Intermediate Respiratory Care Units (IRCUs) are vital during crises like COVID-19. This study evaluated clinical outcomes and operational dynamics of a new Spanish IRCU with specialized staffing. A prospective cohort study (April-August 2021) included 249 adult patients with COVID-19 respiratory failure (UHVN IRCU, Granada). Data on demographics, Non-Invasive Ventilation (NIV), length of stay (LOS), and outcomes (ICU transfer, exitus, recovery) were analyzed. Patient flow was simulated using a data-calibrated deterministic compartmental model (Ordinary Differential Equations, ODEs) that represented state transitions, and an empirical LOS-based stochastic convolution model that incorporated admission variability. The median age was 51; 31% of patients required NIV. NIV patients were older (median 61 vs 42, p<0.001). Overall, 8% needed ICU transfer; 3% experienced in-IRCU exitus. Notably, no ICU transfers or deaths occurred among 172 non-NIV patients. Of 77 high-risk NIV patients, 68% recovered in IRCU without ICU escalation. The ODE model, based on transition rates between patient states, reflected aggregate outcomes. Both modeling approaches demonstrated system strain during admission surges (partially mitigated by simulated care efficiency improvements via parameter modulation) and yielded consistent peak occupancy estimates. This IRCU, with specialized staffing, effectively managed severe COVID-19. High recovery rates, especially for NIV patients, potentially eased ICU pressure. Dynamic modeling confirmed surge vulnerability but highlighted the benefits of care efficiency from modulated transition parameters. Findings underscore positive outcomes in this IRCU model and support such units in pandemic response.
Computational phenotyping is essential for biomedical research but often requires significant time and resources, especially since traditional methods typically involve extensive manual data review. While machine learning and natural language processing advancements have helped, further improvements are needed. Few studies have explored using Large Language Models (LLMs) for these tasks despite known advantages of LLMs for text-based tasks. To facilitate further research in this area, we developed an evaluation framework, Evaluation of PHEnotyping for Observational Health Data (PHEONA), that outlines context-specific considerations. We applied and demonstrated PHEONA on concept classification, a specific task within a broader phenotyping process for Acute Respiratory Failure (ARF) respiratory support therapies. From the sample concepts tested, we achieved high classification accuracy, suggesting the potential for LLM-based methods to improve computational phenotyping processes.
Predicting medical events in advance within critical care settings is paramount for patient outcomes and resource management. Utilizing predictive models, healthcare providers can anticipate issues such as cardiac arrest, sepsis, or respiratory failure before they manifest. Recently, there has been a surge in research focusing on forecasting adverse medical event onsets prior to clinical manifestation using machine learning. However, while these models provide temporal prognostic predictions for the occurrence of a specific adverse event of interest within defined time intervals, their interpretability often remains a challenge. In this work, we explore the applicability of neural temporal point processes in the context of adverse event onset prediction, with the aim of explaining clinical pathways and providing interpretable insights. Our experiments span six state-of-the-art neural point processes and six critical care datasets, each focusing on the onset of distinct adverse events. This work represents a novel application class of neural temporal point processes in event prediction.
Cardiopulmonary resuscitation (CPR) is a critical, life-saving intervention aimed at restoring blood circulation and breathing in individuals experiencing cardiac arrest or respiratory failure. Accurate and real-time analysis of biomedical signals during CPR is essential for monitoring and decision-making, from the pre-hospital stage to the intensive care unit (ICU). However, CPR signals are often corrupted by noise and artifacts, making precise interpretation challenging. Traditional denoising methods, such as filters, struggle to adapt to the varying and complex noise patterns present in CPR signals. Given the high-stakes nature of CPR, where rapid and accurate responses can determine survival, there is a pressing need for more robust and adaptive denoising techniques. In this context, an unsupervised machine learning (ML) methodology is particularly valuable, as it removes the dependence on labeled data, which can be scarce or impractical in emergency scenarios. This paper introduces a novel unsupervised ML approach for denoising CPR signals using a multi-modality framework, which leverages multiple signal sources to enhance the denoising process. The proposed approach not only improves noise reduction and signal fidelity but also preserves critical inter-signal correlations (0.9993) which is crucial for downstream tasks. Furthermore, it outperforms existing methods in an unsupervised context in terms of signal-to-noise ratio (SNR) and peak signal-to-noise ratio (PSNR), making it highly effective for real-time applications. The integration of multi-modality further enhances the system's adaptability to various biomedical signals beyond CPR, improving both automated CPR systems and clinical decision-making.
Intensive Care Units (ICUs) provide critical care and life support for most severely ill and injured patients in the hospital. With the need for ICUs growing rapidly and unprecedentedly, especially during COVID-19, accurately identifying the most critical patients helps hospitals to allocate resources more efficiently and save more lives. The Predicting Intensive Care Transfers and Other Unforeseen Events (PICTURE) model predicts patient deterioration by separating those at high risk for imminent intensive care unit transfer, respiratory failure, or death from those at lower risk. This study aims to implement a deep learning model to benchmark the performance from the XGBoost model, an existing model which has competitive results on prediction.
Acute respiratory distress syndrome (ARDS) is a severe condition characterized by lung inflammation and respiratory failure, with a high mortality rate of approximately 40%. Traditional imaging methods, such as chest X-rays, provide only two-dimensional views, limiting their effectiveness in fully assessing lung pathology. Three-dimensional (3D) computed tomography (CT) offers a more comprehensive visualization, enabling detailed analysis of lung aeration, atelectasis, and the effects of therapeutic interventions. However, the routine use of CT in ARDS management is constrained by practical challenges and risks associated with transporting critically ill patients to remote scanners. In this study, we synthesize high-fidelity 3D lung CT from 2D generated X-ray images with associated physiological parameters using a score-based 3D residual diffusion model. Our preliminary results demonstrate that this approach can produce high-quality 3D CT images that are validated with ground truth, offering a promising solution for enhancing ARDS management.
Sepsis-induced acute respiratory failure (ARF) is a serious complication with a poor prognosis. This paper presents a deep representation learningbased phenotyping method to identify distinct groups of clinical trajectories of septic patients with ARF. For this retrospective study, we created a dataset from electronic medical records (EMR) consisting of data from sepsis patients admitted to medical intensive care units who required at least 24 hours of invasive mechanical ventilation at a quarternary care academic hospital in southeast USA for the years 2016-2021. A total of N=3349 patient encounters were included in this study. Clustering Representation Learning on Incomplete Time Series Data (CRLI) algorithm was applied to a parsimonious set of EMR variables in this data set. To validate the optimal number of clusters, the K-means algorithm was used in conjunction with dynamic time warping. Our model yielded four distinct patient phenotypes that were characterized as liver dysfunction/heterogeneous, hypercapnia, hypoxemia, and multiple organ dysfunction syndrome by a critical care expert. A Kaplan-Meier analysis to compare the 28-day mortality trends exhibited significant differences (p < 0.005) between the four phenotypes. The study demonstrates the utility of our deep representation learning-based approach in unraveling phenotypes that reflect the heterogeneity in sepsis-induced ARF in terms of different mortality outcomes and severity. These phenotypes might reveal important clinical insights into an effective prognosis and tailored treatment strategies.
Noisy training labels can hurt model performance. Most approaches that aim to address label noise assume label noise is independent from the input features. In practice, however, label noise is often feature or \textit{instance-dependent}, and therefore biased (i.e., some instances are more likely to be mislabeled than others). E.g., in clinical care, female patients are more likely to be under-diagnosed for cardiovascular disease compared to male patients. Approaches that ignore this dependence can produce models with poor discriminative performance, and in many healthcare settings, can exacerbate issues around health disparities. In light of these limitations, we propose a two-stage approach to learn in the presence instance-dependent label noise. Our approach utilizes \textit{\anchor points}, a small subset of data for which we know the observed and ground truth labels. On several tasks, our approach leads to consistent improvements over the state-of-the-art in discriminative performance (AUROC) while mitigating bias (area under the equalized odds curve, AUEOC). For example, when predicting acute respiratory failure onset on the MIMIC-III dataset, our approach achieves a harmonic mean (AUROC and AUEOC) of 0.84 (SD [standard deviation] 0.01) while that of the next best baseline is 0.81 (SD 0.01). Overall, our approach improves accuracy while mitigating potential bias compared to existing approaches in the presence of instance-dependent label noise.
Determining clinically relevant physiological states from multivariate time series data with missing values is essential for providing appropriate treatment for acute conditions such as Traumatic Brain Injury (TBI), respiratory failure, and heart failure. Utilizing non-temporal clustering or data imputation and aggregation techniques may lead to loss of valuable information and biased analyses. In our study, we apply the SLAC-Time algorithm, an innovative self-supervision-based approach that maintains data integrity by avoiding imputation or aggregation, offering a more useful representation of acute patient states. By using SLAC-Time to cluster data in a large research dataset, we identified three distinct TBI physiological states and their specific feature profiles. We employed various clustering evaluation metrics and incorporated input from a clinical domain expert to validate and interpret the identified physiological states. Further, we discovered how specific clinical events and interventions can influence patient states and state transitions.
Annually 8500 neonatal deaths are reported in the US due to respiratory failure. Recently, Lung Ultrasound (LUS), due to its radiation free nature, portability, and being cheaper is gaining wide acceptability as a diagnostic tool for lung conditions. However, lack of highly trained medical professionals has limited its use especially in remote areas. To address this, an automated screening system that captures characteristics of the LUS patterns can be of significant assistance to clinicians who are not experts in lung ultrasound (LUS) images. In this paper, we propose a feature extraction method designed to quantify the spatially-localized line patterns and texture patterns found in LUS images. Using the dual-tree complex wavelet transform (DTCWT) and four types of common image features we propose a method to classify the LUS images into 6 common neonatal lung conditions. These conditions are normal lung, pneumothorax (PTX), transient tachypnea of the newborn (TTN), respiratory distress syndrome (RDS), chronic lung disease (CLD) and consolidation (CON) that could be pneumonia or atelectasis. The proposed method using DTCWT decomposition extracted global statistical, grey-level co-occurrence matrix (GLCM), grey-level run length matrix (GLRLM) and linear binary pattern (LBP) features to be fed to a linear discriminative analysis (LDA) based classifier. Using 15 best DTCWT features along with 3 clinical features the proposed approach achieved a per-image classification accuracy of 92.78% with a balanced dataset containing 720 images from 24 patients and 74.39% with the larger unbalanced dataset containing 1550 images from 42 patients. Likewise, the proposed method achieved a maximum per-subject classification accuracy of 81.53% with 43 DTCWT features and 3 clinical features using the balanced dataset and 64.97% with 13 DTCWT features and 3 clinical features using the unbalanced dataset.
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 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 acute respiratory distress syndrome (ARDS) is a severe form of hypoxemic respiratory failure with in-hospital mortality of 35-46%. High mortality is thought to be related in part to challenges in making a prompt diagnosis, which may in turn delay implementation of evidence-based therapies. A deep neural network (DNN) algorithm utilizing unbiased ventilator waveform data (VWD) may help to improve screening for ARDS. We first show that a convolutional neural network-based ARDS detection model can outperform prior work with random forest models in AUC (0.95+/-0.019 vs. 0.88+/-0.064), accuracy (0.84+/-0.026 vs 0.80+/-0.078), and specificity (0.81+/-0.06 vs 0.71+/-0.089). Frequency ablation studies imply that our model can learn features from low frequency domains typically used for expert feature engineering, and high-frequency information that may be difficult to manually featurize. Further experiments suggest that subtle, high-frequency components of physiologic signals may explain the superior performance of DL models over traditional ML when using physiologic waveform data. Our observations may enable improved interpretability of DL-based physiologic models and may improve the understanding of how high-frequency information in physiologic data impacts the performance our DL model.
Respiratory failure is the one of major causes of death in critical care unit. During the outbreak of COVID-19, critical care units experienced an extreme shortage of mechanical ventilation because of respiratory failure related syndromes. To help this, the early mortality risk prediction in patients who suffer respiratory failure can provide timely support for clinical treatment and resource management. In the study, we propose a dynamic modeling approach for early mortality risk prediction of the respiratory failure patients based on the first 24 hours ICU physiological data. Our proposed model is validated on the eICU collaborate database. We achieved a high AUROC performance (80-83%) and significantly improved AUCPR 4% on Day 5 since ICU admission, compared to the state-of-art prediction models. In addition, we illustrated that the survival curve includes the time-varying information for the early ICU admission survival analysis.
Objective: When patients develop acute respiratory failure, accurately identifying the underlying etiology is essential for determining the best treatment. However, differentiating between common medical diagnoses can be challenging in clinical practice. Machine learning models could improve medical diagnosis by aiding in the diagnostic evaluation of these patients. Materials and Methods: Machine learning models were trained to predict the common causes of acute respiratory failure (pneumonia, heart failure, and/or COPD). Models were trained using chest radiographs and clinical data from the electronic health record (EHR) and applied to an internal and external cohort. Results: The internal cohort of 1,618 patients included 508 (31%) with pneumonia, 363 (22%) with heart failure, and 137 (8%) with COPD based on physician chart review. A model combining chest radiographs and EHR data outperformed models based on each modality alone. Models had similar or better performance compared to a randomly selected physician reviewer. For pneumonia, the combined model area under the receiver operating characteristic curve (AUROC) was 0.79 (0.77-0.79), image model AUROC was 0.74 (0.72-0.75), and EHR model AUROC was 0.74 (0.70-0.76). For heart failure, combined: 0.83 (0.77-0.84), image: 0.80 (0.71-0.81), and EHR: 0.79 (0.75-0.82). For COPD, combined: AUROC = 0.88 (0.83-0.91), image: 0.83 (0.77-0.89), and EHR: 0.80 (0.76-0.84). In the external cohort, performance was consistent for heart failure and increased for COPD, but declined slightly for pneumonia. Conclusions: Machine learning models combining chest radiographs and EHR data can accurately differentiate between common causes of acute respiratory failure. Further work is needed to determine how these models could act as a diagnostic aid to clinicians in clinical settings.
The development of respiratory failure is common among patients in intensive care units (ICU). Large data quantities from ICU patient monitoring systems make timely and comprehensive analysis by clinicians difficult but are ideal for automatic processing by machine learning algorithms. Early prediction of respiratory system failure could alert clinicians to patients at risk of respiratory failure and allow for early patient reassessment and treatment adjustment. We propose an early warning system that predicts moderate/severe respiratory failure up to 8 hours in advance. Our system was trained on HiRID-II, a data-set containing more than 60,000 admissions to a tertiary care ICU. An alarm is typically triggered several hours before the beginning of respiratory failure. Our system outperforms a clinical baseline mimicking traditional clinical decision-making based on pulse-oximetric oxygen saturation and the fraction of inspired oxygen. To provide model introspection and diagnostics, we developed an easy-to-use web browser-based system to explore model input data and predictions visually.
Coronavirus disease (COVID-19) is an infectious disease discovered in 2019 and currently in outbreak across the world. Lung injury with severe respiratory failure is the leading cause of death in COVID-19, brought by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there still lacks efficient treatment for COVID-19 induced lung injury and acute respiratory failure. Inhibition of Angiotensin-converting enzyme 2 (ACE2) caused by spike protein of SARS-CoV-2 is the most plausible mechanism of lung injury in COVID-19. We propose two candidate drugs, COL-3 (a chemically modified tetracycline) and CGP-60474 (a cyclin-dependent kinase inhibitor), for treating lung injuries in COVID-19, based on their abilities to reverse the gene expression patterns in HCC515 cells treated with ACE2 inhibitor and in human COVID-19 patient lung tissues. Further bioinformatics analysis shows that twelve significantly enriched pathways (P-value <0.05) overlap between HCC515 cells treated with ACE2 inhibitor and human COVID-19 patient lung tissues, including signaling pathways known to be associated with lung injury such as TNF signaling, MAPK signaling and Chemokine signaling pathways. All these twelve pathways are targeted in COL-3 treated HCC515 cells, in which genes such as RHOA, RAC2, FAS, CDC42 have reduced expression. CGP-60474 shares eleven of twelve pathways with COL-3 with common target genes such as RHOA. It also uniquely targets genes related to lung injury, such as CALR and MMP14. In summary, this study shows that ACE2 inhibition is likely part of the mechanisms leading to lung injury in COVID-19, and that compounds such as COL-3 and CGP-60474 have the potential as repurposed drugs for its treatment.
Pneumonia is caused by viruses, bacteria, or fungi that infect the lungs, which, if not diagnosed, can be fatal and lead to respiratory failure. More than 250,000 individuals in the United States, mainly adults, are diagnosed with pneumonia each year, and 50,000 die from the disease. Chest Radiography (X-ray) is widely used by radiologists to detect pneumonia. It is not uncommon to overlook pneumonia detection for a well-trained radiologist, which triggers the need for improvement in the diagnosis's accuracy. In this work, we propose using transfer learning, which can reduce the neural network's training time and minimize the generalization error. We trained, fine-tuned the state-of-the-art deep learning models such as InceptionResNet, MobileNetV2, Xception, DenseNet201, and ResNet152V2 to classify pneumonia accurately. Later, we created a weighted average ensemble of these models and achieved a test accuracy of 98.46%, precision of 98.38%, recall of 99.53%, and f1 score of 98.96%. These performance metrics of accuracy, precision, and f1 score are at their highest levels ever reported in the literature, which can be considered a benchmark for the accurate pneumonia classification.
While deep learning has shown promise in improving the automated diagnosis of disease based on chest X-rays, deep networks may exhibit undesirable behavior related to shortcuts. This paper studies the case of spurious class skew in which patients with a particular attribute are spuriously more likely to have the outcome of interest. For instance, clinical protocols might lead to a dataset in which patients with pacemakers are disproportionately likely to have congestive heart failure. This skew can lead to models that take shortcuts by heavily relying on the biased attribute. We explore this problem across a number of attributes in the context of diagnosing the cause of acute hypoxemic respiratory failure. Applied to chest X-rays, we show that i) deep nets can accurately identify many patient attributes including sex (AUROC = 0.96) and age (AUROC >= 0.90), ii) they tend to exploit correlations between such attributes and the outcome label when learning to predict a diagnosis, leading to poor performance when such correlations do not hold in the test population (e.g., everyone in the test set is male), and iii) a simple transfer learning approach is surprisingly effective at preventing the shortcut and promoting good generalization performance. On the task of diagnosing congestive heart failure based on a set of chest X-rays skewed towards older patients (age >= 63), the proposed approach improves generalization over standard training from 0.66 (95% CI: 0.54-0.77) to 0.84 (95% CI: 0.73-0.92) AUROC. While simple, the proposed approach has the potential to improve the performance of models across populations by encouraging reliance on clinically relevant manifestations of disease, i.e., those that a clinician would use to make a diagnosis.
Recognition of anomalous events is a challenging but critical task in many scientific and industrial fields, especially when the properties of anomalies are unknown. In this paper, we introduce a new anomaly concept called "unicorn" or unique event and present a new, model-free, unsupervised detection algorithm to detect unicorns. The key component of the new algorithm is the Temporal Outlier Factor (TOF) to measure the uniqueness of events in continuous data sets from dynamic systems. The concept of unique events differs significantly from traditional outliers in many aspects: while repetitive outliers are no longer unique events, a unique event is not necessarily an outlier; it does not necessarily fall out from the distribution of normal activity. The performance of our algorithm was examined in recognizing unique events on different types of simulated data sets with anomalies and it was compared with the Local Outlier Factor (LOF) and discord discovery algorithms. TOF had superior performance compared to LOF and discord algorithms even in recognizing traditional outliers and it also recognized unique events that those did not. The benefits of the unicorn concept and the new detection method were illustrated by example data sets from very different scientific fields. Our algorithm successfully recognized unique events in those cases where they were already known such as the gravitational waves of a binary black hole merger on LIGO detector data and the signs of respiratory failure on ECG data series. Furthermore, unique events were found on the LIBOR data set of the last 30 years.