Daily Papers

In disentangling the heterogeneity observed in psychopathology, personality of the patients is considered crucial. While it has been demonstrated that personality traits are reflected in the language used by a patient, we hypothesize that this enables automatic inference of the personality type directly from speech utterances, potentially more accurately than through a traditional questionnaire-based approach explicitly designed for personality classification. To validate this hypothesis, we adopt natural language processing (NLP) and standard machine learning tools for classification. We test this on a dataset of recorded clinical diagnostic interviews (CDI) on a sample of 79 patients diagnosed with major depressive disorder (MDD) -- a condition for which differentiated treatment based on personality styles has been advocated -- and classified into anaclitic and introjective personality styles. We start by analyzing the interviews to see which linguistic features are associated with each style, in order to gain a better understanding of the styles. Then, we develop automatic classifiers based on (a) standardized questionnaire responses; (b) basic text features, i.e., TF-IDF scores of words and word sequences; (c) more advanced text features, using LIWC (linguistic inquiry and word count) and context-aware features using BERT (bidirectional encoder representations from transformers); (d) audio features. We find that automated classification with language-derived features (i.e., based on LIWC) significantly outperforms questionnaire-based classification models. Furthermore, the best performance is achieved by combining LIWC with the questionnaire features. This suggests that more work should be put into developing linguistically based automated techniques for characterizing personality, however questionnaires still to some extent complement such methods.

Despite extensive standardization, diagnostic interviews for mental health disorders encompass substantial subjective judgment. Previous studies have demonstrated that EEG-based neural measures can function as reliable objective correlates of depression, or even predictors of depression and its course. However, their clinical utility has not been fully realized because of 1) the lack of automated ways to deal with the inherent noise associated with EEG data at scale, and 2) the lack of knowledge of which aspects of the EEG signal may be markers of a clinical disorder. Here we adapt an unsupervised pipeline from the recent deep representation learning literature to address these problems by 1) learning a disentangled representation using beta-VAE to denoise the signal, and 2) extracting interpretable features associated with a sparse set of clinical labels using a Symbol-Concept Association Network (SCAN). We demonstrate that our method is able to outperform the canonical hand-engineered baseline classification method on a number of factors, including participant age and depression diagnosis. Furthermore, our method recovers a representation that can be used to automatically extract denoised Event Related Potentials (ERPs) from novel, single EEG trajectories, and supports fast supervised re-mapping to various clinical labels, allowing clinicians to re-use a single EEG representation regardless of updates to the standardized diagnostic system. Finally, single factors of the learned disentangled representations often correspond to meaningful markers of clinical factors, as automatically detected by SCAN, allowing for human interpretability and post-hoc expert analysis of the recommendations made by the model.

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).

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.

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.

Large language models (LLMs) hold great promise for assisting clinical interviews due to their fluent interactive capabilities and extensive medical knowledge. However, the lack of high-quality interview dialogue data and widely accepted evaluation methods has significantly impeded this process. So we propose CliniChat, a framework that integrates multi-source knowledge to enable LLMs to simulate real-world clinical interviews. It consists of two modules: Clini-Recon and Clini-Eval, each responsible for reconstructing and evaluating interview dialogues, respectively. By incorporating three sources of knowledge, Clini-Recon transforms clinical notes into systematic, professional, and empathetic interview dialogues. Clini-Eval combines a comprehensive evaluation metric system with a two-phase automatic evaluation approach, enabling LLMs to assess interview performance like experts. We contribute MedQA-Dialog, a high-quality synthetic interview dialogue dataset, and CliniChatGLM, a model specialized for clinical interviews. Experimental results demonstrate that CliniChatGLM's interview capabilities undergo a comprehensive upgrade, particularly in history-taking, achieving state-of-the-art performance.

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.

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.

According to the World Health Organization, the number of mental disorder patients, especially depression patients, has grown rapidly and become a leading contributor to the global burden of disease. However, the present common practice of depression diagnosis is based on interviews and clinical scales carried out by doctors, which is not only labor-consuming but also time-consuming. One important reason is due to the lack of physiological indicators for mental disorders. With the rising of tools such as data mining and artificial intelligence, using physiological data to explore new possible physiological indicators of mental disorder and creating new applications for mental disorder diagnosis has become a new research hot topic. However, good quality physiological data for mental disorder patients are hard to acquire. We present a multi-modal open dataset for mental-disorder analysis. The dataset includes EEG and audio data from clinically depressed patients and matching normal controls. All our patients were carefully diagnosed and selected by professional psychiatrists in hospitals. The EEG dataset includes not only data collected using traditional 128-electrodes mounted elastic cap, but also a novel wearable 3-electrode EEG collector for pervasive applications. The 128-electrodes EEG signals of 53 subjects were recorded as both in resting state and under stimulation; the 3-electrode EEG signals of 55 subjects were recorded in resting state; the audio data of 52 subjects were recorded during interviewing, reading, and picture description. We encourage other researchers in the field to use it for testing their methods of mental-disorder analysis.

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.

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.

Artificial intelligence holds great promise for expanding access to expert medical knowledge and reasoning. However, most evaluations of language models rely on static vignettes and multiple-choice questions that fail to reflect the complexity and nuance of evidence-based medicine in real-world settings. In clinical practice, physicians iteratively formulate and revise diagnostic hypotheses, adapting each subsequent question and test to what they've just learned, and weigh the evolving evidence before committing to a final diagnosis. To emulate this iterative process, we introduce the Sequential Diagnosis Benchmark, which transforms 304 diagnostically challenging New England Journal of Medicine clinicopathological conference (NEJM-CPC) cases into stepwise diagnostic encounters. A physician or AI begins with a short case abstract and must iteratively request additional details from a gatekeeper model that reveals findings only when explicitly queried. Performance is assessed not just by diagnostic accuracy but also by the cost of physician visits and tests performed. We also present the MAI Diagnostic Orchestrator (MAI-DxO), a model-agnostic orchestrator that simulates a panel of physicians, proposes likely differential diagnoses and strategically selects high-value, cost-effective tests. When paired with OpenAI's o3 model, MAI-DxO achieves 80% diagnostic accuracy--four times higher than the 20% average of generalist physicians. MAI-DxO also reduces diagnostic costs by 20% compared to physicians, and 70% compared to off-the-shelf o3. When configured for maximum accuracy, MAI-DxO achieves 85.5% accuracy. These performance gains with MAI-DxO generalize across models from the OpenAI, Gemini, Claude, Grok, DeepSeek, and Llama families. We highlight how AI systems, when guided to think iteratively and act judiciously, can advance diagnostic precision and cost-effectiveness in clinical care.

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.

Physicians spend significant time documenting clinical encounters, a burden that contributes to professional burnout. To address this, robust automation tools for medical documentation are crucial. We introduce MedSynth -- a novel dataset of synthetic medical dialogues and notes designed to advance the Dialogue-to-Note (Dial-2-Note) and Note-to-Dialogue (Note-2-Dial) tasks. Informed by an extensive analysis of disease distributions, this dataset includes over 10,000 dialogue-note pairs covering over 2000 ICD-10 codes. We demonstrate that our dataset markedly enhances the performance of models in generating medical notes from dialogues, and dialogues from medical notes. The dataset provides a valuable resource in a field where open-access, privacy-compliant, and diverse training data are scarce. Code is available at https://github.com/ahmadrezarm/MedSynth/tree/main and the dataset is available at https://huggingface.co/datasets/Ahmad0067/MedSynth.

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.

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.

Clinical diagnosis is a highly specialized discipline requiring both domain expertise and strict adherence to rigorous guidelines. While current AI-driven medical research predominantly focuses on knowledge graphs or natural text pretraining paradigms to incorporate medical knowledge, these approaches primarily rely on implicitly encoded knowledge within model parameters, neglecting task-specific knowledge required by diverse downstream tasks. To address this limitation, we propose Retrieval-Augmented Diagnosis (RAD), a novel framework that explicitly injects external knowledge into multimodal models directly on downstream tasks. Specifically, RAD operates through three key mechanisms: retrieval and refinement of disease-centered knowledge from multiple medical sources, a guideline-enhanced contrastive loss that constrains the latent distance between multi-modal features and guideline knowledge, and the dual transformer decoder that employs guidelines as queries to steer cross-modal fusion, aligning the models with clinical diagnostic workflows from guideline acquisition to feature extraction and decision-making. Moreover, recognizing the lack of quantitative evaluation of interpretability for multimodal diagnostic models, we introduce a set of criteria to assess the interpretability from both image and text perspectives. Extensive evaluations across four datasets with different anatomies demonstrate RAD's generalizability, achieving state-of-the-art performance. Furthermore, RAD enables the model to concentrate more precisely on abnormal regions and critical indicators, ensuring evidence-based, trustworthy diagnosis. Our code is available at https://github.com/tdlhl/RAD.

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.

Doctors and patients alike increasingly use Large Language Models (LLMs) to diagnose clinical cases. However, unlike domains such as math or coding, where correctness can be objectively defined by the final answer, medical diagnosis requires both the outcome and the reasoning process to be accurate. Currently, widely used medical benchmarks like MedQA and MMLU assess only accuracy in the final answer, overlooking the quality and faithfulness of the clinical reasoning process. To address this limitation, we introduce MedCaseReasoning, the first open-access dataset for evaluating LLMs on their ability to align with clinician-authored diagnostic reasoning. The dataset includes 14,489 diagnostic question-and-answer cases, each paired with detailed reasoning statements derived from open-access medical case reports. We evaluate state-of-the-art reasoning LLMs on MedCaseReasoning and find significant shortcomings in their diagnoses and reasoning: for instance, the top-performing open-source model, DeepSeek-R1, achieves only 48% 10-shot diagnostic accuracy and mentions only 64% of the clinician reasoning statements (recall). However, we demonstrate that fine-tuning LLMs on the reasoning traces derived from MedCaseReasoning significantly improves diagnostic accuracy and clinical reasoning recall by an average relative gain of 29% and 41%, respectively. The open-source dataset, code, and models are available at https://github.com/kevinwu23/Stanford-MedCaseReasoning.

We present VinDr-CXR-VQA, a large-scale chest X-ray dataset for explainable Medical Visual Question Answering (Med-VQA) with spatial grounding. The dataset contains 17,597 question-answer pairs across 4,394 images, each annotated with radiologist-verified bounding boxes and clinical reasoning explanations. Our question taxonomy spans six diagnostic types-Where, What, Is there, How many, Which, and Yes/No-capturing diverse clinical intents. To improve reliability, we construct a balanced distribution of 41.7% positive and 58.3% negative samples, mitigating hallucinations in normal cases. Benchmarking with MedGemma-4B-it demonstrates improved performance (F1 = 0.624, +11.8% over baseline) while enabling lesion localization. VinDr-CXR-VQA aims to advance reproducible and clinically grounded Med-VQA research. The dataset and evaluation tools are publicly available at huggingface.co/datasets/Dangindev/VinDR-CXR-VQA.

Speech patterns have been identified as potential diagnostic markers for neuropsychiatric conditions. However, most studies only compare a single clinical group to healthy controls, whereas clinical practice often requires differentiating between multiple potential diagnoses (multiclass settings). To address this, we assembled a dataset of repeated recordings from 420 participants (67 with major depressive disorder, 106 with schizophrenia and 46 with autism, as well as matched controls), and tested the performance of a range of conventional machine learning models and advanced Transformer models on both binary and multiclass classification, based on voice and text features. While binary models performed comparably to previous research (F1 scores between 0.54-0.75 for autism spectrum disorder, ASD; 0.67-0.92 for major depressive disorder, MDD; and 0.71-0.83 for schizophrenia); when differentiating between multiple diagnostic groups performance decreased markedly (F1 scores between 0.35-0.44 for ASD, 0.57-0.75 for MDD, 0.15-0.66 for schizophrenia, and 0.38-0.52 macro F1). Combining voice and text-based models yielded increased performance, suggesting that they capture complementary diagnostic information. Our results indicate that models trained on binary classification may learn to rely on markers of generic differences between clinical and non-clinical populations, or markers of clinical features that overlap across conditions, rather than identifying markers specific to individual conditions. We provide recommendations for future research in the field, suggesting increased focus on developing larger transdiagnostic datasets that include more fine-grained clinical features, and that can support the development of models that better capture the complexity of neuropsychiatric conditions and naturalistic diagnostic assessment.

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.

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.

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.

Recent advancements in Large Language Models (LLMs) have demonstrated significant promise in clinical diagnosis. However, current models struggle to emulate the iterative, diagnostic hypothesis-driven reasoning of real clinical scenarios. Specifically, current LLMs suffer from three critical limitations: (1) generating hallucinated medical content due to weak grounding in verified knowledge, (2) asking redundant or inefficient questions rather than discriminative ones that hinder diagnostic progress, and (3) losing coherence over multi-turn dialogues, leading to contradictory or inconsistent conclusions. To address these challenges, we propose MedKGI, a diagnostic framework grounded in clinical practices. MedKGI integrates a medical knowledge graph (KG) to constrain reasoning to validated medical ontologies, selects questions based on information gain to maximize diagnostic efficiency, and adopts an OSCE-format structured state to maintain consistent evidence tracking across turns. Experiments on clinical benchmarks show that MedKGI outperforms strong LLM baselines in both diagnostic accuracy and inquiry efficiency, improving dialogue efficiency by 30% on average while maintaining state-of-the-art accuracy.

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.

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/.

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.

Differential diagnosis is crucial for medicine as it helps healthcare providers systematically distinguish between conditions that share similar symptoms. This study assesses the impact of lab test results on differential diagnoses (DDx) made by large language models (LLMs). Clinical vignettes from 50 case reports from PubMed Central were created incorporating patient demographics, symptoms, and lab results. Five LLMs GPT-4, GPT-3.5, Llama-2-70b, Claude-2, and Mixtral-8x7B were tested to generate Top 10, Top 5, and Top 1 DDx with and without lab data. A comprehensive evaluation involving GPT-4, a knowledge graph, and clinicians was conducted. GPT-4 performed best, achieving 55% accuracy for Top 1 diagnoses and 60% for Top 10 with lab data, with lenient accuracy up to 80%. Lab results significantly improved accuracy, with GPT-4 and Mixtral excelling, though exact match rates were low. Lab tests, including liver function, metabolic/toxicology panels, and serology/immune tests, were generally interpreted correctly by LLMs for differential diagnosis.

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.

Automatic depression detection from conversational data has gained significant interest in recent years. The DAIC-WOZ dataset, interviews conducted by a human-controlled virtual agent, has been widely used for this task. Recent studies have reported enhanced performance when incorporating interviewer's prompts into the model. In this work, we hypothesize that this improvement might be mainly due to a bias present in these prompts, rather than the proposed architectures and methods. Through ablation experiments and qualitative analysis, we discover that models using interviewer's prompts learn to focus on a specific region of the interviews, where questions about past experiences with mental health issues are asked, and use them as discriminative shortcuts to detect depressed participants. In contrast, models using participant responses gather evidence from across the entire interview. Finally, to highlight the magnitude of this bias, we achieve a 0.90 F1 score by intentionally exploiting it, the highest result reported to date on this dataset using only textual information. Our findings underline the need for caution when incorporating interviewers' prompts into models, as they may inadvertently learn to exploit targeted prompts, rather than learning to characterize the language and behavior that are genuinely indicative of the patient's mental health condition.

Medical coding is essential for standardizing clinical data and communication but is often time-consuming and prone to errors. Traditional Natural Language Processing (NLP) methods struggle with automating coding due to the large label space, lengthy text inputs, and the absence of supporting evidence annotations that justify code selection. Recent advancements in Generative Artificial Intelligence (AI) offer promising solutions to these challenges. In this work, we introduce MedCodER, a Generative AI framework for automatic medical coding that leverages extraction, retrieval, and re-ranking techniques as core components. MedCodER achieves a micro-F1 score of 0.60 on International Classification of Diseases (ICD) code prediction, significantly outperforming state-of-the-art methods. Additionally, we present a new dataset containing medical records annotated with disease diagnoses, ICD codes, and supporting evidence texts (https://doi.org/10.5281/zenodo.13308316). Ablation tests confirm that MedCodER's performance depends on the integration of each of its aforementioned components, as performance declines when these components are evaluated in isolation.

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.

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.

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/.

Clinical diagnosis of the eye is performed over multifarious data modalities including scalar clinical labels, vectorized biomarkers, two-dimensional fundus images, and three-dimensional Optical Coherence Tomography (OCT) scans. Clinical practitioners use all available data modalities for diagnosing and treating eye diseases like Diabetic Retinopathy (DR) or Diabetic Macular Edema (DME). Enabling usage of machine learning algorithms within the ophthalmic medical domain requires research into the relationships and interactions between all relevant data over a treatment period. Existing datasets are limited in that they neither provide data nor consider the explicit relationship modeling between the data modalities. In this paper, we introduce the Ophthalmic Labels for Investigating Visual Eye Semantics (OLIVES) dataset that addresses the above limitation. This is the first OCT and near-IR fundus dataset that includes clinical labels, biomarker labels, disease labels, and time-series patient treatment information from associated clinical trials. The dataset consists of 1268 near-IR fundus images each with at least 49 OCT scans, and 16 biomarkers, along with 4 clinical labels and a disease diagnosis of DR or DME. In total, there are 96 eyes' data averaged over a period of at least two years with each eye treated for an average of 66 weeks and 7 injections. We benchmark the utility of OLIVES dataset for ophthalmic data as well as provide benchmarks and concrete research directions for core and emerging machine learning paradigms within medical image analysis.

Large language models (LLMs) often fail to ask effective questions under uncertainty, making them unreliable in domains where proactive information-gathering is essential for decisionmaking. We present ALFA, a framework that improves LLM question-asking by (i) decomposing the notion of a "good" question into a set of theory-grounded attributes (e.g., clarity, relevance), (ii) controllably synthesizing attribute-specific question variations, and (iii) aligning models via preference-based optimization to explicitly learn to ask better questions along these fine-grained attributes. Focusing on clinical reasoning as a case study, we introduce the MediQ-AskDocs dataset, composed of 17k real-world clinical interactions augmented with 80k attribute-specific preference pairs of follow-up questions, as well as a novel expert-annotated interactive healthcare QA task to evaluate question-asking abilities. Models aligned with ALFA reduce diagnostic errors by 56.6% on MediQ-AskDocs compared to SOTA instruction-tuned LLMs, with a question-level win-rate of 64.4% and strong generalizability. Our findings suggest that explicitly guiding question-asking with structured, fine-grained attributes offers a scalable path to improve LLMs, especially in expert application domains.

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.

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.

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.

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.

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.

Depression has proven to be a significant public health issue, profoundly affecting the psychological well-being of individuals. If it remains undiagnosed, depression can lead to severe health issues, which can manifest physically and even lead to suicide. Generally, Diagnosing depression or any other mental disorder involves conducting semi-structured interviews alongside supplementary questionnaires, including variants of the Patient Health Questionnaire (PHQ) by Clinicians and mental health professionals. This approach places significant reliance on the experience and judgment of trained physicians, making the diagnosis susceptible to personal biases. Given that the underlying mechanisms causing depression are still being actively researched, physicians often face challenges in diagnosing and treating the condition, particularly in its early stages of clinical presentation. Recently, significant strides have been made in Artificial neural computing to solve problems involving text, image, and speech in various domains. Our analysis has aimed to leverage these state-of-the-art (SOTA) models in our experiments to achieve optimal outcomes leveraging multiple modalities. The experiments were performed on the Extended Distress Analysis Interview Corpus Wizard of Oz dataset (E-DAIC) corpus presented in the Audio/Visual Emotion Challenge (AVEC) 2019 Challenge. The proposed solutions demonstrate better results achieved by Proprietary and Open-source Large Language Models (LLMs), which achieved a Root Mean Square Error (RMSE) score of 3.98 on Textual Modality, beating the AVEC 2019 challenge baseline results and current SOTA regression analysis architectures. Additionally, the proposed solution achieved an accuracy of 71.43% in the classification task. The paper also includes a novel audio-visual multi-modal network that predicts PHQ-8 scores with an RMSE of 6.51.

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.

Accurate diagnostic coding of medical notes is crucial for enhancing patient care, medical research, and error-free billing in healthcare organizations. Manual coding is a time-consuming task for providers, and diagnostic codes often exhibit low sensitivity and specificity, whereas the free text in medical notes can be a more precise description of a patients status. Thus, accurate automated diagnostic coding of medical notes has become critical for a learning healthcare system. Recent developments in long-document transformer architectures have enabled attention-based deep-learning models to adjudicate medical notes. In addition, contrastive loss functions have been used to jointly pre-train large language and image models with noisy labels. To further improve the automated adjudication of medical notes, we developed an approach based on i) models for ICD-10 diagnostic code sequences using a large real-world data set, ii) large language models for medical notes, and iii) contrastive pre-training to build an integrated model of both ICD-10 diagnostic codes and corresponding medical text. We demonstrate that a contrastive approach for pre-training improves performance over prior state-of-the-art models for the MIMIC-III-50, MIMIC-III-rare50, and MIMIC-III-full diagnostic coding tasks.

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.

Rare diseases, including Inborn Errors of Metabolism (IEM), pose significant diagnostic challenges. Case reports serve as key but computationally underutilized resources to inform diagnosis. Clinical dense information extraction refers to organizing medical information into structured predefined categories. Large Language Models (LLMs) may enable scalable information extraction from case reports but are rarely evaluated for this task. We introduce CaseReportBench, an expert-annotated dataset for dense information extraction of case reports, focusing on IEMs. Using this dataset, we assess various models and prompting strategies, introducing novel approaches such as category-specific prompting and subheading-filtered data integration. Zero-shot chain-of-thought prompting offers little advantage over standard zero-shot prompting. Category-specific prompting improves alignment with the benchmark. The open-source model Qwen2.5-7B outperforms GPT-4o for this task. Our clinician evaluations show that LLMs can extract clinically relevant details from case reports, supporting rare disease diagnosis and management. We also highlight areas for improvement, such as LLMs' limitations in recognizing negative findings important for differential diagnosis. This work advances LLM-driven clinical natural language processing and paves the way for scalable medical AI applications.

Unstructured clinical notes contain essential patient information but are challenging for physicians to search and interpret efficiently. Although large language models (LLMs) have shown promise in question answering (QA), most existing systems lack transparency, usability, and alignment with clinical workflows. This work introduces an interactive QA system that enables physicians to query clinical notes via text or voice and receive extractive answers highlighted directly in the note for traceability. The system was built using OpenAI models with zero-shot prompting and evaluated across multiple metrics, including exact string match, word overlap, SentenceTransformer similarity, and BERTScore. Results show that while exact match scores ranged from 47 to 62 percent, semantic similarity scores exceeded 87 percent, indicating strong contextual alignment even when wording varied. To assess usability, the system was also evaluated using simulated clinical personas. Seven diverse physician and nurse personas interacted with the system across scenario-based tasks and provided structured feedback. The evaluations highlighted strengths in intuitive design and answer accessibility, alongside opportunities for enhancing explanation clarity.

Generating clinical reports from raw recordings such as X-rays and electroencephalogram (EEG) is an essential and routine task for doctors. However, it is often time-consuming to write accurate and detailed reports. Most existing methods try to generate the whole reports from the raw input with limited success because 1) generated reports often contain errors that need manual review and correction, 2) it does not save time when doctors want to write additional information into the report, and 3) the generated reports are not customized based on individual doctors' preference. We propose {\it CL}inic{\it A}l {\it R}eport {\it A}uto-completion (CLARA), an interactive method that generates reports in a sentence by sentence fashion based on doctors' anchor words and partially completed sentences. CLARA searches for most relevant sentences from existing reports as the template for the current report. The retrieved sentences are sequentially modified by combining with the input feature representations to create the final report. In our experimental evaluation, CLARA achieved 0.393 CIDEr and 0.248 BLEU-4 on X-ray reports and 0.482 CIDEr and 0.491 BLEU-4 for EEG reports for sentence-level generation, which is up to 35% improvement over the best baseline. Also via our qualitative evaluation, CLARA is shown to produce reports which have a significantly higher level of approval by doctors in a user study (3.74 out of 5 for CLARA vs 2.52 out of 5 for the baseline).

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.

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.

Clinical dialogue represents a complex duality requiring both the empathetic fluency of natural conversation and the rigorous precision of evidence-based medicine. While Large Language Models possess unprecedented linguistic capabilities, their architectural reliance on reactive and stateless processing often favors probabilistic plausibility over factual veracity. This structural limitation has catalyzed a paradigm shift in medical AI from generative text prediction to agentic autonomy, where the model functions as a central reasoning engine capable of deliberate planning and persistent memory. Moving beyond existing reviews that primarily catalog downstream applications, this survey provides a first-principles analysis of the cognitive architecture underpinning this shift. We introduce a novel taxonomy structured along the orthogonal axes of knowledge source and agency objective to delineate the provenance of clinical knowledge against the system's operational scope. This framework facilitates a systematic analysis of the intrinsic trade-offs between creativity and reliability by categorizing methods into four archetypes: Latent Space Clinicians, Emergent Planners, Grounded Synthesizers, and Verifiable Workflow Automators. For each paradigm, we deconstruct the technical realization across the entire cognitive pipeline, encompassing strategic planning, memory management, action execution, collaboration, and evolution to reveal how distinct architectural choices balance the tension between autonomy and safety.

Large Multimodal Models (LMMs) have shown remarkable progress in the field of medical Visual Question Answering (Med-VQA), achieving high accuracy on existing benchmarks. However, their reliability under robust evaluation is questionable. This study reveals that state-of-the-art models, when subjected to simple probing evaluation, perform worse than random guessing on medical diagnosis questions. To address this critical evaluation problem, we introduce the Probing Evaluation for Medical Diagnosis (ProbMed) dataset to rigorously assess LMM performance in medical imaging through probing evaluation and procedural diagnosis. Particularly, probing evaluation features pairing original questions with negation questions with hallucinated attributes, while procedural diagnosis requires reasoning across various diagnostic dimensions for each image, including modality recognition, organ identification, clinical findings, abnormalities, and positional grounding. Our evaluation reveals that top-performing models like GPT-4V and Gemini Pro perform worse than random guessing on specialized diagnostic questions, indicating significant limitations in handling fine-grained medical inquiries. Besides, models like LLaVA-Med struggle even with more general questions, and results from CheXagent demonstrate the transferability of expertise across different modalities of the same organ, showing that specialized domain knowledge is still crucial for improving performance. This study underscores the urgent need for more robust evaluation to ensure the reliability of LMMs in critical fields like medical diagnosis, and current LMMs are still far from applicable to those fields.

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.

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.

Introduction: Electronic health records (EHR) are a critical medium through which patient stigmatization is perpetuated among healthcare teams. Methods: We identified linguistic features of doubt markers and stigmatizing labels in MIMIC-III EHR via expanded lexicon matching and supervised learning classifiers. Predictors of rates of linguistic features were assessed using Poisson regression models. Results: We found higher rates of stigmatizing labels per chart among patients who were Black or African American (RR: 1.16), patients with Medicare/Medicaid or government-run insurance (RR: 2.46), self-pay (RR: 2.12), and patients with a variety of stigmatizing disease and mental health conditions. Patterns among doubt markers were similar, though male patients had higher rates of doubt markers (RR: 1.25). We found increased stigmatizing labels used by nurses (RR: 1.40), and social workers (RR: 2.25), with similar patterns of doubt markers. Discussion: Stigmatizing language occurred at higher rates among historically stigmatized patients, perpetuated by multiple provider types.

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.

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.

In this paper, we present a framework for training large language models (LLMs) as diagnostic agents with reinforcement learning, enabling them to manage multi-turn diagnostic processes, adaptively select examinations, and commit to final diagnoses. Unlike instruction-tuned models trained on static case summaries, our method acquires diagnostic strategies through interactive exploration and outcome-based feedback. Our contributions are fourfold: (i) We present DiagGym, a diagnostics world model trained with electronic health records that emits examination outcomes conditioned on patient history and recommended examination, serving as a virtual clinical environment for realistic diagnosis training and evaluation; (ii) We train DiagAgent via end-to-end, multi-turn reinforcement learning to learn diagnostic policies that optimize both information yield and diagnostic accuracy; (iii) We introduce DiagBench, a diagnostic benchmark comprising 750 cases with physician-validated examination recommendations and 99 cases annotated with 973 physician-written rubrics on diagnosis process; (iv) we demonstrate superior performance across diverse diagnostic settings. DiagAgent significantly outperforms 10 state-of-the-art LLMs, including DeepSeek-v3 and GPT-4o, as well as two prompt-engineered agents. In single-turn settings, DiagAgent achieves 9.34% higher diagnostic accuracy and 44.03% improvement in examination recommendation hit ratio. In end-to-end settings, it delivers 15.12% increase in diagnostic accuracy and 23.09% boost in examination recommendation F1 score. In rubric-based evaluation, it surpasses the next-best model, Claude-sonnet-4, by 7.1% in weighted rubric score. These findings indicate that learning policies in interactive clinical environments confers dynamic and clinically meaningful diagnostic management abilities unattainable through passive training alone.

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.

Objective: Question answering (QA) systems have the potential to improve the quality of clinical care by providing health professionals with the latest and most relevant evidence. However, QA systems have not been widely adopted. This systematic review aims to characterize current medical QA systems, assess their suitability for healthcare, and identify areas of improvement. Materials and methods: We searched PubMed, IEEE Xplore, ACM Digital Library, ACL Anthology and forward and backward citations on 7th February 2023. We included peer-reviewed journal and conference papers describing the design and evaluation of biomedical QA systems. Two reviewers screened titles, abstracts, and full-text articles. We conducted a narrative synthesis and risk of bias assessment for each study. We assessed the utility of biomedical QA systems. Results: We included 79 studies and identified themes, including question realism, answer reliability, answer utility, clinical specialism, systems, usability, and evaluation methods. Clinicians' questions used to train and evaluate QA systems were restricted to certain sources, types and complexity levels. No system communicated confidence levels in the answers or sources. Many studies suffered from high risks of bias and applicability concerns. Only 8 studies completely satisfied any criterion for clinical utility, and only 7 reported user evaluations. Most systems were built with limited input from clinicians. Discussion: While machine learning methods have led to increased accuracy, most studies imperfectly reflected real-world healthcare information needs. Key research priorities include developing more realistic healthcare QA datasets and considering the reliability of answer sources, rather than merely focusing on accuracy.

The rapid advancement of large-scale vision-language models has showcased remarkable capabilities across various tasks. However, the lack of extensive and high-quality image-text data in medicine has greatly hindered the development of large-scale medical vision-language models. In this work, we present a diagnosis-guided bootstrapping strategy that exploits both image and label information to construct vision-language datasets. Based on the constructed dataset, we developed MedDr, a generalist foundation model for healthcare capable of handling diverse medical data modalities, including radiology, pathology, dermatology, retinography, and endoscopy. Moreover, during inference, we propose a simple but effective retrieval-augmented medical diagnosis strategy, which enhances the model's generalization ability. Extensive experiments on visual question answering, medical report generation, and medical image diagnosis demonstrate the superiority of our method.

Linking clinical narratives to standardized vocabularies and coding systems is a key component of unlocking the information in medical text for analysis. However, many domains of medical concepts lack well-developed terminologies that can support effective coding of medical text. We present a framework for developing natural language processing (NLP) technologies for automated coding of under-studied types of medical information, and demonstrate its applicability via a case study on physical mobility function. Mobility is a component of many health measures, from post-acute care and surgical outcomes to chronic frailty and disability, and is coded in the International Classification of Functioning, Disability, and Health (ICF). However, mobility and other types of functional activity remain under-studied in medical informatics, and neither the ICF nor commonly-used medical terminologies capture functional status terminology in practice. We investigated two data-driven paradigms, classification and candidate selection, to link narrative observations of mobility to standardized ICF codes, using a dataset of clinical narratives from physical therapy encounters. Recent advances in language modeling and word embedding were used as features for established machine learning models and a novel deep learning approach, achieving a macro F-1 score of 84% on linking mobility activity reports to ICF codes. Both classification and candidate selection approaches present distinct strengths for automated coding in under-studied domains, and we highlight that the combination of (i) a small annotated data set; (ii) expert definitions of codes of interest; and (iii) a representative text corpus is sufficient to produce high-performing automated coding systems. This study has implications for the ongoing growth of NLP tools for a variety of specialized applications in clinical care and research.

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.

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

Tumor documentation in Germany is largely done manually, requiring reading patient records and entering data into structured databases. Large language models (LLMs) could potentially enhance this process by improving efficiency and reliability. This evaluation tests eleven different open source LLMs with sizes ranging from 1-70 billion model parameters on three basic tasks of the tumor documentation process: identifying tumor diagnoses, assigning ICD-10 codes, and extracting the date of first diagnosis. For evaluating the LLMs on these tasks, a dataset of annotated text snippets based on anonymized doctors' notes from urology was prepared. Different prompting strategies were used to investigate the effect of the number of examples in few-shot prompting and to explore the capabilities of the LLMs in general. The models Llama 3.1 8B, Mistral 7B, and Mistral NeMo 12 B performed comparably well in the tasks. Models with less extensive training data or having fewer than 7 billion parameters showed notably lower performance, while larger models did not display performance gains. Examples from a different medical domain than urology could also improve the outcome in few-shot prompting, which demonstrates the ability of LLMs to handle tasks needed for tumor documentation. Open source LLMs show a strong potential for automating tumor documentation. Models from 7-12 billion parameters could offer an optimal balance between performance and resource efficiency. With tailored fine-tuning and well-designed prompting, these models might become important tools for clinical documentation in the future. The code for the evaluation is available from https://github.com/stefan-m-lenz/UroLlmEval. We also release the dataset as a new valuable resource that addresses the shortage of authentic and easily accessible benchmarks in German-language medical NLP.

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.

Follow-up question generation is an essential feature of dialogue systems as it can reduce conversational ambiguity and enhance modeling complex interactions. Conversational contexts often pose core NLP challenges such as (i) extracting relevant information buried in fragmented data sources, and (ii) modeling parallel thought processes. These two challenges occur frequently in medical dialogue as a doctor asks questions based not only on patient utterances but also their prior EHR data and current diagnostic hypotheses. Asking medical questions in asynchronous conversations compounds these issues as doctors can only rely on static EHR information to motivate follow-up questions. To address these challenges, we introduce FollowupQ, a novel framework for enhancing asynchronous medical conversation. FollowupQ is a multi-agent framework that processes patient messages and EHR data to generate personalized follow-up questions, clarifying patient-reported medical conditions. FollowupQ reduces requisite provider follow-up communications by 34%. It also improves performance by 17% and 5% on real and synthetic data, respectively. We also release the first public dataset of asynchronous medical messages with linked EHR data alongside 2,300 follow-up questions written by clinical experts for the wider NLP research community.

With the advancement of telemedicine, both researchers and medical practitioners are working hand-in-hand to develop various techniques to automate various medical operations, such as diagnosis report generation. In this paper, we first present a multi-modal clinical conversation summary generation task that takes a clinician-patient interaction (both textual and visual information) and generates a succinct synopsis of the conversation. We propose a knowledge-infused, multi-modal, multi-tasking medical domain identification and clinical conversation summary generation (MM-CliConSummation) framework. It leverages an adapter to infuse knowledge and visual features and unify the fused feature vector using a gated mechanism. Furthermore, we developed a multi-modal, multi-intent clinical conversation summarization corpus annotated with intent, symptom, and summary. The extensive set of experiments, both quantitatively and qualitatively, led to the following findings: (a) critical significance of visuals, (b) more precise and medical entity preserving summary with additional knowledge infusion, and (c) a correlation between medical department identification and clinical synopsis generation. Furthermore, the dataset and source code are available at https://github.com/NLP-RL/MM-CliConSummation.

Medical phrase grounding is crucial for identifying relevant regions in medical images based on phrase queries, facilitating accurate image analysis and diagnosis. However, current methods rely on manual extraction of key phrases from medical reports, reducing efficiency and increasing the workload for clinicians. Additionally, the lack of model confidence estimation limits clinical trust and usability. In this paper, we introduce a novel task called Medical Report Grounding (MRG), which aims to directly identify diagnostic phrases and their corresponding grounding boxes from medical reports in an end-to-end manner. To address this challenge, we propose uMedGround, a robust and reliable framework that leverages a multimodal large language model to predict diagnostic phrases by embedding a unique token, <BOX>, into the vocabulary to enhance detection capabilities. A vision encoder-decoder processes the embedded token and input image to generate grounding boxes. Critically, uMedGround incorporates an uncertainty-aware prediction model, significantly improving the robustness and reliability of grounding predictions. Experimental results demonstrate that uMedGround outperforms state-of-the-art medical phrase grounding methods and fine-tuned large visual-language models, validating its effectiveness and reliability. This study represents a pioneering exploration of the MRG task, marking the first-ever endeavor in this domain. Additionally, we demonstrate the applicability of uMedGround in medical visual question answering and class-based localization tasks, where it highlights visual evidence aligned with key diagnostic phrases, supporting clinicians in interpreting various types of textual inputs, including free-text reports, visual question answering queries, and class labels.

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.

Medical dialogue systems (MDSs) aim to assist doctors and patients with a range of professional medical services, i.e., diagnosis, treatment and consultation. The development of MDSs is hindered because of a lack of resources. In particular. (1) there is no dataset with large-scale medical dialogues that covers multiple medical services and contains fine-grained medical labels (i.e., intents, actions, slots, values), and (2) there is no set of established benchmarks for MDSs for multi-domain, multi-service medical dialogues. In this paper, we present ReMeDi, a set of resource for medical dialogues. ReMeDi consists of two parts, the ReMeDi dataset and the ReMeDi benchmarks. The ReMeDi dataset contains 96,965 conversations between doctors and patients, including 1,557 conversations with fine-gained labels. It covers 843 types of diseases, 5,228 medical entities, and 3 specialties of medical services across 40 domains. To the best of our knowledge, the ReMeDi dataset is the only medical dialogue dataset that covers multiple domains and services, and has fine-grained medical labels. The second part of the ReMeDi resources consists of a set of state-of-the-art models for (medical) dialogue generation. The ReMeDi benchmark has the following methods: (1) pretrained models (i.e., BERT-WWM, BERT-MED, GPT2, and MT5) trained, validated, and tested on the ReMeDi dataset, and (2) a self-supervised contrastive learning(SCL) method to expand the ReMeDi dataset and enhance the training of the state-of-the-art pretrained models. We describe the creation of the ReMeDi dataset, the ReMeDi benchmarking methods, and establish experimental results using the ReMeDi benchmarking methods on the ReMeDi dataset for future research to compare against. With this paper, we share the dataset, implementations of the benchmarks, and evaluation scripts.

Medical multiple-choice question answering (MCQA) is particularly difficult. Questions may describe patient symptoms and ask for the correct diagnosis, which requires domain knowledge and complex reasoning. Standard language modeling pretraining alone is not sufficient to achieve the best results. jin2020disease showed that focusing masked language modeling on disease name prediction when using medical encyclopedic paragraphs as input leads to considerable MCQA accuracy improvement. In this work, we show that (1) fine-tuning on generated MCQA dataset outperforms the masked language modeling based objective and (2) correctly masking the cues to the answers is critical for good performance. We release new pretraining datasets and achieve state-of-the-art results on 4 MCQA datasets, notably +5.7\% with base-size model on MedQA-USMLE.

This study investigates the feasibility of automating clinical coding in Russian, a language with limited biomedical resources. We present a new dataset for ICD coding, which includes diagnosis fields from electronic health records (EHRs) annotated with over 10,000 entities and more than 1,500 unique ICD codes. This dataset serves as a benchmark for several state-of-the-art models, including BERT, LLaMA with LoRA, and RAG, with additional experiments examining transfer learning across domains (from PubMed abstracts to medical diagnosis) and terminologies (from UMLS concepts to ICD codes). We then apply the best-performing model to label an in-house EHR dataset containing patient histories from 2017 to 2021. Our experiments, conducted on a carefully curated test set, demonstrate that training with the automated predicted codes leads to a significant improvement in accuracy compared to manually annotated data from physicians. We believe our findings offer valuable insights into the potential for automating clinical coding in resource-limited languages like Russian, which could enhance clinical efficiency and data accuracy in these contexts.

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.

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.

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.

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.

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.

Radiological imaging is central to diagnosis, treatment planning, and clinical decision-making. Vision-language foundation models have spurred interest in automated radiology report generation (RRG), but safe deployment requires reliable clinical evaluation of generated reports. Existing metrics often rely on surface-level similarity or behave as black boxes, lacking interpretability. We introduce ICARE (Interpretable and Clinically-grounded Agent-based Report Evaluation), an interpretable evaluation framework leveraging large language model agents and dynamic multiple-choice question answering (MCQA). Two agents, each with either the ground-truth or generated report, generate clinically meaningful questions and quiz each other. Agreement on answers captures preservation and consistency of findings, serving as interpretable proxies for clinical precision and recall. By linking scores to question-answer pairs, ICARE enables transparent, and interpretable assessment. Clinician studies show ICARE aligns significantly more with expert judgment than prior metrics. Perturbation analyses confirm sensitivity to clinical content and reproducibility, while model comparisons reveal interpretable error patterns.

The integration of Computer-Assisted Diagnosis (CAD) with Large Language Models (LLMs) holds great potential in clinical applications, specifically in the roles of virtual family doctors and clinic assistants. However, current works in this field are plagued by limitations, specifically a restricted scope of applicable image domains and the provision of unreliable medical advice. This restricts their overall processing capabilities. Furthermore, the mismatch in writing style between LLMs and radiologists undermines their practical usefulness. To tackle these challenges, we introduce ChatCAD+, which is designed to be universal and reliable. It is capable of handling medical images from diverse domains and leveraging up-to-date information from reputable medical websites to provide reliable medical advice. Additionally, it incorporates a template retrieval system that improves report generation performance via exemplar reports. This approach ensures greater consistency with the expertise of human professionals. The source code is available at https://github.com/zhaozh10/ChatCAD.

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.

Current medical language models, adapted from large language models (LLMs), typically predict ICD code-based diagnosis from electronic health records (EHRs) because these labels are readily available. However, ICD codes do not capture the nuanced, context-rich reasoning clinicians use for diagnosis. Clinicians synthesize diverse patient data and reference clinical practice guidelines (CPGs) to make evidence-based decisions. This misalignment limits the clinical utility of existing models. We introduce GARMLE-G, a Generation-Augmented Retrieval framework that grounds medical language model outputs in authoritative CPGs. Unlike conventional Retrieval-Augmented Generation based approaches, GARMLE-G enables hallucination-free outputs by directly retrieving authoritative guideline content without relying on model-generated text. It (1) integrates LLM predictions with EHR data to create semantically rich queries, (2) retrieves relevant CPG knowledge snippets via embedding similarity, and (3) fuses guideline content with model output to generate clinically aligned recommendations. A prototype system for hypertension diagnosis was developed and evaluated on multiple metrics, demonstrating superior retrieval precision, semantic relevance, and clinical guideline adherence compared to RAG-based baselines, while maintaining a lightweight architecture suitable for localized healthcare deployment. This work provides a scalable, low-cost, and hallucination-free method for grounding medical language models in evidence-based clinical practice, with strong potential for broader clinical deployment.

Medical report generation has achieved remarkable advancements yet has still been faced with several challenges. First, the inherent imbalance in the distribution of normal and abnormal cases may lead models to exhibit a biased focus on normal samples, resulting in unreliable diagnoses. Second, the frequent occurrence of common template sentences in the reports may overwhelm the critical abnormal information. Moreover, existing works focus on 2D chest X-rays, leaving CT report generation underexplored due to the high-dimensional nature of CT images and the limited availability of CT-report pairs. Recently, LLM has shown a great ability to generate reliable answers with appropriate prompts, which shed light on addressing the aforementioned challenges. In this paper, we propose Dia-LLaMA, a framework to adapt the LLaMA2-7B for CT report generation by incorporating diagnostic information as guidance prompts. Considering the high dimension of CT, we leverage a pre-trained ViT3D with perceiver to extract the visual information. To tailor the LLM for report generation and emphasize abnormality, we extract additional diagnostic information by referring to a disease prototype memory bank, which is updated during training to capture common disease representations. Furthermore, we introduce disease-aware attention to enable the model to adjust attention for different diseases. Experiments on the chest CT dataset demonstrated that our proposed method outperformed previous methods and achieved state-of-the-art on both clinical efficacy performance and natural language generation metrics. The code will be made publically available.

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.

We present a new text-to-SQL dataset for electronic health records (EHRs). The utterances were collected from 222 hospital staff members, including physicians, nurses, and insurance review and health records teams. To construct the QA dataset on structured EHR data, we conducted a poll at a university hospital and used the responses to create seed questions. We then manually linked these questions to two open-source EHR databases, MIMIC-III and eICU, and included various time expressions and held-out unanswerable questions in the dataset, which were also collected from the poll. Our dataset poses a unique set of challenges: the model needs to 1) generate SQL queries that reflect a wide range of needs in the hospital, including simple retrieval and complex operations such as calculating survival rate, 2) understand various time expressions to answer time-sensitive questions in healthcare, and 3) distinguish whether a given question is answerable or unanswerable. We believe our dataset, EHRSQL, can serve as a practical benchmark for developing and assessing QA models on structured EHR data and take a step further towards bridging the gap between text-to-SQL research and its real-life deployment in healthcare. EHRSQL is available at https://github.com/glee4810/EHRSQL.

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.

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

Depressive and anxiety disorders are widespread, necessitating timely identification and management. Recent advances in Large Language Models (LLMs) offer potential solutions, yet high costs and ethical concerns about training data remain challenges. This paper introduces a pipeline for synthesizing clinical interviews, resulting in 1,157 interactive dialogues (PsyInterview), and presents EmoScan, an LLM-based emotional disorder screening system. EmoScan distinguishes between coarse (e.g., anxiety or depressive disorders) and fine disorders (e.g., major depressive disorders) and conducts high-quality interviews. Evaluations showed that EmoScan exceeded the performance of base models and other LLMs like GPT-4 in screening emotional disorders (F1-score=0.7467). It also delivers superior explanations (BERTScore=0.9408) and demonstrates robust generalizability (F1-score of 0.67 on an external dataset). Furthermore, EmoScan outperforms baselines in interviewing skills, as validated by automated ratings and human evaluations. This work highlights the importance of scalable data-generative pipelines for developing effective mental health LLM tools.

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.

In this paper, we release a largest ever medical Question Answering (QA) dataset with 26 million QA pairs. We benchmark many existing approaches in our dataset in terms of both retrieval and generation. Experimental results show that the existing models perform far lower than expected and the released dataset is still challenging in the pre-trained language model era. Moreover, we also experimentally show the benefit of the proposed dataset in many aspects: (i) trained models for other QA datasets in a zero-shot fashion; and (ii) as external knowledge for retrieval-augmented generation (RAG); and (iii) improving existing pre-trained language models by using the QA pairs as a pre-training corpus in continued training manner. We believe that this dataset will not only contribute to medical research but also facilitate both the patients and clinical doctors. See https://github.com/FreedomIntelligence/Huatuo-26M.

Accurate diagnosis with medical large language models is hindered by knowledge gaps and hallucinations. Retrieval and tool-augmented methods help, but their impact is limited by weak use of external knowledge and poor feedback-reasoning traceability. To address these challenges, We introduce Deep-DxSearch, an agentic RAG system trained end-to-end with reinforcement learning (RL) that enables steer tracebale retrieval-augmented reasoning for medical diagnosis. In Deep-DxSearch, we first construct a large-scale medical retrieval corpus comprising patient records and reliable medical knowledge sources to support retrieval-aware reasoning across diagnostic scenarios. More crutially, we frame the LLM as the core agent and the retrieval corpus as its environment, using tailored rewards on format, retrieval, reasoning structure, and diagnostic accuracy, thereby evolving the agentic RAG policy from large-scale data through RL. Experiments demonstrate that our end-to-end agentic RL training framework consistently outperforms prompt-engineering and training-free RAG approaches across multiple data centers. After training, Deep-DxSearch achieves substantial gains in diagnostic accuracy, surpassing strong diagnostic baselines such as GPT-4o, DeepSeek-R1, and other medical-specific frameworks for both common and rare disease diagnosis under in-distribution and out-of-distribution settings. Moreover, ablation studies on reward design and retrieval corpus components confirm their critical roles, underscoring the uniqueness and effectiveness of our approach compared with traditional implementations. Finally, case studies and interpretability analyses highlight improvements in Deep-DxSearch's diagnostic policy, providing deeper insight into its performance gains and supporting clinicians in delivering more reliable and precise preliminary diagnoses. See https://github.com/MAGIC-AI4Med/Deep-DxSearch.

Medical question-answering (QA) is a critical task for evaluating how effectively large language models (LLMs) encode clinical knowledge and assessing their potential applications in medicine. Despite showing promise on multiple-choice tests, LLMs frequently struggle with open-ended medical questions, producing responses with dangerous hallucinations or lacking comprehensive coverage of critical aspects. Existing approaches attempt to address these challenges through domain-specific fine-tuning, but this proves resource-intensive and difficult to scale across models. To improve the comprehensiveness and factuality of medical responses, we propose a novel approach utilizing structured medical reasoning. Our method guides LLMs through an seven-step cognitive process inspired by clinical diagnosis, enabling more accurate and complete answers without additional training. Experiments on the MedLFQA benchmark demonstrate that our approach achieves the highest Factuality Score of 85.8, surpassing fine-tuned models. Notably, this improvement transfers to smaller models, highlighting the method's efficiency and scalability. Our code and datasets are available.

Hepato-pancreato-biliary (HPB) disorders represent a global public health challenge due to their high morbidity and mortality. Although large language models (LLMs) have shown promising performance in general medical question-answering tasks, the current evaluation benchmarks are mostly derived from standardized examinations or manually designed questions, lacking HPB coverage and clinical cases. To address these issues, we systematically eatablish an HPB disease evaluation benchmark comprising 3,535 closed-ended multiple-choice questions and 337 open-ended real diagnosis cases, which encompasses all the 33 main categories and 465 subcategories of HPB diseases defined in the International Statistical Classification of Diseases, 10th Revision (ICD-10). The multiple-choice questions are curated from public datasets and synthesized data, and the clinical cases are collected from prestigious medical journals, case-sharing platforms, and collaborating hospitals. By evalauting commercial and open-source general and medical LLMs on our established benchmark, namely ClinBench-HBP, we find that while commercial LLMs perform competently on medical exam questions, they exhibit substantial performance degradation on HPB diagnosis tasks, especially on complex, inpatient clinical cases. Those medical LLMs also show limited generalizability to HPB diseases. Our results reveal the critical limitations of current LLMs in the domain of HPB diseases, underscoring the imperative need for future medical LLMs to handle real, complex clinical diagnostics rather than simple medical exam questions. The benchmark will be released at https://clinbench-hpb.github.io.

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).

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.

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.

Skin carcinoma is the most prevalent form of cancer globally, accounting for over $8 billion in annual healthcare expenditures. In clinical settings, physicians document patient visits using detailed SOAP (Subjective, Objective, Assessment, and Plan) notes. However, manually generating these notes is labor-intensive and contributes to clinician burnout. In this work, we propose a weakly supervised multimodal framework to generate clinically structured SOAP notes from limited inputs, including lesion images and sparse clinical text. Our approach reduces reliance on manual annotations, enabling scalable, clinically grounded documentation while alleviating clinician burden and reducing the need for large annotated data. Our method achieves performance comparable to GPT-4o, Claude, and DeepSeek Janus Pro across key clinical relevance metrics. To evaluate clinical quality, we introduce two novel metrics MedConceptEval and Clinical Coherence Score (CCS) which assess semantic alignment with expert medical concepts and input features, respectively.

Chest X-Ray (CXR) report generation is a promising approach to improving the efficiency of CXR interpretation. However, a significant increase in diagnostic accuracy is required before that can be realised. Motivated by this, we propose a framework that is more inline with a radiologist's workflow by considering longitudinal data. Here, the decoder is additionally conditioned on the report from the subject's previous imaging study via a prompt. We also propose a new reward for reinforcement learning based on CXR-BERT, which computes the similarity between reports. We conduct experiments on the MIMIC-CXR dataset. The results indicate that longitudinal data improves CXR report generation. CXR-BERT is also shown to be a promising alternative to the current state-of-the-art reward based on RadGraph. This investigation indicates that longitudinal CXR report generation can offer a substantial increase in diagnostic accuracy. Our Hugging Face model is available at: https://huggingface.co/aehrc/cxrmate and code is available at: https://github.com/aehrc/cxrmate.

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.

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.

Building upon our previous investigations of O1 replication (Part 1: Journey Learning [Qin et al., 2024] and Part 2: Distillation [Huang et al., 2024]), this work explores the potential of inference-time scaling in large language models (LLMs) for medical reasoning tasks, ranging from diagnostic decision-making to treatment planning. Through extensive experiments on medical benchmarks of varying complexity (MedQA, Medbullets, and JAMA Clinical Challenges), our investigation reveals several key insights: (1) Increasing inference time does lead to improved performance. With a modest training set of 500 samples, our model yields substantial performance improvements of 6%-11%. (2) Task complexity directly correlates with the required length of reasoning chains, confirming the necessity of extended thought processes for challenging problems. (3) The differential diagnoses generated by our model adhere to the principles of the hypothetico-deductive method, producing a list of potential conditions that may explain a patient's symptoms and systematically narrowing these possibilities by evaluating the evidence. These findings demonstrate the promising synergy between inference-time scaling and journey learning in advancing LLMs' real-world clinical reasoning capabilities.

There is increasing interest in the application large language models (LLMs) to the medical field, in part because of their impressive performance on medical exam questions. While promising, exam questions do not reflect the complexity of real patient-doctor interactions. In reality, physicians' decisions are shaped by many complex factors, such as patient compliance, personal experience, ethical beliefs, and cognitive bias. Taking a step toward understanding this, our hypothesis posits that when LLMs are confronted with clinical questions containing cognitive biases, they will yield significantly less accurate responses compared to the same questions presented without such biases. In this study, we developed BiasMedQA, a benchmark for evaluating cognitive biases in LLMs applied to medical tasks. Using BiasMedQA we evaluated six LLMs, namely GPT-4, Mixtral-8x70B, GPT-3.5, PaLM-2, Llama 2 70B-chat, and the medically specialized PMC Llama 13B. We tested these models on 1,273 questions from the US Medical Licensing Exam (USMLE) Steps 1, 2, and 3, modified to replicate common clinically-relevant cognitive biases. Our analysis revealed varying effects for biases on these LLMs, with GPT-4 standing out for its resilience to bias, in contrast to Llama 2 70B-chat and PMC Llama 13B, which were disproportionately affected by cognitive bias. Our findings highlight the critical need for bias mitigation in the development of medical LLMs, pointing towards safer and more reliable applications in healthcare.

Randomized controlled trials (RCTs) are the benchmark for causal inference, yet field implementation can deviate. We here present a remote audit - a design-based, preregistrable diagnostic that uses only pre-treatment satellite imagery to test whether assignment is independent of local conditions. The conditional randomization test of the remote audit evaluates whether treatment assignment is more predictable from pre-treatment satellite features than expected under the experiment's registered mechanism, providing a finite-sample valid, design-based diagnostic that requires no parametric assumptions. The procedure is finite-sample valid, honors blocks and clusters, and controls multiplicity across image models and resolutions via a max-statistic. We illustrate with two RCTs: Uganda's Youth Opportunities Program, where the audit corroborates randomization and flags selection and missing-data risks; and a school-based trial in Bangladesh, where assignment is highly predictable from pre-treatment features relative to the stated design, consistent with independent concerns about irregularities. Remote audits complement balance tests, lower early-stage costs, and enable rapid design checks when baseline surveys are expensive or infeasible.

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.

Large language models (LLMs) have shown promise in medical question answering but often struggle with hallucinations and shallow reasoning, particularly in tasks requiring nuanced clinical understanding. Retrieval-augmented generation (RAG) offers a practical and privacy-preserving way to enhance LLMs with external medical knowledge. However, most existing approaches rely on surface-level semantic retrieval and lack the structured reasoning needed for clinical decision support. We introduce MedCoT-RAG, a domain-specific framework that combines causal-aware document retrieval with structured chain-of-thought prompting tailored to medical workflows. This design enables models to retrieve evidence aligned with diagnostic logic and generate step-by-step causal reasoning reflective of real-world clinical practice. Experiments on three diverse medical QA benchmarks show that MedCoT-RAG outperforms strong baselines by up to 10.3% over vanilla RAG and 6.4% over advanced domain-adapted methods, improving accuracy, interpretability, and consistency in complex medical tasks.

Identifying patient cohorts is fundamental to numerous healthcare tasks, including clinical trial recruitment and retrospective studies. Current cohort retrieval methods in healthcare organizations rely on automated queries of structured data combined with manual curation, which are time-consuming, labor-intensive, and often yield low-quality results. Recent advancements in large language models (LLMs) and information retrieval (IR) offer promising avenues to revolutionize these systems. Major challenges include managing extensive eligibility criteria and handling the longitudinal nature of unstructured Electronic Medical Records (EMRs) while ensuring that the solution remains cost-effective for real-world application. This paper introduces a new task, Automatic Cohort Retrieval (ACR), and evaluates the performance of LLMs and commercial, domain-specific neuro-symbolic approaches. We provide a benchmark task, a query dataset, an EMR dataset, and an evaluation framework. Our findings underscore the necessity for efficient, high-quality ACR systems capable of longitudinal reasoning across extensive patient databases.

The second edition of Deep Learning Interviews is home to hundreds of fully-solved problems, from a wide range of key topics in AI. It is designed to both rehearse interview or exam specific topics and provide machine learning MSc / PhD. students, and those awaiting an interview a well-organized overview of the field. The problems it poses are tough enough to cut your teeth on and to dramatically improve your skills-but they're framed within thought-provoking questions and engaging stories. That is what makes the volume so specifically valuable to students and job seekers: it provides them with the ability to speak confidently and quickly on any relevant topic, to answer technical questions clearly and correctly, and to fully understand the purpose and meaning of interview questions and answers. Those are powerful, indispensable advantages to have when walking into the interview room. The book's contents is a large inventory of numerous topics relevant to DL job interviews and graduate level exams. That places this work at the forefront of the growing trend in science to teach a core set of practical mathematical and computational skills. It is widely accepted that the training of every computer scientist must include the fundamental theorems of ML, and AI appears in the curriculum of nearly every university. This volume is designed as an excellent reference for graduates of such programs.

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.

Limited access to mental healthcare, extended wait times, and increasing capabilities of Large Language Models (LLMs) has led individuals to turn to LLMs for fulfilling their mental health needs. However, examining the multi-turn mental health conversation capabilities of LLMs remains under-explored. Existing evaluation frameworks typically focus on diagnostic accuracy and win-rates and often overlook alignment with patient-specific goals, values, and personalities required for meaningful conversations. To address this, we introduce MedAgent, a novel framework for synthetically generating realistic, multi-turn mental health sensemaking conversations and use it to create the Mental Health Sensemaking Dialogue (MHSD) dataset, comprising over 2,200 patient-LLM conversations. Additionally, we present MultiSenseEval, a holistic framework to evaluate the multi-turn conversation abilities of LLMs in healthcare settings using human-centric criteria. Our findings reveal that frontier reasoning models yield below-par performance for patient-centric communication and struggle at advanced diagnostic capabilities with average score of 31%. Additionally, we observed variation in model performance based on patient's persona and performance drop with increasing turns in the conversation. Our work provides a comprehensive synthetic data generation framework, a dataset and evaluation framework for assessing LLMs in multi-turn mental health conversations.

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.

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.

In the medical domain, numerous scenarios necessitate the long-form generation ability of large language models (LLMs). Specifically, when addressing patients' questions, it is essential that the model's response conveys factual claims, highlighting the need for an automated method to evaluate those claims. Thus, we introduce MedLFQA, a benchmark dataset reconstructed using long-form question-answering datasets related to the biomedical domain. We use MedLFQA to facilitate the automatic evaluations of factuality. We also propose OLAPH, a simple and novel framework that enables the improvement of factuality through automatic evaluations. The OLAPH framework iteratively trains LLMs to mitigate hallucinations using sampling predictions and preference optimization. In other words, we iteratively set the highest-scoring response as a preferred response derived from sampling predictions and train LLMs to align with the preferred response that improves factuality. We highlight that, even on evaluation metrics not used during training, LLMs trained with our OLAPH framework demonstrate significant performance improvement in factuality. Our findings reveal that a 7B LLM trained with our OLAPH framework can provide long answers comparable to the medical experts' answers in terms of factuality. We believe that our work could shed light on gauging the long-text generation ability of LLMs in the medical domain. Our code and datasets are available at https://github.com/dmis-lab/OLAPH}{https://github.com/dmis-lab/OLAPH.

The automated generation of imaging reports proves invaluable in alleviating the workload of radiologists. A clinically applicable reports generation algorithm should demonstrate its effectiveness in producing reports that accurately describe radiology findings and attend to patient-specific indications. In this paper, we introduce a novel method, Structural Entities extraction and patient indications Incorporation (SEI) for chest X-ray report generation. Specifically, we employ a structural entities extraction (SEE) approach to eliminate presentation-style vocabulary in reports and improve the quality of factual entity sequences. This reduces the noise in the following cross-modal alignment module by aligning X-ray images with factual entity sequences in reports, thereby enhancing the precision of cross-modal alignment and further aiding the model in gradient-free retrieval of similar historical cases. Subsequently, we propose a cross-modal fusion network to integrate information from X-ray images, similar historical cases, and patient-specific indications. This process allows the text decoder to attend to discriminative features of X-ray images, assimilate historical diagnostic information from similar cases, and understand the examination intention of patients. This, in turn, assists in triggering the text decoder to produce high-quality reports. Experiments conducted on MIMIC-CXR validate the superiority of SEI over state-of-the-art approaches on both natural language generation and clinical efficacy metrics.

Many clinical tasks require an understanding of specialized data, such as medical images and genomics, which is not typically found in general-purpose large multimodal models. Building upon Gemini's multimodal models, we develop several models within the new Med-Gemini family that inherit core capabilities of Gemini and are optimized for medical use via fine-tuning with 2D and 3D radiology, histopathology, ophthalmology, dermatology and genomic data. Med-Gemini-2D sets a new standard for AI-based chest X-ray (CXR) report generation based on expert evaluation, exceeding previous best results across two separate datasets by an absolute margin of 1% and 12%, where 57% and 96% of AI reports on normal cases, and 43% and 65% on abnormal cases, are evaluated as "equivalent or better" than the original radiologists' reports. We demonstrate the first ever large multimodal model-based report generation for 3D computed tomography (CT) volumes using Med-Gemini-3D, with 53% of AI reports considered clinically acceptable, although additional research is needed to meet expert radiologist reporting quality. Beyond report generation, Med-Gemini-2D surpasses the previous best performance in CXR visual question answering (VQA) and performs well in CXR classification and radiology VQA, exceeding SoTA or baselines on 17 of 20 tasks. In histopathology, ophthalmology, and dermatology image classification, Med-Gemini-2D surpasses baselines across 18 out of 20 tasks and approaches task-specific model performance. Beyond imaging, Med-Gemini-Polygenic outperforms the standard linear polygenic risk score-based approach for disease risk prediction and generalizes to genetically correlated diseases for which it has never been trained. Although further development and evaluation are necessary in the safety-critical medical domain, our results highlight the potential of Med-Gemini across a wide range of medical tasks.

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.

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.

Transformers-based models, such as BERT, have dramatically improved the performance for various natural language processing tasks. The clinical knowledge enriched model, namely ClinicalBERT, also achieved state-of-the-art results when performed on clinical named entity recognition and natural language inference tasks. One of the core limitations of these transformers is the substantial memory consumption due to their full self-attention mechanism. To overcome this, long sequence transformer models, e.g. Longformer and BigBird, were proposed with the idea of sparse attention mechanism to reduce the memory usage from quadratic to the sequence length to a linear scale. These models extended the maximum input sequence length from 512 to 4096, which enhanced the ability of modeling long-term dependency and consequently achieved optimal results in a variety of tasks. Inspired by the success of these long sequence transformer models, we introduce two domain enriched language models, namely Clinical-Longformer and Clinical-BigBird, which are pre-trained from large-scale clinical corpora. We evaluate both pre-trained models using 10 baseline tasks including named entity recognition, question answering, and document classification tasks. The results demonstrate that Clinical-Longformer and Clinical-BigBird consistently and significantly outperform ClinicalBERT as well as other short-sequence transformers in all downstream tasks. We have made our source code available at [https://github.com/luoyuanlab/Clinical-Longformer] the pre-trained models available for public download at: [https://huggingface.co/yikuan8/Clinical-Longformer].

With the proliferation of Large Language Models (LLMs) in diverse domains, there is a particular need for unified evaluation standards in clinical medical scenarios, where models need to be examined very thoroughly. We present CliMedBench, a comprehensive benchmark with 14 expert-guided core clinical scenarios specifically designed to assess the medical ability of LLMs across 7 pivot dimensions. It comprises 33,735 questions derived from real-world medical reports of top-tier tertiary hospitals and authentic examination exercises. The reliability of this benchmark has been confirmed in several ways. Subsequent experiments with existing LLMs have led to the following findings: (i) Chinese medical LLMs underperform on this benchmark, especially where medical reasoning and factual consistency are vital, underscoring the need for advances in clinical knowledge and diagnostic accuracy. (ii) Several general-domain LLMs demonstrate substantial potential in medical clinics, while the limited input capacity of many medical LLMs hinders their practical use. These findings reveal both the strengths and limitations of LLMs in clinical scenarios and offer critical insights for medical research.