Daily Papers

As lung cancer evolves, the presence of enlarged and potentially malignant lymph nodes must be assessed to properly estimate disease progression and select the best treatment strategy. Following the clinical guidelines, estimation of short-axis diameter and mediastinum station are paramount for correct diagnosis. A method for accurate and automatic segmentation is hence decisive for quantitatively describing lymph nodes. In this study, the use of 3D convolutional neural networks, either through slab-wise schemes or the leveraging of downsampled entire volumes, is investigated. Furthermore, the potential impact from simple ensemble strategies is considered. As lymph nodes have similar attenuation values to nearby anatomical structures, we suggest using the knowledge of other organs as prior information to guide the segmentation task. To assess the segmentation and instance detection performances, a 5-fold cross-validation strategy was followed over a dataset of 120 contrast-enhanced CT volumes. For the 1178 lymph nodes with a short-axis diameter geq10 mm, our best performing approach reached a patient-wise recall of 92%, a false positive per patient ratio of 5, and a segmentation overlap of 80.5%. The method performs similarly well across all stations. Fusing a slab-wise and a full volume approach within an ensemble scheme generated the best performances. The anatomical priors guiding strategy is promising, yet a larger set than four organs appears needed to generate an optimal benefit. A larger dataset is also mandatory, given the wide range of expressions a lymph node can exhibit (i.e., shape, location, and attenuation), and contrast uptake variations.

Radiotherapy (RT) planning is complex, subjective, and time-intensive. Advances in artificial intelligence (AI) promise to improve its precision, efficiency, and consistency, but progress is often limited by the scarcity of large, standardized datasets. To address this, we introduce the Automated Iterative RT Planning (AIRTP) system, a scalable solution for generating high-quality treatment plans. This scalable solution is designed to generate substantial volumes of consistently high-quality treatment plans, overcoming a key obstacle in the advancement of AI-driven RT planning. Our AIRTP pipeline adheres to clinical guidelines and automates essential steps, including organ-at-risk (OAR) contouring, helper structure creation, beam setup, optimization, and plan quality improvement, using AI integrated with RT planning software like Eclipse of Varian. Furthermore, a novel approach for determining optimization parameters to reproduce 3D dose distributions, i.e. a method to convert dose predictions to deliverable treatment plans constrained by machine limitations. A comparative analysis of plan quality reveals that our automated pipeline produces treatment plans of quality comparable to those generated manually, which traditionally require several hours of labor per plan. Committed to public research, the first data release of our AIRTP pipeline includes nine cohorts covering head-and-neck and lung cancer sites to support an AAPM 2025 challenge. This data set features more than 10 times the number of plans compared to the largest existing well-curated public data set to our best knowledge. Repo:{https://github.com/RiqiangGao/GDP-HMM_AAPMChallenge}

In natural language processing applied to the clinical domain, utilizing large language models has emerged as a promising avenue for error detection and correction on clinical notes, a knowledge-intensive task for which annotated data is scarce. This paper presents MedReAct'N'MedReFlex, which leverages a suite of four LLM-based medical agents. The MedReAct agent initiates the process by observing, analyzing, and taking action, generating trajectories to guide the search to target a potential error in the clinical notes. Subsequently, the MedEval agent employs five evaluators to assess the targeted error and the proposed correction. In cases where MedReAct's actions prove insufficient, the MedReFlex agent intervenes, engaging in reflective analysis and proposing alternative strategies. Finally, the MedFinalParser agent formats the final output, preserving the original style while ensuring the integrity of the error correction process. One core component of our method is our RAG pipeline based on our ClinicalCorp corpora. Among other well-known sources containing clinical guidelines and information, we preprocess and release the open-source MedWiki dataset for clinical RAG application. Our results demonstrate the central role of our RAG approach with ClinicalCorp leveraged through the MedReAct'N'MedReFlex framework. It achieved the ninth rank on the MEDIQA-CORR 2024 final leaderboard.

Large language models have shown promise in clinical decision making, but current approaches struggle to localize and correct errors at specific steps of the reasoning process. This limitation is critical in medicine, where identifying and addressing reasoning errors is essential for accurate diagnosis and effective patient care. We introduce Med-PRM, a process reward modeling framework that leverages retrieval-augmented generation to verify each reasoning step against established medical knowledge bases. By verifying intermediate reasoning steps with evidence retrieved from clinical guidelines and literature, our model can precisely assess the reasoning quality in a fine-grained manner. Evaluations on five medical QA benchmarks and two open-ended diagnostic tasks demonstrate that Med-PRM achieves state-of-the-art performance, with improving the performance of base models by up to 13.50% using Med-PRM. Moreover, we demonstrate the generality of Med-PRM by integrating it in a plug-and-play fashion with strong policy models such as Meerkat, achieving over 80\% accuracy on MedQA for the first time using small-scale models of 8 billion parameters. Our code and data are available at: https://med-prm.github.io/

Large Language Models (LLMs) have great potential in the field of health care, yet they face great challenges in adapting to rapidly evolving medical knowledge. This can lead to outdated or contradictory treatment suggestions. This study investigated how LLMs respond to evolving clinical guidelines, focusing on concept drift and internal inconsistencies. We developed the DriftMedQA benchmark to simulate guideline evolution and assessed the temporal reliability of various LLMs. Our evaluation of seven state-of-the-art models across 4,290 scenarios demonstrated difficulties in rejecting outdated recommendations and frequently endorsing conflicting guidance. Additionally, we explored two mitigation strategies: Retrieval-Augmented Generation and preference fine-tuning via Direct Preference Optimization. While each method improved model performance, their combination led to the most consistent and reliable results. These findings underscore the need to improve LLM robustness to temporal shifts to ensure more dependable applications in clinical practice.

Large Language Models (LLMs) have demonstrated a remarkable potential in medical knowledge acquisition and question-answering. However, LLMs can potentially hallucinate and yield factually incorrect outcomes, even with domain-specific pretraining. Previously, retrieval augmented generation (RAG) has limited success in addressing hallucinations. Unlike previous methods in RAG where the retrieval model was trained separately from the LLM, we introduce JMLR (for Jointly trains LLM and information Retrieval) during the fine-tuning phase. The synchronized training mechanism enhances JMLR's ability to retrieve clinical guidelines and leverage medical knowledge to reason and answer questions and reduces the demand for computational resources. We evaluated JMLR on the important medical question-answering application. Our experimental results demonstrate that JMLR-13B (70.5%) outperforms a previous state-of-the-art open-source model using conventional pre-training and fine-tuning Meditron-70B (68.9%) and Llama2-13B with RAG (67.7%) on a medical question-answering dataset. Comprehensive evaluations reveal JMLR-13B enhances reasoning quality and reduces hallucinations better than Claude3-Opus. Additionally, JMLR-13B (148 GPU hours) also trains much faster than Meditron-70B (42630 GPU hours). Through this work, we provide a new and efficient knowledge enhancement method for healthcare, demonstrating the potential of integrating retrieval and LLM training for medical question-answering systems.

Precision therapeutics require multimodal adaptive models that generate personalized treatment recommendations. We introduce TxAgent, an AI agent that leverages multi-step reasoning and real-time biomedical knowledge retrieval across a toolbox of 211 tools to analyze drug interactions, contraindications, and patient-specific treatment strategies. TxAgent evaluates how drugs interact at molecular, pharmacokinetic, and clinical levels, identifies contraindications based on patient comorbidities and concurrent medications, and tailors treatment strategies to individual patient characteristics. It retrieves and synthesizes evidence from multiple biomedical sources, assesses interactions between drugs and patient conditions, and refines treatment recommendations through iterative reasoning. It selects tools based on task objectives and executes structured function calls to solve therapeutic tasks that require clinical reasoning and cross-source validation. The ToolUniverse consolidates 211 tools from trusted sources, including all US FDA-approved drugs since 1939 and validated clinical insights from Open Targets. TxAgent outperforms leading LLMs, tool-use models, and reasoning agents across five new benchmarks: DrugPC, BrandPC, GenericPC, TreatmentPC, and DescriptionPC, covering 3,168 drug reasoning tasks and 456 personalized treatment scenarios. It achieves 92.1% accuracy in open-ended drug reasoning tasks, surpassing GPT-4o and outperforming DeepSeek-R1 (671B) in structured multi-step reasoning. TxAgent generalizes across drug name variants and descriptions. By integrating multi-step inference, real-time knowledge grounding, and tool-assisted decision-making, TxAgent ensures that treatment recommendations align with established clinical guidelines and real-world evidence, reducing the risk of adverse events and improving therapeutic decision-making.

Multimodal large language models (MLLMs) have shown great potential in general domains but perform poorly in some specific domains due to a lack of domain-specific data, such as image-text data or vedio-text data. In some specific domains, there is abundant graphic and textual data scattered around, but lacks standardized arrangement. In the field of medical ultrasound, there are ultrasonic diagnostic books, ultrasonic clinical guidelines, ultrasonic diagnostic reports, and so on. However, these ultrasonic materials are often saved in the forms of PDF, images, etc., and cannot be directly used for the training of MLLMs. This paper proposes a novel image-text reasoning supervised fine-tuning data generation pipeline to create specific domain quadruplets (image, question, thinking trace, and answer) from domain-specific materials. A medical ultrasound domain dataset ReMUD is established, containing over 45,000 reasoning and non-reasoning supervised fine-tuning Question Answering (QA) and Visual Question Answering (VQA) data. The ReMUD-7B model, fine-tuned on Qwen2.5-VL-7B-Instruct, outperforms general-domain MLLMs in medical ultrasound field. To facilitate research, the ReMUD dataset, data generation codebase, and ReMUD-7B parameters will be released at https://github.com/ShiDaizi/ReMUD, addressing the data shortage issue in specific domain MLLMs.

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

Understanding causal narratives communicated in clinical notes can help make strides towards personalized healthcare. Extracted causal information from clinical notes can be combined with structured EHR data such as patients' demographics, diagnoses, and medications. This will enhance healthcare providers' ability to identify aspects of a patient's story communicated in the clinical notes and help make more informed decisions. In this work, we propose annotation guidelines, develop an annotated corpus and provide baseline scores to identify types and direction of causal relations between a pair of biomedical concepts in clinical notes; communicated implicitly or explicitly, identified either in a single sentence or across multiple sentences. We annotate a total of 2714 de-identified examples sampled from the 2018 n2c2 shared task dataset and train four different language model based architectures. Annotation based on our guidelines achieved a high inter-annotator agreement i.e. Fleiss' kappa (kappa) score of 0.72, and our model for identification of causal relations achieved a macro F1 score of 0.56 on the test data. The high inter-annotator agreement for clinical text shows the quality of our annotation guidelines while the provided baseline F1 score sets the direction for future research towards understanding narratives in clinical texts.

Natural language tasks like Named Entity Recognition (NER) in the clinical domain on non-English texts can be very time-consuming and expensive due to the lack of annotated data. Cross-lingual transfer (CLT) is a way to circumvent this issue thanks to the ability of multilingual large language models to be fine-tuned on a specific task in one language and to provide high accuracy for the same task in another language. However, other methods leveraging translation models can be used to perform NER without annotated data in the target language, by either translating the training set or test set. This paper compares cross-lingual transfer with these two alternative methods, to perform clinical NER in French and in German without any training data in those languages. To this end, we release MedNERF a medical NER test set extracted from French drug prescriptions and annotated with the same guidelines as an English dataset. Through extensive experiments on this dataset and on a German medical dataset (Frei and Kramer, 2021), we show that translation-based methods can achieve similar performance to CLT but require more care in their design. And while they can take advantage of monolingual clinical language models, those do not guarantee better results than large general-purpose multilingual models, whether with cross-lingual transfer or translation.

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.

In Vitro Fertilization is among the most widespread treatments for infertility. One of its main challenges is the evaluation and selection of embryo for implantation, a process with large inter- and intra-clinician variability. Deep learning based methods are gaining attention, but their opaque nature compromises their acceptance in the clinical context, where transparency in the decision making is key. In this paper we analyze the current work in the explainability of AI-assisted embryo analysis models, identifying the limitations. We also discuss how these models could be integrated in the clinical context as decision support systems, considering the needs of clinicians and patients. Finally, we propose guidelines for the sake of increasing interpretability and trustworthiness, pushing this technology forward towards established clinical practice.

Clinical evidence, derived from rigorous research and data analysis, provides healthcare professionals with reliable scientific foundations for informed decision-making. Integrating clinical evidence into real-time practice is challenging due to the enormous workload, complex professional processes, and time constraints. This highlights the need for tools that automate evidence synthesis to support more efficient and accurate decision making in clinical settings. This study introduces Quicker, an evidence-based clinical decision support system powered by large language models (LLMs), designed to automate evidence synthesis and generate clinical recommendations modeled after standard clinical guideline development processes. Quicker implements a fully automated chain that covers all phases, from questions to clinical recommendations, and further enables customized decision-making through integrated tools and interactive user interfaces. To evaluate Quicker's capabilities, we developed the Q2CRBench-3 benchmark dataset, based on clinical guideline development records for three different diseases. Experimental results highlighted Quicker's strong performance, with fine-grained question decomposition tailored to user preferences, retrieval sensitivities comparable to human experts, and literature screening performance approaching comprehensive inclusion of relevant studies. In addition, Quicker-assisted evidence assessment effectively supported human reviewers, while Quicker's recommendations were more comprehensive and logically coherent than those of clinicians. In system-level testing, collaboration between a single reviewer and Quicker reduced the time required for recommendation development to 20-40 minutes. In general, our findings affirm the potential of Quicker to help physicians make quicker and more reliable evidence-based clinical decisions.

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.

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.

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.

With the introduction of ChatGPT, Large Language Models (LLMs) have received enormous attention in healthcare. Despite their potential benefits, researchers have underscored various ethical implications. While individual instances have drawn much attention, the debate lacks a systematic overview of practical applications currently researched and ethical issues connected to them. Against this background, this work aims to map the ethical landscape surrounding the current stage of deployment of LLMs in medicine and healthcare. Electronic databases and preprint servers were queried using a comprehensive search strategy. Studies were screened and extracted following a modified rapid review approach. Methodological quality was assessed using a hybrid approach. For 53 records, a meta-aggregative synthesis was performed. Four fields of applications emerged and testify to a vivid exploration phase. Advantages of using LLMs are attributed to their capacity in data analysis, personalized information provisioning, support in decision-making, mitigating information loss and enhancing information accessibility. However, we also identifies recurrent ethical concerns connected to fairness, bias, non-maleficence, transparency, and privacy. A distinctive concern is the tendency to produce harmful misinformation or convincingly but inaccurate content. A recurrent plea for ethical guidance and human oversight is evident. Given the variety of use cases, it is suggested that the ethical guidance debate be reframed to focus on defining what constitutes acceptable human oversight across the spectrum of applications. This involves considering diverse settings, varying potentials for harm, and different acceptable thresholds for performance and certainty in healthcare. In addition, a critical inquiry is necessary to determine the extent to which the current experimental use of LLMs is necessary and justified.

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/.

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

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

Systematic literature review is essential for evidence-based medicine, requiring comprehensive analysis of clinical trial publications. However, the application of artificial intelligence (AI) models for medical literature mining has been limited by insufficient training and evaluation across broad therapeutic areas and diverse tasks. Here, we present LEADS, an AI foundation model for study search, screening, and data extraction from medical literature. The model is trained on 633,759 instruction data points in LEADSInstruct, curated from 21,335 systematic reviews, 453,625 clinical trial publications, and 27,015 clinical trial registries. We showed that LEADS demonstrates consistent improvements over four cutting-edge generic large language models (LLMs) on six tasks. Furthermore, LEADS enhances expert workflows by providing supportive references following expert requests, streamlining processes while maintaining high-quality results. A study with 16 clinicians and medical researchers from 14 different institutions revealed that experts collaborating with LEADS achieved a recall of 0.81 compared to 0.77 experts working alone in study selection, with a time savings of 22.6%. In data extraction tasks, experts using LEADS achieved an accuracy of 0.85 versus 0.80 without using LEADS, alongside a 26.9% time savings. These findings highlight the potential of specialized medical literature foundation models to outperform generic models, delivering significant quality and efficiency benefits when integrated into expert workflows for medical literature mining.

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.

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

Large language models (LLMs) have 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.

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

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.

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.

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.

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

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

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

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.

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.

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

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.

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.

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

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.

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.

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

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

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

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

The recommendation of medication is a vital aspect of intelligent healthcare systems, as it involves prescribing the most suitable drugs based on a patient's specific health needs. Unfortunately, many sophisticated models currently in use tend to overlook the nuanced semantics of medical data, while only relying heavily on identities. Furthermore, these models face significant challenges in handling cases involving patients who are visiting the hospital for the first time, as they lack prior prescription histories to draw upon. To tackle these issues, we harness the powerful semantic comprehension and input-agnostic characteristics of Large Language Models (LLMs). Our research aims to transform existing medication recommendation methodologies using LLMs. In this paper, we introduce a novel approach called Large Language Model Distilling Medication Recommendation (LEADER). We begin by creating appropriate prompt templates that enable LLMs to suggest medications effectively. However, the straightforward integration of LLMs into recommender systems leads to an out-of-corpus issue specific to drugs. We handle it by adapting the LLMs with a novel output layer and a refined tuning loss function. Although LLM-based models exhibit remarkable capabilities, they are plagued by high computational costs during inference, which is impractical for the healthcare sector. To mitigate this, we have developed a feature-level knowledge distillation technique, which transfers the LLM's proficiency to a more compact model. Extensive experiments conducted on two real-world datasets, MIMIC-III and MIMIC-IV, demonstrate that our proposed model not only delivers effective results but also is efficient. To ease the reproducibility of our experiments, we release the implementation code online.

A long-running goal of the clinical NLP community is the extraction of important variables trapped in clinical notes. However, roadblocks have included dataset shift from the general domain and a lack of public clinical corpora and annotations. In this work, we show that large language models, such as InstructGPT, perform well at zero- and few-shot information extraction from clinical text despite not being trained specifically for the clinical domain. Whereas text classification and generation performance have already been studied extensively in such models, here we additionally demonstrate how to leverage them to tackle a diverse set of NLP tasks which require more structured outputs, including span identification, token-level sequence classification, and relation extraction. Further, due to the dearth of available data to evaluate these systems, we introduce new datasets for benchmarking few-shot clinical information extraction based on a manual re-annotation of the CASI dataset for new tasks. On the clinical extraction tasks we studied, the GPT-3 systems significantly outperform existing zero- and few-shot baselines.

Background: Natural Language Processing (NLP) is widely used to extract clinical insights from Electronic Health Records (EHRs). However, the lack of annotated data, automated tools, and other challenges hinder the full utilisation of NLP for EHRs. Various Machine Learning (ML), Deep Learning (DL) and NLP techniques are studied and compared to understand the limitations and opportunities in this space comprehensively. Methodology: After screening 261 articles from 11 databases, we included 127 papers for full-text review covering seven categories of articles: 1) medical note classification, 2) clinical entity recognition, 3) text summarisation, 4) deep learning (DL) and transfer learning architecture, 5) information extraction, 6) Medical language translation and 7) other NLP applications. This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Result and Discussion: EHR was the most commonly used data type among the selected articles, and the datasets were primarily unstructured. Various ML and DL methods were used, with prediction or classification being the most common application of ML or DL. The most common use cases were: the International Classification of Diseases, Ninth Revision (ICD-9) classification, clinical note analysis, and named entity recognition (NER) for clinical descriptions and research on psychiatric disorders. Conclusion: We find that the adopted ML models were not adequately assessed. In addition, the data imbalance problem is quite important, yet we must find techniques to address this underlining problem. Future studies should address key limitations in studies, primarily identifying Lupus Nephritis, Suicide Attempts, perinatal self-harmed and ICD-9 classification.

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.

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

We introduce Biomed-Enriched, a biomedical text dataset constructed from PubMed via a two-stage annotation process. In the first stage, a large language model annotates 400K paragraphs from PubMed scientific articles, assigning scores for their type (review, study, clinical case, other), domain (clinical, biomedical, other), and educational quality. The educational quality score (rated 1 to 5) estimates how useful a paragraph is for college-level learning. These annotations are then used to fine-tune a small language model, which propagates the labels across the full PMC-OA corpus. The resulting metadata allows us to extract refined subsets, including 2M clinical case paragraphs with over 450K high-quality ones from articles with commercial-use licenses, and to construct several variants via quality filtering and domain upsampling. Clinical text is typically difficult to access due to privacy constraints, as hospital records cannot be publicly shared. Hence, our dataset provides an alternative large-scale, openly available collection of clinical cases from PubMed, making it a valuable resource for biomedical and clinical NLP. Preliminary continual-pretraining experiments with OLMo2 suggest these curated subsets enable targeted improvements, with clinical upsampling boosting performance by ~5% on MMLU ProfMed and educational quality filtering improving MedQA and MedMCQA by ~1%. Combinations of these techniques led to faster convergence, reaching same performance with a third of training tokens, indicating potential for more efficient and effective biomedical pretraining strategies.

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.

Concerns about the reproducibility of deep learning research are more prominent than ever, with no clear solution in sight. The relevance of machine learning research can only be improved if we also employ empirical rigor that incorporates reproducibility guidelines, especially so in the medical imaging field. The Medical Imaging with Deep Learning (MIDL) conference has made advancements in this direction by advocating open access, and recently also recommending authors to make their code public - both aspects being adopted by the majority of the conference submissions. This helps the reproducibility of the methods, however, there is currently little or no support for further evaluation of these supplementary material, making them vulnerable to poor quality, which affects the impact of the entire submission. We have evaluated all accepted full paper submissions to MIDL between 2018 and 2022 using established, but slightly adjusted guidelines on reproducibility and the quality of the public repositories. The evaluations show that publishing repositories and using public datasets are becoming more popular, which helps traceability, but the quality of the repositories has not improved over the years, leaving room for improvement in every aspect of designing repositories. Merely 22% of all submissions contain a repository that were deemed repeatable using our evaluations. From the commonly encountered issues during the evaluations, we propose a set of guidelines for machine learning-related research for medical imaging applications, adjusted specifically for future submissions to MIDL.

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

Synthesizing clinical evidence largely relies on systematic reviews of clinical trials and retrospective analyses from medical literature. However, the rapid expansion of publications presents challenges in efficiently identifying, summarizing, and updating clinical evidence. Here, we introduce TrialMind, a generative artificial intelligence (AI) pipeline for facilitating human-AI collaboration in three crucial tasks for evidence synthesis: study search, screening, and data extraction. To assess its performance, we chose published systematic reviews to build the benchmark dataset, named TrialReviewBench, which contains 100 systematic reviews and the associated 2,220 clinical studies. Our results show that TrialMind excels across all three tasks. In study search, it generates diverse and comprehensive search queries to achieve high recall rates (Ours 0.711-0.834 v.s. Human baseline 0.138-0.232). For study screening, TrialMind surpasses traditional embedding-based methods by 30% to 160%. In data extraction, it outperforms a GPT-4 baseline by 29.6% to 61.5%. We further conducted user studies to confirm its practical utility. Compared to manual efforts, human-AI collaboration using TrialMind yielded a 71.4% recall lift and 44.2% time savings in study screening and a 23.5% accuracy lift and 63.4% time savings in data extraction. Additionally, when comparing synthesized clinical evidence presented in forest plots, medical experts favored TrialMind's outputs over GPT-4's outputs in 62.5% to 100% of cases. These findings show the promise of LLM-based approaches like TrialMind to accelerate clinical evidence synthesis via streamlining study search, screening, and data extraction from medical literature, with exceptional performance improvement when working with human experts.

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

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.

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

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

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.

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

Background: Large language models (LLMs) are trained to follow directions, but this introduces a vulnerability to blindly comply with user requests even if they generate wrong information. In medicine, this could accelerate the generation of misinformation that impacts human well-being. Objectives/Methods: We analyzed compliance to requests to generate misleading content about medications in settings where models know the request is illogical. We investigated whether in-context directions and instruction-tuning of LLMs to prioritize logical reasoning over compliance reduced misinformation risk. Results: While all frontier LLMs complied with misinformation requests, both prompt-based and parameter-based approaches can improve the detection of logic flaws in requests and prevent the dissemination of medical misinformation. Conclusion: Shifting LLMs to prioritize logic over compliance could reduce risks of exploitation for medical misinformation.

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

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.

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

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

This paper describes the results of SemEval 2023 task 7 -- Multi-Evidence Natural Language Inference for Clinical Trial Data (NLI4CT) -- consisting of 2 tasks, a Natural Language Inference (NLI) task, and an evidence selection task on clinical trial data. The proposed challenges require multi-hop biomedical and numerical reasoning, which are of significant importance to the development of systems capable of large-scale interpretation and retrieval of medical evidence, to provide personalized evidence-based care. Task 1, the entailment task, received 643 submissions from 40 participants, and Task 2, the evidence selection task, received 364 submissions from 23 participants. The tasks are challenging, with the majority of submitted systems failing to significantly outperform the majority class baseline on the entailment task, and we observe significantly better performance on the evidence selection task than on the entailment task. Increasing the number of model parameters leads to a direct increase in performance, far more significant than the effect of biomedical pre-training. Future works could explore the limitations of large models for generalization and numerical inference, and investigate methods to augment clinical datasets to allow for more rigorous testing and to facilitate fine-tuning. We envisage that the dataset, models, and results of this task will be useful to the biomedical NLI and evidence retrieval communities. The dataset, competition leaderboard, and website are publicly available.

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.

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

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.

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

The introduction of computerized medical records in hospitals has reduced burdensome operations like manual writing and information fetching. However, the data contained in medical records are still far underutilized, primarily because extracting them from unstructured textual medical records takes time and effort. Information Extraction, a subfield of Natural Language Processing, can help clinical practitioners overcome this limitation, using automated text-mining pipelines. In this work, we created the first Italian neuropsychiatric Named Entity Recognition dataset, PsyNIT, and used it to develop a Large Language Model for this task. Moreover, we conducted several experiments with three external independent datasets to implement an effective multicenter model, with overall F1-score 84.77%, Precision 83.16%, Recall 86.44%. The lessons learned are: (i) the crucial role of a consistent annotation process and (ii) a fine-tuning strategy that combines classical methods with a "few-shot" approach. This allowed us to establish methodological guidelines that pave the way for future implementations in this field and allow Italian hospitals to tap into important research opportunities.

The Novelties corpus is a collection of novels (and parts of novels) annotated for Named Entity Recognition (NER) among other tasks. This document describes the guidelines applied during its annotation. It contains the instructions used by the annotators, as well as a number of examples retrieved from the annotated novels, and illustrating expressions that should be marked as entities as well as expressions that should not.

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

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

Wider access to therapeutic care is one of the biggest challenges in mental health treatment. Due to institutional barriers, some people seeking mental health support have turned to large language models (LLMs) for personalized therapy, even though these models are largely unsanctioned and untested. We investigate the potential and limitations of using LLMs as providers of evidence-based therapy by using mixed methods clinical metrics. Using HELPERT, a prompt run on a large language model using the same process and training as a comparative group of peer counselors, we replicated publicly accessible mental health conversations rooted in Cognitive Behavioral Therapy (CBT) to compare session dynamics and counselor's CBT-based behaviors between original peer support sessions and their reconstructed HELPERT sessions. Two licensed, CBT-trained clinical psychologists evaluated the sessions using the Cognitive Therapy Rating Scale and provided qualitative feedback. Our findings show that the peer sessions are characterized by empathy, small talk, therapeutic alliance, and shared experiences but often exhibit therapist drift. Conversely, HELPERT reconstructed sessions exhibit minimal therapist drift and higher adherence to CBT methods but display a lack of collaboration, empathy, and cultural understanding. Through CTRS ratings and psychologists' feedback, we highlight the importance of human-AI collaboration for scalable mental health. Our work outlines the ethical implication of imparting human-like subjective qualities to LLMs in therapeutic settings, particularly the risk of deceptive empathy, which may lead to unrealistic patient expectations and potential harm.

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

The Novelties corpus is a collection of novels (and parts of novels) annotated for Alias Resolution, among other tasks. This document describes the guidelines applied during the annotation process. It contains the instructions used by the annotators, as well as a number of examples retrieved from the annotated novels, and illustrating how canonical names should be defined, and which names should be considered as referring to the same entity.

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

Developing clinical prediction models (e.g., mortality prediction) based on electronic health records (EHRs) typically relies on expert opinion for feature selection and adjusting observation window size. This burdens experts and creates a bottleneck in the development process. We propose Retrieval-Enhanced Medical prediction model (REMed) to address such challenges. REMed can essentially evaluate an unlimited number of clinical events, select the relevant ones, and make predictions. This approach effectively eliminates the need for manual feature selection and enables an unrestricted observation window. We verified these properties through experiments on 27 clinical tasks and two independent cohorts from publicly available EHR datasets, where REMed outperformed other contemporary architectures that aim to handle as many events as possible. Notably, we found that the preferences of REMed align closely with those of medical experts. We expect our approach to significantly expedite the development of EHR prediction models by minimizing clinicians' need for manual involvement.

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.

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

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.

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

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

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

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

We present Eir Thai Medical LLM, a large language model with 8 billion parameters, specifically designed to enhance the accuracy of handling medical tasks in the Thai language. This model focuses on providing clear and easy-to-understand answers for both healthcare professionals and patients, thereby improving the efficiency of diagnosis and treatment processes. Human evaluation was conducted to ensure that the model adheres to care standards and provides unbiased answers. To prioritize data security, the model is deployed within the hospital's internal network, ensuring both high security and faster processing speeds. The internal API connection is secured with encryption and strict authentication measures to prevent data leaks and unauthorized access. We evaluated several open-source large language models with 8 billion parameters on four medical benchmarks: MedQA, MedMCQA, PubMedQA, and the medical subset of MMLU. The best-performing baselines were used to develop Eir Thai Medical LLM. Our evaluation employed multiple questioning strategies, including zero-shot, few-shot, chain-of-thought reasoning, and ensemble/self-consistency voting methods. Our model outperformed commercially available Thai-language large language models by more than 10%. In addition, we developed enhanced model testing tailored for clinical use in Thai across 18 clinical tasks, where our model exceeded GPT-4o performance by more than 11%

Predictive artificial intelligence (AI) offers an opportunity to improve clinical practice and patient outcomes, but risks perpetuating biases if fairness is inadequately addressed. However, the definition of "fairness" remains unclear. We conducted a scoping review to identify and critically appraise fairness metrics for clinical predictive AI. We defined a "fairness metric" as a measure quantifying whether a model discriminates (societally) against individuals or groups defined by sensitive attributes. We searched five databases (2014-2024), screening 820 records, to include 41 studies, and extracted 62 fairness metrics. Metrics were classified by performance-dependency, model output level, and base performance metric, revealing a fragmented landscape with limited clinical validation and overreliance on threshold-dependent measures. Eighteen metrics were explicitly developed for healthcare, including only one clinical utility metric. Our findings highlight conceptual challenges in defining and quantifying fairness and identify gaps in uncertainty quantification, intersectionality, and real-world applicability. Future work should prioritise clinically meaningful metrics.

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.

The process of annotating data within the legal sector is filled with distinct challenges that differ from other fields, primarily due to the inherent complexities of legal language and documentation. The initial task usually involves selecting an appropriate raw dataset that captures the intricate aspects of legal texts. Following this, extracting text becomes a complicated task, as legal documents often have complex structures, footnotes, references, and unique terminology. The importance of data cleaning is magnified in this context, ensuring that redundant information is eliminated while maintaining crucial legal details and context. Creating comprehensive yet straightforward annotation guidelines is imperative, as these guidelines serve as the road map for maintaining uniformity and addressing the subtle nuances of legal terminology. Another critical aspect is the involvement of legal professionals in the annotation process. Their expertise is valuable in ensuring that the data not only remains contextually accurate but also adheres to prevailing legal standards and interpretations. This paper provides an expanded view of these challenges and aims to offer a foundational understanding and guidance for researchers and professionals engaged in legal data annotation projects. In addition, we provide links to our created and fine-tuned datasets and language models. These resources are outcomes of our discussed projects and solutions to challenges faced while working on them.

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

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

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.

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.

Medical tasks such as diagnosis and treatment planning require precise and complex reasoning, particularly in life-critical domains. Unlike mathematical reasoning, medical reasoning demands meticulous, verifiable thought processes to ensure reliability and accuracy. However, there is a notable lack of datasets that provide transparent, step-by-step reasoning to validate and enhance the medical reasoning ability of AI models. To bridge this gap, we introduce MedReason, a large-scale high-quality medical reasoning dataset designed to enable faithful and explainable medical problem-solving in large language models (LLMs). We utilize a structured medical knowledge graph (KG) to convert clinical QA pairs into logical chains of reasoning, or ``thinking paths'', which trace connections from question elements to answers via relevant KG entities. Each path is validated for consistency with clinical logic and evidence-based medicine. Our pipeline generates detailed reasoning for various medical questions from 7 medical datasets, resulting in a dataset of 32,682 question-answer pairs, each with detailed, step-by-step explanations. Experiments demonstrate that fine-tuning with our dataset consistently boosts medical problem-solving capabilities, achieving significant gains of up to 7.7% for DeepSeek-Ditill-8B. Our top-performing model, MedReason-8B, outperforms the Huatuo-o1-8B, a state-of-the-art medical reasoning model, by up to 4.2% on the clinical benchmark MedBullets. We also engage medical professionals from diverse specialties to assess our dataset's quality, ensuring MedReason offers accurate and coherent medical reasoning. Our data, models, and code will be publicly available.

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

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.

The rapid advancement of large language models (LLMs) has significantly impacted various domains, including healthcare and biomedicine. However, the phenomenon of hallucination, where LLMs generate outputs that deviate from factual accuracy or context, poses a critical challenge, especially in high-stakes domains. This paper conducts a scoping study of existing techniques for mitigating hallucinations in knowledge-based task in general and especially for medical domains. Key methods covered in the paper include Retrieval-Augmented Generation (RAG)-based techniques, iterative feedback loops, supervised fine-tuning, and prompt engineering. These techniques, while promising in general contexts, require further adaptation and optimization for the medical domain due to its unique demands for up-to-date, specialized knowledge and strict adherence to medical guidelines. Addressing these challenges is crucial for developing trustworthy AI systems that enhance clinical decision-making and patient safety as well as accuracy of biomedical scientific research.

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.

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

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

There are substantial instructional videos on the Internet, which provide us tutorials for completing various tasks. Existing instructional video datasets only focus on specific steps at the video level, lacking experiential guidelines at the task level, which can lead to beginners struggling to learn new tasks due to the lack of relevant experience. Moreover, the specific steps without guidelines are trivial and unsystematic, making it difficult to provide a clear tutorial. To address these problems, we present the GUIDE (Guideline-Guided) dataset, which contains 3.5K videos of 560 instructional tasks in 8 domains related to our daily life. Specifically, we annotate each instructional task with a guideline, representing a common pattern shared by all task-related videos. On this basis, we annotate systematic specific steps, including their associated guideline steps, specific step descriptions and timestamps. Our proposed benchmark consists of three sub-tasks to evaluate comprehension ability of models: (1) Step Captioning: models have to generate captions for specific steps from videos. (2) Guideline Summarization: models have to mine the common pattern in task-related videos and summarize a guideline from them. (3) Guideline-Guided Captioning: models have to generate captions for specific steps under the guide of guideline. We evaluate plenty of foundation models with GUIDE and perform in-depth analysis. Given the diversity and practicality of GUIDE, we believe that it can be used as a better benchmark for instructional video comprehension.

Patient recruitment is challenging for clinical trials. We introduce TrialGPT, an end-to-end framework for zero-shot patient-to-trial matching with large language models. TrialGPT comprises three modules: it first performs large-scale filtering to retrieve candidate trials (TrialGPT-Retrieval); then predicts criterion-level patient eligibility (TrialGPT-Matching); and finally generates trial-level scores (TrialGPT-Ranking). We evaluate TrialGPT on three cohorts of 183 synthetic patients with over 75,000 trial annotations. TrialGPT-Retrieval can recall over 90% of relevant trials using less than 6% of the initial collection. Manual evaluations on 1,015 patient-criterion pairs show that TrialGPT-Matching achieves an accuracy of 87.3% with faithful explanations, close to the expert performance. The TrialGPT-Ranking scores are highly correlated with human judgments and outperform the best-competing models by 43.8% in ranking and excluding trials. Furthermore, our user study reveals that TrialGPT can reduce the screening time by 42.6% in patient recruitment. Overall, these results have demonstrated promising opportunities for patient-to-trial matching with TrialGPT.

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

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

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

Objective:Develop and validate an algorithm for analyzing the layout of PDF clinical documents to improve the performance of downstream natural language processing tasks. Materials and Methods: We designed an algorithm to process clinical PDF documents and extract only clinically relevant text. The algorithm consists of several steps: initial text extraction using a PDF parser, followed by classification into categories such as body text, left notes, and footers using a Transformer deep neural network architecture, and finally an aggregation step to compile the lines of a given label in the text. We evaluated the technical performance of the body text extraction algorithm by applying it to a random sample of documents that were annotated. Medical performance was evaluated by examining the extraction of medical concepts of interest from the text in their respective sections. Finally, we tested an end-to-end system on a medical use case of automatic detection of acute infection described in the hospital report. Results:Our algorithm achieved per-line precision, recall, and F1 score of 98.4, 97.0, and 97.7, respectively, for body line extraction. The precision, recall, and F1 score per document for the acute infection detection algorithm were 82.54 (95CI 72.86-91.60), 85.24 (95CI 76.61-93.70), 83.87 (95CI 76, 92-90.08) with exploitation of the results of the advanced body extraction algorithm, respectively. Conclusion:We have developed and validated a system for extracting body text from clinical documents in PDF format by identifying their layout. We were able to demonstrate that this preprocessing allowed us to obtain better performances for a common downstream task, i.e., the extraction of medical concepts in their respective sections, thus proving the interest of this method on a clinical use case.

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

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

Large Language Models (LLMs) provide a possibility to make a great breakthrough in medicine. The establishment of a standardized medical benchmark becomes a fundamental cornerstone to measure progression. However, medical environments in different regions have their local characteristics, e.g., the ubiquity and significance of traditional Chinese medicine within China. Therefore, merely translating English-based medical evaluation may result in contextual incongruities to a local region. To solve the issue, we propose a localized medical benchmark called CMB, a Comprehensive Medical Benchmark in Chinese, designed and rooted entirely within the native Chinese linguistic and cultural framework. While traditional Chinese medicine is integral to this evaluation, it does not constitute its entirety. Using this benchmark, we have evaluated several prominent large-scale LLMs, including ChatGPT, GPT-4, dedicated Chinese LLMs, and LLMs specialized in the medical domain. It is worth noting that our benchmark is not devised as a leaderboard competition but as an instrument for self-assessment of model advancements. We hope this benchmark could facilitate the widespread adoption and enhancement of medical LLMs within China. Check details in https://cmedbenchmark.llmzoo.com/.

Clinical texts, represented in electronic medical records (EMRs), contain rich medical information and are essential for disease prediction, personalised information recommendation, clinical decision support, and medication pattern mining and measurement. Relation extractions between medication mentions and temporal information can further help clinicians better understand the patients' treatment history. To evaluate the performances of deep learning (DL) and large language models (LLMs) in medication extraction and temporal relations classification, we carry out an empirical investigation of MedTem project using several advanced learning structures including BiLSTM-CRF and CNN-BiLSTM for a clinical domain named entity recognition (NER), and BERT-CNN for temporal relation extraction (RE), in addition to the exploration of different word embedding techniques. Furthermore, we also designed a set of post-processing roles to generate structured output on medications and the temporal relation. Our experiments show that CNN-BiLSTM slightly wins the BiLSTM-CRF model on the i2b2-2009 clinical NER task yielding 75.67, 77.83, and 78.17 for precision, recall, and F1 scores using Macro Average. BERT-CNN model also produced reasonable evaluation scores 64.48, 67.17, and 65.03 for P/R/F1 using Macro Avg on the temporal relation extraction test set from i2b2-2012 challenges. Code and Tools from MedTem will be hosted at https://github.com/HECTA-UoM/MedTem

Seeking health-related advice on the internet has become a common practice in the digital era. Determining the trustworthiness of medical claims found online and finding appropriate evidence for this information is increasingly challenging. Fact-checking has emerged as an approach to assess the veracity of factual claims using evidence from credible knowledge sources. To help advance the automation of this task, in this paper, we introduce a novel dataset of 750 health-related claims, labeled for veracity by medical experts and backed with evidence from appropriate clinical studies. We provide an analysis of the dataset, highlighting its characteristics and challenges. The dataset can be used for Machine Learning tasks related to automated fact-checking such as evidence retrieval, veracity prediction, and explanation generation. For this purpose, we provide baseline models based on different approaches, examine their performance, and discuss the findings.

Checklists are simple decision aids that are often used to promote safety and reliability in clinical applications. In this paper, we present a method to learn checklists for clinical decision support. We represent predictive checklists as discrete linear classifiers with binary features and unit weights. We then learn globally optimal predictive checklists from data by solving an integer programming problem. Our method allows users to customize checklists to obey complex constraints, including constraints to enforce group fairness and to binarize real-valued features at training time. In addition, it pairs models with an optimality gap that can inform model development and determine the feasibility of learning sufficiently accurate checklists on a given dataset. We pair our method with specialized techniques that speed up its ability to train a predictive checklist that performs well and has a small optimality gap. We benchmark the performance of our method on seven clinical classification problems, and demonstrate its practical benefits by training a short-form checklist for PTSD screening. Our results show that our method can fit simple predictive checklists that perform well and that can easily be customized to obey a rich class of custom constraints.

The utilization of clinical reports for various secondary purposes, including health research and treatment monitoring, is crucial for enhancing patient care. Natural Language Processing (NLP) tools have emerged as valuable assets for extracting and processing relevant information from these reports. However, the availability of specialized language models for the clinical domain in Spanish has been limited. In this paper, we introduce EriBERTa, a bilingual domain-specific language model pre-trained on extensive medical and clinical corpora. We demonstrate that EriBERTa outperforms previous Spanish language models in the clinical domain, showcasing its superior capabilities in understanding medical texts and extracting meaningful information. Moreover, EriBERTa exhibits promising transfer learning abilities, allowing for knowledge transfer from one language to another. This aspect is particularly beneficial given the scarcity of Spanish clinical data.

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

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

Daily progress notes are common types in the electronic health record (EHR) where healthcare providers document the patient's daily progress and treatment plans. The EHR is designed to document all the care provided to patients, but it also enables note bloat with extraneous information that distracts from the diagnoses and treatment plans. Applications of natural language processing (NLP) in the EHR is a growing field with the majority of methods in information extraction. Few tasks use NLP methods for downstream diagnostic decision support. We introduced the 2022 National NLP Clinical Challenge (N2C2) Track 3: Progress Note Understanding - Assessment and Plan Reasoning as one step towards a new suite of tasks. The Assessment and Plan Reasoning task focuses on the most critical components of progress notes, Assessment and Plan subsections where health problems and diagnoses are contained. The goal of the task was to develop and evaluate NLP systems that automatically predict causal relations between the overall status of the patient contained in the Assessment section and its relation to each component of the Plan section which contains the diagnoses and treatment plans. The goal of the task was to identify and prioritize diagnoses as the first steps in diagnostic decision support to find the most relevant information in long documents like daily progress notes. We present the results of 2022 n2c2 Track 3 and provide a description of the data, evaluation, participation and system performance.

Hypertension, defined as blood pressure (BP) that is above normal, holds paramount significance in the realm of public health, as it serves as a critical precursor to various cardiovascular diseases (CVDs) and significantly contributes to elevated mortality rates worldwide. However, many existing BP measurement technologies and standards might be biased because they do not consider clinical outcomes, comorbidities, or demographic factors, making them inconclusive for diagnostic purposes. There is limited data-driven research focused on studying the variance in BP measurements across these variables. In this work, we employed GPT-35-turbo, a large language model (LLM), to automatically extract the mean and standard deviation values of BP for both males and females from a dataset comprising 25 million abstracts sourced from PubMed. 993 article abstracts met our predefined inclusion criteria (i.e., presence of references to blood pressure, units of blood pressure such as mmHg, and mention of biological sex). Based on the automatically-extracted information from these articles, we conducted an analysis of the variations of BP values across biological sex. Our results showed the viability of utilizing LLMs to study the BP variations across different demographic factors.

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.

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

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

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

In this study, we investigated the ability of the large language model (LLM) to enhance healthcare data interoperability. We leveraged the LLM to convert clinical texts into their corresponding FHIR resources. Our experiments, conducted on 3,671 snippets of clinical text, demonstrated that the LLM not only streamlines the multi-step natural language processing and human calibration processes but also achieves an exceptional accuracy rate of over 90% in exact matches when compared to human annotations.

Brief hospital course (BHC) summaries are common clinical documents generated by summarizing clinical notes. While large language models (LLMs) depict remarkable capabilities in automating real-world tasks, their capabilities for healthcare applications such as BHC synthesis have not been shown. To enable the adaptation of LLMs for BHC synthesis, we introduce a novel benchmark consisting of a pre-processed dataset extracted from MIMIC-IV notes, encapsulating clinical note, and brief hospital course (BHC) pairs. We assess the performance of two general-purpose LLMs and three healthcare-adapted LLMs to improve BHC synthesis from clinical notes. Using clinical notes as input for generating BHCs, we apply prompting-based (using in-context learning) and fine-tuning-based adaptation strategies to three open-source LLMs (Clinical-T5-Large, Llama2-13B, FLAN-UL2) and two proprietary LLMs (GPT-3.5, GPT-4). We quantitatively evaluate the performance of these LLMs across varying context-length inputs using conventional natural language similarity metrics. We further perform a qualitative study where five diverse clinicians blindly compare clinician-written BHCs and two LLM-generated BHCs for 30 samples across metrics of comprehensiveness, conciseness, factual correctness, and fluency. Overall, we present a new benchmark and pre-processed dataset for using LLMs in BHC synthesis from clinical notes. We observe high-quality summarization performance for both in-context proprietary and fine-tuned open-source LLMs using both quantitative metrics and a qualitative clinical reader study. We propose our work as a benchmark to motivate future works to adapt and assess the performance of LLMs in BHC synthesis.

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

Background: Clinical documentation represents a significant burden for healthcare providers, with physicians spending up to 2 hours daily on administrative tasks. Recent advances in large language models (LLMs) offer promising solutions, but privacy concerns and computational requirements limit their adoption in healthcare settings. Objective: To develop and evaluate a privacy-preserving, on-device medical transcription system using a fine-tuned Llama 3.2 1B model capable of generating structured medical notes from medical transcriptions while maintaining complete data sovereignty entirely in the browser. Methods: We fine-tuned a Llama 3.2 1B model using Parameter-Efficient Fine-Tuning (PEFT) with LoRA on 1,500 synthetic medical transcription-to-structured note pairs. The model was evaluated against the base Llama 3.2 1B on two datasets: 100 endocrinology transcripts and 140 modified ACI benchmark cases. Evaluation employed both statistical metrics (ROUGE, BERTScore, BLEURT) and LLM-as-judge assessments across multiple clinical quality dimensions. Results: The fine-tuned OnDevice model demonstrated substantial improvements over the base model. On the ACI benchmark, ROUGE-1 scores increased from 0.346 to 0.496, while BERTScore F1 improved from 0.832 to 0.866. Clinical quality assessments showed marked reduction in major hallucinations (from 85 to 35 cases) and enhanced factual correctness (2.81 to 3.54 on 5-point scale). Similar improvements were observed on the internal evaluation dataset, with composite scores increasing from 3.13 to 4.43 (+41.5%). Conclusions: Fine-tuning compact LLMs for medical transcription yields clinically meaningful improvements while enabling complete on-device browser deployment. This approach addresses key barriers to AI adoption in healthcare: privacy preservation, cost reduction, and accessibility for resource-constrained environments.

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

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

The absence of transparency and explainability hinders the clinical adoption of Machine learning (ML) algorithms. Although various methods of explainable artificial intelligence (XAI) have been suggested, there is a lack of literature that delves into their practicality and assesses them based on criteria that could foster trust in clinical environments. To address this gap this study evaluates two popular XAI methods used for explaining predictive models in the healthcare context in terms of whether they (i) generate domain-appropriate representation, i.e. coherent with respect to the application task, (ii) impact clinical workflow and (iii) are consistent. To that end, explanations generated at the cohort and patient levels were analysed. The paper reports the first benchmarking of the XAI methods applied to risk prediction models obtained by evaluating the concordance between generated explanations and the trigger of a future clinical deterioration episode recorded by the data collection system. We carried out an analysis using two Electronic Medical Records (EMR) datasets sourced from Australian major hospitals. The findings underscore the limitations of state-of-the-art XAI methods in the clinical context and their potential benefits. We discuss these limitations and contribute to the theoretical development of trustworthy XAI solutions where clinical decision support guides the choice of intervention by suggesting the pattern or drivers for clinical deterioration in the future.

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

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

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

Meta-analyses statistically aggregate the findings of different randomized controlled trials (RCTs) to assess treatment effectiveness. Because this yields robust estimates of treatment effectiveness, results from meta-analyses are considered the strongest form of evidence. However, rigorous evidence syntheses are time-consuming and labor-intensive, requiring manual extraction of data from individual trials to be synthesized. Ideally, language technologies would permit fully automatic meta-analysis, on demand. This requires accurately extracting numerical results from individual trials, which has been beyond the capabilities of natural language processing (NLP) models to date. In this work, we evaluate whether modern large language models (LLMs) can reliably perform this task. We annotate (and release) a modest but granular evaluation dataset of clinical trial reports with numerical findings attached to interventions, comparators, and outcomes. Using this dataset, we evaluate the performance of seven LLMs applied zero-shot for the task of conditionally extracting numerical findings from trial reports. We find that massive LLMs that can accommodate lengthy inputs are tantalizingly close to realizing fully automatic meta-analysis, especially for dichotomous (binary) outcomes (e.g., mortality). However, LLMs -- including ones trained on biomedical texts -- perform poorly when the outcome measures are complex and tallying the results requires inference. This work charts a path toward fully automatic meta-analysis of RCTs via LLMs, while also highlighting the limitations of existing models for this aim.

Although recent advances in scaling large language models (LLMs) have resulted in improvements on many NLP tasks, it remains unclear whether these models trained primarily with general web text are the right tool in highly specialized, safety critical domains such as clinical text. Recent results have suggested that LLMs encode a surprising amount of medical knowledge. This raises an important question regarding the utility of smaller domain-specific language models. With the success of general-domain LLMs, is there still a need for specialized clinical models? To investigate this question, we conduct an extensive empirical analysis of 12 language models, ranging from 220M to 175B parameters, measuring their performance on 3 different clinical tasks that test their ability to parse and reason over electronic health records. As part of our experiments, we train T5-Base and T5-Large models from scratch on clinical notes from MIMIC III and IV to directly investigate the efficiency of clinical tokens. We show that relatively small specialized clinical models substantially outperform all in-context learning approaches, even when finetuned on limited annotated data. Further, we find that pretraining on clinical tokens allows for smaller, more parameter-efficient models that either match or outperform much larger language models trained on general text. We release the code and the models used under the PhysioNet Credentialed Health Data license and data use agreement.

Knowledge of the medical decision process, which can be modeled as medical decision trees (MDTs), is critical to build clinical decision support systems. However, the current MDT construction methods rely heavily on time-consuming and laborious manual annotation. In this work, we propose a novel task, Text2MDT, to explore the automatic extraction of MDTs from medical texts such as medical guidelines and textbooks. We normalize the form of the MDT and create an annotated Text-to-MDT dataset in Chinese with the participation of medical experts. We investigate two different methods for the Text2MDT tasks: (a) an end-to-end framework which only relies on a GPT style large language models (LLM) instruction tuning to generate all the node information and tree structures. (b) The pipeline framework which decomposes the Text2MDT task to three subtasks. Experiments on our Text2MDT dataset demonstrate that: (a) the end-to-end method basd on LLMs (7B parameters or larger) show promising results, and successfully outperform the pipeline methods. (b) The chain-of-thought (COT) prompting method Wei2022ChainOT can improve the performance of the fine-tuned LLMs on the Text2MDT test set. (c) the lightweight pipelined method based on encoder-based pretrained models can perform comparably with LLMs with model complexity two magnititudes smaller. Our Text2MDT dataset is open-sourced at https://tianchi.aliyun.com/dataset/95414, and the source codes are open-sourced at https://github.com/michael-wzhu/text2dt.

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

We introduce a general, flexible, parametric survival modelling framework which encompasses key shapes of hazard function (constant, increasing, decreasing, up-then-down, down-then-up), various common survival distributions (log-logistic, Burr type XII, Weibull, Gompertz), and includes defective distributions (i.e., cure models). This generality is achieved using four basic distributional parameters: two scale-type parameters and two shape parameters. Generalising to covariate dependence, the scale-type regression components correspond to accelerated failure time (AFT) and proportional hazards (PH) models. Therefore, this general formulation unifies the most popular survival models which allows us to consider the practical value of possible modelling choices for survival data. Furthermore, in line with our proposed flexible baseline distribution, we advocate the use of multi-parameter regression in which more than one distributional parameter depends on covariates - rather than the usual convention of having a single covariate-dependent (scale) parameter. While many choices are available, we suggest introducing covariates through just one or other of the two scale parameters, which covers AFT and PH models, in combination with a `power' shape parameter, which allows for more complex non-AFT/non-PH effects, while the other shape parameter remains covariate-independent, and handles automatic selection of the baseline distribution. We explore inferential issues in simulations, both with and without a covariate, with particular focus on evidence concerning the need, or otherwise, to include both AFT and PH parameters. We illustrate the efficacy of our modelling framework by investigating differences between treatment groups using data from a lung cancer study and a melanoma study. Censoring is accommodated throughout.

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.

Cancer patients are increasingly turning to large language models (LLMs) as a new form of internet search for medical information, making it critical to assess how well these models handle complex, personalized questions. However, current medical benchmarks focus on medical exams or consumer-searched questions and do not evaluate LLMs on real patient questions with detailed clinical contexts. In this paper, we first evaluate LLMs on cancer-related questions drawn from real patients, reviewed by three hematology oncology physicians. While responses are generally accurate, with GPT-4-Turbo scoring 4.13 out of 5, the models frequently fail to recognize or address false presuppositions in the questions-posing risks to safe medical decision-making. To study this limitation systematically, we introduce Cancer-Myth, an expert-verified adversarial dataset of 585 cancer-related questions with false presuppositions. On this benchmark, no frontier LLM -- including GPT-4o, Gemini-1.Pro, and Claude-3.5-Sonnet -- corrects these false presuppositions more than 30% of the time. Even advanced medical agentic methods do not prevent LLMs from ignoring false presuppositions. These findings expose a critical gap in the clinical reliability of LLMs and underscore the need for more robust safeguards in medical AI systems.

BACKGROUND: Radiology reports are typically written in a free-text format, making clinical information difficult to extract and use. Recently the adoption of structured reporting (SR) has been recommended by various medical societies thanks to the advantages it offers, e.g. standardization, completeness and information retrieval. We propose a pipeline to extract information from free-text radiology reports, that fits with the items of the reference SR registry proposed by a national society of interventional and medical radiology, focusing on CT staging of patients with lymphoma. METHODS: Our work aims to leverage the potential of Natural Language Processing (NLP) and Transformer-based models to deal with automatic SR registry filling. With the availability of 174 radiology reports, we investigate a rule-free generative Question Answering approach based on a domain-specific version of T5 (IT5). Two strategies (batch-truncation and ex-post combination) are implemented to comply with the model's context length limitations. Performance is evaluated in terms of strict accuracy, F1, and format accuracy, and compared with the widely used GPT-3.5 Large Language Model. A 5-point Likert scale questionnaire is used to collect human-expert feedback on the similarity between medical annotations and generated answers. RESULTS: The combination of fine-tuning and batch splitting allows IT5 to achieve notable results; it performs on par with GPT-3.5 albeit its size being a thousand times smaller in terms of parameters. Human-based assessment scores show a high correlation (Spearman's correlation coefficients>0.88, p-values<0.001) with AI performance metrics (F1) and confirm the superior ability of LLMs (i.e., GPT-3.5, 175B of parameters) in generating plausible human-like statements.

There are two main barriers to using large language models (LLMs) in clinical reasoning. Firstly, while LLMs exhibit significant promise in Natural Language Processing (NLP) tasks, their performance in complex reasoning and planning falls short of expectations. Secondly, LLMs use uninterpretable methods to make clinical decisions that are fundamentally different from the clinician's cognitive processes. This leads to user distrust. In this paper, we present a multi-agent framework called ArgMed-Agents, which aims to enable LLM-based agents to make explainable clinical decision reasoning through interaction. ArgMed-Agents performs self-argumentation iterations via Argumentation Scheme for Clinical Discussion (a reasoning mechanism for modeling cognitive processes in clinical reasoning), and then constructs the argumentation process as a directed graph representing conflicting relationships. Ultimately, use symbolic solver to identify a series of rational and coherent arguments to support decision. We construct a formal model of ArgMed-Agents and present conjectures for theoretical guarantees. ArgMed-Agents enables LLMs to mimic the process of clinical argumentative reasoning by generating explanations of reasoning in a self-directed manner. The setup experiments show that ArgMed-Agents not only improves accuracy in complex clinical decision reasoning problems compared to other prompt methods, but more importantly, it provides users with decision explanations that increase their confidence.

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.

Decisions about managing patients on the heart transplant waitlist are currently made by committees of doctors who consider multiple factors, but the process remains largely ad-hoc. With the growing volume of longitudinal patient, donor, and organ data collected by the United Network for Organ Sharing (UNOS) since 2018, there is increasing interest in analytical approaches to support clinical decision-making at the time of organ availability. In this study, we benchmark machine learning models that leverage longitudinal waitlist history data for time-dependent, time-to-event modeling of waitlist mortality. We train on 23,807 patient records with 77 variables and evaluate both survival prediction and discrimination at a 1-year horizon. Our best model achieves a C-Index of 0.94 and AUROC of 0.89, significantly outperforming previous models. Key predictors align with known risk factors while also revealing novel associations. Our findings can support urgency assessment and policy refinement in heart transplant decision making.

The rapid evolution of Large Language Models (LLMs) offers promising potential to alleviate the global scarcity of mental health professionals. However, LLMs' alignment with essential mental health counseling competencies remains understudied. We introduce CounselingBench, a novel NCMHCE-based benchmark evaluating LLMs across five key mental health counseling competencies. Testing 22 general-purpose and medical-finetuned LLMs, we find frontier models exceed minimum thresholds but fall short of expert-level performance, with significant variations: they excel in Intake, Assessment & Diagnosis yet struggle with Core Counseling Attributes and Professional Practice & Ethics. Medical LLMs surprisingly underperform generalist models accuracy-wise, while at the same time producing slightly higher-quality justifications but making more context-related errors. Our findings highlight the complexities of developing AI systems for mental health counseling, particularly for competencies requiring empathy and contextual understanding. We found that frontier LLMs perform at a level exceeding the minimal required level of aptitude for all key mental health counseling competencies, but fall short of expert-level performance, and that current medical LLMs do not significantly improve upon generalist models in mental health counseling competencies. This underscores the critical need for specialized, mental health counseling-specific fine-tuned LLMs that rigorously aligns with core competencies combined with appropriate human supervision before any responsible real-world deployment can be considered.

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.

Sifting through vast textual data and summarizing key information imposes a substantial burden on how clinicians allocate their time. Although large language models (LLMs) have shown immense promise in natural language processing (NLP) tasks, their efficacy across diverse clinical summarization tasks has not yet been rigorously examined. In this work, we employ domain adaptation methods on eight LLMs, spanning six datasets and four distinct summarization tasks: radiology reports, patient questions, progress notes, and doctor-patient dialogue. Our thorough quantitative assessment reveals trade-offs between models and adaptation methods in addition to instances where recent advances in LLMs may not lead to improved results. Further, in a clinical reader study with six physicians, we depict that summaries from the best adapted LLM are preferable to human summaries in terms of completeness and correctness. Our ensuing qualitative analysis delineates mutual challenges faced by both LLMs and human experts. Lastly, we correlate traditional quantitative NLP metrics with reader study scores to enhance our understanding of how these metrics align with physician preferences. Our research marks the first evidence of LLMs outperforming human experts in clinical text summarization across multiple tasks. This implies that integrating LLMs into clinical workflows could alleviate documentation burden, empowering clinicians to focus more on personalized patient care and other irreplaceable human aspects of medicine.

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

With Artificial Intelligence (AI) increasingly permeating various aspects of society, including healthcare, the adoption of the Transformers neural network architecture is rapidly changing many applications. Transformer is a type of deep learning architecture initially developed to solve general-purpose Natural Language Processing (NLP) tasks and has subsequently been adapted in many fields, including healthcare. In this survey paper, we provide an overview of how this architecture has been adopted to analyze various forms of data, including medical imaging, structured and unstructured Electronic Health Records (EHR), social media, physiological signals, and biomolecular sequences. Those models could help in clinical diagnosis, report generation, data reconstruction, and drug/protein synthesis. We identified relevant studies using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We also discuss the benefits and limitations of using transformers in healthcare and examine issues such as computational cost, model interpretability, fairness, alignment with human values, ethical implications, and environmental impact.

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.

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

Detecting breast cancer early is of the utmost importance to effectively treat the millions of women afflicted by breast cancer worldwide every year. Although mammography is the primary imaging modality for screening breast cancer, there is an increasing interest in adding magnetic resonance imaging (MRI) to screening programmes, particularly for women at high risk. Recent guidelines by the European Society of Breast Imaging (EUSOBI) recommended breast MRI as a supplemental screening tool for women with dense breast tissue. However, acquiring and reading MRI scans requires significantly more time from expert radiologists. This highlights the need to develop new automated methods to detect cancer accurately using MRI and Artificial Intelligence (AI), which have the potential to support radiologists in breast MRI interpretation and classification and help detect cancer earlier. For this reason, the ODELIA consortium has made this multi-centre dataset publicly available to assist in developing AI tools for the detection of breast cancer on MRI.

We introduce SoftTiger, a clinical large language model (CLaM) designed as a foundation model for healthcare workflows. The narrative and unstructured nature of clinical notes is a major obstacle for healthcare intelligentization. We address a critical problem of structuring clinical notes into clinical data, according to international interoperability standards. We collect and annotate data for three subtasks, namely, international patient summary, clinical impression and medical encounter. We then supervised fine-tuned a state-of-the-art LLM using public and credentialed clinical data. The training is orchestrated in a way that the target model can first support basic clinical tasks such as abbreviation expansion and temporal information extraction, and then learn to perform more complex downstream clinical tasks. Moreover, we address several modeling challenges in the healthcare context, e.g., extra long context window. Our blind pairwise evaluation shows that SoftTiger outperforms other popular open-source models and GPT-3.5, comparable to Gemini-pro, with a mild gap from GPT-4. We believe that LLMs may become a step-stone towards healthcare digitalization and democratization. Therefore, we publicly release SoftTiger models at scales of 13 billion and 70 billion parameters, as well as datasets and code for our innovative scalable evaluation, hopefully, making a significant contribution to the healthcare industry.

Introduction. Generative Artificial Intelligence, particularly large language models (LLMs), offers transformative potential for Health Economics and Outcomes Research (HEOR). However, evaluating the quality, transparency, and rigor of LLM-assisted research lacks standardized guidance. This article introduces the ELEVATE AI LLMs framework and checklist, designed to support researchers and reviewers in assessing LLM use in HEOR. Methods. The ELEVATE AI LLMs framework was developed through a targeted review of existing guidelines and evaluation frameworks. The framework comprises ten evaluation domains, including model characteristics, accuracy, comprehensiveness, and fairness. The accompanying checklist operationalizes the framework. To validate the framework, we applied it to two published studies, demonstrating its usability across different HEOR tasks. Results. The ELEVATE AI LLMs framework provides a comprehensive structure for evaluating LLM-assisted research, while the checklist facilitates practical application. Validation of the framework and checklist on studies of systematic literature reviews and health economic modeling highlighted their ability to identify strengths and gaps in reporting. Limitations. While the ELEVATE AI LLMs framework provides robust guidance, its broader generalizability and applicability to diverse HEOR tasks require further empirical testing. Additionally, several metrics adapted from computer science need further validation in HEOR contexts. Conclusion. The ELEVATE AI LLMs framework and checklist fill a critical gap in HEOR by offering structured guidance for evaluating LLM-assisted research. By promoting transparency, accuracy, and reproducibility, they aim to standardize and improve the integration of LLMs into HEOR, ensuring their outputs meet the field's rigorous standards.

Over the course of the COVID-19 pandemic, large volumes of biomedical information concerning this new disease have been published on social media. Some of this information can pose a real danger to people's health, particularly when false information is shared, for instance recommendations on how to treat diseases without professional medical advice. Therefore, automatic fact-checking resources and systems developed specifically for the medical domain are crucial. While existing fact-checking resources cover COVID-19-related information in news or quantify the amount of misinformation in tweets, there is no dataset providing fact-checked COVID-19-related Twitter posts with detailed annotations for biomedical entities, relations and relevant evidence. We contribute CoVERT, a fact-checked corpus of tweets with a focus on the domain of biomedicine and COVID-19-related (mis)information. The corpus consists of 300 tweets, each annotated with medical named entities and relations. We employ a novel crowdsourcing methodology to annotate all tweets with fact-checking labels and supporting evidence, which crowdworkers search for online. This methodology results in moderate inter-annotator agreement. Furthermore, we use the retrieved evidence extracts as part of a fact-checking pipeline, finding that the real-world evidence is more useful than the knowledge indirectly available in pretrained language models.

Nowadays the medical domain is receiving more and more attention in applications involving Artificial Intelligence. Clinicians have to deal with an enormous amount of unstructured textual data to make a conclusion about patients' health in their everyday life. Argument mining helps to provide a structure to such data by detecting argumentative components in the text and classifying the relations between them. However, as it is the case for many tasks in Natural Language Processing in general and in medical text processing in particular, the large majority of the work on computational argumentation has been done only for English. This is also the case with the only dataset available for argumentation in the medical domain, namely, the annotated medical data of abstracts of Randomized Controlled Trials (RCT) from the MEDLINE database. In order to mitigate the lack of annotated data for other languages, we empirically investigate several strategies to perform argument mining and classification in medical texts for a language for which no annotated data is available. This project shows that automatically translating and project annotations from English to a target language (Spanish) is an effective way to generate annotated data without manual intervention. Furthermore, our experiments demonstrate that the translation and projection approach outperforms zero-shot cross-lingual approaches using a large masked multilingual language model. Finally, we show how the automatically generated data in Spanish can also be used to improve results in the original English evaluation setting.

Generalist foundation models such as GPT-4 have displayed surprising capabilities in a wide variety of domains and tasks. Yet, there is a prevalent assumption that they cannot match specialist capabilities of fine-tuned models. For example, most explorations to date on medical competency benchmarks have leveraged domain-specific training, as exemplified by efforts on BioGPT and Med-PaLM. We build on a prior study of GPT-4's capabilities on medical challenge benchmarks in the absence of special training. Rather than using simple prompting to highlight the model's out-of-the-box capabilities, we perform a systematic exploration of prompt engineering. We find that prompting innovation can unlock deeper specialist capabilities and show that GPT-4 easily tops prior leading results for medical benchmarks. The prompting methods we explore are general purpose, and make no specific use of domain expertise, removing the need for expert-curated content. Our experimental design carefully controls for overfitting during the prompt engineering process. We introduce Medprompt, based on a composition of several prompting strategies. With Medprompt, GPT-4 achieves state-of-the-art results on all nine of the benchmark datasets in the MultiMedQA suite. The method outperforms leading specialist models such as Med-PaLM 2 by a significant margin with an order of magnitude fewer calls to the model. Steering GPT-4 with Medprompt achieves a 27% reduction in error rate on the MedQA dataset over the best methods to date achieved with specialist models and surpasses a score of 90% for the first time. Beyond medical problems, we show the power of Medprompt to generalize to other domains and provide evidence for the broad applicability of the approach via studies of the strategy on exams in electrical engineering, machine learning, philosophy, accounting, law, nursing, and clinical psychology.

With the growing use of language models (LMs) in clinical environments, there is an immediate need to evaluate the accuracy and safety of LM-generated medical text. Currently, such evaluation relies solely on manual physician review. However, detecting errors in LM-generated text is challenging because 1) manual review is costly and 2) expert-composed reference outputs are often unavailable in real-world settings. While the "LM-as-judge" paradigm (a LM evaluating another LM) offers scalable evaluation, even frontier LMs can miss subtle but clinically significant errors. To address these challenges, we propose MedVAL, a self-supervised framework that leverages synthetic data to train evaluator LMs to assess whether LM-generated medical outputs are factually consistent with inputs, without requiring physician labels or reference outputs. To evaluate LM performance, we introduce MedVAL-Bench, a dataset containing 840 outputs annotated by physicians, following a physician-defined taxonomy of risk levels and error categories. Across 6 diverse medical tasks and 10 state-of-the-art LMs spanning open-source, proprietary, and medically adapted models, MedVAL fine-tuning significantly improves (p < 0.001) alignment with physicians on both seen and unseen tasks, increasing average F1 scores from 66% to 83%, with per-sample safety classification scores up to 86%. MedVAL improves the performance of even the best-performing proprietary LM (GPT-4o) by 8%. To support a scalable, risk-aware pathway towards clinical integration, we open-source the 1) codebase ( https://github.com/StanfordMIMI/MedVAL ), 2) MedVAL-Bench ( https://huggingface.co/datasets/stanfordmimi/MedVAL-Bench ), and 3) MedVAL-4B ( https://huggingface.co/stanfordmimi/MedVAL-4B ), the best-performing open-source LM. Our research provides the first evidence of LMs approaching expert-level validation ability for medical text.

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

Skin conditions affect an estimated 1.9 billion people worldwide. A shortage of dermatologists causes long wait times and leads patients to seek dermatologic care from general practitioners. However, the diagnostic accuracy of general practitioners has been reported to be only 0.24-0.70 (compared to 0.77-0.96 for dermatologists), resulting in referral errors, delays in care, and errors in diagnosis and treatment. In this paper, we developed a deep learning system (DLS) to provide a differential diagnosis of skin conditions for clinical cases (skin photographs and associated medical histories). The DLS distinguishes between 26 skin conditions that represent roughly 80% of the volume of skin conditions seen in primary care. The DLS was developed and validated using de-identified cases from a teledermatology practice serving 17 clinical sites via a temporal split: the first 14,021 cases for development and the last 3,756 cases for validation. On the validation set, where a panel of three board-certified dermatologists defined the reference standard for every case, the DLS achieved 0.71 and 0.93 top-1 and top-3 accuracies respectively. For a random subset of the validation set (n=963 cases), 18 clinicians reviewed the cases for comparison. On this subset, the DLS achieved a 0.67 top-1 accuracy, non-inferior to board-certified dermatologists (0.63, p<0.001), and higher than primary care physicians (PCPs, 0.45) and nurse practitioners (NPs, 0.41). The top-3 accuracy showed a similar trend: 0.90 DLS, 0.75 dermatologists, 0.60 PCPs, and 0.55 NPs. These results highlight the potential of the DLS to augment general practitioners to accurately diagnose skin conditions by suggesting differential diagnoses that may not have been considered. Future work will be needed to prospectively assess the clinical impact of using this tool in actual clinical workflows.