Sagar Nagaraj Simha, Juliette Ortholand, Dave Dongelmans, Jessica D. Workum, Olivier W. M. Thijssens, Ameen Abu-Hanna, Giovanni Cinà
In this applied paper, we address the difficult open problem of when to discharge patients from the Intensive Care Unit. This can be conceived as an optimal stopping scenario with three added challenges: 1) the evaluation of a stopping strategy from observational data is itself a complex causal inference problem, 2) the composite objective is to minimize the length of intervention and maximize the outcome, but the two cannot be collapsed to a single dimension, and 3) the recording of variables stops when the intervention is discontinued. Our contributions are two-fold. First, we generalize the implementation of the g-formula Python package, providing a framework to evaluate stopping strategies for problems with the aforementioned structure, including positivity and coverage checks. Second, with a fully open-source pipeline, we apply this approach to MIMIC-IV, a public ICU dataset, demonstrating the potential for strategies that improve upon current care.
Miguel Rios, Ameen Abu-Hanna
Neural models, with their ability to provide novel representations, have shown promising results in prediction tasks in healthcare. However, patient demographics, medical technology, and quality of care change over time. This often leads to drop in the performance of neural models for prospective patients, especially in terms of their calibration. The deep kernel learning (DKL) framework may be robust to such changes as it combines neural models with Gaussian processes, which are aware of prediction uncertainty. Our hypothesis is that out-of-distribution test points will result in probabilities closer to the global mean and hence prevent overconfident predictions. This in turn, we hypothesise, will result in better calibration on prospective data. This paper investigates DKL's behaviour when facing a temporal shift, which was naturally introduced when an information system that feeds a cohort database was changed. We compare DKL's performance to that of a neural baseline based on recurrent neural networks. We show that DKL indeed produced superior calibrated predictions. We also confirm that the DKL's predictions were indeed less sharp. In addition, DKL's discrimination ability was even improved: its AUC was 0.746 (+- 0.014 std), compared to 0.739 (+- 0.028 std) for the baseline. The paper demonstrated the importance of including uncertainty in neural computing, especially for their prospective use.
Vittorio Torri, Machteld J. Boonstra, Marielle C. van de Veerdonk, Deborah N. Kalkman, Alicia Uijl, Francesca Ieva, Ameen Abu-Hanna, Folkert W. Asselbergs, Iacer Calixto
Objective: Heart failure (HF) patients present with diverse phenotypes affecting treatment and prognosis. This study evaluates models for phenotyping HF patients based on left ventricular ejection fraction (LVEF) classes, using structured and unstructured data, assessing performance and interpretability. Materials and Methods: The study analyzes all HF hospitalizations at both Amsterdam UMC hospitals (AMC and VUmc) from 2015 to 2023 (33,105 hospitalizations, 16,334 patients). Data from AMC were used for model training, and from VUmc for external validation. The dataset was unlabelled and included tabular clinical measurements and discharge letters. Silver labels for LVEF classes were generated by combining diagnosis codes, echocardiography results, and textual mentions. Gold labels were manually annotated for 300 patients for testing. Multiple Transformer-based (black-box) and Aug-Linear (white-box) models were trained and compared with baselines on structured and unstructured data. To evaluate interpretability, two clinicians annotated 20 discharge letters by highlighting information they considered relevant for LVEF classification. These were compared to SHAP and LIME explanations from black-box models and the inherent explanations of Aug-Linear models. Results: BERT-based and Aug-Linear models, using discharge letters alone, achieved the highest classification results (AUC=0.84 for BERT, 0.81 for Aug-Linear on external validation), outperforming baselines. Aug-Linear explanations aligned more closely with clinicians' explanations than post-hoc explanations on black-box models. Conclusions: Discharge letters emerged as the most informative source for phenotyping HF patients. Aug-Linear models matched black-box performance while providing clinician-aligned interpretability, supporting their use in transparent clinical decision-making.
Tsvetan R. Yordanov, Ameen Abu-Hanna, Anita CJ Ravelli, Iacopo Vagliano
Availability of diagnostic codes in Electronic Health Records (EHRs) is crucial for patient care as well as reimbursement purposes. However, entering them in the EHR is tedious, and some clinical codes may be overlooked. Given an in-complete list of clinical codes, we investigate the performance of ML methods on predicting the complete ones, and assess the added predictive value of including other clinical patient data in this task. We used the MIMIC-III dataset and frame the task of completing the clinical codes as a recommendation problem. We con-sider various autoencoder approaches plus two strong baselines; item co-occurrence and Singular Value Decomposition (SVD). Inputs are 1) a record's known clinical codes, 2) the codes plus variables. The co-occurrence-based ap-proach performed slightly better (F1 score=0.26, Mean Average Precision [MAP]=0.19) than the SVD (F1=0.24, MAP=0.18). However, the adversarial autoencoder achieved the best performance when using the codes plus variables (F1=0.32, MAP=0.25). Adversarial autoencoders performed best in terms of F1 and were equal to vanilla and denoising autoencoders in term of MAP. Using clinical variables in addition to the incomplete codes list, improves the predictive performance of the models.
Auke Elfrink, Iacopo Vagliano, Ameen Abu-Hanna, Iacer Calixto
We investigate different natural language processing (NLP) approaches based on contextualised word representations for the problem of early prediction of lung cancer using free-text patient medical notes of Dutch primary care physicians. Because lung cancer has a low prevalence in primary care, we also address the problem of classification under highly imbalanced classes. Specifically, we use large Transformer-based pretrained language models (PLMs) and investigate: 1) how \textit{soft prompt-tuning} -- an NLP technique used to adapt PLMs using small amounts of training data -- compares to standard model fine-tuning; 2) whether simpler static word embedding models (WEMs) can be more robust compared to PLMs in highly imbalanced settings; and 3) how models fare when trained on notes from a small number of patients. We find that 1) soft-prompt tuning is an efficient alternative to standard model fine-tuning; 2) PLMs show better discrimination but worse calibration compared to simpler static word embedding models as the classification problem becomes more imbalanced; and 3) results when training models on small number of patients are mixed and show no clear differences between PLMs and WEMs. All our code is available open source in \url{https://bitbucket.org/aumc-kik/prompt_tuning_cancer_prediction/}.
Mohammad Azizmalayeri, Ameen Abu-Hanna, Giovanni Ciná
Despite their success, Machine Learning (ML) models do not generalize effectively to data not originating from the training distribution. To reliably employ ML models in real-world healthcare systems and avoid inaccurate predictions on out-of-distribution (OOD) data, it is crucial to detect OOD samples. Numerous OOD detection approaches have been suggested in other fields - especially in computer vision - but it remains unclear whether the challenge is resolved when dealing with medical tabular data. To answer this pressing need, we propose an extensive reproducible benchmark to compare different methods across a suite of tests including both near and far OODs. Our benchmark leverages the latest versions of eICU and MIMIC-IV, two public datasets encompassing tens of thousands of ICU patients in several hospitals. We consider a wide array of density-based methods and SOTA post-hoc detectors across diverse predictive architectures, including MLP, ResNet, and Transformer. Our findings show that i) the problem appears to be solved for far-OODs, but remains open for near-OODs; ii) post-hoc methods alone perform poorly, but improve substantially when coupled with distance-based mechanisms; iii) the transformer architecture is far less overconfident compared to MLP and ResNet.
Miguel Rios, Ameen Abu-Hanna
Intensive Care in-hospital mortality prediction has various clinical applications. Neural prediction models, especially when capitalising on clinical notes, have been put forward as improvement on currently existing models. However, to be acceptable these models should be performant and transparent. This work studies different attention mechanisms for clinical neural prediction models in terms of their discrimination and calibration. Specifically, we investigate sparse attention as an alternative to dense attention weights in the task of in-hospital mortality prediction from clinical notes. We evaluate the attention mechanisms based on: i) local self-attention over words in a sentence, and ii) global self-attention with a transformer architecture across sentences. We demonstrate that the sparse mechanism approach outperforms the dense one for the local self-attention in terms of predictive performance with a publicly available dataset, and puts higher attention to prespecified relevant directive words. The performance at the sentence level, however, deteriorates as sentences including the influential directive words tend to be dropped all together.
Nishant Mishra, Gaurav Sahu, Iacer Calixto, Ameen Abu-Hanna, Issam H. Laradji
Generating high-quality summaries for chat dialogs often requires large labeled datasets. We propose a method to efficiently use unlabeled data for extractive summarization of customer-agent dialogs. In our method, we frame summarization as a question-answering problem and use state-of-the-art large language models (LLMs) to generate pseudo-labels for a dialog. We then use these pseudo-labels to fine-tune a chat summarization model, effectively transferring knowledge from the large LLM into a smaller specialized model. We demonstrate our method on the \tweetsumm dataset, and show that using 10% of the original labelled data set we can achieve 65.9/57.0/61.0 ROUGE-1/-2/-L, whereas the current state-of-the-art trained on the entire training data set obtains 65.16/55.81/64.37 ROUGE-1/-2/-L. In other words, in the worst case (i.e., ROUGE-L) we still effectively retain 94.7% of the performance while using only 10% of the data.
Rachel M. Murphy, Nishant Mishra, Nicolette F. de Keizer, Dave A. Dongelmans, Kitty J. Jager, Ameen Abu-Hanna, Joanna E. Klopotowska, Iacer Calixto
In this study, we establish a benchmark for adverse drug event (ADE) detection in Dutch clinical free-text documents using several transformer models, clinical scenarios, and fit-for-purpose performance measures. We trained a Bidirectional Long Short-Term Memory (Bi-LSTM) model and four transformer-based Dutch and/or multilingual encoder models (BERTje, RobBERT, MedRoBERTa(.)nl, and NuNER) for the tasks of named entity recognition (NER) and relation classification (RC) using 102 richly annotated Dutch ICU clinical progress notes. Anonymized free-text clinical progress notes of patients admitted to the intensive care unit (ICU) of one academic hospital and discharge letters of patients admitted to Internal Medicine wards of two non-academic hospitals were reused. We evaluated our ADE RC models internally using the gold standard (two-step task) and predicted entities (end-to-end task). In addition, all models were externally validated for detecting ADEs at the document level. We report both micro- and macro-averaged F1 scores, given the dataset imbalance in ADEs. Although differences for the ADE RC task between the models were small, MedRoBERTa(.)nl was the best performing model with a macro-averaged F1 score of 0.63 using the gold standard and 0.62 using predicted entities. The MedRoBERTa(.)nl models also performed the best in our external validation and achieved a recall of between 0.67 to 0.74 using predicted entities, meaning between 67 to 74% of discharge letters with ADEs were detected. Our benchmark study presents a robust and clinically meaningful approach for evaluating language models for ADE detection in clinical free-text documents. Our study highlights the need to use appropriate performance measures fit for the task of ADE detection in clinical free-text documents and envisioned future clinical use.
Mohammad Azizmalayeri, Ameen Abu-Hanna, Giovanni Cinà
Detecting out-of-distribution (OOD) instances is crucial for the reliable deployment of machine learning models in real-world scenarios. OOD inputs are commonly expected to cause a more uncertain prediction in the primary task; however, there are OOD cases for which the model returns a highly confident prediction. This phenomenon, denoted as "overconfidence", presents a challenge to OOD detection. Specifically, theoretical evidence indicates that overconfidence is an intrinsic property of certain neural network architectures, leading to poor OOD detection. In this work, we address this issue by measuring extreme activation values in the penultimate layer of neural networks and then leverage this proxy of overconfidence to improve on several OOD detection baselines. We test our method on a wide array of experiments spanning synthetic data and real-world data, tabular and image datasets, multiple architectures such as ResNet and Transformer, different training loss functions, and include the scenarios examined in previous theoretical work. Compared to the baselines, our method often grants substantial improvements, with double-digit increases in OOD detection AUC, and it does not damage performance in any scenario.
Izak Yasrebi-de Kom, Joanna Klopotowska, Dave Dongelmans, Nicolette De Keizer, Kitty Jager, Ameen Abu-Hanna, Giovanni Cinà
The current best practice approach for the retrospective diagnosis of adverse drug events (ADEs) in hospitalized patients relies on a full patient chart review and a formal causality assessment by multiple medical experts. This evaluation serves to qualitatively estimate the probability of causation (PC); the probability that a drug was a necessary cause of an adverse event. This practice is manual, resource intensive and prone to human biases, and may thus benefit from data-driven decision support. Here, we pioneer a causal modeling approach using observational data to estimate a lower bound of the PC (PC$_{low}$). This method includes two key causal inference components: (1) the target trial emulation framework and (2) estimation of individualized treatment effects using machine learning. We apply our method to the clinically relevant use-case of vancomycin-induced acute kidney injury in intensive care patients, and compare our causal model-based PC$_{low}$ estimates to qualitative estimates of the PC provided by a medical expert. Important limitations and potential improvements are discussed, and we conclude that future improved causal models could provide essential data-driven support for medication safety monitoring in hospitalized patients.
Michele Miranda, Xinlan Yan, Nishant Mishra, Rachel Murphy, Ameen Abu-Hanna, Sébastien Bratières, Iacer Calixto
Protecting patient privacy in clinical narratives is essential for enabling secondary use of healthcare data under regulations such as GDPR and HIPAA. While manual de-identification remains the gold standard, it is costly and slow, motivating the need for automated methods that combine privacy guarantees with high utility. Most automated text de-identification pipelines employed named entity recognition (NER) to identify protected entities for redaction. Although methods based on differential privacy (DP) provide formal privacy guarantees, more recently also large language models (LLMs) are increasingly used for text de-identification in the clinical domain. In this work, we present the first comparative study of DP, NER, and LLMs for Dutch clinical text de-identification. We investigate these methods separately as well as hybrid strategies that apply NER or LLM preprocessing prior to DP, and assess performance in terms of privacy leakage and extrinsic evaluation (entity and relation classification). We show that DP mechanisms alone degrade utility substantially, but combining them with linguistic preprocessing, especially LLM-based redaction, significantly improves the privacy-utility trade-off.