Daily Papers

Electronic Health Records (EHRs) contain rich temporal dynamics that conventional encoding approaches fail to adequately capture. While Large Language Models (LLMs) show promise for EHR modeling, they struggle to reason about sequential clinical events and temporal dependencies. We propose Next Event Prediction (NEP), a framework that enhances LLMs' temporal reasoning through autoregressive fine-tuning on clinical event sequences. By reformulating EHRs as timestamped event chains and predicting future medical events, NEP explicitly models disease progression patterns and causal relationships. Extensive evaluations across oncology survival prediction and clinical diagnosis tasks demonstrate NEP's superiority, outperforming specialized EHR models by 4.6% AUROC and general-purpose LLMs by 7.2% C-index in temporal reasoning tasks. Our analyses reveal dual benefits: state-of-the-art prediction accuracy combined with clinically interpretable attention patterns that align with known disease pathways.

Foundation Models (FMs) trained on Electronic Health Records (EHRs) have achieved state-of-the-art results on numerous clinical prediction tasks. However, most existing EHR FMs have context windows of <1k tokens. This prevents them from modeling full patient EHRs which can exceed 10k's of events. Recent advancements in subquadratic long-context architectures (e.g., Mamba) offer a promising solution. However, their application to EHR data has not been well-studied. We address this gap by presenting the first systematic evaluation of the effect of context length on modeling EHR data. We find that longer context models improve predictive performance -- our Mamba-based model surpasses the prior state-of-the-art on 9/14 tasks on the EHRSHOT prediction benchmark. For clinical applications, however, model performance alone is insufficient -- robustness to the unique properties of EHR is crucial. Thus, we also evaluate models across three previously underexplored properties of EHR data: (1) the prevalence of "copy-forwarded" diagnoses which creates artificial repetition of tokens within EHR sequences; (2) the irregular time intervals between EHR events which can lead to a wide range of timespans within a context window; and (3) the natural increase in disease complexity over time which makes later tokens in the EHR harder to predict than earlier ones. Stratifying our EHRSHOT results, we find that higher levels of each property correlate negatively with model performance, but that longer context models are more robust to more extreme levels of these properties. Our work highlights the potential for using long-context architectures to model EHR data, and offers a case study for identifying new challenges in modeling sequential data motivated by domains outside of natural language. We release our models and code at: https://github.com/som-shahlab/long_context_clues

Event sequences (ESs) arise in many practical domains including finance, retail, social networks, and healthcare. In the context of machine learning, event sequences can be seen as a special type of tabular data with annotated timestamps. Despite the importance of ESs modeling and analysis, little effort was made in adapting large language models (LLMs) to the ESs domain. In this paper, we highlight the common difficulties of ESs processing and propose a novel solution capable of solving multiple downstream tasks with little or no finetuning. In particular, we solve the problem of working with long sequences and improve time and numeric features processing. The resulting method, called ESQA, effectively utilizes the power of LLMs and, according to extensive experiments, achieves state-of-the-art results in the ESs domain.

Event sequences, characterized by irregular sampling intervals and a mix of categorical and numerical features, are common data structures in various real-world domains such as healthcare, finance, and user interaction logs. Despite advances in temporal data modeling techniques, there is no standardized benchmarks for evaluating their performance on event sequences. This complicates result comparison across different papers due to varying evaluation protocols, potentially misleading progress in this field. We introduce EBES, a comprehensive benchmarking tool with standardized evaluation scenarios and protocols, focusing on regression and classification problems with sequence-level targets. Our library simplifies benchmarking, dataset addition, and method integration through a unified interface. It includes a novel synthetic dataset and provides preprocessed real-world datasets, including the largest publicly available banking dataset. Our results provide an in-depth analysis of datasets, identifying some as unsuitable for model comparison. We investigate the importance of modeling temporal and sequential components, as well as the robustness and scaling properties of the models. These findings highlight potential directions for future research. Our benchmark aim is to facilitate reproducible research, expediting progress and increasing real-world impacts.

Models that can predict the occurrence of events ahead of time with low false-alarm rates are critical to the acceptance of decision support systems in the medical community. This challenging task is typically treated as a simple binary classification, ignoring temporal dependencies between samples, whereas we propose to exploit this structure. We first introduce a common theoretical framework unifying dynamic survival analysis and early event prediction. Following an analysis of objectives from both fields, we propose Temporal Label Smoothing (TLS), a simpler, yet best-performing method that preserves prediction monotonicity over time. By focusing the objective on areas with a stronger predictive signal, TLS improves performance over all baselines on two large-scale benchmark tasks. Gains are particularly notable along clinically relevant measures, such as event recall at low false-alarm rates. TLS reduces the number of missed events by up to a factor of two over previously used approaches in early event prediction.

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

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

The primary goal of drug safety researchers and regulators is to promptly identify adverse drug reactions. Doing so may in turn prevent or reduce the harm to patients and ultimately improve public health. Evaluating and monitoring drug safety (i.e., pharmacovigilance) involves analyzing an ever growing collection of spontaneous reports from health professionals, physicians, and pharmacists, and information voluntarily submitted by patients. In this scenario, facilitating analysis of such reports via automation has the potential to rapidly identify safety signals. Unfortunately, public resources for developing natural language models for this task are scant. We present PHEE, a novel dataset for pharmacovigilance comprising over 5000 annotated events from medical case reports and biomedical literature, making it the largest such public dataset to date. We describe the hierarchical event schema designed to provide coarse and fine-grained information about patients' demographics, treatments and (side) effects. Along with the discussion of the dataset, we present a thorough experimental evaluation of current state-of-the-art approaches for biomedical event extraction, point out their limitations, and highlight open challenges to foster future research in this area.

Discrete event sequences are ubiquitous, such as an ordered event series of process interactions in Information and Communication Technology systems. Recent years have witnessed increasing efforts in detecting anomalies with discrete-event sequences. However, it still remains an extremely difficult task due to several intrinsic challenges including data imbalance issues, the discrete property of the events, and sequential nature of the data. To address these challenges, in this paper, we propose OC4Seq, a multi-scale one-class recurrent neural network for detecting anomalies in discrete event sequences. Specifically, OC4Seq integrates the anomaly detection objective with recurrent neural networks (RNNs) to embed the discrete event sequences into latent spaces, where anomalies can be easily detected. In addition, given that an anomalous sequence could be caused by either individual events, subsequences of events, or the whole sequence, we design a multi-scale RNN framework to capture different levels of sequential patterns simultaneously. Experimental results on three benchmark datasets show that OC4Seq consistently outperforms various representative baselines by a large margin. Moreover, through both quantitative and qualitative analysis, the importance of capturing multi-scale sequential patterns for event anomaly detection is verified.

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.

Continuous-time event sequences play a vital role in real-world domains such as healthcare, finance, online shopping, social networks, and so on. To model such data, temporal point processes (TPPs) have emerged as the most natural and competitive models, making a significant impact in both academic and application communities. Despite the emergence of many powerful models in recent years, there hasn't been a central benchmark for these models and future research endeavors. This lack of standardization impedes researchers and practitioners from comparing methods and reproducing results, potentially slowing down progress in this field. In this paper, we present EasyTPP, the first central repository of research assets (e.g., data, models, evaluation programs, documentations) in the area of event sequence modeling. Our EasyTPP makes several unique contributions to this area: a unified interface of using existing datasets and adding new datasets; a wide range of evaluation programs that are easy to use and extend as well as facilitate reproducible research; implementations of popular neural TPPs, together with a rich library of modules by composing which one could quickly build complex models. All the data and implementation can be found at https://github.com/ant-research/EasyTemporalPointProcess. We will actively maintain this benchmark and welcome contributions from other researchers and practitioners. Our benchmark will help promote reproducible research in this field, thus accelerating research progress as well as making more significant real-world impacts.

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

Surgical future prediction, driven by real-time AI analysis of surgical video, is critical for operating room safety and efficiency. It provides actionable insights into upcoming events, their timing, and risks-enabling better resource allocation, timely instrument readiness, and early warnings for complications (e.g., bleeding, bile duct injury). Despite this need, current surgical AI research focuses on understanding what is happening rather than predicting future events. Existing methods target specific tasks in isolation, lacking unified approaches that span both short-term (action triplets, events) and long-term horizons (remaining surgery duration, phase transitions). These methods rely on coarse-grained supervision while fine-grained surgical action triplets and steps remain underexplored. Furthermore, methods based only on future feature prediction struggle to generalize across different surgical contexts and procedures. We address these limits by reframing surgical future prediction as state-change learning. Rather than forecasting raw observations, our approach classifies state transitions between current and future timesteps. We introduce SurgFUTR, implementing this through a teacher-student architecture. Video clips are compressed into state representations via Sinkhorn-Knopp clustering; the teacher network learns from both current and future clips, while the student network predicts future states from current videos alone, guided by our Action Dynamics (ActDyn) module. We establish SFPBench with five prediction tasks spanning short-term (triplets, events) and long-term (remaining surgery duration, phase and step transitions) horizons. Experiments across four datasets and three procedures show consistent improvements. Cross-procedure transfer validates generalizability.

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.

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

The long-term effects of Postacute Sequelae of SARS-CoV-2, known as PASC, pose a significant challenge to healthcare systems worldwide. Accurate identification of progression events, such as hospitalization and reinfection, is essential for effective patient management and resource allocation. However, traditional models trained on structured data struggle to capture the nuanced progression of PASC. In this study, we introduce the first publicly available cohort of 18 PASC patients, with text time series features based on Large Language Model Llama-3.1-70B-Instruct and clinical risk annotated by clinical expert. We propose an Active Attention Network to predict the clinical risk and identify progression events related to the risk. By integrating human expertise with active learning, we aim to enhance clinical risk prediction accuracy and enable progression events identification with fewer number of annotation. The ultimate goal is to improves patient care and decision-making for SARS-CoV-2 patient.

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

MRI is an indispensable clinical tool, offering a rich variety of tissue contrasts to support broad diagnostic and research applications. Clinical exams routinely acquire multiple structural sequences that provide complementary information for differential diagnosis, while research protocols often incorporate advanced functional, diffusion, spectroscopic, and relaxometry sequences to capture multidimensional insights into tissue structure and composition. However, these capabilities come at the cost of prolonged scan times, which reduce patient throughput, increase susceptibility to motion artifacts, and may require trade-offs in image quality or diagnostic scope. Over the last two decades, advances in image reconstruction algorithms--alongside improvements in hardware and pulse sequence design--have made it possible to accelerate acquisitions while preserving diagnostic quality. Central to this progress is the ability to incorporate prior information to regularize the solutions to the reconstruction problem. In this tutorial, we overview the basics of MRI reconstruction and highlight state-of-the-art approaches, beginning with classical methods that rely on explicit hand-crafted priors, and then turning to deep learning methods that leverage a combination of learned and crafted priors to further push the performance envelope. We also explore the translational aspects and eventual clinical implications of these methods. We conclude by discussing future directions to address remaining challenges in MRI reconstruction. The tutorial is accompanied by a Python toolbox (https://github.com/tutorial-MRI-recon/tutorial) to demonstrate select methods discussed in the article.

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

We present PubMed 200k RCT, a new dataset based on PubMed for sequential sentence classification. The dataset consists of approximately 200,000 abstracts of randomized controlled trials, totaling 2.3 million sentences. Each sentence of each abstract is labeled with their role in the abstract using one of the following classes: background, objective, method, result, or conclusion. The purpose of releasing this dataset is twofold. First, the majority of datasets for sequential short-text classification (i.e., classification of short texts that appear in sequences) are small: we hope that releasing a new large dataset will help develop more accurate algorithms for this task. Second, from an application perspective, researchers need better tools to efficiently skim through the literature. Automatically classifying each sentence in an abstract would help researchers read abstracts more efficiently, especially in fields where abstracts may be long, such as the medical field.

Data of sequential nature arise in many application domains in forms of, e.g. textual data, DNA sequences, and software execution traces. Different research disciplines have developed methods to learn sequence models from such datasets: (i) in the machine learning field methods such as (hidden) Markov models and recurrent neural networks have been developed and successfully applied to a wide-range of tasks, (ii) in process mining process discovery techniques aim to generate human-interpretable descriptive models, and (iii) in the grammar inference field the focus is on finding descriptive models in the form of formal grammars. Despite their different focuses, these fields share a common goal - learning a model that accurately describes the behavior in the underlying data. Those sequence models are generative, i.e, they can predict what elements are likely to occur after a given unfinished sequence. So far, these fields have developed mainly in isolation from each other and no comparison exists. This paper presents an interdisciplinary experimental evaluation that compares sequence modeling techniques on the task of next-element prediction on four real-life sequence datasets. The results indicate that machine learning techniques that generally have no aim at interpretability in terms of accuracy outperform techniques from the process mining and grammar inference fields that aim to yield interpretable models.

A radiology report comprises several sections, including the Findings and Impression of the diagnosis. Automatically generating the Impression from the Findings is crucial for reducing radiologists' workload and improving diagnostic accuracy. Pretrained models that excel in common abstractive summarization problems encounter challenges when applied to specialized medical domains largely due to the complex terminology and the necessity for accurate clinical context. Such tasks in medical domains demand extracting core information, avoiding context shifts, and maintaining proper flow. Misuse of medical terms can lead to drastic clinical errors. To address these issues, we introduce a sequential transfer learning that ensures key content extraction and coherent summarization. Sequential transfer learning often faces challenges like initial parameter decay and knowledge loss, which we resolve with the Fisher matrix regularization. Using MIMIC-CXR and Open-I datasets, our model, CSTRL - Context-driven Sequential TRansfer Learning - achieved state-of-the-art performance, showing 56.2% improvement in BLEU-1, 40.5% in BLEU-2, 84.3% in BLEU-3, 28.9% in ROUGE-1, 41.0% in ROUGE-2 and 26.5% in ROGUE-3 score over benchmark studies. We also analyze factual consistency scores while preserving the medical context. Our code is publicly available at https://github.com/fahmidahossain/Report_Summarization.

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

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

Longitudinal multimodal data, including electronic health records (EHR) and sequential chest X-rays (CXRs), is critical for modeling disease progression, yet remains underutilized due to two key challenges: (1) redundancy in consecutive CXR sequences, where static anatomical regions dominate over clinically-meaningful dynamics, and (2) temporal misalignment between sparse, irregular imaging and continuous EHR data. We introduce DiPro, a novel framework that addresses these challenges through region-aware disentanglement and multi-timescale alignment. First, we disentangle static (anatomy) and dynamic (pathology progression) features in sequential CXRs, prioritizing disease-relevant changes. Second, we hierarchically align these static and dynamic CXR features with asynchronous EHR data via local (pairwise interval-level) and global (full-sequence) synchronization to model coherent progression pathways. Extensive experiments on the MIMIC dataset demonstrate that DiPro could effectively extract temporal clinical dynamics and achieve state-of-the-art performance on both disease progression identification and general ICU prediction tasks.

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

We present a foundation model-derived method to identify highly informative tokens and events in electronic health records. Our approach considers incoming data in the entire context of a patient's hospitalization and so can flag anomalous events that rule-based approaches would consider within a normal range. We demonstrate that the events our model flags are significant for predicting downstream patient outcomes and that a fraction of events identified as carrying little information can safely be dropped. Additionally, we show how informativeness can help interpret the predictions of prognostic models trained on foundation model-derived representations.

Multilingual speech translation (ST) in the medical domain enhances patient care by enabling efficient communication across language barriers, alleviating specialized workforce shortages, and facilitating improved diagnosis and treatment, particularly during pandemics. In this work, we present the first systematic study on medical ST, to our best knowledge, by releasing MultiMed-ST, a large-scale ST dataset for the medical domain, spanning all translation directions in five languages: Vietnamese, English, German, French, Traditional Chinese and Simplified Chinese, together with the models. With 290,000 samples, our dataset is the largest medical machine translation (MT) dataset and the largest many-to-many multilingual ST among all domains. Secondly, we present the most extensive analysis study in ST research to date, including: empirical baselines, bilingual-multilingual comparative study, end-to-end vs. cascaded comparative study, task-specific vs. multi-task sequence-to-sequence (seq2seq) comparative study, code-switch analysis, and quantitative-qualitative error analysis. All code, data, and models are available online: https://github.com/leduckhai/MultiMed-ST.

Counterfactual medical image generation enables clinicians to explore clinical hypotheses, such as predicting disease progression, facilitating their decision-making. While existing methods can generate visually plausible images from disease progression prompts, they produce silent predictions that lack interpretation to verify how the generation reflects the hypothesized progression -- a critical gap for medical applications that require traceable reasoning. In this paper, we propose Interpretable Counterfactual Generation (ICG), a novel task requiring the joint generation of counterfactual images that reflect the clinical hypothesis and interpretation texts that outline the visual changes induced by the hypothesis. To enable ICG, we present ICG-CXR, the first dataset pairing longitudinal medical images with hypothetical progression prompts and textual interpretations. We further introduce ProgEmu, an autoregressive model that unifies the generation of counterfactual images and textual interpretations. We demonstrate the superiority of ProgEmu in generating progression-aligned counterfactuals and interpretations, showing significant potential in enhancing clinical decision support and medical education. Project page: https://progemu.github.io.

In this work, we focus on the task of procedure planning from instructional videos with text supervision, where a model aims to predict an action sequence to transform the initial visual state into the goal visual state. A critical challenge of this task is the large semantic gap between observed visual states and unobserved intermediate actions, which is ignored by previous works. Specifically, this semantic gap refers to that the contents in the observed visual states are semantically different from the elements of some action text labels in a procedure. To bridge this semantic gap, we propose a novel event-guided paradigm, which first infers events from the observed states and then plans out actions based on both the states and predicted events. Our inspiration comes from that planning a procedure from an instructional video is to complete a specific event and a specific event usually involves specific actions. Based on the proposed paradigm, we contribute an Event-guided Prompting-based Procedure Planning (E3P) model, which encodes event information into the sequential modeling process to support procedure planning. To further consider the strong action associations within each event, our E3P adopts a mask-and-predict approach for relation mining, incorporating a probabilistic masking scheme for regularization. Extensive experiments on three datasets demonstrate the effectiveness of our proposed model.

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

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.

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

Clinical trials disruption has always represented a non negligible part of the ending of interventional studies. While the SARS-CoV-2 (COVID-19) pandemic has led to an impressive and unprecedented initiation of clinical research, it has also led to considerable disruption of clinical trials in other disease areas, with around 80% of non-COVID-19 trials stopped or interrupted during the pandemic. In many cases the disrupted trials will not have the planned statistical power necessary to yield interpretable results. This paper describes methods to compensate for the information loss arising from trial disruptions by incorporating additional information available from auxiliary data sources. The methods described include the use of auxiliary data on baseline and early outcome data available from the trial itself and frequentist and Bayesian approaches for the incorporation of information from external data sources. The methods are illustrated by application to the analysis of artificial data based on the Primary care pediatrics Learning Activity Nutrition (PLAN) study, a clinical trial assessing a diet and exercise intervention for overweight children, that was affected by the COVID-19 pandemic. We show how all of the methods proposed lead to an increase in precision relative to use of complete case data only.

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.

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

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

Many events occur in the world. Some event types are stochastically excited or inhibited---in the sense of having their probabilities elevated or decreased---by patterns in the sequence of previous events. Discovering such patterns can help us predict which type of event will happen next and when. We model streams of discrete events in continuous time, by constructing a neurally self-modulating multivariate point process in which the intensities of multiple event types evolve according to a novel continuous-time LSTM. This generative model allows past events to influence the future in complex and realistic ways, by conditioning future event intensities on the hidden state of a recurrent neural network that has consumed the stream of past events. Our model has desirable qualitative properties. It achieves competitive likelihood and predictive accuracy on real and synthetic datasets, including under missing-data conditions.

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

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

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

For monitoring crises, political events are extracted from the news. The large amount of unstructured full-text event descriptions makes a case-by-case analysis unmanageable, particularly for low-resource humanitarian aid organizations. This creates a demand to classify events into event types, a task referred to as event coding. Typically, domain experts craft an event type ontology, annotators label a large dataset and technical experts develop a supervised coding system. In this work, we propose PR-ENT, a new event coding approach that is more flexible and resource-efficient, while maintaining competitive accuracy: first, we extend an event description such as "Military injured two civilians'' by a template, e.g. "People were [Z]" and prompt a pre-trained (cloze) language model to fill the slot Z. Second, we select answer candidates Z* = {"injured'', "hurt"...} by treating the event description as premise and the filled templates as hypothesis in a textual entailment task. This allows domain experts to draft the codebook directly as labeled prompts and interpretable answer candidates. This human-in-the-loop process is guided by our interactive codebook design tool. We evaluate PR-ENT in several robustness checks: perturbing the event description and prompt template, restricting the vocabulary and removing contextual information.

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

We present a self-supervised, time-to-event (TTE) foundation model called MOTOR (Many Outcome Time Oriented Representations) which is pretrained on timestamped sequences of events in electronic health records (EHR) and health insurance claims. TTE models are used for estimating the probability distribution of the time until a specific event occurs, which is an important task in medical settings. TTE models provide many advantages over classification using fixed time horizons, including naturally handling censored observations, but are challenging to train with limited labeled data. MOTOR addresses this challenge by pretraining on up to 55M patient records (9B clinical events). We evaluate MOTOR's transfer learning performance on 19 tasks, across 3 patient databases (a private EHR system, MIMIC-IV, and Merative claims data). Task-specific models adapted from MOTOR improve time-dependent C statistics by 4.6% over state-of-the-art, improve label efficiency by up to 95% ,and are more robust to temporal distributional shifts. We further evaluate cross-site portability by adapting our MOTOR foundation model for six prediction tasks on the MIMIC-IV dataset, where it outperforms all baselines. MOTOR is the first foundation model for medical TTE predictions and we release a 143M parameter pretrained model for research use at [redacted URL].

Accurate prediction of major adverse cardiovascular events recurrence risk in acute myocardial infarction patients based on postoperative cardiac MRI and associated clinical notes is crucial for precision treatment and personalized intervention. Existing methods primarily focus on risk stratification capability while overlooking the need for intermediate robust reasoning and model interpretability in clinical practice. Moreover, end-to-end risk prediction using LLM/VLM faces significant challenges due to data limitations and modeling complexity. To bridge this gap, we propose CardioCoT, a novel two-stage hierarchical reasoning-enhanced survival analysis framework designed to enhance both model interpretability and predictive performance. In the first stage, we employ an evidence-augmented self-refinement mechanism to guide LLM/VLMs in generating robust hierarchical reasoning trajectories based on associated radiological findings. In the second stage, we integrate the reasoning trajectories with imaging data for risk model training and prediction. CardioCoT demonstrates superior performance in MACE recurrence risk prediction while providing interpretable reasoning processes, offering valuable insights for clinical decision-making.

This paper is dedicated to the design and evaluation of the first AMR parser tailored for clinical notes. Our objective was to facilitate the precise transformation of the clinical notes into structured AMR expressions, thereby enhancing the interpretability and usability of clinical text data at scale. Leveraging the colon cancer dataset from the Temporal Histories of Your Medical Events (THYME) corpus, we adapted a state-of-the-art AMR parser utilizing continuous training. Our approach incorporates data augmentation techniques to enhance the accuracy of AMR structure predictions. Notably, through this learning strategy, our parser achieved an impressive F1 score of 88% on the THYME corpus's colon cancer dataset. Moreover, our research delved into the efficacy of data required for domain adaptation within the realm of clinical notes, presenting domain adaptation data requirements for AMR parsing. This exploration not only underscores the parser's robust performance but also highlights its potential in facilitating a deeper understanding of clinical narratives through structured semantic representations.

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

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

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

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.

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

We address a challenging and practical task of labeling questions in speech in real time during telephone calls to emergency medical services in English, which embeds within a broader decision support system for emergency call-takers. We propose a novel multimodal approach to real-time sequence labeling in speech. Our model treats speech and its own textual representation as two separate modalities or views, as it jointly learns from streamed audio and its noisy transcription into text via automatic speech recognition. Our results show significant gains of jointly learning from the two modalities when compared to text or audio only, under adverse noise and limited volume of training data. The results generalize to medical symptoms detection where we observe a similar pattern of improvements with multimodal learning.

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

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.

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

With the advent of LLMs, various tasks across the natural language processing domain have been transformed. However, their application in predictive tasks remains less researched. This study compares large language models, including GatorTron-Base (trained on clinical data), Llama 8B, and Mistral 7B, against models like BioBERT, DocBERT, BioClinicalBERT, Word2Vec, and Doc2Vec, setting benchmarks for predicting Shock in critically ill patients. Timely prediction of shock can enable early interventions, thus improving patient outcomes. Text data from 17,294 ICU stays of patients in the MIMIC III database were scored for length of stay > 24 hours and shock index (SI) > 0.7 to yield 355 and 87 patients with normal and abnormal SI-index, respectively. Both focal and cross-entropy losses were used during finetuning to address class imbalances. Our findings indicate that while GatorTron Base achieved the highest weighted recall of 80.5%, the overall performance metrics were comparable between SLMs and LLMs. This suggests that LLMs are not inherently superior to SLMs in predicting future clinical events despite their strong performance on text-based tasks. To achieve meaningful clinical outcomes, future efforts in training LLMs should prioritize developing models capable of predicting clinical trajectories rather than focusing on simpler tasks such as named entity recognition or phenotyping.

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.

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

Digital healthcare infrastructure is crucial for global medical service delivery. Egypt faces EHR adoption barriers: only 314 hospitals had such systems as of Oct 2024. This limits data management and decision-making. This project introduces an EHR system for Egypt's Universal Health Insurance and healthcare ecosystem. It simplifies data management by centralizing medical histories with a scalable micro-services architecture and polyglot persistence for real-time access and provider communication. Clinical workflows are enhanced via patient examination and history tracking. The system uses the Llama3-OpenBioLLM-70B model to generate summaries of medical histories, provide chatbot features, and generate AI-based medical reports, enabling efficient searches during consultations. A Vision Transformer (ViT) aids in pneumonia classification. Evaluations show the AI excels in capturing details (high recall) but needs improvement in concise narratives. With optimization (retrieval-augmented generation, local data fine-tuning, interoperability protocols), this AI-driven EHR could enhance diagnostic support, decision-making, and healthcare delivery in Egypt.

Clinical information extraction, which involves structuring clinical concepts from unstructured medical text, remains a challenging problem that could benefit from the inclusion of tabular background information available in electronic health records. Existing open-source datasets lack explicit links between structured features and clinical concepts in the text, motivating the need for a new research dataset. We introduce SimSUM, a benchmark dataset of 10,000 simulated patient records that link unstructured clinical notes with structured background variables. Each record simulates a patient encounter in the domain of respiratory diseases and includes tabular data (e.g., symptoms, diagnoses, underlying conditions) generated from a Bayesian network whose structure and parameters are defined by domain experts. A large language model (GPT-4o) is prompted to generate a clinical note describing the encounter, including symptoms and relevant context. These notes are annotated with span-level symptom mentions. We conduct an expert evaluation to assess note quality and run baseline predictive models on both the tabular and textual data. The SimSUM dataset is primarily designed to support research on clinical information extraction in the presence of tabular background variables, which can be linked through domain knowledge to concepts of interest to be extracted from the text -- namely, symptoms in the case of SimSUM. Secondary uses include research on the automation of clinical reasoning over both tabular data and text, causal effect estimation in the presence of tabular and/or textual confounders, and multi-modal synthetic data generation. SimSUM is not intended for training clinical decision support systems or production-grade models, but rather to facilitate reproducible research in a simplified and controlled setting.

Lung cancer patients frequently experience breakthrough pain episodes, with up to 91% requiring timely intervention. To enable proactive pain management, we propose a hybrid machine learning and large language model pipeline that predicts pain episodes within 48 and 72 hours of hospitalization using both structured and unstructured electronic health record data. A retrospective cohort of 266 inpatients was analyzed, with features including demographics, tumor stage, vital signs, and WHO-tiered analgesic use. The machine learning module captured temporal medication trends, while the large language model interpreted ambiguous dosing records and free-text clinical notes. Integrating these modalities improved sensitivity and interpretability. Our framework achieved an accuracy of 0.874 (48h) and 0.917 (72h), with an improvement in sensitivity of 8.6% and 10.4% due to the augmentation of large language model. This hybrid approach offers a clinically interpretable and scalable tool for early pain episode forecasting, with potential to enhance treatment precision and optimize resource allocation in oncology care.

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.

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

The emergence of advanced reasoning capabilities in Large Language Models (LLMs) marks a transformative development in healthcare applications. Beyond merely expanding functional capabilities, these reasoning mechanisms enhance decision transparency and explainability-critical requirements in medical contexts. This survey examines the transformation of medical LLMs from basic information retrieval tools to sophisticated clinical reasoning systems capable of supporting complex healthcare decisions. We provide a thorough analysis of the enabling technological foundations, with a particular focus on specialized prompting techniques like Chain-of-Thought and recent breakthroughs in Reinforcement Learning exemplified by DeepSeek-R1. Our investigation evaluates purpose-built medical frameworks while also examining emerging paradigms such as multi-agent collaborative systems and innovative prompting architectures. The survey critically assesses current evaluation methodologies for medical validation and addresses persistent challenges in field interpretation limitations, bias mitigation strategies, patient safety frameworks, and integration of multimodal clinical data. Through this survey, we seek to establish a roadmap for developing reliable LLMs that can serve as effective partners in clinical practice and medical research.

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

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

Medical care follows complex clinical pathways that extend beyond isolated physician-patient encounters, emphasizing decision-making and transitions between different stages. Current benchmarks focusing on static exams or isolated dialogues inadequately evaluate large language models (LLMs) in dynamic clinical scenarios. We introduce CP-Env, a controllable agentic hospital environment designed to evaluate LLMs across end-to-end clinical pathways. CP-Env simulates a hospital ecosystem with patient and physician agents, constructing scenarios ranging from triage and specialist consultation to diagnostic testing and multidisciplinary team meetings for agent interaction. Following real hospital adaptive flow of healthcare, it enables branching, long-horizon task execution. We propose a three-tiered evaluation framework encompassing Clinical Efficacy, Process Competency, and Professional Ethics. Results reveal that most models struggle with pathway complexity, exhibiting hallucinations and losing critical diagnostic details. Interestingly, excessive reasoning steps can sometimes prove counterproductive, while top models tend to exhibit reduced tool dependency through internalized knowledge. CP-Env advances medical AI agents development through comprehensive end-to-end clinical evaluation. We provide the benchmark and evaluation tools for further research and development at https://github.com/SPIRAL-MED/CP_ENV.

Medical dialogue systems (MDS) aim to provide patients with medical services, such as diagnosis and prescription. Since most patients cannot precisely describe their symptoms, dialogue understanding is challenging for MDS. Previous studies mainly addressed this by extracting the mentioned medical entities as critical dialogue history information. In this work, we argue that it is also essential to capture the transitions of the medical entities and the doctor's dialogue acts in each turn, as they help the understanding of how the dialogue flows and enhance the prediction of the entities and dialogue acts to be adopted in the following turn. Correspondingly, we propose a Dual Flow enhanced Medical (DFMed) dialogue generation framework. It extracts the medical entities and dialogue acts used in the dialogue history and models their transitions with an entity-centric graph flow and a sequential act flow, respectively. We employ two sequential models to encode them and devise an interweaving component to enhance their interactions. Experiments on two datasets demonstrate that our method exceeds baselines in both automatic and manual evaluations.

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

Automatically summarizing patients' main problems from daily progress notes using natural language processing methods helps to battle against information and cognitive overload in hospital settings and potentially assists providers with computerized diagnostic decision support. Problem list summarization requires a model to understand, abstract, and generate clinical documentation. In this work, we propose a new NLP task that aims to generate a list of problems in a patient's daily care plan using input from the provider's progress notes during hospitalization. We investigate the performance of T5 and BART, two state-of-the-art seq2seq transformer architectures, in solving this problem. We provide a corpus built on top of progress notes from publicly available electronic health record progress notes in the Medical Information Mart for Intensive Care (MIMIC)-III. T5 and BART are trained on general domain text, and we experiment with a data augmentation method and a domain adaptation pre-training method to increase exposure to medical vocabulary and knowledge. Evaluation methods include ROUGE, BERTScore, cosine similarity on sentence embedding, and F-score on medical concepts. Results show that T5 with domain adaptive pre-training achieves significant performance gains compared to a rule-based system and general domain pre-trained language models, indicating a promising direction for tackling the problem summarization task.

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

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

The neural Hawkes process (Mei & Eisner, 2017) is a generative model of irregularly spaced sequences of discrete events. To handle complex domains with many event types, Mei et al. (2020a) further consider a setting in which each event in the sequence updates a deductive database of facts (via domain-specific pattern-matching rules); future events are then conditioned on the database contents. They show how to convert such a symbolic system into a neuro-symbolic continuous-time generative model, in which each database fact and the possible event has a time-varying embedding that is derived from its symbolic provenance. In this paper, we modify both models, replacing their recurrent LSTM-based architectures with flatter attention-based architectures (Vaswani et al., 2017), which are simpler and more parallelizable. This does not appear to hurt our accuracy, which is comparable to or better than that of the original models as well as (where applicable) previous attention-based methods (Zuo et al., 2020; Zhang et al., 2020a).

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.

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

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

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

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.

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

Automating radiology report generation can significantly alleviate radiologists' workloads. Previous research has primarily focused on realizing highly concise observations while neglecting the precise attributes that determine the severity of diseases (e.g., small pleural effusion). Since incorrect attributes will lead to imprecise radiology reports, strengthening the generation process with precise attribute modeling becomes necessary. Additionally, the temporal information contained in the historical records, which is crucial in evaluating a patient's current condition (e.g., heart size is unchanged), has also been largely disregarded. To address these issues, we propose RECAP, which generates precise and accurate radiology reports via dynamic disease progression reasoning. Specifically, RECAP first predicts the observations and progressions (i.e., spatiotemporal information) given two consecutive radiographs. It then combines the historical records, spatiotemporal information, and radiographs for report generation, where a disease progression graph and dynamic progression reasoning mechanism are devised to accurately select the attributes of each observation and progression. Extensive experiments on two publicly available datasets demonstrate the effectiveness of our model.

Electronic Health Records (EHRs) are integral for storing comprehensive patient medical records, combining structured data (e.g., medications) with detailed clinical notes (e.g., physician notes). These elements are essential for straightforward data retrieval and provide deep, contextual insights into patient care. However, they often suffer from discrepancies due to unintuitive EHR system designs and human errors, posing serious risks to patient safety. To address this, we developed EHRCon, a new dataset and task specifically designed to ensure data consistency between structured tables and unstructured notes in EHRs. EHRCon was crafted in collaboration with healthcare professionals using the MIMIC-III EHR dataset, and includes manual annotations of 3,943 entities across 105 clinical notes checked against database entries for consistency. EHRCon has two versions, one using the original MIMIC-III schema, and another using the OMOP CDM schema, in order to increase its applicability and generalizability. Furthermore, leveraging the capabilities of large language models, we introduce CheckEHR, a novel framework for verifying the consistency between clinical notes and database tables. CheckEHR utilizes an eight-stage process and shows promising results in both few-shot and zero-shot settings. The code is available at https://github.com/dustn1259/EHRCon.

Large language models (LLMs) such as GPT-4o and o1 have demonstrated strong performance on clinical natural language processing (NLP) tasks across multiple medical benchmarks. Nonetheless, two high-impact NLP tasks - structured tabular reporting from nurse dictations and medical order extraction from doctor-patient consultations - remain underexplored due to data scarcity and sensitivity, despite active industry efforts. Practical solutions to these real-world clinical tasks can significantly reduce the documentation burden on healthcare providers, allowing greater focus on patient care. In this paper, we investigate these two challenging tasks using private and open-source clinical datasets, evaluating the performance of both open- and closed-weight LLMs, and analyzing their respective strengths and limitations. Furthermore, we propose an agentic pipeline for generating realistic, non-sensitive nurse dictations, enabling structured extraction of clinical observations. To support further research in both areas, we release SYNUR and SIMORD, the first open-source datasets for nurse observation extraction and medical order extraction.

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

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.

Large language models (LLMs) integrated into agent-driven workflows hold immense promise for healthcare, yet a significant gap exists between their potential and practical implementation within clinical settings. To address this, we present a practitioner-oriented field manual for deploying generative agents that use electronic health record (EHR) data. This guide is informed by our experience deploying the "irAE-Agent", an automated system to detect immune-related adverse events from clinical notes at Mass General Brigham, and by structured interviews with 21 clinicians, engineers, and informatics leaders involved in the project. Our analysis reveals a critical misalignment in clinical AI development: less than 20% of our effort was dedicated to prompt engineering and model development, while over 80% was consumed by the sociotechnical work of implementation. We distill this effort into five "heavy lifts": data integration, model validation, ensuring economic value, managing system drift, and governance. By providing actionable solutions for each of these challenges, this field manual shifts the focus from algorithmic development to the essential infrastructure and implementation work required to bridge the "valley of death" and successfully translate generative AI from pilot projects into routine clinical care.

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

The mining of adverse drug events (ADEs) is pivotal in pharmacovigilance, enhancing patient safety by identifying potential risks associated with medications, facilitating early detection of adverse events, and guiding regulatory decision-making. Traditional ADE detection methods are reliable but slow, not easily adaptable to large-scale operations, and offer limited information. With the exponential increase in data sources like social media content, biomedical literature, and Electronic Medical Records (EMR), extracting relevant ADE-related information from these unstructured texts is imperative. Previous ADE mining studies have focused on text-based methodologies, overlooking visual cues, limiting contextual comprehension, and hindering accurate interpretation. To address this gap, we present a MultiModal Adverse Drug Event (MMADE) detection dataset, merging ADE-related textual information with visual aids. Additionally, we introduce a framework that leverages the capabilities of LLMs and VLMs for ADE detection by generating detailed descriptions of medical images depicting ADEs, aiding healthcare professionals in visually identifying adverse events. Using our MMADE dataset, we showcase the significance of integrating visual cues from images to enhance overall performance. This approach holds promise for patient safety, ADE awareness, and healthcare accessibility, paving the way for further exploration in personalized healthcare.

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

A crucial step within secondary analysis of electronic health records (EHRs) is to identify the patient cohort under investigation. While EHRs contain medical billing codes that aim to represent the conditions and treatments patients may have, much of the information is only present in the patient notes. Therefore, it is critical to develop robust algorithms to infer patients' conditions and treatments from their written notes. In this paper, we introduce a dataset for patient phenotyping, a task that is defined as the identification of whether a patient has a given medical condition (also referred to as clinical indication or phenotype) based on their patient note. Nursing Progress Notes and Discharge Summaries from the Intensive Care Unit of a large tertiary care hospital were manually annotated for the presence of several high-context phenotypes relevant to treatment and risk of re-hospitalization. This dataset contains 1102 Discharge Summaries and 1000 Nursing Progress Notes. Each Discharge Summary and Progress Note has been annotated by at least two expert human annotators (one clinical researcher and one resident physician). Annotated phenotypes include treatment non-adherence, chronic pain, advanced/metastatic cancer, as well as 10 other phenotypes. This dataset can be utilized for academic and industrial research in medicine and computer science, particularly within the field of medical natural language processing.

Health conditions among patients in intensive care units (ICUs) are monitored via electronic health records (EHRs), composed of numerical time series and lengthy clinical note sequences, both taken at irregular time intervals. Dealing with such irregularity in every modality, and integrating irregularity into multimodal representations to improve medical predictions, is a challenging problem. Our method first addresses irregularity in each single modality by (1) modeling irregular time series by dynamically incorporating hand-crafted imputation embeddings into learned interpolation embeddings via a gating mechanism, and (2) casting a series of clinical note representations as multivariate irregular time series and tackling irregularity via a time attention mechanism. We further integrate irregularity in multimodal fusion with an interleaved attention mechanism across temporal steps. To the best of our knowledge, this is the first work to thoroughly model irregularity in multimodalities for improving medical predictions. Our proposed methods for two medical prediction tasks consistently outperforms state-of-the-art (SOTA) baselines in each single modality and multimodal fusion scenarios. Specifically, we observe relative improvements of 6.5\%, 3.6\%, and 4.3\% in F1 for time series, clinical notes, and multimodal fusion, respectively. These results demonstrate the effectiveness of our methods and the importance of considering irregularity in multimodal EHRs.

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

Pretext training followed by task-specific fine-tuning has been a successful approach in vision and language domains. This paper proposes a self-supervised pretext training framework tailored to event sequence data. We introduce a novel alignment verification task that is specialized to event sequences, building on good practices in masked reconstruction and contrastive learning. Our pretext tasks unlock foundational representations that are generalizable across different down-stream tasks, including next-event prediction for temporal point process models, event sequence classification, and missing event interpolation. Experiments on popular public benchmarks demonstrate the potential of the proposed method across different tasks and data domains.

Following each patient visit, physicians draft long semi-structured clinical summaries called SOAP notes. While invaluable to clinicians and researchers, creating digital SOAP notes is burdensome, contributing to physician burnout. In this paper, we introduce the first complete pipelines to leverage deep summarization models to generate these notes based on transcripts of conversations between physicians and patients. After exploring a spectrum of methods across the extractive-abstractive spectrum, we propose Cluster2Sent, an algorithm that (i) extracts important utterances relevant to each summary section; (ii) clusters together related utterances; and then (iii) generates one summary sentence per cluster. Cluster2Sent outperforms its purely abstractive counterpart by 8 ROUGE-1 points, and produces significantly more factual and coherent sentences as assessed by expert human evaluators. For reproducibility, we demonstrate similar benefits on the publicly available AMI dataset. Our results speak to the benefits of structuring summaries into sections and annotating supporting evidence when constructing summarization corpora.

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

This study investigates self-supervised learning techniques to obtain representations of Event Sequences. It is a key modality in various applications, including but not limited to banking, e-commerce, and healthcare. We perform a comprehensive study of generative and contrastive approaches in self-supervised learning, applying them both independently. We find that there is no single supreme method. Consequently, we explore the potential benefits of combining these approaches. To achieve this goal, we introduce a novel method that aligns generative and contrastive embeddings as distinct modalities, drawing inspiration from contemporary multimodal research. Generative and contrastive approaches are often treated as mutually exclusive, leaving a gap for their combined exploration. Our results demonstrate that this aligned model performs at least on par with, and mostly surpasses, existing methods and is more universal across a variety of tasks. Furthermore, we demonstrate that self-supervised methods consistently outperform the supervised approach on our datasets.

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

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

Procedural activities, ranging from routine cooking to complex surgical operations, are highly structured as a set of actions conducted in a specific temporal order. Despite their success on static images and short clips, current self-supervised learning methods often overlook the procedural nature that underpins such activities. We expose the lack of procedural awareness in current SSL methods with a motivating experiment: models pretrained on forward and time-reversed sequences produce highly similar features, confirming that their representations are blind to the underlying procedural order. To address this shortcoming, we propose PL-Stitch, a self-supervised framework that harnesses the inherent temporal order of video frames as a powerful supervisory signal. Our approach integrates two novel probabilistic objectives based on the Plackett-Luce (PL) model. The primary PL objective trains the model to sort sampled frames chronologically, compelling it to learn the global workflow progression. The secondary objective, a spatio-temporal jigsaw loss, complements the learning by capturing fine-grained, cross-frame object correlations. Our approach consistently achieves superior performance across five surgical and cooking benchmarks. Specifically, PL-Stitch yields significant gains in surgical phase recognition (e.g., +11.4 pp k-NN accuracy on Cholec80) and cooking action segmentation (e.g., +5.7 pp linear probing accuracy on Breakfast), demonstrating its effectiveness for procedural video representation learning.

Accurate and contrast-free Major Adverse Cardiac Events (MACE) prediction from Cine MRI sequences remains a critical challenge. Existing methods typically necessitate supervised learning based on human-refined masks in the ventricular myocardium, which become impractical without contrast agents. We introduce a self-supervised framework, namely Codebook-based Temporal-Spatial Learning (CTSL), that learns dynamic, spatiotemporal representations from raw Cine data without requiring segmentation masks. CTSL decouples temporal and spatial features through a multi-view distillation strategy, where the teacher model processes multiple Cine views, and the student model learns from reduced-dimensional Cine-SA sequences. By leveraging codebook-based feature representations and dynamic lesion self-detection through motion cues, CTSL captures intricate temporal dependencies and motion patterns. High-confidence MACE risk predictions are achieved through our model, providing a rapid, non-invasive solution for cardiac risk assessment that outperforms traditional contrast-dependent methods, thereby enabling timely and accessible heart disease diagnosis in clinical settings.

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.

Electronic health records (EHR) contain narrative notes that provide extensive details on the medical condition and management of patients. Natural language processing (NLP) of clinical notes can use observed frequencies of clinical terms as predictive features for downstream applications such as clinical decision making and patient trajectory prediction. However, due to the vast number of highly similar and related clinical concepts, a more effective modeling strategy is to represent clinical terms as semantic embeddings via representation learning and use the low dimensional embeddings as feature vectors for predictive modeling. To achieve efficient representation, fine-tuning pretrained language models with biomedical knowledge graphs may generate better embeddings for biomedical terms than those from standard language models alone. These embeddings can effectively discriminate synonymous pairs of from those that are unrelated. However, they often fail to capture different degrees of similarity or relatedness for concepts that are hierarchical in nature. To overcome this limitation, we propose HiPrBERT, a novel biomedical term representation model trained on additionally complied data that contains hierarchical structures for various biomedical terms. We modify an existing contrastive loss function to extract information from these hierarchies. Our numerical experiments demonstrate that HiPrBERT effectively learns the pair-wise distance from hierarchical information, resulting in a substantially more informative embeddings for further biomedical applications

We consider the problem of automatically generating a narrative biomedical evidence summary from multiple trial reports. We evaluate modern neural models for abstractive summarization of relevant article abstracts from systematic reviews previously conducted by members of the Cochrane collaboration, using the authors conclusions section of the review abstract as our target. We enlist medical professionals to evaluate generated summaries, and we find that modern summarization systems yield consistently fluent and relevant synopses, but that they are not always factual. We propose new approaches that capitalize on domain-specific models to inform summarization, e.g., by explicitly demarcating snippets of inputs that convey key findings, and emphasizing the reports of large and high-quality trials. We find that these strategies modestly improve the factual accuracy of generated summaries. Finally, we propose a new method for automatically evaluating the factuality of generated narrative evidence syntheses using models that infer the directionality of reported findings.

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

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

Electrocardiograms (ECGs) are non-invasive diagnostic tools crucial for detecting cardiac arrhythmic diseases in clinical practice. While ECG Self-supervised Learning (eSSL) methods show promise in representation learning from unannotated ECG data, they often overlook the clinical knowledge that can be found in reports. This oversight and the requirement for annotated samples for downstream tasks limit eSSL's versatility. In this work, we address these issues with the Multimodal ECG Representation Learning (MERL}) framework. Through multimodal learning on ECG records and associated reports, MERL is capable of performing zero-shot ECG classification with text prompts, eliminating the need for training data in downstream tasks. At test time, we propose the Clinical Knowledge Enhanced Prompt Engineering (CKEPE) approach, which uses Large Language Models (LLMs) to exploit external expert-verified clinical knowledge databases, generating more descriptive prompts and reducing hallucinations in LLM-generated content to boost zero-shot classification. Based on MERL, we perform the first benchmark across six public ECG datasets, showing the superior performance of MERL compared against eSSL methods. Notably, MERL achieves an average AUC score of 75.2% in zero-shot classification (without training data), 3.2% higher than linear probed eSSL methods with 10\% annotated training data, averaged across all six datasets. Code and models are available at https://github.com/cheliu-computation/MERL

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

Medical calculators are fundamental to quantitative, evidence-based clinical practice. However, their real-world use is an adaptive, multi-stage process, requiring proactive EHR data acquisition, scenario-dependent calculator selection, and multi-step computation, whereas current benchmarks focus only on static single-step calculations with explicit instructions. To address these limitations, we introduce MedMCP-Calc, the first benchmark for evaluating LLMs in realistic medical calculator scenarios through Model Context Protocol (MCP) integration. MedMCP-Calc comprises 118 scenario tasks across 4 clinical domains, featuring fuzzy task descriptions mimicking natural queries, structured EHR database interaction, external reference retrieval, and process-level evaluation. Our evaluation of 23 leading models reveals critical limitations: even top performers like Claude Opus 4.5 exhibit substantial gaps, including difficulty selecting appropriate calculators for end-to-end workflows given fuzzy queries, poor performance in iterative SQL-based database interactions, and marked reluctance to leverage external tools for numerical computation. Performance also varies considerably across clinical domains. Building on these findings, we develop CalcMate, a fine-tuned model incorporating scenario planning and tool augmentation, achieving state-of-the-art performance among open-source models. Benchmark and Codes are available in https://github.com/SPIRAL-MED/MedMCP-Calc.

This study investigates GPT-4's assessment of its performance in healthcare applications. A simple prompting technique was used to prompt the LLM with questions taken from the United States Medical Licensing Examination (USMLE) questionnaire and it was tasked to evaluate its confidence score before posing the question and after asking the question. The questionnaire was categorized into two groups-questions with feedback (WF) and questions with no feedback(NF) post-question. The model was asked to provide absolute and relative confidence scores before and after each question. The experimental findings were analyzed using statistical tools to study the variability of confidence in WF and NF groups. Additionally, a sequential analysis was conducted to observe the performance variation for the WF and NF groups. Results indicate that feedback influences relative confidence but doesn't consistently increase or decrease it. Understanding the performance of LLM is paramount in exploring its utility in sensitive areas like healthcare. This study contributes to the ongoing discourse on the reliability of AI, particularly of LLMs like GPT-4, within healthcare, offering insights into how feedback mechanisms might be optimized to enhance AI-assisted medical education and decision support.

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

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.

User event modeling plays a central role in many machine learning applications, with use cases spanning e-commerce, social media, finance, cybersecurity, and other domains. User events can be broadly categorized into personal events, which involve individual actions, and relational events, which involve interactions between two users. These two types of events are typically modeled separately, using sequence-based methods for personal events and graph-based methods for relational events. Despite the need to capture both event types in real-world systems, prior work has rarely considered them together. This is often due to the convenient simplification that user behavior can be adequately represented by a single formalization, either as a sequence or a graph. To address this gap, there is a need for public datasets and prediction tasks that explicitly incorporate both personal and relational events. In this work, we introduce a collection of such datasets, propose a unified formalization, and empirically show that models benefit from incorporating both event types. Our results also indicate that current methods leave a notable room for improvements. We release these resources to support further research in unified user event modeling and encourage progress in this direction.

Human organs constantly undergo anatomical changes due to a complex mix of short-term (e.g., heartbeat) and long-term (e.g., aging) factors. Evidently, prior knowledge of these factors will be beneficial when modeling their future state, i.e., via image generation. However, most of the medical image generation tasks only rely on the input from a single image, thus ignoring the sequential dependency even when longitudinal data is available. Sequence-aware deep generative models, where model input is a sequence of ordered and timestamped images, are still underexplored in the medical imaging domain that is featured by several unique challenges: 1) Sequences with various lengths; 2) Missing data or frame, and 3) High dimensionality. To this end, we propose a sequence-aware diffusion model (SADM) for the generation of longitudinal medical images. Recently, diffusion models have shown promising results in high-fidelity image generation. Our method extends this new technique by introducing a sequence-aware transformer as the conditional module in a diffusion model. The novel design enables learning longitudinal dependency even with missing data during training and allows autoregressive generation of a sequence of images during inference. Our extensive experiments on 3D longitudinal medical images demonstrate the effectiveness of SADM compared with baselines and alternative methods. The code is available at https://github.com/ubc-tea/SADM-Longitudinal-Medical-Image-Generation.

Purpose: Surgical performance depends not only on surgeons' technical skills but also on team communication within and across the different professional groups present during the operation. Therefore, automatically identifying team communication in the OR is crucial for patient safety and advances in the development of computer-assisted surgical workflow analysis and intra-operative support systems. To take the first step, we propose a new task of detecting communication briefings involving all OR team members, i.e. the team Time-out and the StOP?-protocol, by localizing their start and end times in video recordings of surgical operations. Methods: We generate an OR dataset of real surgeries, called Team-OR, with more than one hundred hours of surgical videos captured by the multi-view camera system in the OR. The dataset contains temporal annotations of 33 Time-out and 22 StOP?-protocol activities in total. We then propose a novel group activity detection approach, where we encode both scene context and action features, and use an efficient neural network model to output the results. Results: The experimental results on the Team-OR dataset show that our approach outperforms existing state-of-the-art temporal action detection approaches. It also demonstrates the lack of research on group activities in the OR, proving the significance of our dataset. Conclusion: We investigate the Team Time-Out and the StOP?-protocol in the OR, by presenting the first OR dataset with temporal annotations of group activities protocols, and introducing a novel group activity detection approach that outperforms existing approaches. Code is available at https://github.com/CAMMA-public/Team-OR.

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

Intra-operative recognition of surgical phases holds significant potential for enhancing real-time contextual awareness in the operating room. However, we argue that online recognition, while beneficial, primarily lends itself to post-operative video analysis due to its limited direct impact on the actual surgical decisions and actions during ongoing procedures. In contrast, we contend that the prediction and anticipation of surgical phases are inherently more valuable for intra-operative assistance, as they can meaningfully influence a surgeon's immediate and long-term planning by providing foresight into future steps. To address this gap, we propose a dual approach that simultaneously recognises the current surgical phase and predicts upcoming ones, thus offering comprehensive intra-operative assistance and guidance on the expected remaining workflow. Our novel method, Surgical Phase Recognition and Anticipation (SuPRA), leverages past and current information for accurate intra-operative phase recognition while using future segments for phase prediction. This unified approach challenges conventional frameworks that treat these objectives separately. We have validated SuPRA on two reputed datasets, Cholec80 and AutoLaparo21, where it demonstrated state-of-the-art performance with recognition accuracies of 91.8% and 79.3%, respectively. Additionally, we introduce and evaluate our model using new segment-level evaluation metrics, namely Edit and F1 Overlap scores, for a more temporal assessment of segment classification. In conclusion, SuPRA presents a new multi-task approach that paves the way for improved intra-operative assistance through surgical phase recognition and prediction of future events.

This paper presents LLM4ES, a novel framework that exploits large pre-trained language models (LLMs) to derive user embeddings from event sequences. Event sequences are transformed into a textual representation, which is subsequently used to fine-tune an LLM through next-token prediction to generate high-quality embeddings. We introduce a text enrichment technique that enhances LLM adaptation to event sequence data, improving representation quality for low-variability domains. Experimental results demonstrate that LLM4ES achieves state-of-the-art performance in user classification tasks in financial and other domains, outperforming existing embedding methods. The resulting user embeddings can be incorporated into a wide range of applications, from user segmentation in finance to patient outcome prediction in healthcare.

Medical imaging is widely used in clinical practice for diagnosis and treatment. Report-writing can be error-prone for unexperienced physicians, and time- consuming and tedious for experienced physicians. To address these issues, we study the automatic generation of medical imaging reports. This task presents several challenges. First, a complete report contains multiple heterogeneous forms of information, including findings and tags. Second, abnormal regions in medical images are difficult to identify. Third, the re- ports are typically long, containing multiple sentences. To cope with these challenges, we (1) build a multi-task learning framework which jointly performs the pre- diction of tags and the generation of para- graphs, (2) propose a co-attention mechanism to localize regions containing abnormalities and generate narrations for them, (3) develop a hierarchical LSTM model to generate long paragraphs. We demonstrate the effectiveness of the proposed methods on two publicly available datasets.

The recent phenomenal success of language models has reinvigorated machine learning research, and large sequence models such as transformers are being applied to a variety of domains. One important problem class that has remained relatively elusive however is purposeful adaptive behavior. Currently there is a common perception that sequence models "lack the understanding of the cause and effect of their actions" leading them to draw incorrect inferences due to auto-suggestive delusions. In this report we explain where this mismatch originates, and show that it can be resolved by treating actions as causal interventions. Finally, we show that in supervised learning, one can teach a system to condition or intervene on data by training with factual and counterfactual error signals respectively.

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

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.