Munib Mesinovic

Munib Mesinovic, Peter Watkinson, Tingting Zhu

Recent advancements in AI applications to healthcare have shown incredible promise in surpassing human performance in diagnosis and disease prognosis. With the increasing complexity of AI models, however, concerns regarding their opacity, potential biases, and the need for interpretability. To ensure trust and reliability in AI systems, especially in clinical risk prediction models, explainability becomes crucial. Explainability is usually referred to as an AI system's ability to provide a robust interpretation of its decision-making logic or the decisions themselves to human stakeholders. In clinical risk prediction, other aspects of explainability like fairness, bias, trust, and transparency also represent important concepts beyond just interpretability. In this review, we address the relationship between these concepts as they are often used together or interchangeably. This review also discusses recent progress in developing explainable models for clinical risk prediction, highlighting the importance of quantitative and clinical evaluation and validation across multiple common modalities in clinical practice. It emphasizes the need for external validation and the combination of diverse interpretability methods to enhance trust and fairness. Adopting rigorous testing, such as using synthetic datasets with known generative factors, can further improve the reliability of explainability methods. Open access and code-sharing resources are essential for transparency and reproducibility, enabling the growth and trustworthiness of explainable research. While challenges exist, an end-to-end approach to explainability in clinical risk prediction, incorporating stakeholders from clinicians to developers, is essential for success.

Munib Mesinovic, Tingting Zhu

Electronic health record (EHR) data present tremendous opportunities for advancing survival analysis through deep learning, yet reproducibility remains severely constrained by inconsistent preprocessing methodologies. We present SurvBench, a comprehensive, open-source preprocessing pipeline that transforms raw PhysioNet datasets into standardised, model-ready tensors for multi-modal survival analysis. SurvBench provides data loaders for three major critical care databases, MIMIC-IV, eICU, and MC-MED, supporting diverse modalities including time-series vitals, static demographics, ICD diagnosis codes, and radiology reports. The pipeline implements rigorous data quality controls, patient-level splitting to prevent data leakage, explicit missingness tracking, and standardised temporal aggregation. SurvBench handles both single-risk (e.g., in-hospital mortality) and competing-risks scenarios (e.g., multiple discharge outcomes). The outputs are compatible with pycox library packages and implementations of standard statistical and deep learning models. By providing reproducible, configuration-driven preprocessing with comprehensive documentation, SurvBench addresses the "preprocessing gap" that has hindered fair comparison of deep learning survival models, enabling researchers to focus on methodological innovation rather than data engineering.

Munib Mesinovic, Peter Watkinson, Tingting Zhu

Machine learning applications for longitudinal electronic health records often forecast the risk of events at fixed time points, whereas survival analysis achieves dynamic risk prediction by estimating time-to-event distributions. Here, we propose a novel conditional variational autoencoder-based method, DySurv, which uses a combination of static and longitudinal measurements from electronic health records to estimate the individual risk of death dynamically. DySurv directly estimates the cumulative risk incidence function without making any parametric assumptions on the underlying stochastic process of the time-to-event. We evaluate DySurv on 6 time-to-event benchmark datasets in healthcare, as well as 2 real-world intensive care unit (ICU) electronic health records (EHR) datasets extracted from the eICU Collaborative Research (eICU) and the Medical Information Mart for Intensive Care database (MIMIC-IV). DySurv outperforms other existing statistical and deep learning approaches to time-to-event analysis across concordance and other metrics. It achieves time-dependent concordance of over 60% in the eICU case. It is also over 12% more accurate and 22% more sensitive than in-use ICU scores like Acute Physiology and Chronic Health Evaluation (APACHE) and Sequential Organ Failure Assessment (SOFA) scores. The predictive capacity of DySurv is consistent and the survival estimates remain disentangled across different datasets. Our interdisciplinary framework successfully incorporates deep learning, survival analysis, and intensive care to create a novel method for time-to-event prediction from longitudinal health records. We test our method on several held-out test sets from a variety of healthcare datasets and compare it to existing in-use clinical risk scoring benchmarks.

Munib Mesinovic, Max Buhlan, Tingting Zhu

Healthcare artificial intelligence systems routinely fail when deployed across institutions, with documented performance drops and perpetuation of discriminatory patterns embedded in historical data. This brittleness stems, in part, from learning statistical associations rather than causal mechanisms. Causal graph neural networks address this triple crisis of distribution shift, discrimination, and inscrutability by combining graph-based representations of biomedical data with causal inference principles to learn invariant mechanisms rather than spurious correlations. This Review examines methodological foundations spanning structural causal models, disentangled causal representation learning, and techniques for interventional prediction and counterfactual reasoning on graphs. We analyse applications demonstrating clinical value across psychiatric diagnosis through brain network analysis, cancer subtyping via multi-omics causal integration, continuous physiological monitoring with mechanistic interpretation, and drug recommendation correcting prescription bias. These advances establish foundations for patient-specific Causal Digital Twins, enabling in silico clinical experimentation, with integration of large language models for hypothesis generation and causal graph neural networks for mechanistic validation. Substantial barriers remain, including computational requirements precluding real-time deployment, validation challenges demanding multi-modal evidence triangulation beyond cross-validation, and risks of causal-washing where methods employ causal terminology without rigorous evidentiary support. We propose tiered frameworks distinguishing causally-inspired architectures from causally-validated discoveries and identify critical research priorities making causal rather than purely associational claims.

Munib Mesinovic, Soheila Molaei, Peter Watkinson et al.

Learning from longitudinal electronic health records is limited if it does not capture the temporal trajectories of the patient's state in a clinical setting. Graph models allow us to capture the hidden dependencies of the multivariate time-series when the graphs are constructed in a similar dynamic manner. Previous dynamic graph models require a pre-defined and/or static graph structure, which is unknown in most cases, or they only capture the spatial relations between the features. Furthermore in healthcare, the interpretability of the model is an essential requirement to build trust with clinicians. In addition to previously proposed attention mechanisms, there has not been an interpretable dynamic graph framework for data from multivariate electronic health records (EHRs). Here, we propose DynaGraph, an end-to-end interpretable contrastive graph model that learns the dynamics of multivariate time-series EHRs as part of optimisation. We validate our model in four real-world clinical datasets, ranging from primary care to secondary care settings with broad demographics, in challenging settings where tasks are imbalanced and multi-labelled. Compared to state-of-the-art models, DynaGraph achieves significant improvements in balanced accuracy and sensitivity over the nearest complex competitors in time-series or dynamic graph modelling across three ICU and one primary care datasets. Through a pseudo-attention approach to graph construction, our model also indicates the importance of clinical covariates over time, providing means for clinical validation.

Munib Mesinovic, Xin Ci Wong, Giri Shan Rajahram et al.

By September, 2022, more than 600 million cases of SARS-CoV-2 infection have been reported globally, resulting in over 6.5 million deaths. COVID-19 mortality risk estimators are often, however, developed with small unrepresentative samples and with methodological limitations. It is highly important to develop predictive tools for pulmonary embolism (PE) in COVID-19 patients as one of the most severe preventable complications of COVID-19. Using a dataset of more than 800,000 COVID-19 patients from an international cohort, we propose a cost-sensitive gradient-boosted machine learning model that predicts occurrence of PE and death at admission. Logistic regression, Cox proportional hazards models, and Shapley values were used to identify key predictors for PE and death. Our prediction model had a test AUROC of 75.9% and 74.2%, and sensitivities of 67.5% and 72.7% for PE and all-cause mortality respectively on a highly diverse and held-out test set. The PE prediction model was also evaluated on patients in UK and Spain separately with test results of 74.5% AUROC, 63.5% sensitivity and 78.9% AUROC, 95.7% sensitivity. Age, sex, region of admission, comorbidities (chronic cardiac and pulmonary disease, dementia, diabetes, hypertension, cancer, obesity, smoking), and symptoms (any, confusion, chest pain, fatigue, headache, fever, muscle or joint pain, shortness of breath) were the most important clinical predictors at admission. Our machine learning model developed from an international cohort can serve to better regulate hospital risk prioritisation of at-risk patients.

Munib Mesinovic, Peter Watkinson, Tingting Zhu

Heart attack remain one of the greatest contributors to mortality in the United States and globally. Patients admitted to the intensive care unit (ICU) with diagnosed heart attack (myocardial infarction or MI) are at higher risk of death. In this study, we use two retrospective cohorts extracted from the eICU and MIMIC-IV databases, to develop a novel pseudo-dynamic machine learning framework for mortality prediction in the ICU with interpretability and clinical risk analysis. The method provides accurate prediction for ICU patients up to 24 hours before the event and provide time-resolved interpretability results. The performance of the framework relying on extreme gradient boosting was evaluated on a held-out test set from eICU, and externally validated on the MIMIC-IV cohort using the most important features identified by time-resolved Shapley values achieving AUCs of 91.0 (balanced accuracy of 82.3) for 6-hour prediction of mortality respectively. We show that our framework successfully leverages time-series physiological measurements by translating them into stacked static prediction problems to be robustly predictive through time in the ICU stay and can offer clinical insight from time-resolved interpretability

Miroslav Fil, Munib Mesinovic, Matthew Morris et al.

$β$-VAE is a follow-up technique to variational autoencoders that proposes special weighting of the KL divergence term in the VAE loss to obtain disentangled representations. Unsupervised learning is known to be brittle even on toy datasets and a meaningful, mathematically precise definition of disentanglement remains difficult to find. Here we investigate the original $β$-VAE paper and add evidence to the results previously obtained indicating its lack of reproducibility. We also further expand the experimentation of the models and include further more complex datasets in the analysis. We also implement an FID scoring metric for the $β$-VAE model and conclude a qualitative analysis of the results obtained. We end with a brief discussion on possible future investigations that can be conducted to add more robustness to the claims.