Machine learning for early prediction in medicine has recently shown breakthrough performance, however, the focus on improving prediction accuracy has led to a neglect of faithful explanations that are required to gain the trust of medical practitioners. The goal of this paper is to teach LLMs to follow medical consensus guidelines step-by-step in their reasoning and prediction process. Since consensus guidelines are ubiquitous in medicine, instantiations of verbalized medical inference rules to electronic health records provide data for fine-tuning LLMs to learn consensus rules and possible exceptions thereof for many medical areas. Consensus rules also enable an automatic evaluation of the model's inference process regarding its derivation correctness (evaluating correct and faithful deduction of a conclusion from given premises) and value correctness (comparing predicted values against real-world measurements). We exemplify our work using the complex Sepsis-3 consensus definition. Our experiments show that small fine-tuned models outperform one-shot learning of considerably larger LLMs that are prompted with the explicit definition and models that are trained on medical texts including consensus definitions. Since fine-tuning on verbalized rule instantiations of a specific medical area yields nearly perfect derivation correctness for rules (and exceptions) on unseen patient data in that area, the bottleneck for early prediction is not out-of-distribution generalization, but the orthogonal problem of generalization into the future by forecasting sparsely and irregularly sampled clinical variables. We show that the latter results can be improved by integrating the output representations of a time series forecasting model with the LLM in a multimodal setup.

In intensive care units (ICUs), patients with complex clinical conditions require vigilant monitoring and prompt interventions. Chest X-rays (CXRs) are a vital diagnostic tool, providing insights into clinical trajectories, but their irregular acquisition limits their utility. Existing tools for CXR interpretation are constrained by cross-sectional analysis, failing to capture temporal dynamics. To address this, we introduce CXR-TFT, a novel multi-modal framework that integrates temporally sparse CXR imaging and radiology reports with high-frequency clinical data, such as vital signs, laboratory values, and respiratory flow sheets, to predict the trajectory of CXR findings in critically ill patients. CXR-TFT leverages latent embeddings from a vision encoder that are temporally aligned with hourly clinical data through interpolation. A transformer model is then trained to predict CXR embeddings at each hour, conditioned on previous embeddings and clinical measurements. In a retrospective study of 20,000 ICU patients, CXR-TFT demonstrated high accuracy in forecasting abnormal CXR findings up to 12 hours before they became radiographically evident. This predictive capability in clinical data holds significant potential for enhancing the management of time-sensitive conditions like acute respiratory distress syndrome, where early intervention is crucial and diagnoses are often delayed. By providing distinctive temporal resolution in prognostic CXR analysis, CXR-TFT offers actionable 'whole patient' insights that can directly improve clinical outcomes.

Radiographic knee alignment (KA) measurement is important for predicting joint health and surgical outcomes after total knee replacement. Traditional methods for KA measurements are manual, time-consuming and require long-leg radiographs. This study proposes a deep learning-based method to measure KA in anteroposterior knee radiographs via automatically localized knee anatomical landmarks. Our method builds on hourglass networks and incorporates an attention gate structure to enhance robustness and focus on key anatomical features. To our knowledge, this is the first deep learning-based method to localize over 100 knee anatomical landmarks to fully outline the knee shape while integrating KA measurements on both pre-operative and post-operative images. It provides highly accurate and reliable anatomical varus/valgus KA measurements using the anatomical tibiofemoral angle, achieving mean absolute differences ~1° when compared to clinical ground truth measurements. Agreement between automated and clinical measurements was excellent pre-operatively (intra-class correlation coefficient (ICC) = 0.97) and good post-operatively (ICC = 0.86). Our findings demonstrate that KA assessment can be automated with high accuracy, creating opportunities for digitally enhanced clinical workflows.

Clinical measurements such as blood pressures and respiration rates are critical in diagnosing and monitoring patient outcomes. It is an important component of biomedical data, which can be used to train transformer-based language models (LMs) for improving healthcare delivery. It is, however, unclear whether LMs can effectively interpret and use clinical measurements. We investigate two questions: First, can LMs effectively leverage clinical measurements to answer related medical questions? Second, how to enhance an LM's performance on medical question-answering (QA) tasks that involve measurements? We performed a case study on blood pressure readings (BPs), a vital sign routinely monitored by medical professionals. We evaluated the performance of four LMs: BERT, BioBERT, MedAlpaca, and GPT-3.5, on our newly developed dataset, BPQA (Blood Pressure Question Answering). BPQA contains $100$ medical QA pairs that were verified by medical students and designed to rely on BPs . We found that GPT-3.5 and MedAlpaca (larger and medium sized LMs) benefit more from the inclusion of BPs than BERT and BioBERT (small sized LMs). Further, augmenting measurements with labels improves the performance of BioBERT and Medalpaca (domain specific LMs), suggesting that retrieval may be useful for improving domain-specific LMs.

A patient undergoes multiple examinations in each hospital stay, where each provides different facets of the health status. These assessments include temporal data with varying sampling rates, discrete single-point measurements, therapeutic interventions such as medication administration, and images. While physicians are able to process and integrate diverse modalities intuitively, neural networks need specific modeling for each modality complicating the training procedure. We demonstrate that this complexity can be significantly reduced by visualizing all information as images along with unstructured text and subsequently training a conventional vision-text transformer. Our approach, Vision Transformer for irregular sampled Multi-modal Measurements (ViTiMM), not only simplifies data preprocessing and modeling but also outperforms current state-of-the-art methods in predicting in-hospital mortality and phenotyping, as evaluated on 6,175 patients from the MIMIC-IV dataset. The modalities include patient's clinical measurements, medications, X-ray images, and electrocardiography scans. We hope our work inspires advancements in multi-modal medical AI by reducing the training complexity to (visual) prompt engineering, thus lowering entry barriers and enabling no-code solutions for training. The source code will be made publicly available.

Insufficiently precise diagnosis of clinical disease is likely responsible for many treatment failures, even for common conditions and treatments. With a large enough dataset, it may be possible to use unsupervised machine learning to define clinical disease patterns more precisely. We present an approach to learning these patterns by using probabilistic independence to disentangle the imprint on the medical record of causal latent sources of disease. We inferred a broad set of 2000 clinical signatures of latent sources from 9195 variables in 269,099 Electronic Health Records. The learned signatures produced better discrimination than the original variables in a lung cancer prediction task unknown to the inference algorithm, predicting 3-year malignancy in patients with no history of cancer before a solitary lung nodule was discovered. More importantly, the signatures' greater explanatory power identified pre-nodule signatures of apparently undiagnosed cancer in many of those patients.

The generation of virtual populations (VPs) of anatomy is essential for conducting in silico trials of medical devices. Typically, the generated VP should capture sufficient variability while remaining plausible and should reflect the specific characteristics and demographics of the patients observed in real populations. In several applications, it is desirable to synthesise virtual populations in a \textit{controlled} manner, where relevant covariates are used to conditionally synthesise virtual populations that fit a specific target population/characteristics. We propose to equip a conditional variational autoencoder (cVAE) with normalising flows to boost the flexibility and complexity of the approximate posterior learnt, leading to enhanced flexibility for controllable synthesis of VPs of anatomical structures. We demonstrate the performance of our conditional flow VAE using a data set of cardiac left ventricles acquired from 2360 patients, with associated demographic information and clinical measurements (used as covariates/conditional information). The results obtained indicate the superiority of the proposed method for conditional synthesis of virtual populations of cardiac left ventricles relative to a cVAE. Conditional synthesis performance was evaluated in terms of generalisation and specificity errors and in terms of the ability to preserve clinically relevant biomarkers in synthesised VPs, that is, the left ventricular blood pool and myocardial volume, relative to the real observed population.

The aim of survival analysis in healthcare is to estimate the probability of occurrence of an event, such as a patient's death in an intensive care unit (ICU). Recent developments in deep neural networks (DNNs) for survival analysis show the superiority of these models in comparison with other well-known models in survival analysis applications. Ensuring the reliability and explainability of deep survival models deployed in healthcare is a necessity. Since DNN models often behave like a black box, their predictions might not be easily trusted by clinicians, especially when predictions are contrary to a physician's opinion. A deep survival model that explains and justifies its decision-making process could potentially gain the trust of clinicians. In this research, we propose the reverse survival model (RSM) framework that provides detailed insights into the decision-making process of survival models. For each patient of interest, RSM can extract similar patients from a dataset and rank them based on the most relevant features that deep survival models rely on for their predictions.

Advances in computational science offer a principled pipeline for predictive modeling of cardiovascular flows and aspire to provide a valuable tool for monitoring, diagnostics and surgical planning. Such models can be nowadays deployed on large patient-specific topologies of systemic arterial networks and return detailed predictions on flow patterns, wall shear stresses, and pulse wave propagation. However, their success heavily relies on tedious pre-processing and calibration procedures that typically induce a significant computational cost, thus hampering their clinical applicability. In this work we put forth a machine learning framework that enables the seamless synthesis of non-invasive in-vivo measurement techniques and computational flow dynamics models derived from first physical principles. We illustrate this new paradigm by showing how one-dimensional models of pulsatile flow can be used to constrain the output of deep neural networks such that their predictions satisfy the conservation of mass and momentum principles. Once trained on noisy and scattered clinical data of flow and wall displacement, these networks can return physically consistent predictions for velocity, pressure and wall displacement pulse wave propagation, all without the need to employ conventional simulators. A simple post-processing of these outputs can also provide a cheap and effective way for estimating Windkessel model parameters that are required for the calibration of traditional computational models. The effectiveness of the proposed techniques is demonstrated through a series of prototype benchmarks, as well as a realistic clinical case involving in-vivo measurements near the aorta/carotid bifurcation of a healthy human subject.