Daily Papers

This study presents a comprehensive analysis and comparison of two predominant fine-tuning methodologies - full-parameter fine-tuning and parameter-efficient tuning - within the context of medical Large Language Models (LLMs). We developed and refined a series of LLMs, based on the Llama-2 architecture, specifically designed to enhance medical knowledge retrieval, reasoning, and question-answering capabilities. Our experiments systematically evaluate the effectiveness of these tuning strategies across various well-known medical benchmarks. Notably, our medical LLM Med42 showed an accuracy level of 72% on the US Medical Licensing Examination (USMLE) datasets, setting a new standard in performance for openly available medical LLMs. Through this comparative analysis, we aim to identify the most effective and efficient method for fine-tuning LLMs in the medical domain, thereby contributing significantly to the advancement of AI-driven healthcare applications.

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.

Recent advancements in machine learning and natural language processing have led to the rapid development of artificial intelligence (AI) as a valuable tool in the healthcare industry. Using large language models (LLMs) as conversational agents or chatbots has the potential to assist doctors in diagnosing patients, detecting early symptoms of diseases, and providing health advice to patients. This paper focuses on the role of chatbots in healthcare and explores the use of avatars to make AI interactions more appealing to patients. A framework of a general-purpose AI avatar application is demonstrated by using a three-category prompt dictionary and prompt improvement mechanism. A two-phase approach is suggested to fine-tune a general-purpose AI language model and create different AI avatars to discuss medical issues with users. Prompt engineering enhances the chatbot's conversational abilities and personality traits, fostering a more human-like interaction with patients. Ultimately, the injection of personality into the chatbot could potentially increase patient engagement. Future directions for research include investigating ways to improve chatbots' understanding of context and ensuring the accuracy of their outputs through fine-tuning with specialized medical data sets.

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

The utilization of large language models (LLMs) in the Healthcare domain has generated both excitement and concern due to their ability to effectively respond to freetext queries with certain professional knowledge. This survey outlines the capabilities of the currently developed LLMs for Healthcare and explicates their development process, with the aim of providing an overview of the development roadmap from traditional Pretrained Language Models (PLMs) to LLMs. Specifically, we first explore the potential of LLMs to enhance the efficiency and effectiveness of various Healthcare applications highlighting both the strengths and limitations. Secondly, we conduct a comparison between the previous PLMs and the latest LLMs, as well as comparing various LLMs with each other. Then we summarize related Healthcare training data, training methods, optimization strategies, and usage. Finally, the unique concerns associated with deploying LLMs in Healthcare settings are investigated, particularly regarding fairness, accountability, transparency and ethics. Our survey provide a comprehensive investigation from perspectives of both computer science and Healthcare specialty. Besides the discussion about Healthcare concerns, we supports the computer science community by compiling a collection of open source resources, such as accessible datasets, the latest methodologies, code implementations, and evaluation benchmarks in the Github. Summarily, we contend that a significant paradigm shift is underway, transitioning from PLMs to LLMs. This shift encompasses a move from discriminative AI approaches to generative AI approaches, as well as a shift from model-centered methodologies to datacentered methodologies.

Artificial Intelligence (AI) is a broad field that is upturning mental health care in many ways, from addressing anxiety, depression, and stress to increasing access, personalization of treatment, and real-time monitoring that enhances patient outcomes. The current paper discusses the evolution, present application, and future challenges in the field of AI for mental health and well-being. From the early chatbot models, such as ELIZA, to modern machine learning systems, the integration of AI in mental health has grown rapidly to augment traditional treatment and open innovative solutions. AI-driven tools provide continuous support, offering personalized interventions and addressing issues such as treatment access and patient stigma. AI also enables early diagnosis through the analysis of complex datasets, including speech patterns and social media behavior, to detect early signs of conditions like depression and Post-Traumatic Stress Disorder (PTSD). Ethical challenges persist, however, most notably around privacy, data security, and algorithmic bias. With AI at the core of mental health care, there is a dire need to develop strong ethical frameworks that ensure patient rights are protected, access is equitable, and transparency is maintained in AI applications. Going forward, the role of AI in mental health will continue to evolve, and continued research and policy development will be needed to meet the diverse needs of patients while mitigating associated risks.

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.

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

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

This paper explores the application of large language models (LLMs) in nursing and elderly care, focusing on AI-driven patient monitoring and interaction. We introduce a novel Chinese nursing dataset and implement incremental pre-training (IPT) and supervised fine-tuning (SFT) techniques to enhance LLM performance in specialized tasks. Using LangChain, we develop a dynamic nursing assistant capable of real-time care and personalized interventions. Experimental results demonstrate significant improvements, paving the way for AI-driven solutions to meet the growing demands of healthcare in aging populations.

With the rapid advance of computer graphics and artificial intelligence technologies, the ways we interact with the world have undergone a transformative shift. Virtual Reality (VR) technology, aided by artificial intelligence (AI), has emerged as a dominant interaction media in multiple application areas, thanks to its advantage of providing users with immersive experiences. Among those applications, medicine is considered one of the most promising areas. In this paper, we present a comprehensive examination of the burgeoning field of AI-enhanced VR applications in medical care and services. By introducing a systematic taxonomy, we meticulously classify the pertinent techniques and applications into three well-defined categories based on different phases of medical diagnosis and treatment: Visualization Enhancement, VR-related Medical Data Processing, and VR-assisted Intervention. This categorization enables a structured exploration of the diverse roles that AI-powered VR plays in the medical domain, providing a framework for a more comprehensive understanding and evaluation of these technologies. To our best knowledge, this is the first systematic survey of AI-powered VR systems in medical settings, laying a foundation for future research in this interdisciplinary domain.

Artificial intelligence has significantly impacted medical applications, particularly with the advent of Medical Large Vision Language Models (Med-LVLMs), sparking optimism for the future of automated and personalized healthcare. However, the trustworthiness of Med-LVLMs remains unverified, posing significant risks for future model deployment. In this paper, we introduce CARES and aim to comprehensively evaluate the Trustworthiness of Med-LVLMs across the medical domain. We assess the trustworthiness of Med-LVLMs across five dimensions, including trustfulness, fairness, safety, privacy, and robustness. CARES comprises about 41K question-answer pairs in both closed and open-ended formats, covering 16 medical image modalities and 27 anatomical regions. Our analysis reveals that the models consistently exhibit concerns regarding trustworthiness, often displaying factual inaccuracies and failing to maintain fairness across different demographic groups. Furthermore, they are vulnerable to attacks and demonstrate a lack of privacy awareness. We publicly release our benchmark and code in https://github.com/richard-peng-xia/CARES.

We present a novel approach to personalized sleep health management using few-shot Chain-of-Thought (CoT) distillation, enabling small-scale language models (> 2B parameters) to rival the performance of large language models (LLMs) in specialized health domains. Our method simultaneously distills problem-solving strategies, long-tail expert knowledge, and personalized recommendation capabilities from larger models into more efficient, compact models. Unlike existing systems, our approach offers three key functionalities: generating personalized sleep health recommendations, supporting user-specific follow-up inquiries, and providing responses to domain-specific knowledge questions. We focus on sleep health due to its measurability via wearable devices and its impact on overall well-being. Our experimental setup, involving GPT-4o for data synthesis, Qwen-max for instruction set creation, and Qwen2.5 1.5B for model distillation, demonstrates significant improvements over baseline small-scale models in penalization, reasoning, and knowledge application. Experiments using 100 simulated sleep reports and 1,000 domain-specific questions shows our model achieves comparable performance to larger models while maintaining efficiency for real-world deployment. This research not only advances AI-driven health management but also provides a novel approach to leveraging LLM capabilities in resource-constrained environments, potentially enhancing the accessibility of personalized healthcare solutions.

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

The integration of Large Language Models (LLMs) into healthcare promises to transform medical diagnostics, research, and patient care. Yet, the progression of medical LLMs faces obstacles such as complex training requirements, rigorous evaluation demands, and the dominance of proprietary models that restrict academic exploration. Transparent, comprehensive access to LLM resources is essential for advancing the field, fostering reproducibility, and encouraging innovation in healthcare AI. We present Hippocrates, an open-source LLM framework specifically developed for the medical domain. In stark contrast to previous efforts, it offers unrestricted access to its training datasets, codebase, checkpoints, and evaluation protocols. This open approach is designed to stimulate collaborative research, allowing the community to build upon, refine, and rigorously evaluate medical LLMs within a transparent ecosystem. Also, we introduce Hippo, a family of 7B models tailored for the medical domain, fine-tuned from Mistral and LLaMA2 through continual pre-training, instruction tuning, and reinforcement learning from human and AI feedback. Our models outperform existing open medical LLMs models by a large-margin, even surpassing models with 70B parameters. Through Hippocrates, we aspire to unlock the full potential of LLMs not just to advance medical knowledge and patient care but also to democratize the benefits of AI research in healthcare, making them available across the globe.

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

AI-driven medical history-taking is an important component in symptom checking, automated patient intake, triage, and other AI virtual care applications. As history-taking is extremely varied, machine learning models require a significant amount of data to train. To overcome this challenge, existing systems are developed using indirect data or expert knowledge. This leads to a training-inference gap as models are trained on different kinds of data than what they observe at inference time. In this work, we present a two-stage re-ranking approach that helps close the training-inference gap by re-ranking the first-stage question candidates using a dialogue-contextualized model. For this, we propose a new model, global re-ranker, which cross-encodes the dialogue with all questions simultaneously, and compare it with several existing neural baselines. We test both transformer and S4-based language model backbones. We find that relative to the expert system, the best performance is achieved by our proposed global re-ranker with a transformer backbone, resulting in a 30% higher normalized discount cumulative gain (nDCG) and a 77% higher mean average precision (mAP).

Traditional applications of natural language processing (NLP) in healthcare have predominantly focused on patient-centered services, enhancing patient interactions and care delivery, such as through medical dialogue systems. However, the potential of NLP to benefit inexperienced doctors, particularly in areas such as communicative medical coaching, remains largely unexplored. We introduce ``ChatCoach,'' an integrated human-AI cooperative framework. Within this framework, both a patient agent and a coaching agent collaboratively support medical learners in practicing their medical communication skills during consultations. Unlike traditional dialogue systems, ChatCoach provides a simulated environment where a human doctor can engage in medical dialogue with a patient agent. Simultaneously, a coaching agent provides real-time feedback to the doctor. To construct the ChatCoach system, we developed a dataset and integrated Large Language Models such as ChatGPT and Llama2, aiming to assess their effectiveness in communicative medical coaching tasks. Our comparative analysis demonstrates that instruction-tuned Llama2 significantly outperforms ChatGPT's prompting-based approaches.

Large Action Models (LAMs) have revolutionized intelligent automation, but their application in healthcare faces challenges due to privacy concerns, latency, and dependency on internet access. This report introduces an ondevice, multi-agent healthcare assistant that overcomes these limitations. The system utilizes smaller, task-specific agents to optimize resources, ensure scalability and high performance. Our proposed system acts as a one-stop solution for health care needs with features like appointment booking, health monitoring, medication reminders, and daily health reporting. Powered by the Qwen Code Instruct 2.5 7B model, the Planner and Caller Agents achieve an average RougeL score of 85.5 for planning and 96.5 for calling for our tasks while being lightweight for on-device deployment. This innovative approach combines the benefits of ondevice systems with multi-agent architectures, paving the way for user-centric healthcare solutions.

Artificial Intelligence (AI) has demonstrated significant potential in healthcare, particularly in disease diagnosis and treatment planning. Recent progress in Medical Large Vision-Language Models (Med-LVLMs) has opened up new possibilities for interactive diagnostic tools. However, these models often suffer from factual hallucination, which can lead to incorrect diagnoses. Fine-tuning and retrieval-augmented generation (RAG) have emerged as methods to address these issues. However, the amount of high-quality data and distribution shifts between training data and deployment data limit the application of fine-tuning methods. Although RAG is lightweight and effective, existing RAG-based approaches are not sufficiently general to different medical domains and can potentially cause misalignment issues, both between modalities and between the model and the ground truth. In this paper, we propose a versatile multimodal RAG system, MMed-RAG, designed to enhance the factuality of Med-LVLMs. Our approach introduces a domain-aware retrieval mechanism, an adaptive retrieved contexts selection method, and a provable RAG-based preference fine-tuning strategy. These innovations make the RAG process sufficiently general and reliable, significantly improving alignment when introducing retrieved contexts. Experimental results across five medical datasets (involving radiology, ophthalmology, pathology) on medical VQA and report generation demonstrate that MMed-RAG can achieve an average improvement of 43.8% in the factual accuracy of Med-LVLMs. Our data and code are available in https://github.com/richard-peng-xia/MMed-RAG.

Diagnosing and managing a patient is a complex, sequential decision making process that requires physicians to obtain information -- such as which tests to perform -- and to act upon it. Recent advances in artificial intelligence (AI) and large language models (LLMs) promise to profoundly impact clinical care. However, current evaluation schemes overrely on static medical question-answering benchmarks, falling short on interactive decision-making that is required in real-life clinical work. Here, we present AgentClinic: a multimodal benchmark to evaluate LLMs in their ability to operate as agents in simulated clinical environments. In our benchmark, the doctor agent must uncover the patient's diagnosis through dialogue and active data collection. We present two open medical agent benchmarks: a multimodal image and dialogue environment, AgentClinic-NEJM, and a dialogue-only environment, AgentClinic-MedQA. We embed cognitive and implicit biases both in patient and doctor agents to emulate realistic interactions between biased agents. We find that introducing bias leads to large reductions in diagnostic accuracy of the doctor agents, as well as reduced compliance, confidence, and follow-up consultation willingness in patient agents. Evaluating a suite of state-of-the-art LLMs, we find that several models that excel in benchmarks like MedQA are performing poorly in AgentClinic-MedQA. We find that the LLM used in the patient agent is an important factor for performance in the AgentClinic benchmark. We show that both having limited interactions as well as too many interaction reduces diagnostic accuracy in doctor agents. The code and data for this work is publicly available at https://AgentClinic.github.io.

Clinical predictive models often rely on patients' electronic health records (EHR), but integrating medical knowledge to enhance predictions and decision-making is challenging. This is because personalized predictions require personalized knowledge graphs (KGs), which are difficult to generate from patient EHR data. To address this, we propose GraphCare, an open-world framework that uses external KGs to improve EHR-based predictions. Our method extracts knowledge from large language models (LLMs) and external biomedical KGs to build patient-specific KGs, which are then used to train our proposed Bi-attention AugmenTed (BAT) graph neural network (GNN) for healthcare predictions. On two public datasets, MIMIC-III and MIMIC-IV, GraphCare surpasses baselines in four vital healthcare prediction tasks: mortality, readmission, length of stay (LOS), and drug recommendation. On MIMIC-III, it boosts AUROC by 17.6\% and 6.6\% for mortality and readmission, and F1-score by 7.9\% and 10.8\% for LOS and drug recommendation, respectively. Notably, GraphCare demonstrates a substantial edge in scenarios with limited data availability. Our findings highlight the potential of using external KGs in healthcare prediction tasks and demonstrate the promise of GraphCare in generating personalized KGs for promoting personalized medicine.

The remarkable capabilities of Large Language Models (LLMs) make them increasingly compelling for adoption in real-world healthcare applications. However, the risks associated with using LLMs in medical applications have not been systematically characterized. We propose using five key principles for safe and trustworthy medical AI: Truthfulness, Resilience, Fairness, Robustness, and Privacy, along with ten specific aspects. Under this comprehensive framework, we introduce a novel MedGuard benchmark with 1,000 expert-verified questions. Our evaluation of 11 commonly used LLMs shows that the current language models, regardless of their safety alignment mechanisms, generally perform poorly on most of our benchmarks, particularly when compared to the high performance of human physicians. Despite recent reports indicate that advanced LLMs like ChatGPT can match or even exceed human performance in various medical tasks, this study underscores a significant safety gap, highlighting the crucial need for human oversight and the implementation of AI safety guardrails.

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.

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.

As machine learning models become increasingly prevalent in medical diagnostics, the need for interpretability and transparency becomes paramount. The XAI Renaissance signifies a significant shift in the field, aiming to redefine the interpretability of medical diagnostic models. This paper explores the innovative approaches and methodologies within the realm of Explainable AI (XAI) that are revolutionizing the interpretability of medical diagnostic models. By shedding light on the underlying decision-making process, XAI techniques empower healthcare professionals to understand, trust, and effectively utilize these models for accurate and reliable medical diagnoses. This review highlights the key advancements in XAI for medical diagnostics and their potential to transform the healthcare landscape, ultimately improving patient outcomes and fostering trust in AI-driven diagnostic systems.

The deployment of large language models (LLMs) within the healthcare sector has sparked both enthusiasm and apprehension. These models exhibit the remarkable capability to provide proficient responses to free-text queries, demonstrating a nuanced understanding of professional medical knowledge. This comprehensive survey delves into the functionalities of existing LLMs designed for healthcare applications, elucidating the trajectory of their development, starting from traditional Pretrained Language Models (PLMs) to the present state of LLMs in healthcare sector. First, we explore the potential of LLMs to amplify the efficiency and effectiveness of diverse healthcare applications, particularly focusing on clinical language understanding tasks. These tasks encompass a wide spectrum, ranging from named entity recognition and relation extraction to natural language inference, multi-modal medical applications, document classification, and question-answering. Additionally, we conduct an extensive comparison of the most recent state-of-the-art LLMs in the healthcare domain, while also assessing the utilization of various open-source LLMs and highlighting their significance in healthcare applications. Furthermore, we present the essential performance metrics employed to evaluate LLMs in the biomedical domain, shedding light on their effectiveness and limitations. Finally, we summarize the prominent challenges and constraints faced by large language models in the healthcare sector, offering a holistic perspective on their potential benefits and shortcomings. This review provides a comprehensive exploration of the current landscape of LLMs in healthcare, addressing their role in transforming medical applications and the areas that warrant further research and development.

Biomedical data is inherently multimodal, consisting of electronic health records, medical imaging, digital pathology, genome sequencing, wearable sensors, and more. The application of artificial intelligence tools to these multifaceted sensing technologies has the potential to revolutionize the prognosis, diagnosis, and management of human health and disease. However, current approaches to biomedical AI typically only train and evaluate with one or a small set of medical modalities and tasks. This limitation hampers the development of comprehensive tools that can leverage the rich interconnected information across many heterogeneous biomedical sensors. To address this challenge, we present MultiMed, a benchmark designed to evaluate and enable large-scale learning across a wide spectrum of medical modalities and tasks. MultiMed consists of 2.56 million samples across ten medical modalities such as medical reports, pathology, genomics, and protein data, and is structured into eleven challenging tasks, including disease prognosis, protein structure prediction, and medical question answering. Using MultiMed, we conduct comprehensive experiments benchmarking state-of-the-art unimodal, multimodal, and multitask models. Our analysis highlights the advantages of training large-scale medical models across many related modalities and tasks. Moreover, MultiMed enables studies of generalization across related medical concepts, robustness to real-world noisy data and distribution shifts, and novel modality combinations to improve prediction performance. MultiMed will be publicly available and regularly updated and welcomes inputs from the community.

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.

In this paper, we introduce a simulacrum of hospital called Agent Hospital that simulates the entire process of treating illness. All patients, nurses, and doctors are autonomous agents powered by large language models (LLMs). Our central goal is to enable a doctor agent to learn how to treat illness within the simulacrum. To do so, we propose a method called MedAgent-Zero. As the simulacrum can simulate disease onset and progression based on knowledge bases and LLMs, doctor agents can keep accumulating experience from both successful and unsuccessful cases. Simulation experiments show that the treatment performance of doctor agents consistently improves on various tasks. More interestingly, the knowledge the doctor agents have acquired in Agent Hospital is applicable to real-world medicare benchmarks. After treating around ten thousand patients (real-world doctors may take over two years), the evolved doctor agent achieves a state-of-the-art accuracy of 93.06% on a subset of the MedQA dataset that covers major respiratory diseases. This work paves the way for advancing the applications of LLM-powered agent techniques in medical scenarios.

The widespread adoption of electronic health records and digital healthcare data has created a demand for data-driven insights to enhance patient outcomes, diagnostics, and treatments. However, using real patient data presents privacy and regulatory challenges, including compliance with HIPAA and GDPR. Synthetic data generation, using generative AI models like GANs and VAEs offers a promising solution to balance valuable data access and patient privacy protection. In this paper, we examine generative AI models for creating realistic, anonymized patient data for research and training, explore synthetic data applications in healthcare, and discuss its benefits, challenges, and future research directions. Synthetic data has the potential to revolutionize healthcare by providing anonymized patient data while preserving privacy and enabling versatile applications.

Recent immense breakthroughs in generative models such as in GPT4 have precipitated re-imagined ubiquitous usage of these models in all applications. One area that can benefit by improvements in artificial intelligence (AI) is healthcare. The note generation task from doctor-patient encounters, and its associated electronic medical record documentation, is one of the most arduous time-consuming tasks for physicians. It is also a natural prime potential beneficiary to advances in generative models. However with such advances, benchmarking is more critical than ever. Whether studying model weaknesses or developing new evaluation metrics, shared open datasets are an imperative part of understanding the current state-of-the-art. Unfortunately as clinic encounter conversations are not routinely recorded and are difficult to ethically share due to patient confidentiality, there are no sufficiently large clinic dialogue-note datasets to benchmark this task. Here we present the Ambient Clinical Intelligence Benchmark (ACI-BENCH) corpus, the largest dataset to date tackling the problem of AI-assisted note generation from visit dialogue. We also present the benchmark performances of several common state-of-the-art approaches.

With the increasing availability of structured and unstructured data and the swift progress of analytical techniques, Artificial Intelligence (AI) is bringing a revolution to the healthcare industry. With the increasingly indispensable role of AI in healthcare, there are growing concerns over the lack of transparency and explainability in addition to potential bias encountered by predictions of the model. This is where Explainable Artificial Intelligence (XAI) comes into the picture. XAI increases the trust placed in an AI system by medical practitioners as well as AI researchers, and thus, eventually, leads to an increasingly widespread deployment of AI in healthcare. In this paper, we present different interpretability techniques. The aim is to enlighten practitioners on the understandability and interpretability of explainable AI systems using a variety of techniques available which can be very advantageous in the health-care domain. Medical diagnosis model is responsible for human life and we need to be confident enough to treat a patient as instructed by a black-box model. Our paper contains examples based on the heart disease dataset and elucidates on how the explainability techniques should be preferred to create trustworthiness while using AI systems in healthcare.

The rise of chronic diseases and pandemics like COVID-19 has emphasized the need for effective patient data processing while ensuring privacy through anonymization and de-identification of protected health information (PHI). Anonymized data facilitates research without compromising patient confidentiality. This paper introduces expert small AI models developed using the LLM-in-the-loop methodology to meet the demand for domain-specific de-identification NER models. These models overcome the privacy risks associated with large language models (LLMs) used via APIs by eliminating the need to transmit or store sensitive data. More importantly, they consistently outperform LLMs in de-identification tasks, offering superior performance and reliability. Our de-identification NER models, developed in eight languages (English, German, Italian, French, Romanian, Turkish, Spanish, and Arabic) achieved f1-micro score averages of 0.966, 0.975, 0.976, 0.970, 0.964, 0.974, 0.978, and 0.953 respectively. These results establish them as the most accurate healthcare anonymization solutions, surpassing existing small models and even general-purpose LLMs such as GPT-4o. While Part-1 of this series introduced the LLM-in-the-loop methodology for bio-medical document translation, this second paper showcases its success in developing cost-effective expert small NER models in de-identification tasks. Our findings lay the groundwork for future healthcare AI innovations, including biomedical entity and relation extraction, demonstrating the value of specialized models for domain-specific challenges.

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

The advancement in healthcare has shifted focus toward patient-centric approaches, particularly in self-care and patient education, facilitated by access to Electronic Health Records (EHR). However, medical jargon in EHRs poses significant challenges in patient comprehension. To address this, we introduce a new task of automatically generating lay definitions, aiming to simplify complex medical terms into patient-friendly lay language. We first created the README dataset, an extensive collection of over 50,000 unique (medical term, lay definition) pairs and 300,000 mentions, each offering context-aware lay definitions manually annotated by domain experts. We have also engineered a data-centric Human-AI pipeline that synergizes data filtering, augmentation, and selection to improve data quality. We then used README as the training data for models and leveraged a Retrieval-Augmented Generation method to reduce hallucinations and improve the quality of model outputs. Our extensive automatic and human evaluations demonstrate that open-source mobile-friendly models, when fine-tuned with high-quality data, are capable of matching or even surpassing the performance of state-of-the-art closed-source large language models like ChatGPT. This research represents a significant stride in closing the knowledge gap in patient education and advancing patient-centric healthcare solutions.

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.

In recent years, the machine learning research community has benefited tremendously from the availability of openly accessible benchmark datasets. Clinical data are usually not openly available due to their highly confidential nature. This has hampered the development of reproducible and generalisable machine learning applications in health care. Here we introduce the Health Gym - a growing collection of highly realistic synthetic medical datasets that can be freely accessed to prototype, evaluate, and compare machine learning algorithms, with a specific focus on reinforcement learning. The three synthetic datasets described in this paper present patient cohorts with acute hypotension and sepsis in the intensive care unit, and people with human immunodeficiency virus (HIV) receiving antiretroviral therapy in ambulatory care. The datasets were created using a novel generative adversarial network (GAN). The distributions of variables, and correlations between variables and trends over time in the synthetic datasets mirror those in the real datasets. Furthermore, the risk of sensitive information disclosure associated with the public distribution of the synthetic datasets is estimated to be very low.

Digital twin technology has is anticipated to transform healthcare, enabling personalized medicines and support, earlier diagnoses, simulated treatment outcomes, and optimized surgical plans. Digital twins are readily gaining traction in industries like manufacturing, supply chain logistics, and civil infrastructure. Not in patient care, however. The challenge of modeling complex diseases with multimodal patient data and the computational complexities of analyzing it have stifled digital twin adoption in the biomedical vertical. Yet, these major obstacles can potentially be handled by approaching these models in a different way. This paper proposes a novel framework for addressing the barriers to clinical twin modeling created by computational costs and modeling complexities. We propose structuring patient health data as a knowledge graph and using closed-form continuous-time liquid neural networks, for real-time analytics. By synthesizing multimodal patient data and leveraging the flexibility and efficiency of closed form continuous time networks and knowledge graph ontologies, our approach enables real time insights, personalized medicine, early diagnosis and intervention, and optimal surgical planning. This novel approach provides a comprehensive and adaptable view of patient health along with real-time analytics, paving the way for digital twin simulations and other anticipated benefits 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.

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.

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.

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

Integrating large language models (LLMs) like DeepSeek R1 into healthcare requires rigorous evaluation of their reasoning alignment with clinical expertise. This study assesses DeepSeek R1's medical reasoning against expert patterns using 100 MedQA clinical cases. The model achieved 93% diagnostic accuracy, demonstrating systematic clinical judgment through differential diagnosis, guideline-based treatment selection, and integration of patient-specific factors. However, error analysis of seven incorrect cases revealed persistent limitations: anchoring bias, challenges reconciling conflicting data, insufficient exploration of alternatives, overthinking, knowledge gaps, and premature prioritization of definitive treatment over intermediate care. Crucially, reasoning length correlated with accuracy - shorter responses (<5,000 characters) were more reliable, suggesting extended explanations may signal uncertainty or rationalization of errors. While DeepSeek R1 exhibits foundational clinical reasoning capabilities, recurring flaws highlight critical areas for refinement, including bias mitigation, knowledge updates, and structured reasoning frameworks. These findings underscore LLMs' potential to augment medical decision-making through artificial reasoning but emphasize the need for domain-specific validation, interpretability safeguards, and confidence metrics (e.g., response length thresholds) to ensure reliability in real-world applications.

Recent breakthroughs in large language models (LLMs) offer unprecedented natural language understanding and generation capabilities. However, existing surveys on LLMs in biomedicine often focus on specific applications or model architectures, lacking a comprehensive analysis that integrates the latest advancements across various biomedical domains. This review, based on an analysis of 484 publications sourced from databases including PubMed, Web of Science, and arXiv, provides an in-depth examination of the current landscape, applications, challenges, and prospects of LLMs in biomedicine, distinguishing itself by focusing on the practical implications of these models in real-world biomedical contexts. Firstly, we explore the capabilities of LLMs in zero-shot learning across a broad spectrum of biomedical tasks, including diagnostic assistance, drug discovery, and personalized medicine, among others, with insights drawn from 137 key studies. Then, we discuss adaptation strategies of LLMs, including fine-tuning methods for both uni-modal and multi-modal LLMs to enhance their performance in specialized biomedical contexts where zero-shot fails to achieve, such as medical question answering and efficient processing of biomedical literature. Finally, we discuss the challenges that LLMs face in the biomedicine domain including data privacy concerns, limited model interpretability, issues with dataset quality, and ethics due to the sensitive nature of biomedical data, the need for highly reliable model outputs, and the ethical implications of deploying AI in healthcare. To address these challenges, we also identify future research directions of LLM in biomedicine including federated learning methods to preserve data privacy and integrating explainable AI methodologies to enhance the transparency of LLMs.

Disease risk prediction has attracted increasing attention in the field of modern healthcare, especially with the latest advances in artificial intelligence (AI). Electronic health records (EHRs), which contain heterogeneous patient information, are widely used in disease risk prediction tasks. One challenge of applying AI models for risk prediction lies in generating interpretable evidence to support the prediction results while retaining the prediction ability. In order to address this problem, we propose the method of jointly embedding words and labels whereby attention modules learn the weights of words from medical notes according to their relevance to the names of risk prediction labels. This approach boosts interpretability by employing an attention mechanism and including the names of prediction tasks in the model. However, its application is only limited to the handling of textual inputs such as medical notes. In this paper, we propose a label dependent attention model LDAM to 1) improve the interpretability by exploiting Clinical-BERT (a biomedical language model pre-trained on a large clinical corpus) to encode biomedically meaningful features and labels jointly; 2) extend the idea of joint embedding to the processing of time-series data, and develop a multi-modal learning framework for integrating heterogeneous information from medical notes and time-series health status indicators. To demonstrate our method, we apply LDAM to the MIMIC-III dataset to predict different disease risks. We evaluate our method both quantitatively and qualitatively. Specifically, the predictive power of LDAM will be shown, and case studies will be carried out to illustrate its interpretability.

Echocardiography is the most widely used cardiac imaging modality, capturing ultrasound video data to assess cardiac structure and function. Artificial intelligence (AI) in echocardiography has the potential to streamline manual tasks and improve reproducibility and precision. However, most echocardiography AI models are single-view, single-task systems that do not synthesize complementary information from multiple views captured during a full exam, and thus lead to limited performance and scope of applications. To address this problem, we introduce EchoPrime, a multi-view, view-informed, video-based vision-language foundation model trained on over 12 million video-report pairs. EchoPrime uses contrastive learning to train a unified embedding model for all standard views in a comprehensive echocardiogram study with representation of both rare and common diseases and diagnoses. EchoPrime then utilizes view-classification and a view-informed anatomic attention model to weight video-specific interpretations that accurately maps the relationship between echocardiographic views and anatomical structures. With retrieval-augmented interpretation, EchoPrime integrates information from all echocardiogram videos in a comprehensive study and performs holistic comprehensive clinical echocardiography interpretation. In datasets from two independent healthcare systems, EchoPrime achieves state-of-the art performance on 23 diverse benchmarks of cardiac form and function, surpassing the performance of both task-specific approaches and prior foundation models. Following rigorous clinical evaluation, EchoPrime can assist physicians in the automated preliminary assessment of comprehensive echocardiography.

Curated datasets for healthcare are often limited due to the need of human annotations from experts. In this paper, we present MedEval, a multi-level, multi-task, and multi-domain medical benchmark to facilitate the development of language models for healthcare. MedEval is comprehensive and consists of data from several healthcare systems and spans 35 human body regions from 8 examination modalities. With 22,779 collected sentences and 21,228 reports, we provide expert annotations at multiple levels, offering a granular potential usage of the data and supporting a wide range of tasks. Moreover, we systematically evaluated 10 generic and domain-specific language models under zero-shot and finetuning settings, from domain-adapted baselines in healthcare to general-purposed state-of-the-art large language models (e.g., ChatGPT). Our evaluations reveal varying effectiveness of the two categories of language models across different tasks, from which we notice the importance of instruction tuning for few-shot usage of large language models. Our investigation paves the way toward benchmarking language models for healthcare and provides valuable insights into the strengths and limitations of adopting large language models in medical domains, informing their practical applications and future advancements.

Large language models (LLMs), particularly those with reasoning capabilities, have rapidly advanced in recent years, demonstrating significant potential across a wide range of applications. However, their deployment in healthcare, especially in disease reasoning tasks, is hindered by the challenge of acquiring expert-level cognitive data. In this paper, we introduce Citrus, a medical language model that bridges the gap between clinical expertise and AI reasoning by emulating the cognitive processes of medical experts. The model is trained on a large corpus of simulated expert disease reasoning data, synthesized using a novel approach that accurately captures the decision-making pathways of clinicians. This approach enables Citrus to better simulate the complex reasoning processes involved in diagnosing and treating medical conditions.To further address the lack of publicly available datasets for medical reasoning tasks, we release the last-stage training data, including a custom-built medical diagnostic dialogue dataset. This open-source contribution aims to support further research and development in the field. Evaluations using authoritative benchmarks such as MedQA, covering tasks in medical reasoning and language understanding, show that Citrus achieves superior performance compared to other models of similar size. These results highlight Citrus potential to significantly enhance medical decision support systems, providing a more accurate and efficient tool for clinical decision-making.

Healthcare monitoring is crucial for early detection, timely intervention, and the ongoing management of health conditions, ultimately improving individuals' quality of life. Recent research shows that Large Language Models (LLMs) have demonstrated impressive performance in supporting healthcare tasks. However, existing LLM-based healthcare solutions typically rely on cloud-based systems, which raise privacy concerns and increase the risk of personal information leakage. As a result, there is growing interest in running these models locally on devices like mobile phones and wearables to protect users' privacy. Small Language Models (SLMs) are potential candidates to solve privacy and computational issues, as they are more efficient and better suited for local deployment. However, the performance of SLMs in healthcare domains has not yet been investigated. This paper examines the capability of SLMs to accurately analyze health data, such as steps, calories, sleep minutes, and other vital statistics, to assess an individual's health status. Our results show that, TinyLlama, which has 1.1 billion parameters, utilizes 4.31 GB memory, and has 0.48s latency, showing the best performance compared other four state-of-the-art (SOTA) SLMs on various healthcare applications. Our results indicate that SLMs could potentially be deployed on wearable or mobile devices for real-time health monitoring, providing a practical solution for efficient and privacy-preserving healthcare.

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

Healthcare systems continuously generate vast amounts of electronic health records (EHRs), commonly stored in the Fast Healthcare Interoperability Resources (FHIR) standard. Despite the wealth of information in these records, their complexity and volume make it difficult for users to retrieve and interpret crucial health insights. Recent advances in Large Language Models (LLMs) offer a solution, enabling semantic question answering (QA) over medical data, allowing users to interact with their health records more effectively. However, ensuring privacy and compliance requires edge and private deployments of LLMs. This paper proposes a novel approach to semantic QA over EHRs by first identifying the most relevant FHIR resources for a user query (Task1) and subsequently answering the query based on these resources (Task2). We explore the performance of privately hosted, fine-tuned LLMs, evaluating them against benchmark models such as GPT-4 and GPT-4o. Our results demonstrate that fine-tuned LLMs, while 250x smaller in size, outperform GPT-4 family models by 0.55% in F1 score on Task1 and 42% on Meteor Task in Task2. Additionally, we examine advanced aspects of LLM usage, including sequential fine-tuning, model self-evaluation (narcissistic evaluation), and the impact of training data size on performance. The models and datasets are available here: https://huggingface.co/genloop

Chest X-rays (CXRs) play an integral role in driving critical decisions in disease management and patient care. While recent innovations have led to specialized models for various CXR interpretation tasks, these solutions often operate in isolation, limiting their practical utility in clinical practice. We present MedRAX, the first versatile AI agent that seamlessly integrates state-of-the-art CXR analysis tools and multimodal large language models into a unified framework. MedRAX dynamically leverages these models to address complex medical queries without requiring additional training. To rigorously evaluate its capabilities, we introduce ChestAgentBench, a comprehensive benchmark containing 2,500 complex medical queries across 7 diverse categories. Our experiments demonstrate that MedRAX achieves state-of-the-art performance compared to both open-source and proprietary models, representing a significant step toward the practical deployment of automated CXR interpretation systems. Data and code have been publicly available at https://github.com/bowang-lab/MedRAX

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.

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

Developing reliable AI systems to assist human clinicians in multi-modal medical diagnosis has long been a key objective for researchers. Recently, Multi-modal Large Language Models (MLLMs) have gained significant attention and achieved success across various domains. With strong reasoning capabilities and the ability to perform diverse tasks based on user instructions, they hold great potential for enhancing medical diagnosis. However, directly applying MLLMs to the medical domain still presents challenges. They lack detailed perception of visual inputs, limiting their ability to perform quantitative image analysis, which is crucial for medical diagnostics. Additionally, MLLMs often exhibit hallucinations and inconsistencies in reasoning, whereas clinical diagnoses must adhere strictly to established criteria. To address these challenges, we propose MedAgent-Pro, an evidence-based reasoning agentic system designed to achieve reliable, explainable, and precise medical diagnoses. This is accomplished through a hierarchical workflow: at the task level, knowledge-based reasoning generate reliable diagnostic plans for specific diseases following retrieved clinical criteria. While at the case level, multiple tool agents process multi-modal inputs, analyze different indicators according to the plan, and provide a final diagnosis based on both quantitative and qualitative evidence. Comprehensive experiments on both 2D and 3D medical diagnosis tasks demonstrate the superiority and effectiveness of MedAgent-Pro, while case studies further highlight its reliability and interpretability. The code is available at https://github.com/jinlab-imvr/MedAgent-Pro.

The rapid evolution of artificial intelligence, especially in large language models (LLMs), has significantly impacted various domains, including healthcare. In chest X-ray (CXR) analysis, previous studies have employed LLMs, but with limitations: either underutilizing the multi-tasking capabilities of LLMs or lacking clinical accuracy. This paper presents M4CXR, a multi-modal LLM designed to enhance CXR interpretation. The model is trained on a visual instruction-following dataset that integrates various task-specific datasets in a conversational format. As a result, the model supports multiple tasks such as medical report generation (MRG), visual grounding, and visual question answering (VQA). M4CXR achieves state-of-the-art clinical accuracy in MRG by employing a chain-of-thought prompting strategy, in which it identifies findings in CXR images and subsequently generates corresponding reports. The model is adaptable to various MRG scenarios depending on the available inputs, such as single-image, multi-image, and multi-study contexts. In addition to MRG, M4CXR performs visual grounding at a level comparable to specialized models and also demonstrates outstanding performance in VQA. Both quantitative and qualitative assessments reveal M4CXR's versatility in MRG, visual grounding, and VQA, while consistently maintaining clinical accuracy.

Transformers have significantly advanced the modeling of Electronic Health Records (EHR), yet their deployment in real-world healthcare is limited by several key challenges. Firstly, the quadratic computational cost and insufficient context length of these models pose significant obstacles for hospitals in processing the extensive medical histories typical in EHR data. Additionally, existing models employ separate finetuning for each clinical task, complicating maintenance in healthcare environments. Moreover, these models focus exclusively on either clinical prediction or EHR forecasting, lacking the flexibility to perform well across both. To overcome these limitations, we introduce EHRMamba, a robust foundation model built on the Mamba architecture. EHRMamba can process sequences up to four times longer than previous models due to its linear computational cost. We also introduce a novel approach to Multitask Prompted Finetuning (MTF) for EHR data, which enables EHRMamba to simultaneously learn multiple clinical tasks in a single finetuning phase, significantly enhancing deployment and cross-task generalization. Furthermore, our model leverages the HL7 FHIR data standard to simplify integration into existing hospital systems. Alongside EHRMamba, we open-source Odyssey, a toolkit designed to support the development and deployment of EHR foundation models, with an emphasis on data standardization and interpretability. Our evaluations on the MIMIC-IV dataset demonstrate that EHRMamba advances state-of-the-art performance across 6 major clinical tasks and excels in EHR forecasting, marking a significant leap forward in the field.

Despite the remarkable progress in the development of predictive models for healthcare, applying these algorithms on a large scale has been challenging. Algorithms trained on a particular task, based on specific data formats available in a set of medical records, tend to not generalize well to other tasks or databases in which the data fields may differ. To address this challenge, we propose General Healthcare Predictive Framework (GenHPF), which is applicable to any EHR with minimal preprocessing for multiple prediction tasks. GenHPF resolves heterogeneity in medical codes and schemas by converting EHRs into a hierarchical textual representation while incorporating as many features as possible. To evaluate the efficacy of GenHPF, we conduct multi-task learning experiments with single-source and multi-source settings, on three publicly available EHR datasets with different schemas for 12 clinically meaningful prediction tasks. Our framework significantly outperforms baseline models that utilize domain knowledge in multi-source learning, improving average AUROC by 1.2%P in pooled learning and 2.6%P in transfer learning while also showing comparable results when trained on a single EHR dataset. Furthermore, we demonstrate that self-supervised pretraining using multi-source datasets is effective when combined with GenHPF, resulting in a 0.6%P AUROC improvement compared to models without pretraining. By eliminating the need for preprocessing and feature engineering, we believe that this work offers a solid framework for multi-task and multi-source learning that can be leveraged to speed up the scaling and usage of predictive algorithms in healthcare.

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.

Passively collected behavioral health data from ubiquitous sensors holds significant promise to provide mental health professionals insights from patient's daily lives; however, developing analysis tools to use this data in clinical practice requires addressing challenges of generalization across devices and weak or ambiguous correlations between the measured signals and an individual's mental health. To address these challenges, we take a novel approach that leverages large language models (LLMs) to synthesize clinically useful insights from multi-sensor data. We develop chain of thought prompting methods that use LLMs to generate reasoning about how trends in data such as step count and sleep relate to conditions like depression and anxiety. We first demonstrate binary depression classification with LLMs achieving accuracies of 61.1% which exceed the state of the art. While it is not robust for clinical use, this leads us to our key finding: even more impactful and valued than classification is a new human-AI collaboration approach in which clinician experts interactively query these tools and combine their domain expertise and context about the patient with AI generated reasoning to support clinical decision-making. We find models like GPT-4 correctly reference numerical data 75% of the time, and clinician participants express strong interest in using this approach to interpret self-tracking data.

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.

To generate evidence regarding the safety and efficacy of artificial intelligence (AI) enabled medical devices, AI models need to be evaluated on a diverse population of patient cases, some of which may not be readily available. We propose an evaluation approach for testing medical imaging AI models that relies on in silico imaging pipelines in which stochastic digital models of human anatomy (in object space) with and without pathology are imaged using a digital replica imaging acquisition system to generate realistic synthetic image datasets. Here, we release M-SYNTH, a dataset of cohorts with four breast fibroglandular density distributions imaged at different exposure levels using Monte Carlo x-ray simulations with the publicly available Virtual Imaging Clinical Trial for Regulatory Evaluation (VICTRE) toolkit. We utilize the synthetic dataset to analyze AI model performance and find that model performance decreases with increasing breast density and increases with higher mass density, as expected. As exposure levels decrease, AI model performance drops with the highest performance achieved at exposure levels lower than the nominal recommended dose for the breast type.

Predicting disease trajectories from electronic health records (EHRs) is a complex task due to major challenges such as data non-stationarity, high granularity of medical codes, and integration of multimodal data. EHRs contain both structured data, such as diagnostic codes, and unstructured data, such as clinical notes, which hold essential information often overlooked. Current models, primarily based on structured data, struggle to capture the complete medical context of patients, resulting in a loss of valuable information. To address this issue, we propose an approach that integrates unstructured clinical notes into transformer-based deep learning models for sequential disease prediction. This integration enriches the representation of patients' medical histories, thereby improving the accuracy of diagnosis predictions. Experiments on MIMIC-IV datasets demonstrate that the proposed approach outperforms traditional models relying solely on structured data.

Machine translation is indispensable in healthcare for enabling the global dissemination of medical knowledge across languages. However, complex medical terminology poses unique challenges to achieving adequate translation quality and accuracy. This study introduces a novel "LLMs-in-the-loop" approach to develop supervised neural machine translation models optimized specifically for medical texts. While large language models (LLMs) have demonstrated powerful capabilities, this research shows that small, specialized models trained on high-quality in-domain (mostly synthetic) data can outperform even vastly larger LLMs. Custom parallel corpora in six languages were compiled from scientific articles, synthetically generated clinical documents, and medical texts. Our LLMs-in-the-loop methodology employs synthetic data generation, rigorous evaluation, and agent orchestration to enhance performance. We developed small medical translation models using the MarianMT base model. We introduce a new medical translation test dataset to standardize evaluation in this domain. Assessed using BLEU, METEOR, ROUGE, and BERT scores on this test set, our MarianMT-based models outperform Google Translate, DeepL, and GPT-4-Turbo. Results demonstrate that our LLMs-in-the-loop approach, combined with fine-tuning high-quality, domain-specific data, enables specialized models to outperform general-purpose and some larger systems. This research, part of a broader series on expert small models, paves the way for future healthcare-related AI developments, including deidentification and bio-medical entity extraction models. Our study underscores the potential of tailored neural translation models and the LLMs-in-the-loop methodology to advance the field through improved data generation, evaluation, agent, and modeling techniques.

Medicine is inherently multimodal, with rich data modalities spanning text, imaging, genomics, and more. Generalist biomedical artificial intelligence (AI) systems that flexibly encode, integrate, and interpret this data at scale can potentially enable impactful applications ranging from scientific discovery to care delivery. To enable the development of these models, we first curate MultiMedBench, a new multimodal biomedical benchmark. MultiMedBench encompasses 14 diverse tasks such as medical question answering, mammography and dermatology image interpretation, radiology report generation and summarization, and genomic variant calling. We then introduce Med-PaLM Multimodal (Med-PaLM M), our proof of concept for a generalist biomedical AI system. Med-PaLM M is a large multimodal generative model that flexibly encodes and interprets biomedical data including clinical language, imaging, and genomics with the same set of model weights. Med-PaLM M reaches performance competitive with or exceeding the state of the art on all MultiMedBench tasks, often surpassing specialist models by a wide margin. We also report examples of zero-shot generalization to novel medical concepts and tasks, positive transfer learning across tasks, and emergent zero-shot medical reasoning. To further probe the capabilities and limitations of Med-PaLM M, we conduct a radiologist evaluation of model-generated (and human) chest X-ray reports and observe encouraging performance across model scales. In a side-by-side ranking on 246 retrospective chest X-rays, clinicians express a pairwise preference for Med-PaLM M reports over those produced by radiologists in up to 40.50% of cases, suggesting potential clinical utility. While considerable work is needed to validate these models in real-world use cases, our results represent a milestone towards the development of generalist biomedical AI systems.

The detailed clinical records drafted by doctors after each patient's visit are crucial for medical practitioners and researchers. Automating the creation of these notes with language models can reduce the workload of doctors. However, training such models can be difficult due to the limited public availability of conversations between patients and doctors. In this paper, we introduce NoteChat, a cooperative multi-agent framework leveraging Large Language Models (LLMs) for generating synthetic doctor-patient conversations conditioned on clinical notes. NoteChat consists of Planning, Roleplay, and Polish modules. We provide a comprehensive automatic and human evaluation of NoteChat, comparing it with state-of-the-art models, including OpenAI's ChatGPT and GPT-4. Results demonstrate that NoteChat facilitates high-quality synthetic doctor-patient conversations, underscoring the untapped potential of LLMs in healthcare. This work represents the first instance of multiple LLMs cooperating to complete a doctor-patient conversation conditioned on clinical notes, offering promising avenues for the intersection of AI and healthcare

While recent advancements in commercial large language models (LM) have shown promising results in medical tasks, their closed-source nature poses significant privacy and security concerns, hindering their widespread use in the medical field. Despite efforts to create open-source models, their limited parameters often result in insufficient multi-step reasoning capabilities required for solving complex medical problems. To address this, we introduce Meerkat-7B, a novel medical AI system with 7 billion parameters. Meerkat-7B was trained using our new synthetic dataset consisting of high-quality chain-of-thought reasoning paths sourced from 18 medical textbooks, along with diverse instruction-following datasets. Our system achieved remarkable accuracy across seven medical benchmarks, surpassing GPT-3.5 by 13.1%, as well as outperforming the previous best 7B models such as MediTron-7B and BioMistral-7B by 13.4% and 9.8%, respectively. Notably, it surpassed the passing threshold of the United States Medical Licensing Examination (USMLE) for the first time for a 7B-parameter model. Additionally, our system offered more detailed free-form responses to clinical queries compared to existing 7B and 13B models, approaching the performance level of GPT-3.5. This significantly narrows the performance gap with large LMs, showcasing its effectiveness in addressing complex medical challenges.

Large Language Models (LLMs) are transforming artificial intelligence, enabling autonomous agents to perform diverse tasks across various domains. These agents, proficient in human-like text comprehension and generation, have the potential to revolutionize sectors from customer service to healthcare. However, they face challenges such as multimodality, human value alignment, hallucinations, and evaluation. Techniques like prompting, reasoning, tool utilization, and in-context learning are being explored to enhance their capabilities. Evaluation platforms like AgentBench, WebArena, and ToolLLM provide robust methods for assessing these agents in complex scenarios. These advancements are leading to the development of more resilient and capable autonomous agents, anticipated to become integral in our digital lives, assisting in tasks from email responses to disease diagnosis. The future of AI, with LLMs at the forefront, is promising.

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.

Artificial Intelligence (AI) in healthcare, especially in white blood cell cancer diagnosis, is hindered by two primary challenges: the lack of large-scale labeled datasets for white blood cell (WBC) segmentation and outdated segmentation methods. These challenges inhibit the development of more accurate and modern techniques to diagnose cancer relating to white blood cells. To address the first challenge, a semi-supervised learning framework should be devised to efficiently capitalize on the scarcity of the dataset available. In this work, we address this issue by proposing a novel self-training pipeline with the incorporation of FixMatch. Self-training is a technique that utilizes the model trained on labeled data to generate pseudo-labels for the unlabeled data and then re-train on both of them. FixMatch is a consistency-regularization algorithm to enforce the model's robustness against variations in the input image. We discover that by incorporating FixMatch in the self-training pipeline, the performance improves in the majority of cases. Our performance achieved the best performance with the self-training scheme with consistency on DeepLab-V3 architecture and ResNet-50, reaching 90.69%, 87.37%, and 76.49% on Zheng 1, Zheng 2, and LISC datasets, respectively.

As the capabilities of Large Language Models (LLMs) in healthcare and medicine continue to advance, there is a growing need for competitive open-source models that can safeguard public interest. With the increasing availability of highly competitive open base models, the impact of continued pre-training is increasingly uncertain. In this work, we explore the role of instruct tuning, model merging, alignment, red teaming and advanced inference schemes, as means to improve current open models. To that end, we introduce the Aloe family, a set of open medical LLMs highly competitive within its scale range. Aloe models are trained on the current best base models (Mistral, LLaMA 3), using a new custom dataset which combines public data sources improved with synthetic Chain of Thought (CoT). Aloe models undergo an alignment phase, becoming one of the first few policy-aligned open healthcare LLM using Direct Preference Optimization, setting a new standard for ethical performance in healthcare LLMs. Model evaluation expands to include various bias and toxicity datasets, a dedicated red teaming effort, and a much-needed risk assessment for healthcare LLMs. Finally, to explore the limits of current LLMs in inference, we study several advanced prompt engineering strategies to boost performance across benchmarks, yielding state-of-the-art results for open healthcare 7B LLMs, unprecedented at this scale.

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.

Advancements in artificial intelligence, machine learning, and deep learning have catalyzed the transformation of big data analytics and management into pivotal domains for research and application. This work explores the theoretical foundations, methodological advancements, and practical implementations of these technologies, emphasizing their role in uncovering actionable insights from massive, high-dimensional datasets. The study presents a systematic overview of data preprocessing techniques, including data cleaning, normalization, integration, and dimensionality reduction, to prepare raw data for analysis. Core analytics methodologies such as classification, clustering, regression, and anomaly detection are examined, with a focus on algorithmic innovation and scalability. Furthermore, the text delves into state-of-the-art frameworks for data mining and predictive modeling, highlighting the role of neural networks, support vector machines, and ensemble methods in tackling complex analytical challenges. Special emphasis is placed on the convergence of big data with distributed computing paradigms, including cloud and edge computing, to address challenges in storage, computation, and real-time analytics. The integration of ethical considerations, including data privacy and compliance with global standards, ensures a holistic perspective on data management. Practical applications across healthcare, finance, marketing, and policy-making illustrate the real-world impact of these technologies. Through comprehensive case studies and Python-based implementations, this work equips researchers, practitioners, and data enthusiasts with the tools to navigate the complexities of modern data analytics. It bridges the gap between theory and practice, fostering the development of innovative solutions for managing and leveraging data in the era of artificial intelligence.

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

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.

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

The advancement in generative AI could be boosted with more accessible mathematics. Beyond human-AI chat, large language models (LLMs) are emerging in programming, algorithm discovery, and theorem proving, yet their genomics application is limited. This project introduces Math Agents and mathematical embedding as fresh entries to the "Moore's Law of Mathematics", using a GPT-based workflow to convert equations from literature into LaTeX and Python formats. While many digital equation representations exist, there's a lack of automated large-scale evaluation tools. LLMs are pivotal as linguistic user interfaces, providing natural language access for human-AI chat and formal languages for large-scale AI-assisted computational infrastructure. Given the infinite formal possibility spaces, Math Agents, which interact with math, could potentially shift us from "big data" to "big math". Math, unlike the more flexible natural language, has properties subject to proof, enabling its use beyond traditional applications like high-validation math-certified icons for AI alignment aims. This project aims to use Math Agents and mathematical embeddings to address the ageing issue in information systems biology by applying multiscalar physics mathematics to disease models and genomic data. Generative AI with episodic memory could help analyse causal relations in longitudinal health records, using SIR Precision Health models. Genomic data is suggested for addressing the unsolved Alzheimer's disease problem.

Recent advancements in artificial intelligence (AI) have precipitated significant breakthroughs in healthcare, particularly in refining diagnostic procedures. However, previous studies have often been constrained to limited functionalities. This study introduces MiniGPT-Med, a vision-language model derived from large-scale language models and tailored for medical applications. MiniGPT-Med demonstrates remarkable versatility across various imaging modalities, including X-rays, CT scans, and MRIs, enhancing its utility. The model is capable of performing tasks such as medical report generation, visual question answering (VQA), and disease identification within medical imagery. Its integrated processing of both image and textual clinical data markedly improves diagnostic accuracy. Our empirical assessments confirm MiniGPT-Med's superior performance in disease grounding, medical report generation, and VQA benchmarks, representing a significant step towards reducing the gap in assisting radiology practice. Furthermore, it achieves state-of-the-art performance on medical report generation, higher than the previous best model by 19\% accuracy. MiniGPT-Med promises to become a general interface for radiology diagnoses, enhancing diagnostic efficiency across a wide range of medical imaging applications.

In the era of digital healthcare, the huge volumes of textual information generated every day in hospitals constitute an essential but underused asset that could be exploited with task-specific, fine-tuned biomedical language representation models, improving patient care and management. For such specialized domains, previous research has shown that fine-tuning models stemming from broad-coverage checkpoints can largely benefit additional training rounds over large-scale in-domain resources. However, these resources are often unreachable for less-resourced languages like Italian, preventing local medical institutions to employ in-domain adaptation. In order to reduce this gap, our work investigates two accessible approaches to derive biomedical language models in languages other than English, taking Italian as a concrete use-case: one based on neural machine translation of English resources, favoring quantity over quality; the other based on a high-grade, narrow-scoped corpus natively written in Italian, thus preferring quality over quantity. Our study shows that data quantity is a harder constraint than data quality for biomedical adaptation, but the concatenation of high-quality data can improve model performance even when dealing with relatively size-limited corpora. The models published from our investigations have the potential to unlock important research opportunities for Italian hospitals and academia. Finally, the set of lessons learned from the study constitutes valuable insights towards a solution to build biomedical language models that are generalizable to other less-resourced languages and different domain settings.

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.

The integration of Large Language Models (LLMs) into healthcare applications offers promising advancements in medical diagnostics, treatment recommendations, and patient care. However, the susceptibility of LLMs to adversarial attacks poses a significant threat, potentially leading to harmful outcomes in delicate medical contexts. This study investigates the vulnerability of LLMs to two types of adversarial attacks in three medical tasks. Utilizing real-world patient data, we demonstrate that both open-source and proprietary LLMs are susceptible to manipulation across multiple tasks. This research further reveals that domain-specific tasks demand more adversarial data in model fine-tuning than general domain tasks for effective attack execution, especially for more capable models. We discover that while integrating adversarial data does not markedly degrade overall model performance on medical benchmarks, it does lead to noticeable shifts in fine-tuned model weights, suggesting a potential pathway for detecting and countering model attacks. This research highlights the urgent need for robust security measures and the development of defensive mechanisms to safeguard LLMs in medical applications, to ensure their safe and effective deployment in healthcare settings.

Clinicians spend large amounts of time on clinical documentation, and inefficiencies impact quality of care and increase clinician burnout. Despite the promise of electronic medical records (EMR), the transition from paper-based records has been negatively associated with clinician wellness, in part due to poor user experience, increased burden of documentation, and alert fatigue. In this study, we present Almanac Copilot, an autonomous agent capable of assisting clinicians with EMR-specific tasks such as information retrieval and order placement. On EHR-QA, a synthetic evaluation dataset of 300 common EHR queries based on real patient data, Almanac Copilot obtains a successful task completion rate of 74% (n = 221 tasks) with a mean score of 2.45 over 3 (95% CI:2.34-2.56). By automating routine tasks and streamlining the documentation process, our findings highlight the significant potential of autonomous agents to mitigate the cognitive load imposed on clinicians by current EMR systems.

This work proposes a framework for optimizing machine learning algorithms. The practicality of the framework is illustrated using an important case study from the healthcare domain, which is predicting the admission status of emergency department (ED) patients (e.g., admitted vs. discharged) using patient data at the time of triage. The proposed framework can mitigate the crowding problem by proactively planning the patient boarding process. A large retrospective dataset of patient records is obtained from the electronic health record database of all ED visits over three years from three major locations of a healthcare provider in the Midwest of the US. Three machine learning algorithms are proposed: T-XGB, T-ADAB, and T-MLP. T-XGB integrates extreme gradient boosting (XGB) and Tabu Search (TS), T-ADAB integrates Adaboost and TS, and T-MLP integrates multi-layer perceptron (MLP) and TS. The proposed algorithms are compared with the traditional algorithms: XGB, ADAB, and MLP, in which their parameters are tunned using grid search. The three proposed algorithms and the original ones are trained and tested using nine data groups that are obtained from different feature selection methods. In other words, 54 models are developed. Performance was evaluated using five measures: Area under the curve (AUC), sensitivity, specificity, F1, and accuracy. The results show that the newly proposed algorithms resulted in high AUC and outperformed the traditional algorithms. The T-ADAB performs the best among the newly developed algorithms. The AUC, sensitivity, specificity, F1, and accuracy of the best model are 95.4%, 99.3%, 91.4%, 95.2%, 97.2%, respectively.

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.

Electronic health records (EHRs) contain vast amounts of complex data, but harmonizing and processing this information remains a challenging and costly task requiring significant clinical expertise. While large language models (LLMs) have shown promise in various healthcare applications, their potential for abstracting medical concepts from EHRs remains largely unexplored. We introduce EHRmonize, a framework leveraging LLMs to abstract medical concepts from EHR data. Our study uses medication data from two real-world EHR databases to evaluate five LLMs on two free-text extraction and six binary classification tasks across various prompting strategies. GPT-4o's with 10-shot prompting achieved the highest performance in all tasks, accompanied by Claude-3.5-Sonnet in a subset of tasks. GPT-4o achieved an accuracy of 97% in identifying generic route names, 82% for generic drug names, and 100% in performing binary classification of antibiotics. While EHRmonize significantly enhances efficiency, reducing annotation time by an estimated 60%, we emphasize that clinician oversight remains essential. Our framework, available as a Python package, offers a promising tool to assist clinicians in EHR data abstraction, potentially accelerating healthcare research and improving data harmonization processes.

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.

The ability of large language models (LLMs) to follow natural language instructions with human-level fluency suggests many opportunities in healthcare to reduce administrative burden and improve quality of care. However, evaluating LLMs on realistic text generation tasks for healthcare remains challenging. Existing question answering datasets for electronic health record (EHR) data fail to capture the complexity of information needs and documentation burdens experienced by clinicians. To address these challenges, we introduce MedAlign, a benchmark dataset of 983 natural language instructions for EHR data. MedAlign is curated by 15 clinicians (7 specialities), includes clinician-written reference responses for 303 instructions, and provides 276 longitudinal EHRs for grounding instruction-response pairs. We used MedAlign to evaluate 6 general domain LLMs, having clinicians rank the accuracy and quality of each LLM response. We found high error rates, ranging from 35% (GPT-4) to 68% (MPT-7B-Instruct), and an 8.3% drop in accuracy moving from 32k to 2k context lengths for GPT-4. Finally, we report correlations between clinician rankings and automated natural language generation metrics as a way to rank LLMs without human review. We make MedAlign available under a research data use agreement to enable LLM evaluations on tasks aligned with clinician needs and preferences.

Artificial intelligence (AI) has demonstrated significant potential in ECG analysis and cardiovascular disease assessment. Recently, foundation models have played a remarkable role in advancing medical AI. The development of an ECG foundation model holds the promise of elevating AI-ECG research to new heights. However, building such a model faces several challenges, including insufficient database sample sizes and inadequate generalization across multiple domains. Additionally, there is a notable performance gap between single-lead and multi-lead ECG analyses. We introduced an ECG Foundation Model (ECGFounder), a general-purpose model that leverages real-world ECG annotations from cardiology experts to broaden the diagnostic capabilities of ECG analysis. ECGFounder was trained on over 10 million ECGs with 150 label categories from the Harvard-Emory ECG Database, enabling comprehensive cardiovascular disease diagnosis through ECG analysis. The model is designed to be both an effective out-of-the-box solution, and a to be fine-tunable for downstream tasks, maximizing usability. Importantly, we extended its application to lower rank ECGs, and arbitrary single-lead ECGs in particular. ECGFounder is applicable to supporting various downstream tasks in mobile monitoring scenarios. Experimental results demonstrate that ECGFounder achieves expert-level performance on internal validation sets, with AUROC exceeding 0.95 for eighty diagnoses. It also shows strong classification performance and generalization across various diagnoses on external validation sets. When fine-tuned, ECGFounder outperforms baseline models in demographic analysis, clinical event detection, and cross-modality cardiac rhythm diagnosis. The trained model and data will be publicly released upon publication through the bdsp.io. Our code is available at https://github.com/bdsp-core/ECGFounder

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

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

Large language models (LLMs) are transforming the ways the general public accesses and consumes information. Their influence is particularly pronounced in pivotal sectors like healthcare, where lay individuals are increasingly appropriating LLMs as conversational agents for everyday queries. While LLMs demonstrate impressive language understanding and generation proficiencies, concerns regarding their safety remain paramount in these high-stake domains. Moreover, the development of LLMs is disproportionately focused on English. It remains unclear how these LLMs perform in the context of non-English languages, a gap that is critical for ensuring equity in the real-world use of these systems.This paper provides a framework to investigate the effectiveness of LLMs as multi-lingual dialogue systems for healthcare queries. Our empirically-derived framework XlingEval focuses on three fundamental criteria for evaluating LLM responses to naturalistic human-authored health-related questions: correctness, consistency, and verifiability. Through extensive experiments on four major global languages, including English, Spanish, Chinese, and Hindi, spanning three expert-annotated large health Q&A datasets, and through an amalgamation of algorithmic and human-evaluation strategies, we found a pronounced disparity in LLM responses across these languages, indicating a need for enhanced cross-lingual capabilities. We further propose XlingHealth, a cross-lingual benchmark for examining the multilingual capabilities of LLMs in the healthcare context. Our findings underscore the pressing need to bolster the cross-lingual capacities of these models, and to provide an equitable information ecosystem accessible to all.

Medical coding is the task of assigning medical codes to clinical free-text documentation. Healthcare professionals manually assign such codes to track patient diagnoses and treatments. Automated medical coding can considerably alleviate this administrative burden. In this paper, we reproduce, compare, and analyze state-of-the-art automated medical coding machine learning models. We show that several models underperform due to weak configurations, poorly sampled train-test splits, and insufficient evaluation. In previous work, the macro F1 score has been calculated sub-optimally, and our correction doubles it. We contribute a revised model comparison using stratified sampling and identical experimental setups, including hyperparameters and decision boundary tuning. We analyze prediction errors to validate and falsify assumptions of previous works. The analysis confirms that all models struggle with rare codes, while long documents only have a negligible impact. Finally, we present the first comprehensive results on the newly released MIMIC-IV dataset using the reproduced models. We release our code, model parameters, and new MIMIC-III and MIMIC-IV training and evaluation pipelines to accommodate fair future comparisons.

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).

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

Explainable Artificial Intelligence (XAI) addresses the growing need for transparency and interpretability in AI systems, enabling trust and accountability in decision-making processes. This book offers a comprehensive guide to XAI, bridging foundational concepts with advanced methodologies. It explores interpretability in traditional models such as Decision Trees, Linear Regression, and Support Vector Machines, alongside the challenges of explaining deep learning architectures like CNNs, RNNs, and Large Language Models (LLMs), including BERT, GPT, and T5. The book presents practical techniques such as SHAP, LIME, Grad-CAM, counterfactual explanations, and causal inference, supported by Python code examples for real-world applications. Case studies illustrate XAI's role in healthcare, finance, and policymaking, demonstrating its impact on fairness and decision support. The book also covers evaluation metrics for explanation quality, an overview of cutting-edge XAI tools and frameworks, and emerging research directions, such as interpretability in federated learning and ethical AI considerations. Designed for a broad audience, this resource equips readers with the theoretical insights and practical skills needed to master XAI. Hands-on examples and additional resources are available at the companion GitHub repository: https://github.com/Echoslayer/XAI_From_Classical_Models_to_LLMs.

Medical Dialogue Generation serves a critical role in telemedicine by facilitating the dissemination of medical expertise to patients. Existing studies focus on incorporating textual representations, which have limited their ability to represent the semantics of text, such as ignoring important medical entities. To enhance the model's understanding of the textual semantics and the medical knowledge including entities and relations, we introduce the use of Abstract Meaning Representations (AMR) to construct graphical representations that delineate the roles of language constituents and medical entities within the dialogues. In this paper, We propose a novel framework that models dialogues between patients and healthcare professionals using AMR graphs, where the neural networks incorporate textual and graphical knowledge with a dual attention mechanism. Experimental results show that our framework outperforms strong baseline models in medical dialogue generation, demonstrating the effectiveness of AMR graphs in enhancing the representations of medical knowledge and logical relationships. Furthermore, to support future research in this domain, we provide the corresponding source code at https://github.com/Bernard-Yang/MedDiaAMR.

As large language models (LLMs) like OpenAI's GPT series continue to make strides, we witness the emergence of artificial intelligence applications in an ever-expanding range of fields. In medicine, these LLMs hold considerable promise for improving medical workflows, diagnostics, patient care, and education. Yet, there is an urgent need for open-source models that can be deployed on-premises to safeguard patient privacy. In our work, we present an innovative dataset consisting of over 160,000 entries, specifically crafted to fine-tune LLMs for effective medical applications. We investigate the impact of fine-tuning these datasets on publicly accessible pre-trained LLMs, and subsequently, we juxtapose the performance of pre-trained-only models against the fine-tuned models concerning the examinations that future medical doctors must pass to achieve certification.

Panoramic X-rays are frequently used in dentistry for treatment planning, but their interpretation can be both time-consuming and prone to error. Artificial intelligence (AI) has the potential to aid in the analysis of these X-rays, thereby improving the accuracy of dental diagnoses and treatment plans. Nevertheless, designing automated algorithms for this purpose poses significant challenges, mainly due to the scarcity of annotated data and variations in anatomical structure. To address these issues, the Dental Enumeration and Diagnosis on Panoramic X-rays Challenge (DENTEX) has been organized in association with the International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) in 2023. This challenge aims to promote the development of algorithms for multi-label detection of abnormal teeth, using three types of hierarchically annotated data: partially annotated quadrant data, partially annotated quadrant-enumeration data, and fully annotated quadrant-enumeration-diagnosis data, inclusive of four different diagnoses. In this paper, we present the results of evaluating participant algorithms on the fully annotated data, additionally investigating performance variation for quadrant, enumeration, and diagnosis labels in the detection of abnormal teeth. The provision of this annotated dataset, alongside the results of this challenge, may lay the groundwork for the creation of AI-powered tools that can offer more precise and efficient diagnosis and treatment planning in the field of dentistry. The evaluation code and datasets can be accessed at https://github.com/ibrahimethemhamamci/DENTEX

Large Language Models (LLMs) present immense potential in the medical field, yet concerns over data privacy, regulatory compliance, and model stability restrict their widespread adoption. Although the distillation of high-performing closed-source LLMs has proven effective for general tasks, their application in healthcare is limited due to reduced domain knowledge and remnants of alignment behavior hindering clinical tasks. To address these challenges, we propose Dialogue-Based Knowledge Encoding (DBKE). DBKE enhances models' implicit knowledge base and primes them for conversational recall, augmenting their conversational capabilities and enabling a soft alignment for subsequent use cases. By transforming dense academic source text into synthetic dialogue, DBKE broadens the model's knowledge base and enables a soft alignment that guides downstream behaviours. We present Clinical Camel, an open-source, healthcare-focused conversational model, to showcase the effectiveness of DBKE. Clinical Camel outperforms GPT-3.5 on the United States Medical Licensing Examination (USMLE) Step 1 and Step 3 with scores of 53.2 % and 58.2 %, respectively, compared to GPT-3.5's scores of 36.1 % and 55.7 %. Clinical Camel adeptly handles multi-stage clinical case problems, provides adaptive counseling, and generates clinical notes. However, it is prone to hallucinations, which pose a significant obstacle in safety-critical settings. The performance of Clinical Camel underscores the importance of continued research and development of open-source models for the safe and effective integration of LLMs in healthcare settings.

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

Recent large language models (LLMs) offer the potential to support public health monitoring by facilitating health disclosure through open-ended conversations but rarely preserve the knowledge gained about individuals across repeated interactions. Augmenting LLMs with long-term memory (LTM) presents an opportunity to improve engagement and self-disclosure, but we lack an understanding of how LTM impacts people's interaction with LLM-driven chatbots in public health interventions. We examine the case of CareCall -- an LLM-driven voice chatbot with LTM -- through the analysis of 1,252 call logs and interviews with nine users. We found that LTM enhanced health disclosure and fostered positive perceptions of the chatbot by offering familiarity. However, we also observed challenges in promoting self-disclosure through LTM, particularly around addressing chronic health conditions and privacy concerns. We discuss considerations for LTM integration in LLM-driven chatbots for public health monitoring, including carefully deciding what topics need to be remembered in light of public health goals.

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

Building an intelligent and efficient medical assistant is still a challenging AI problem. The major limitation comes from the data modality scarceness, which reduces comprehensive patient perception. This demo paper presents the GigaPevt, the first multimodal medical assistant that combines the dialog capabilities of large language models with specialized medical models. Such an approach shows immediate advantages in dialog quality and metric performance, with a 1.18% accuracy improvement in the question-answering task.

Artificial Intelligence (AI) advancement is heavily dependent on access to large-scale, high-quality training data. However, in specialized domains such as healthcare, data acquisition faces significant constraints due to privacy regulations, ethical considerations, and limited availability. While synthetic data generation offers a promising solution, conventional approaches typically require substantial real data for training generative models. The emergence of large-scale prompt-based models presents new opportunities for synthetic data generation without direct access to protected data. However, crafting effective prompts for domain-specific data generation remains challenging, and manual prompt engineering proves insufficient for achieving output with sufficient precision and authenticity. We review recent developments in automatic prompt optimization, following PRISMA guidelines. We analyze six peer-reviewed studies published between 2020 and 2024 that focus on automatic data-free prompt optimization methods. Our analysis reveals three approaches: feedback-driven, error-based, and control-theoretic. Although all approaches demonstrate promising capabilities in prompt refinement and adaptation, our findings suggest the need for an integrated framework that combines complementary optimization techniques to enhance synthetic data generation while minimizing manual intervention. We propose future research directions toward developing robust, iterative prompt optimization frameworks capable of improving the quality of synthetic data. This advancement can be particularly crucial for sensitive fields and in specialized domains where data access is restricted, potentially transforming how we approach synthetic data generation for AI development.

Ensuring the accuracy of responses provided by large language models (LLMs) is crucial, particularly in clinical settings where incorrect information may directly impact patient health. To address this challenge, we construct K-QA, a dataset containing 1,212 patient questions originating from real-world conversations held on K Health (an AI-driven clinical platform). We employ a panel of in-house physicians to answer and manually decompose a subset of K-QA into self-contained statements. Additionally, we formulate two NLI-based evaluation metrics approximating recall and precision: (1) comprehensiveness, measuring the percentage of essential clinical information in the generated answer and (2) hallucination rate, measuring the number of statements from the physician-curated response contradicted by the LLM answer. Finally, we use K-QA along with these metrics to evaluate several state-of-the-art models, as well as the effect of in-context learning and medically-oriented augmented retrieval schemes developed by the authors. Our findings indicate that in-context learning improves the comprehensiveness of the models, and augmented retrieval is effective in reducing hallucinations. We make K-QA available to to the community to spur research into medically accurate NLP applications.

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.

This review paper explores recent advances in deep learning approaches for non-invasive cognitive impairment detection. We examine various non-invasive indicators of cognitive decline, including speech and language, facial, and motoric mobility. The paper provides an overview of relevant datasets, feature-extracting techniques, and deep-learning architectures applied to this domain. We have analyzed the performance of different methods across modalities and observed that speech and language-based methods generally achieved the highest detection performance. Studies combining acoustic and linguistic features tended to outperform those using a single modality. Facial analysis methods showed promise for visual modalities but were less extensively studied. Most papers focused on binary classification (impaired vs. non-impaired), with fewer addressing multi-class or regression tasks. Transfer learning and pre-trained language models emerged as popular and effective techniques, especially for linguistic analysis. Despite significant progress, several challenges remain, including data standardization and accessibility, model explainability, longitudinal analysis limitations, and clinical adaptation. Lastly, we propose future research directions, such as investigating language-agnostic speech analysis methods, developing multi-modal diagnostic systems, and addressing ethical considerations in AI-assisted healthcare. By synthesizing current trends and identifying key obstacles, this review aims to guide further development of deep learning-based cognitive impairment detection systems to improve early diagnosis and ultimately patient outcomes.

Retrieval-augmented generation (RAG) is a well-suited technique for retrieving privacy-sensitive Electronic Health Records (EHR). It can serve as a key module of the healthcare copilot, helping reduce misdiagnosis for healthcare practitioners and patients. However, the diagnostic accuracy and specificity of existing heuristic-based RAG models used in the medical domain are inadequate, particularly for diseases with similar manifestations. This paper proposes MedRAG, a RAG model enhanced by knowledge graph (KG)-elicited reasoning for the medical domain that retrieves diagnosis and treatment recommendations based on manifestations. MedRAG systematically constructs a comprehensive four-tier hierarchical diagnostic KG encompassing critical diagnostic differences of various diseases. These differences are dynamically integrated with similar EHRs retrieved from an EHR database, and reasoned within a large language model. This process enables more accurate and specific decision support, while also proactively providing follow-up questions to enhance personalized medical decision-making. MedRAG is evaluated on both a public dataset DDXPlus and a private chronic pain diagnostic dataset (CPDD) collected from Tan Tock Seng Hospital, and its performance is compared against various existing RAG methods. Experimental results show that, leveraging the information integration and relational abilities of the KG, our MedRAG provides more specific diagnostic insights and outperforms state-of-the-art models in reducing misdiagnosis rates. Our code will be available at https://github.com/SNOWTEAM2023/MedRAG

The increasing complexity of Artificial Intelligence models poses challenges to interpretability, particularly in the healthcare sector. This study investigates the impact of deep learning model complexity and Explainable AI (XAI) efficacy, utilizing four ResNet architectures (ResNet-18, 34, 50, 101). Through methodical experimentation on 4,369 lung X-ray images of COVID-19-infected and healthy patients, the research evaluates models' classification performance and the relevance of corresponding XAI explanations with respect to the ground-truth disease masks. Results indicate that the increase in model complexity is associated with a decrease in classification accuracy and AUC-ROC scores (ResNet-18: 98.4%, 0.997; ResNet-101: 95.9%, 0.988). Notably, in eleven out of twelve statistical tests performed, no statistically significant differences occurred between XAI quantitative metrics - Relevance Rank Accuracy and the proposed Positive Attribution Ratio - across trained models. These results suggest that increased model complexity does not consistently lead to higher performance or relevance of explanations for models' decision-making processes.

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.

Machine learning (ML) has the potential to revolutionize various domains, but its adoption is often hindered by the disconnect between the needs of domain experts and translating these needs into robust and valid ML tools. Despite recent advances in LLM-based co-pilots to democratize ML for non-technical domain experts, these systems remain predominantly focused on model-centric aspects while overlooking critical data-centric challenges. This limitation is problematic in complex real-world settings where raw data often contains complex issues, such as missing values, label noise, and domain-specific nuances requiring tailored handling. To address this we introduce CliMB-DC, a human-guided, data-centric framework for LLM co-pilots that combines advanced data-centric tools with LLM-driven reasoning to enable robust, context-aware data processing. At its core, CliMB-DC introduces a novel, multi-agent reasoning system that combines a strategic coordinator for dynamic planning and adaptation with a specialized worker agent for precise execution. Domain expertise is then systematically incorporated to guide the reasoning process using a human-in-the-loop approach. To guide development, we formalize a taxonomy of key data-centric challenges that co-pilots must address. Thereafter, to address the dimensions of the taxonomy, we integrate state-of-the-art data-centric tools into an extensible, open-source architecture, facilitating the addition of new tools from the research community. Empirically, using real-world healthcare datasets we demonstrate CliMB-DC's ability to transform uncurated datasets into ML-ready formats, significantly outperforming existing co-pilot baselines for handling data-centric challenges. CliMB-DC promises to empower domain experts from diverse domains -- healthcare, finance, social sciences and more -- to actively participate in driving real-world impact using ML.

The emergence of vision-language models has transformed medical AI, enabling unprecedented advances in diagnostic capability and clinical applications. However, progress in dermatology has lagged behind other medical domains due to the lack of standard image-text pairs. Existing dermatological datasets are limited in both scale and depth, offering only single-label annotations across a narrow range of diseases instead of rich textual descriptions, and lacking the crucial clinical context needed for real-world applications. To address these limitations, we present Derm1M, the first large-scale vision-language dataset for dermatology, comprising 1,029,761 image-text pairs. Built from diverse educational resources and structured around a standard ontology collaboratively developed by experts, Derm1M provides comprehensive coverage for over 390 skin conditions across four hierarchical levels and 130 clinical concepts with rich contextual information such as medical history, symptoms, and skin tone. To demonstrate Derm1M potential in advancing both AI research and clinical application, we pretrained a series of CLIP-like models, collectively called DermLIP, on this dataset. The DermLIP family significantly outperforms state-of-the-art foundation models on eight diverse datasets across multiple tasks, including zero-shot skin disease classification, clinical and artifacts concept identification, few-shot/full-shot learning, and cross-modal retrieval. Our dataset and code will be public.

AI agents are increasingly autonomous in their interactions with human users and tools, leading to increased interactional safety risks. We present HAICOSYSTEM, a framework examining AI agent safety within diverse and complex social interactions. HAICOSYSTEM features a modular sandbox environment that simulates multi-turn interactions between human users and AI agents, where the AI agents are equipped with a variety of tools (e.g., patient management platforms) to navigate diverse scenarios (e.g., a user attempting to access other patients' profiles). To examine the safety of AI agents in these interactions, we develop a comprehensive multi-dimensional evaluation framework that uses metrics covering operational, content-related, societal, and legal risks. Through running 1840 simulations based on 92 scenarios across seven domains (e.g., healthcare, finance, education), we demonstrate that HAICOSYSTEM can emulate realistic user-AI interactions and complex tool use by AI agents. Our experiments show that state-of-the-art LLMs, both proprietary and open-sourced, exhibit safety risks in over 50\% cases, with models generally showing higher risks when interacting with simulated malicious users. Our findings highlight the ongoing challenge of building agents that can safely navigate complex interactions, particularly when faced with malicious users. To foster the AI agent safety ecosystem, we release a code platform that allows practitioners to create custom scenarios, simulate interactions, and evaluate the safety and performance of their agents.

Reproducibility remains a significant challenge in machine learning (ML) for healthcare. In this field, datasets, model pipelines, and even task/cohort definitions are often private, leading to a significant barrier in sharing, iterating, and understanding ML results on electronic health record (EHR) datasets. In this paper, we address a significant part of this problem by introducing the Automatic Cohort Extraction System for Event-Stream Datasets (ACES). This tool is designed to simultaneously simplify the development of task/cohorts for ML in healthcare and enable the reproduction of these cohorts, both at an exact level for single datasets and at a conceptual level across datasets. To accomplish this, ACES provides (1) a highly intuitive and expressive configuration language for defining both dataset-specific concepts and dataset-agnostic inclusion/exclusion criteria, and (2) a pipeline to automatically extract patient records that meet these defined criteria from real-world data. ACES can be automatically applied to any dataset in either the Medical Event Data Standard (MEDS) or EventStreamGPT (ESGPT) formats, or to *any* dataset for which the necessary task-specific predicates can be extracted in an event-stream form. ACES has the potential to significantly lower the barrier to entry for defining ML tasks, redefine the way researchers interact with EHR datasets, and significantly improve the state of reproducibility for ML studies in this modality. ACES is available at https://github.com/justin13601/aces.

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.

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.

Large language models (LLMs) hold immense promise to serve complex health information needs but also have the potential to introduce harm and exacerbate health disparities. Reliably evaluating equity-related model failures is a critical step toward developing systems that promote health equity. In this work, we present resources and methodologies for surfacing biases with potential to precipitate equity-related harms in long-form, LLM-generated answers to medical questions and then conduct an empirical case study with Med-PaLM 2, resulting in the largest human evaluation study in this area to date. Our contributions include a multifactorial framework for human assessment of LLM-generated answers for biases, and EquityMedQA, a collection of seven newly-released datasets comprising both manually-curated and LLM-generated questions enriched for adversarial queries. Both our human assessment framework and dataset design process are grounded in an iterative participatory approach and review of possible biases in Med-PaLM 2 answers to adversarial queries. Through our empirical study, we find that the use of a collection of datasets curated through a variety of methodologies, coupled with a thorough evaluation protocol that leverages multiple assessment rubric designs and diverse rater groups, surfaces biases that may be missed via narrower evaluation approaches. Our experience underscores the importance of using diverse assessment methodologies and involving raters of varying backgrounds and expertise. We emphasize that while our framework can identify specific forms of bias, it is not sufficient to holistically assess whether the deployment of an AI system promotes equitable health outcomes. We hope the broader community leverages and builds on these tools and methods towards realizing a shared goal of LLMs that promote accessible and equitable healthcare for all.

This position paper emphasizes the critical gap in the evaluation of Explainable AI (XAI) due to the lack of standardized and reliable metrics, which diminishes its practical value, trustworthiness, and ability to meet regulatory requirements. Current evaluation methods are often fragmented, subjective, and biased, making them prone to manipulation and complicating the assessment of complex models. A central issue is the absence of a ground truth for explanations, complicating comparisons across various XAI approaches. To address these challenges, we advocate for widespread research into developing robust, context-sensitive evaluation metrics. These metrics should be resistant to manipulation, relevant to each use case, and based on human judgment and real-world applicability. We also recommend creating domain-specific evaluation benchmarks that align with the user and regulatory needs of sectors such as healthcare and finance. By encouraging collaboration among academia, industry, and regulators, we can create standards that balance flexibility and consistency, ensuring XAI explanations are meaningful, trustworthy, and compliant with evolving regulations.

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

Recently, large language model (LLM) based artificial intelligence (AI) systems have demonstrated remarkable capabilities in natural language understanding and generation. However, these models face a significant challenge when it comes to sensitive applications, such as reasoning over medical knowledge and answering medical questions in a physician-like manner. Prior studies attempted to overcome this challenge by increasing the model size (>100B) to learn more general medical knowledge, while there is still room for improvement in LLMs with smaller-scale model sizes (<100B). In this work, we start from a pre-trained general LLM model (AntGLM-10B) and fine-tune it from a medical beginner towards a medical expert (called AntGLM-Med-10B), which leverages a 3-stage optimization procedure, i.e., general medical knowledge injection, medical domain instruction tuning, and specific medical task adaptation. Our contributions are threefold: (1) We specifically investigate how to adapt a pre-trained general LLM in medical domain, especially for a specific medical task. (2) We collect and construct large-scale medical datasets for each stage of the optimization process. These datasets encompass various data types and tasks, such as question-answering, medical reasoning, multi-choice questions, and medical conversations. (3) Specifically for multi-choice questions in the medical domain, we propose a novel Verification-of-Choice approach for prompting engineering, which significantly enhances the reasoning ability of LLMs. Remarkably, by combining the above approaches, our AntGLM-Med-10B model can outperform the most of LLMs on PubMedQA, including both general and medical LLMs, even when these LLMs have larger model size.

Over 85 million computed tomography (CT) scans are performed annually in the US, of which approximately one quarter focus on the abdomen. Given the current radiologist shortage, there is a large impetus to use artificial intelligence to alleviate the burden of interpreting these complex imaging studies. Prior state-of-the-art approaches for automated medical image interpretation leverage vision language models (VLMs). However, current medical VLMs are generally limited to 2D images and short reports, and do not leverage electronic health record (EHR) data for supervision. We introduce Merlin - a 3D VLM that we train using paired CT scans (6+ million images from 15,331 CTs), EHR diagnosis codes (1.8+ million codes), and radiology reports (6+ million tokens). We evaluate Merlin on 6 task types and 752 individual tasks. The non-adapted (off-the-shelf) tasks include zero-shot findings classification (31 findings), phenotype classification (692 phenotypes), and zero-shot cross-modal retrieval (image to findings and image to impressions), while model adapted tasks include 5-year disease prediction (6 diseases), radiology report generation, and 3D semantic segmentation (20 organs). We perform internal validation on a test set of 5,137 CTs, and external validation on 7,000 clinical CTs and on two public CT datasets (VerSe, TotalSegmentator). Beyond these clinically-relevant evaluations, we assess the efficacy of various network architectures and training strategies to depict that Merlin has favorable performance to existing task-specific baselines. We derive data scaling laws to empirically assess training data needs for requisite downstream task performance. Furthermore, unlike conventional VLMs that require hundreds of GPUs for training, we perform all training on a single GPU.

Developing the required technology to assist medical experts in their everyday activities is currently a hot topic in the Artificial Intelligence research field. Thus, a number of large language models (LLMs) and automated benchmarks have recently been proposed with the aim of facilitating information extraction in Evidence-Based Medicine (EBM) using natural language as a tool for mediating in human-AI interaction. The most representative benchmarks are limited to either multiple-choice or long-form answers and are available only in English. In order to address these shortcomings, in this paper we present a new dataset which, unlike previous work: (i) includes not only explanatory arguments for the correct answer, but also arguments to reason why the incorrect answers are not correct; (ii) the explanations are written originally by medical doctors to answer questions from the Spanish Residency Medical Exams. Furthermore, this new benchmark allows us to setup a novel extractive task which consists of identifying the explanation of the correct answer written by medical doctors. An additional benefit of our setting is that we can leverage the extractive QA paradigm to automatically evaluate performance of LLMs without resorting to costly manual evaluation by medical experts. Comprehensive experimentation with language models for Spanish shows that sometimes multilingual models fare better than monolingual ones, even outperforming models which have been adapted to the medical domain. Furthermore, results across the monolingual models are mixed, with supposedly smaller and inferior models performing competitively. In any case, the obtained results show that our novel dataset and approach can be an effective technique to help medical practitioners in identifying relevant evidence-based explanations for medical questions.

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

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

Large language models (LLMs) have shown impressive capabilities in natural language processing tasks, including dialogue generation. This research aims to conduct a novel comparative analysis of two prominent techniques, fine-tuning with LoRA (Low-Rank Adaptation) and the Retrieval-Augmented Generation (RAG) framework, in the context of doctor-patient chat conversations with multiple datasets of mixed medical domains. The analysis involves three state-of-the-art models: Llama-2, GPT, and the LSTM model. Employing real-world doctor-patient dialogues, we comprehensively evaluate the performance of models, assessing key metrics such as language quality (perplexity, BLEU score), factual accuracy (fact-checking against medical knowledge bases), adherence to medical guidelines, and overall human judgments (coherence, empathy, safety). The findings provide insights into the strengths and limitations of each approach, shedding light on their suitability for healthcare applications. Furthermore, the research investigates the robustness of the models in handling diverse patient queries, ranging from general health inquiries to specific medical conditions. The impact of domain-specific knowledge integration is also explored, highlighting the potential for enhancing LLM performance through targeted data augmentation and retrieval strategies.

Recent advancements in mixed-modal generative models have enabled flexible integration of information across image-text content. These models have opened new avenues for developing unified biomedical assistants capable of analyzing biomedical images, answering complex questions about them, and predicting the impact of medical procedures on a patient's health. However, existing resources face challenges such as limited data availability, narrow domain coverage, and restricted sources (e.g., medical papers). To address these gaps, we present MedMax, the first large-scale multimodal biomedical instruction-tuning dataset for mixed-modal foundation models. With 1.47 million instances, MedMax encompasses a diverse range of tasks, including multimodal content generation (interleaved image-text data), biomedical image captioning and generation, visual chatting, and report understanding. These tasks span diverse medical domains such as radiology and histopathology. Subsequently, we fine-tune a mixed-modal foundation model on the MedMax dataset, achieving significant performance improvements: a 26% gain over the Chameleon model and an 18.3% improvement over GPT-4o across 12 downstream biomedical visual question-answering tasks. Additionally, we introduce a unified evaluation suite for biomedical tasks, providing a robust framework to guide the development of next-generation mixed-modal biomedical AI assistants.

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.

Rare diseases present unique challenges in healthcare, often suffering from delayed diagnosis and fragmented information landscapes. The scarcity of reliable knowledge in these conditions poses a distinct challenge for Large Language Models (LLMs) in supporting clinical management and delivering precise patient information underscoring the need for focused training on these 'zebra' cases. We present Zebra-Llama, a specialized context-aware language model with high precision Retrieval Augmented Generation (RAG) capability, focusing on Ehlers-Danlos Syndrome (EDS) as our case study. EDS, affecting 1 in 5,000 individuals, exemplifies the complexities of rare diseases with its diverse symptoms, multiple subtypes, and evolving diagnostic criteria. By implementing a novel context-aware fine-tuning methodology trained on questions derived from medical literature, patient experiences, and clinical resources, along with expertly curated responses, Zebra-Llama demonstrates unprecedented capabilities in handling EDS-related queries. On a test set of real-world questions collected from EDS patients and clinicians, medical experts evaluated the responses generated by both models, revealing Zebra-Llama's substantial improvements over base model (Llama 3.1-8B-Instruct) in thoroughness (77.5% vs. 70.1%), accuracy (83.0% vs. 78.8%), clarity (74.7% vs. 72.0%) and citation reliability (70.6% vs. 52.3%). Released as an open-source resource, Zebra-Llama not only provides more accessible and reliable EDS information but also establishes a framework for developing specialized AI solutions for other rare conditions. This work represents a crucial step towards democratizing expert-level knowledge in rare disease management, potentially transforming how healthcare providers and patients navigate the complex landscape of rare diseases.

LLMs have become increasingly capable at accomplishing a range of specialized-tasks and can be utilized to expand equitable access to medical knowledge. Most medical LLMs have involved extensive fine-tuning, leveraging specialized medical data and significant, thus costly, amounts of computational power. Many of the top performing LLMs are proprietary and their access is limited to very few research groups. However, open-source (OS) models represent a key area of growth for medical LLMs due to significant improvements in performance and an inherent ability to provide the transparency and compliance required in healthcare. We present OpenMedLM, a prompting platform which delivers state-of-the-art (SOTA) performance for OS LLMs on medical benchmarks. We evaluated a range of OS foundation LLMs (7B-70B) on four medical benchmarks (MedQA, MedMCQA, PubMedQA, MMLU medical-subset). We employed a series of prompting strategies, including zero-shot, few-shot, chain-of-thought (random selection and kNN selection), and ensemble/self-consistency voting. We found that OpenMedLM delivers OS SOTA results on three common medical LLM benchmarks, surpassing the previous best performing OS models that leveraged computationally costly extensive fine-tuning. The model delivers a 72.6% accuracy on the MedQA benchmark, outperforming the previous SOTA by 2.4%, and achieves 81.7% accuracy on the MMLU medical-subset, establishing itself as the first OS LLM to surpass 80% accuracy on this benchmark. Our results highlight medical-specific emergent properties in OS LLMs which have not yet been documented to date elsewhere, and showcase the benefits of further leveraging prompt engineering to improve the performance of accessible LLMs for medical applications.

Synthetic data generation offers a promising solution to enhance the usefulness of Electronic Healthcare Records (EHR) by generating realistic de-identified data. However, the existing literature primarily focuses on the quality of synthetic health data, neglecting the crucial aspect of fairness in downstream predictions. Consequently, models trained on synthetic EHR have faced criticism for producing biased outcomes in target tasks. These biases can arise from either spurious correlations between features or the failure of models to accurately represent sub-groups. To address these concerns, we present Bias-transforming Generative Adversarial Networks (Bt-GAN), a GAN-based synthetic data generator specifically designed for the healthcare domain. In order to tackle spurious correlations (i), we propose an information-constrained Data Generation Process that enables the generator to learn a fair deterministic transformation based on a well-defined notion of algorithmic fairness. To overcome the challenge of capturing exact sub-group representations (ii), we incentivize the generator to preserve sub-group densities through score-based weighted sampling. This approach compels the generator to learn from underrepresented regions of the data manifold. We conduct extensive experiments using the MIMIC-III database. Our results demonstrate that Bt-GAN achieves SOTA accuracy while significantly improving fairness and minimizing bias amplification. We also perform an in-depth explainability analysis to provide additional evidence supporting the validity of our study. In conclusion, our research introduces a novel and professional approach to addressing the limitations of synthetic data generation in the healthcare domain. By incorporating fairness considerations and leveraging advanced techniques such as GANs, we pave the way for more reliable and unbiased predictions in healthcare applications.

People experiencing severe distress increasingly use Large Language Model (LLM) chatbots as mental health support tools. Discussions on social media have described how engagements were lifesaving for some, but evidence suggests that general-purpose LLM chatbots also have notable risks that could endanger the welfare of users if not designed responsibly. In this study, we investigate the lived experiences of people who have used LLM chatbots for mental health support. We build on interviews with 21 individuals from globally diverse backgrounds to analyze how users create unique support roles for their chatbots, fill in gaps in everyday care, and navigate associated cultural limitations when seeking support from chatbots. We ground our analysis in psychotherapy literature around effective support, and introduce the concept of therapeutic alignment, or aligning AI with therapeutic values for mental health contexts. Our study offers recommendations for how designers can approach the ethical and effective use of LLM chatbots and other AI mental health support tools in mental health care.

In this paper, we introduce InMD-X, a collection of multiple large language models specifically designed to cater to the unique characteristics and demands of Internal Medicine Doctors (IMD). InMD-X represents a groundbreaking development in natural language processing, offering a suite of language models fine-tuned for various aspects of the internal medicine field. These models encompass a wide range of medical sub-specialties, enabling IMDs to perform more efficient and accurate research, diagnosis, and documentation. InMD-X's versatility and adaptability make it a valuable tool for improving the healthcare industry, enhancing communication between healthcare professionals, and advancing medical research. Each model within InMD-X is meticulously tailored to address specific challenges faced by IMDs, ensuring the highest level of precision and comprehensiveness in clinical text analysis and decision support. This paper provides an overview of the design, development, and evaluation of InMD-X, showcasing its potential to revolutionize the way internal medicine practitioners interact with medical data and information. We present results from extensive testing, demonstrating the effectiveness and practical utility of InMD-X in real-world medical scenarios.

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

Cancer is a complex disease, the understanding and treatment of which are being aided through increases in the volume of collected data and in the scale of deployed computing power. Consequently, there is a growing need for the development of data-driven and, in particular, deep learning methods for various tasks such as cancer diagnosis, detection, prognosis, and prediction. Despite recent successes, however, designing high-performing deep learning models for nonimage and nontext cancer data is a time-consuming, trial-and-error, manual task that requires both cancer domain and deep learning expertise. To that end, we develop a reinforcement-learning-based neural architecture search to automate deep-learning-based predictive model development for a class of representative cancer data. We develop custom building blocks that allow domain experts to incorporate the cancer-data-specific characteristics. We show that our approach discovers deep neural network architectures that have significantly fewer trainable parameters, shorter training time, and accuracy similar to or higher than those of manually designed architectures. We study and demonstrate the scalability of our approach on up to 1,024 Intel Knights Landing nodes of the Theta supercomputer at the Argonne Leadership Computing Facility.

Mobile mental health applications are seen as a promising way to fulfill the growing need for mental health care. Although there are more than ten thousand mental health apps available on app marketplaces, such as Google Play and Apple App Store, many of them are not evidence-based, or have been minimally evaluated or regulated. The real-life experience and concerns of the app users are largely unknown. To address this knowledge gap, we analyzed 2159 user reviews from 117 Android apps and 2764 user reviews from 76 iOS apps. Our findings include the critiques around inconsistent moderation standards and lack of transparency. App-embedded social features and chatbots were criticized for providing little support during crises. We provide research and design implications for future mental health app developers, discuss the necessity of developing a comprehensive and centralized app development guideline, and the opportunities of incorporating existing AI technology in mental health chatbots.

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.

Adherence to prescribed treatments is crucial for individuals with chronic conditions to avoid costly or adverse health outcomes. For certain patient groups, intensive lifestyle interventions are vital for enhancing medication adherence. Accurate forecasting of treatment adherence can open pathways to developing an on-demand intervention tool, enabling timely and personalized support. With the increasing popularity of smartphones and wearables, it is now easier than ever to develop and deploy smart activity monitoring systems. However, effective forecasting systems for treatment adherence based on wearable sensors are still not widely available. We close this gap by proposing Adherence Forecasting and Intervention with Machine Intelligence (AIMI). AIMI is a knowledge-guided adherence forecasting system that leverages smartphone sensors and previous medication history to estimate the likelihood of forgetting to take a prescribed medication. A user study was conducted with 27 participants who took daily medications to manage their cardiovascular diseases. We designed and developed CNN and LSTM-based forecasting models with various combinations of input features and found that LSTM models can forecast medication adherence with an accuracy of 0.932 and an F-1 score of 0.936. Moreover, through a series of ablation studies involving convolutional and recurrent neural network architectures, we demonstrate that leveraging known knowledge about future and personalized training enhances the accuracy of medication adherence forecasting. Code available: https://github.com/ab9mamun/AIMI.

Medical language models (MLMs) have become pivotal in advancing medical natural language processing. However, prior models that rely on pre-training or supervised fine-tuning often exhibit low data efficiency and limited practicality in real-world clinical applications. While OpenAIs O1 highlights test-time scaling in mathematics, attempts to replicate this approach in medicine typically distill responses from GPT-series models to open-source models, focusing primarily on multiple-choice tasks. This strategy, though straightforward, neglects critical concerns like data privacy and realistic deployment in clinical settings. In this work, we present a deployable, small-scale medical language model, \mone, designed for long-chain reasoning in clinical tasks using a self-evolution paradigm. Starting with a seed dataset of around 8,000 instances spanning five domains and 16 datasets, we prompt a base policy model to perform Monte Carlo Tree Search (MCTS) to construct verifiable reasoning chains. Each reasoning step is assigned an evolution rollout value, allowing verified trajectories to train the policy model and the reward model. During inference, the policy model generates multiple responses, and the reward model selects the one with the highest reward score. Experiments on eleven evaluation datasets demonstrate that \mone outperforms prior open-source models by 2 points, with the addition of the reward model further boosting performance (sim13 points), surpassing GPT-4o-mini. Code and data are available at https://github.com/pixas/MedSSS.

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

Quantitative tools are increasingly appealing for decision support in healthcare, driven by the growing capabilities of advanced AI systems. However, understanding the predictive uncertainties surrounding a tool's output is crucial for decision-makers to ensure reliable and transparent decisions. In this paper, we present a case study on pulmonary nodule detection for lung cancer screening, enhancing an advanced detection model with an uncertainty quantification technique called conformal risk control (CRC). We demonstrate that prediction sets with conformal guarantees are attractive measures of predictive uncertainty in the safety-critical healthcare domain, allowing end-users to achieve arbitrary validity by trading off false positives and providing formal statistical guarantees on model performance. Among ground-truth nodules annotated by at least three radiologists, our model achieves a sensitivity that is competitive with that generally achieved by individual radiologists, with a slight increase in false positives. Furthermore, we illustrate the risks of using off-the-shelve prediction models when faced with ontological uncertainty, such as when radiologists disagree on what constitutes the ground truth on pulmonary nodules.

Multimodal Large Language Models (MLLMs) have tremendous potential to improve the accuracy, availability, and cost-effectiveness of healthcare by providing automated solutions or serving as aids to medical professionals. Despite promising first steps in developing medical MLLMs in the past few years, their capabilities and limitations are not well-understood. Recently, many benchmark datasets have been proposed that test the general medical knowledge of such models across a variety of medical areas. However, the systematic failure modes and vulnerabilities of such models are severely underexplored with most medical benchmarks failing to expose the shortcomings of existing models in this safety-critical domain. In this paper, we introduce MediConfusion, a challenging medical Visual Question Answering (VQA) benchmark dataset, that probes the failure modes of medical MLLMs from a vision perspective. We reveal that state-of-the-art models are easily confused by image pairs that are otherwise visually dissimilar and clearly distinct for medical experts. Strikingly, all available models (open-source or proprietary) achieve performance below random guessing on MediConfusion, raising serious concerns about the reliability of existing medical MLLMs for healthcare deployment. We also extract common patterns of model failure that may help the design of a new generation of more trustworthy and reliable MLLMs in healthcare.

This paper gives an overview of the latest applications of Large Language Models (LLMs) in the healthcare sector, highlighting their transformative role in enhancing medical care quality. By processing vast amounts of data from diverse medical domains, LLMs have become pivotal in assisting doctors, healthcare providers, and patients. We explore their utilization in various medical specialties, such as cancer diagnostics, dentistry, nephrology, dermatology, etc. The paper includes the LLM methodologies applied in various medical specialties, different data types in the medical domains and the relevant input formatting for LLMs, along with practical use-cases of LLMs in the healthcare domain.

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

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.

Despite the significant demand for assistive technology among vulnerable groups (e.g., the elderly, children, and the disabled) in daily tasks, research into advanced AI-driven assistive solutions that genuinely accommodate their diverse needs remains sparse. Traditional human-machine interaction tasks often require machines to simply help without nuanced consideration of human abilities and feelings, such as their opportunity for practice and learning, sense of self-improvement, and self-esteem. Addressing this gap, we define a pivotal and novel challenge Smart Help, which aims to provide proactive yet adaptive support to human agents with diverse disabilities and dynamic goals in various tasks and environments. To establish this challenge, we leverage AI2-THOR to build a new interactive 3D realistic household environment for the Smart Help task. We introduce an innovative opponent modeling module that provides a nuanced understanding of the main agent's capabilities and goals, in order to optimize the assisting agent's helping policy. Rigorous experiments validate the efficacy of our model components and show the superiority of our holistic approach against established baselines. Our findings illustrate the potential of AI-imbued assistive robots in improving the well-being of vulnerable groups.

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.

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}

Excellence in a wide variety of medical applications poses considerable challenges for AI, requiring advanced reasoning, access to up-to-date medical knowledge and understanding of complex multimodal data. Gemini models, with strong general capabilities in multimodal and long-context reasoning, offer exciting possibilities in medicine. Building on these core strengths of Gemini, we introduce Med-Gemini, a family of highly capable multimodal models that are specialized in medicine with the ability to seamlessly use web search, and that can be efficiently tailored to novel modalities using custom encoders. We evaluate Med-Gemini on 14 medical benchmarks, establishing new state-of-the-art (SoTA) performance on 10 of them, and surpass the GPT-4 model family on every benchmark where a direct comparison is viable, often by a wide margin. On the popular MedQA (USMLE) benchmark, our best-performing Med-Gemini model achieves SoTA performance of 91.1% accuracy, using a novel uncertainty-guided search strategy. On 7 multimodal benchmarks including NEJM Image Challenges and MMMU (health & medicine), Med-Gemini improves over GPT-4V by an average relative margin of 44.5%. We demonstrate the effectiveness of Med-Gemini's long-context capabilities through SoTA performance on a needle-in-a-haystack retrieval task from long de-identified health records and medical video question answering, surpassing prior bespoke methods using only in-context learning. Finally, Med-Gemini's performance suggests real-world utility by surpassing human experts on tasks such as medical text summarization, alongside demonstrations of promising potential for multimodal medical dialogue, medical research and education. Taken together, our results offer compelling evidence for Med-Gemini's potential, although further rigorous evaluation will be crucial before real-world deployment in this safety-critical domain.

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.

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.

Large language models (LLMs) demonstrate remarkable medical expertise, but data privacy concerns impede their direct use in healthcare environments. Although offering improved data privacy protection, domain-specific small language models (SLMs) often underperform LLMs, emphasizing the need for methods that reduce this performance gap while alleviating privacy concerns. In this paper, we present a simple yet effective method that harnesses LLMs' medical proficiency to boost SLM performance in medical tasks under privacy-restricted scenarios. Specifically, we mitigate patient privacy issues by extracting keywords from medical data and prompting the LLM to generate a medical knowledge-intensive context by simulating clinicians' thought processes. This context serves as additional input for SLMs, augmenting their decision-making capabilities. Our method significantly enhances performance in both few-shot and full training settings across three medical knowledge-intensive tasks, achieving up to a 22.57% increase in absolute accuracy compared to SLM fine-tuning without context, and sets new state-of-the-art results in two medical tasks within privacy-restricted scenarios. Further out-of-domain testing and experiments in two general domain datasets showcase its generalizability and broad applicability.

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

In recent years, the application of Large Language Models (LLMs) in healthcare has shown significant promise in improving the accessibility and dissemination of medical knowledge. This paper presents a detailed study of various LLMs trained on the MedQuAD medical question-answering dataset, with a focus on identifying the most effective model for providing accurate medical information. Among the models tested, the Sentence-t5 combined with Mistral 7B demonstrated superior performance, achieving a precision score of 0.762. This model's enhanced capabilities are attributed to its advanced pretraining techniques, robust architecture, and effective prompt construction methodologies. By leveraging these strengths, the Sentence-t5 + Mistral 7B model excels in understanding and generating precise medical answers. Our findings highlight the potential of integrating sophisticated LLMs in medical contexts to facilitate efficient and accurate medical knowledge retrieval, thus significantly enhancing patient education and support.

Automatically classifying electronic health records (EHRs) into diagnostic codes has been challenging to the NLP community. State-of-the-art methods treated this problem as a multilabel classification problem and proposed various architectures to model this problem. However, these systems did not leverage the superb performance of pretrained language models, which achieved superb performance on natural language understanding tasks. Prior work has shown that pretrained language models underperformed on this task with the regular finetuning scheme. Therefore, this paper aims at analyzing the causes of the underperformance and developing a framework for automatic ICD coding with pretrained language models. We spotted three main issues through the experiments: 1) large label space, 2) long input sequences, and 3) domain mismatch between pretraining and fine-tuning. We propose PLMICD, a framework that tackles the challenges with various strategies. The experimental results show that our proposed framework can overcome the challenges and achieves state-of-the-art performance in terms of multiple metrics on the benchmark MIMIC data. The source code is available at https://github.com/MiuLab/PLM-ICD

Despite significant advancements in general artificial intelligence, such as GPT-4, their effectiveness in the medical domain (general medical AI, GMAI) remains constrained due to the absence of specialized medical knowledge. To address this challenge, we present GMAI-VL-5.5M, a comprehensive multimodal medical dataset created by converting hundreds of specialized medical datasets into meticulously constructed image-text pairs. This dataset features comprehensive task coverage, diverse modalities, and high-quality image-text data. Building upon this multimodal dataset, we propose GMAI-VL, a general medical vision-language model with a progressively three-stage training strategy. This approach significantly enhances the model's ability by integrating visual and textual information, thereby improving its ability to process multimodal data and support accurate diagnosis and clinical decision-making. Experimental evaluations demonstrate that GMAI-VL achieves state-of-the-art results across a wide range of multimodal medical tasks, such as visual question answering and medical image diagnosis. Our contributions include the development of the GMAI-VL-5.5M dataset, the introduction of the GMAI-VL model, and the establishment of new benchmarks in multiple medical domains. Code and dataset will be released at https://github.com/uni-medical/GMAI-VL.

The lack of transparency and explainability hinders the clinical adoption of Machine learning (ML) algorithms. While explainable artificial intelligence (XAI) methods have been proposed, little research has focused on the agreement between these methods and expert clinical knowledge. This study applies current state-of-the-art explainability methods to clinical decision support algorithms developed for Electronic Medical Records (EMR) data to analyse the concordance between these factors and discusses causes for identified discrepancies from a clinical and technical perspective. Important factors for achieving trustworthy XAI solutions for clinical decision support are also discussed.

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.