Daily Papers

In recent years, pre-trained language models (PLMs) achieve the best performance on a wide range of natural language processing (NLP) tasks. While the first models were trained on general domain data, specialized ones have emerged to more effectively treat specific domains. In this paper, we propose an original study of PLMs in the medical domain on French language. We compare, for the first time, the performance of PLMs trained on both public data from the web and private data from healthcare establishments. We also evaluate different learning strategies on a set of biomedical tasks. In particular, we show that we can take advantage of already existing biomedical PLMs in a foreign language by further pre-train it on our targeted data. Finally, we release the first specialized PLMs for the biomedical field in French, called DrBERT, as well as the largest corpus of medical data under free license on which these models are trained.

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.

Recently, pretrained language models based on BERT have been introduced for the French biomedical domain. Although these models have achieved state-of-the-art results on biomedical and clinical NLP tasks, they are constrained by a limited input sequence length of 512 tokens, which poses challenges when applied to clinical notes. In this paper, we present a comparative study of three adaptation strategies for long-sequence models, leveraging the Longformer architecture. We conducted evaluations of these models on 16 downstream tasks spanning both biomedical and clinical domains. Our findings reveal that further pre-training an English clinical model with French biomedical texts can outperform both converting a French biomedical BERT to the Longformer architecture and pre-training a French biomedical Longformer from scratch. The results underscore that long-sequence French biomedical models improve performance across most downstream tasks regardless of sequence length, but BERT based models remain the most efficient for named entity recognition tasks.

In this study, we investigate the potential of Large Language Models to complement biomedical knowledge graphs in the training of semantic models for the biomedical and clinical domains. Drawing on the wealth of the UMLS knowledge graph and harnessing cutting-edge Large Language Models, we propose a new state-of-the-art approach for obtaining high-fidelity representations of biomedical concepts and sentences, consisting of three steps: an improved contrastive learning phase, a novel self-distillation phase, and a weight averaging phase. Through rigorous evaluations via the extensive BioLORD testing suite and diverse downstream tasks, we demonstrate consistent and substantial performance improvements over the previous state of the art (e.g. +2pts on MedSTS, +2.5pts on MedNLI-S, +6.1pts on EHR-Rel-B). Besides our new state-of-the-art biomedical model for English, we also distill and release a multilingual model compatible with 50+ languages and finetuned on 7 European languages. Many clinical pipelines can benefit from our latest models. Our new multilingual model enables a range of languages to benefit from our advancements in biomedical semantic representation learning, opening a new avenue for bioinformatics researchers around the world. As a result, we hope to see BioLORD-2023 becoming a precious tool for future biomedical applications.

Pathology text mining is a challenging task given the reporting variability and constant new findings in cancer sub-type definitions. However, successful text mining of a large pathology database can play a critical role to advance 'big data' cancer research like similarity-based treatment selection, case identification, prognostication, surveillance, clinical trial screening, risk stratification, and many others. While there is a growing interest in developing language models for more specific clinical domains, no pathology-specific language space exist to support the rapid data-mining development in pathology space. In literature, a few approaches fine-tuned general transformer models on specialized corpora while maintaining the original tokenizer, but in fields requiring specialized terminology, these models often fail to perform adequately. We propose PathologyBERT - a pre-trained masked language model which was trained on 347,173 histopathology specimen reports and publicly released in the Huggingface repository. Our comprehensive experiments demonstrate that pre-training of transformer model on pathology corpora yields performance improvements on Natural Language Understanding (NLU) and Breast Cancer Diagnose Classification when compared to nonspecific language models.

Recent proprietary large language models (LLMs), such as GPT-4, have achieved a milestone in tackling diverse challenges in the biomedical domain, ranging from multiple-choice questions to long-form generations. To address challenges that still cannot be handled with the encoded knowledge of LLMs, various retrieval-augmented generation (RAG) methods have been developed by searching documents from the knowledge corpus and appending them unconditionally or selectively to the input of LLMs for generation. However, when applying existing methods to different domain-specific problems, poor generalization becomes apparent, leading to fetching incorrect documents or making inaccurate judgments. In this paper, we introduce Self-BioRAG, a framework reliable for biomedical text that specializes in generating explanations, retrieving domain-specific documents, and self-reflecting generated responses. We utilize 84k filtered biomedical instruction sets to train Self-BioRAG that can assess its generated explanations with customized reflective tokens. Our work proves that domain-specific components, such as a retriever, domain-related document corpus, and instruction sets are necessary for adhering to domain-related instructions. Using three major medical question-answering benchmark datasets, experimental results of Self-BioRAG demonstrate significant performance gains by achieving a 7.2% absolute improvement on average over the state-of-the-art open-foundation model with a parameter size of 7B or less. Overall, we analyze that Self-BioRAG finds the clues in the question, retrieves relevant documents if needed, and understands how to answer with information from retrieved documents and encoded knowledge as a medical expert does. We release our data and code for training our framework components and model weights (7B and 13B) to enhance capabilities in biomedical and clinical domains.

Over the past few years, various domain-specific pretrained language models (PLMs) have been proposed and have outperformed general-domain PLMs in specialized areas such as biomedical, scientific, and clinical domains. In addition, financial PLMs have been studied because of the high economic impact of financial data analysis. However, we found that financial PLMs were not pretrained on sufficiently diverse financial data. This lack of diverse training data leads to a subpar generalization performance, resulting in general-purpose PLMs, including BERT, often outperforming financial PLMs on many downstream tasks. To address this issue, we collected a broad range of financial corpus and trained the Financial Language Model (FiLM) on these diverse datasets. Our experimental results confirm that FiLM outperforms not only existing financial PLMs but also general domain PLMs. Furthermore, we provide empirical evidence that this improvement can be achieved even for unseen corpus groups.

Segmenting stroke lesions in Magnetic Resonance Imaging (MRI) is challenging due to diverse clinical imaging domains, with existing models struggling to generalise across different MRI acquisition parameters and sequences. In this work, we propose two novel physics-constrained approaches using synthetic quantitative MRI (qMRI) images to enhance the robustness and generalisability of segmentation models. We trained a qMRI estimation model to predict qMRI maps from MPRAGE images, which were used to simulate diverse MRI sequences for segmentation training. A second approach built upon prior work in synthetic data for stroke lesion segmentation, generating qMRI maps from a dataset of tissue labels. The proposed approaches improved over the baseline nnUNet on a variety of out-of-distribution datasets, with the second approach outperforming the prior synthetic data method.

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

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.

Prompt learning is a new paradigm in the Natural Language Processing (NLP) field which has shown impressive performance on a number of natural language tasks with common benchmarking text datasets in full, few-shot, and zero-shot train-evaluation setups. Recently, it has even been observed that large but frozen pre-trained language models (PLMs) with prompt learning outperform smaller but fine-tuned models. However, as with many recent NLP trends, the performance of even the largest PLMs such as GPT-3 do not perform well on specialized domains (e.g. medical text), and the common practice to achieve State of the Art (SoTA) results still consists of pre-training and fine-tuning the PLMs on downstream tasks. The reliance on fine-tuning large PLMs is problematic in clinical settings where data is often held in non-GPU environments, and more resource efficient methods of training specialized domain models is crucial. We investigated the viability of prompt learning on clinically meaningful decision tasks and directly compared with more traditional fine-tuning methods. Results are partially in line with the prompt learning literature, with prompt learning able to match or improve on traditional fine-tuning with substantially fewer trainable parameters and requiring less training data. We argue that prompt learning therefore provides lower computational resource costs applicable to clinical settings, that can serve as an alternative to fine-tuning ever increasing in size PLMs. Complementary code to reproduce experiments presented in this work can be found at: https://github.com/NtaylorOX/Public_Clinical_Prompt.

Adapting pretrained language models to novel domains, such as clinical applications, traditionally involves retraining their entire set of parameters. Parameter-Efficient Fine-Tuning (PEFT) techniques for fine-tuning language models significantly reduce computational requirements by selectively fine-tuning small subsets of parameters. In this study, we propose a two-step PEFT framework and evaluate it in the clinical domain. Our approach combines a specialised PEFT adapter layer designed for clinical domain adaptation with another adapter specialised for downstream tasks. We evaluate the framework on multiple clinical outcome prediction datasets, comparing it to clinically trained language models. Our framework achieves a better AUROC score averaged across all clinical downstream tasks compared to clinical language models. In particular, we observe large improvements of 4-5% AUROC in large-scale multilabel classification tasks, such as diagnoses and procedures classification. To our knowledge, this study is the first to provide an extensive empirical analysis of the interplay between PEFT techniques and domain adaptation in an important real-world domain of clinical applications.

Large-scale language models (LLMs), such as ChatGPT, are capable of generating human-like responses for various downstream tasks, such as task-oriented dialogues and question answering. However, applying LLMs to medical domains remains challenging due to their inability to leverage domain-specific knowledge. In this study, we present the Large-scale Language Models Augmented with Medical Textbooks (LLM-AMT), which integrates authoritative medical textbooks as the cornerstone of its design, enhancing its proficiency in the specialized domain through plug-and-play modules, comprised of a Hybrid Textbook Retriever, supplemented by the Query Augmenter and the LLM Reader. Experimental evaluation on three open-domain medical question-answering tasks reveals a substantial enhancement in both the professionalism and accuracy of the LLM responses when utilizing LLM-AMT, exhibiting an improvement ranging from 11.4% to 13.2%. Despite being 100 times smaller, we found that medical textbooks as the retrieval corpus serves as a more valuable external knowledge source than Wikipedia in the medical domain. Our experiments show that textbook augmentation results in a performance improvement ranging from 9.7% to 12.2% over Wikipedia augmentation.

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

Pre-trained transformers are often fine-tuned to aid clinical decision-making using limited clinical notes. Model interpretability is crucial, especially in high-stakes domains like medicine, to establish trust and ensure safety, which requires human engagement. We introduce SUFO, a systematic framework that enhances interpretability of fine-tuned transformer feature spaces. SUFO utilizes a range of analytic and visualization techniques, including Supervised probing, Unsupervised similarity analysis, Feature dynamics, and Outlier analysis to address key questions about model trust and interpretability. We conduct a case study investigating the impact of pre-training data where we focus on real-world pathology classification tasks, and validate our findings on MedNLI. We evaluate five 110M-sized pre-trained transformer models, categorized into general-domain (BERT, TNLR), mixed-domain (BioBERT, Clinical BioBERT), and domain-specific (PubMedBERT) groups. Our SUFO analyses reveal that: (1) while PubMedBERT, the domain-specific model, contains valuable information for fine-tuning, it can overfit to minority classes when class imbalances exist. In contrast, mixed-domain models exhibit greater resistance to overfitting, suggesting potential improvements in domain-specific model robustness; (2) in-domain pre-training accelerates feature disambiguation during fine-tuning; and (3) feature spaces undergo significant sparsification during this process, enabling clinicians to identify common outlier modes among fine-tuned models as demonstrated in this paper. These findings showcase the utility of SUFO in enhancing trust and safety when using transformers in medicine, and we believe SUFO can aid practitioners in evaluating fine-tuned language models for other applications in medicine and in more critical domains.

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.

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

Large language models (LLMs) have demonstrated impressive capabilities in natural language understanding and generation, but the quality bar for medical and clinical applications is high. Today, attempts to assess models' clinical knowledge typically rely on automated evaluations on limited benchmarks. There is no standard to evaluate model predictions and reasoning across a breadth of tasks. To address this, we present MultiMedQA, a benchmark combining six existing open question answering datasets spanning professional medical exams, research, and consumer queries; and HealthSearchQA, a new free-response dataset of medical questions searched online. We propose a framework for human evaluation of model answers along multiple axes including factuality, precision, possible harm, and bias. In addition, we evaluate PaLM (a 540-billion parameter LLM) and its instruction-tuned variant, Flan-PaLM, on MultiMedQA. Using a combination of prompting strategies, Flan-PaLM achieves state-of-the-art accuracy on every MultiMedQA multiple-choice dataset (MedQA, MedMCQA, PubMedQA, MMLU clinical topics), including 67.6% accuracy on MedQA (US Medical License Exam questions), surpassing prior state-of-the-art by over 17%. However, human evaluation reveals key gaps in Flan-PaLM responses. To resolve this we introduce instruction prompt tuning, a parameter-efficient approach for aligning LLMs to new domains using a few exemplars. The resulting model, Med-PaLM, performs encouragingly, but remains inferior to clinicians. We show that comprehension, recall of knowledge, and medical reasoning improve with model scale and instruction prompt tuning, suggesting the potential utility of LLMs in medicine. Our human evaluations reveal important limitations of today's models, reinforcing the importance of both evaluation frameworks and method development in creating safe, helpful LLM models for clinical applications.

Recent advances in natural language processing (NLP) can be largely attributed to the advent of pre-trained language models such as BERT and RoBERTa. While these models demonstrate remarkable performance on general datasets, they can struggle in specialized domains such as medicine, where unique domain-specific terminologies, domain-specific abbreviations, and varying document structures are common. This paper explores strategies for adapting these models to domain-specific requirements, primarily through continuous pre-training on domain-specific data. We pre-trained several German medical language models on 2.4B tokens derived from translated public English medical data and 3B tokens of German clinical data. The resulting models were evaluated on various German downstream tasks, including named entity recognition (NER), multi-label classification, and extractive question answering. Our results suggest that models augmented by clinical and translation-based pre-training typically outperform general domain models in medical contexts. We conclude that continuous pre-training has demonstrated the ability to match or even exceed the performance of clinical models trained from scratch. Furthermore, pre-training on clinical data or leveraging translated texts have proven to be reliable methods for domain adaptation in medical NLP tasks.

Diabetic Retinopathy (DR), induced by diabetes, poses a significant risk of visual impairment. Accurate and effective grading of DR aids in the treatment of this condition. Yet existing models experience notable performance degradation on unseen domains due to domain shifts. Previous methods address this issue by simulating domain style through simple visual transformation and mitigating domain noise via learning robust representations. However, domain shifts encompass more than image styles. They overlook biases caused by implicit factors such as ethnicity, age, and diagnostic criteria. In our work, we propose a novel framework where representations of paired data from different domains are decoupled into semantic features and domain noise. The resulting augmented representation comprises original retinal semantics and domain noise from other domains, aiming to generate enhanced representations aligned with real-world clinical needs, incorporating rich information from diverse domains. Subsequently, to improve the robustness of the decoupled representations, class and domain prototypes are employed to interpolate the disentangled representations while data-aware weights are designed to focus on rare classes and domains. Finally, we devise a robust pixel-level semantic alignment loss to align retinal semantics decoupled from features, maintaining a balance between intra-class diversity and dense class features. Experimental results on multiple benchmarks demonstrate the effectiveness of our method on unseen domains. The code implementations are accessible on https://github.com/richard-peng-xia/DECO.

Large Language Models (LLMs) constitute a breakthrough state-of-the-art Artificial Intelligence (AI) technology which is rapidly evolving and promises to aid in medical diagnosis either by assisting doctors or by simulating a doctor's workflow in more advanced and complex implementations. In this technical paper, we outline Cognitive Network Evaluation Toolkit for Medical Domains (COGNET-MD), which constitutes a novel benchmark for LLM evaluation in the medical domain. Specifically, we propose a scoring-framework with increased difficulty to assess the ability of LLMs in interpreting medical text. The proposed framework is accompanied with a database of Multiple Choice Quizzes (MCQs). To ensure alignment with current medical trends and enhance safety, usefulness, and applicability, these MCQs have been constructed in collaboration with several associated medical experts in various medical domains and are characterized by varying degrees of difficulty. The current (first) version of the database includes the medical domains of Psychiatry, Dentistry, Pulmonology, Dermatology and Endocrinology, but it will be continuously extended and expanded to include additional medical domains.

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

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

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

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

The field of natural language processing (NLP) has recently seen a large change towards using pre-trained language models for solving almost any task. Despite showing great improvements in benchmark datasets for various tasks, these models often perform sub-optimal in non-standard domains like the clinical domain where a large gap between pre-training documents and target documents is observed. In this paper, we aim at closing this gap with domain-specific training of the language model and we investigate its effect on a diverse set of downstream tasks and settings. We introduce the pre-trained CLIN-X (Clinical XLM-R) language models and show how CLIN-X outperforms other pre-trained transformer models by a large margin for ten clinical concept extraction tasks from two languages. In addition, we demonstrate how the transformer model can be further improved with our proposed task- and language-agnostic model architecture based on ensembles over random splits and cross-sentence context. Our studies in low-resource and transfer settings reveal stable model performance despite a lack of annotated data with improvements of up to 47 F1 points when only 250 labeled sentences are available. Our results highlight the importance of specialized language models as CLIN-X for concept extraction in non-standard domains, but also show that our task-agnostic model architecture is robust across the tested tasks and languages so that domain- or task-specific adaptations are not required.

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.

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.

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

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

The medical domain is vast and diverse, with many existing embedding models focused on general healthcare applications. However, these models often struggle to capture a deep understanding of diseases due to their broad generalization across the entire medical field. To address this gap, I present DisEmbed, a disease-focused embedding model. DisEmbed is trained on a synthetic dataset specifically curated to include disease descriptions, symptoms, and disease-related Q\&A pairs, making it uniquely suited for disease-related tasks. For evaluation, I benchmarked DisEmbed against existing medical models using disease-specific datasets and the triplet evaluation method. My results demonstrate that DisEmbed outperforms other models, particularly in identifying disease-related contexts and distinguishing between similar diseases. This makes DisEmbed highly valuable for disease-specific use cases, including retrieval-augmented generation (RAG) tasks, where its performance is particularly robust.

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.

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

Contextual word embedding models such as ELMo (Peters et al., 2018) and BERT (Devlin et al., 2018) have dramatically improved performance for many natural language processing (NLP) tasks in recent months. However, these models have been minimally explored on specialty corpora, such as clinical text; moreover, in the clinical domain, no publicly-available pre-trained BERT models yet exist. In this work, we address this need by exploring and releasing BERT models for clinical text: one for generic clinical text and another for discharge summaries specifically. We demonstrate that using a domain-specific model yields performance improvements on three common clinical NLP tasks as compared to nonspecific embeddings. These domain-specific models are not as performant on two clinical de-identification tasks, and argue that this is a natural consequence of the differences between de-identified source text and synthetically non de-identified task text.

We present SciRIFF (Scientific Resource for Instruction-Following and Finetuning), a dataset of 137K instruction-following demonstrations for 54 tasks covering five essential scientific literature understanding capabilities: information extraction, summarization, question answering, claim verification, and classification. SciRIFF demonstrations are notable for their long input contexts, detailed task specifications, and complex structured outputs. While instruction-following resources are available in specific domains such as clinical medicine and chemistry, SciRIFF is the first dataset focused on extracting and synthesizing information from research literature across a wide range of scientific fields. To demonstrate the utility of SciRIFF, we develop a sample-efficient strategy to adapt a general instruction-following model for science by performing additional finetuning on a mix of general-domain and SciRIFF demonstrations. In evaluations on nine held-out scientific tasks, our model -- called SciTulu -- improves over a strong LLM baseline by 28.1% and 6.5% at the 7B and 70B scales respectively, while maintaining general instruction-following performance within 2% of the baseline. We are optimistic that SciRIFF will facilitate the development and evaluation of LLMs to help researchers navigate the ever-growing body of scientific literature. We release our dataset, model checkpoints, and data processing and evaluation code to enable further research.

DIHARD III was the third in a series of speaker diarization challenges intended to improve the robustness of diarization systems to variability in recording equipment, noise conditions, and conversational domain. Speaker diarization was evaluated under two speech activity conditions (diarization from a reference speech activity vs. diarization from scratch) and 11 diverse domains. The domains span a range of recording conditions and interaction types, including read audio-books, meeting speech, clinical interviews, web videos, and, for the first time, conversational telephone speech. A total of 30 organizations (forming 21teams) from industry and academia submitted 499 valid system outputs. The evaluation results indicate that speaker diarization has improved markedly since DIHARD I, particularly for two-party interactions, but that for many domains (e.g., web video) the problem remains far from solved.

Summarization models often generate text that is poorly calibrated to quality metrics because they are trained to maximize the likelihood of a single reference (MLE). To address this, recent work has added a calibration step, which exposes a model to its own ranked outputs to improve relevance or, in a separate line of work, contrasts positive and negative sets to improve faithfulness. While effective, much of this work has focused on how to generate and optimize these sets. Less is known about why one setup is more effective than another. In this work, we uncover the underlying characteristics of effective sets. For each training instance, we form a large, diverse pool of candidates and systematically vary the subsets used for calibration fine-tuning. Each selection strategy targets distinct aspects of the sets, such as lexical diversity or the size of the gap between positive and negatives. On three diverse scientific long-form summarization datasets (spanning biomedical, clinical, and chemical domains), we find, among others, that faithfulness calibration is optimal when the negative sets are extractive and more likely to be generated, whereas for relevance calibration, the metric margin between candidates should be maximized and surprise--the disagreement between model and metric defined candidate rankings--minimized. Code to create, select, and optimize calibration sets is available at https://github.com/griff4692/calibrating-summaries

Foundation models (FMs) are able to leverage large volumes of unlabeled data to demonstrate superior performance across a wide range of tasks. However, FMs developed for biomedical domains have largely remained unimodal, i.e., independently trained and used for tasks on protein sequences alone, small molecule structures alone, or clinical data alone. To overcome this limitation of biomedical FMs, we present BioBridge, a novel parameter-efficient learning framework, to bridge independently trained unimodal FMs to establish multimodal behavior. BioBridge achieves it by utilizing Knowledge Graphs (KG) to learn transformations between one unimodal FM and another without fine-tuning any underlying unimodal FMs. Our empirical results demonstrate that BioBridge can beat the best baseline KG embedding methods (on average by around 76.3%) in cross-modal retrieval tasks. We also identify BioBridge demonstrates out-of-domain generalization ability by extrapolating to unseen modalities or relations. Additionally, we also show that BioBridge presents itself as a general purpose retriever that can aid biomedical multimodal question answering as well as enhance the guided generation of novel drugs.

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

In Natural Language Processing (NLP), Machine Reading Comprehension (MRC) is the task of answering a question based on a given context. To handle questions in the medical domain, modern language models such as BioBERT, SciBERT and even ChatGPT are trained on vast amounts of in-domain medical corpora. However, in-domain pre-training is expensive in terms of time and resources. In this paper, we propose a resource-efficient approach for injecting domain knowledge into a model without relying on such domain-specific pre-training. Knowledge graphs are powerful resources for accessing medical information. Building on existing work, we introduce a method using Multi-Layer Perceptrons (MLPs) for aligning and integrating embeddings extracted from medical knowledge graphs with the embedding spaces of pre-trained language models (LMs). The aligned embeddings are fused with open-domain LMs BERT and RoBERTa that are fine-tuned for two MRC tasks, span detection (COVID-QA) and multiple-choice questions (PubMedQA). We compare our method to prior techniques that rely on a vocabulary overlap for embedding alignment and show how our method circumvents this requirement to deliver better performance. On both datasets, our method allows BERT/RoBERTa to either perform on par (occasionally exceeding) with stronger domain-specific models or show improvements in general over prior techniques. With the proposed approach, we signal an alternative method to in-domain pre-training to achieve domain proficiency.

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.

Large Language Models (LLMs) have recently showcased their remarkable capacities, not only in natural language processing tasks but also across diverse domains such as clinical medicine, legal consultation, and education. LLMs become more than mere applications, evolving into assistants capable of addressing diverse user requests. This narrows the distinction between human beings and artificial intelligence agents, raising intriguing questions regarding the potential manifestation of personalities, temperaments, and emotions within LLMs. In this paper, we propose a framework, PsychoBench, for evaluating diverse psychological aspects of LLMs. Comprising thirteen scales commonly used in clinical psychology, PsychoBench further classifies these scales into four distinct categories: personality traits, interpersonal relationships, motivational tests, and emotional abilities. Our study examines five popular models, namely text-davinci-003, ChatGPT, GPT-4, LLaMA-2-7b, and LLaMA-2-13b. Additionally, we employ a jailbreak approach to bypass the safety alignment protocols and test the intrinsic natures of LLMs. We have made PsychoBench openly accessible via https://github.com/CUHK-ARISE/PsychoBench.

The success of automated medical image analysis depends on large-scale and expert-annotated training sets. Unsupervised domain adaptation (UDA) has been raised as a promising approach to alleviate the burden of labeled data collection. However, they generally operate under the closed-set adaptation setting assuming an identical label set between the source and target domains, which is over-restrictive in clinical practice where new classes commonly exist across datasets due to taxonomic inconsistency. While several methods have been presented to tackle both domain shifts and incoherent label sets, none of them take into account the common characteristics of the two issues and consider the learning dynamics along network training. In this work, we propose optimization trajectory distillation, a unified approach to address the two technical challenges from a new perspective. It exploits the low-rank nature of gradient space and devises a dual-stream distillation algorithm to regularize the learning dynamics of insufficiently annotated domain and classes with the external guidance obtained from reliable sources. Our approach resolves the issue of inadequate navigation along network optimization, which is the major obstacle in the taxonomy adaptive cross-domain adaptation scenario. We evaluate the proposed method extensively on several tasks towards various endpoints with clinical and open-world significance. The results demonstrate its effectiveness and improvements over previous methods.

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

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

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

This work presents biomedical and clinical language models for Spanish by experimenting with different pretraining choices, such as masking at word and subword level, varying the vocabulary size and testing with domain data, looking for better language representations. Interestingly, in the absence of enough clinical data to train a model from scratch, we applied mixed-domain pretraining and cross-domain transfer approaches to generate a performant bio-clinical model suitable for real-world clinical data. We evaluated our models on Named Entity Recognition (NER) tasks for biomedical documents and challenging hospital discharge reports. When compared against the competitive mBERT and BETO models, we outperform them in all NER tasks by a significant margin. Finally, we studied the impact of the model's vocabulary on the NER performances by offering an interesting vocabulary-centric analysis. The results confirm that domain-specific pretraining is fundamental to achieving higher performances in downstream NER tasks, even within a mid-resource scenario. To the best of our knowledge, we provide the first biomedical and clinical transformer-based pretrained language models for Spanish, intending to boost native Spanish NLP applications in biomedicine. Our best models are freely available in the HuggingFace hub: https://huggingface.co/BSC-TeMU.

Contextual word embedding models, such as BioBERT and Bio_ClinicalBERT, have achieved state-of-the-art results in biomedical natural language processing tasks by focusing their pre-training process on domain-specific corpora. However, such models do not take into consideration expert domain knowledge. In this work, we introduced UmlsBERT, a contextual embedding model that integrates domain knowledge during the pre-training process via a novel knowledge augmentation strategy. More specifically, the augmentation on UmlsBERT with the Unified Medical Language System (UMLS) Metathesaurus was performed in two ways: i) connecting words that have the same underlying `concept' in UMLS, and ii) leveraging semantic group knowledge in UMLS to create clinically meaningful input embeddings. By applying these two strategies, UmlsBERT can encode clinical domain knowledge into word embeddings and outperform existing domain-specific models on common named-entity recognition (NER) and clinical natural language inference clinical NLP tasks.

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

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.

Predictive process monitoring is a process mining task aimed at forecasting information about a running process trace, such as the most correct next activity to be executed. In medical domains, predictive process monitoring can provide valuable decision support in atypical and nontrivial situations. Decision support and quality assessment in medicine cannot ignore domain knowledge, in order to be grounded on all the available information (which is not limited to data) and to be really acceptable by end users. In this paper, we propose a predictive process monitoring approach relying on the use of a {\em transformer}, a deep learning architecture based on the attention mechanism. A major contribution of our work lies in the incorporation of ontological domain-specific knowledge, carried out through a graph positional encoding technique. The paper presents and discusses the encouraging experimental result we are collecting in the domain of stroke management.

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

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

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

Generating synthetic text addresses the challenge of data availability in privacy-sensitive domains such as healthcare. This study explores the applicability of synthetic data in real-world medical settings. We introduce MedSyn, a novel medical text generation framework that integrates large language models with a Medical Knowledge Graph (MKG). We use MKG to sample prior medical information for the prompt and generate synthetic clinical notes with GPT-4 and fine-tuned LLaMA models. We assess the benefit of synthetic data through application in the ICD code prediction task. Our research indicates that synthetic data can increase the classification accuracy of vital and challenging codes by up to 17.8% compared to settings without synthetic data. Furthermore, to provide new data for further research in the healthcare domain, we present the largest open-source synthetic dataset of clinical notes for the Russian language, comprising over 41k samples covering 219 ICD-10 codes.

Medicine, by its nature, is a multifaceted domain that requires the synthesis of information across various modalities. Medical generative vision-language models (VLMs) make a first step in this direction and promise many exciting clinical applications. However, existing models typically have to be fine-tuned on sizeable down-stream datasets, which poses a significant limitation as in many medical applications data is scarce, necessitating models that are capable of learning from few examples in real-time. Here we propose Med-Flamingo, a multimodal few-shot learner adapted to the medical domain. Based on OpenFlamingo-9B, we continue pre-training on paired and interleaved medical image-text data from publications and textbooks. Med-Flamingo unlocks few-shot generative medical visual question answering (VQA) abilities, which we evaluate on several datasets including a novel challenging open-ended VQA dataset of visual USMLE-style problems. Furthermore, we conduct the first human evaluation for generative medical VQA where physicians review the problems and blinded generations in an interactive app. Med-Flamingo improves performance in generative medical VQA by up to 20\% in clinician's rating and firstly enables multimodal medical few-shot adaptations, such as rationale generation. We release our model, code, and evaluation app under https://github.com/snap-stanford/med-flamingo.

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.

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

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.

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

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.

Several recent works seek to develop foundation models specifically for medical applications, adapting general-purpose large language models (LLMs) and vision-language models (VLMs) via continued pretraining on publicly available biomedical corpora. These works typically claim that such domain-adaptive pretraining (DAPT) improves performance on downstream medical tasks, such as answering medical licensing exam questions. In this paper, we compare seven public "medical" LLMs and two VLMs against their corresponding base models, arriving at a different conclusion: all medical VLMs and nearly all medical LLMs fail to consistently improve over their base models in the zero-/few-shot prompting regime for medical question-answering (QA) tasks. For instance, across the tasks and model pairs we consider in the 3-shot setting, medical LLMs only outperform their base models in 12.1% of cases, reach a (statistical) tie in 49.8% of cases, and are significantly worse than their base models in the remaining 38.2% of cases. Our conclusions are based on (i) comparing each medical model head-to-head, directly against the corresponding base model; (ii) optimizing the prompts for each model separately; and (iii) accounting for statistical uncertainty in comparisons. While these basic practices are not consistently adopted in the literature, our ablations show that they substantially impact conclusions. Our findings suggest that state-of-the-art general-domain models may already exhibit strong medical knowledge and reasoning capabilities, and offer recommendations to strengthen the conclusions of future studies.

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

Pretrained language models have been used in various natural language processing applications. In the mental health domain, domain-specific language models are pretrained and released, which facilitates the early detection of mental health conditions. Social posts, e.g., on Reddit, are usually long documents. However, there are no domain-specific pretrained models for long-sequence modeling in the mental health domain. This paper conducts domain-specific continued pretraining to capture the long context for mental health. Specifically, we train and release MentalXLNet and MentalLongformer based on XLNet and Longformer. We evaluate the mental health classification performance and the long-range ability of these two domain-specific pretrained models. Our models are released in HuggingFace.

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

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

Domain generalization (DG) is proposed to deal with the issue of domain shift, which occurs when statistical differences exist between source and target domains. However, most current methods do not account for a common realistic scenario where the source and target domains have different classes. To overcome this deficiency, open set domain generalization (OSDG) then emerges as a more practical setting to recognize unseen classes in unseen domains. An intuitive approach is to use multiple one-vs-all classifiers to define decision boundaries for each class and reject the outliers as unknown. However, the significant class imbalance between positive and negative samples often causes the boundaries biased towards positive ones, resulting in misclassification for known samples in the unseen target domain. In this paper, we propose a novel meta-learning-based framework called dualistic MEta-learning with joint DomaIn-Class matching (MEDIC), which considers gradient matching towards inter-domain and inter-class splits simultaneously to find a generalizable boundary balanced for all tasks. Experimental results demonstrate that MEDIC not only outperforms previous methods in open set scenarios, but also maintains competitive close set generalization ability at the same time. Our code is available at https://github.com/zzwdx/MEDIC.

Machine learning models are often trained to predict the outcome resulting from a human decision. For example, if a doctor decides to test a patient for disease, will the patient test positive? A challenge is that historical decision-making determines whether the outcome is observed: we only observe test outcomes for patients doctors historically tested. Untested patients, for whom outcomes are unobserved, may differ from tested patients along observed and unobserved dimensions. We propose a Bayesian model class which captures this setting. The purpose of the model is to accurately estimate risk for both tested and untested patients. Estimating this model is challenging due to the wide range of possibilities for untested patients. To address this, we propose two domain constraints which are plausible in health settings: a prevalence constraint, where the overall disease prevalence is known, and an expertise constraint, where the human decision-maker deviates from purely risk-based decision-making only along a constrained feature set. We show theoretically and on synthetic data that domain constraints improve parameter inference. We apply our model to a case study of cancer risk prediction, showing that the model's inferred risk predicts cancer diagnoses, its inferred testing policy captures known public health policies, and it can identify suboptimalities in test allocation. Though our case study is in healthcare, our analysis reveals a general class of domain constraints which can improve model estimation in many settings.

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

We perform a comprehensive benchmarking of contrastive frameworks for learning multimodal representations in the medical domain. Through this study, we aim to answer the following research questions: (i) How transferable are general-domain representations to the medical domain? (ii) Is multimodal contrastive training sufficient, or does it benefit from unimodal training as well? (iii) What is the impact of feature granularity on the effectiveness of multimodal medical representation learning? To answer these questions, we investigate eight contrastive learning approaches under identical training setups, and train them on 2.8 million image-text pairs from four datasets, and evaluate them on 25 downstream tasks, including classification (zero-shot and linear probing), image-to-text and text-to-image retrieval, and visual question-answering. Our findings suggest a positive answer to the first question, a negative answer to the second question, and the benefit of learning fine-grained features. Finally, we make our code publicly available.

Objective: We investigate whether deep learning techniques for natural language processing (NLP) can be used efficiently for patient phenotyping. Patient phenotyping is a classification task for determining whether a patient has a medical condition, and is a crucial part of secondary analysis of healthcare data. We assess the performance of deep learning algorithms and compare them with classical NLP approaches. Materials and Methods: We compare convolutional neural networks (CNNs), n-gram models, and approaches based on cTAKES that extract pre-defined medical concepts from clinical notes and use them to predict patient phenotypes. The performance is tested on 10 different phenotyping tasks using 1,610 discharge summaries extracted from the MIMIC-III database. Results: CNNs outperform other phenotyping algorithms in all 10 tasks. The average F1-score of our model is 76 (PPV of 83, and sensitivity of 71) with our model having an F1-score up to 37 points higher than alternative approaches. We additionally assess the interpretability of our model by presenting a method that extracts the most salient phrases for a particular prediction. Conclusion: We show that NLP methods based on deep learning improve the performance of patient phenotyping. Our CNN-based algorithm automatically learns the phrases associated with each patient phenotype. As such, it reduces the annotation complexity for clinical domain experts, who are normally required to develop task-specific annotation rules and identify relevant phrases. Our method performs well in terms of both performance and interpretability, which indicates that deep learning is an effective approach to patient phenotyping based on clinicians' notes.

There has been an influx of biomedical domain-specific language models, showing language models pre-trained on biomedical text perform better on biomedical domain benchmarks than those trained on general domain text corpora such as Wikipedia and Books. Yet, most works do not study the factors affecting each domain language application deeply. Additionally, the study of model size on domain-specific models has been mostly missing. We empirically study and evaluate several factors that can affect performance on domain language applications, such as the sub-word vocabulary set, model size, pre-training corpus, and domain transfer. We show consistent improvements on benchmarks with our larger BioMegatron model trained on a larger domain corpus, contributing to our understanding of domain language model applications. We demonstrate noticeable improvements over the previous state-of-the-art (SOTA) on standard biomedical NLP benchmarks of named entity recognition, relation extraction, and question answering. Model checkpoints and code are available at [https://ngc.nvidia.com] and [https://github.com/NVIDIA/NeMo].

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

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.

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

While deep networks have achieved broad success in analyzing natural images, when applied to medical scans, they often fail in unexcepted situations. We investigate this challenge and focus on model sensitivity to domain shifts, such as data sampled from different hospitals or data confounded by demographic variables such as sex, race, etc, in the context of chest X-rays and skin lesion images. A key finding we show empirically is that existing visual backbones lack an appropriate prior from the architecture for reliable generalization in these settings. Taking inspiration from medical training, we propose giving deep networks a prior grounded in explicit medical knowledge communicated in natural language. To this end, we introduce Knowledge-enhanced Bottlenecks (KnoBo), a class of concept bottleneck models that incorporates knowledge priors that constrain it to reason with clinically relevant factors found in medical textbooks or PubMed. KnoBo uses retrieval-augmented language models to design an appropriate concept space paired with an automatic training procedure for recognizing the concept. We evaluate different resources of knowledge and recognition architectures on a broad range of domain shifts across 20 datasets. In our comprehensive evaluation with two imaging modalities, KnoBo outperforms fine-tuned models on confounded datasets by 32.4% on average. Finally, evaluations reveal that PubMed is a promising resource for making medical models less sensitive to domain shift, outperforming other resources on both diversity of information and final prediction performance.

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.

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

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

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

Recently, Large Language Models (LLMs) have showcased remarkable capabilities in natural language understanding. While demonstrating proficiency in everyday conversations and question-answering situations, these models frequently struggle in domains that require precision, such as medical applications, due to their lack of domain-specific knowledge. In this paper, we describe the procedure for building a powerful, open-source language model specifically designed for medicine applications, termed as PMC-LLaMA. Our contributions are threefold: (i) we systematically investigate the process of adapting a general-purpose foundation language model towards medical domain, this involves data-centric knowledge injection through the integration of 4.8M biomedical academic papers and 30K medical textbooks, as well as comprehensive fine-tuning for alignment with domain-specific instructions; (ii) we contribute a large-scale, comprehensive dataset for instruction tuning. This dataset encompasses medical question-answering (QA), rationale for reasoning, and conversational dialogues, comprising a total of 202M tokens; (iii) we conduct thorough ablation studies to demonstrate the effectiveness of each proposed component. While evaluating on various public medical question-answering benchmarks, our lightweight PMCLLaMA, which consists of only 13 billion parameters, exhibits superior performance, even surpassing ChatGPT. All models, codes, datasets can be found in https://github.com/chaoyi-wu/PMC-LLaMA.

This paper introduces MedTrinity-25M, a comprehensive, large-scale multimodal dataset for medicine, covering over 25 million images across 10 modalities, with multigranular annotations for more than 65 diseases. These enriched annotations encompass both global textual information, such as disease/lesion type, modality, region-specific descriptions, and inter-regional relationships, as well as detailed local annotations for regions of interest (ROIs), including bounding boxes, segmentation masks. Unlike existing approach which is limited by the availability of image-text pairs, we have developed the first automated pipeline that scales up multimodal data by generating multigranular visual and texual annotations (in the form of image-ROI-description triplets) without the need for any paired text descriptions. Specifically, data from over 90 different sources have been collected, preprocessed, and grounded using domain-specific expert models to identify ROIs related to abnormal regions. We then build a comprehensive knowledge base and prompt multimodal large language models to perform retrieval-augmented generation with the identified ROIs as guidance, resulting in multigranular texual descriptions. Compared to existing datasets, MedTrinity-25M provides the most enriched annotations, supporting a comprehensive range of multimodal tasks such as captioning and report generation, as well as vision-centric tasks like classification and segmentation. Pretraining on MedTrinity-25M, our model achieves state-of-the-art performance on VQA-RAD and PathVQA, surpassing both multimodal large language models and other representative SoTA approaches. This dataset can also be utilized to support large-scale pre-training of multimodal medical AI models, contributing to the development of future foundation models in the medical domain.

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

Large-language models 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.

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

Recent advances in large language models (LLMs) have demonstrated exceptional performance in various natural language processing (NLP) tasks. However, their effective application in the medical domain is hampered by a lack of medical domain knowledge. In this study, we present SA-MDKIF, a scalable and adaptable framework that aims to inject medical knowledge into general-purpose LLMs through instruction tuning, thereby enabling adaptability for various downstream tasks. SA-MDKIF consists of two stages: skill training and skill adaptation. In the first stage, we define 12 basic medical skills and use AdaLoRA to train these skills based on uniformly formatted instructional datasets that we have constructed. In the next stage, we train the skill router using task-specific downstream data and use this router to integrate the acquired skills with LLMs during inference. Experimental results on 9 different medical tasks show that SA-MDKIF improves performance by 10-20% compared to the original LLMs. Notably, this improvement is particularly pronounced for unseen medical tasks, showing an improvement of up to 30%.

Large language models (LLMs) have shown potential in biomedical applications, leading to efforts to fine-tune them on domain-specific data. However, the effectiveness of this approach remains unclear. This study evaluates the performance of biomedically fine-tuned LLMs against their general-purpose counterparts on a variety of clinical tasks. We evaluated their performance on clinical case challenges from the New England Journal of Medicine (NEJM) and the Journal of the American Medical Association (JAMA) and on several clinical tasks (e.g., information extraction, document summarization, and clinical coding). Using benchmarks specifically chosen to be likely outside the fine-tuning datasets of biomedical models, we found that biomedical LLMs mostly perform inferior to their general-purpose counterparts, especially on tasks not focused on medical knowledge. While larger models showed similar performance on case tasks (e.g., OpenBioLLM-70B: 66.4% vs. Llama-3-70B-Instruct: 65% on JAMA cases), smaller biomedical models showed more pronounced underperformance (e.g., OpenBioLLM-8B: 30% vs. Llama-3-8B-Instruct: 64.3% on NEJM cases). Similar trends were observed across the CLUE (Clinical Language Understanding Evaluation) benchmark tasks, with general-purpose models often performing better on text generation, question answering, and coding tasks. Our results suggest that fine-tuning LLMs to biomedical data may not provide the expected benefits and may potentially lead to reduced performance, challenging prevailing assumptions about domain-specific adaptation of LLMs and highlighting the need for more rigorous evaluation frameworks in healthcare AI. Alternative approaches, such as retrieval-augmented generation, may be more effective in enhancing the biomedical capabilities of LLMs without compromising their general knowledge.

Pretraining large neural language models, such as BERT, has led to impressive gains on many natural language processing (NLP) tasks. However, most pretraining efforts focus on general domain corpora, such as newswire and Web. A prevailing assumption is that even domain-specific pretraining can benefit by starting from general-domain language models. In this paper, we challenge this assumption by showing that for domains with abundant unlabeled text, such as biomedicine, pretraining language models from scratch results in substantial gains over continual pretraining of general-domain language models. To facilitate this investigation, we compile a comprehensive biomedical NLP benchmark from publicly-available datasets. Our experiments show that domain-specific pretraining serves as a solid foundation for a wide range of biomedical NLP tasks, leading to new state-of-the-art results across the board. Further, in conducting a thorough evaluation of modeling choices, both for pretraining and task-specific fine-tuning, we discover that some common practices are unnecessary with BERT models, such as using complex tagging schemes in named entity recognition (NER). To help accelerate research in biomedical NLP, we have released our state-of-the-art pretrained and task-specific models for the community, and created a leaderboard featuring our BLURB benchmark (short for Biomedical Language Understanding & Reasoning Benchmark) at https://aka.ms/BLURB.

Since the emergence of the Transformer architecture, language model development has increased, driven by their promising potential. However, releasing these models into production requires properly understanding their behavior, particularly in sensitive domains such as medicine. Despite this need, the medical literature still lacks technical assessments of pre-trained language models, which are especially valuable in resource-constrained settings in terms of computational power or limited budget. To address this gap, we provide a comprehensive survey of language models in the medical domain. In addition, we selected a subset of these models for thorough evaluation, focusing on classification and text generation tasks. Our subset encompasses 53 models, ranging from 110 million to 13 billion parameters, spanning the three families of Transformer-based models and from diverse knowledge domains. This study employs a series of approaches for text classification together with zero-shot prompting instead of model training or fine-tuning, which closely resembles the limited resource setting in which many users of language models find themselves. Encouragingly, our findings reveal remarkable performance across various tasks and datasets, underscoring the latent potential of certain models to contain medical knowledge, even without domain specialization. Consequently, our study advocates for further exploration of model applications in medical contexts, particularly in resource-constrained settings. The code is available on https://github.com/anpoc/Language-models-in-medicine.

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.

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

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

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

Domain generalization is critical for real-world applications of machine learning to microscopy images, including histopathology and fluorescence imaging. Artifacts in these modalities arise through a complex combination of factors relating to tissue collection and laboratory processing, as well as factors intrinsic to patient samples. In fluorescence imaging, these artifacts stem from variations across experimental batches. The complexity and subtlety of these artifacts make the enumeration of data domains intractable. Therefore, augmentation-based methods of domain generalization that require domain identifiers and manual fine-tuning are inadequate in this setting. To overcome this challenge, we introduce ContriMix, a domain generalization technique that learns to generate synthetic images by disentangling and permuting the biological content ("content") and technical variations ("attributes") in microscopy images. ContriMix does not rely on domain identifiers or handcrafted augmentations and makes no assumptions about the input characteristics of images. We assess the performance of ContriMix on two pathology datasets dealing with patch classification and Whole Slide Image label prediction tasks respectively (Camelyon17-WILDS and RCC subtyping), and one fluorescence microscopy dataset (RxRx1-WILDS). Without any access to domain identifiers at train or test time, ContriMix performs similar or better than current state-of-the-art methods in all these datasets, motivating its usage for microscopy image analysis in real-world settings where domain information is hard to come by. The code for ContriMix can be found at https://gitlab.com/huutan86/contrimix

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

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.

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

User-generated data sources have gained significance in uncovering Adverse Drug Reactions (ADRs), with an increasing number of discussions occurring in the digital world. However, the existing clinical corpora predominantly revolve around scientific articles in English. This work presents a multilingual corpus of texts concerning ADRs gathered from diverse sources, including patient fora, social media, and clinical reports in German, French, and Japanese. Our corpus contains annotations covering 12 entity types, four attribute types, and 13 relation types. It contributes to the development of real-world multilingual language models for healthcare. We provide statistics to highlight certain challenges associated with the corpus and conduct preliminary experiments resulting in strong baselines for extracting entities and relations between these entities, both within and across languages.

This paper presents the development of a prototype Automatic Speech Recognition (ASR) system specifically designed for Bengali biomedical data. Recent advancements in Bengali ASR are encouraging, but a lack of domain-specific data limits the creation of practical healthcare ASR models. This project bridges this gap by developing an ASR system tailored for Bengali medical terms like symptoms, severity levels, and diseases, encompassing two major dialects: Bengali and Sylheti. We train and evaluate two popular ASR frameworks on a comprehensive 46-hour Bengali medical corpus. Our core objective is to create deployable health-domain ASR systems for digital health applications, ultimately increasing accessibility for non-technical users in the healthcare sector.

Electronic health record (EHR) systems are used extensively throughout the healthcare domain. However, data interchangeability between EHR systems is limited due to the use of different coding standards across systems. Existing methods of mapping coding standards based on manual human experts mapping, dictionary mapping, symbolic NLP and classification are unscalable and cannot accommodate large scale EHR datasets. In this work, we present Text2Node, a cross-domain mapping system capable of mapping medical phrases to concepts in a large taxonomy (such as SNOMED CT). The system is designed to generalize from a limited set of training samples and map phrases to elements of the taxonomy that are not covered by training data. As a result, our system is scalable, robust to wording variants between coding systems and can output highly relevant concepts when no exact concept exists in the target taxonomy. Text2Node operates in three main stages: first, the lexicon is mapped to word embeddings; second, the taxonomy is vectorized using node embeddings; and finally, the mapping function is trained to connect the two embedding spaces. We compared multiple algorithms and architectures for each stage of the training, including GloVe and FastText word embeddings, CNN and Bi-LSTM mapping functions, and node2vec for node embeddings. We confirmed the robustness and generalisation properties of Text2Node by mapping ICD-9-CM Diagnosis phrases to SNOMED CT and by zero-shot training at comparable accuracy. This system is a novel methodological contribution to the task of normalizing and linking phrases to a taxonomy, advancing data interchangeability in healthcare. When applied, the system can use electronic health records to generate an embedding that incorporates taxonomical medical knowledge to improve clinical predictive models.

Adapting a language model into a specific domain, a.k.a `domain adaption', is a common practice when specialized knowledge, e.g. medicine, is not encapsulated in a general language model like Llama2. The challenge lies in the heterogeneity of data across the two training stages, as it varies in languages, genres, or formats. To tackle this and simplify the learning protocol, we propose to transform heterogeneous data, from the both pre-training and supervised stages, into a unified, simple input-output pair format. We validate the new protocol in the domains where proprietary LLMs like ChatGPT perform relatively poorly, such as Traditional Chinese Medicine. The developed model, HuatuoGPT-II, has shown state-of-the-art performance in Chinese medicine domain on a number of benchmarks, e.g. medical licensing exams. It even outperforms proprietary models like ChatGPT and GPT-4 in some aspects, especially in Traditional Chinese Medicine. Expert manual evaluations further validate HuatuoGPT-II's advantages over existing LLMs. Notably, HuatuoGPT-II was benchmarked in a fresh Chinese National Medical Licensing Examination where it achieved the best performance, showcasing not only its effectiveness but also its generalization capabilities.

Large language models, particularly GPT-3, are able to produce high quality summaries of general domain news articles in few- and zero-shot settings. However, it is unclear if such models are similarly capable in more specialized, high-stakes domains such as biomedicine. In this paper, we enlist domain experts (individuals with medical training) to evaluate summaries of biomedical articles generated by GPT-3, given zero supervision. We consider both single- and multi-document settings. In the former, GPT-3 is tasked with generating regular and plain-language summaries of articles describing randomized controlled trials; in the latter, we assess the degree to which GPT-3 is able to synthesize evidence reported across a collection of articles. We design an annotation scheme for evaluating model outputs, with an emphasis on assessing the factual accuracy of generated summaries. We find that while GPT-3 is able to summarize and simplify single biomedical articles faithfully, it struggles to provide accurate aggregations of findings over multiple documents. We release all data and annotations used in this work.

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.

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.

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].

Mental health disorders are one of the most serious diseases in the world. Most people with such a disease lack access to adequate care, which highlights the importance of training models for the diagnosis and treatment of mental health disorders. However, in the mental health domain, privacy concerns limit the accessibility of personalized treatment data, making it challenging to build powerful models. In this paper, we introduce MentalArena, a self-play framework to train language models by generating domain-specific personalized data, where we obtain a better model capable of making a personalized diagnosis and treatment (as a therapist) and providing information (as a patient). To accurately model human-like mental health patients, we devise Symptom Encoder, which simulates a real patient from both cognition and behavior perspectives. To address intent bias during patient-therapist interactions, we propose Symptom Decoder to compare diagnosed symptoms with encoded symptoms, and dynamically manage the dialogue between patient and therapist according to the identified deviations. We evaluated MentalArena against 6 benchmarks, including biomedicalQA and mental health tasks, compared to 6 advanced models. Our models, fine-tuned on both GPT-3.5 and Llama-3-8b, significantly outperform their counterparts, including GPT-4o. We hope that our work can inspire future research on personalized care. Code is available in https://github.com/Scarelette/MentalArena/tree/main

Clinical data in hospitals are increasingly accessible for research through clinical data warehouses, however these documents are unstructured. It is therefore necessary to extract information from medical reports to conduct clinical studies. Transfer learning with BERT-like models such as CamemBERT has allowed major advances, especially for named entity recognition. However, these models are trained for plain language and are less efficient on biomedical data. This is why we propose a new French public biomedical dataset on which we have continued the pre-training of CamemBERT. Thus, we introduce a first version of CamemBERT-bio, a specialized public model for the French biomedical domain that shows 2.54 points of F1 score improvement on average on different biomedical named entity recognition tasks. Our findings demonstrate the success of continual pre-training from a French model and contrast with recent proposals on the same domain and language. One of our key contributions highlights the importance of using a standard evaluation protocol that enables a clear view of the current state-of-the-art for French biomedical models.

In the expanding field of language model applications, medical knowledge representation remains a significant challenge due to the specialized nature of the domain. Large language models, such as GPT-4, obtain reasonable scores on medical question answering tasks, but smaller models are far behind. In this work, we introduce a method to improve the proficiency of a small language model in the medical domain by employing a two-fold approach. We first fine-tune the model on a corpus of medical textbooks. Then, we use GPT-4 to generate questions similar to the downstream task, prompted with textbook knowledge, and use them to fine-tune the model. Additionally, we introduce ECN-QA, a novel medical question answering dataset containing ``progressive questions'' composed of related sequential questions. We show the benefits of our training strategy on this dataset. The study's findings highlight the potential of small language models in the medical domain when appropriately fine-tuned. The code and weights are available at https://github.com/raidium-med/MQG.

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

Due to privacy restrictions, there's a shortage of publicly available speech recognition datasets in the medical domain. In this work, we present VietMed - a Vietnamese speech recognition dataset in the medical domain comprising 16h of labeled medical speech, 1000h of unlabeled medical speech and 1200h of unlabeled general-domain speech. To our best knowledge, VietMed is by far the world's largest public medical speech recognition dataset in 7 aspects: total duration, number of speakers, diseases, recording conditions, speaker roles, unique medical terms and accents. VietMed is also by far the largest public Vietnamese speech dataset in terms of total duration. Additionally, we are the first to present a medical ASR dataset covering all ICD-10 disease groups and all accents within a country. Moreover, we release the first public large-scale pre-trained models for Vietnamese ASR, w2v2-Viet and XLSR-53-Viet, along with the first public large-scale fine-tuned models for medical ASR. Even without any medical data in unsupervised pre-training, our best pre-trained model XLSR-53-Viet generalizes very well to the medical domain by outperforming state-of-the-art XLSR-53, from 51.8% to 29.6% WER on test set (a relative reduction of more than 40%). All code, data and models are made publicly available here: https://github.com/leduckhai/MultiMed.

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

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

Generalist vision language models (VLMs) have made significant strides in computer vision, but they fall short in specialized fields like healthcare, where expert knowledge is essential. In traditional computer vision tasks, creative or approximate answers may be acceptable, but in healthcare, precision is paramount.Current large multimodal models like Gemini and GPT-4o are insufficient for medical tasks due to their reliance on memorized internet knowledge rather than the nuanced expertise required in healthcare. VLMs are usually trained in three stages: vision pre-training, vision-language pre-training, and instruction fine-tuning (IFT). IFT has been typically applied using a mixture of generic and healthcare data. In contrast, we propose that for medical VLMs, a fourth stage of specialized IFT is necessary, which focuses on medical data and includes information from domain expert models. Domain expert models developed for medical use are crucial because they are specifically trained for certain clinical tasks, e.g. to detect tumors and classify abnormalities through segmentation and classification, which learn fine-grained features of medical data-features that are often too intricate for a VLM to capture effectively especially in radiology. This paper introduces a new framework, VILA-M3, for medical VLMs that utilizes domain knowledge via expert models. Through our experiments, we show an improved state-of-the-art (SOTA) performance with an average improvement of ~9% over the prior SOTA model Med-Gemini and ~6% over models trained on the specific tasks. Our approach emphasizes the importance of domain expertise in creating precise, reliable VLMs for medical applications.

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

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

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

Breast cancer is a prevalent form of cancer among women, with over 1.5 million women being diagnosed each year. Unfortunately, the survival rates for breast cancer patients in certain third-world countries, like South Africa, are alarmingly low, with only 40% of diagnosed patients surviving beyond five years. The inadequate availability of resources, including qualified pathologists, delayed diagnoses, and ineffective therapy planning, contribute to this low survival rate. To address this pressing issue, medical specialists and researchers have turned to domain-specific AI approaches, specifically deep learning models, to develop end-to-end solutions that can be integrated into computer-aided diagnosis (CAD) systems. By improving the workflow of pathologists, these AI models have the potential to enhance the detection and diagnosis of breast cancer. This research focuses on evaluating the performance of various cutting-edge convolutional neural network (CNN) architectures in comparison to a relatively new model called the Vision Trans-former (ViT). The objective is to determine the superiority of these models in terms of their accuracy and effectiveness. The experimental results reveal that the ViT models outperform the other selected state-of-the-art CNN architectures, achieving an impressive accuracy rate of 95.15%. This study signifies a significant advancement in the field, as it explores the utilization of data augmentation and other relevant preprocessing techniques in conjunction with deep learning models for the detection and diagnosis of breast cancer using datasets of Breast Cancer Histopathological Image Classification.

In health, most large language model (LLM) research has focused on clinical tasks. However, mobile and wearable devices, which are rarely integrated into such tasks, provide rich, longitudinal data for personal health monitoring. Here we present Personal Health Large Language Model (PH-LLM), fine-tuned from Gemini for understanding and reasoning over numerical time-series personal health data. We created and curated three datasets that test 1) production of personalized insights and recommendations from sleep patterns, physical activity, and physiological responses, 2) expert domain knowledge, and 3) prediction of self-reported sleep outcomes. For the first task we designed 857 case studies in collaboration with domain experts to assess real-world scenarios in sleep and fitness. Through comprehensive evaluation of domain-specific rubrics, we observed that Gemini Ultra 1.0 and PH-LLM are not statistically different from expert performance in fitness and, while experts remain superior for sleep, fine-tuning PH-LLM provided significant improvements in using relevant domain knowledge and personalizing information for sleep insights. We evaluated PH-LLM domain knowledge using multiple choice sleep medicine and fitness examinations. PH-LLM achieved 79% on sleep and 88% on fitness, exceeding average scores from a sample of human experts. Finally, we trained PH-LLM to predict self-reported sleep quality outcomes from textual and multimodal encoding representations of wearable data, and demonstrate that multimodal encoding is required to match performance of specialized discriminative models. Although further development and evaluation are necessary in the safety-critical personal health domain, these results demonstrate both the broad knowledge and capabilities of Gemini models and the benefit of contextualizing physiological data for personal health applications as done with PH-LLM.

This work introduces BioLORD, a new pre-training strategy for producing meaningful representations for clinical sentences and biomedical concepts. State-of-the-art methodologies operate by maximizing the similarity in representation of names referring to the same concept, and preventing collapse through contrastive learning. However, because biomedical names are not always self-explanatory, it sometimes results in non-semantic representations. BioLORD overcomes this issue by grounding its concept representations using definitions, as well as short descriptions derived from a multi-relational knowledge graph consisting of biomedical ontologies. Thanks to this grounding, our model produces more semantic concept representations that match more closely the hierarchical structure of ontologies. BioLORD establishes a new state of the art for text similarity on both clinical sentences (MedSTS) and biomedical concepts (MayoSRS).

Medical Image Analysis (MedIA) has become an essential tool in medicine and healthcare, aiding in disease diagnosis, prognosis, and treatment planning, and recent successes in deep learning (DL) have made significant contributions to its advances. However, DL models for MedIA remain challenging to deploy in real-world situations, failing for generalization under the distributional gap between training and testing samples, known as a distribution shift problem. Researchers have dedicated their efforts to developing various DL methods to adapt and perform robustly on unknown and out-of-distribution data distributions. This paper comprehensively reviews domain generalization studies specifically tailored for MedIA. We provide a holistic view of how domain generalization techniques interact within the broader MedIA system, going beyond methodologies to consider the operational implications on the entire MedIA workflow. Specifically, we categorize domain generalization methods into data-level, feature-level, model-level, and analysis-level methods. We show how those methods can be used in various stages of the MedIA workflow with DL equipped from data acquisition to model prediction and analysis. Furthermore, we include benchmark datasets and applications used to evaluate these approaches and analyze the strengths and weaknesses of various methods, unveiling future research opportunities.

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 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.

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.

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

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.

Pre-trained language models have attracted increasing attention in the biomedical domain, inspired by their great success in the general natural language domain. Among the two main branches of pre-trained language models in the general language domain, i.e., BERT (and its variants) and GPT (and its variants), the first one has been extensively studied in the biomedical domain, such as BioBERT and PubMedBERT. While they have achieved great success on a variety of discriminative downstream biomedical tasks, the lack of generation ability constrains their application scope. In this paper, we propose BioGPT, a domain-specific generative Transformer language model pre-trained on large scale biomedical literature. We evaluate BioGPT on six biomedical NLP tasks and demonstrate that our model outperforms previous models on most tasks. Especially, we get 44.98%, 38.42% and 40.76% F1 score on BC5CDR, KD-DTI and DDI end-to-end relation extraction tasks respectively, and 78.2% accuracy on PubMedQA, creating a new record. Our larger model BioGPT-Large achieves 81.0% on PubMedQA. Our case study on text generation further demonstrates the advantage of BioGPT on biomedical literature to generate fluent descriptions for biomedical terms. Code is available at https://github.com/microsoft/BioGPT.

Building generalizable AI models is one of the primary challenges in the healthcare domain. While radiologists rely on generalizable descriptive rules of abnormality, Neural Network (NN) models suffer even with a slight shift in input distribution (e.g., scanner type). Fine-tuning a model to transfer knowledge from one domain to another requires a significant amount of labeled data in the target domain. In this paper, we develop an interpretable model that can be efficiently fine-tuned to an unseen target domain with minimal computational cost. We assume the interpretable component of NN to be approximately domain-invariant. However, interpretable models typically underperform compared to their Blackbox (BB) variants. We start with a BB in the source domain and distill it into a mixture of shallow interpretable models using human-understandable concepts. As each interpretable model covers a subset of data, a mixture of interpretable models achieves comparable performance as BB. Further, we use the pseudo-labeling technique from semi-supervised learning (SSL) to learn the concept classifier in the target domain, followed by fine-tuning the interpretable models in the target domain. We evaluate our model using a real-life large-scale chest-X-ray (CXR) classification dataset. The code is available at: https://github.com/batmanlab/MICCAI-2023-Route-interpret-repeat-CXRs.

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

Large Language Models (LLMs) have demonstrated remarkable versatility in recent years, offering potential applications across specialized domains such as healthcare and medicine. Despite the availability of various open-source LLMs tailored for health contexts, adapting general-purpose LLMs to the medical domain presents significant challenges. In this paper, we introduce BioMistral, an open-source LLM tailored for the biomedical domain, utilizing Mistral as its foundation model and further pre-trained on PubMed Central. We conduct a comprehensive evaluation of BioMistral on a benchmark comprising 10 established medical question-answering (QA) tasks in English. We also explore lightweight models obtained through quantization and model merging approaches. Our results demonstrate BioMistral's superior performance compared to existing open-source medical models and its competitive edge against proprietary counterparts. Finally, to address the limited availability of data beyond English and to assess the multilingual generalization of medical LLMs, we automatically translated and evaluated this benchmark into 7 other languages. This marks the first large-scale multilingual evaluation of LLMs in the medical domain. Datasets, multilingual evaluation benchmarks, scripts, and all the models obtained during our experiments are freely released.

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.

State-of-the-art information extraction methods are limited by OCR errors. They work well for printed text in form-like documents, but unstructured, handwritten documents still remain a challenge. Adapting existing models to domain-specific training data is quite expensive, because of two factors, 1) limited availability of the domain-specific documents (such as handwritten prescriptions, lab notes, etc.), and 2) annotations become even more challenging as one needs domain-specific knowledge to decode inscrutable handwritten document images. In this work, we focus on the complex problem of extracting medicine names from handwritten prescriptions using only weakly labeled data. The data consists of images along with the list of medicine names in it, but not their location in the image. We solve the problem by first identifying the regions of interest, i.e., medicine lines from just weak labels and then injecting a domain-specific medicine language model learned using only synthetically generated data. Compared to off-the-shelf state-of-the-art methods, our approach performs >2.5x better in medicine names extraction from prescriptions.

Contrastive pretraining on parallel image-text data has attained great success in vision-language processing (VLP), as exemplified by CLIP and related methods. However, prior explorations tend to focus on general domains in the web. Biomedical images and text are rather different, but publicly available datasets are small and skew toward chest X-ray, thus severely limiting progress. In this paper, we conducted by far the largest study on biomedical VLP, using 15 million figure-caption pairs extracted from biomedical research articles in PubMed Central. Our dataset (PMC-15M) is two orders of magnitude larger than existing biomedical image-text datasets such as MIMIC-CXR, and spans a diverse range of biomedical images. The standard CLIP method is suboptimal for the biomedical domain. We propose BiomedCLIP with domain-specific adaptations tailored to biomedical VLP. We conducted extensive experiments and ablation studies on standard biomedical imaging tasks from retrieval to classification to visual question-answering (VQA). BiomedCLIP established new state of the art in a wide range of standard datasets, substantially outperformed prior VLP approaches. Surprisingly, BiomedCLIP even outperformed radiology-specific state-of-the-art models such as BioViL on radiology-specific tasks such as RSNA pneumonia detection, thus highlighting the utility in large-scale pretraining across all biomedical image types. We will release our models at https://aka.ms/biomedclip to facilitate future research in biomedical VLP.

Multilingual automatic speech recognition (ASR) in the medical domain serves as a foundational task for various downstream applications such as speech translation, spoken language understanding, and voice-activated assistants. This technology 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 introduce MultiMed, a collection of small-to-large end-to-end ASR models for the medical domain, spanning five languages: Vietnamese, English, German, French, and Mandarin Chinese, together with the corresponding real-world ASR dataset. To our best knowledge, MultiMed stands as the largest and the first multilingual medical ASR dataset, in terms of total duration, number of speakers, diversity of diseases, recording conditions, speaker roles, unique medical terms, accents, and ICD-10 codes. Secondly, we establish the empirical baselines, present the first reproducible study of multilinguality in medical ASR, conduct a layer-wise ablation study for end-to-end ASR training, and provide the first linguistic analysis for multilingual medical ASR. All code, data, and models are available online https://github.com/leduckhai/MultiMed/tree/master/MultiMed

Research on language technology for the development of medical applications is currently a hot topic in Natural Language Understanding and Generation. Thus, a number of large language models (LLMs) have recently been adapted to the medical domain, so that they can be used as a tool for mediating in human-AI interaction. While these LLMs display competitive performance on automated medical texts benchmarks, they have been pre-trained and evaluated with a focus on a single language (English mostly). This is particularly true of text-to-text models, which typically require large amounts of domain-specific pre-training data, often not easily accessible for many languages. In this paper, we address these shortcomings by compiling, to the best of our knowledge, the largest multilingual corpus for the medical domain in four languages, namely English, French, Italian and Spanish. This new corpus has been used to train Medical mT5, the first open-source text-to-text multilingual model for the medical domain. Additionally, we present two new evaluation benchmarks for all four languages with the aim of facilitating multilingual research in this domain. A comprehensive evaluation shows that Medical mT5 outperforms both encoders and similarly sized text-to-text models for the Spanish, French, and Italian benchmarks, while being competitive with current state-of-the-art LLMs in English.

Histopathology plays a central role in clinical medicine and biomedical research. While artificial intelligence shows promising results on many pathological tasks, generalization and dealing with rare diseases, where training data is scarce, remains a challenge. Distilling knowledge from unlabeled data into a foundation model before learning from, potentially limited, labeled data provides a viable path to address these challenges. In this work, we extend the state of the art of foundation models for digital pathology whole slide images by semi-automated data curation and incorporating pathologist domain knowledge. Specifically, we combine computational and pathologist domain knowledge (1) to curate a diverse dataset of 103k slides corresponding to 750 million image patches covering data from different fixation, staining, and scanning protocols as well as data from different indications and labs across the EU and US, (2) for grouping semantically similar slides and tissue patches, and (3) to augment the input images during training. We evaluate the resulting model on a set of public and internal benchmarks and show that although our foundation model is trained with an order of magnitude less slides, it performs on par or better than competing models. We expect that scaling our approach to more data and larger models will further increase its performance and capacity to deal with increasingly complex real world tasks in diagnostics and biomedical research.

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

Decision-makers are often experts of their domain and take actions based on their domain knowledge. Doctors, for instance, may prescribe treatments by predicting the likely outcome of each available treatment. Actions of an expert thus naturally encode part of their domain knowledge, and can help make inferences within the same domain: Knowing doctors try to prescribe the best treatment for their patients, we can tell treatments prescribed more frequently are likely to be more effective. Yet in machine learning, the fact that most decision-makers are experts is often overlooked, and "expertise" is seldom leveraged as an inductive bias. This is especially true for the literature on treatment effect estimation, where often the only assumption made about actions is that of overlap. In this paper, we argue that expertise - particularly the type of expertise the decision-makers of a domain are likely to have - can be informative in designing and selecting methods for treatment effect estimation. We formally define two types of expertise, predictive and prognostic, and demonstrate empirically that: (i) the prominent type of expertise in a domain significantly influences the performance of different methods in treatment effect estimation, and (ii) it is possible to predict the type of expertise present in a dataset, which can provide a quantitative basis for model selection.

The integration of large language model (LLM) techniques in the field of medical analysis has brought about significant advancements, yet the scarcity of large, diverse, and well-annotated datasets remains a major challenge. Medical data and tasks, which vary in format, size, and other parameters, require extensive preprocessing and standardization for effective use in training LLMs. To address these challenges, we introduce MedINST, the Meta Dataset of Biomedical Instructions, a novel multi-domain, multi-task instructional meta-dataset. MedINST comprises 133 biomedical NLP tasks and over 7 million training samples, making it the most comprehensive biomedical instruction dataset to date. Using MedINST as the meta dataset, we curate MedINST32, a challenging benchmark with different task difficulties aiming to evaluate LLMs' generalization ability. We fine-tune several LLMs on MedINST and evaluate on MedINST32, showcasing enhanced cross-task generalization.

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.

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

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.

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.

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

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

Foundation models trained on large-scale dataset gain a recent surge in CV and NLP. In contrast, development in biomedical domain lags far behind due to data scarcity. To address this issue, we build and release PMC-OA, a biomedical dataset with 1.6M image-caption pairs collected from PubMedCentral's OpenAccess subset, which is 8 times larger than before. PMC-OA covers diverse modalities or diseases, with majority of the image-caption samples aligned at finer-grained level, i.e., subfigure and subcaption. While pretraining a CLIP-style model on PMC-OA, our model named PMC-CLIP achieves state-of-the-art results on various downstream tasks, including image-text retrieval on ROCO, MedMNIST image classification, Medical VQA, i.e. +8.1% R@10 on image-text retrieval, +3.9% accuracy on image classification.

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

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

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.

The entry of large language models (LLMs) into research and commercial spaces has led to a trend of ever-larger models, with initial promises of generalisability, followed by a widespread desire to downsize and create specialised models without the need for complete fine-tuning, using Parameter Efficient Fine-tuning (PEFT) methods. We present an investigation into the suitability of different PEFT methods to clinical decision-making tasks, across a range of model sizes, including extremely small models with as few as 25 million parameters. Our analysis shows that the performance of most PEFT approaches varies significantly from one task to another, with the exception of LoRA, which maintains relatively high performance across all model sizes and tasks, typically approaching or matching full fine-tuned performance. The effectiveness of PEFT methods in the clinical domain is evident, particularly for specialised models which can operate on low-cost, in-house computing infrastructure. The advantages of these models, in terms of speed and reduced training costs, dramatically outweighs any performance gain from large foundation LLMs. Furthermore, we highlight how domain-specific pre-training interacts with PEFT methods and model size, and discuss how these factors interplay to provide the best efficiency-performance trade-off. Full code available at: tbd.

We introduce Latent Meaning Cells, a deep latent variable model which learns contextualized representations of words by combining local lexical context and metadata. Metadata can refer to granular context, such as section type, or to more global context, such as unique document ids. Reliance on metadata for contextualized representation learning is apropos in the clinical domain where text is semi-structured and expresses high variation in topics. We evaluate the LMC model on the task of zero-shot clinical acronym expansion across three datasets. The LMC significantly outperforms a diverse set of baselines at a fraction of the pre-training cost and learns clinically coherent representations. We demonstrate that not only is metadata itself very helpful for the task, but that the LMC inference algorithm provides an additional large benefit.

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.

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

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

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

Medical images and radiology reports are crucial for diagnosing medical conditions, highlighting the importance of quantitative analysis for clinical decision-making. However, the diversity and cross-source heterogeneity of these data challenge the generalizability of current data-mining methods. Multimodal large language models (MLLMs) have recently transformed many domains, significantly affecting the medical field. Notably, Gemini-Vision-series (Gemini) and GPT-4-series (GPT-4) models have epitomized a paradigm shift in Artificial General Intelligence (AGI) for computer vision, showcasing their potential in the biomedical domain. In this study, we evaluated the performance of the Gemini, GPT-4, and 4 popular large models for an exhaustive evaluation across 14 medical imaging datasets, including 5 medical imaging categories (dermatology, radiology, dentistry, ophthalmology, and endoscopy), and 3 radiology report datasets. The investigated tasks encompass disease classification, lesion segmentation, anatomical localization, disease diagnosis, report generation, and lesion detection. Our experimental results demonstrated that Gemini-series models excelled in report generation and lesion detection but faces challenges in disease classification and anatomical localization. Conversely, GPT-series models exhibited proficiency in lesion segmentation and anatomical localization but encountered difficulties in disease diagnosis and lesion detection. Additionally, both the Gemini series and GPT series contain models that have demonstrated commendable generation efficiency. While both models hold promise in reducing physician workload, alleviating pressure on limited healthcare resources, and fostering collaboration between clinical practitioners and artificial intelligence technologies, substantial enhancements and comprehensive validations remain imperative before clinical deployment.

A key component of deep learning (DL) for natural language processing (NLP) is word embeddings. Word embeddings that effectively capture the meaning and context of the word that they represent can significantly improve the performance of downstream DL models for various NLP tasks. Many existing word embeddings techniques capture the context of words based on word co-occurrence in documents and text; however, they often cannot capture broader domain-specific relationships between concepts that may be crucial for the NLP task at hand. In this paper, we propose a method to integrate external knowledge from medical terminology ontologies into the context captured by word embeddings. Specifically, we use a medical knowledge graph, such as the unified medical language system (UMLS), to find connections between clinical terms in cancer pathology reports. This approach aims to minimize the distance between connected clinical concepts. We evaluate the proposed approach using a Multitask Convolutional Neural Network (MT-CNN) to extract six cancer characteristics -- site, subsite, laterality, behavior, histology, and grade -- from a dataset of ~900K cancer pathology reports. The results show that the MT-CNN model which uses our domain informed embeddings outperforms the same MT-CNN using standard word2vec embeddings across all tasks, with an improvement in the overall micro- and macro-F1 scores by 4.97\%and 22.5\%, respectively.

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

Large Language Models (LLMs) have demonstrated significant potential in transforming clinical applications. In this study, we investigate the efficacy of four techniques in adapting LLMs for clinical use-cases: continuous pretraining, instruct fine-tuning, NEFTune, and prompt engineering. We employ these methods on Mistral 7B and Mixtral 8x7B models, leveraging a large-scale clinical pretraining dataset of 50 billion tokens and an instruct fine-tuning dataset of 500 million tokens. Our evaluation across various clinical tasks reveals the impact of each technique. While continuous pretraining beyond 250 billion tokens yields marginal improvements on its own, it establishes a strong foundation for instruct fine-tuning. Notably, NEFTune, designed primarily to enhance generation quality, surprisingly demonstrates additional gains on our benchmark. Complex prompt engineering methods further enhance performance. These findings show the importance of tailoring fine-tuning strategies and exploring innovative techniques to optimize LLM performance in the clinical domain.

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

The performance of deep learning-based natural language processing systems is based on large amounts of labeled training data which, in the clinical domain, are not easily available or affordable. Weak supervision and in-context learning offer partial solutions to this issue, particularly using large language models (LLMs), but their performance still trails traditional supervised methods with moderate amounts of gold-standard data. In particular, inferencing with LLMs is computationally heavy. We propose an approach leveraging fine-tuning LLMs and weak supervision with virtually no domain knowledge that still achieves consistently dominant performance. Using a prompt-based approach, the LLM is used to generate weakly-labeled data for training a downstream BERT model. The weakly supervised model is then further fine-tuned on small amounts of gold standard data. We evaluate this approach using Llama2 on three different n2c2 datasets. With no more than 10 gold standard notes, our final BERT models weakly supervised by fine-tuned Llama2-13B consistently outperformed out-of-the-box PubMedBERT by 4.7% to 47.9% in F1 scores. With only 50 gold standard notes, our models achieved close performance to fully fine-tuned systems.

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

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

Extraction of relevant pathological terms from radiology reports is important for correct image label generation and disease population studies. In this letter, we compare the performance of some known application program interface (APIs) for the task of thoracic abnormality extraction from radiology reports. We explored several medical domain specific annotation tools like Medical Text Indexer(MTI) with Non-MEDLINE and Mesh On Demand(MOD) options and generic Natural Language Understanding (NLU) API provided by the IBM cloud. Our results show that although MTI and MOD are intended for extracting medical terms, their performance is worst compared to generic extraction API like IBM NLU. Finally, we trained a DNN-based Named Entity Recognition (NER) model to extract the key concept words from radiology reports. Our model outperforms the medical specific and generic API performance by a large margin. Our results demonstrate the inadequacy of generic APIs for pathology extraction task and establish the importance of domain specific model training for improved results. We hope that these results motivate the research community to release larger de-identified radiology reports corpus for building high accuracy machine learning models for the important task of pathology extraction.

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

Large Language Models (LLMs) such as GPT & Llama have demonstrated significant achievements in summarization tasks but struggle with factual inaccuracies, a critical issue in clinical NLP applications where errors could lead to serious consequences. To counter the high costs and limited availability of expert-annotated data for factual alignment, this study introduces an innovative pipeline that utilizes >100B parameter GPT variants like GPT-3.5 & GPT-4 to act as synthetic experts to generate high-quality synthetics feedback aimed at enhancing factual consistency in clinical note summarization. Our research primarily focuses on edit feedback generated by these synthetic feedback experts without additional human annotations, mirroring and optimizing the practical scenario in which medical professionals refine AI system outputs. Although such 100B+ parameter GPT variants have proven to demonstrate expertise in various clinical NLP tasks, such as the Medical Licensing Examination, there is scant research on their capacity to act as synthetic feedback experts and deliver expert-level edit feedback for improving the generation quality of weaker (<10B parameter) LLMs like GPT-2 (1.5B) & Llama 2 (7B) in clinical domain. So in this work, we leverage 100B+ GPT variants to act as synthetic feedback experts offering expert-level edit feedback, that is used to reduce hallucinations and align weaker (<10B parameter) LLMs with medical facts using two distinct alignment algorithms (DPO & SALT), endeavoring to narrow the divide between AI-generated content and factual accuracy. This highlights the substantial potential of LLM-based synthetic edits in enhancing the alignment of clinical factuality.

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.

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

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

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

The current generation of large language models (LLMs) is typically designed for broad, general-purpose applications, while domain-specific LLMs, especially in vertical fields like medicine, remain relatively scarce. In particular, the development of highly efficient and practical LLMs for the medical domain is challenging due to the complexity of medical knowledge and the limited availability of high-quality data. To bridge this gap, we introduce Baichuan-M1, a series of large language models specifically optimized for medical applications. Unlike traditional approaches that simply continue pretraining on existing models or apply post-training to a general base model, Baichuan-M1 is trained from scratch with a dedicated focus on enhancing medical capabilities. Our model is trained on 20 trillion tokens and incorporates a range of effective training methods that strike a balance between general capabilities and medical expertise. As a result, Baichuan-M1 not only performs strongly across general domains such as mathematics and coding but also excels in specialized medical fields. We have open-sourced Baichuan-M1-14B, a mini version of our model, which can be accessed through the following links.

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

Foundation models (FMs) have exhibited remarkable performance across a wide range of downstream tasks in many domains. Nevertheless, general-purpose FMs often face challenges when confronted with domain-specific problems, due to their limited access to the proprietary training data in a particular domain. In biomedicine, there are various biological modalities, such as molecules, proteins, and cells, which are encoded by the language of life and exhibit significant modality gaps with human natural language. In this paper, we introduce BioMedGPT, an open multimodal generative pre-trained transformer (GPT) for biomedicine, to bridge the gap between the language of life and human natural language. BioMedGPT allows users to easily ``communicate'' with diverse biological modalities through free text, which is the first of its kind. BioMedGPT aligns different biological modalities with natural language via a large generative language model, namely, BioMedGPT-LM. We publish BioMedGPT-10B, which unifies the feature spaces of molecules, proteins, and natural language via encoding and alignment. Through fine-tuning, BioMedGPT-10B outperforms or is on par with human and significantly larger general-purpose foundation models on the biomedical QA task. It also demonstrates promising performance in the molecule QA and protein QA tasks, which could greatly accelerate the discovery of new drugs and therapeutic targets. In addition, BioMedGPT-LM-7B is the first large generative language model based on Llama2 in the biomedical domain, therefore is commercial friendly. Both BioMedGPT-10B and BioMedGPT-LM-7B are open-sourced to the research community. In addition, we publish the datasets that are meticulously curated for the alignment of multi-modalities, i.e., PubChemQA and UniProtQA. All the models, codes, and datasets are available at https://github.com/PharMolix/OpenBioMed.

People increasingly search online for answers to their medical questions but the rate at which medical questions are asked online significantly exceeds the capacity of qualified people to answer them. This leaves many questions unanswered or inadequately answered. Many of these questions are not unique, and reliable identification of similar questions would enable more efficient and effective question answering schema. COVID-19 has only exacerbated this problem. Almost every government agency and healthcare organization has tried to meet the informational need of users by building online FAQs, but there is no way for people to ask their question and know if it is answered on one of these pages. While many research efforts have focused on the problem of general question similarity, these approaches do not generalize well to domains that require expert knowledge to determine semantic similarity, such as the medical domain. In this paper, we show how a double fine-tuning approach of pretraining a neural network on medical question-answer pairs followed by fine-tuning on medical question-question pairs is a particularly useful intermediate task for the ultimate goal of determining medical question similarity. While other pretraining tasks yield an accuracy below 78.7% on this task, our model achieves an accuracy of 82.6% with the same number of training examples, an accuracy of 80.0% with a much smaller training set, and an accuracy of 84.5% when the full corpus of medical question-answer data is used. We also describe a currently live system that uses the trained model to match user questions to COVID-related FAQs.

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

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

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

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

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

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

Domain experts across engineering, healthcare, and education follow strict standards for producing quality content such as technical manuals, medication instructions, and children's reading materials. However, current works in controllable text generation have yet to explore using these standards as references for control. Towards this end, we introduce Standardize, a retrieval-style in-context learning-based framework to guide large language models to align with expert-defined standards. Focusing on English language standards in the education domain as a use case, we consider the Common European Framework of Reference for Languages (CEFR) and Common Core Standards (CCS) for the task of open-ended content generation. Our findings show that models can gain 40% to 100% increase in precise accuracy for Llama2 and GPT-4, respectively, demonstrating that the use of knowledge artifacts extracted from standards and integrating them in the generation process can effectively guide models to produce better standard-aligned content.