostics, and administrative processes. Emerging biomedical LLMs address healthcare-specific challenges, including privacy demands and computational constraints. However, evaluation of these models has primarily been limited to non-clinical tasks, which do not reflect the complexity of practical clinical applications. Additionally, there has been no thorough comparison between biomedical and general-domain LLMs for clinical tasks. To fill this gap, we present the Clinical Language Understanding Evaluation (CLUE), a benchmark tailored to evaluate LLMs on real-world clinical tasks. CLUE includes two novel datasets derived from MIMIC IV discharge letters and four existing tasks designed to test the practical applicability of LLMs in healthcare settings. Our evaluation covers several biomedical and general domain LLMs, providing insights into their clinical performance and applicability. CLUE represents a step towards a standardized approach to evaluating and developing LLMs in healthcare to align future model development with the real-world needs of clinical application. We publish our evaluation and data generation scripts: https://github.com/dadaamin/CLUE

The successes of foundation models such as ChatGPT and AlphaFold have spurred significant interest in building similar models for electronic medical records (EMRs) to improve patient care and hospital operations. However, recent hype has obscured critical gaps in our understanding of these models' capabilities. We review over 80 foundation models trained on non-imaging EMR data (i.e. clinical text and/or structured data) and create a taxonomy delineating their architectures, training data, and potential use cases. We find that most models are trained on small, narrowly-scoped clinical datasets (e.g. MIMIC-III) or broad, public biomedical corpora (e.g. PubMed) and are evaluated on tasks that do not provide meaningful insights on their usefulness to health systems. In light of these findings, we propose an improved evaluation framework for measuring the benefits of clinical foundation models that is more closely grounded to metrics that matter in healthcare.

The field of computer vision applied to videos of minimally invasive surgery is ever-growing. Workflow recognition pertains to the automated recognition of various aspects of a surgery: including which surgical steps are performed; and which surgical instruments are used. This information can later be used to assist clinicians when learning the surgery; during live surgery; and when writing operation notes. The Pituitary Vision (PitVis) 2023 Challenge tasks the community to step and instrument recognition in videos of endoscopic pituitary surgery. This is a unique task when compared to other minimally invasive surgeries due to the smaller working space, which limits and distorts vision; and higher frequency of instrument and step switching, which requires more precise model predictions. Participants were provided with 25-videos, with results presented at the MICCAI-2023 conference as part of the Endoscopic Vision 2023 Challenge in Vancouver, Canada, on 08-Oct-2023. There were 18-submissions from 9-teams across 6-countries, using a variety of deep learning models. A commonality between the top performing models was incorporating spatio-temporal and multi-task methods, with greater than 50% and 10% macro-F1-score improvement over purely spacial single-task models in step and instrument recognition respectively. The PitVis-2023 Challenge therefore demonstrates state-of-the-art computer vision models in minimally invasive surgery are transferable to a new dataset, with surgery specific techniques used to enhance performance, progressing the field further. Benchmark results are provided in the paper, and the dataset is publicly available at: https://doi.org/10.5522/04/26531686.

This research tests the role of Large Language Models (LLMs) as formal second opinion tools in professional decision-making, particularly focusing on complex medical cases where even experienced physicians seek peer consultation. The work analyzed 183 challenging medical cases from Medscape over a 20-month period, testing multiple LLMs' performance against crowd-sourced physician responses. A key finding was the high overall score possible in the latest foundational models (>80% accuracy compared to consensus opinion), which exceeds most human metrics reported on the same clinical cases (450 pages of patient profiles, test results). The study rates the LLMs' performance disparity between straightforward cases (>81% accuracy) and complex scenarios (43% accuracy), particularly in these cases generating substantial debate among human physicians. The research demonstrates that LLMs may be valuable as generators of comprehensive differential diagnoses rather than as primary diagnostic tools, potentially helping to counter cognitive biases in clinical decision-making, reduce cognitive loads, and thus remove some sources of medical error. The inclusion of a second comparative legal dataset (Supreme Court cases, N=21) provides added empirical context to the AI use to foster second opinions, though these legal challenges proved considerably easier for LLMs to analyze. In addition to the original contributions of empirical evidence for LLM accuracy, the research aggregated a novel benchmark for others to score highly contested question and answer reliability between both LLMs and disagreeing human practitioners. These results suggest that the optimal deployment of LLMs in professional settings may differ substantially from current approaches that emphasize automation of routine tasks.

Background: Social media platforms have become a viable source of medical information, with patients and healthcare professionals using them to share health-related information and track diseases. Similarly, YouTube, the largest video-sharing platform in the world contains vlogs where individuals talk about their illnesses. The aim of our study was to investigate the use of Natural Language Processing (NLP) to identify the spoken content of YouTube vlogs related to the diagnosis of Coronavirus disease of 2019 (COVID-19) for public health screening. Methods: COVID-19 videos on YouTube were searched using relevant keywords. A total of 1000 videos being spoken in English were downloaded out of which 791 were classified as vlogs, 192 were non-vlogs, and 17 were deleted by the channel. The videos were converted into a textual format using Microsoft Streams. The textual data was preprocessed using basic and advanced preprocessing methods. A lexicon of 200 words was created which contained words related to COVID-19. The data was analyzed using topic modeling, word clouds, and lexicon matching. Results: The word cloud results revealed discussions about COVID-19 symptoms like "fever", along with generic terms such as "mask" and "isolation". Lexical analysis demonstrated that in 96.46% of videos, patients discussed generic terms, and in 95.45% of videos, people talked about COVID-19 symptoms. LDA Topic Modeling results also generated topics that successfully captured key themes and content related to our investigation of COVID-19 diagnoses in YouTube vlogs. Conclusion: By leveraging NLP techniques on YouTube vlogs public health practitioners can enhance their ability to mitigate the effects of pandemics and effectively respond to public health challenges.

The development of large language models tailored for handling patients' clinical notes is often hindered by the limited accessibility and usability of these notes due to strict privacy regulations. To address these challenges, we first create synthetic large-scale clinical notes using publicly available case reports extracted from biomedical literature. We then use these synthetic notes to train our specialized clinical large language model, Asclepius. While Asclepius is trained on synthetic data, we assess its potential performance in real-world applications by evaluating it using real clinical notes. We benchmark Asclepius against several other large language models, including GPT-3.5-turbo and other open-source alternatives. To further validate our approach using synthetic notes, we also compare Asclepius with its variants trained on real clinical notes. Our findings convincingly demonstrate that synthetic clinical notes can serve as viable substitutes for real ones when constructing high-performing clinical language models. This conclusion is supported by detailed evaluations conducted by both GPT-4 and medical professionals. All resources including weights, codes, and data used in the development of Asclepius are made publicly accessible for future research.

Machine learning (ML) approaches have demonstrated promising results in a wide range of healthcare applications. Data plays a crucial role in developing ML-based healthcare systems that directly affect people's lives. Many of the ethical issues surrounding the use of ML in healthcare stem from structural inequalities underlying the way we collect, use, and handle data. Developing guidelines to improve documentation practices regarding the creation, use, and maintenance of ML healthcare datasets is therefore of critical importance. In this work, we introduce Healthsheet, a contextualized adaptation of the original datasheet questionnaire ~gebru2018datasheets for health-specific applications. Through a series of semi-structured interviews, we adapt the datasheets for healthcare data documentation. As part of the Healthsheet development process and to understand the obstacles researchers face in creating datasheets, we worked with three publicly-available healthcare datasets as our case studies, each with different types of structured data: Electronic health Records (EHR), clinical trial study data, and smartphone-based performance outcome measures. Our findings from the interviewee study and case studies show 1) that datasheets should be contextualized for healthcare, 2) that despite incentives to adopt accountability practices such as datasheets, there is a lack of consistency in the broader use of these practices 3) how the ML for health community views datasheets and particularly Healthsheets as diagnostic tool to surface the limitations and strength of datasets and 4) the relative importance of different fields in the datasheet to healthcare concerns.

This paper introduces the Pandemic PACT Advanced Categorisation Engine (PPACE) along with its associated dataset. PPACE is a fine-tuned model developed to automatically classify research abstracts from funded biomedical projects according to WHO-aligned research priorities. This task is crucial for monitoring research trends and identifying gaps in global health preparedness and response. Our approach builds on human-annotated projects, which are allocated one or more categories from a predefined list. A large language model is then used to generate `rationales' explaining the reasoning behind these annotations. This augmented data, comprising expert annotations and rationales, is subsequently used to fine-tune a smaller, more efficient model. Developed as part of the Pandemic PACT project, which aims to track and analyse research funding and clinical evidence for a wide range of diseases with outbreak potential, PPACE supports informed decision-making by research funders, policymakers, and independent researchers. We introduce and release both the trained model and the instruction-based dataset used for its training. Our evaluation shows that PPACE significantly outperforms its baselines. The release of PPACE and its associated dataset offers valuable resources for researchers in multilabel biomedical document classification and supports advancements in aligning biomedical research with key global health priorities.

Deep neural networks are often applied to medical images to automate the problem of medical diagnosis. However, a more clinically relevant question that practitioners usually face is how to predict the future trajectory of a disease. Current methods for prognosis or disease trajectory forecasting often require domain knowledge and are complicated to apply. In this paper, we formulate the prognosis prediction problem as a one-to-many prediction problem. Inspired by a clinical decision-making process with two agents -- a radiologist and a general practitioner -- we predict prognosis with two transformer-based components that share information with each other. The first transformer in this framework aims to analyze the imaging data, and the second one leverages its internal states as inputs, also fusing them with auxiliary clinical data. The temporal nature of the problem is modeled within the transformer states, allowing us to treat the forecasting problem as a multi-task classification, for which we propose a novel loss. We show the effectiveness of our approach in predicting the development of structural knee osteoarthritis changes and forecasting Alzheimer's disease clinical status directly from raw multi-modal data. The proposed method outperforms multiple state-of-the-art baselines with respect to performance and calibration, both of which are needed for real-world applications. An open-source implementation of our method is made publicly available at https://github.com/Oulu-IMEDS/CLIMATv2.

An accurate differential diagnosis (DDx) is a cornerstone of medical care, often reached through an iterative process of interpretation that combines clinical history, physical examination, investigations and procedures. Interactive interfaces powered by Large Language Models (LLMs) present new opportunities to both assist and automate aspects of this process. In this study, we introduce an LLM optimized for diagnostic reasoning, and evaluate its ability to generate a DDx alone or as an aid to clinicians. 20 clinicians evaluated 302 challenging, real-world medical cases sourced from the New England Journal of Medicine (NEJM) case reports. Each case report was read by two clinicians, who were randomized to one of two assistive conditions: either assistance from search engines and standard medical resources, or LLM assistance in addition to these tools. All clinicians provided a baseline, unassisted DDx prior to using the respective assistive tools. Our LLM for DDx exhibited standalone performance that exceeded that of unassisted clinicians (top-10 accuracy 59.1% vs 33.6%, [p = 0.04]). Comparing the two assisted study arms, the DDx quality score was higher for clinicians assisted by our LLM (top-10 accuracy 51.7%) compared to clinicians without its assistance (36.1%) (McNemar's Test: 45.7, p < 0.01) and clinicians with search (44.4%) (4.75, p = 0.03). Further, clinicians assisted by our LLM arrived at more comprehensive differential lists than those without its assistance. Our study suggests that our LLM for DDx has potential to improve clinicians' diagnostic reasoning and accuracy in challenging cases, meriting further real-world evaluation for its ability to empower physicians and widen patients' access to specialist-level expertise.

We introduce Radiology-GPT, a large language model for radiology. Using an instruction tuning approach on an extensive dataset of radiology domain knowledge, Radiology-GPT demonstrates superior performance compared to general language models such as StableLM, Dolly and LLaMA. It exhibits significant versatility in radiological diagnosis, research, and communication. This work serves as a catalyst for future developments in clinical NLP. The successful implementation of Radiology-GPT is indicative of the potential of localizing generative large language models, specifically tailored for distinctive medical specialties, while ensuring adherence to privacy standards such as HIPAA. The prospect of developing individualized, large-scale language models that cater to specific needs of various hospitals presents a promising direction. The fusion of conversational competence and domain-specific knowledge in these models is set to foster future development in healthcare AI. A demo of Radiology-GPT is available at https://huggingface.co/spaces/allen-eric/radiology-gpt.

Spoken medical dialogue systems are increasingly attracting interest to enhance access to healthcare services and improve quality and traceability of patient care. In this paper, we focus on medical drug prescriptions acquired on smartphones through spoken dialogue. Such systems would facilitate the traceability of care and would free clinicians' time. However, there is a lack of speech corpora to develop such systems since most of the related corpora are in text form and in English. To facilitate the research and development of spoken medical dialogue systems, we present, to the best of our knowledge, the first spoken medical drug prescriptions corpus, named PxSLU. It contains 4 hours of transcribed and annotated dialogues of drug prescriptions in French acquired through an experiment with 55 participants experts and non-experts in prescriptions. We also present some experiments that demonstrate the interest of this corpus for the evaluation and development of medical dialogue systems.

Recently, the increasing demand for superior medical services has highlighted the discrepancies in the medical infrastructure. With big data, especially texts, forming the foundation of medical services, there is an exigent need for effective natural language processing (NLP) solutions tailored to the healthcare domain. Conventional approaches leveraging pre-trained models present promising results in this domain and current large language models (LLMs) offer advanced foundation for medical text processing. However, most medical LLMs are trained only with supervised fine-tuning (SFT), even though it efficiently empowers LLMs to understand and respond to medical instructions but is ineffective in learning domain knowledge and aligning with human preference. Another engineering barrier that prevents current medical LLM from better text processing ability is their restricted context length (e.g., 2,048 tokens), making it hard for the LLMs to process long context, which is frequently required in the medical domain. In this work, we propose ChiMed-GPT, a new benchmark LLM designed explicitly for Chinese medical domain, with enlarged context length to 4,096 tokens and undergoes a comprehensive training regime with pre-training, SFT, and RLHF. Evaluations on real-world tasks including information extraction, question answering, and dialogue generation demonstrate ChiMed-GPT's superior performance over general domain LLMs. Furthermore, we analyze possible biases through prompting ChiMed-GPT to perform attitude scales regarding discrimination of patients, so as to contribute to further responsible development of LLMs in the medical domain. The code and model are released at https://github.com/synlp/ChiMed-GPT.

We describe a Magnetic Resonance Imaging (MRI) dataset from individuals from the African nation of Nigeria. The dataset contains pseudonymized structural MRI (T1w, T2w, FLAIR) data of clinical quality. The dataset contains data from 36 images from healthy control subjects, 32 images from individuals diagnosed with age-related dementia and 20 from individuals with Parkinson's disease. There is currently a paucity of data from the African continent. Given the potential for Africa to contribute to the global neuroscience community, this first MRI dataset represents both an opportunity and benchmark for future studies to share data from the African continent.

Large language models (LLMs) offer a promising pre-screening tool, improving early disease detection and providing enhanced healthcare access for underprivileged communities. The early diagnosis of various diseases continues to be a significant challenge in healthcare, primarily due to the nonspecific nature of early symptoms, the shortage of expert medical practitioners, and the need for prolonged clinical evaluations, all of which can delay treatment and adversely affect patient outcomes. With impressive accuracy in prediction across a range of diseases, LLMs have the potential to revolutionize clinical pre-screening and decision-making for various medical conditions. In this work, we study the diagnostic capability of LLMs for Rheumatoid Arthritis (RA) with real world patients data. Patient data was collected alongside diagnoses from medical experts, and the performance of LLMs was evaluated in comparison to expert diagnoses for RA disease prediction. We notice an interesting pattern in disease diagnosis and find an unexpected misalignment between prediction and explanation. We conduct a series of multi-round analyses using different LLM agents. The best-performing model accurately predicts rheumatoid arthritis (RA) diseases approximately 95\% of the time. However, when medical experts evaluated the reasoning generated by the model, they found that nearly 68\% of the reasoning was incorrect. This study highlights a clear misalignment between LLMs high prediction accuracy and its flawed reasoning, raising important questions about relying on LLM explanations in clinical settings. LLMs provide incorrect reasoning to arrive at the correct answer for RA disease diagnosis.

We propose DISC-MedLLM, a comprehensive solution that leverages Large Language Models (LLMs) to provide accurate and truthful medical response in end-to-end conversational healthcare services. To construct high-quality Supervised Fine-Tuning (SFT) datasets, we employ three strategies: utilizing medical knowledge-graphs, reconstructing real-world dialogues, and incorporating human-guided preference rephrasing. These datasets are instrumental in training DISC-MedLLM, surpassing existing medical LLMs in both single-turn and multi-turn consultation scenarios. Extensive experimental results demonstrate the effectiveness of the proposed model in bridging the gap between general language models and real-world medical consultation. Additionally, we release the constructed dataset and model weights to further contribute to research and development. Further details and resources can be found at https://github.com/FudanDISC/DISC-MedLLM

Several studies have shown that speech and language features, automatically extracted from clinical interviews or spontaneous discourse, have diagnostic value for mental disorders such as schizophrenia and bipolar disorder. They typically make use of a large feature set to train a classifier for distinguishing between two groups of interest, i.e. a clinical and control group. However, a purely data-driven approach runs the risk of overfitting to a particular data set, especially when sample sizes are limited. Here, we first down-select the set of language features to a small subset that is related to a well-validated test of functional ability, the Social Skills Performance Assessment (SSPA). This helps establish the concurrent validity of the selected features. We use only these features to train a simple classifier to distinguish between groups of interest. Linear regression reveals that a subset of language features can effectively model the SSPA, with a correlation coefficient of 0.75. Furthermore, the same feature set can be used to build a strong binary classifier to distinguish between healthy controls and a clinical group (AUC = 0.96) and also between patients within the clinical group with schizophrenia and bipolar I disorder (AUC = 0.83).

Clinicians spend a significant amount of time reviewing medical images and transcribing their findings regarding patient diagnosis, referral and treatment in text form. Vision-language models (VLMs), which automatically interpret images and summarize their findings as text, have enormous potential to alleviate clinical workloads and increase patient access to high-quality medical care. While foundational models have stirred considerable interest in the medical community, it is unclear whether their general capabilities translate to real-world clinical utility. In this work, we show that foundation VLMs markedly underperform compared to practicing ophthalmologists on specialist tasks crucial to the care of patients with age-related macular degeneration (AMD). To address this, we initially identified the essential capabilities required for image-based clinical decision-making, and then developed a curriculum to selectively train VLMs in these skills. The resulting model, RetinaVLM, can be instructed to write reports that significantly outperform those written by leading foundation medical VLMs in disease staging (F1 score of 0.63 vs. 0.11) and patient referral (0.67 vs. 0.39), and approaches the diagnostic performance of junior ophthalmologists (who achieve 0.77 and 0.78 on the respective tasks). Furthermore, in a reader study involving two senior ophthalmologists with up to 32 years of experience, RetinaVLM's reports were found to be similarly correct (78.6% vs. 82.1%) and complete (both 78.6%) as reports written by junior ophthalmologists with up to 10 years of experience. These results demonstrate that our curriculum-based approach provides a blueprint for specializing generalist foundation medical VLMs to handle real-world clinical tasks.

Recent large language models (LLMs) have demonstrated significant advancements, particularly in their ability to serve as agents thereby surpassing their traditional role as chatbots. These agents can leverage their planning and tool utilization capabilities to address tasks specified at a high level. However, a standardized dataset to benchmark the agent capabilities of LLMs in medical applications is currently lacking, making the evaluation of LLMs on complex tasks in interactive healthcare environments challenging. To address this gap, we introduce MedAgentBench, a broad evaluation suite designed to assess the agent capabilities of large language models within medical records contexts. MedAgentBench encompasses 300 patient-specific clinically-derived tasks from 10 categories written by human physicians, realistic profiles of 100 patients with over 700,000 data elements, a FHIR-compliant interactive environment, and an accompanying codebase. The environment uses the standard APIs and communication infrastructure used in modern EMR systems, so it can be easily migrated into live EMR systems. MedAgentBench presents an unsaturated agent-oriented benchmark that current state-of-the-art LLMs exhibit some ability to succeed at. The best model (Claude 3.5 Sonnet v2) achieves a success rate of 69.67%. However, there is still substantial space for improvement which gives the community a next direction to optimize. Furthermore, there is significant variation in performance across task categories. MedAgentBench establishes this and is publicly available at https://github.com/stanfordmlgroup/MedAgentBench , offering a valuable framework for model developers to track progress and drive continuous improvements in the agent capabilities of large language models within the medical domain.

Large language models (LLMs) have demonstrated impressive capabilities in disease diagnosis. However, their effectiveness in identifying rarer diseases, which are inherently more challenging to diagnose, remains an open question. Rare disease performance is critical with the increasing use of LLMs in healthcare settings. This is especially true if a primary care physician needs to make a rarer prognosis from only a patient conversation so that they can take the appropriate next step. To that end, several clinical decision support systems are designed to support providers in rare disease identification. Yet their utility is limited due to their lack of knowledge of common disorders and difficulty of use. In this paper, we propose RareScale to combine the knowledge LLMs with expert systems. We use jointly use an expert system and LLM to simulate rare disease chats. This data is used to train a rare disease candidate predictor model. Candidates from this smaller model are then used as additional inputs to black-box LLM to make the final differential diagnosis. Thus, RareScale allows for a balance between rare and common diagnoses. We present results on over 575 rare diseases, beginning with Abdominal Actinomycosis and ending with Wilson's Disease. Our approach significantly improves the baseline performance of black-box LLMs by over 17% in Top-5 accuracy. We also find that our candidate generation performance is high (e.g. 88.8% on gpt-4o generated chats).

This paper explores the advancements and applications of large-scale models in the medical field, with a particular focus on Medical Large Models (MedLMs). These models, encompassing Large Language Models (LLMs), Vision Models, 3D Large Models, and Multimodal Models, are revolutionizing healthcare by enhancing disease prediction, diagnostic assistance, personalized treatment planning, and drug discovery. The integration of graph neural networks in medical knowledge graphs and drug discovery highlights the potential of Large Graph Models (LGMs) in understanding complex biomedical relationships. The study also emphasizes the transformative role of Vision-Language Models (VLMs) and 3D Large Models in medical image analysis, anatomical modeling, and prosthetic design. Despite the challenges, these technologies are setting new benchmarks in medical innovation, improving diagnostic accuracy, and paving the way for personalized healthcare solutions. This paper aims to provide a comprehensive overview of the current state and future directions of large models in medicine, underscoring their significance in advancing global health.

Clinical Natural Language Processing (NLP) has become an emerging technology in healthcare that leverages a large amount of free-text data in electronic health records (EHRs) to improve patient care, support clinical decisions, and facilitate clinical and translational science research. Recently, deep learning has achieved state-of-the-art performance in many clinical NLP tasks. However, training deep learning models usually requires large annotated datasets, which are normally not publicly available and can be time-consuming to build in clinical domains. Working with smaller annotated datasets is typical in clinical NLP and therefore, ensuring that deep learning models perform well is crucial for the models to be used in real-world applications. A widely adopted approach is fine-tuning existing Pre-trained Language Models (PLMs), but these attempts fall short when the training dataset contains only a few annotated samples. Few-Shot Learning (FSL) has recently been investigated to tackle this problem. Siamese Neural Network (SNN) has been widely utilized as an FSL approach in computer vision, but has not been studied well in NLP. Furthermore, the literature on its applications in clinical domains is scarce. In this paper, we propose two SNN-based FSL approaches for clinical NLP, including Pre-Trained SNN (PT-SNN) and SNN with Second-Order Embeddings (SOE-SNN). We evaluated the proposed approaches on two clinical tasks, namely clinical text classification and clinical named entity recognition. We tested three few-shot settings including 4-shot, 8-shot, and 16-shot learning. Both clinical NLP tasks were benchmarked using three PLMs, including BERT,BioBERT, and BioClinicalBERT. The experimental results verified the effectiveness of the proposed SNN-based FSL approaches in both NLP tasks.

Purpose: With advancements in Large Language Models (LLMs) for healthcare, the need arises for competitive open-source models to protect the public interest. This work contributes to the field of open medical LLMs by optimizing key stages of data preprocessing and training, while showing how to improve model safety (through DPO) and efficacy (through RAG). The evaluation methodology used, which includes four different types of tests, defines a new standard for the field. The resultant models, shown to be competitive with the best private alternatives, are released with a permisive license. Methods: Building on top of strong base models like Llama 3.1 and Qwen 2.5, Aloe Beta uses a custom dataset to enhance public data with synthetic Chain of Thought examples. The models undergo alignment with Direct Preference Optimization, emphasizing ethical and policy-aligned performance in the presence of jailbreaking attacks. Evaluation includes close-ended, open-ended, safety and human assessments, to maximize the reliability of results. Results: Recommendations are made across the entire pipeline, backed by the solid performance of the Aloe Family. These models deliver competitive performance across healthcare benchmarks and medical fields, and are often preferred by healthcare professionals. On bias and toxicity, the Aloe Beta models significantly improve safety, showing resilience to unseen jailbreaking attacks. For a responsible release, a detailed risk assessment specific to healthcare is attached to the Aloe Family models. Conclusion: The Aloe Beta models, and the recipe that leads to them, are a significant contribution to the open-source medical LLM field, offering top-of-the-line performance while maintaining high ethical requirements. This work sets a new standard for developing and reporting aligned LLMs in healthcare.

We present a new dataset for machine comprehension in the medical domain. Our dataset uses clinical case reports with around 100,000 gap-filling queries about these cases. We apply several baselines and state-of-the-art neural readers to the dataset, and observe a considerable gap in performance (20% F1) between the best human and machine readers. We analyze the skills required for successful answering and show how reader performance varies depending on the applicable skills. We find that inferences using domain knowledge and object tracking are the most frequently required skills, and that recognizing omitted information and spatio-temporal reasoning are the most difficult for the machines.

As mental health care systems worldwide struggle to meet demand, there is increasing focus on using language models to infer neuropsychiatric conditions or psychopathological traits from language production. Yet, so far, this research has only delivered solutions with limited clinical applicability, due to insufficient consideration of ethical questions crucial to ensuring the synergy between possible applications and model design. To accelerate progress towards clinically applicable models, our paper charts the ethical landscape of research on language-based inference of psychopathology and provides a practical tool for researchers to navigate it. We identify seven core ethical principles that should guide model development and deployment in this domain, translate them into ELLIPS, an ethical toolkit operationalizing these principles into questions that can guide researchers' choices with respect to data selection, architectures, evaluation, and model deployment, and provide a case study exemplifying its use. With this, we aim to facilitate the emergence of model technology with concrete potential for real-world applicability.

The advancement of natural language processing (NLP) systems in healthcare hinges on language model ability to interpret the intricate information contained within clinical notes. This process often requires integrating information from various time points in a patient's medical history. However, most earlier clinical language models were pretrained with a context length limited to roughly one clinical document. In this study, We introduce ClinicalMamba, a specialized version of the Mamba language model, pretrained on a vast corpus of longitudinal clinical notes to address the unique linguistic characteristics and information processing needs of the medical domain. ClinicalMamba, with 130 million and 2.8 billion parameters, demonstrates a superior performance in modeling clinical language across extended text lengths compared to Mamba and clinical Llama. With few-shot learning, ClinicalMamba achieves notable benchmarks in speed and accuracy, outperforming existing clinical language models and general domain large models like GPT-4 in longitudinal clinical notes information extraction tasks.

In this article, we conduct data mining to discover the countries, universities and companies, produced or collaborated the most research on Covid-19 since the pandemic started. We present some interesting findings, but despite analysing all available records on COVID-19 from the Web of Science Core Collection, we failed to reach any significant conclusions on how the world responded to the COVID-19 pandemic. Therefore, we increased our analysis to include all available data records on pandemics and epidemics from 1900 to 2020. We discover some interesting results on countries, universities and companies, that produced collaborated most the most in research on pandemic and epidemics. Then we compared the results with the analysing on COVID-19 data records. This has created some interesting findings that are explained and graphically visualised in the article.

In today's interconnected globe, moving abroad is more and more prevalent, whether it's for employment, refugee resettlement, or other causes. Language difficulties between natives and immigrants present a common issue on a daily basis, especially in medical domain. This can make it difficult for patients and doctors to communicate during anamnesis or in the emergency room, which compromises patient care. The goal of the HYKIST Project is to develop a speech translation system to support patient-doctor communication with ASR and MT. ASR systems have recently displayed astounding performance on particular tasks for which enough quantities of training data are available, such as LibriSpeech. Building a good model is still difficult due to a variety of speaking styles, acoustic and recording settings, and a lack of in-domain training data. In this thesis, we describe our efforts to construct ASR systems for a conversational telephone speech recognition task in the medical domain for Vietnamese language to assist emergency room contact between doctors and patients across linguistic barriers. In order to enhance the system's performance, we investigate various training schedules and data combining strategies. We also examine how best to make use of the little data that is available. The use of publicly accessible models like XLSR-53 is compared to the use of customized pre-trained models, and both supervised and unsupervised approaches are utilized using wav2vec 2.0 as architecture.

Explaining Artificial Intelligence (AI) decisions is a major challenge nowadays in AI, in particular when applied to sensitive scenarios like medicine and law. However, the need to explain the rationale behind decisions is a main issue also for human-based deliberation as it is important to justify why a certain decision has been taken. Resident medical doctors for instance are required not only to provide a (possibly correct) diagnosis, but also to explain how they reached a certain conclusion. Developing new tools to aid residents to train their explanation skills is therefore a central objective of AI in education. In this paper, we follow this direction, and we present, to the best of our knowledge, the first multilingual dataset for Medical Question Answering where correct and incorrect diagnoses for a clinical case are enriched with a natural language explanation written by doctors. These explanations have been manually annotated with argument components (i.e., premise, claim) and argument relations (i.e., attack, support), resulting in the Multilingual CasiMedicos-Arg dataset which consists of 558 clinical cases in four languages (English, Spanish, French, Italian) with explanations, where we annotated 5021 claims, 2313 premises, 2431 support relations, and 1106 attack relations. We conclude by showing how competitive baselines perform over this challenging dataset for the argument mining task.

The rapid development of Large Language Models (LLMs) for healthcare applications has spurred calls for holistic evaluation beyond frequently-cited benchmarks like USMLE, to better reflect real-world performance. While real-world assessments are valuable indicators of utility, they often lag behind the pace of LLM evolution, likely rendering findings obsolete upon deployment. This temporal disconnect necessitates a comprehensive upfront evaluation that can guide model selection for specific clinical applications. We introduce MEDIC, a framework assessing LLMs across five critical dimensions of clinical competence: medical reasoning, ethics and bias, data and language understanding, in-context learning, and clinical safety. MEDIC features a novel cross-examination framework quantifying LLM performance across areas like coverage and hallucination detection, without requiring reference outputs. We apply MEDIC to evaluate LLMs on medical question-answering, safety, summarization, note generation, and other tasks. Our results show performance disparities across model sizes, baseline vs medically finetuned models, and have implications on model selection for applications requiring specific model strengths, such as low hallucination or lower cost of inference. MEDIC's multifaceted evaluation reveals these performance trade-offs, bridging the gap between theoretical capabilities and practical implementation in healthcare settings, ensuring that the most promising models are identified and adapted for diverse healthcare applications.

In this technical report we present our collected dataset of laparoscopic cholecystectomies (LapChole). Laparoscopic videos of a total of 20 surgeries were recorded and annotated with surgical phase labels, of which 15 were randomly pre-determined as training data, while the remaining 5 videos are selected as test data. This dataset was later included as part of the M2CAI 2016 workflow detection challenge during MICCAI 2016 in Athens.

Databases of electronic health records (EHRs) are increasingly used to inform clinical decisions. Machine learning methods can find patterns in EHRs that are predictive of future adverse outcomes. However, statistical models may be built upon patterns of health-seeking behavior that vary across patient subpopulations, leading to poor predictive performance when training on one patient population and predicting on another. This note proposes two tests to better measure and understand model generalization. We use these tests to compare models derived from two data sources: (i) historical medical records, and (ii) electrocardiogram (EKG) waveforms. In a predictive task, we show that EKG-based models can be more stable than EHR-based models across different patient populations.

Accurately forecasting patient arrivals at Urgent Care Clinics (UCCs) and Emergency Departments (EDs) is important for effective resourcing and patient care. However, correctly estimating patient flows is not straightforward since it depends on many drivers. The predictability of patient arrivals has recently been further complicated by the COVID-19 pandemic conditions and the resulting lockdowns. This study investigates how a suite of novel quasi-real-time variables like Google search terms, pedestrian traffic, the prevailing incidence levels of influenza, as well as the COVID-19 Alert Level indicators can both generally improve the forecasting models of patient flows and effectively adapt the models to the unfolding disruptions of pandemic conditions. This research also uniquely contributes to the body of work in this domain by employing tools from the eXplainable AI field to investigate more deeply the internal mechanics of the models than has previously been done. The Voting ensemble-based method combining machine learning and statistical techniques was the most reliable in our experiments. Our study showed that the prevailing COVID-19 Alert Level feature together with Google search terms and pedestrian traffic were effective at producing generalisable forecasts. The implications of this study are that proxy variables can effectively augment standard autoregressive features to ensure accurate forecasting of patient flows. The experiments showed that the proposed features are potentially effective model inputs for preserving forecast accuracies in the event of future pandemic outbreaks.

Prior to the deep learning era, shape was commonly used to describe the objects. Nowadays, state-of-the-art (SOTA) algorithms in medical imaging are predominantly diverging from computer vision, where voxel grids, meshes, point clouds, and implicit surface models are used. This is seen from numerous shape-related publications in premier vision conferences as well as the growing popularity of ShapeNet (about 51,300 models) and Princeton ModelNet (127,915 models). For the medical domain, we present a large collection of anatomical shapes (e.g., bones, organs, vessels) and 3D models of surgical instrument, called MedShapeNet, created to facilitate the translation of data-driven vision algorithms to medical applications and to adapt SOTA vision algorithms to medical problems. As a unique feature, we directly model the majority of shapes on the imaging data of real patients. As of today, MedShapeNet includes 23 dataset with more than 100,000 shapes that are paired with annotations (ground truth). Our data is freely accessible via a web interface and a Python application programming interface (API) and can be used for discriminative, reconstructive, and variational benchmarks as well as various applications in virtual, augmented, or mixed reality, and 3D printing. Exemplary, we present use cases in the fields of classification of brain tumors, facial and skull reconstructions, multi-class anatomy completion, education, and 3D printing. In future, we will extend the data and improve the interfaces. The project pages are: https://medshapenet.ikim.nrw/ and https://github.com/Jianningli/medshapenet-feedback

The advent of foundation models (FMs) as an emerging suite of AI techniques has struck a wave of opportunities in computational healthcare. The interactive nature of these models, guided by pre-training data and human instructions, has ignited a data-centric AI paradigm that emphasizes better data characterization, quality, and scale. In healthcare AI, obtaining and processing high-quality clinical data records has been a longstanding challenge, ranging from data quantity, annotation, patient privacy, and ethics. In this survey, we investigate a wide range of data-centric approaches in the FM era (from model pre-training to inference) towards improving the healthcare workflow. We discuss key perspectives in AI security, assessment, and alignment with human values. Finally, we offer a promising outlook of FM-based analytics to enhance the performance of patient outcome and clinical workflow in the evolving landscape of healthcare and medicine. We provide an up-to-date list of healthcare-related foundation models and datasets at https://github.com/Yunkun-Zhang/Data-Centric-FM-Healthcare .

Current medical retrieval benchmarks primarily emphasize lexical or shallow semantic similarity, overlooking the reasoning-intensive demands that are central to clinical decision-making. In practice, physicians often retrieve authoritative medical evidence to support diagnostic hypotheses. Such evidence typically aligns with an inferred diagnosis rather than the surface form of a patient's symptoms, leading to low lexical or semantic overlap between queries and relevant documents. To address this gap, we introduce R2MED, the first benchmark explicitly designed for reasoning-driven medical retrieval. It comprises 876 queries spanning three tasks: Q&A reference retrieval, clinical evidence retrieval, and clinical case retrieval. These tasks are drawn from five representative medical scenarios and twelve body systems, capturing the complexity and diversity of real-world medical information needs. We evaluate 15 widely-used retrieval systems on R2MED and find that even the best model achieves only 31.4 nDCG@10, demonstrating the benchmark's difficulty. Classical re-ranking and generation-augmented retrieval methods offer only modest improvements. Although large reasoning models improve performance via intermediate inference generation, the best results still peak at 41.4 nDCG@10. These findings underscore a substantial gap between current retrieval techniques and the reasoning demands of real clinical tasks. We release R2MED as a challenging benchmark to foster the development of next-generation medical retrieval systems with enhanced reasoning capabilities. Data and code are available at https://github.com/R2MED/R2MED

Purpose: In radiology, large language models (LLMs), including ChatGPT, have recently gained attention, and their utility is being rapidly evaluated. However, concerns have emerged regarding their reliability in clinical applications due to limitations such as hallucinations and insufficient referencing. To address these issues, we focus on the latest technology, retrieval-augmented generation (RAG), which enables LLMs to reference reliable external knowledge (REK). Specifically, this study examines the utility and reliability of a recently released RAG-equipped LLM (RAG-LLM), NotebookLM, for staging lung cancer. Materials and methods: We summarized the current lung cancer staging guideline in Japan and provided this as REK to NotebookLM. We then tasked NotebookLM with staging 100 fictional lung cancer cases based on CT findings and evaluated its accuracy. For comparison, we performed the same task using a gold-standard LLM, GPT-4 Omni (GPT-4o), both with and without the REK. Results: NotebookLM achieved 86% diagnostic accuracy in the lung cancer staging experiment, outperforming GPT-4o, which recorded 39% accuracy with the REK and 25% without it. Moreover, NotebookLM demonstrated 95% accuracy in searching reference locations within the REK. Conclusion: NotebookLM successfully performed lung cancer staging by utilizing the REK, demonstrating superior performance compared to GPT-4o. Additionally, it provided highly accurate reference locations within the REK, allowing radiologists to efficiently evaluate the reliability of NotebookLM's responses and detect possible hallucinations. Overall, this study highlights the potential of NotebookLM, a RAG-LLM, in image diagnosis.

Advances in large language models (LLMs) provide new opportunities in healthcare for improved patient care, clinical decision-making, and enhancement of physician and administrator workflows. However, the potential of these models importantly depends on their ability to generalize effectively across clinical environments and populations, a challenge often underestimated in early development. To better understand reasons for these challenges and inform mitigation approaches, we evaluated ClinicLLM, an LLM trained on [HOSPITAL]'s clinical notes, analyzing its performance on 30-day all-cause readmission prediction focusing on variability across hospitals and patient characteristics. We found poorer generalization particularly in hospitals with fewer samples, among patients with government and unspecified insurance, the elderly, and those with high comorbidities. To understand reasons for lack of generalization, we investigated sample sizes for fine-tuning, note content (number of words per note), patient characteristics (comorbidity level, age, insurance type, borough), and health system aspects (hospital, all-cause 30-day readmission, and mortality rates). We used descriptive statistics and supervised classification to identify features. We found that, along with sample size, patient age, number of comorbidities, and the number of words in notes are all important factors related to generalization. Finally, we compared local fine-tuning (hospital specific), instance-based augmented fine-tuning and cluster-based fine-tuning for improving generalization. Among these, local fine-tuning proved most effective, increasing AUC by 0.25% to 11.74% (most helpful in settings with limited data). Overall, this study provides new insights for enhancing the deployment of large language models in the societally important domain of healthcare, and improving their performance for broader populations.