Antibiotic resistance is one of the major global threats to human health and occurs when antibiotics lose their ability to combat bacterial infections. In this problem, a clinical decision support system could use phenotypes in order to alert clinicians of the emergence of patterns of antibiotic resistance in patients. Patient phenotyping is the task of finding a set of patient characteristics related to a specific medical problem such as the one described in this work. However, a single explanation of a medical phenomenon might be useless in the eyes of a clinical expert and be discarded. The discovery of multiple patient phenotypes for the same medical phenomenon would be useful in such cases. Therefore, in this work, we define the problem of mining diverse top-k phenotypes and propose the EDSLM algorithm, which is based on the Subgroup Discovery technique, the subgroup list model, and the Minimum Description Length principle. Our proposal provides clinicians with a method with which to obtain multiple and diverse phenotypes of a set of patients. We show a real use case of phenotyping in antimicrobial resistance using the well-known MIMIC-III dataset.
Catheter ablation of Atrial Fibrillation (AF) consists of a one-size-fits-all treatment with limited success in persistent AF. This may be due to our inability to map the dynamics of AF with the limited resolution and coverage provided by sequential contact mapping catheters, preventing effective patient phenotyping for personalised, targeted ablation. Here we introduce FibMap, a graph recurrent neural network model that reconstructs global AF dynamics from sparse measurements. Trained and validated on 51 non-contact whole atria recordings, FibMap reconstructs whole atria dynamics from 10% surface coverage, achieving a 210% lower mean absolute error and an order of magnitude higher performance in tracking phase singularities compared to baseline methods. Clinical utility of FibMap is demonstrated on real-world contact mapping recordings, achieving reconstruction fidelity comparable to non-contact mapping. FibMap's state-spaces and patient-specific parameters offer insights for electrophenotyping AF. Integrating FibMap into clinical practice could enable personalised AF care and improve outcomes.
Developing an integrated many-to-many framework leveraging multimodal data for multiple tasks is crucial to unifying healthcare applications ranging from diagnoses to operations. In resource-constrained hospital environments, a scalable and unified machine learning framework that improves previous forecast performances could improve hospital operations and save costs. We introduce M3H, an explainable Multimodal Multitask Machine Learning for Healthcare framework that consolidates learning from tabular, time-series, language, and vision data for supervised binary/multiclass classification, regression, and unsupervised clustering. It features a novel attention mechanism balancing self-exploitation (learning source-task), and cross-exploration (learning cross-tasks), and offers explainability through a proposed TIM score, shedding light on the dynamics of task learning interdependencies. M3H encompasses an unprecedented range of medical tasks and machine learning problem classes and consistently outperforms traditional single-task models by on average 11.6% across 40 disease diagnoses from 16 medical departments, three hospital operation forecasts, and one patient phenotyping task. The modular design of the framework ensures its generalizability in data processing, task definition, and rapid model prototyping, making it production ready for both clinical and operational healthcare settings, especially those in constrained environments.
In Intensive Care Units (ICU), the abundance of multivariate time series presents an opportunity for machine learning (ML) to enhance patient phenotyping. In contrast to previous research focused on electronic health records (EHR), here we propose an ML approach for phenotyping using routinely collected physiological time series data. Our new algorithm integrates Long Short-Term Memory (LSTM) networks with collaborative filtering concepts to identify common physiological states across patients. Tested on real-world ICU clinical data for intracranial hypertension (IH) detection in patients with brain injury, our method achieved an area under the curve (AUC) of 0.889 and average precision (AP) of 0.725. Moreover, our algorithm outperforms autoencoders in learning more structured latent representations of the physiological signals. These findings highlight the promise of our methodology for patient phenotyping, leveraging routinely collected multivariate time series to improve clinical care practices.
Sickle Cell Disease (SCD) is a chronic genetic disorder characterized by recurrent acute painful episodes. Opioids are often used to manage these painful episodes; the extent of their use in managing pain in this disorder is an issue of debate. The risk of addiction and side effects of these opioid treatments can often lead to more pain episodes in the future. Hence, it is crucial to forecast future patient pain trajectories to help patients manage their SCD to improve their quality of life without compromising their treatment. It is challenging to obtain many pain records to design forecasting models since it is mainly recorded by patients' self-report. Therefore, it is expensive and painful (due to the need for patient compliance) to solve pain forecasting problems in a purely supervised manner. In light of this challenge, we propose to solve the pain forecasting problem using self-supervised learning methods. Also, clustering such time-series data is crucial for patient phenotyping, anticipating patients' prognoses by identifying "similar" patients, and designing treatment guidelines tailored to homogeneous patient subgroups. Hence, we propose a self-supervised learning approach for clustering time-series data, where each cluster comprises patients who share similar future pain profiles. Experiments on five years of real-world datasets show that our models achieve superior performance over state-of-the-art benchmarks and identify meaningful clusters that can be translated into actionable information for clinical decision-making.
Objective For the UK Biobank standardized phenotype codes are associated with patients who have been hospitalized but are missing for many patients who have been treated exclusively in an outpatient setting. We describe a method for phenotype recognition that imputes phenotype codes for all UK Biobank participants. Materials and Methods POPDx (Population-based Objective Phenotyping by Deep Extrapolation) is a bilinear machine learning framework for simultaneously estimating the probabilities of 1,538 phenotype codes. We extracted phenotypic and health-related information of 392,246 individuals from the UK Biobank for POPDx development and evaluation. A total of 12,803 ICD-10 diagnosis codes of the patients were converted to 1,538 Phecodes as gold standard labels. The POPDx framework was evaluated and compared to other available methods on automated multi-phenotype recognition. Results POPDx can predict phenotypes that are rare or even unobserved in training. We demonstrate substantial improvement of automated multi-phenotype recognition across 22 disease categories, and its application in identifying key epidemiological features associated with each phenotype. Conclusions POPDx helps provide well-defined cohorts for downstream studies. It is a general purpose method that can be applied to other biobanks with diverse but incomplete data.
The recent success of machine learning methods applied to time series collected from Intensive Care Units (ICU) exposes the lack of standardized machine learning benchmarks for developing and comparing such methods. While raw datasets, such as MIMIC-IV or eICU, can be freely accessed on Physionet, the choice of tasks and pre-processing is often chosen ad-hoc for each publication, limiting comparability across publications. In this work, we aim to improve this situation by providing a benchmark covering a large spectrum of ICU-related tasks. Using the HiRID dataset, we define multiple clinically relevant tasks in collaboration with clinicians. In addition, we provide a reproducible end-to-end pipeline to construct both data and labels. Finally, we provide an in-depth analysis of current state-of-the-art sequence modeling methods, highlighting some limitations of deep learning approaches for this type of data. With this benchmark, we hope to give the research community the possibility of a fair comparison of their work.
The healthcare domain is characterized by heterogeneous data modalities, such as imaging and physiological data. In practice, the variety of medical data assists clinicians in decision-making. However, most of the current state-of-the-art deep learning models solely rely upon carefully curated data of a single modality. In this paper, we propose a dynamic training approach to learn modality-specific data representations and to integrate auxiliary features, instead of solely relying on a single modality. Our preliminary experiments results for a patient phenotyping task using physiological data in MIMIC-IV & chest radiographs in the MIMIC- CXR dataset show that our proposed approach achieves the highest area under the receiver operating characteristic curve (AUROC) (0.764 AUROC) compared to the performance of the benchmark method in previous work, which only used physiological data (0.740 AUROC). For a set of five recurring or chronic diseases with periodic acute episodes, including cardiac dysrhythmia, conduction disorders, and congestive heart failure, the AUROC improves from 0.747 to 0.798. This illustrates the benefit of leveraging the chest imaging modality in the phenotyping task and highlights the potential of multi-modal learning in medical applications.
Due to the wider availability of modern electronic health records, patient care data is often being stored in the form of time-series. Clustering such time-series data is crucial for patient phenotyping, anticipating patients' prognoses by identifying "similar" patients, and designing treatment guidelines that are tailored to homogeneous patient subgroups. In this paper, we develop a deep learning approach for clustering time-series data, where each cluster comprises patients who share similar future outcomes of interest (e.g., adverse events, the onset of comorbidities). To encourage each cluster to have homogeneous future outcomes, the clustering is carried out by learning discrete representations that best describe the future outcome distribution based on novel loss functions. Experiments on two real-world datasets show that our model achieves superior clustering performance over state-of-the-art benchmarks and identifies meaningful clusters that can be translated into actionable information for clinical decision-making.
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.
Progress of machine learning in critical care has been difficult to track, in part due to absence of public benchmarks. Other fields of research (such as computer vision and natural language processing) have established various competitions and public benchmarks. Recent availability of large clinical datasets has enabled the possibility of establishing public benchmarks. Taking advantage of this opportunity, we propose a public benchmark suite to address four areas of critical care, namely mortality prediction, estimation of length of stay, patient phenotyping and risk of decompensation. We define each task and compare the performance of both clinical models as well as baseline and deep learning models using eICU critical care dataset of around 73,000 patients. This is the first public benchmark on a multi-centre critical care dataset, comparing the performance of clinical gold standard with our predictive model. We also investigate the impact of numerical variables as well as handling of categorical variables on each of the defined tasks. The source code, detailing our methods and experiments is publicly available such that anyone can replicate our results and build upon our work.
Visual summarization of clinical data collected on patients contained within the electronic health record (EHR) may enable precise and rapid triage at the time of patient presentation to an emergency department (ED). The triage process is critical in the appropriate allocation of resources and in anticipating eventual patient disposition, typically admission to the hospital or discharge home. EHR data are high-dimensional and complex, but offer the opportunity to discover and characterize underlying data-driven patient phenotypes. These phenotypes will enable improved, personalized therapeutic decision making and prognostication. In this work, we focus on the challenge of two-dimensional patient projections. A low dimensional embedding offers visual interpretability lost in higher dimensions. While linear dimensionality reduction techniques such as principal component analysis are often used towards this aim, they are insufficient to describe the variance of patient data. In this work, we employ the newly-described non-linear embedding technique called uniform manifold approximation and projection (UMAP). UMAP seeks to capture both local and global structures in high-dimensional data. We then use Gaussian mixture models to identify clusters in the embedded data and use the adjusted Rand index (ARI) to establish stability in the discovery of these clusters. This technique is applied to five common clinical chief complaints from a real-world ED EHR dataset, describing the emergent properties of discovered clusters. We observe clinically-relevant cluster attributes, suggesting that visual embeddings of EHR data using non-linear dimensionality reduction is a promising approach to reveal data-driven patient phenotypes. In the five chief complaints, we find between 2 and 6 clusters, with the peak mean pairwise ARI between subsequent training iterations to range from 0.35 to 0.74.
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.