Daily Papers

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

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.

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.

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.

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.

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

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.

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

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.

Despite decades of clinical research, sepsis remains a global public health crisis with high mortality, and morbidity. Currently, when sepsis is detected and the underlying pathogen is identified, organ damage may have already progressed to irreversible stages. Effective sepsis management is therefore highly time-sensitive. By systematically analysing trends in the plethora of clinical data available in the intensive care unit (ICU), an early prediction of sepsis could lead to earlier pathogen identification, resistance testing, and effective antibiotic and supportive treatment, and thereby become a life-saving measure. Here, we developed and validated a machine learning (ML) system for the prediction of sepsis in the ICU. Our analysis represents the largest multi-national, multi-centre in-ICU study for sepsis prediction using ML to date. Our dataset contains 156,309 unique ICU admissions, which represent a refined and harmonised subset of five large ICU databases originating from three countries. Using the international consensus definition Sepsis-3, we derived hourly-resolved sepsis label annotations, amounting to 26,734 (17.1%) septic stays. We compared our approach, a deep self-attention model, to several clinical baselines as well as ML baselines and performed an extensive internal and external validation within and across databases. On average, our model was able to predict sepsis with an AUROC of 0.847 pm 0.050 (internal out-of sample validation) and 0.761 pm 0.052 (external validation). For a harmonised prevalence of 17%, at 80% recall our model detects septic patients with 39% precision 3.7 hours in advance.

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.

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

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

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

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

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.

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

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.

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

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.

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.

Social determinants of health (SDoH) have an important impact on patient outcomes but are incompletely collected from the electronic health records (EHR). This study researched the ability of large language models to extract SDoH from free text in EHRs, where they are most commonly documented, and explored the role of synthetic clinical text for improving the extraction of these scarcely documented, yet extremely valuable, clinical data. 800 patient notes were annotated for SDoH categories, and several transformer-based models were evaluated. The study also experimented with synthetic data generation and assessed for algorithmic bias. Our best-performing models were fine-tuned Flan-T5 XL (macro-F1 0.71) for any SDoH, and Flan-T5 XXL (macro-F1 0.70). The benefit of augmenting fine-tuning with synthetic data varied across model architecture and size, with smaller Flan-T5 models (base and large) showing the greatest improvements in performance (delta F1 +0.12 to +0.23). Model performance was similar on the in-hospital system dataset but worse on the MIMIC-III dataset. Our best-performing fine-tuned models outperformed zero- and few-shot performance of ChatGPT-family models for both tasks. These fine-tuned models were less likely than ChatGPT to change their prediction when race/ethnicity and gender descriptors were added to the text, suggesting less algorithmic bias (p<0.05). At the patient-level, our models identified 93.8% of patients with adverse SDoH, while ICD-10 codes captured 2.0%. Our method can effectively extracted SDoH information from clinic notes, performing better compare to GPT zero- and few-shot settings. These models could enhance real-world evidence on SDoH and aid in identifying patients needing social support.

Social and behavioral determinants of health (SDOH) play a significant role in shaping health outcomes, and extracting these determinants from clinical notes is a first step to help healthcare providers systematically identify opportunities to provide appropriate care and address disparities. Progress on using NLP methods for this task has been hindered by the lack of high-quality publicly available labeled data, largely due to the privacy and regulatory constraints on the use of real patients' information. This paper introduces a new dataset, SDOH-NLI, that is based on publicly available notes and which we release publicly. We formulate SDOH extraction as a natural language inference (NLI) task, and provide binary textual entailment labels obtained from human raters for a cross product of a set of social history snippets as premises and SDOH factors as hypotheses. Our dataset differs from standard NLI benchmarks in that our premises and hypotheses are obtained independently. We evaluate both "off-the-shelf" entailment models as well as models fine-tuned on our data, and highlight the ways in which our dataset appears more challenging than commonly used NLI datasets.

Background: Rapid advancements in natural language processing have led to the development of large language models with the potential to revolutionize mental health care. These models have shown promise in assisting clinicians and providing support to individuals experiencing various psychological challenges. Objective: This study aims to compare the performance of two large language models, GPT-4 and Chat-GPT, in responding to a set of 18 psychological prompts, to assess their potential applicability in mental health care settings. Methods: A blind methodology was employed, with a clinical psychologist evaluating the models' responses without knowledge of their origins. The prompts encompassed a diverse range of mental health topics, including depression, anxiety, and trauma, to ensure a comprehensive assessment. Results: The results demonstrated a significant difference in performance between the two models (p > 0.05). GPT-4 achieved an average rating of 8.29 out of 10, while Chat-GPT received an average rating of 6.52. The clinical psychologist's evaluation suggested that GPT-4 was more effective at generating clinically relevant and empathetic responses, thereby providing better support and guidance to potential users. Conclusions: This study contributes to the growing body of literature on the applicability of large language models in mental health care settings. The findings underscore the importance of continued research and development in the field to optimize these models for clinical use. Further investigation is necessary to understand the specific factors underlying the performance differences between the two models and to explore their generalizability across various populations and mental health conditions.

Epidemiologists aiming to model the dynamics of global events face a significant challenge in identifying the factors linked with anomalies such as disease outbreaks. In this paper, we present a novel method for identifying the most important development sectors sensitive to disease outbreaks by using global development indicators as markers. We use statistical methods to assess the causative linkages between these indicators and disease outbreaks, as well as to find the most often ranked indicators. We used data imputation techniques in addition to statistical analysis to convert raw real-world data sets into meaningful data for causal inference. The application of various algorithms for the detection of causal linkages between the indicators is the subject of this research. Despite the fact that disparities in governmental policies between countries account for differences in causal linkages, several indicators emerge as important determinants sensitive to disease outbreaks over the world in the 21st Century.

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

We 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.

Social and behavioral determinants of health (SBDH) play a crucial role in health outcomes and are frequently documented in clinical text. Automatically extracting SBDH information from clinical text relies on publicly available good-quality datasets. However, existing SBDH datasets exhibit substantial limitations in their availability and coverage. In this study, we introduce Synth-SBDH, a novel synthetic dataset with detailed SBDH annotations, encompassing status, temporal information, and rationale across 15 SBDH categories. We showcase the utility of Synth-SBDH on three tasks using real-world clinical datasets from two distinct hospital settings, highlighting its versatility, generalizability, and distillation capabilities. Models trained on Synth-SBDH consistently outperform counterparts with no Synth-SBDH training, achieving up to 62.5% macro-F improvements. Additionally, Synth-SBDH proves effective for rare SBDH categories and under-resource constraints. Human evaluation demonstrates a Human-LLM alignment of 71.06% and uncovers areas for future refinements.

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.

At the heart of medicine lies the physician-patient dialogue, where skillful history-taking paves the way for accurate diagnosis, effective management, and enduring trust. Artificial Intelligence (AI) systems capable of diagnostic dialogue could increase accessibility, consistency, and quality of care. However, approximating clinicians' expertise is an outstanding grand challenge. Here, we introduce AMIE (Articulate Medical Intelligence Explorer), a Large Language Model (LLM) based AI system optimized for diagnostic dialogue. AMIE uses a novel self-play based simulated environment with automated feedback mechanisms for scaling learning across diverse disease conditions, specialties, and contexts. We designed a framework for evaluating clinically-meaningful axes of performance including history-taking, diagnostic accuracy, management reasoning, communication skills, and empathy. We compared AMIE's performance to that of primary care physicians (PCPs) in a randomized, double-blind crossover study of text-based consultations with validated patient actors in the style of an Objective Structured Clinical Examination (OSCE). The study included 149 case scenarios from clinical providers in Canada, the UK, and India, 20 PCPs for comparison with AMIE, and evaluations by specialist physicians and patient actors. AMIE demonstrated greater diagnostic accuracy and superior performance on 28 of 32 axes according to specialist physicians and 24 of 26 axes according to patient actors. Our research has several limitations and should be interpreted with appropriate caution. Clinicians were limited to unfamiliar synchronous text-chat which permits large-scale LLM-patient interactions but is not representative of usual clinical practice. While further research is required before AMIE could be translated to real-world settings, the results represent a milestone towards conversational diagnostic AI.

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

This paper introduces a novel, entity-aware metric, termed as Radiological Report (Text) Evaluation (RaTEScore), to assess the quality of medical reports generated by AI models. RaTEScore emphasizes crucial medical entities such as diagnostic outcomes and anatomical details, and is robust against complex medical synonyms and sensitive to negation expressions. Technically, we developed a comprehensive medical NER dataset, RaTE-NER, and trained an NER model specifically for this purpose. This model enables the decomposition of complex radiological reports into constituent medical entities. The metric itself is derived by comparing the similarity of entity embeddings, obtained from a language model, based on their types and relevance to clinical significance. Our evaluations demonstrate that RaTEScore aligns more closely with human preference than existing metrics, validated both on established public benchmarks and our newly proposed RaTE-Eval benchmark.

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.

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.

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 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.

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.

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.

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.

The COVID-19 pandemic has posed a heavy burden to the healthcare system worldwide and caused huge social disruption and economic loss. Many deep learning models have been proposed to conduct clinical predictive tasks such as mortality prediction for COVID-19 patients in intensive care units using Electronic Health Record (EHR) data. Despite their initial success in certain clinical applications, there is currently a lack of benchmarking results to achieve a fair comparison so that we can select the optimal model for clinical use. Furthermore, there is a discrepancy between the formulation of traditional prediction tasks and real-world clinical practice in intensive care. To fill these gaps, we propose two clinical prediction tasks, Outcome-specific length-of-stay prediction and Early mortality prediction for COVID-19 patients in intensive care units. The two tasks are adapted from the naive length-of-stay and mortality prediction tasks to accommodate the clinical practice for COVID-19 patients. We propose fair, detailed, open-source data-preprocessing pipelines and evaluate 17 state-of-the-art predictive models on two tasks, including 5 machine learning models, 6 basic deep learning models and 6 deep learning predictive models specifically designed for EHR data. We provide benchmarking results using data from two real-world COVID-19 EHR datasets. One dataset is publicly available without needing any inquiry and another dataset can be accessed on request. We provide fair, reproducible benchmarking results for two tasks. We deploy all experiment results and models on an online platform. We also allow clinicians and researchers to upload their data to the platform and get quick prediction results using our trained models. We hope our efforts can further facilitate deep learning and machine learning research for COVID-19 predictive modeling.

Alzheimer's disease (AD) is a degenerative brain disease impairing a person's ability to perform day to day activities. The clinical manifestations of Alzheimer's disease are characterized by heterogeneity in age, disease span, progression rate, impairment of memory and cognitive abilities. Due to these variabilities, personalized care and treatment planning, as well as patient counseling about their individual progression is limited. Recent developments in machine learning to detect hidden patterns in complex, multi-dimensional datasets provides significant opportunities to address this critical need. In this work, we use unsupervised and supervised machine learning approaches for subtype identification and prediction. We apply machine learning methods to the extensive clinical observations available at the Alzheimer's Disease Neuroimaging Initiative (ADNI) data set to identify patient subtypes and to predict disease progression. Our analysis depicts the progression space for the Alzheimer's disease into low, moderate and high disease progression zones. The proposed work will enable early detection and characterization of distinct disease subtypes based on clinical heterogeneity. We anticipate that our models will enable patient counseling, clinical trial design, and ultimately individualized clinical care.

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/

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.

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

The 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.

The World Health Organization added Disease X to their shortlist of blueprint priority diseases to represent a hypothetical, unknown pathogen that could cause a future epidemic. During different virus outbreaks of the past, such as COVID-19, Influenza, Lyme Disease, and Zika virus, researchers from various disciplines utilized Google Trends to mine multimodal components of web behavior to study, investigate, and analyze the global awareness, preparedness, and response associated with these respective virus outbreaks. As the world prepares for Disease X, a dataset on web behavior related to Disease X would be crucial to contribute towards the timely advancement of research in this field. Furthermore, none of the prior works in this field have focused on the development of a dataset to compile relevant web behavior data, which would help to prepare for Disease X. To address these research challenges, this work presents a dataset of web behavior related to Disease X, which emerged from different geographic regions of the world, between February 2018 and August 2023. Specifically, this dataset presents the search interests related to Disease X from 94 geographic regions. The dataset was developed by collecting data using Google Trends. The relevant search interests for all these regions for each month in this time range are available in this dataset. This paper also discusses the compliance of this dataset with the FAIR principles of scientific data management. Finally, an analysis of this dataset is presented to uphold the applicability, relevance, and usefulness of this dataset for the investigation of different research questions in the interrelated fields of Big Data, Data Mining, Healthcare, Epidemiology, and Data Analysis with a specific focus on Disease X.

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.

Accurately forecasting patient arrivals at Urgent Care Clinics (UCCs) and Emergency Departments (EDs) is important for effective resourcing and patient care. However, correctly estimating patient flows is not straightforward since it depends on many drivers. The predictability of patient arrivals has recently been further complicated by the COVID-19 pandemic conditions and the resulting lockdowns. This study investigates how a suite of novel quasi-real-time variables like Google search terms, pedestrian traffic, the prevailing incidence levels of influenza, as well as the COVID-19 Alert Level indicators can both generally improve the forecasting models of patient flows and effectively adapt the models to the unfolding disruptions of pandemic conditions. This research also uniquely contributes to the body of work in this domain by employing tools from the eXplainable AI field to investigate more deeply the internal mechanics of the models than has previously been done. The Voting ensemble-based method combining machine learning and statistical techniques was the most reliable in our experiments. Our study showed that the prevailing COVID-19 Alert Level feature together with Google search terms and pedestrian traffic were effective at producing generalisable forecasts. The implications of this study are that proxy variables can effectively augment standard autoregressive features to ensure accurate forecasting of patient flows. The experiments showed that the proposed features are potentially effective model inputs for preserving forecast accuracies in the event of future pandemic outbreaks.

With the increasing availability of wearable devices, photoplethysmography (PPG) has emerged as a promising non-invasive tool for monitoring human hemodynamics. We propose a deep learning framework to estimate vascular age (AI-vascular age) from PPG signals, incorporating a distribution-aware loss to address biases caused by imbalanced data. The model was developed using data from the UK Biobank (UKB), with 98,672 participants in the development cohort and 113,559 participants (144,683 data pairs) for clinical evaluation. After adjusting for key confounders, individuals with a vascular age gap (AI-vascular age minus calendar age) exceeding 9 years had a significantly higher risk of major adverse cardiovascular and cerebrovascular events (MACCE) (HR = 2.37, p < 0.005) and secondary outcomes, including diabetes (HR = 2.69, p < 0.005), hypertension (HR = 2.88, p < 0.005), coronary heart disease (HR = 2.20, p < 0.005), heart failure (HR = 2.15, p < 0.005), myocardial infarction (HR = 2.51, p < 0.005), stroke (HR = 2.55, p < 0.005), and all-cause mortality (HR = 2.51, p < 0.005). Conversely, participants with a vascular age gap below -9 years exhibited a significantly lower incidence of these outcomes. We further evaluated the longitudinal applicability of AI-vascular age using serial PPG data from the UKB, demonstrating its value in risk stratification by leveraging AI-vascular age at two distinct time points to predict future MACCE incidence. External validation was performed on a MIMIC-III-derived cohort (n = 2,343), where each one-year increase in vascular age gap was significantly associated with elevated in-hospital mortality risk (OR = 1.02, p < 0.005). In conclusion, our study establishes AI-vascular age as a novel, non-invasive digital biomarker for cardiovascular health assessment.

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.

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.

Background: Health datasets from clinical sources do not reflect the breadth and diversity of disease in the real world, impacting research, medical education, and artificial intelligence (AI) tool development. Dermatology is a suitable area to develop and test a new and scalable method to create representative health datasets. Methods: We used Google Search advertisements to invite contributions to an open access dataset of images of dermatology conditions, demographic and symptom information. With informed contributor consent, we describe and release this dataset containing 10,408 images from 5,033 contributions from internet users in the United States over 8 months starting March 2023. The dataset includes dermatologist condition labels as well as estimated Fitzpatrick Skin Type (eFST) and Monk Skin Tone (eMST) labels for the images. Results: We received a median of 22 submissions/day (IQR 14-30). Female (66.72%) and younger (52% < age 40) contributors had a higher representation in the dataset compared to the US population, and 32.6% of contributors reported a non-White racial or ethnic identity. Over 97.5% of contributions were genuine images of skin conditions. Dermatologist confidence in assigning a differential diagnosis increased with the number of available variables, and showed a weaker correlation with image sharpness (Spearman's P values <0.001 and 0.01 respectively). Most contributions were short-duration (54% with onset < 7 days ago ) and 89% were allergic, infectious, or inflammatory conditions. eFST and eMST distributions reflected the geographical origin of the dataset. The dataset is available at github.com/google-research-datasets/scin . Conclusion: Search ads are effective at crowdsourcing images of health conditions. The SCIN dataset bridges important gaps in the availability of representative images of common skin conditions.

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.

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

Users of social platforms often perceive these sites as supportive spaces to post about their mental health issues. Those conversations contain important traces about individuals' health risks. Recently, researchers have exploited this online information to construct mental health detection models, which aim to identify users at risk on platforms like Twitter, Reddit or Facebook. Most of these models are centred on achieving good classification results, ignoring the explainability and interpretability of the decisions. Recent research has pointed out the importance of using clinical markers, such as the use of symptoms, to improve trust in the computational models by health professionals. In this paper, we propose using transformer-based architectures to detect and explain the appearance of depressive symptom markers in the users' writings. We present two approaches: i) train a model to classify, and another one to explain the classifier's decision separately and ii) unify the two tasks simultaneously using a single model. Additionally, for this latter manner, we also investigated the performance of recent conversational LLMs when using in-context learning. Our natural language explanations enable clinicians to interpret the models' decisions based on validated symptoms, enhancing trust in the automated process. We evaluate our approach using recent symptom-based datasets, employing both offline and expert-in-the-loop metrics to assess the quality of the explanations generated by our models. The experimental results show that it is possible to achieve good classification results while generating interpretable symptom-based explanations.

Automatic disease diagnosis has become increasingly valuable in clinical practice. The advent of large language models (LLMs) has catalyzed a paradigm shift in artificial intelligence, with growing evidence supporting the efficacy of LLMs in diagnostic tasks. Despite the increasing attention in this field, a holistic view is still lacking. Many critical aspects remain unclear, such as the diseases and clinical data to which LLMs have been applied, the LLM techniques employed, and the evaluation methods used. In this article, we perform a comprehensive review of LLM-based methods for disease diagnosis. Our review examines the existing literature across various dimensions, including disease types and associated clinical specialties, clinical data, LLM techniques, and evaluation methods. Additionally, we offer recommendations for applying and evaluating LLMs for diagnostic tasks. Furthermore, we assess the limitations of current research and discuss future directions. To our knowledge, this is the first comprehensive review for LLM-based disease diagnosis.

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.

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

Mental health is a significant and growing public health concern. As language usage can be leveraged to obtain crucial insights into mental health conditions, there is a need for large-scale, labeled, mental health-related datasets of users who have been diagnosed with one or more of such conditions. In this paper, we investigate the creation of high-precision patterns to identify self-reported diagnoses of nine different mental health conditions, and obtain high-quality labeled data without the need for manual labelling. We introduce the SMHD (Self-reported Mental Health Diagnoses) dataset and make it available. SMHD is a novel large dataset of social media posts from users with one or multiple mental health conditions along with matched control users. We examine distinctions in users' language, as measured by linguistic and psychological variables. We further explore text classification methods to identify individuals with mental conditions through their language.

Objective: We develop a deep learning framework based on the pre-trained Bidirectional Encoder Representations from Transformers (BERT) model using unstructured clinical notes from electronic health records (EHRs) to predict the risk of disease progression from Mild Cognitive Impairment (MCI) to Alzheimer's Disease (AD). Materials and Methods: We identified 3657 patients diagnosed with MCI together with their progress notes from Northwestern Medicine Enterprise Data Warehouse (NMEDW) between 2000-2020. The progress notes no later than the first MCI diagnosis were used for the prediction. We first preprocessed the notes by deidentification, cleaning and splitting, and then pretrained a BERT model for AD (AD-BERT) based on the publicly available Bio+Clinical BERT on the preprocessed notes. The embeddings of all the sections of a patient's notes processed by AD-BERT were combined by MaxPooling to compute the probability of MCI-to-AD progression. For replication, we conducted a similar set of experiments on 2563 MCI patients identified at Weill Cornell Medicine (WCM) during the same timeframe. Results: Compared with the 7 baseline models, the AD-BERT model achieved the best performance on both datasets, with Area Under receiver operating characteristic Curve (AUC) of 0.8170 and F1 score of 0.4178 on NMEDW dataset and AUC of 0.8830 and F1 score of 0.6836 on WCM dataset. Conclusion: We developed a deep learning framework using BERT models which provide an effective solution for prediction of MCI-to-AD progression using clinical note analysis.

Large language models (LLMs) are increasingly applied to clinical decision-making. However, their potential to exhibit bias poses significant risks to clinical equity. Currently, there is a lack of benchmarks that systematically evaluate such clinical bias in LLMs. While in downstream tasks, some biases of LLMs can be avoided such as by instructing the model to answer "I'm not sure...", the internal bias hidden within the model still lacks deep studies. We introduce CLIMB (shorthand for A Benchmark of Clinical Bias in Large Language Models), a pioneering comprehensive benchmark to evaluate both intrinsic (within LLMs) and extrinsic (on downstream tasks) bias in LLMs for clinical decision tasks. Notably, for intrinsic bias, we introduce a novel metric, AssocMAD, to assess the disparities of LLMs across multiple demographic groups. Additionally, we leverage counterfactual intervention to evaluate extrinsic bias in a task of clinical diagnosis prediction. Our experiments across popular and medically adapted LLMs, particularly from the Mistral and LLaMA families, unveil prevalent behaviors with both intrinsic and extrinsic bias. This work underscores the critical need to mitigate clinical bias and sets a new standard for future evaluations of LLMs' clinical bias.

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

Several studies have shown that speech and language features, automatically extracted from clinical interviews or spontaneous discourse, have diagnostic value for mental disorders such as schizophrenia and bipolar disorder. They typically make use of a large feature set to train a classifier for distinguishing between two groups of interest, i.e. a clinical and control group. However, a purely data-driven approach runs the risk of overfitting to a particular data set, especially when sample sizes are limited. Here, we first down-select the set of language features to a small subset that is related to a well-validated test of functional ability, the Social Skills Performance Assessment (SSPA). This helps establish the concurrent validity of the selected features. We use only these features to train a simple classifier to distinguish between groups of interest. Linear regression reveals that a subset of language features can effectively model the SSPA, with a correlation coefficient of 0.75. Furthermore, the same feature set can be used to build a strong binary classifier to distinguish between healthy controls and a clinical group (AUC = 0.96) and also between patients within the clinical group with schizophrenia and bipolar I disorder (AUC = 0.83).

Stroke remains a leading cause of global morbidity and mortality, placing a heavy socioeconomic burden. Over the past decade, advances in endovascular reperfusion therapy and the use of CT and MRI imaging for treatment guidance have significantly improved patient outcomes and are now standard in clinical practice. To develop machine learning algorithms that can extract meaningful and reproducible models of brain function for both clinical and research purposes from stroke images - particularly for lesion identification, brain health quantification, and prognosis - large, diverse, and well-annotated public datasets are essential. While only a few datasets with (sub-)acute stroke data were previously available, several large, high-quality datasets have recently been made publicly accessible. However, these existing datasets include only MRI data. In contrast, our dataset is the first to offer comprehensive longitudinal stroke data, including acute CT imaging with angiography and perfusion, follow-up MRI at 2-9 days, as well as acute and longitudinal clinical data up to a three-month outcome. The dataset includes a training dataset of n = 150 and a test dataset of n = 100 scans. Training data is publicly available, while test data will be used exclusively for model validation. We are making this dataset available as part of the 2024 edition of the Ischemic Stroke Lesion Segmentation (ISLES) challenge (https://www.isles-challenge.org/), which continuously aims to establish benchmark methods for acute and sub-acute ischemic stroke lesion segmentation, aiding in creating open stroke imaging datasets and evaluating cutting-edge image processing algorithms.

Databases of electronic health records (EHRs) are increasingly used to inform clinical decisions. Machine learning methods can find patterns in EHRs that are predictive of future adverse outcomes. However, statistical models may be built upon patterns of health-seeking behavior that vary across patient subpopulations, leading to poor predictive performance when training on one patient population and predicting on another. This note proposes two tests to better measure and understand model generalization. We use these tests to compare models derived from two data sources: (i) historical medical records, and (ii) electrocardiogram (EKG) waveforms. In a predictive task, we show that EKG-based models can be more stable than EHR-based models across different patient populations.

Medical applications of machine learning (ML) have experienced a surge in popularity in recent years. The intensive care unit (ICU) is a natural habitat for ML given the abundance of available data from electronic health records. Models have been proposed to address numerous ICU prediction tasks like the early detection of complications. While authors frequently report state-of-the-art performance, it is challenging to verify claims of superiority. Datasets and code are not always published, and cohort definitions, preprocessing pipelines, and training setups are difficult to reproduce. This work introduces Yet Another ICU Benchmark (YAIB), a modular framework that allows researchers to define reproducible and comparable clinical ML experiments; we offer an end-to-end solution from cohort definition to model evaluation. The framework natively supports most open-access ICU datasets (MIMIC III/IV, eICU, HiRID, AUMCdb) and is easily adaptable to future ICU datasets. Combined with a transparent preprocessing pipeline and extensible training code for multiple ML and deep learning models, YAIB enables unified model development. Our benchmark comes with five predefined established prediction tasks (mortality, acute kidney injury, sepsis, kidney function, and length of stay) developed in collaboration with clinicians. Adding further tasks is straightforward by design. Using YAIB, we demonstrate that the choice of dataset, cohort definition, and preprocessing have a major impact on the prediction performance - often more so than model class - indicating an urgent need for YAIB as a holistic benchmarking tool. We provide our work to the clinical ML community to accelerate method development and enable real-world clinical implementations. Software Repository: https://github.com/rvandewater/YAIB.

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

We study multiple rule-based and machine learning (ML) models for sepsis detection. We report the first neural network detection and prediction results on three categories of sepsis. We have used the retrospective Medical Information Mart for Intensive Care (MIMIC)-III dataset, restricted to intensive care unit (ICU) patients. Features for prediction were created from only common vital sign measurements. We show significant improvement of AUC score using neural network based ensemble model compared to single ML and rule-based models. For the detection of sepsis, severe sepsis, and septic shock, our model achieves an AUC of 0.97, 0.96 and 0.91, respectively. Four hours before the positive hours, it predicts the same three categories with an AUC of 0.90, 0.91 and 0.90 respectively. Further, we ranked the features and found that using six vital signs consistently provides higher detection and prediction AUC for all the models tested. Our novel ensemble model achieves highest AUC in detecting and predicting sepsis, severe sepsis, and septic shock in the MIMIC-III ICU patients, and is amenable to deployment in hospital settings.

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

Background:Speech patterns have emerged as potential diagnostic markers for conditions with varying etiologies. Machine learning (ML) presents an opportunity to harness these patterns for accurate disease diagnosis. Objective: This review synthesized findings from studies exploring ML's capability in leveraging speech for the diagnosis of neurological, laryngeal and mental disorders. Methods: A systematic examination of 564 articles was conducted with 91 articles included in the study, which encompassed a wide spectrum of conditions, ranging from voice pathologies to mental and neurological disorders. Methods for speech classifications were assessed based on the relevant studies and scored between 0-10 based on the reported diagnostic accuracy of their ML models. Results: High diagnostic accuracies were consistently observed for laryngeal disorders, dysarthria, and changes related to speech in Parkinsons disease. These findings indicate the robust potential of speech as a diagnostic tool. Disorders like depression, schizophrenia, mild cognitive impairment and Alzheimers dementia also demonstrated high accuracies, albeit with some variability across studies. Meanwhile, disorders like OCD and autism highlighted the need for more extensive research to ascertain the relationship between speech patterns and the respective conditions. Conclusion: ML models utilizing speech patterns demonstrate promising potential in diagnosing a range of mental, laryngeal, and neurological disorders. However, the efficacy varies across conditions, and further research is needed. The integration of these models into clinical practice could potentially revolutionize the evaluation and diagnosis of a number of different medical conditions.

The timely identification of socio-economic sectors vulnerable to a disease outbreak presents an important challenge to the civic authorities and healthcare workers interested in outbreak mitigation measures. This problem was traditionally solved by studying the aberrances in small-scale healthcare data. In this paper, we leverage data driven models to determine the relationship between the trends of World Development Indicators and occurrence of disease outbreaks using worldwide historical data from 2000-2019, and treat it as a classic supervised classification problem. CART based feature selection was employed in an unorthodox fashion to determine the covariates getting affected by the disease outbreak, thus giving the most vulnerable sectors. The result involves a comprehensive analysis of different classification algorithms and is indicative of the relationship between the disease outbreak occurrence and the magnitudes of various development indicators.

Clinical natural language processing requires methods that can address domain-specific challenges, such as complex medical terminology and clinical contexts. Recently, large language models (LLMs) have shown promise in this domain. Yet, their direct deployment can lead to privacy issues and are constrained by resources. To address this challenge, we delve into synthetic clinical text generation using LLMs for clinical NLP tasks. We propose an innovative, resource-efficient approach, ClinGen, which infuses knowledge into the process. Our model involves clinical knowledge extraction and context-informed LLM prompting. Both clinical topics and writing styles are drawn from external domain-specific knowledge graphs and LLMs to guide data generation. Our extensive empirical study across 7 clinical NLP tasks and 16 datasets reveals that ClinGen consistently enhances performance across various tasks, effectively aligning the distribution of real datasets and significantly enriching the diversity of generated training instances. We will publish our code and all the generated data in https://github.com/ritaranx/ClinGen.

The approval success rate of drug candidates is very low with the majority of failure due to safety and efficacy. Increasingly available high dimensional information on targets, drug molecules and indications provides an opportunity for ML methods to integrate multiple data modalities and better predict clinically promising drug targets. Notably, drug targets with human genetics evidence are shown to have better odds to succeed. However, a recent tensor factorization-based approach found that additional information on targets and indications might not necessarily improve the predictive accuracy. Here we revisit this approach by integrating different types of human genetics evidence collated from publicly available sources to support each target-indication pair. We use Bayesian tensor factorization to show that models incorporating all available human genetics evidence (rare disease, gene burden, common disease) modestly improves the clinical outcome prediction over models using single line of genetics evidence. We provide additional insight into the relative predictive power of different types of human genetics evidence for predicting the success of clinical outcomes.

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

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.

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.

Medical research generates a large number of publications with the PubMed database already containing >35 million research articles. Integration of the knowledge scattered across this large body of literature could provide key insights into physiological mechanisms and disease processes leading to novel medical interventions. However, it is a great challenge for researchers to utilize this information in full since the scale and complexity of the data greatly surpasses human processing abilities. This becomes especially problematic in cases of extreme urgency like the COVID-19 pandemic. Automated text mining can help extract and connect information from the large body of medical research articles. The first step in text mining is typically the identification of specific classes of keywords (e.g., all protein or disease names), so called Named Entity Recognition (NER). Here we present an end-to-end pipeline for NER of typical entities found in medical research articles, including diseases, cells, chemicals, genes/proteins, and species. The pipeline can access and process large medical research article collections (PubMed, CORD-19) or raw text and incorporates a series of deep learning models fine-tuned on the HUNER corpora collection. In addition, the pipeline can perform dictionary-based NER related to COVID-19 and other medical topics. Users can also load their own NER models and dictionaries to include additional entities. The output consists of publication-ready ranked lists and graphs of detected entities and files containing the annotated texts. An associated script allows rapid inspection of the results for specific entities of interest. As model use cases, the pipeline was deployed on two collections of autophagy-related abstracts from PubMed and on the CORD19 dataset, a collection of 764 398 research article abstracts related to COVID-19.

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

We present the findings of "The Alzheimer's Disease Prediction Of Longitudinal Evolution" (TADPOLE) Challenge, which compared the performance of 92 algorithms from 33 international teams at predicting the future trajectory of 219 individuals at risk of Alzheimer's disease. Challenge participants were required to make a prediction, for each month of a 5-year future time period, of three key outcomes: clinical diagnosis, Alzheimer's Disease Assessment Scale Cognitive Subdomain (ADAS-Cog13), and total volume of the ventricles. The methods used by challenge participants included multivariate linear regression, machine learning methods such as support vector machines and deep neural networks, as well as disease progression models. No single submission was best at predicting all three outcomes. For clinical diagnosis and ventricle volume prediction, the best algorithms strongly outperform simple baselines in predictive ability. However, for ADAS-Cog13 no single submitted prediction method was significantly better than random guesswork. Two ensemble methods based on taking the mean and median over all predictions, obtained top scores on almost all tasks. Better than average performance at diagnosis prediction was generally associated with the additional inclusion of features from cerebrospinal fluid (CSF) samples and diffusion tensor imaging (DTI). On the other hand, better performance at ventricle volume prediction was associated with inclusion of summary statistics, such as the slope or maxima/minima of biomarkers. TADPOLE's unique results suggest that current prediction algorithms provide sufficient accuracy to exploit biomarkers related to clinical diagnosis and ventricle volume, for cohort refinement in clinical trials for Alzheimer's disease. However, results call into question the usage of cognitive test scores for patient selection and as a primary endpoint in clinical trials.

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

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.

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.

Pathology Foundation Models (FMs) hold great promise for healthcare. Before they can be used in clinical practice, it is essential to ensure they are robust to variations between medical centers. We measure whether pathology FMs focus on biological features like tissue and cancer type, or on the well known confounding medical center signatures introduced by staining procedure and other differences. We introduce the Robustness Index. This novel robustness metric reflects to what degree biological features dominate confounding features. Ten current publicly available pathology FMs are evaluated. We find that all current pathology foundation models evaluated represent the medical center to a strong degree. Significant differences in the robustness index are observed. Only one model so far has a robustness index greater than one, meaning biological features dominate confounding features, but only slightly. A quantitative approach to measure the influence of medical center differences on FM-based prediction performance is described. We analyze the impact of unrobustness on classification performance of downstream models, and find that cancer-type classification errors are not random, but specifically attributable to same-center confounders: images of other classes from the same medical center. We visualize FM embedding spaces, and find these are more strongly organized by medical centers than by biological factors. As a consequence, the medical center of origin is predicted more accurately than the tissue source and cancer type. The robustness index introduced here is provided with the aim of advancing progress towards clinical adoption of robust and reliable pathology FMs.

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.

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

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.

Combination therapies have become the standard of care for diseases such as cancer, tuberculosis, malaria and HIV. However, the combinatorial set of available multi-drug treatments creates a challenge in identifying effective combination therapies available in a situation. To assist medical professionals in identifying beneficial drug-combinations, we construct an expert-annotated dataset for extracting information about the efficacy of drug combinations from the scientific literature. Beyond its practical utility, the dataset also presents a unique NLP challenge, as the first relation extraction dataset consisting of variable-length relations. Furthermore, the relations in this dataset predominantly require language understanding beyond the sentence level, adding to the challenge of this task. We provide a promising baseline model and identify clear areas for further improvement. We release our dataset, code, and baseline models publicly to encourage the NLP community to participate in this task.

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

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

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.

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

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

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.

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.

Despite growing interest in using large language models (LLMs) in healthcare, current explorations do not assess the real-world utility and safety of LLMs in clinical settings. Our objective was to determine whether two LLMs can serve information needs submitted by physicians as questions to an informatics consultation service in a safe and concordant manner. Sixty six questions from an informatics consult service were submitted to GPT-3.5 and GPT-4 via simple prompts. 12 physicians assessed the LLM responses' possibility of patient harm and concordance with existing reports from an informatics consultation service. Physician assessments were summarized based on majority vote. For no questions did a majority of physicians deem either LLM response as harmful. For GPT-3.5, responses to 8 questions were concordant with the informatics consult report, 20 discordant, and 9 were unable to be assessed. There were 29 responses with no majority on "Agree", "Disagree", and "Unable to assess". For GPT-4, responses to 13 questions were concordant, 15 discordant, and 3 were unable to be assessed. There were 35 responses with no majority. Responses from both LLMs were largely devoid of overt harm, but less than 20% of the responses agreed with an answer from an informatics consultation service, responses contained hallucinated references, and physicians were divided on what constitutes harm. These results suggest that while general purpose LLMs are able to provide safe and credible responses, they often do not meet the specific information need of a given question. A definitive evaluation of the usefulness of LLMs in healthcare settings will likely require additional research on prompt engineering, calibration, and custom-tailoring of general purpose models.

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.

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

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.

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

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.

Inspire therapy is an FDA-approved internal neurostimulation treatment for obstructive sleep apnea. However, not all patients respond to this therapy, posing a challenge even for experienced otolaryngologists to determine candidacy. This paper makes the first attempt to leverage both machine learning and deep learning techniques in discerning patient responsiveness to Inspire therapy using medical data and videos captured through Drug-Induced Sleep Endoscopy (DISE), an essential procedure for Inspire therapy. To achieve this, we gathered and annotated three datasets from 127 patients. Two of these datasets comprise endoscopic videos focused on the Base of the Tongue and Velopharynx. The third dataset composes the patient's clinical information. By utilizing these datasets, we benchmarked and compared the performance of six deep learning models and five classical machine learning algorithms. The results demonstrate the potential of employing machine learning and deep learning techniques to determine a patient's eligibility for Inspire therapy, paving the way for future advancements in this field.

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

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.

Healthcare is an important aspect of human life. Use of technologies in healthcare has increased manifolds after the pandemic. Internet of Things based systems and devices proposed in literature can help elders, children and adults facing/experiencing health problems. This paper exhaustively reviews thirty-nine wearable based datasets which can be used for evaluating the system to recognize Activities of Daily Living and Falls. A comparative analysis on the SisFall dataset using five machine learning methods i.e., Logistic Regression, Linear Discriminant Analysis, K-Nearest Neighbor, Decision Tree and Naive Bayes is performed in python. The dataset is modified in two ways, in first all the attributes present in dataset are used as it is and labelled in binary form. In second, magnitude of three axes(x,y,z) for three sensors value are computed and then used in experiment with label attribute. The experiments are performed on one subject, ten subjects and all the subjects and compared in terms of accuracy, precision and recall. The results obtained from this study proves that KNN outperforms other machine learning methods in terms of accuracy, precision and recall. It is also concluded that personalization of data improves accuracy.

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

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

In the pharmaceutical industry, the use of artificial intelligence (AI) has seen consistent growth over the past decade. This rise is attributed to major advancements in statistical machine learning methodologies, computational capabilities and the increased availability of large datasets. AI techniques are applied throughout different stages of drug development, ranging from drug discovery to post-marketing benefit-risk assessment. Kolluri et al. provided a review of several case studies that span these stages, featuring key applications such as protein structure prediction, success probability estimation, subgroup identification, and AI-assisted clinical trial monitoring. From a regulatory standpoint, there was a notable uptick in submissions incorporating AI components in 2021. The most prevalent therapeutic areas leveraging AI were oncology (27%), psychiatry (15%), gastroenterology (12%), and neurology (11%). The paradigm of personalized or precision medicine has gained significant traction in recent research, partly due to advancements in AI techniques hamburg2010path. This shift has had a transformative impact on the pharmaceutical industry. Departing from the traditional "one-size-fits-all" model, personalized medicine incorporates various individual factors, such as environmental conditions, lifestyle choices, and health histories, to formulate customized treatment plans. By utilizing sophisticated machine learning algorithms, clinicians and researchers are better equipped to make informed decisions in areas such as disease prevention, diagnosis, and treatment selection, thereby optimizing health outcomes for each individual.

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

The global cost of drug discovery and development exceeds $200 billion annually. The main results of drug discovery and development are the outcomes of clinical trials, which directly influence the regulatory approval of new drug candidates and ultimately affect patient outcomes. Despite their significance, large-scale, high-quality clinical trial outcome data are not readily available to the public. Suppose a large clinical trial outcome dataset is provided; machine learning researchers can potentially develop accurate prediction models using past trials and outcome labels, which could help prioritize and optimize therapeutic programs, ultimately benefiting patients. This paper introduces Clinical Trial Outcome (CTO) dataset, the largest trial outcome dataset with around 479K clinical trials, aggregating outcomes from multiple sources of weakly supervised labels, minimizing the noise from individual sources, and eliminating the need for human annotation. These sources include large language model (LLM) decisions on trial-related documents, news headline sentiments, stock prices of trial sponsors, trial linkages across phases, and other signals such as patient dropout rates and adverse events. CTO's labels show unprecedented agreement with supervised clinical trial outcome labels from test split of the supervised TOP dataset, with a 91 F1.

In this study, we aimed to determine if fine-tuned large language models (LLMs) can generate accurate, personalized impressions for whole-body PET reports. Twelve language models were trained on a corpus of PET reports using the teacher-forcing algorithm, with the report findings as input and the clinical impressions as reference. An extra input token encodes the reading physician's identity, allowing models to learn physician-specific reporting styles. Our corpus comprised 37,370 retrospective PET reports collected from our institution between 2010 and 2022. To identify the best LLM, 30 evaluation metrics were benchmarked against quality scores from two nuclear medicine (NM) physicians, with the most aligned metrics selecting the model for expert evaluation. In a subset of data, model-generated impressions and original clinical impressions were assessed by three NM physicians according to 6 quality dimensions (3-point scale) and an overall utility score (5-point scale). Each physician reviewed 12 of their own reports and 12 reports from other physicians. Bootstrap resampling was used for statistical analysis. Of all evaluation metrics, domain-adapted BARTScore and PEGASUSScore showed the highest Spearman's rank correlations (0.568 and 0.563) with physician preferences. Based on these metrics, the fine-tuned PEGASUS model was selected as the top LLM. When physicians reviewed PEGASUS-generated impressions in their own style, 89% were considered clinically acceptable, with a mean utility score of 4.08 out of 5. Physicians rated these personalized impressions as comparable in overall utility to the impressions dictated by other physicians (4.03, P=0.41). In conclusion, personalized impressions generated by PEGASUS were clinically useful, highlighting its potential to expedite PET reporting.

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.

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

Adverse Drug Reactions (ADRs) from psychiatric medications are the leading cause of hospitalizations among mental health patients. With healthcare systems and online communities facing limitations in resolving ADR-related issues, Large Language Models (LLMs) have the potential to fill this gap. Despite the increasing capabilities of LLMs, past research has not explored their capabilities in detecting ADRs related to psychiatric medications or in providing effective harm reduction strategies. To address this, we introduce the Psych-ADR benchmark and the Adverse Drug Reaction Response Assessment (ADRA) framework to systematically evaluate LLM performance in detecting ADR expressions and delivering expert-aligned mitigation strategies. Our analyses show that LLMs struggle with understanding the nuances of ADRs and differentiating between types of ADRs. While LLMs align with experts in terms of expressed emotions and tone of the text, their responses are more complex, harder to read, and only 70.86% aligned with expert strategies. Furthermore, they provide less actionable advice by a margin of 12.32% on average. Our work provides a comprehensive benchmark and evaluation framework for assessing LLMs in strategy-driven tasks within high-risk domains.

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.

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.

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

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

In the era of modern healthcare, swiftly generating medical question summaries is crucial for informed and timely patient care. Despite the increasing complexity and volume of medical data, existing studies have focused solely on text-based summarization, neglecting the integration of visual information. Recognizing the untapped potential of combining textual queries with visual representations of medical conditions, we introduce the Multimodal Medical Question Summarization (MMQS) Dataset. This dataset, a major contribution to our work, pairs medical queries with visual aids, facilitating a richer and more nuanced understanding of patient needs. We also propose a framework, utilizing the power of Contrastive Language Image Pretraining(CLIP) and Large Language Models(LLMs), consisting of four modules that identify medical disorders, generate relevant context, filter medical concepts, and craft visually aware summaries. Our comprehensive framework harnesses the power of CLIP, a multimodal foundation model, and various general-purpose LLMs, comprising four main modules: the medical disorder identification module, the relevant context generation module, the context filtration module for distilling relevant medical concepts and knowledge, and finally, a general-purpose LLM to generate visually aware medical question summaries. Leveraging our MMQS dataset, we showcase how visual cues from images enhance the generation of medically nuanced summaries. This multimodal approach not only enhances the decision-making process in healthcare but also fosters a more nuanced understanding of patient queries, laying the groundwork for future research in personalized and responsive medical care

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.

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.

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

Global rates of mental health concerns are rising and there is increasing realization that existing models of mental healthcare will not adequately expand to meet the demand. With the emergence of large language models (LLMs) has come great optimism regarding their promise to create novel, large-scale solutions to support mental health. Despite their nascence, LLMs have already been applied to mental health-related tasks. In this review, we summarize the extant literature on efforts to use LLMs to provide mental health education, assessment, and intervention and highlight key opportunities for positive impact in each area. We then highlight risks associated with LLMs application to mental health and encourage adoption of strategies to mitigate these risks. The urgent need for mental health support must be balanced with responsible development, testing, and deployment of mental health LLMs. Especially critical is ensuring that mental health LLMs are fine-tuned for mental health, enhance mental health equity, adhere to ethical standards, and that people, including those with lived experience with mental health concerns, are involved in all stages from development through deployment. Prioritizing these efforts will minimize potential harms to mental health and maximize the likelihood that LLMs will positively impact mental health globally.

We introduce RJUA-QA, a novel medical dataset for question answering (QA) and reasoning with clinical evidence, contributing to bridge the gap between general large language models (LLMs) and medical-specific LLM applications. RJUA-QA is derived from realistic clinical scenarios and aims to facilitate LLMs in generating reliable diagnostic and advice. The dataset contains 2,132 curated Question-Context-Answer pairs, corresponding about 25,000 diagnostic records and clinical cases. The dataset covers 67 common urological disease categories, where the disease coverage exceeds 97.6\% of the population seeking medical services in urology. Each data instance in RJUA-QA comprises: (1) a question mirroring real patient to inquiry about clinical symptoms and medical conditions, (2) a context including comprehensive expert knowledge, serving as a reference for medical examination and diagnosis, (3) a doctor response offering the diagnostic conclusion and suggested examination guidance, (4) a diagnosed clinical disease as the recommended diagnostic outcome, and (5) clinical advice providing recommendations for medical examination. RJUA-QA is the first medical QA dataset for clinical reasoning over the patient inquiries, where expert-level knowledge and experience are required for yielding diagnostic conclusions and medical examination advice. A comprehensive evaluation is conducted to evaluate the performance of both medical-specific and general LLMs on the RJUA-QA dataset.

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.

Heart disease, also known as cardiovascular disease, is a prevalent and critical medical condition characterized by the impairment of the heart and blood vessels, leading to various complications such as coronary artery disease, heart failure, and myocardial infarction. The timely and accurate detection of heart disease is of paramount importance in clinical practice. Early identification of individuals at risk enables proactive interventions, preventive measures, and personalized treatment strategies to mitigate the progression of the disease and reduce adverse outcomes. In recent years, the field of heart disease detection has witnessed notable advancements due to the integration of sophisticated technologies and computational approaches. These include machine learning algorithms, data mining techniques, and predictive modeling frameworks that leverage vast amounts of clinical and physiological data to improve diagnostic accuracy and risk stratification. In this work, we propose to detect heart disease from ECG images using cutting-edge technologies, namely vision transformer models. These models are Google-Vit, Microsoft-Beit, and Swin-Tiny. To the best of our knowledge, this is the initial endeavor concentrating on the detection of heart diseases through image-based ECG data by employing cuttingedge technologies namely, transformer models. To demonstrate the contribution of the proposed framework, the performance of vision transformer models are compared with state-of-the-art studies. Experiment results show that the proposed framework exhibits remarkable classification results.

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.

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

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

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

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.

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

We present the full-size Russian complexly NER-labeled corpus of Internet user reviews, along with an evaluation of accuracy levels reached on this corpus by a set of advanced deep learning neural networks to extract the pharmacologically meaningful entities from Russian texts. The corpus annotation includes mentions of the following entities: Medication (33005 mentions), Adverse Drug Reaction (1778), Disease (17403), and Note (4490). Two of them - Medication and Disease - comprise a set of attributes. A part of the corpus has the coreference annotation with 1560 coreference chains in 300 documents. Special multi-label model based on a language model and the set of features is developed, appropriate for presented corpus labeling. The influence of the choice of different modifications of the models: word vector representations, types of language models pre-trained for Russian, text normalization styles, and other preliminary processing are analyzed. The sufficient size of our corpus allows to study the effects of particularities of corpus labeling and balancing entities in the corpus. As a result, the state of the art for the pharmacological entity extraction problem for Russian is established on a full-size labeled corpus. In case of the adverse drug reaction (ADR) recognition, it is 61.1 by the F1-exact metric that, as our analysis shows, is on par with the accuracy level for other language corpora with similar characteristics and the ADR representativnes. The evaluated baseline precision of coreference relation extraction on the corpus is 71, that is higher the results reached on other Russian corpora.

In psychotherapy, therapeutic outcome assessment, or treatment outcome evaluation, is essential for enhancing mental health care by systematically evaluating therapeutic processes and outcomes. Existing large language model approaches often focus on therapist-centered, single-session evaluations, neglecting the client's subjective experience and longitudinal progress across multiple sessions. To address these limitations, we propose IPAEval, a client-Informed Psychological Assessment-based Evaluation framework that automates treatment outcome evaluations from the client's perspective using clinical interviews. IPAEval integrates cross-session client-contextual assessment and session-focused client-dynamics assessment to provide a comprehensive understanding of therapeutic progress. Experiments on our newly developed TheraPhase dataset demonstrate that IPAEval effectively tracks symptom severity and treatment outcomes over multiple sessions, outperforming previous single-session models and validating the benefits of items-aware reasoning mechanisms.

While the general machine learning (ML) community has benefited from public datasets, tasks, and models, the progress of ML in healthcare has been hampered by a lack of such shared assets. The success of foundation models creates new challenges for healthcare ML by requiring access to shared pretrained models to validate performance benefits. We help address these challenges through three contributions. First, we publish a new dataset, EHRSHOT, which contains deidentified structured data from the electronic health records (EHRs) of 6,739 patients from Stanford Medicine. Unlike MIMIC-III/IV and other popular EHR datasets, EHRSHOT is longitudinal and not restricted to ICU/ED patients. Second, we publish the weights of CLMBR-T-base, a 141M parameter clinical foundation model pretrained on the structured EHR data of 2.57M patients. We are one of the first to fully release such a model for coded EHR data; in contrast, most prior models released for clinical data (e.g. GatorTron, ClinicalBERT) only work with unstructured text and cannot process the rich, structured data within an EHR. We provide an end-to-end pipeline for the community to validate and build upon its performance. Third, we define 15 few-shot clinical prediction tasks, enabling evaluation of foundation models on benefits such as sample efficiency and task adaptation. Our model and dataset are available via a research data use agreement from the Stanford AIMI Center. Code to reproduce our results are available at our Github repo: https://github.com/som-shahlab/ehrshot-benchmark

With the rapid development of large language models (LLMs), assessing their performance on health-related inquiries has become increasingly essential. It is critical that these models provide accurate and trustworthy health information, as their application in real-world contexts--where misinformation can have serious consequences for individuals seeking medical advice and support--depends on their reliability. In this work, we present CHBench, the first comprehensive Chinese Health-related Benchmark designed to evaluate LLMs' capabilities in understanding physical and mental health across diverse scenarios. CHBench includes 6,493 entries related to mental health and 2,999 entries focused on physical health, covering a broad spectrum of topics. This dataset serves as a foundation for evaluating Chinese LLMs' capacity to comprehend and generate accurate health-related information. Our extensive evaluations of four popular Chinese LLMs demonstrate that there remains considerable room for improvement in their understanding of health-related information. The code is available at https://github.com/TracyGuo2001/CHBench.

In recent years, there is strong emphasis on mining medical data using machine learning techniques. A common problem is to obtain a noiseless set of textual documents, with a relevant content for the research question, and developing a Question Answering (QA) model for a specific medical field. The purpose of this paper is to present a new methodology for building a medical dataset and obtain a QA model for analysis of symptoms and impact on daily life for a specific disease domain. The ``Mental Health'' forum was used, a forum dedicated to people suffering from schizophrenia and different mental disorders. Relevant posts of active users, who regularly participate, were extrapolated providing a new method of obtaining low-bias content and without privacy issues. Furthermore, it is shown how to pre-process the dataset to convert it into a QA dataset. The Bidirectional Encoder Representations from Transformers (BERT), DistilBERT, RoBERTa, and BioBERT models were fine-tuned and evaluated via F1-Score, Exact Match, Precision and Recall. Accurate empirical experiments demonstrated the effectiveness of the proposed method for obtaining an accurate dataset for QA model implementation. By fine-tuning the BioBERT QA model, we achieved an F1 score of 0.885, showing a considerable improvement and outperforming the state-of-the-art model for mental disorders domain.

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

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

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

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.

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.

How do we most effectively treat a disease or condition? Ideally, we could consult a database of evidence gleaned from clinical trials to answer such questions. Unfortunately, no such database exists; clinical trial results are instead disseminated primarily via lengthy natural language articles. Perusing all such articles would be prohibitively time-consuming for healthcare practitioners; they instead tend to depend on manually compiled systematic reviews of medical literature to inform care. NLP may speed this process up, and eventually facilitate immediate consult of published evidence. The Evidence Inference dataset was recently released to facilitate research toward this end. This task entails inferring the comparative performance of two treatments, with respect to a given outcome, from a particular article (describing a clinical trial) and identifying supporting evidence. For instance: Does this article report that chemotherapy performed better than surgery for five-year survival rates of operable cancers? In this paper, we collect additional annotations to expand the Evidence Inference dataset by 25\%, provide stronger baseline models, systematically inspect the errors that these make, and probe dataset quality. We also release an abstract only (as opposed to full-texts) version of the task for rapid model prototyping. The updated corpus, documentation, and code for new baselines and evaluations are available at http://evidence-inference.ebm-nlp.com/.

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.

In this study, we present MedS-Bench, a comprehensive benchmark designed to evaluate the performance of large language models (LLMs) in clinical contexts. Unlike existing benchmarks that focus on multiple-choice question answering, MedS-Bench spans 11 high-level clinical tasks, including clinical report summarization, treatment recommendations, diagnosis, named entity recognition, and medical concept explanation, among others. We evaluated six leading LLMs, e.g., MEDITRON, Mistral, InternLM 2, Llama 3, GPT-4, and Claude-3.5 using few-shot prompting, and found that even the most sophisticated models struggle with these complex tasks. To address these limitations, we developed MedS-Ins, a large-scale instruction tuning dataset for medicine. MedS-Ins comprises 58 medically oriented language corpora, totaling 13.5 million samples across 122 tasks. To demonstrate the dataset's utility, we conducted a proof-of-concept experiment by performing instruction tuning on a lightweight, open-source medical language model. The resulting model, MMedIns-Llama 3, significantly outperformed existing models across nearly all clinical tasks. To promote further advancements in the application of LLMs to clinical challenges, we have made the MedS-Ins dataset fully accessible and invite the research community to contribute to its expansion.Additionally, we have launched a dynamic leaderboard for MedS-Bench, which we plan to regularly update the test set to track progress and enhance the adaptation of general LLMs to the medical domain. Leaderboard: https://henrychur.github.io/MedS-Bench/. Github: https://github.com/MAGIC-AI4Med/MedS-Ins.

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.

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.

LLMs have demonstrated impressive performance in answering medical questions, such as passing scores on medical licensing examinations. However, medical board exam questions or general clinical questions do not capture the complexity of realistic clinical cases. Moreover, the lack of reference explanations means we cannot easily evaluate the reasoning of model decisions, a crucial component of supporting doctors in making complex medical decisions. To address these challenges, we construct two new datasets: JAMA Clinical Challenge and Medbullets. JAMA Clinical Challenge consists of questions based on challenging clinical cases, while Medbullets comprises USMLE Step 2&3 style clinical questions. Both datasets are structured as multiple-choice question-answering tasks, where each question is accompanied by an expert-written explanation. We evaluate four LLMs on the two datasets using various prompts. Experiments demonstrate that our datasets are harder than previous benchmarks. The inconsistency between automatic and human evaluations of model-generated explanations highlights the need to develop new metrics to support future research on explainable medical QA.

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

Over the past several years, across the globe, there has been an increase in people seeking care in emergency departments (EDs). ED resources, including nurse staffing, are strained by such increases in patient volume. Accurate forecasting of incoming patient volume in emergency departments (ED) is crucial for efficient utilization and allocation of ED resources. Working with a suburban ED in the Pacific Northwest, we developed a tool powered by machine learning models, to forecast ED arrivals and ED patient volume to assist end-users, such as ED nurses, in resource allocation. In this paper, we discuss the results from our predictive models, the challenges, and the learnings from users' experiences with the tool in active clinical deployment in a real world setting.

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.

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

We present a labeled large-scale, high resolution chest x-ray dataset for the automated exploration of medical images along with their associated reports. This dataset includes more than 160,000 images obtained from 67,000 patients that were interpreted and reported by radiologists at Hospital San Juan Hospital (Spain) from 2009 to 2017, covering six different position views and additional information on image acquisition and patient demography. The reports were labeled with 174 different radiographic findings, 19 differential diagnoses and 104 anatomic locations organized as a hierarchical taxonomy and mapped onto standard Unified Medical Language System (UMLS) terminology. Of these reports, 27% were manually annotated by trained physicians and the remaining set was labeled using a supervised method based on a recurrent neural network with attention mechanisms. The labels generated were then validated in an independent test set achieving a 0.93 Micro-F1 score. To the best of our knowledge, this is one of the largest public chest x-ray database suitable for training supervised models concerning radiographs, and the first to contain radiographic reports in Spanish. The PadChest dataset can be downloaded from http://bimcv.cipf.es/bimcv-projects/padchest/.

Deep Learning (DL) in neuroimaging has become increasingly relevant for detecting neurological conditions and neurodegenerative disorders. One of the most predominant biomarkers in neuroimaging is represented by brain age, which has been shown to be a good indicator for different conditions, such as Alzheimer's Disease. Using brain age for weakly supervised pre-training of DL models in transfer learning settings has also recently shown promising results, especially when dealing with data scarcity of different conditions. On the other hand, anatomical information of brain MRIs (e.g. cortical thickness) can provide important information for learning good representations that can be transferred to many downstream tasks. In this work, we propose AnatCL, an anatomical foundation model for brain MRIs that i.) leverages anatomical information in a weakly contrastive learning approach, and ii.) achieves state-of-the-art performances across many different downstream tasks. To validate our approach we consider 12 different downstream tasks for the diagnosis of different conditions such as Alzheimer's Disease, autism spectrum disorder, and schizophrenia. Furthermore, we also target the prediction of 10 different clinical assessment scores using structural MRI data. Our findings show that incorporating anatomical information during pre-training leads to more robust and generalizable representations. Pre-trained models can be found at: https://github.com/EIDOSLAB/AnatCL.

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.

In clinical radiology reports, doctors capture important information about the patient's health status. They convey their observations from raw medical imaging data about the inner structures of a patient. As such, formulating reports requires medical experts to possess wide-ranging knowledge about anatomical regions with their normal, healthy appearance as well as the ability to recognize abnormalities. This explicit grasp on both the patient's anatomy and their appearance is missing in current medical image-processing systems as annotations are especially difficult to gather. This renders the models to be narrow experts e.g. for identifying specific diseases. In this work, we recover this missing link by adding human anatomy into the mix and enable the association of content in medical reports to their occurrence in associated imagery (medical phrase grounding). To exploit anatomical structures in this scenario, we present a sophisticated automatic pipeline to gather and integrate human bodily structures from computed tomography datasets, which we incorporate in our PAXRay: A Projected dataset for the segmentation of Anatomical structures in X-Ray data. Our evaluation shows that methods that take advantage of anatomical information benefit heavily in visually grounding radiologists' findings, as our anatomical segmentations allow for up to absolute 50% better grounding results on the OpenI dataset as compared to commonly used region proposals. The PAXRay dataset is available at https://constantinseibold.github.io/paxray/.